Alcohol decomposition composition and uses thereof

Abstract

The present invention provides an alcoholysis composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate. Methods of using the composition are also provided herein.

Description

[Technical field]

[0001] The present invention provides an alcoholysis composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate. Methods of using the composition are also provided herein. [Background technology]

[0002] Fermentation of sugars to ethanol is one of the oldest biotechnologies used by humans. The intoxicating effects of ethanol consumption have been known since ancient times. Ethanol has been used by humans since prehistoric times as the intoxicating ingredient in alcoholic beverages. Dried residues found on 9000-year-old pottery found in China suggest that Neolithic people consumed alcoholic beverages. Today, social drinking is tolerated in many cultures around the world. It is accepted as a legitimate way to celebrate special occasions or simply relax after a tiring day at work. Moderate drinking tends to be seen as a harmless activity.

[0003] There are many benefits that people derive from drinking socially, which explains why the activity has been popular for thousands of years. Alcohol is often described as a social lubricant; people tend to feel more relaxed and a little less self-conscious after a drink or two. There are many social events that revolve around alcohol consumption. Some research even suggests that moderate drinking may have certain health benefits. It is these beneficial aspects of alcohol that ensure its continued popularity.

[0004] However, even moderate drinkers may experience alcohol-related problems. Alcohol is a toxin that can damage the body even in small doses. People who regularly drink alcohol above the safe limit are at increased risk of health problems, including but not limited to certain cancers, cardiovascular events, high blood pressure, alcohol-related accidents, and the progression to alcohol abuse and alcoholism. For some people, it may not be safe to drink any alcohol.

[0005] Alcohol intoxication, also known as intoxication or alcoholism, is the undesirable behavior and physical effects that occur as a result of recent alcohol consumption. At lower doses, symptoms can include mild sedation and poor coordination. At higher doses, slurred speech, difficulty walking, and vomiting can occur. At extreme doses, respiratory depression, coma, or death can occur. Complications can include seizures, aspiration pneumonia, trauma including suicide, and hypoglycemia.

[0006] Alcohol is primarily metabolized in the liver, which is therefore at particular risk for liver damage. Heavy alcohol consumption significantly increases the risk of alcoholic fatty liver disease, an early and reversible consequence of excessive alcohol intake. Chronic alcohol consumption alters the liver's fat metabolism, causing excess fat to accumulate in the liver. Other effects on the liver include long-term inflammation (alcoholic hepatitis), which can lead to scar tissue and ultimately cirrhosis.

[0007] There is a need for new compositions, supplements, and / or treatments that reduce the undesirable effects associated with alcohol consumption. Summary of the Invention

[0008] The present invention is based on the surprising finding that L-cysteine ​​can be used to enhance alcohol degradation by one or more species of bacteria of the genus Bacillus. The inventors have surprisingly found that L-cysteine ​​can be used to enhance alcohol degradation by one or more species of bacteria of the genus Bacillus, especially when combined with a high molecular weight, low osmolality carbohydrate such as dextrin. The inventors have found that L-cysteine ​​can be used to enhance alcohol degradation by one or more species of bacteria of the genus Bacillus in the gastrointestinal tract, especially when combined with a high molecular weight, low osmolality carbohydrate such as dextrin. Advantageously, the inventors have developed a novel composition that reduces alcohol uptake into the blood, thus reducing the undesirable effects associated with alcohol intake.

[0009] The inventors have surprisingly found that the compositions described herein promote alcohol processing in the body, particularly by promoting alcohol decomposition in the digestive tract. Generally, about 80% of ingested alcohol remains in the small intestine before being absorbed into the blood. The compositions described herein advantageously reduce the amount of alcohol absorbed from the digestive tract into the blood (thus reducing the amount of alcohol processed by the liver). The inventors have found that taking the compositions described herein before alcohol consumption significantly reduces blood alcohol levels and breath alcohol levels after alcohol consumption compared to placebo.

[0010] Thus, in one aspect, there is provided an alcoholysis composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate.

[0011] High molecular weight low osmolality carbohydrates (e.g., dextrin) and / or L-cysteine ​​create a microenvironment in the digestive tract, which suggests that the microbial consortium of the compositions provided herein, when resuscitated in the intestinal tract, will excrete enzyme cascades that target short carbon chains, such as ethanol / alcohol, resulting in preferential targeting of these substrates.The targeted enzymes preferentially act on the alcohol that remains in the intestinal tract, breaking it down into carbon dioxide and water, thus avoiding the hepatic process of converting alcohol into acetaldehyde and acetic acid / acetate, which are hangover metabolites that would otherwise be formed by the liver's conversion of alcohol.Therefore, the compositions described herein facilitate the body's disposal of alcohol (keeping it away from the liver).

[0012] Upon resuscitation in the intestinal tract, the Bacillus spp. of the composition (and their endospores) begin to discern the biochemical conditions of their microenvironment and excrete a unique selection of bioactive substances that optimize the conditions, e.g., pH, conductivity, electrolytes, for their survival and reproduction. Nutrients and substrates are essential for survival and subsequent reproduction. The presence of alcohol / ethanol / ethyl alcohol in the microenvironment results in the excretion of alcohol-targeting enzymes, which break the alcohol down into carbon-containing fragments. Carbon that cannot be used as a nutrient by the microorganism or nearby tissue cells will be biochemically metabolized into water and carbon dioxide, which can exit the body system without any biological consequences / symptoms. This environmental discernment and selective excretion of bioactive substances for the optimization of enzymatic conditions is enhanced by high molecular weight low osmolality carbohydrates (e.g., dextrins) and / or L-cysteine ​​provided in the compositions described herein.

[0013] Advantageously, the compositions provided herein can be formulated as acid-resistant tablets or capsules. Such formulations are known to be resistant to the acid in the stomach and dissolve only when they reach the duodenum. The Bacillus species of the composition are then released to colonize the upper intestinal tract, where they can remain for about one day, and then are excreted from the body through feces. The bacterial species of the compositions described herein can be used to metabolize ethyl alcohol into CO2. 2 and water, thus reducing further reabsorption of alcohol from the intestinal tract. As a result, less alcohol is expected to be absorbed into the body, and organ damage from alcohol breakdown products is expected to be reduced.

[0014] As discussed above, in one aspect, the present invention provides an alcoholysis composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate.

[0015] Suitably, the one or more bacterial species of the genus Bacillus may be selected from B. subtilis and B. coagulans.

[0016] Suitably the composition may include B. subtilis and B. coagulans.

[0017] Appropriately, a) the B. subtilis species may be selected from the group consisting of Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900); and / or c) The B. coagulans species can be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0018] Suitably the high molecular weight low osmolality carbohydrate may be a dextrin.

[0019] Suitably the alcohol may be ethyl alcohol (ethanol).

[0020] Suitably, the composition may further comprise one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

[0021] Suitably, the composition may comprise at least about 10% (w / w) L-cysteine.

[0022] Suitably, the composition may comprise at least about 10000 cfu / g of bacteria of the Bacillus genus.

[0023] Suitably, the composition may comprise at least about 67% (w / w) rice bran.

[0024] Suitably, the composition may comprise at least about 0.5% (w / w) of a high molecular weight, low osmolality carbohydrate.

[0025] Suitably, the composition may further comprise one or more of vitamin B12, a magnesium salt of a fatty acid, calcium phosphate, potassium phosphate, silicon dioxide, and cellulose, where optionally the magnesium salt of a fatty acid is magnesium stearate.

[0026] Suitably, the composition may be formulated as an acid-resistant tablet or capsule. Suitably, the acid-resistant tablet or capsule may be provided with a film coating, where the film coating comprises hydroxypropylmethylcellulose (HPMC).

[0027] Suitably, in some embodiments, the one or more bacterial species of the genus Bacillus is not genetically modified.

[0028] The present invention also provides methods of using the alcoholysis compositions described herein to break down alcohol.

[0029] The present invention further provides the use of L-cysteine ​​to enhance alcohol degradation by one or more bacterial species of the genus Bacillus.

[0030] Suitably, L-cysteine ​​may be combined with a high molecular weight low osmolality carbohydrate, optionally wherein the high molecular weight low osmolality carbohydrate is a dextrin.

[0031] Suitably, L-cysteine ​​may be combined with rice bran.

[0032] Suitably, the one or more bacterial species of the genus Bacillus may be selected from B. subtilis and B. coagulans, where, optionally, the composition comprises B. subtilis and B. coagulans.

[0033] Appropriately, a) the B. subtilis species may be selected from the group consisting of Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900); and / or c) The B. coagulans species can be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0034] Suitably the alcohol may be ethyl alcohol (ethanol).

[0035] Suitably, the use may be for degrading alcohol in a subject. Suitably, the use is for metabolizing alcohol in the digestive tract of the subject, where, optionally, the use is for metabolizing alcohol in the intestine of the subject, and further, optionally, the use is for metabolizing alcohol in the small intestine of the subject.

[0036] Suitably the use may be for reducing the absorption of alcohol into the blood of a subject.

[0037] Suitably the use may be for reducing breath or blood alcohol concentration in a subject.

[0038] The present invention further provides a composition as described herein for use as a medicament.

[0039] The present invention further provides a composition as described herein for use in the breakdown of alcohol in a subject.

[0040] There is also provided a composition as described herein for use in the prevention and / or treatment of alcohol-induced organ damage in a subject. Suitably, the organ may be the liver and / or the pancreas.

[0041] Suitably, the composition may be for use in the prevention and / or treatment of a disease, condition or illness selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, liver cirrhosis, alcohol-induced cancer, cardiovascular conditions, obesity, neurological disorders, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache, and / or acetaldehyde poisoning. Suitably, the cancer may be selected from liver cancer, pancreatic cancer, breast cancer, esophageal cancer, and oropharyngeal cancer.

[0042] Suitably the composition may be administered prior to alcohol consumption.

[0043] Methods for degrading alcohol in a subject are provided, comprising administering to the subject a composition described herein.

[0044] The present invention further provides a method of preventing and / or treating alcohol-induced organ damage in a subject comprising administering to the subject a composition as described herein. Suitably, the organ may be the liver and / or the pancreas.

[0045] Suitably, the method may be for preventing and / or treating a disease, condition or illness selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, liver cirrhosis, alcohol-induced cancer, cardiovascular conditions, obesity, neurological disorders, neurodegenerative diseases, hangover symptoms, flushing syndrome, headaches, and / or acetaldehyde poisoning. Suitably, the cancer may be selected from liver cancer, pancreatic cancer, breast cancer, esophageal cancer, and oropharyngeal cancer.

[0046] Suitably, the composition may be administered prior to alcohol consumption.

[0047] The present invention provides an alcoholysis composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate. Methods of using the composition are also provided herein.

[0048] In each of the aspects and embodiments of the invention described herein, unless the context dictates otherwise, rice bran may be replaced by any suitable grain (e.g., cereal grain). In such aspects and embodiments, the suitable grain may be any suitable cereal bran. Suitable grains and suitable cereal brans are discussed elsewhere in this specification.

[0049] Throughout the detailed description and claims of this specification, the words "comprise" and "contain" and variations thereof mean "including but not limited to" and are not intended to, and do not, exclude other ingredients, additives, components, integers, or steps.

[0050] Throughout the detailed description and claims of this specification, the singular encompasses the plural unless the context otherwise requires. In particular, where the indefinite article is used, it shall be understood that the specification contemplates the plural as well as the singular, unless the context otherwise requires.

[0051] It is to be understood that any feature, integer, property, compound, chemical moiety, or group described in connection with a particular aspect, embodiment, or example of the invention is also applicable to any other aspect, embodiment, or example described herein, unless inconsistent therewith.

[0052] Various aspects of the invention are described in further detail below.

[0053] Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure Several strains of Bacillus species described in this application have been deposited with the International Depository Authority, the Microbiology Laboratory-Bacterial Collection (LMG) of the Belgian Collaborative Collection of Microorganisms (BCCM), Ghent University, KL Ledeganckstraat 35, 9000 Ghent, Belgium. The deposits were made under the terms of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure. [Brief description of the drawings]

[0054] Embodiments of the present invention are further described below with reference to the accompanying drawings, in which:

[0055] [Figure 1] FIG. 1 shows blood alcohol concentration (n=24) after ingestion of 0.3 g / kg body weight. [Diagram 2] FIG. 1 shows the reduction in alcohol absorption into the blood by AB001. [Diagram 3] FIG. 1 shows breath alcohol concentration after ingestion of 0.3 g / kg body weight (n=24). [Figure 4] FIG. 1 shows reduction of breath alcohol levels by AB001. [Diagram 5] FIG. 1 shows blood alcohol concentrations (n=24) after two doses of 0.3 g / kg body weight separated by a light breakfast (30 min). [Figure 6] FIG. 1 shows the reduction in alcohol absorption into the blood by AB001. [Figure 7] FIG. 1 shows breath alcohol concentrations (n=24) after two intakes of 0.3 g / kg body weight separated by a light breakfast (30 min). [Figure 8] Figure 1 shows data generated from individuals (74 males and females aged 26-66 years) who consumed 60cc of wine (14%) in 1 hour. Individuals were given the following composition at 600mg per dose: 414mg fermented rice bran, 120mg L-cysteine, 10mg dextrin, 0.90mcg vitamin B12, 26mg excipients, HPMC capsule. [Figure 9] Figure 1 shows data generated from individuals (84 men (56) and women (28) ages 26-72) who consumed 60cc of wine (14%) over a 1 hour period. Individuals were given the following composition at the indicated dosages: 69% fermented rice bran, 20% L-cysteine, 2% dextrin, 0.00002% Vitamin B12, 9% excipients, HPMC capsule. [Figure 10] Figure 1 shows data generated from individuals (87 males and females aged 26-66 years) who consumed 60cc of wine (14%) over a 1 hour period. Response times were determined from individuals given the following composition at 750mg per dose: 518mg fermented rice bran, 150mg L-cysteine, 15mg dextrin, 0.90mcg Vitamin B12, 67mg excipients, HPMC capsule. [Figure 11] Figure 1 shows data generated from individuals (62 males and females aged 26-66 years) ingesting 60cc of wine (14%) and consuming it in 1 hour. Individuals were given the following composition: 69% fermented rice bran, 20% L-cysteine, 2% dextrin, 0.00002% Vitamin B12, 9% excipients, HPMC capsule. % reduction in time to 0.05‰ compared to "predicted time to sober" from the iBAC manual (sc.edu*(*https: / / sc.edu / about / offices_and_divisions / fraternity_and_sorority_life / documents / bac-charts1617.pdf)). [Figure 12] Figure 2: Changes in plasma bilirubin content (data generated from an in vivo alcohol study in mice). IC = intact control group fed standard rodent chow, CMD = placebo group fed high fat and high carbohydrate diet (Western Diet) with 10% ethanol and maltodextrin. PB = probiotic group fed high fat and high carbohydrate diet (Western Diet) with 10% ethanol and AB001. [Figure 13] FIG. 1 shows body weight changes during an in vivo alcohol study in mice. [Figure 14] FIG. 1 outlines the experimental design for the in vivo alcohol study in mice.

[0056] The patent, scientific, and technical literature referenced herein establishes knowledge available to those skilled in the art at the time of filing. Issued patents, published and pending patent applications, and other publications cited herein are incorporated by reference as if each was specifically and individually indicated to be incorporated by reference. In the event of any discrepancy, the present disclosure shall control.

[0057] Various aspects of the invention are described in further detail below.

[0058] Detailed Description The present invention is based on the surprising finding that L-cysteine ​​can be used to enhance alcohol degradation by one or more species of bacteria of the genus Bacillus.The inventors have surprisingly found that L-cysteine ​​can enhance alcohol degradation by one or more species of bacteria of the genus Bacillus, especially when combined with a high molecular weight, low osmolality carbohydrate such as dextrin.The data presented herein demonstrate that L-cysteine ​​can be used to enhance alcohol degradation by one or more species of bacteria of the genus Bacillus in the gastrointestinal tract, especially when combined with a high molecular weight, low osmolality carbohydrate such as dextrin.Advantageously, the inventors have developed a novel composition that reduces alcohol uptake into the blood, thus reducing the undesirable effects associated with alcohol intake.

[0059] Thus, provided herein is an alcoholysis composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate.

[0060] The compositions provided herein may be referred to as "MYRKL" and / or "AB001". Additionally, the compositions provided herein may be referred to as "Pinch" unless the context specifically defines "Pinch" (see Example 1).

[0061] As used herein, "alcohol" refers to any of a class of organic compounds characterized by one or more hydroxyl (-OH) groups attached to a carbon atom of an alkyl group (hydrocarbon chain). Alcohols are the only organic compounds that are hydrolyzed by water (H 2 O) in which one of the hydrogen atoms has been replaced by an alkyl group, typically represented in the organic structure by R. For example, in ethanol (or ethyl alcohol), the alkyl group is an ethyl group, i.e., -CH 2 CH 3Alcohols can be classified as primary, secondary, or tertiary depending on which carbon of the alkyl group is attached to the hydroxyl group. Most alcohols are colorless liquids or solids at room temperature. Low molecular weight alcohols are very soluble in water, and as the molecular weight increases, they become less soluble in water and their boiling points, vapor pressures, densities, and viscosities increase. A person skilled in the art would be able to easily identify alcohols using routine methods in the art. Non-limiting examples of alcohols include methanol and ethanol.

[0062] As will be apparent to those skilled in the art, the "alcohol degrading composition" referred to herein is a composition that degrades alcohol. In other words, the "alcohol degrading composition" as used herein is a composition that breaks down (e.g., biochemically breaks down) alcohol. In the context of the present invention, the decomposition (e.g., destruction) of a substance (such as alcohol) includes converting the substance into one or more other different substances. Furthermore, as will be appreciated by those skilled in the art, "alcohol degrading" as used herein refers to breaking down alcohol, and "alcohol degradation" as used herein refers to the destruction of alcohol. As will be apparent to those skilled in the art, the compositions described herein can be used in vitro or in vivo.

[0063] Alcohol may be degraded (e.g., broken down) in a number of different ways. Of particular relevance in the context of the present invention is biochemical degradation. Thus, in one embodiment, alcohol may be degraded (e.g., broken down) biochemically. As known to those of skill in the art, biochemical destruction of a substance may involve enzyme-catalyzed reactions. Thus, in one embodiment, alcohol may be degraded enzymatically.

[0064] In the body, alcohol is metabolized by several processes or pathways. The most common of these pathways involves two enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). These enzymes help break apart alcohol molecules so they can be excreted from the body. After alcohol consumption, most of the ethanol in the body is destroyed by ADH in the liver. First, ADH metabolizes alcohol to acetaldehyde, a highly toxic substance and known carcinogen. Then, in a second step, acetaldehyde is further metabolized by acetaldehyde dehydrogenase to another less active by-product called acetate, which is then broken down into water and carbon dioxide, which is easily excreted. Acetate is broken down into carbon dioxide and water, mainly in tissues other than the liver. Alcohol dehydrogenase produces oxygen free radicals that affect genes. The enzymes cytochrome P450 2E1 (CYP2E1) and catalase also break down alcohol to acetaldehyde. However, CYP2E1 is only active after a person has consumed large amounts of alcohol, and catalase metabolizes only a small portion of the alcohol in the body. Small amounts of alcohol are also eliminated by interacting with fatty acids to form compounds called fatty acid ethyl esters (FAEEs). These compounds have been shown to contribute to damage to the liver and pancreas.

[0065] Advantageously, the compositions described herein promote the breakdown (e.g., destruction) of alcohol in the digestive tract to carbon dioxide and water while avoiding the liver's conversion of alcohol to harmful metabolites, including acetaldehyde, which is considered a hangover metabolite formed by the liver's conversion of alcohol, and also acetic acid. The compositions described herein can promote the breakdown of alcohol in the digestive tract to carbon dioxide and water via intermediate metabolites that are not acetaldehyde and / or acetic acid.

[0066] As used herein, "metabolism" is a term used to describe all biochemical reactions involved in maintaining the survival of cells and organisms. For example, metabolism includes all biochemical reactions involved in converting one molecule into another, thus essentially maintaining the survival of a cell or organism. Metabolism includes processes involved in cell growth, reproduction, response to the environment, survival mechanisms, life support, and maintaining the structure and integrity of cells. Biochemical reactions involved in metabolism utilize various enzymes.

[0067] In one embodiment, alcohol may be metabolized (i.e., alcohol may be broken down via metabolism). Thus, in one embodiment, an alcohol metabolizing composition is provided that includes one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate (e.g., dextrin). As known to those skilled in the art, metabolism may be enzymatic, so in some embodiments, alcohol may be enzymatically metabolized.

[0068] Metabolism can be categorized into two categories: catabolism and anabolism. Catabolism involves a series of degradative biochemical reactions that break down complex molecules into smaller units, usually releasing energy in the process. For example, catabolism can be used to refer to all biochemical or enzymatic reactions involved in the destruction of organic or inorganic substances such as proteins, sugars, fatty acids, etc. Anabolism involves a series of biochemical reactions that build or synthesize molecules from smaller units, usually requiring the input of energy (ATP) in the process. Thus, catabolism refers to the destructive biochemical reactions that occur within an organism, whereas metabolism refers to the entire series of biochemical reactions within an organism that can be either constructive or destructive.

[0069] In some embodiments, the breakdown of alcohol via metabolism may be considered catabolism. Thus, in some embodiments, alcohol may be catabolized (i.e., alcohol may be broken down via catabolism). In further embodiments, alcohol may be enzymatically catabolized.

[0070] In some embodiments, alcohol is broken down in the subject. By way of non-limiting example, alcohol may be enzymatically broken down, metabolized, or catabolized in the subject. When alcohol breakdown occurs in the subject (e.g., particularly in the duodenum and / or small intestine), this may be referred to as digestion. In some embodiments, alcohol may be broken down by biochemical digestion.

[0071] In one embodiment, the alcohol is ethyl alcohol (also known as ethanol).

[0072] Ethanol is an organic chemical compound. It has the chemical formula C 2 H 6 It is a simple alcohol with 1,2-dihydropyridine. Its formula is CH 3 -CH 2 -OH or C 2 H 5 It can also be written as OH (an ethyl group linked to a hydroxyl group) and is often abbreviated as EtOH. Ethanol is a volatile, flammable, colorless liquid with a characteristic wine-like odor and a pungent taste. Ethanol is an active ingredient in psychoactive drugs, recreational drugs, and alcoholic beverages. Thus, in one embodiment, alcohol is contained within an alcoholic beverage. Non-limiting examples of alcoholic beverages include beer, wine, and spirits (e.g., vodka).

[0073] Thus, in one embodiment, provided herein is an ethanolytic composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate (e.g., dextrin).

[0074] In another example, provided herein is an ethanol metabolism composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmolality carbohydrate (e.g., dextrin).

[0075] As discussed elsewhere herein, the alcoholysis compositions provided herein include one or more bacterial species of the genus Bacillus. For example, the composition may include two or more bacterial species of the genus Bacillus. In another embodiment, the composition may include three or more bacterial species of the genus Bacillus. In a further embodiment, the composition may include four or more bacterial species of the genus Bacillus. In another embodiment, the composition may include five or more bacterial species of the genus Bacillus. In a further embodiment, the composition may include six or more bacterial species of the genus Bacillus. In another embodiment, the composition may include seven or more bacterial species of the genus Bacillus.

[0076] As is known in the art, a genus is composed of multiple species. Thus, the genus "Bacillus" includes, but is not limited to, Bacillus alkalophilus, Bacillus amyloliquefaciens, Bacillus brevis, Bacillus circulans, Bacillus clausii, Bacillus coagulans, Bacillus firmus, Bacillus lautus, Bacillus lentus, Bacillus licheniformis, Bacillus megaterium, Bacillus pumilus, Bacillus ketosporum ... The term "Bacillus" includes all species within the genus "Bacillus" known to those of skill in the art, including Bacillus pumilus, Bacillus stearothermophilus, Bacillus subtilis, Bacillus velezensis, Bacillus species MT 03, Bacillus atrophaeus, and Bacillus thuringiensis. It is recognized that the genus Bacillus continues to undergo taxonomic reorganization. Thus, the genus is intended to include reclassified species, including, but not limited to, organisms such as B. stearothermophilus, which is now named "Geobacillus stearothermophilus."The production of resistant endospores in the presence of oxygen is considered to be the defining characteristic of the genus Bacillus, although this property also applies to the more recently named genera Alicyclobacillus, Amphibacillus, Aneurinibacillus, Anoxybacillus, Brevibacillus, Filobacillus, Gracilibacillus, Halobacillus, Paenibacillus, Salibacillus, Thermobacillus, Ureibacillus, and Virgibacillus.

[0077] Species within the genus Bacillus are gram-positive bacteria classified as members of the family Bacillaceae within the order Bacillales of the class Bacilli. As used herein, "Bacillus sp." refers to a species within the genus "Bacillus."

[0078] Bacillus species found to be particularly important in the context of the present invention include Bacillus subtilis and Bacillus coagulans. As illustrated in the Examples below, these bacteria are abundant in the compositions of the present invention and are particularly effective at breaking down (e.g., metabolizing) ethyl alcohol into carbon dioxide and water, particularly in the gastrointestinal tract.

[0079] Thus, in one embodiment, the one or more bacterial species of the genus Bacillus is selected from B. subtilis and B. coagulans.

[0080] In another embodiment, the compositions provided herein comprise B. subtilis and B. coagulans.

[0081] According to the present invention, any suitable B. subtilis and / or B. coagulans strain can be used. A person skilled in the art will be able to easily identify suitable strains. Bacillus subtilis strain DFM 0326 (LMG P-32899), Bacillus subtilis strain DFM 1015 (LMG P-32900), and Bacillus coagulans strain DFM 0705 (LMG P-32921) have been found to be particularly important in the context of the present invention.

[0082] The Bacillus subtilis strain deposited under LMG-P accession number 32899 may be referred to herein as "DFM 0326" or "strain DFM 0326." Bacillus subtilis strain DFM 0326 (deposited under LMG-P accession number 32899) was deposited under the Budapest Treaty of 1977 on November 22, 2022 at the Belgian Collaborative Collection of Microorganisms (BCCM), the Institute of Microbiology - Bacterial Collection (LMG) of Ghent University (KL Redegangstraat 35, 9000 Ghent, Belgium).

[0083] The Bacillus subtilis strain deposited under LMG-P accession number 32900 may be referred to herein as "DFM 1015" or "strain DFM 1015". Bacillus subtilis strain DFM 1015 (deposited under LMG-P accession number 32900) was deposited under the Budapest Treaty of 1977 on November 22, 2022 at the Belgian Collaborative Collection of Microorganisms (BCCM), the Institute of Microbiology - Bacterial Collection (LMG) of Ghent University (KL Redegangstraat 35, 9000 Ghent, Belgium).

[0084] The Bacillus coagulans strain deposited under LMG-P accession number 32921 may be referred to herein as "DFM 0705" or "strain DFM 0705". Bacillus coagulans strain DFM 0705 (deposited under LMG-P accession number 32921) was deposited under the Budapest Treaty of 1977 on December 14, 2022 at the Belgian Collaborative Collection of Microorganisms (BCCM), the Institute of Microbiology - Bacterial Collection (LMG) of Ghent University (KL Redegangstraat 35, 9000 Ghent, Belgium).

[0085] Thus, in some embodiments, the B. subtilis species can be selected from the group consisting of Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900), and / or the B. coagulans species can be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0086] Thus, in embodiments where the composition comprises B. subtilis and B. coagulans, the B. subtilis species can be Bacillus subtilis strain DFM 0326 (LMG P-32899) and the B. coagulans species can be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0087] In another embodiment where the composition comprises B. subtilis and B. coagulans, the B. subtilis species can be Bacillus subtilis strain DFM 1015 (LMG P-32900) and the B. coagulans species can be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0088] In some embodiments, compositions according to the present invention may include B. subtilis strain DFM 0326 (LMG P-32899) in combination with Bacillus subtilis strain DFM 1015 (LMG P-32900).

[0089] In another example where the composition comprises B. subtilis and B. coagulans, the composition may comprise B. subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900) and Bacillus coagulans species strain DFM 0705 (LMG P-32921). Notably, the composition used in the examples provided herein comprises B. subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900) and B. coagulans strain DFM 0705 (LMG P-32921).

[0090] Thus, a composition according to the invention may comprise Bacillus subtilis strain DFM 0326 (LMG P-32899), Bacillus subtilis strain DFM 1015 (LMG P-32900), and Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0091] The inventors have also identified several other bacterial species that are particularly relevant in the context of the compositions described herein. Thus, in one embodiment, the composition may further comprise one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus verzensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus. In another embodiment, the composition may further comprise two or more, or three or more, or four or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus verzensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

[0092] In another embodiment, the composition may further comprise Bacillus amyloliquefaciens, Bacillus veresensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

[0093] The bacterial strains contained in the alcohol decomposition composition provided herein have been confirmed to favorably and effectively metabolize ethyl alcohol to carbon dioxide and water. Advantageously, the inventors have demonstrated that the ingestion of the compositions described herein before alcohol consumption significantly reduces blood alcohol levels and breath alcohol levels after alcohol consumption compared to placebo, demonstrating that the compositions described herein reduce further alcohol absorption from the intestinal tract after alcohol consumption.

[0094] The compositions provided herein include one or more bacterial species of the genus Bacillus in an appropriate amount or concentration. Thus, the amount or concentration of one or more bacterial species of the genus Bacillus can be described by referring to the number of colony forming units (cfu) per gram of the composition (cfu / g) or by referring to the total number of colony forming units (cfu) per dose of the composition (in other words, cfu per effective dose). As will be apparent to those skilled in the art, and as described in more detail elsewhere herein, a dose can include one or more dosage units (e.g., two dosage units). In embodiments where multiple dosage units are used to provide an effective dose, the cfu per dose corresponds to the total cfu across the multiple dosage units.

[0095] In one embodiment, the compositions described herein contain between about 10,000 cfu / g of Bacillus bacteria and about 1×10 8 Contains Bacillus spp. cfu / g.

[0096] In one embodiment, the compositions described herein contain at least about 1×10 8 In another embodiment, the compositions described herein comprise at least about 1×10 cfu / g of bacteria of the genus Bacillus. 7 In another embodiment, the compositions described herein comprise at least about 1×10 cfu / g of bacteria of the genus Bacillus. 6 In a further embodiment, the compositions described herein comprise at least about 1×10 cfu / g of bacteria of the genus Bacillus. 5Contains Bacillus spp. cfu / g.

[0097] In one embodiment, the compositions described herein have a concentration of at least about 10,000 cfu / g (i.e., at least about 1.0×10 4 cfu / g) of bacteria of the genus Bacillus.

[0098] In another embodiment, the compositions described herein have a virulence factor of at least about 11,000 cfu / g (i.e., at least about 1.1×10 4 In a further embodiment, the compositions described herein comprise at least about 12,000 cfu / g (i.e., at least about 1.2×10 4 cfu / g) of bacteria of the genus Bacillus.

[0099] In another embodiment, the compositions described herein have a virulence factor of at least about 13,000 cfu / g (i.e., at least about 1.3×10 4 cfu / g) of bacteria of the genus Bacillus.

[0100] In another embodiment, the compositions described herein have a virulence factor of at least about 14,000 cfu / g (i.e., at least about 1.4×10 4 In another embodiment, the compositions described herein comprise at least about 15,000 cfu / g (i.e., at least about 1.5×10 4 cfu / g) of bacteria of the genus Bacillus.

[0101] In one embodiment, the compositions described herein contain about 1×10 8 cfu / g of bacteria of the genus Bacillus. In another embodiment, the compositions described herein contain about 1×10 7 cfu / g of bacteria of the genus Bacillus. In another embodiment, the compositions described herein contain about 1×10 6 cfu / g of bacteria of the genus Bacillus. In a further embodiment, the compositions described herein contain about 1×10 5Contains Bacillus spp. cfu / g.

[0102] In one embodiment, the compositions described herein contain about 10,000 cfu / g (i.e., about 1.0×10 4 cfu / g) of bacteria of the genus Bacillus.

[0103] In another embodiment, the compositions described herein contain about 11,000 cfu / g (i.e., about 1.1×10 4 In a further embodiment, the compositions described herein comprise about 12,000 cfu / g (i.e., about 1.2×10 4 cfu / g) of bacteria of the genus Bacillus.

[0104] In another embodiment, the compositions described herein contain about 13,000 cfu / g (i.e., about 1.3×10 4 cfu / g) of bacteria of the genus Bacillus.

[0105] In another embodiment, the compositions described herein contain about 14,000 cfu / g (i.e., about 1.4×10 4 In a further embodiment, the compositions described herein comprise about 15,000 cfu / g (i.e., about 1.5×10 4 cfu / g) of bacteria of the genus Bacillus.

[0106] A person skilled in the art can easily determine the amount or concentration of bacteria present in a composition using routine methods known in the art. For example, the total viable count (TVC) of live Bacillus cells can be determined by established culture methods based on specific Bacillus media, such as Chrome Select agar. Alternative methods are known in the art.

[0107] In one embodiment, the compositions described herein contain between about 5000 cfu of Bacillus bacteria per dose and about 1×10 8 Contains cfu of Bacillus spp.

[0108] In one embodiment, the compositions described herein contain at least about 1×10 8 In another embodiment, the compositions described herein comprise at least about 1 x 10 cfu of bacteria of the genus Bacillus per dose. 7 In another embodiment, the compositions described herein comprise at least about 1 x 10 cfu of bacteria of the genus Bacillus per dose. 6 Contains cfu of Bacillus spp.

[0109] In further embodiments, the compositions described herein contain at least about 1×10 5 Contains cfu of Bacillus spp.

[0110] In one example, the compositions described herein contain at least about 5000 cfu per dose (i.e., at least about 0.5×10 4 cfu) of bacteria of the genus Bacillus.

[0111] In another embodiment, the compositions described herein contain at least about 10,000 cfu per dose (i.e., at least about 1.0×10 4 In another embodiment, the compositions described herein comprise at least about 11,000 cfu (i.e., at least about 1.1×10 4 In a further embodiment, the compositions described herein comprise at least about 12,000 cfu (i.e., at least about 1.2×10 4 In another embodiment, the compositions described herein comprise at least about 13,000 cfu (i.e., at least about 1.3×10 4 In another embodiment, the compositions described herein comprise at least about 14,000 cfu (i.e., at least about 1.4×10 4In another embodiment, the compositions described herein comprise at least about 15,000 cfu (i.e., at least about 1.5×10 4 cfu) of bacteria of the genus Bacillus.

[0112] In one embodiment, the compositions described herein contain about 1×10 8 In another embodiment, the compositions described herein contain about 1×10 cfu of bacteria of the genus Bacillus per dose. 7 In another embodiment, the compositions described herein contain about 1×10 cfu of bacteria of the genus Bacillus per dose. 6 Contains cfu of Bacillus spp.

[0113] In a further embodiment, the compositions described herein contain about 1×10 5 Contains cfu of Bacillus spp.

[0114] In one embodiment, the compositions described herein contain about 5000 cfu per dose (i.e., about 0.5×10 4 In one embodiment, the compositions described herein contain about 10,000 cfu (i.e., about 1.0×10 4 In another embodiment, the compositions described herein contain about 11,000 cfu (i.e., about 1.1×10 4 In a further embodiment, the compositions described herein contain about 12,000 cfu (i.e., about 1.2×10 4 In another embodiment, the compositions described herein contain about 13,000 cfu (i.e., about 1.3×10 4 In another embodiment, the compositions described herein contain about 14,000 cfu (i.e., about 1.4×10 4In a further embodiment, the compositions described herein contain about 15,000 cfu (i.e., about 1.5×10 4 cfu) of bacteria of the genus Bacillus.

[0115] As will be apparent to those skilled in the art, the amount or concentration of one or more bacterial species of the genus Bacillus in the composition may be composed of any individual species of the genus Bacillus, or any combination of species of the genus Bacillus. For example, the amount or concentration of one or more bacterial species of the genus Bacillus in the composition may be composed exclusively of one species of Bacillus (e.g., the concentration may be composed exclusively of B. subtilis or exclusively of B. coagulans). Alternatively, the amount or concentration of one or more bacterial species of the genus Bacillus in the composition may be composed of two or more, three or more, four or more, or five or more species of Bacillus (e.g., the concentration may be composed of B. subtilis and B. coagulans). Thus, in one embodiment, the amount or concentration of one or more bacterial species of the genus Bacillus in the composition refers to the amount or concentration of the combination of Bacillus species present.

[0116] In some embodiments, the compositions provided herein comprise a suitable concentration of bacteria, where the concentration ratio is comprised of one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans). In one embodiment, the compositions described herein comprise a concentration of about 10,000 cfu / g (i.e., about 1.0×10 4 cfu / g) of bacteria ~ approx. 1 x 10 8 In one embodiment, the compositions described herein contain at least about 1×10 cfu / g of bacteria. 8 In another embodiment, the compositions described herein contain at least about 1×10 cfu / g of bacteria. 7 In another embodiment, the compositions described herein contain at least about 1×10 cfu / g of bacteria. 6 In further embodiments, the compositions described herein contain at least about 1×10 cfu / g of bacteria. 5In one embodiment, the compositions described herein contain at least about 10,000 cfu / g (i.e., at least about 1.0×10 4 In another embodiment, the compositions described herein comprise at least about 11,000 cfu / g (i.e., at least about 1.1×10 4 In further embodiments, the compositions described herein contain at least about 12,000 cfu / g (i.e., at least about 1.2×10 4 In another embodiment, the compositions described herein comprise at least about 13,000 cfu / g (i.e., at least about 1.3×10 4 In another embodiment, the compositions described herein comprise at least about 14,000 cfu / g (i.e., at least about 1.4×10 4 In another embodiment, the compositions described herein comprise at least about 15,000 cfu / g (i.e., at least about 1.5×10 4 cfu / g of bacteria. In one embodiment, the compositions described herein contain about 1×10 8 In another embodiment, the compositions described herein contain about 1×10 cfu / g of bacteria. 7 In another embodiment, the compositions described herein contain about 1×10 cfu / g of bacteria. 6 In a further embodiment, the compositions described herein contain about 1×10 cfu / g of bacteria. 5 In one embodiment, the compositions described herein contain about 10,000 cfu / g (i.e., about 1.0×10 4 In another embodiment, the compositions described herein contain about 11,000 cfu / g (i.e., about 1.1×10 4 In a further embodiment, the compositions described herein contain about 12000 cfu / g (i.e., about 1.2×10 4In another embodiment, the compositions described herein contain about 13,000 cfu / g (i.e., about 1.3×10 4 In another embodiment, the compositions described herein contain about 14,000 cfu / g (i.e., about 1.4×10 4 In a further embodiment, the compositions described herein contain about 15,000 cfu / g (i.e., about 1.5×10 4 cfu / g) of bacteria.

[0117] In some embodiments, the compositions provided herein comprise a suitable amount of bacteria, where the proportion of the amount consists of one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0118] In one embodiment, the compositions described herein contain between about 5000 cfu of bacteria per dose and about 1.0×10 8 In one embodiment, the compositions described herein contain at least about 1 x 10 cfu of bacteria per dose. 8 In another embodiment, the compositions described herein contain at least about 1 x 10 cfu of bacteria per dose. 7 In another embodiment, the compositions described herein contain at least about 1 x 10 cfu of bacteria per dose. 6 In further embodiments, the compositions described herein contain at least about 1 x 10 cfu of bacteria per dose. 5 In one example, the compositions described herein contain at least about 5000 cfu of bacteria per dose (i.e., at least about 0.5×10 4 In another embodiment, the compositions described herein contain at least about 10,000 cfu (i.e., at least about 1.0×10 4 In another embodiment, the compositions described herein contain at least about 11,000 cfu (i.e., at least about 1.1×10 4In a further embodiment, the compositions described herein contain at least about 12,000 cfu (i.e., at least about 1.2×10 4 In another embodiment, the compositions described herein contain at least about 13,000 cfu (i.e., at least about 1.3×10 4 In another embodiment, the compositions described herein contain at least about 14,000 cfu (i.e., at least about 1.4×10 4 In another embodiment, the compositions described herein contain at least about 15,000 cfu (i.e., at least about 1.5×10 4 In one embodiment, the compositions described herein contain about 1×10 cfu of bacteria per dose. 8 In another embodiment, the compositions described herein contain about 1×10 cfu of bacteria per dose. 7 In another embodiment, the compositions described herein contain about 1×10 cfu of bacteria per dose. 6 In a further embodiment, the compositions described herein contain about 1 x 10 cfu of bacteria per dose. 5 In one example, the compositions described herein contain about 5000 cfu (i.e., about 0.5×10 4 In one example, the compositions described herein contain about 10,000 cfu (i.e., about 1.0×10 4 In another embodiment, the compositions described herein contain about 11,000 cfu (i.e., about 1.1×10 4 In a further embodiment, the compositions described herein contain about 12000 cfu (i.e., about 1.2×10 4 In another embodiment, the compositions described herein contain about 13,000 cfu (i.e., about 1.3×10 4In another embodiment, the compositions described herein contain about 14,000 cfu (i.e., about 1.4×10 4 In a further embodiment, the compositions described herein contain about 15,000 cfu (i.e., about 1.5×10 4 cfu) of bacteria.

[0119] As will be apparent to one of skill in the art, the amount or concentration of bacteria, wherein the proportion is comprised of one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans), may further include any suitable individual species or any combination of species. For example, the amount or concentration of bacteria, wherein the proportion is comprised of one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans), may further include a proportion of one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus berezensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

[0120] In one embodiment, one or more bacterial species of the genus Bacillus are genetically modified.

[0121] As used herein, "genetic modification" and "genetic engineering" refer to the direct manipulation (e.g., modification) of one or more genes, for example, using recombinant DNA technology. Traditionally, humans have manipulated genomes indirectly by controlling reproduction and selecting offspring with desired traits, but genetic engineering involves the direct manipulation (e.g., modification) of one or more genes. For example, a gene from another species can be added to the genome of an organism to give it a desired phenotype.

[0122] In other embodiments, the one or more bacterial species of the Bacillus genus are not genetically modified, i.e., the one or more bacterial species of the Bacillus genus may be naturally occurring.

[0123] One or more bacterial species of the genus Bacillus may be present in a microbial consortium. As used herein, a "microbial consortium" refers to a group of microorganisms (e.g., bacteria) where the group includes two or more different microorganisms (e.g., two or more bacteria that may be from the same species (e.g., two or more different strains) or different species (e.g., two or more different species)).

[0124] The microbial consortium may be a naturally occurring microbial consortium (e.g., a consortium that is naturally generated during the fermentation of a grain, such as rice bran). In other words, one or more bacterial species of the genus Bacillus may be part of the composition by virtue of the presence of a fermented grain, such as rice bran, in the composition (along with the naturally occurring microbial consortium associated therewith). Thus, one or more bacterial species of the genus Bacillus may be a natural component of a fermented grain, such as rice bran.

[0125] The inventors have found that Bacillus subtilis strain DFM 0326 (LMG P-32899), Bacillus subtilis strain DFM 1015 (LMG P-32900), and Bacillus coagulans strain DFM 0705 (LMG P-32921) can be isolated from the compositions (particularly fermented rice bran) used in the examples provided herein. Thus, by virtue of the presence of a fermented grain such as rice bran (along with its associated naturally occurring microbial consortium) in the composition, Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900) and B. coagulans strain DFM 0705 (LMG P-32921) can be part of the compositions described herein.

[0126] In another embodiment, one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus veresensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be (part of) a naturally occurring microbial consortium (e.g., a consortium naturally generated during the fermentation of a grain, such as rice bran). In other words, by virtue of the presence of a fermented grain, such as rice bran, in the composition (with its associated naturally occurring microbial consortium), one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus veresensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be part of the composition. Thus, one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus veresensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be natural components of fermented grains such as rice bran.

[0127] In another embodiment, one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans) and one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus veresensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be (part of) a naturally occurring microbial consortium (e.g., a consortium naturally produced during fermentation of a grain such as rice bran). In other words, by virtue of the presence of a fermented grain such as rice bran in the composition (with its associated naturally occurring microbial consortium), one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans) and one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus verzensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be part of the composition. Thus, one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans) and one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus verzensis, Bacillus sp. MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be natural constituents of a fermented grain such as rice bran.

[0128] As will be apparent to those skilled in the art, the present invention is not limited to naturally occurring microbial consortia. Thus, the microbial consortia discussed above can also be artificially created, for example, by combining one or more bacterial isolates with each other. Thus, in one embodiment, one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans) can be added individually to the composition.

[0129] Thus, the alcoholyzed composition may also include grains such as rice bran (e.g., fermented rice bran), which are discussed in more detail elsewhere herein. For example, fermented rice bran may be a natural source of one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans) present in the composition.

[0130] The present inventors have surprisingly found that L-cysteine ​​can be used to enhance alcohol degradation by one or more bacterial species of the genus Bacillus, particularly when combined with a high molecular weight, low osmolality carbohydrate such as dextrin.

[0131] Thus, the alcoholyzing compositions described herein include L-cysteine ​​in combination with one or more bacterial species of the genus Bacillus (e.g., where the bacteria are added to the composition as a bacterial supplement or as part of a natural product, such as fermented rice bran).

[0132] L-cysteine ​​(L-cys) is a non-essential amino acid and is therefore one of the building blocks required for the synthesis of proteins. L-cysteine ​​contains sulfur in the form of a thiol group (-SH) at the end of its side chain. The -SH group is responsible for the high reactive capacity of the amino acid and is therefore responsible for many of its biological functions in humans. L-cysteine ​​occupies an important position in the sulfur metabolism of all living organisms and is used in the synthesis of proteins, glutathione, biotin, lipoic acid, methionine, and other sulfur-containing metabolites. Furthermore, L-cysteine ​​serves as a precursor for the biosynthesis of coenzyme A. The biosynthesis of L-cysteine ​​has been studied in detail in bacteria, especially in enterobacteria. The amino acid L-cysteine ​​is not only biologically important, but also economically important. L-cysteine ​​is used, for example, as a starting material in food additives (especially in the bakery industry), cosmetics, and for the preparation of active pharmaceutical ingredients (especially N-acetylcysteine ​​and S-carboxymethylcysteine).

[0133] As will be apparent to those skilled in the art, references herein to L-cysteine ​​refer to any suitable form of the amino acid L-cysteine. Thus, the term "L-cysteine" encompasses not only L-cysteine ​​salts, but also the free form of L-cysteine.

[0134] In the context of the present invention, in one embodiment, L-cysteine ​​can be in free form, a salt thereof, or a mixture thereof.

[0135] Exemplary salts include, for example, sulfate, hydrochloride, carbonate, ammonium, sodium, and potassium salts. In one embodiment, the L-cysteine ​​is a crystalline fraction greater than 0.1 mm.

[0136] L-cysteine ​​is available from several suppliers and can be easily obtained by those skilled in the art. Furthermore, those skilled in the art can easily detect the presence of L-cysteine ​​in a substance (e.g., the compositions described herein) using methods known in the art. For example, L-cysteine ​​crystals can be macroscopically detected as white particles in the compositions described herein. HPLC (high performance liquid chromatography) on an Inertsil ODs-3 column is an established method for detecting L-cysteine.

[0137] L-cysteine ​​can be obtained industrially by hydrolysis of animal materials such as poultry feathers or pig hair. In contrast, synthetic L-cys can be obtained from the fermentation of genetically modified E. coli or Pseudomonas thiazolinophilum. Thus, in some embodiments, L-cysteine ​​is of animal origin. In other embodiments, L-cysteine ​​is of synthetic origin.

[0138] In one embodiment, the L-cysteine ​​is derived from a plant.

[0139] In some embodiments, the compositions described herein may include an L-cysteine ​​derivative instead of or in addition to L-cysteine.

[0140] L-cysteine ​​derivatives are well known to those skilled in the art. N-acetylcysteine ​​(NAC) is an example of an L-cysteine ​​derivative, since it is the N-acetylated form of the amino acid L-cysteine. Thus, in some embodiments, the compositions described herein may include N-acetylcysteine ​​(NAC). NAC is readily available in the art.

[0141] L-cysteine ​​is present in the alcoholysis composition described herein in a suitable concentration or amount. Thus, the amount or concentration of L-cysteine ​​can be described by referring to the % (weight / weight) of the composition or by the total weight (e.g., mg) per dose of the composition (in other words, the weight per effective dose). As will be apparent to those skilled in the art and as described in more detail elsewhere herein, a dose can include one or more dosage units (e.g., two dosage units). In the example where multiple dosage units are used to provide an effective dose, the weight per dose corresponds to the total weight of L-cysteine ​​across the multiple dosage units.

[0142] In one embodiment, the composition comprises about 10% (w / w) L-cysteine ​​to about 40% (w / w) L-cysteine.

[0143] In another embodiment, the composition comprises from about 15% (w / w) L-cysteine ​​to about 35% (w / w) L-cysteine, hi another embodiment, the composition comprises from about 20% (w / w) L-cysteine ​​to about 30% (w / w) L-cysteine.

[0144] In one embodiment, the composition comprises at least about 10% (w / w) L-cysteine.

[0145] In another embodiment, the composition comprises at least about 15% (w / w) L-cysteine. In a further embodiment, the composition comprises at least about 20% (w / w) L-cysteine. In another embodiment, the composition comprises at least about 25% (w / w) L-cysteine. In another embodiment, the composition comprises at least about 30% (w / w) L-cysteine. In a further embodiment, the composition comprises at least about 35% (w / w) L-cysteine. In a further embodiment, the composition comprises at least about 40% (w / w) L-cysteine.

[0146] In some embodiments, the composition comprises about 10% (w / w) L-cysteine.

[0147] In another embodiment, the composition comprises about 15% (w / w) L-cysteine. In another embodiment, the composition comprises about 20% (w / w) L-cysteine. In a further embodiment, the composition comprises about 25% (w / w) L-cysteine. In another embodiment, the composition comprises about 30% (w / w) L-cysteine. In another embodiment, the composition comprises about 35% (w / w) L-cysteine. In a further embodiment, the composition comprises about 40% (w / w) L-cysteine.

[0148] In one embodiment, the composition contains about 38 mg of L-cysteine ​​per dose to about 200 mg of L-cysteine ​​per dose.

[0149] In one embodiment, the composition comprises at least about 38 mg of L-cysteine ​​per dose.

[0150] In one embodiment, the composition comprises at least about 50 mg of L-cysteine ​​per dose. In one embodiment, the composition comprises at least about 75 mg of L-cysteine ​​per dose. In one embodiment, the composition comprises at least about 100 mg of L-cysteine ​​per dose.

[0151] In one embodiment, the composition comprises at least about 150 mg of L-cysteine ​​per dose.

[0152] In one embodiment, the composition comprises at least about 160 mg of L-cysteine ​​per dose.In one embodiment, the composition comprises at least about 180 mg of L-cysteine ​​per dose.

[0153] In one embodiment, the composition contains about 38 mg of L-cysteine ​​per dose.

[0154] In one embodiment, the composition contains about 50 mg of L-cysteine ​​per dose. In one embodiment, the composition contains about 75 mg of L-cysteine ​​per dose. In one embodiment, the composition contains about 100 mg of L-cysteine ​​per dose.

[0155] In one embodiment, the composition contains about 150 mg of L-cysteine ​​per dose.

[0156] In one embodiment, the composition contains about 160 mg of L-cysteine ​​per dose.In one embodiment, the composition contains about 180 mg of L-cysteine ​​per dose.

[0157] The data presented herein show that the addition of L-cysteine ​​to a composition comprising a high molecular weight, low osmolality carbohydrate (e.g., dextrin) and one or more bacterial species of the genus Bacillus reprograms the bacteria so that they degrade alcohol more efficiently compared to the rate of alcohol degradation in the absence of L-cysteine.

[0158] Thus, the alcoholysis compositions described herein include L-cysteine ​​in combination with one or more bacterial species of the genus Bacillus and a high molecular weight, low osmolality carbohydrate (eg, dextrin).

[0159] As used herein, "high molecular weight low osmolality carbohydrate" refers to a carbohydrate with a low osmolality, having a molecular weight of about 500,000 g / mol to about 700,000 g / mol. A person skilled in the art can easily identify a suitable carbohydrate with low osmolality using routine tests known in the art. For the avoidance of doubt, as used herein, a low osmolality carbohydrate is a carbohydrate that has about 50% higher glycogen recovery than maltodextrin.

[0160] The high molecular weight low osmolality carbohydrate is present in the alcoholysis composition described herein in a suitable concentration or amount. Thus, the amount or concentration of the high molecular weight low osmolality carbohydrate can be described by referring to the % (weight / weight) of the composition, or by the total weight (e.g., mg) per dose of the composition (in other words, the weight per effective dose). As will be clear to those skilled in the art, and as described in more detail elsewhere herein, a dose can include one or more dosage units (e.g., two dosage units). In the example where multiple dosage units are used to provide an effective dose, the weight per dose corresponds to the total weight of the high molecular weight low osmolality carbohydrate across the multiple dosage units.

[0161] In one embodiment, the composition comprises about 0.5% (w / w) to about 5% (w / w) of a high molecular weight, low osmolality carbohydrate.

[0162] In another embodiment, the composition comprises from about 0.5% (w / w) to about 3% (w / w) of a high molecular weight, low osmolarity carbohydrate. In one embodiment, the composition comprises from about 0.5% (w / w) to about 2% (w / w) of a high molecular weight, low osmolarity carbohydrate.

[0163] In one embodiment, the composition comprises at least about 0.5% (w / w) of a high molecular weight, low osmolality carbohydrate.

[0164] In another embodiment, the composition comprises at least about 1% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises at least about 1.5% (w / w) high molecular weight low osmolarity carbohydrate. In a further embodiment, the composition comprises at least about 2% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises at least about 2.5% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises at least about 3% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises at least about 3.5% (w / w) high molecular weight low osmolarity carbohydrate. In a further embodiment, the composition comprises at least about 4% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises at least about 4.5% (w / w) high molecular weight low osmolarity carbohydrate. In a further embodiment, the composition comprises at least about 5% (w / w) high molecular weight low osmolarity carbohydrate.

[0165] In one embodiment, the composition comprises about 0.5% (w / w) of a high molecular weight, low osmolality carbohydrate.

[0166] In another embodiment, the composition comprises about 1% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises about 1.5% (w / w) high molecular weight low osmolarity carbohydrate. In a further embodiment, the composition comprises about 2% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises about 2.5% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises about 3% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises about 3.5% (w / w) high molecular weight low osmolarity carbohydrate. In a further embodiment, the composition comprises about 4% (w / w) high molecular weight low osmolarity carbohydrate. In another embodiment, the composition comprises about 4.5% (w / w) high molecular weight low osmolarity carbohydrate. In a further embodiment, the composition comprises about 5% (w / w) high molecular weight low osmolarity carbohydrate.

[0167] In one embodiment, the composition comprises about 2 mg to about 50 mg of high molecular weight, low osmolality carbohydrate per dose.

[0168] In one embodiment, the composition comprises at least about 2 mg of high molecular weight, low osmolality carbohydrate per dose.

[0169] In one embodiment, the composition comprises at least about 2 mg of high molecular weight, low osmolality carbohydrate per dose.

[0170] In one embodiment, the composition comprises at least about 4 mg of high molecular weight low osmolality carbohydrate per dose.

[0171] In one embodiment, the composition comprises at least about 10 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises at least about 15 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises at least about 20 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises at least about 25 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises at least about 30 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises at least about 35 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises at least about 40 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises at least about 45 mg of high molecular weight low osmolarity carbohydrate per dose.

[0172] In one embodiment, the composition comprises about 2 mg of high molecular weight, low osmolality carbohydrate per dose.

[0173] In one embodiment, the composition comprises about 4 mg of high molecular weight, low osmolality carbohydrate per dose.

[0174] In one embodiment, the composition comprises about 10 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises about 15 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises about 20 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises about 25 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises about 30 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises about 35 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises about 40 mg of high molecular weight low osmolarity carbohydrate per dose. In one embodiment, the composition comprises about 45 mg of high molecular weight low osmolarity carbohydrate per dose.

[0175] In one embodiment, the high molecular weight low osmolality carbohydrate is dextrin.

[0176] Dextrin is a general term applied to various products obtained by heating starch in the presence of small amounts of moisture and acid. Dextrins are a group of low molecular weight carbohydrates produced by hydrolysis of starch or glycogen. "Dextrin" refers to glucose polymers produced by hydrolysis of starch (or glycogen) that contain glucose units linked together mainly by α-1,4 bonds. In a particular dextrin, in addition to α-1,4 bonds, there may be a portion of α-1,6 bonds, the amount of which depends on the starch starting material. Since the biodegradation rate of α-1,6 bonds is typically lower than that of α-1,4 bonds, for many applications, it is preferred that the proportion of α-1,6 bonds is less than 10%, and more preferably less than 5%. Thus, in some embodiments, dextrins are mixtures of polymers of D-glucose units linked by α-(1→4) glycosidic bonds or α-(1→6) glycosidic bonds.

[0177] Dextrins can be produced from starch using enzymes such as amylase during human digestion, as well as during malting and saccharification, or by the application of dry heat under acidic conditions (pyrolysis or roasting). The latter process is used industrially. Dextrins produced by heat are also known as pyrodextrins. Typically, dextrins are produced by hydrolysis of starch obtained from various natural products such as wheat, rice, corn, maize, and tapioca.

[0178] Dextrins are typically white, yellow, or brown powders that are partially or completely water-soluble, resulting in low-viscosity, optically active solutions. Dextrins are available from several suppliers and can be readily sourced by those skilled in the art. Those skilled in the art will be able to readily identify suitable dextrins for use in the context of the present invention. Those skilled in the art will be able to readily detect the presence of dextrins in a substance (e.g., a composition described herein) using methods known in the art. For example, most dextrins can be detected using iodine solutions.

[0179] The term "dextrin" includes pyrodextrin, digestible dextrin, and hydrogenated products thereof (including derivatives thereof). The term "dextrin derivative" as used herein means a compound obtained by chemically or enzymatically treating dextrin, and includes, for example, in addition to the above-mentioned polydextrose, branched dextrin obtained by the action of glycosyltransferase on dextrin, and cyclodextrin obtained by the action of cyclodextrin-forming enzyme on starch.

[0180] In some embodiments, the dextrin is enzymatically treated.

[0181] In one embodiment, the dextrin, and thus the high molecular weight low osmolality carbohydrate, is cluster dextrin (also called highly branched cyclic dextrin). Cluster dextrin is a maltodextrin that has a high molecular weight but a narrow weight distribution, is soluble, and its osmolality is near zero. Typical macromolecular carbohydrates are less soluble than cluster dextrin. On the other hand, low molecular weight carbohydrates exhibit a higher osmolality, as does a pure glucose solution. This, together with other digestible contents typically found in sports drinks, slows their descent into the small intestine. Cluster dextrin reaches the small intestine faster and increases endurance more quickly. Solubility is at the core of cluster dextrin's function. High molecular weight cluster dextrin also breaks down slowly, balancing insulin secretion and lipid destruction. Cluster dextrin is manufactured by Glico Nutrition.

[0182] In some embodiments, the dextrin, and thus the high molecular weight low osmolality carbohydrate, is derived from wheat or corn (eg, in some embodiments, the dextrin is wheat dextrin or corn dextrin).

[0183] In some embodiments, the dextrin is enzyme treated wheat or corn.

[0184] In one embodiment, the dextrin is derived from wheat (e.g., wheat dextrin). For example, the dextrin can be wheat dextrin powder (such as Surbex Nutri-Fiber wheat dextrin powder, which is a soluble, non-viscous fiber).

[0185] In another embodiment, the dextrin is derived from corn (eg, corn dextrin).

[0186] In a particular embodiment, the dextrin is hydrolyzed corn dextrin (eg, Vitargo).

[0187] In some embodiments, dextrin is present in any suitable concentration or amount in the alcoholysis compositions described herein.

[0188] In one embodiment, the composition comprises from about 0.5% (w / w) to about 5% (w / w) dextrin.

[0189] In another embodiment, the composition comprises from about 0.5% (w / w) to about 3% (w / w) dextrin, hi another embodiment, the composition comprises from about 0.5% (w / w) to about 2% (w / w) dextrin.

[0190] In one embodiment, the composition comprises at least about 0.5% (w / w) dextrin.

[0191] In another embodiment, the composition comprises at least about 1% (w / w) dextrin. In another embodiment, the composition comprises at least about 1.5% (w / w) dextrin. In a further embodiment, the composition comprises at least about 2% (w / w) dextrin. In another embodiment, the composition comprises at least about 2.5% (w / w) dextrin. In another embodiment, the composition comprises at least about 3% (w / w) dextrin. In another embodiment, the composition comprises at least about 3.5% (w / w) dextrin. In a further embodiment, the composition comprises at least about 4% (w / w) dextrin. In another embodiment, the composition comprises at least about 4.5% (w / w) dextrin. In a further embodiment, the composition comprises at least about 5% (w / w) dextrin.

[0192] In one embodiment, the composition comprises about 0.5% (w / w) dextrin.

[0193] In another embodiment, the composition comprises about 1% (w / w) dextrin. In another embodiment, the composition comprises about 1.5% (w / w) dextrin. In a further embodiment, the composition comprises about 2% (w / w) dextrin. In another embodiment, the composition comprises about 2.5% (w / w) dextrin. In another embodiment, the composition comprises about 3% (w / w) dextrin. In another embodiment, the composition comprises about 3.5% (w / w) dextrin. In a further embodiment, the composition comprises about 4% (w / w) dextrin. In another embodiment, the composition comprises about 4.5% (w / w) dextrin. In a further embodiment, the composition comprises about 5% (w / w) dextrin.

[0194] In one embodiment, the composition contains from about 2 mg to about 50 mg of dextrin per dose.

[0195] In one embodiment, the composition comprises at least about 2 mg of dextrin per dose.

[0196] In one embodiment, the composition comprises at least about 4 mg of dextrin per dose.

[0197] In one embodiment, the composition comprises at least about 5 mg of dextrin per dose. In one embodiment, the composition comprises at least about 10 mg of dextrin per dose. In one embodiment, the composition comprises at least about 15 mg of dextrin per dose. In one embodiment, the composition comprises at least about 20 mg of dextrin per dose. In one embodiment, the composition comprises at least about 25 mg of dextrin per dose. In one embodiment, the composition comprises at least about 30 mg of dextrin per dose. In one embodiment, the composition comprises at least about 35 mg of dextrin per dose. In one embodiment, the composition comprises at least about 40 mg of dextrin per dose. In one embodiment, the composition comprises at least about 45 mg of dextrin per dose.

[0198] In one embodiment, the composition comprises about 2 mg of dextrin per dose.

[0199] In one embodiment, the composition comprises about 4 mg of dextrin per dose.

[0200] In one embodiment, the composition comprises about 10 mg of dextrin per dose. In one embodiment, the composition comprises about 15 mg of dextrin per dose. In one embodiment, the composition comprises about 20 mg of dextrin per dose. In one embodiment, the composition comprises about 25 mg of dextrin per dose. In one embodiment, the composition comprises about 30 mg of dextrin per dose. In one embodiment, the composition comprises about 35 mg of dextrin per dose. In one embodiment, the composition comprises about 40 mg of dextrin per dose. In one embodiment, the composition comprises about 45 mg of dextrin per dose.

[0201] In one embodiment, the compositions described herein include L-cysteine ​​and dextrin. L-cysteine ​​and dextrin may be present in any suitable concentration in the alcoholysis compositions described herein. Suitable concentrations or amounts of L-cysteine ​​and dextrin are described elsewhere herein and apply equally to the compositions described herein that include both L-cysteine ​​and dextrin. Illustrative examples of suitable concentrations or amounts are provided below.

[0202] In one embodiment, the composition comprises about 0.5% (w / w) to 5% (w / w) dextrin and about 10% (w / w) to about 40% (w / w) L-cysteine. In each of these embodiments, the composition may also comprise about 50% (w / w) to about 90% (w / w) rice bran (e.g., fermented rice bran) and / or about 10,000 cfu / g to about 15,000 cfu / g of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans).

[0203] In one example, the compositions described herein include at least about 0.5% (w / w) dextrin and at least about 10% (w / w) L-cysteine. For example, the compositions described herein may include about 0.5% (w / w) dextrin and about 10% (w / w) L-cysteine. This example corresponds to the composition tested in Test 7B of Example 1. In each of these examples, the compositions may also include at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran) and / or at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans). For example, in each of these examples, the composition may include about 67% (w / w) rice bran (e.g., about 67% (w / w) fermented rice bran) and / or 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0204] In one example, the compositions described herein include at least about 0.5% (w / w) dextrin and at least about 20% (w / w) L-cysteine. For example, the compositions described herein may include about 0.5% (w / w) dextrin and about 20% (w / w) L-cysteine. This example corresponds to the composition tested in Test 6B of Example 1. In each of these examples, the compositions may also include at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran) and / or at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans). For example, in each of these examples, the composition may include about 67% (w / w) rice bran (e.g., about 67% (w / w) fermented rice bran) and / or 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0205] In one example, the compositions described herein include at least about 0.5% (w / w) dextrin and at least about 30% (w / w) L-cysteine. For example, the compositions described herein may include about 0.5% (w / w) dextrin and about 30% (w / w) L-cysteine. This example corresponds to the composition tested in Test 5B of Example 1. In each of these examples, the compositions may also include at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran) and / or at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans). For example, in each of these examples, the composition may include about 67% (w / w) rice bran (e.g., about 67% (w / w) fermented rice bran) and / or 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0206] In one example, the compositions described herein include at least about 5% (w / w) dextrin and at least about 20% (w / w) L-cysteine. For example, the compositions described herein may include about 5% (w / w) dextrin and about 20% (w / w) L-cysteine. This example corresponds to the composition tested in Test 8B of Example 1. In each of these examples, the compositions may also include at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran) and / or at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans). For example, in each of these examples, the composition may include about 67% (w / w) rice bran (e.g., about 67% (w / w) fermented rice bran) and / or 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0207] In one embodiment, the compositions described herein comprise at least about 3% (w / w) dextrin and at least about 30% (w / w) L-cysteine. For example, the compositions described herein may comprise about 3% (w / w) dextrin and about 30% (w / w) L-cysteine. In each of these embodiments, the compositions may also comprise at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran) and / or at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans). For example, in each of these embodiments, the compositions may comprise at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran) and / or at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0208] In one embodiment, the composition comprises from about 2 mg to about 50 mg of dextrin per dose and from about 38 mg to about 200 mg of L-cysteine ​​per dose. In each of these embodiments, the composition also comprises from about 300 mg to about 600 mg of rice bran per dose (e.g., fermented rice bran / dose) and / or from about 5,000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose to about 1×10 per dose. 8 The composition may contain up to cfu of bacteria of the genus Bacillus.

[0209] In one example, the compositions described herein include at least about 2 mg of dextrin per dose and at least about 38 mg of L-cysteine ​​per dose. For example, the compositions described herein may include about 2 mg of dextrin per dose and about 38 mg of L-cysteine ​​per dose. This example corresponds to the composition tested in Study 7B of Example 1. In each of these examples, the compositions may also include at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose) and / or at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose. For example, in each of these examples, the compositions may include at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose) and / or at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose.

[0210] In one example, the compositions described herein include at least about 2 mg of dextrin and at least about 76 mg of L-cysteine ​​per dose. For example, the compositions described herein may include about 2 mg of dextrin per dose and about 76 mg of L-cysteine ​​per dose. This example corresponds to the composition tested in Study 6B of Example 1. In each of these examples, the compositions may also include at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose) and / or at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose. For example, in each of these examples, the compositions may include at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose) and / or at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose.

[0211] In one example, the compositions described herein contain at least about 2 mg of dextrin per dose and at least about 114 mg of L-cysteine ​​per dose. For example, the compositions described herein may contain about 2 mg of dextrin per dose and about 114 mg of L-cysteine ​​per dose. This example corresponds to the composition tested in Study 5B of Example 1. In each of these examples, the compositions may also contain at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose) and / or at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose. For example, in each of these examples, the composition may include about 300 mg of rice bran per dose (e.g., about 300 mg of fermented rice bran per dose) and / or 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose.

[0212] In one example, the compositions described herein include at least about 20 mg of dextrin per dose and at least about 76 mg of L-cysteine ​​per dose. For example, the compositions described herein may include about 20 mg of dextrin per dose and about 76 mg of L-cysteine ​​per dose. This example corresponds to the composition tested in Study 8B of Example 1. In each of these examples, the compositions may also include at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose) and / or at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose. For example, in each of these examples, the composition may include about 300 mg of rice bran per dose (e.g., about 300 mg of fermented rice bran per dose) and / or 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose.

[0213] High molecular weight low osmolality carbohydrates (e.g., dextrin) and / or L-cysteine ​​create a microenvironment at the cellular level, which suggests that the microbial consortium of the composition provided herein, when resuscitated in the intestinal tract, will excrete enzyme cascades that target short carbon chains, such as ethanol / alcohol, resulting in preferential targeting of these substrates.As discussed above, generally, about 80% of the alcohol intake will remain in the small intestine for a long time before being absorbed into the blood.The targeted enzymes act only on alcohol in the tract, breaking it down into carbon dioxide and water, thus avoiding the liver process of converting alcohol into acetaldehyde and acetic acid, the hangover metabolites formed by the liver's conversion of alcohol.

[0214] Upon resuscitation of Bacillus cells and their endospores, particularly in the duodenum and small intestine, the cells begin to scan the biochemical conditions of their microenvironment and secrete a unique selection of bioactive substances that optimize the conditions, e.g., pH, conductivity, electrolytes, for their survival and growth. Nutrients and substrates are essential for survival and subsequent growth. The presence of alcohol / ethanol / ethyl alcohol in the microenvironment results in the excretion of alcohol-targeting enzymes, which break the alcohol down into carbon-containing fragments. Carbon that cannot be used as a nutrient by the microorganism or nearby tissue cells will be biochemically metabolized into water and carbon dioxide, which can exit the body system without any biological consequences / symptoms. It is suggested that high molecular weight low osmolality carbohydrates (e.g., dextrins) and / or L-cysteine ​​enhance this environmental screening and selective excretion of bioactive substances, optimizing the enzymatic conditions.

[0215] As mentioned elsewhere herein, the alcoholyzed compositions described herein may include cereals (e.g., grains), such as rice bran. A grain is any grass that is cultivated (grown) for the edible components of the grain (botanically, a type of fruit called a cereal) that is composed of endosperm, germ, and bran. The term grain may also refer to the resulting grain itself (specifically, the "grain"). Grains are seeds obtained from grasses, such as wheat, millet, rice, barley, oats, rye, triticale, sorghum, and maize (corn).

[0216] In some embodiments, the alcoholyzed compositions described herein may include a grain (e.g., a cereal grain) selected from the group consisting of wheat, millet, rice, barley, oats, rye, triticale, sorghum, and maize (corn). A person skilled in the art would be able to readily identify suitable grains (e.g., a cereal grain) for use in the compositions described herein.

[0217] Bran, also known as milled bran, is the tough outer layer of the grain. It includes the aleurone and the pericarp. Corn (maize) bran also includes the pedicels (top caps). Bran is an integral part of the whole grain along with the germ and is often produced as a milling by-product in the production of refined grains. Bran is present in grains including rice, corn (maize), wheat, oats, barley, rye, and millet.

[0218] Thus, in some embodiments, the alcoholyzed compositions described herein may include cereal bran. In some embodiments, the alcoholyzed compositions described herein may include cereal bran selected from the group consisting of rice bran, corn (maize) bran, wheat bran, oat bran, barley bran, rye bran, and millet bran.

[0219] In some embodiments, the alcoholysis compositions described herein may include oat bran.

[0220] In some embodiments, the alcoholysis compositions described herein may include rice bran.

[0221] Rice bran is a by-product of the rice milling process. Generally, milling results in about 15% (wt / wt) broken rice kernels, about 10% (wt / wt) rice bran, about 20% hulls, and about 55% (wt / wt) whole grains. The composition of rice bran (by weight percentage) is generally 11%-13% water, 18%-21% crude oil, 14%-16% crude protein, 8%-10% crude fiber, 9%-12% ash, and 33%-36% carbohydrate. Rice bran contains naturally occurring lipases that hydrolyze oil to glycerol and free fatty acids, which give the product a rancid odor and taste. As used herein, "rice bran" refers to the tough outer layer of rice, including aleurone and pericarp. Rice bran is an integral part of whole rice along with the germ, and, as mentioned above, is often produced as a by-product of rice milling in the production of polished rice.

[0222] The alcoholyzed compositions described herein may include rice bran in any suitable form. Suitable forms include raw rice bran, freshly milled (unhydrolyzed) full-fat rice bran, low-fat rice bran, defatted rice bran, fermented rice bran, stabilized rice bran, and the like. Raw rice bran is rice bran obtained after milling. Low-fat rice bran and defatted rice bran are obtained from full-fat rice bran, such as by solvent extraction. Full-fat rice bran has a fat content of about 14% to about 18% by weight, while low-fat rice bran and defatted rice bran contain about 3% to about 14% and less than 3% fat, respectively, by weight.

[0223] In one embodiment, the rice bran is formulated as raw rice bran, freshly milled (non-hydrolyzed) full fat rice bran, reduced fat rice bran, defatted rice bran, fermented rice bran, and / or stabilized rice bran.

[0224] In another more preferred embodiment, the rice bran is formulated as fermented rice bran and / or stabilized rice bran.

[0225] In a further embodiment, the rice bran is fermented rice bran. The rice bran undergoes a natural / spontaneous fermentation process by naturally occurring microbial strains, typically those found in soil, such as Bacillus and Pediococcus.

[0226] As used herein, "fermented rice bran" refers to rice bran that has undergone a fermentation process. Fermented rice bran contains probiotic microorganisms that stabilize the microflora of the small intestine.

[0227] As used herein, "stabilized rice bran" refers to rice bran that has been heated for a short time, for example by passing it through a high-temperature, high-pressure extruder. Heat stabilizes the rice bran. In other words, therefore, "stabilized rice bran" is rice bran that has been heat-treated. For example, rice bran can be stabilized by heating the rice bran at 130 degrees Celsius for less than 10 seconds after milling. In some embodiments, the stabilized rice bran is a dietary fiber. Typically, the stabilized rice bran is a dietary fiber that can be catabolized in the colon. As a dietary fiber, the stabilized rice bran is a prebiotic that interacts with the colonic microflora.

[0228] The microbial content of fermented rice bran may have a probiotic and stabilizing effect on the small intestinal microflora, and rice bran, being a dietary fiber, stabilizes conditions in the colon. Another mechanism of action may be the reduction of intestinal oxidative stress, which may normalize the barrier function of the intestinal mucosa and result in less alcohol absorption.

[0229] Rice bran (e.g., fermented rice bran) is present in the alcoholysis (e.g., alcohol metabolism) compositions described herein in suitable amounts or concentrations as described below. Thus, the amount or concentration of rice bran can be described by reference to the % (w / w) of the composition or by the total weight (e.g., mg) per dose of the composition (in other words, the weight per effective dose). As will be apparent to one of skill in the art and as described in more detail elsewhere herein, a dose can include one or more dosage units (e.g., two dosage units). In instances where multiple dosage units are used to provide an effective dose, the weight per dose corresponds to the total weight of rice bran across the multiple dosage units.

[0230] In one embodiment, the composition comprises about 50% (w / w) to about 90% (w / w) rice bran.

[0231] In another embodiment, the composition comprises from about 60% (w / w) to about 80% (w / w) rice bran. In another embodiment, the composition comprises from about 73% (w / w) to about 79% (w / w) rice bran.

[0232] In one embodiment, the composition comprises at least about 50% (w / w) rice bran. In another embodiment, the composition comprises at least about 55% (w / w) rice bran. In one embodiment, the composition comprises at least about 60% (w / w) rice bran. In a further embodiment, the composition comprises at least about 65% (w / w) rice bran. In one embodiment, the composition comprises at least about 73% (w / w) rice bran. In one embodiment, the composition comprises at least about 75% (w / w) rice bran. In one embodiment, the composition comprises at least about 79% (w / w) rice bran. In a further embodiment, the composition comprises at least about 85% (w / w) rice bran. In one embodiment, the composition comprises at least about 90% (w / w) rice bran.

[0233] In one embodiment, the composition comprises about 50% (w / w) rice bran. In another embodiment, the composition comprises about 55% (w / w) rice bran. In one embodiment, the composition comprises about 60% (w / w) rice bran. In a further embodiment, the composition comprises about 65% (w / w) rice bran. In one embodiment, the composition comprises about 73% (w / w) rice bran. In one embodiment, the composition comprises about 75% (w / w) rice bran. In one embodiment, the composition comprises about 79% (w / w) rice bran. In a further embodiment, the composition comprises about 85% (w / w) rice bran. In one embodiment, the composition comprises about 90% (w / w) rice bran.

[0234] In certain embodiments, the composition comprises at least about 67% (w / w) rice bran.

[0235] For example, the composition may include about 67% (w / w) rice bran.

[0236] In certain examples, the composition comprises at least about 73% (w / w) rice bran. For example, the composition may comprise about 73% (w / w) rice bran.

[0237] In another embodiment, the composition comprises at least about 79% (w / w) rice bran. For example, the composition may comprise about 79% (w / w) rice bran.

[0238] In another embodiment, the composition comprises at least about 79.5% (w / w) rice bran. For example, the composition may comprise about 79.5% (w / w) rice bran.

[0239] In one example, the composition contains at least about 300 mg of rice bran (e.g., fermented rice bran) per dose. As described elsewhere herein, a dose may be formulated as two capsules.

[0240] In one embodiment, the composition comprises at least about 300 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises at least about 350 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises at least about 400 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises at least about 450 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises at least about 500 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises at least about 550 mg of rice bran (e.g., fermented rice bran) per dose.

[0241] In one embodiment, the composition comprises about 300 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises about 350 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises about 400 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises about 450 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises about 500 mg of rice bran (e.g., fermented rice bran) per dose. In one embodiment, the composition comprises about 550 mg of rice bran (e.g., fermented rice bran) per dose.

[0242] As discussed elsewhere herein, an alcoholysis composition is provided that includes one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans), rice bran (e.g., fermented rice bran), L-cysteine, and high molecular weight low osmolality carbohydrates (e.g., dextrin). One or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans), rice bran (e.g., fermented rice bran), L-cysteine, and high molecular weight low osmolality carbohydrates (e.g., dextrin) may be present in any suitable amount or concentration in the alcoholysis composition described herein. Suitable amounts and concentrations of one or more bacterial species of the genus Bacillus (e.g., B. subtilis and / or B. coagulans), rice bran (e.g., fermented rice bran), L-cysteine, and high molecular weight low osmolality carbohydrates (e.g., dextrin) are described elsewhere herein. Illustrative examples of suitable concentrations are provided below.

[0243] In one embodiment, the composition comprises about 0.5% (w / w) to 5% (w / w) dextrin, about 10% (w / w) to about 40% (w / w) L-cysteine, about 50% (w / w) to about 90% (w / w) rice bran (e.g., fermented rice bran), and about 10,000 cfu / g to about 15,000 cfu / g of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans).

[0244] In one example, the compositions described herein comprise at least about 0.5% (w / w) dextrin, at least about 10% (w / w) L-cysteine, at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran), and at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0245] In one example, the compositions described herein comprise at least about 0.5% (w / w) dextrin, at least about 20% (w / w) L-cysteine, at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran), and at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0246] In one example, the compositions described herein comprise at least about 0.5% (w / w) dextrin, at least about 30% (w / w) L-cysteine, at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran), and at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0247] In one example, the compositions described herein comprise at least about 5% (w / w) dextrin, at least about 20% (w / w) L-cysteine, at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran), and at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0248] In one example, the compositions described herein comprise at least about 3% (w / w) dextrin, at least about 30% (w / w) L-cysteine, at least about 67% (w / w) rice bran (e.g., at least about 67% (w / w) fermented rice bran), and at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans).

[0249] In one embodiment, the composition comprises about 2 mg to about 50 mg of dextrin per dose, about 38 mg to about 200 mg of L-cysteine ​​per dose, about 300 mg to about 600 mg of rice bran per dose (e.g., fermented rice bran / dose), and about 5,000 cfu of bacteria of the genus Bacillus (e.g., B. subtilis and / or B. coagulans) per dose to about 1×10 per dose. 8 Contains cfu of Bacillus spp.

[0250] In one example, the compositions described herein include at least about 2 mg of dextrin per dose, at least about 38 mg of L-cysteine ​​per dose, at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose), and at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose.

[0251] In one example, the compositions described herein include at least about 2 mg dextrin, at least about 76 mg L-cysteine ​​per dose, at least about 300 mg rice bran per dose (e.g., at least about 300 mg fermented rice bran per dose), and at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose.

[0252] In one example, the compositions described herein include at least about 2 mg of dextrin per dose, at least about 114 mg of L-cysteine ​​per dose, at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose), and at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose.

[0253] In one example, the compositions described herein include at least about 20 mg of dextrin per dose, at least about 76 mg of L-cysteine ​​per dose, at least about 300 mg of rice bran per dose (e.g., at least about 300 mg of fermented rice bran per dose), and at least 5000 cfu of Bacillus bacteria (e.g., B. subtilis and / or B. coagulans) per dose.

[0254] A composition of 79.5% (w / w) fermented rice bran (containing one or more bacterial species of the genus Bacillus), 0.5% (w / w) dextrin, and 20.0% (w / w) L-cysteine ​​has been evaluated to be particularly effective in alcohol digestion in the intestinal tract, digesting alcohol about 50% faster than the liver digests alcohol, as described in the Examples below. Thus, in certain examples, the compositions described herein include about 79.5% (w / w) fermented rice bran (containing one or more bacterial species of the genus Bacillus), about 0.5% (w / w) dextrin, and about 20.0% (w / w) L-cysteine.

[0255] The alcoholysis composition described herein may include one or more additional components, such as one or more additional ingredients. For example, the composition described herein may further include an emulsifier, a filler, and / or an inactive ingredient. Those skilled in the art will easily understand what "emulsifier", "filler", and "inactive ingredient" mean in the context of the compositions provided herein. Non-limiting examples of additional components include vitamin B12, fatty acid magnesium salt (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose).

[0256] The additional components described herein may be in any suitable form, the suitable form being readily identifiable by one of ordinary skill in the art.

[0257] Thus, in one embodiment, the alcoholysis composition described herein may further comprise one or more of vitamin B12, fatty acid magnesium salt (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose). In another embodiment, the alcoholysis composition described herein may further comprise two or more of vitamin B12, fatty acid magnesium salt (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose). In another embodiment, the alcoholysis composition described herein may further comprise three or more of vitamin B12, fatty acid magnesium salt (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose). In another embodiment, the alcoholysis composition described herein may further comprise four or more of vitamin B12, fatty acid magnesium salt (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose).

[0258] In one embodiment, the alcoholysis compositions described herein further comprise vitamin B12, a magnesium salt of a fatty acid (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose).

[0259] An example of a fatty acid magnesium salt includes magnesium stearate. Thus, in one embodiment, the composition described herein may further include magnesium stearate. Magnesium stearate is a magnesium salt of stearic acid, a fatty acid. Magnesium salts of fatty acids (e.g., magnesium stearate) may be excipients, inactive ingredients, and / or may be used as lubricants for manufacturing machinery. Magnesium stearate is a GRAS listed ingredient.

[0260] In some embodiments, Vitamin B12 is added for regulatory purposes.

[0261] In some embodiments, the magnesium salts (e.g., magnesium stearate), calcium salts, and / or potassium salts are non-active ingredients (e.g., they have no clinical effect). For example, the magnesium salts (e.g., magnesium stearate), calcium salts, and / or potassium salts can be added as filling aids (e.g., bulking agents), which help capsule filling machines operate efficiently.

[0262] In one embodiment, the compositions described herein further comprise microcrystalline cellulose. Microcrystalline cellulose can be used as an emulsifier, a filler, and / or a non-active ingredient. Microcrystalline cellulose (and also maltodextrin) can be used as a mass forming excipient in tablet compression and as a flow agent in capsule formulations. In some embodiments, the compositions described herein further comprise maltodextrin.

[0263] In one embodiment, the composition comprises from about 5% (w / w) to about 50% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises from about 5% (w / w) to about 35% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises from about 5% (w / w) to about 20% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises from about 5% (w / w) to about 15% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises from about 5% (w / w) to about 8% (w / w) microcrystalline cellulose.

[0264] In one embodiment, the composition comprises at least about 5% (w / w) microcrystalline cellulose. In one embodiment, the composition comprises at least about 8% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises at least about 10% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises at least about 15% (w / w) microcrystalline cellulose. In a further embodiment, the composition comprises at least about 20% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises at least about 25% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises at least about 30% (w / w) microcrystalline cellulose. In yet a further embodiment, the composition comprises at least about 35% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises at least about 40% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises at least about 45% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises at least about 50% (w / w) microcrystalline cellulose.

[0265] In one embodiment, the composition comprises about 5% (w / w) microcrystalline cellulose. In one embodiment, the composition comprises about 8% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises about 10% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises about 15% (w / w) microcrystalline cellulose. In a further embodiment, the composition comprises about 20% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises about 25% (w / w) microcrystalline cellulose. In yet a further embodiment, the composition comprises about 30% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises about 35% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises about 40% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises about 45% (w / w) microcrystalline cellulose. In another embodiment, the composition comprises about 50% (w / w) microcrystalline cellulose.

[0266] In one embodiment, the compositions described herein contain at least about 30 mg of microcrystalline cellulose per dose, which may be formulated into two capsules, as described elsewhere herein.

[0267] In one embodiment, the compositions described herein contain at least about 40 mg of microcrystalline cellulose per dose. In one embodiment, the compositions described herein contain at least about 50 mg of microcrystalline cellulose per dose. In one embodiment, the compositions described herein contain at least about 60 mg of microcrystalline cellulose per dose. In one embodiment, the compositions described herein contain at least about 70 mg of microcrystalline cellulose per dose. In one embodiment, the compositions described herein contain at least about 80 mg of microcrystalline cellulose per dose. In one embodiment, the compositions described herein contain at least about 90 mg of microcrystalline cellulose per dose. In one embodiment, the compositions described herein contain at least about 100 mg of microcrystalline cellulose per dose.

[0268] In one embodiment, the compositions described herein further comprise magnesium stearate, which may be used as an emulsifier, a filling aid, and / or a non-active ingredient.

[0269] In one embodiment, the composition comprises from about 0.2% (w / w) to about 1.5% (w / w) magnesium stearate. In another embodiment, the composition comprises from about 0.5% (w / w) to about 1.4% (w / w) magnesium stearate. In another embodiment, the composition comprises from about 0.6% (w / w) to about 1.3% (w / w) magnesium stearate.

[0270] In one embodiment, the composition comprises at least about 0.2% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 0.3% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 0.4% (w / w) magnesium stearate. In a further embodiment, the composition comprises at least about 0.5% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 0.6% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 0.7% (w / w) magnesium stearate. In yet a further embodiment, the composition comprises at least about 0.8% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 0.9% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 1.0% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 1.1% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 1.2% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 1.3% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 1.4% (w / w) magnesium stearate. In another embodiment, the composition comprises at least about 1.5% (w / w) magnesium stearate.

[0271] In one embodiment, the composition comprises about 0.2% (w / w) magnesium stearate. In another embodiment, the composition comprises about 0.3% (w / w) magnesium stearate. In another embodiment, the composition comprises about 0.4% (w / w) magnesium stearate. In a further embodiment, the composition comprises about 0.5% (w / w) magnesium stearate. In another embodiment, the composition comprises about 0.6% (w / w) magnesium stearate. In another embodiment, the composition comprises about 0.7% (w / w) magnesium stearate. In yet a further embodiment, the composition comprises about 0.8% (w / w) magnesium stearate. In another embodiment, the composition comprises about 0.9% (w / w) magnesium stearate. In another embodiment, the composition comprises about 1.0% (w / w) magnesium stearate. In another embodiment, the composition comprises about 1.1% (w / w) magnesium stearate. In another embodiment, the composition comprises about 1.2% (w / w) magnesium stearate. In another embodiment, the composition comprises about 1.3% (w / w) magnesium stearate. In another embodiment, the composition comprises about 1.4% (w / w) magnesium stearate. In another embodiment, the composition comprises about 1.5% (w / w) magnesium stearate.

[0272] In one embodiment, the compositions described herein contain at least about 4 mg of magnesium stearate per dose, which may be formulated into two capsules, as described elsewhere herein.

[0273] In one embodiment, the compositions described herein contain at least about 5 mg of magnesium stearate per dose. In one embodiment, the compositions described herein contain at least about 6 mg of magnesium stearate per dose. In one embodiment, the compositions described herein contain at least about 7 mg of magnesium stearate per dose. In one embodiment, the compositions described herein contain at least about 8 mg of magnesium stearate per dose. In one embodiment, the compositions described herein contain at least about 9 mg of magnesium stearate per dose. In one embodiment, the compositions described herein contain at least about 10 mg of magnesium stearate per dose.

[0274] In one embodiment, the compositions described herein further comprise silicon dioxide, which may be used as an emulsifier, a loading aid, and / or a non-active ingredient.

[0275] In one embodiment, the composition comprises from about 0.5% (w / w) to about 4% (w / w) silicon dioxide. In another embodiment, the composition comprises from about 0.7% (w / w) to about 3% (w / w) silicon dioxide. In another embodiment, the composition comprises from about 0.9% (w / w) to about 2% (w / w) silicon dioxide.

[0276] In one embodiment, the composition comprises at least about 0.5% (w / w) silicon dioxide. In another embodiment, the composition comprises at least about 1% (w / w) silicon dioxide. In another embodiment, the composition comprises at least about 1.5% (w / w) silicon dioxide. In a further embodiment, the composition comprises at least about 2% (w / w) silicon dioxide. In another embodiment, the composition comprises at least about 2.5% (w / w) silicon dioxide. In another embodiment, the composition comprises at least about 3% (w / w) silicon dioxide. In yet a further embodiment, the composition comprises at least about 3.5% (w / w) silicon dioxide. In another embodiment, the composition comprises at least about 4% (w / w) silicon dioxide.

[0277] In one embodiment, the composition comprises about 0.5% (w / w) silicon dioxide. In another embodiment, the composition comprises about 1% (w / w) silicon dioxide. In another embodiment, the composition comprises about 1.5% (w / w) silicon dioxide. In a further embodiment, the composition comprises about 2% (w / w) silicon dioxide. In another embodiment, the composition comprises about 2.5% (w / w) silicon dioxide. In another embodiment, the composition comprises about 3% (w / w) silicon dioxide. In yet a further embodiment, the composition comprises about 3.5% (w / w) silicon dioxide. In another embodiment, the composition comprises about 4% (w / w) silicon dioxide.

[0278] In one embodiment, the compositions described herein contain at least about 4 mg of silicon dioxide per dose. As described elsewhere herein, a dose may be formulated in two capsules.

[0279] In one embodiment, the compositions described herein contain at least about 5 mg of silicon dioxide per dose.In one embodiment, the compositions described herein contain at least about 6 mg of silicon dioxide per dose.In one embodiment, the compositions described herein contain at least about 7 mg of silicon dioxide per dose.In one embodiment, the compositions described herein contain at least about 8 mg of silicon dioxide per dose.

[0280] In one embodiment, the compositions described herein further comprise vitamin B12. For regulatory purposes, vitamin B12 may be included in the compositions described herein. In one embodiment, the compositions comprise at least 15% of the Recommended Daily Intake (RDI), i.e., 0.38mcg to 2.4mcg (for the EU) and 2.5mcg for the US.

[0281] In one embodiment, the compositions described herein contain at least about 0.76 μg (mcg) of vitamin B12 per dose. In one embodiment, the compositions described herein contain at least about 0.9 μg (mcg) of vitamin B12 per dose.

[0282] The composition may be formulated in any suitable form. For example, the composition may be in the form of a tablet or capsule. In one embodiment, the composition is formulated as an acid-resistant tablet or capsule. In general, "capsule" refers to both empty and filled capsules, while "shell" refers specifically to an empty capsule, unless the context requires otherwise.

[0283] In some embodiments, the compositions described herein are contained within a capsule (e.g., within a shell). In some embodiments, the compositions described herein are contained within an acid-resistant capsule (e.g., within an acid-resistant shell). As will be apparent to those skilled in the art, when referring to the % (wt / wt) of an ingredient present within a composition, this does not take into account any weight attributable to the capsule (and therefore only takes into account the % (wt / wt) of the composition within the capsule).

[0284] In one embodiment, the acid-resistant tablet or capsule is provided with a film coating, where the film coating comprises hydroxypropylmethylcellulose (HPMC). HPMC is a semi-synthetic, inert, viscoelastic polymer that is used in a variety of applications. For example, HPMC may be used as an excipient in oral tablet and capsule formulations, where, depending on the grade, it acts as a controlled release agent that delays the release of pharmaceutical compounds into the digestive tract. In tablets, HPMC may also be used as a binder and / or as a component of tablet coating.

[0285] In one embodiment, the compositions described herein are contained within a (capsule) shell, wherein the shell comprises hydroxypropyl methylcellulose (HPMC).

[0286] Those of skill in the art will understand the meaning of "acid-resistant" in the context of the present invention, particularly within the context of the ingestible compositions described herein. For example, the compositions described herein may be formulated as acid-resistant tablets or capsules, or may be contained within an acid-resistant capsule (e.g., an acid-resistant shell) that dissolves upon reaching the duodenum, thus releasing microbial cells and spores, which can then colonize the upper intestinal tract.

[0287] In one embodiment, the composition is present in a capsule, wherein the capsule comprises about 80 mg to about 100 mg of HPMC. For example, the capsule may comprise at least about 80 mg of HPMC. In one embodiment, the capsule comprises at least about 90 mg of HPMC. In one embodiment, the capsule comprises at least about 100 mg of HPMC. In one embodiment, the capsule comprises about 80 mg of HPMC. In one embodiment, the capsule comprises about 90 mg of HPMC. In another embodiment, the capsule comprises about 100 mg of HPMC.

[0288] Typically, the HPMC is present as a film coating on the exterior surface of the capsules described herein.

[0289] The compositions described herein may be in unit dosage form. When the compositions described herein are in unit dosage form, one tablet or capsule may be administered and constitute one dose, or alternatively, two tablets or capsules may be administered and constitute one dose. The appropriate dosage and administration schedule can be determined by those skilled in the art based on the following examples. Thus, in one embodiment, one dose of the composition according to the present invention includes several small tablets or capsules (e.g., two).

[0290] The term "dosage form" as used herein refers to an amount of a drug taken at one time, optionally at regular intervals, which is also referred to herein as a "dose."

[0291] In one embodiment, the present invention provides a solid unit dosage form for oral administration.

[0292] In a specific embodiment, one dose of the composition described herein comprises about 300 mg fermented rice bran, about 38 mg L-cysteine, about 30 mg microcrystalline cellulose, about 4 mg magnesium stearate, about 4 mg silicon dioxide, about 2 mg dextrin, about 0.76 μg (mcg) vitamin B12, and about 5000 cfu of Bacillus bacteria. In this specific embodiment, this dose can be formulated as two tablets or capsules. In other words, the amount of components can represent the total amount of components present in this dose (i.e., two tablets or capsules). This corresponds to the composition used in Test 7B of Example 1. Therefore, a person skilled in the art will understand that at least each of these components, at least in these amounts, represents an effective dose according to the present invention. Thus, in one example, a dose of the compositions described herein comprises at least about 300 mg fermented rice bran, at least about 38 mg L-cysteine, at least about 30 mg microcrystalline cellulose, at least about 4 mg magnesium stearate, at least about 4 mg silicon dioxide, at least about 2 mg dextrin, at least about 0.76 μg (mcg) vitamin B12, and at least about 5000 cfu of bacteria of the genus Bacillus.

[0293] In a specific embodiment, one dose of the composition described herein comprises about 552 mg of fermented rice bran, about 150 mg of L-cysteine, about 40 mg of microcrystalline cellulose, about 4.8 mg of magnesium stearate, about 4 mg of silicon dioxide, about 4 mg of dextrin, about 0.9 μg (mcg) of vitamin B12, and about 100,000 cfu of bacteria of the genus Bacillus. In this specific embodiment, the dose can be formulated as two tablets or capsules. In other words, the amount of the components can represent the total amount of the components present in the dose (i.e., two tablets or capsules). Thus, a person skilled in the art will understand that at least each of these components, at least in these amounts, represents an effective dose according to the present invention. Thus, in one example, a dose of the composition described herein comprises at least about 552 mg of fermented rice bran, at least about 150 mg of L-cysteine, at least about 40 mg of microcrystalline cellulose, at least about 4.8 mg of magnesium stearate, at least about 4 mg of silicon dioxide, at least about 4 mg of dextrin, at least about 0.9 μg (mcg) of vitamin B12, and at least about 100,000 cfu of bacteria of the genus Bacillus.

[0294] Typically, the HPMC is present as a film coating on the exterior surface of the capsules described herein.

[0295] The compositions described herein may be used (or be used as part of) a dietary supplement, a functional food, a food composition, a medical food, or a medicine.

[0296] The term "dietary supplement" or "supplement" as used herein refers to a composition consumed in addition to or between meals on a daily basis.

[0297] The term "food composition" as used herein refers to any type of composition that can be eaten and / or drunk without causing toxic symptoms in a subject eating or drinking the respective composition.

[0298] Thus, provided herein is the use of the compositions described herein to break down alcohol. The term "break down alcohol" is explained elsewhere herein and applies here as well.

[0299] The composition may be used to break down alcohol in a subject (e.g., the use may be in vivo). The subject may be any suitable subject, for example, the subject may be a human. The subject may be a human who will consume alcohol or has consumed alcohol.

[0300] In one embodiment, the composition may be used to metabolize alcohol in the digestive tract of a subject. The term "metabolizing alcohol" is explained elsewhere herein and applies here as well. In one embodiment, the composition may be used to metabolize alcohol in the intestine of a subject. In a particular embodiment, the composition may be used to metabolize alcohol in the small intestine of a subject. More specifically, the composition may be used to metabolize alcohol in the duodenum of a subject.

[0301] In one embodiment, the composition can be used to reduce the absorption of alcohol into the blood of a subject. A person skilled in the art can use methods known in the art (e.g., the methods described in the Examples section below) to confirm the reduction in the absorption of alcohol into the blood in the presence of the composition provided herein (compared to the absence of the composition).

[0302] When the composition is used to break down alcohol in a subject, it can be used to reduce the breath alcohol concentration or blood alcohol concentration in the subject.Those skilled in the art can use methods known in the art (e.g., the methods described in the Examples section below) to confirm the reduction of breath alcohol concentration or blood alcohol concentration in the presence of the composition provided herein (compared to the absence of the composition).For example, those skilled in the art can easily confirm the reduction of breath alcohol concentration or blood alcohol concentration in the presence of the composition provided herein (compared to the absence of the composition) about 30 minutes after alcohol intake (alcohol consumption) using methods known in the art (e.g., the methods described in the Examples section below).

[0303] Using L-cysteine ​​to enhance alcohol metabolism Provided herein is the use of L-cysteine ​​to enhance alcohol decomposition by one or more species of bacteria of the genus Bacillus.L-cysteine ​​can be used in vitro or in vivo to enhance alcohol decomposition.For example, when L-cysteine ​​is used (or used as part of) a dietary supplement, functional food, medical food, or medicine, it can be used to enhance alcohol decomposition by one or more species of bacteria of the genus Bacillus.

[0304] The terms "L-cysteine," "alcohololysis," and "one or more bacterial species of the genus Bacillus" are defined elsewhere herein with examples of what is encompassed by these terms, and those definitions and embodiments apply here as well.

[0305] One of skill in the art would be able to confirm increased alcohol breakdown in the presence of L-cysteine ​​(compared to the absence of L-cysteine) using methods known in the art (e.g., the methods described in the Examples section below).

[0306] In a specific embodiment, L-cysteine ​​can be used to enhance alcohol degradation by one or more bacterial species of the genus Bacillus selected from B. subtilis and B. coagulans. As described elsewhere herein, the one or more bacterial species of the genus Bacillus can include B. subtilis. Alternatively, the one or more bacterial species of the genus Bacillus can include B. coagulans. In an embodiment, the one or more bacterial species of the genus Bacillus can include B. subtilis and B. coagulans. Characteristics of these bacterial species are described elsewhere herein and apply to this embodiment as well.

[0307] Suitable concentrations, amounts, ratios, etc. of one or more bacterial species of the Bacillus genus are described elsewhere herein and apply equally to this embodiment.

[0308] In one particular embodiment, L-cysteine ​​can be used to enhance alcohol degradation by one or more bacterial species of the genus Bacillus when the alcohol is ethyl alcohol.

[0309] In one embodiment, when used to enhance alcohol degradation by one or more bacterial species of the genus Bacillus, L-cysteine ​​can be combined with a high molecular weight, low osmolality carbohydrate, such as dextrin. Additionally or alternatively, L-cysteine ​​can be combined with rice bran.

[0310] In one example, L-cysteine, when used (or used as part of) a dietary supplement, functional food, or medical food (e.g., when it is part of a composition described herein), can be used to enhance alcohol degradation by one or more bacterial species of the genus Bacillus.

[0311] Treatment Methods and Uses As described elsewhere herein, the compositions described herein may be used in vitro or in vivo to degrade alcohol, and thus the compositions described herein may be used as medicines.

[0312] In one embodiment, the compositions described herein can be used as medicines to break down alcohol in a subject. The compositions provided herein can be particularly advantageous, for example, for preventing and / or treating alcohol-induced organ damage in a subject. For example, the compositions provided herein can be useful for preventing and / or treating alcohol-induced damage to the liver and / or pancreas of a subject.

[0313] As used herein, "alcohol-induced organ damage" includes both acute and chronic alcohol-induced organ damage. Typically, alcohol-induced damage involves inflammation and / or inflammatory disease that causes dysfunction of internal organs and tissues, leading to severe secondary, sometimes life-threatening, diseases. The liver is the primary site of ethanol metabolism and therefore suffers the greatest degree of tissue damage from heavy alcohol consumption. For example, chronic and excessive alcohol consumption causes a wide range of liver lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis / cirrhosis. Steatosis is the earliest response to heavy alcohol consumption and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, a more severe inflammatory type of liver damage. This stage of liver disease can lead to the development of fibrosis, during which excessive deposition of extracellular matrix proteins is seen. The fibrotic response begins with active pericellular fibrosis and can progress to cirrhosis, characterized by excessive liver scarring, vascular changes, and eventual liver failure.

[0314] Other examples of alcohol-induced injury include pancreatitis, both acute and chronic. Pancreatitis is defined as inflammation of the pancreas, leading to damage and dysfunction of the retroperitoneal organ. There are various etiologies of pancreatitis, the most common being alcohol and gallstones. Acute pancreatitis (AP) is a necrotizing inflammatory disease resulting from destruction of exocrine cells by infiltrating inflammatory cells. Diagnostic criteria are typically when patients present with characteristic symptoms, elevated lipase levels, and clear imaging findings. Acute pancreatitis either resolves with complete regeneration of the pancreas, causes temporary organ failure, or progresses to cause systemic inflammation and multi-organ failure. Chronic pancreatitis (CP) is thought to result from recurrent attacks of acute pancreatitis, leading to pancreatic insufficiency, steatorrhea, diabetes, pancreatic calcification, and fibrosis. Alcohol predisposes the pancreas to injury from otherwise harmless agents. As a result, one of the main strategies to prevent recurrent attacks involves providing patients with alcohol abstinence (and smoking cessation) counseling and strategies.

[0315] The compositions provided herein may be useful for preventing and / or treating a disease, condition, or illness selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, cirrhosis, alcohol-induced cancer, cardiovascular conditions, obesity, neurological disorders, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache, and / or acetaldehyde poisoning. In one embodiment, the compositions provided herein may be useful for preventing and / or treating a disease, condition, or illness selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, cirrhosis, and alcohol-induced cancer.

[0316] Alcohol-induced fatty liver is also referred to herein as alcoholic fatty liver. Similarly, alcohol-induced hepatitis is also referred to herein as alcoholic hepatitis.

[0317] Examples of alcohol-induced cancers are well known in the art and include liver cancer, pancreatic cancer, breast cancer, esophageal cancer, and oropharyngeal cancer. The term "oropharyngeal cancer" as used herein refers to cancer originating from the oral cavity, pharynx, larynx, or upper esophagus. At early stages of cancer in this region, it is possible to identify its origin. However, cancers in this site are very often found at a later stage of invasion, and its origin cannot be determined. Thus, cancers originating from this source are collectively referred to as "oropharyngeal cancer". A person skilled in the art would be able to easily identify the cancers associated with the various parts of the body as described above.

[0318] The term "neuropathy" as used herein refers to any disease or abnormality of neurons in the nervous system. In particular, "neuropathy" refers to damage to the peripheral nervous system that affects nerves anywhere except the brain and spinal cord. A non-limiting example of neuropathy is alcoholic polyneuropathy, which is characterized by numbness, abnormal sensations called paresthesia and allodynia that occur either spontaneously or in response to external stimuli, and a characteristic form of pain called neuropathic pain or neuralgia.

[0319] The term "neurodegenerative disease" as used herein refers to any disease or abnormality of the nervous system caused by neuronal deterioration, including neuronal death and neurotransmitter function loss.Non-limiting examples of neurodegenerative disease are Alzheimer's disease (e.g., late-onset Alzheimer's disease) and Parkinson's disease.The term "late-onset Alzheimer's disease" as used herein refers to the onset of Alzheimer's disease in elderly people, particularly people aged 65 or older.

[0320] In one embodiment, the neurodegenerative disease is Alzheimer's disease, and optionally, the neurodegenerative disease is late-onset Alzheimer's disease.

[0321] As used herein, "hangover" refers to the general discomfort that typically occurs when a person wakes up after (excessively) drinking (e.g., consuming and / or ingesting) alcohol. In other words, a hangover is the result of intoxication of an organism caused by the consumption of (excessive amounts of) alcohol. A hangover is a set of symptoms that occurs the day after drinking too much alcohol and may be worse if the person smokes excessively. The organism protects itself from intoxication by secreting enzymes that metabolize and excrete toxins. However, if alcohol is consumed in excess, the organism's ability to metabolize alcohol decreases and the symptoms of a hangover appear. "Hangover symptoms" include headaches caused by the dilation of blood vessels caused by the accumulation of histamine, bloodshot eyes, occasional memory loss, vomiting, possible flatulence, intense thirst that begins as the body's response to the dehydration caused by alcohol, abdominal pain and muscle pain that cause weakness and sometimes diarrhea. In particular, headaches are common to all people who suffer from hangovers, and are caused by the expansion of blood vessels due to the influence of certain vasodilator substances (such as histamine).

[0322] The term "flushing syndrome" as used herein refers to flushing that occurs as a result of drinking alcohol. Flushing is associated with erythema (redness caused by dilation of capillaries) of the face, neck, and shoulders after alcohol consumption. Flushing after alcohol consumption is often accompanied by a variety of symptoms, including dizziness, nausea, headache, increased pulse rate, occasional extreme drowsiness, and occasional swelling and itching of the skin. These symptoms are collectively referred to as "flushing syndrome" or "Asian flush."

[0323] The compositions provided herein can break down alcohol in the digestive tract (intestine) of a subject, thereby reducing the amount of alcohol absorbed into the blood.Thus, the compositions provided herein can break down alcohol before it is transported to the liver.Thus, the compositions provided herein can be used to protect the liver and related organs from alcohol-induced liver damage.

[0324] The compositions provided herein are effective for breaking down alcohol when administered to a subject at any time before, during (e.g., simultaneously with or between alcohol consumption, e.g., between the first and second alcoholic beverages), or after alcohol consumption. From the standpoint of efficacy, it is preferred that the agent be taken before or during alcohol consumption, and most preferably at least one hour before alcohol consumption. In some embodiments, the composition is administered before or simultaneously with alcohol consumption.

[0325] In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken at least 5 hours prior to alcohol consumption. In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken at least 4 hours prior to alcohol consumption. In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken at least 3 hours prior to alcohol consumption. In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken at least 2 hours prior to alcohol consumption.

[0326] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 1 hour prior to alcohol consumption.

[0327] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 30 minutes prior to ingesting alcohol.

[0328] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 15 minutes prior to ingesting alcohol.

[0329] When using AB001 to protect against alcohol ingested through occasional drinking, it may be beneficial to take two doses, two hours apart, prior to drinking, with the final dose being taken at least two hours before alcohol consumption.

[0330] In some embodiments, the composition (eg, an effective amount of a composition described herein) is taken at least one day prior to alcohol consumption.

[0331] In one embodiment, the composition described herein (e.g., one dose of the composition described herein) is taken daily. In some embodiments, the composition (e.g., an effective amount of the composition described herein) is taken daily for at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, or at least 7 days before alcohol consumption. For example, one dose (e.g., two capsules or tablets of the composition described herein) can be taken daily for at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, or at least 7 days before alcohol consumption. For example, one dose (e.g., two capsules or tablets of the composition described herein) can be taken daily for 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days before alcohol consumption.

[0332] In certain embodiments, one dose (e.g., two capsules or tablets of the composition described herein) is taken every day for seven days prior to alcohol consumption. In other words, a composition described herein (e.g., an effective amount of a composition described herein, e.g., one dose of a composition described herein) is taken every day for one week prior to alcohol consumption.

[0333] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 15 minutes prior to ingesting alcohol.

[0334] In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken in parallel with the alcohol. In other words, the composition (e.g., an effective amount of a composition described herein) is taken at the same time as the alcohol.

[0335] In other examples, the composition (e.g., an effective amount of a composition described herein) is ingested after (e.g., following) alcohol consumption. For example, the composition (e.g., an effective amount of a composition described herein) can be ingested after ingesting a first alcoholic beverage. In another example, the composition (e.g., an effective amount of a composition described herein) can be ingested after ingesting a first alcoholic beverage but before ingesting a second alcoholic beverage, etc., for example, the composition (e.g., an effective amount of a composition described herein) can be ingested after ingesting a second alcoholic beverage but before ingesting a third alcoholic beverage.

[0336] In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken at least 5 hours after alcohol consumption. In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken at least 4 hours after alcohol consumption. In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken at least 3 hours after alcohol consumption. In some embodiments, the composition (e.g., an effective amount of a composition described herein) is taken at least 2 hours after alcohol consumption.

[0337] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 1 hour after ingesting alcohol.

[0338] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 30 minutes after ingesting alcohol.

[0339] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 15 minutes after ingesting alcohol.

[0340] It will be apparent to one of skill in the art that the compositions described herein can be administered to a subject at any time before, during, or after ingestion of alcohol. As noted above, from the standpoint of efficacy, it is preferred that the agent be taken before or during alcohol ingestion, and most preferably at least one hour before alcohol ingestion.

[0341] As used herein, "ingestion" refers to the taking in of a substance (e.g., consumption) by an organism. Thus, as used herein, "alcohol intake" refers to the act or process of taking alcohol into an organism (e.g., a subject, preferably a human). In the context of the present invention, when the subject is a human, alcohol is preferably taken via the mouth. As used herein, "alcohol intake" and "alcohol consumption" can be used interchangeably.

[0342] The composition may be taken orally in the form of an aqueous solution, tablet, capsule, granule, etc. Additionally, the composition may be added to an alcoholic beverage (or other alcohol source) prior to its consumption. For example, the composition may be added as an additional ingredient during the production of an alcoholic beverage.

[0343] The appropriate amount of the compositions disclosed herein to be consumed will depend on the mass of alcohol being (or will be) consumed.

[0344] Also provided herein is a pharmaceutical formulation comprising the composition of the present invention.As will be apparent to those skilled in the art, the pharmaceutical formulation is a formulation suitable for administration to a subject to break down alcohol.The pharmaceutical formulation may be administered to a subject to prevent and / or treat a disease, condition, or illness selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, liver cirrhosis, alcohol-induced cancer, cardiovascular pathology, obesity, neurological disorders, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache, and / or acetaldehyde poisoning.The pharmaceutical formulation used herein comprises an effective dose of the composition of the present invention.

[0345] The compositions described herein are intended for administration to a subject (preferably a human) in an effective amount (effective dose). An "effective amount" is an amount that, alone or together with further doses, causes the desired (therapeutic or non-therapeutic) response. The effective amount used will depend, for example, on the therapeutic (or non-therapeutic) purpose, the route of administration, and the condition of the subject. For example, a suitable dosage of the composition of the invention for a given subject can be determined by a physician (or the person administering the composition) taking into account various factors known to modify the action of the composition of the invention, such as alcohol intake, body weight, sex, diet, time and route of administration, other medications, and other relevant clinical factors. Dosage amounts and schedules may vary depending on the particular condition, disorder, or symptom, and the overall condition of the subject. Effective dosages can be determined by either in vitro or in vivo methods.

[0346] The compositions described herein are advantageously provided in dosage units. For example, the compositions may be provided in the form of capsules or tablets. Other suitable dosage units are described elsewhere herein.

[0347] An "effective amount" can include administration of one or more dosage units. For example, an effective amount can be achieved by administration of one or two capsules or tablets. When an effective amount includes multiple dosage units, the dosage units can be administered together or they can be taken at intervals throughout the day.

[0348] Those of ordinary skill in the art will be able to readily identify alternative suitable effective amounts and dosage forms using routine experimentation based on the examples below.

[0349] As used herein, the terms "treat" and "treatment" refer to administering a composition to a subject (e.g., a symptomatic subject suffering from an adverse condition, disorder, illness, or disease) to affect the reduction in severity and / or frequency of symptoms, elimination of symptoms and / or their underlying causes, and / or to promote the amelioration or correction of damage, and / or the prevention of an adverse condition, disorder, illness, or disease in an asymptomatic subject susceptible to or suspected of or at risk of developing a particular adverse condition, disorder, illness, or disease.

[0350] The term "prevention" as used herein means avoiding the occurrence or recurrence of a symptom and / or its underlying cause, damage, adverse condition, disorder, illness, and / or disease. For example, "prevention" in the context of the present invention may be avoiding the appearance of one or more symptoms associated with a hangover.

[0351] As discussed elsewhere herein, the subject may be any suitable subject, for example, the subject may be a human. The subject may be a human who will consume alcohol or who has consumed alcohol.

[0352] As used herein, a "pharmaceutical composition" refers to a composition having pharmacological activity or other direct effect in mitigating, treating, or preventing disease, and / or its finished dosage form or formulation, and is intended for human use. A pharmaceutical composition or pharmaceutical preparation is typically produced under Good Manufacturing Practice (GMP) conditions. A pharmaceutical composition or pharmaceutical preparation may be sterile or non-sterile. If non-sterile, such a pharmaceutical composition or pharmaceutical preparation typically meets the microbiological specifications and standards for non-sterile medicinal products as set forth in the United States Pharmacopoeia (USP) or the European Pharmacopoeia (EP). Thus, the compositions described herein may be formulated as pharmaceutical compositions. In some embodiments, the pharmaceutical composition is non-sterile.

[0353] Unless otherwise specified herein, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs. For example, Singleton and Sainsbury's Dictionary of Microbiology and Molecular Biology, 2nd Edition, John Wiley and Sons, NY (1994), and Hale and Malham's The Harper Collins Dictionary of Biology, Harper Perennial, NY (1991) provide those skilled in the art with a general dictionary of many of the terms used in the present invention. Although any methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred methods and materials are described herein. Thus, the terms defined immediately below are more fully described by reference to the entire specification. Also, as used herein, the singular terms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Unless otherwise indicated, nucleic acids are written left to right in 5' to 3' orientation, and amino acid sequences are written left to right in amino to carboxy orientation, respectively. It is to be understood that the invention is not limited to the particular methodology, protocols, and reagents described, which may vary depending on the context in which they are used by those of skill in the art.

[0354] Aspects of the present invention are illustrated by the following non-limiting examples. EXAMPLES

[0355] Example 1 - Development of the compositions described herein background The inventors had previously developed a food-grade quality fermented rice bran for evaluation purposes. A case study design was applied to initiate a safety study. Approximately 1400 people were made to take the product regularly over a long period of time. No side effects / adverse reactions were reported. However, indications of an anti-hangover effect were reported. The inventors decided to investigate this effect further.

[0356] experiment A controlled study was organised to confirm the effectiveness of fermented rice bran in preventing hangovers. Eight men in their 30s to 50s drank four pints of beer (4.2%) each over the first hour and a half. The hangover reduction was on average 1.24‰ 30 minutes after drinking, and below 0.20‰ from 5.5 hours.

[0357] Two weeks later, the same group underwent the same procedure, but took 0.75g of fermented rice bran powder before drinking alcohol. The mean blood glucose level was 0.91‰ 30 minutes after drinking, and below 0.20‰ 4.0 hours after drinking, 25% faster than the liver digests alcohol. Measurements were taken with a breathalyzer.

[0358] A more comprehensive study was then conducted, including participants of both genders and a wide range of ages and weights. All studies were of crossover design, i.e., the same groups were administered on two separate occasions using either the iBAC or the Dräger breathalyzer without and with fermented rice bran (herein referred to as "Pinch", noting that "Pinch" as used herein may further include other components such as dextrin and / or L-cysteine, as explained below). Participants were provided with tea / coffee and a cheese roll, after which they drank 60cl red wine (13.5%) over a 4-hour period. Breathalyzer measurements were taken hourly, starting 15 minutes after drinking, with an end point of 0.20‰ or lower. The study results are shown below. The composition of the fermented rice bran powder used in each study is also described below. The data are summarized in Figures 8-11.

[0359] Test 1 Test 1a 16 participants, 11 men and 5 women, ages 24-68, weights 46kg-92kg (without pinch) 15 minutes: average 0.97‰ 1 hour: average 0.89‰ 2 hours: average 0.52‰ 3 hours: average 0.42‰ 4 hours: average 0.29‰ 5 hours: average 0.16‰

[0360] Test 1b, Pinch = fermented rice bran only 13 participants, 9 men and 4 women, ages 24-68, weights 46kg-92kg (using Pinch) 15 minutes: average 1.03‰ 1 hour: average 0.78‰ 2 hours: average 0.41‰ 3 hours: average 0.22‰ 4 hours: average 0.07‰

[0361] Test 2 Test 2a 14 participants, 10 men and 4 women, ages 22-62, weights 46kg-87kg (without pinches) 15 minutes: average 0.91‰ 1 hour: average 0.80‰ 2 hours: average 0.52‰ 3 hours: average 0.44‰ 4 hours: average 0.24‰ 5 hours: average 0.11‰

[0362] Test 2b, Pinch = Fermented rice bran + 5% dextrin 14 participants, 10 men and 4 women, ages 22-62, weights 46kg-87kg (using Pinch) 15 minutes: average 0.93‰ 1 hour: average 0.72‰ 2 hours: average 0.36‰ 3 hours: average 0.19‰ 4 hours: average 0.03

[0363] Test 3 Test 3a 17 participants, 12 men and 5 women, ages 20-59, weights 42kg-97kg (without pinch) 15 minutes: average 1.04‰ 1 hour: average 0.90‰ 2 hours: average 0.61‰ 3 hours: average 0.42‰ 4 hours: average 0.21‰ 5 hours: average 0.11‰

[0364] Test 3b, Pinch = Fermented rice bran + 2% dextrin 13 participants, 9 men and 4 women, ages 20-48, weights 46kg-84kg (using Pinch) 15 minutes: average 0.96‰ 1 hour: average 0.76‰ 2 hours: average 0.34‰ 3 hours: average 0.18‰ 4 hours: average 0.08‰

[0365] Test 4 Test 4a 18 participants, 11 men and 7 women, ages 20-69, weights 42kg-125kg (without pinch) 15 minutes: average 0.96‰ 1 hour: average 0.87‰ 2 hours: average 0.62‰ 3 hours: average 0.39‰ 4 hours: average 0.20‰ 5 hours: average 0.08‰

[0366] Test 4b, Pinch = Fermented rice bran + 0.5% dextrin 15 participants, 10 men and 5 women, ages 24-64, weights 42kg-125kg (using Pinch) 15 minutes: average 0.96‰ 1 hour: average 0.76‰ 2 hours: average 0.35‰ 3 hours: average 0.16‰ 4 hours: average 0.04‰

[0367] Test 5 Test 5a 17 participants, 11 men and 6 women, ages 28-64, weights 43kg-125kg (without pinch) 15 minutes: average 0.92‰ 1 hour: average 0.81‰ 2 hours: average 0.65‰ 3 hours: average 0.44‰ 4 hours: average 0.23‰ 5 hours: average 0.06‰

[0368] Test 5b, Pinch = Fermented rice bran + 0.5% dextrin + 30% L-cysteine 16 participants, 11 men and 5 women, ages 28-64, weights 43kg-125kg (using Pinch) 15 minutes: average 0.98‰ 1 hour: average 0.71‰ 2 hours: average 0.32‰ 3 hours: average 0.05‰

[0369] Test 6 Test 6a 14 participants, 8 men and 6 women, ages 22-69, weights 41kg-125kg (without pinch) 15 minutes: average 0.92‰ 1 hour: average 0.84‰ 2 hours: average 0.61‰ 3 hours: average 0.42‰ 4 hours: average 0.27‰ 5 hours: average 0.08‰

[0370] Test 6b, Pinch = Fermented rice bran + 0.5% dextrin + 20% L-cysteine 16 participants, 11 men and 5 women, ages 28-62, weights 43kg-125kg (using Pinch) 15 minutes: average 0.98‰ 1 hour: average 0.65‰ 2 hours: average 0.28‰ 3 hours: average 0.06‰

[0371] Test 7 Test 7a 16 participants, 8 men and 8 women, ages 21-65, weights 42kg-125kg (without pinch) 15 minutes: average 1.03‰ 1 hour: average 0.90‰ 2 hours: average 0.73‰ 3 hours: average 0.52‰ 4 hours: average 0.28‰ 5 hours: average 0.10‰

[0372] Test 7b, Pinch = Fermented rice bran + 0.5% dextrin + 10% L-cysteine 15 participants, 10 men and 5 women, ages 21-65, weights 42kg-125kg (using Pinch) 15 minutes: average 0.96‰ 1 hour: average 0.68‰ 2 hours: average 0.31‰ 3 hours: average 0.17‰ 4 hours: average 0.03‰

[0373] Test 8 Test 8a 14 participants, 9 men and 5 women, ages 26-65, weights 44kg-125kg (without pinch) 15 minutes: average 0.93‰ 1 hour: average 0.78‰ 2 hours: average 0.63‰ 3 hours: average 0.48‰ 4 hours: average 0.24‰ 5 hours: average 0.07‰

[0374] Test 8b, Pinch = Fermented rice bran + 5% dextrin + 20% L-cysteine 12 participants, 8 men and 4 women, ages 26-65, weights 44kg-125kg (using the Pinch) 15 minutes: average 0.96‰ 1 hour: average 0.75‰ 2 hours: average 0.44‰ 3 hours: average 0.21‰ 4 hours: average 0.03‰

[0375] Microbial characterization Using Sanger DNA sequencing, the predominant bacterial strains found in the compositions used were identified to be Bacillus subtilis and Bacillus coagulans. Other genera / species identified were Bacillus amyloliquefaciens, Bacillus veresensis, Bacillus species MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

[0376] Dextrin and L-cysteine Dextrin is available from several suppliers. Dextrin from three different suppliers was tested and found to work (data not shown). The preferred dextrin used here was hydrolyzed corn dextrin (e.g., Vitargo).

[0377] L-cysteine ​​is also available from several suppliers. L-cysteine ​​from three different suppliers was tested and found to work (data not shown). The preferred L-cysteine ​​used here was of plant origin.

[0378] conclusion It was concluded that fermented rice bran containing two dominant Bacillus strains, namely subtilis and coagulans, had a basic alcohol digestion effect that was 25%-30% faster than the liver digestion alone. Furthermore, the above results show that dextrin further accelerates alcohol digestion, making it approximately 35%-40% faster than the liver digestion. Only a slight difference was observed in the additional effect when 0.5%-5% dextrin was used. The composition of 79.5% (wt / wt) fermented rice bran (containing at least 10,000 cfu / g of Bacillus bacteria), 0.5% (wt / wt) dextrin, and 20.0% (wt / wt) L-cysteine ​​was evaluated as the optimal mixture for alcohol digestion in the intestinal tract from a clinical point of view, digesting alcohol approximately 50% faster than the liver digestion. Thus, in the following Examples 2 and 3, a combination of 0.5% (w / w) dextrin and 20.0% (w / w) L-cysteine ​​was used. Thus, the composition used in Examples 2 and 3 contained, per dose (2 capsules), 73% (w / w) fermented rice bran (552 mg), 20% (w / w) L-cysteine ​​(150 mg), 5% (w / w) microcrystalline cellulose (40 mg), 0.64% (w / w) magnesium stearate (4.8 mg), 0.5% (w / w) dextrin (4 mg), 0.53% (w / w) silicon dioxide (4 mg), 0.00012% (w / w) vitamin B12 (0.0009 mg), and at least 1×10 5 The bacteria contained 100 cfu of Bacillus spp.

[0379] Mechanism of action Without being bound by this hypothesis, the inventors believe that both dextrin and / or L-cysteine ​​create a microenvironment at the cellular level that allows the microbial consortium, when resuscitated in the intestinal tract, to excrete enzyme cascades that target short carbon chains, e.g., ethanol / alcohol, resulting in preferential targeting / preferential use of ethanol / alcohol as a substrate.

[0380] Typically, about 80% of the alcohol intake remains in the small intestine for a significant period of time before being absorbed into the blood. The targeted enzyme acts only on the alcohol in the tract, breaking it down into carbon dioxide and water, thus bypassing the liver's process of converting alcohol to acetaldehyde and acetic acid, the hangover metabolites.

[0381] Example 2 - Comparative Dietary Supplement Trial PERA-ATX-001: A clinical study evaluating the effect of a bacteria-based dietary supplement (AB001) on ethyl alcohol absorption in the intestinal tract [Table 1]

[0382] Introduction As discussed elsewhere herein, the inventors have developed an alcohol-splitting composition (AB001) that helps to avoid problems associated with alcohol intake. It is composed of naturally fermented rice bran, Bacillus subtilis and Bacillus coagulans, L-cysteine ​​and dextrin. It also contains magnesium stearate, calcium phosphate and potassium phosphate. The supplement is contained in an acid-resistant capsule (HPMC) that dissolves upon reaching the duodenum. The culture is released and colonizes the upper intestinal tract where it remains for approximately one day before being excreted from the body through the stool. The bacterial strain contained in the composition converts ethyl alcohol into CO2. 2 and water, thus reducing further absorption of alcohol from the intestinal tract. As a result, less alcohol is expected to be absorbed by the body, and organ damage from alcohol breakdown products is expected to be reduced.

[0383] The aim of this study was to evaluate the reduction in blood alcohol absorption and breath alcohol levels following a defined amount of alcohol consumption in healthy subjects after one week of dietary supplementation with either AB001 or placebo, as well as cognitive function one hour after alcohol ingestion and the tolerability of both interventions.

[0384] Patients and methods Clinical trial population The study was planned to be carried out as a prospective, double-blind, randomized crossover study in 24 healthy adult volunteers who were not known to suffer from any diseases that may affect alcohol digestion or tolerance (e.g., gastrointestinal or metabolic disorders, alcoholism, allergies, etc.).

[0385] Research Schedule The study was carried out in accordance with international and local ethical and scientific standards. The experimental design was approved by a responsible ethical review committee (The Medical Association of Rhineland-Palatinate, Mainz, Germany) and notified to a responsible national authority (Federal Office for Consumer Protection and Food Safety). Before participation, participants signed written informed consent. Subsequently, blood samples were taken for safety analyses, potential exclusion criteria were identified, and randomization into the two study arms took place (Visit 1).

[0386] Enrolled subjects were asked to participate in two experimental treatments (Visit 2 and Visit 3) after one week of regular administration of placebo or 2 capsules per day of AB001, respectively. After arriving at the study site, subjects had a light breakfast and then consumed high-alcohol spirits (vodka) with 0.3 g alcohol per kg body weight. Alcohol was measured at the central laboratory (Labor Augsburg, Augsburg, Germany, gas chromatography) by breath tests (Dräger Alcotest 3820, Dräger Safety AG, Lübeck, Germany) and blood samples at 0, 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 min. Participants were asked to perform a number-chasing test before and 60 min after drinking alcohol. The time required to complete the test was documented. The experiment was carried out for at least 120 min until no alcohol was detected in breath tests at two consecutive time points.

[0387] After the second examination (visit 3), the patient was discharged from the study.

[0388] statistical analysis The area under the curve (AUC) of blood alcohol levels over time was used to calculate the reduction in alcohol absorption by AB001. Broadly, this can be done in two ways: A. The AUC can be calculated for each participant separately by using the following formula for each time point Tk: AUC(0-180)=Σ_(k=0)^180(C[k+1]-C[k]) / 2*([k+1]-[k]

[0389] where T[k] and T[k+1] are two consecutive time points, C[k+1] and C[k] are the alcohol concentrations measured at each time point, and T[k+1]-T[k] is the time interval between measurements. This was done for each individual and for both treatment groups. A two-tailed Student's T-test was used to calculate p-values ​​(5% error, 80% power, type 1) for differences between groups.

[0390] B. Alternatively, the mean ± standard deviation of blood alcohol results for each time point was calculated and the area under the curve was calculated for each treatment. The contribution of each time point to the AUC was calculated and a two-tailed Student's T-test was used to calculate p-values ​​(5% error, 80% power, type 1) for differences between groups.

[0391] The results of these calculations for blood alcohol were p=0.0030 (A) and p=0.0023 (B), and p=0.0463 (A) and p=0.0041 (B), respectively (see Results section below).

[0392] result Experimental design deviations No deviations from the study design were observed in this study. However, the sponsor notified the study site that a mix-up had occurred with the treatment package for subject 13, and the correct order of supplements was active drug (box 1) followed by placebo (box 2). The same problem was reported to have potentially occurred for patients 21-24. This information was confirmed after unblinding by their respective results, and these patients were included in the reversed randomization order in the final analysis.

[0393] patient As planned, 24 healthy subjects were enrolled in the study (13 men, 11 women, mean age: 25.4 ± 7.7 years (range: 18-55 years), BMI: 23.6 ± 2.5 kg / m 2 (Range: 19.1 kg / m 2 ~29.1kg / m 2 A list of patients and their individual characteristics, as well as blood pressure and amount of alcohol consumed, are shown in Tables 2 and 3.

[0394] [Table 2]

[0395] [Table 3]

[0396] Statistical Analysis Group All patients were studied according to the study protocol and were included in the safety and efficacy analyses.

[0397] Efficacy Results In general, the IRB approved alcohol intake (0.3 g / kg body weight) was low (47 mL to 89 mL of spirits containing 32% alcohol), and six subjects (25%) did not achieve measurable blood alcohol concentrations with either of the two interventions. Four of the remaining participants did not show blood alcohol concentrations above 0.1‰ with either the active or placebo (17% of the tested population). Three subjects did not show any detectable breath alcohol concentrations in the placebo experiment. In 18 subjects in this group, values ​​with breath alcohol levels above 0.1‰ were detected. The highest alcohol concentrations observed, both of which were confirmed in the placebo experiment, were 0.33‰ (breath) and 0.27‰ (blood), respectively (active: 0.30‰ and 0.21‰).

[0398] Blood Alcohol Results The mean blood concentrations after one week of regular supplementation with either investigational product or placebo, two capsules per day, are shown in Figure 1.

[0399] In no individual study was there any measurable alcohol level detectable in the blood beyond 180 minutes. AUC 血中(0-180分) was calculated to be 8.5 ± 0.6‰ × min from the placebo study and 2.5 ± 0.2 × min from the active study (-70.3%, p < 0.005, see Figure 2).

[0400] Breath alcohol results The mean breath alcohol concentrations after one week of regular supplementation with two capsules of investigational product or placebo per day and ingesting 0.3 g of alcohol per kg of body weight are shown in FIG.

[0401] In no individual experiment was there a measurable level of alcohol in the breath detectable beyond 180 min. AUC calculated from the mean concentrations 呼気(0-180分) was 14.0‰×mL from the placebo trial and 9.7‰×mL from the active trial (−30.7%, p<0.005, see Figure 4).

[0402] Number Tracking Test Alcohol intake did not affect patients' cognitive function, as assessed by measuring the time required to complete a standardized digit tracing test. Individual results are shown in Table 4.

[0403] [Table 4]

[0404] There was no difference between the active drug and placebo in the time it took to complete cognitive tests before the study began and again one hour after intake.

[0405] Safety analysis The supplement was well tolerated and no adverse events or serious adverse events were reported in this study. It can be concluded that the supplement had no side effects in this study.

[0406] Furthermore, safety biochemistry panel tests performed before and after the study showed no clinically relevant deviations from normal values.

[0407] Observations and Conclusions As shown here, a significant reduction of more than 70% in alcohol absorption into the blood was observed after one week of AB001 supplementation compared to placebo. The reduction in measurable alcohol in the breath was also significantly reduced, but to a lesser extent (approximately 30%). Although it is well known that breath alcohol and blood alcohol concentration are highly correlated, the results of breath alcohol measurements are more subject to physiological variations such as body and breath temperature, lung function, and breathing patterns before exhalation (Jones et al, 2000). Therefore, the final alcohol content in the breath may be more dependent on the alcohol that is usually absorbed early in the upper uptake tract, i.e., in the oral mucosa and in the stomach. This explains why the effects measured were more pronounced in the blood tests than in the breath tests.

[0408] It is noted that in 10 cases (42%), the amount of alcohol ingested (0.3 g / kg body weight) did not result in measurable relevant blood alcohol concentrations. The amount of alcohol ingested in this study was regulated by the IRB during the study approval process.

[0409] In conclusion, regular supplementation with AB001 for one week significantly lowered alcohol uptake into the blood, resulting in greater than 70% lower uptake into whole body metabolism. Therefore, regular intake of AB001 as a dietary supplement may help prevent liver and other organ damage known to be associated with regular alcohol intake, and may reduce the adverse medical and economic impacts of social drinking on individuals and society.

[0410] References for Example 2 Jones AW, "Medicolegal Alcohol Determination - Blood - or breath alcohol concentration." Forensic Sci. Rev. 12:23-47, 2000.

[0411] Example 3 - Comparative Dietary Supplement Trial PERA-ATX-002: A Prospective Randomized Study to Evaluate the Effect of a Single Dose of Dietary Supplement (AB001) on Alcohol Absorption in Healthy Subjects [Table 5]

[0412] As mentioned above, the inventors have developed an alcohol decomposition supplement (AB001) that helps to avoid the problems associated with alcohol consumption. It is composed of naturally fermented rice bran, Bacillus subtilis and Bacillus coagulans, L-cysteine ​​and dextrin. It also contains magnesium stearate, calcium phosphate and potassium phosphate. The supplement is in an acid-resistant capsule (HPMC) that dissolves when it reaches the duodenum. The culture is released and colonizes the upper intestinal tract where it remains for about a day before being excreted from the body through the stool. The bacterial strain converts ethyl alcohol into CO2. 2 and water, thus reducing further absorption of alcohol from the intestinal tract. As a result, less alcohol is expected to be absorbed by the body, and organ damage from alcohol breakdown products is expected to be reduced.

[0413] Example 2 presents the first randomized, placebo-controlled, double-blind, crossover study in which 24 healthy subjects (13 males, 11 females, age: 25.4±7.7 years, BMI: 23.6±2.5 kg / m 2 ) were randomized to receive 2 capsules of AB001 or placebo per day for 1 week prior to the alcohol exposure experiment. On the day of the experiment, subjects had a light breakfast and consumed one moderate glass of spirits (0.3 g / kg body weight). Breath alcohol tests and blood sampling to measure blood alcohol levels were performed for up to 6 hours. Alcohol absorption was calculated by calculating the area under the curve. A significant reduction of 70.3% (p<0.005 vs. placebo) in blood alcohol levels was observed with AB001 (breath test: -30.7%, p<0.005 vs. placebo). No differences were observed in cognitive function tests performed 60 minutes after alcohol intake (22.4±7.7 s vs. 22.7±5.6 s, ns). No adverse or serious adverse events were reported in this study.

[0414] The purpose of the study in Example 3 was to continue the scientific investigation of the performance of AB001 and answer the following questions:

[0415] 1. What results would you expect if you only took a single dose of AB001 immediately prior to alcohol consumption, as opposed to the 7-day supplementation in the previous study? 2. Are the observed inhibitory effects maintained at higher alcohol doses?

[0416] Patients and methods Clinical trial population The study was planned to be carried out as a prospective, double-blind, randomized crossover study in 24 healthy adult volunteers who were not known to suffer from any diseases that may affect alcohol digestion or tolerance (e.g., gastrointestinal or metabolic disorders, alcoholism, allergies, etc.) (see study experimental design for detailed inclusion and exclusion criteria).

[0417] Research Schedule The study was carried out in accordance with international and local ethical and scientific standards. The experimental protocol was approved by the responsible ethical review committee (The Medical Association of Rhineland-Palatinate, Mainz, Germany) and notified to the responsible national authority (Federal Office for Consumer Protection and Food Safety).

[0418] Prior to enrollment, participants signed written informed consent, after which blood was drawn for safety analyses, potential exclusion criteria were checked, and randomization to the two study arms took place (Visit 0).

[0419] Enrolled subjects were asked to participate in two experimental treatments (Visit 1 and Visit 2). After arriving at the study site in the morning after an overnight fast, subjects were randomized to receive either placebo or AB001 supplementation. One hour after ingesting the study drug, participants drank their first glass of high alcoholic strength spirits (vodka, 0.3 g / kg body weight, time 0) and had a light breakfast of bread rolls, ham or jam, and tea or coffee. Subjects then drank their second glass of alcohol (vodka, 0.3 g / kg body weight, time 30). Blood was drawn to determine plasma alcohol concentration, and breathalyzer assessments were performed at 0, 15, 30, 45, 60, 75, 90, 120, 180, 240, 300, 360, and 420 minutes to determine breath alcohol concentration. Participants remained in the study facility throughout the study. A standard lunch was provided 4 hours later. In addition, participants were given a cognitive test (Digit Tracking Test, NCT-A) at 0 and 60 minutes. Information on adverse events was documented. The study was terminated if no alcohol could be detected in the breath at two consecutive times after the second alcohol intake.

[0420] A second study was performed 3-5 days later following the same experimental design. After the second study (Visit 2), the patient was dismissed from the study.

[0421] statistical analysis The area under the curve (AUC) of blood alcohol levels over time was used to calculate the reduction in alcohol absorption by AB001. Generally, this can be done in two ways:

[0422] A. The AUC can be calculated for each participant individually by using the following formula for each time point Tk: AUC(0-180)=Σ_(k=0)^180(C[k+1]-C[k]) / 2*([k+1]-[k]

[0423] where T[k] and T[k+1] are two consecutive time points, C[k+1] and C[k] are the alcohol concentrations measured at each time point, and T[k+1]-T[k] is the time interval between measurements. This was done for each individual and for both treatment groups. A two-tailed Student's T-test was used to calculate p-values ​​(5% error, 80% power, type 1) for differences between groups.

[0424] B. Alternatively, the mean ± standard deviation of blood alcohol results for each time point was calculated and the area under the curve was calculated for each treatment. The contribution of each time point to the AUC was calculated and a two-tailed Student's T-test was used to calculate p-values ​​(5% error, 80% power, type 1) for differences between groups.

[0425] The results of these calculations were p=0.014 (A) and p=0.000019 (B) for blood alcohol, respectively, and p=0.0448 (A) and p=0.000074 (B) for breath alcohol, respectively (see Results section below).

[0426] result Experimental design deviations No deviations from the experimental design were observed in this study.

[0427] patient As planned, 24 healthy subjects were enrolled in the study (12 men, 12 women, mean age: 28.3 ± 10.8 years (range: 20-56 years), BMI: 23.5 ± 5.7 kg / m 2 (Range: 16.9 kg / m 2 ~31.1kg / m 2 A list of patients and their individual characteristics, as well as blood pressure and amount of alcohol consumed, are shown in Tables 6 and 7.

[0428] [Table 6]

[0429] [Table 7]

[0430] Statistical Analysis Group All patients were studied according to the study protocol and were included in the safety and efficacy analyses.

[0431] Efficacy Results In general, the IRB approved alcohol intake (0.3 g / kg body weight twice) resulted in measurable blood alcohol levels in all subjects. The highest alcohol concentrations observed were 0.88‰ (breath) and 0.91‰ (blood) in both placebo studies, respectively (AB001: 0.77‰ and 0.72‰).

[0432] Blood Alcohol Results The mean blood concentrations after supplementation with two capsules of investigational product or placebo one hour before the study are shown in FIG.

[0433] AUC 血中(0-420分) was calculated to be 116 ± 32‰ × min from the placebo experiment and 104 ± 24‰ × min from the AB001 experiment (-10.1%, p < 0.05, see Figure 6).

[0434] Breath alcohol results The mean breath alcohol concentrations after supplementation with two capsules of investigational product or placebo one hour before the experiment are shown in FIG.

[0435] AUC calculated from mean concentration 呼気(0-420分) was 98 ± 29 ‰ × min from the placebo study and 91 ± 25 ‰ × min from the AB001 study (-7.2%, p < 0.05).

[0436] Number Tracking Test The intake of alcohol did not affect the cognitive function of the patients, as assessed by measuring the time required to complete a standardized digit tracing test. Individual results are shown in Table 8.

[0437] [Table 8]

[0438] Following alcohol ingestion, there was a small decrease in individual subject performance that was statistically significant (p<0.05) in the AB001 experiment and nearly significant (p=0.057) in the placebo experiment.

[0439] Safety analysis The supplement was well tolerated. Two adverse events were reported in the study.

[0440] One case of mild anemia was reported in Subject 6 (female, age 27) at Screening and Visit 3 prior to uptake of AB001. Mild anemia was diagnosed based on the following laboratory results (Screening / Visit 3 - Reference Range): Red blood cells: 3.74 / 3.64 Mio / μL (reference range: 3.9 Mio / μL to 5.2 Mio / μL) Hemoglobin: 11 / 2 / 11.0g / dL (reference range: 12g / dL to 16g / dL) Hematocrit: 34 / 33% (reference range: 36%-46%)

[0441] At screening, the subinvestigators characterized these results as "clinically insignificant" and allowed the subject to be enrolled. The subject was encouraged to follow up on the condition with his or her physician after completion of the study. The event was classified by the investigator as "unrelated" to the study intervention.

[0442] Subject 9 (male, age 30) reported one case of moderate headache (migraine) at Visit 3 prior to the ingestion of AB001. This subject reported that this was in fact a known ongoing event that was treated with the ingestion of 200 mg of ibuprofen. This event was classified by the investigator as "unrelated" to the study intervention.

[0443] Furthermore, no serious adverse events were reported from this study.

[0444] It can be concluded that the intake of the nutritional supplement was not associated with any side effects in this study. Furthermore, no other clinically relevant deviations from normal values ​​were found in the safety biochemistry panel tests performed before and after the study.

[0445] Observations and Conclusions In Example 2 (PERA-ATX-001), a significant reduction of over 70% in alcohol absorption into the blood was observed after one week of AB001 supplementation compared to placebo when 0.3 g / kg of alcohol was consumed after a light breakfast. The reduction in measurable alcohol in the breath was also significantly reduced, but to a lesser extent (approximately 30%).

[0446] In this example, it was also observed that ingestion of a single dose of AB001 taken only 1 hour before two 0.3 g / kg alcohol drinks, separated by a 30 minute interval and with a light snack in between, was effective in lowering blood and breath alcohol, specifically, blood alcohol levels were significantly reduced by approximately 10% and breath alcohol by 7% with AB001 compared to placebo.

[0447] In conclusion, taking a single dose of AB001 within one hour before drinking alcohol reduces the amount of alcohol absorbed in the intestinal tract and induces significant reductions in blood alcohol and breath alcohol of approximately 10% and 7%, respectively.

[0448] Example 4 - In vivo alcohol studies An in vivo study was conducted as shown below. The composition described in Examples 2 and 3 (also referred to herein as AB001) was used to demonstrate the efficacy of fermented rice bran and natural health-beneficial Bacillus species. The study found that consumption of AB001 reduced plasma bilirubin production in males during and after consumption of 10% alcohol and a high-fat, high-carbohydrate diet. For the female group, after removing outlying values ​​from the raw data, the CMD (placebo group) increased bilirubin 3.7-fold (mean 1.68 mg / dl) compared to the IC (control group) (mean 0.46 mg / dl), while the PB (probiotic group) increased bilirubin 1.8-fold (mean 0.82 mg / dl), i.e., suppression of bilirubin increase compared to the CMD. Using a similar analysis, in the male group, excluding outlying values ​​from the raw data, it was shown that CMD and PB each had lower bilirubin (down to 0.44-0.45) compared to 0.91 mg / dl in IC, indicating that AB001 consumption was not detrimental to bilirubin levels. See Figure 12.

[0449] In vivo studies also demonstrated that AB001 (i.e., the compositions of Examples 2 and 3) also inhibited excessive weight gain in animals fed a high-fat and high-carbohydrate diet (Western diet) (Figure 13).

[0450] The experimental design for the in vivo alcohol study is outlined in Figure 14. The animal study was developed using 90 mice (C57BL / 6JRj, Javier Labs, France) separated by sex, 8 weeks of age upon arrival at the experimental facility and beginning acclimation (5 days). Mice were separated and fed as listed below: 1) The intact group was provided with water and fed standard rodent chow (standard rodent pellet chow, Lactamin, Vadstena, Sweden) and is referred to here as the "IC" group. 2) The placebo group was given a 10% ethanol solution in water and fed 12% maltodextrin mixed with a Western high-fat, high-carbohydrate diet (D12492M diet, Research Diets, New Brunswick, NJ 08901, USA), and is referred to here as the "CMD" group. 3) DFM product was drank 10% ethanol solution and fed 12% DFM product mixed with Western high fat high carbohydrate diet (D12492M diet, Research Diets, Inc., New Brunswick, NJ (08901), USA). This group is referred to herein as the "PB" group. DFM as used herein refers to the composition of the present invention, in this case AB001, as described in Examples 2 and 3.

[0451] Mice were kept on a 12-hour day / night cycle for 6 weeks. They were housed in IVC cages with Beta-Tip bedding per 5 individuals. Drinking solution was provided by bottle (ad libitum) during the adaptation period and throughout the study. Animals' body weight, food and water intake were measured weekly. Differences in body weight, food and water consumption were calculated between the first and last experimental day.

[0452] Blood and tissue samples were collected from anesthetized animals. Livers and spleens were collected after death by intracardiac injection of pentobarbital (Allfatal, Omnidea). Plasma was collected from blood to measure bilirubin levels. The left lateral lobe of the liver was stored in 10% neutral formalin solution for 24 hours after sampling for morphological analysis. For fat content of the liver, samples were stored at -80°C.

[0453] Statistical analysis was performed using Prism version 9.1.0 (GraphPad Software, Inc, San Diego, CA, USA) to determine if significant differences were found or observed between samples. Groups were considered to have statistical differences when p ≤ 0.05.

[0454] [Table 9]

[0455] The reader's attention is directed to all articles and documents related to this application that have been filed contemporaneously or prior to this application and that have been made available for public inspection together with this application, and the contents of all such articles and documents are incorporated herein by reference.

[0456] All features disclosed in this specification (including any accompanying claims, abstract, and drawings), and / or all steps of any method or process so disclosed, may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive.

[0457] Each feature disclosed in this specification (including any accompanying claims, abstract, and drawings), unless expressly stated otherwise, may be replaced by alternative features serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.

[0458] The invention is not limited to the details of any of the foregoing embodiments.The invention extends to any novel or any novel combination of features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any novel or any novel combination of method or process steps so disclosed.

Claims

1. An alcohol decomposition composition comprising one or more bacterial species of the genus Bacillus, rice bran, L-cysteine, and high molecular weight, low osmolality carbohydrates.

2. The composition according to claim 1, wherein one or more bacterial species of the genus Bacillus is at least one selected from the group consisting of B. subtilis and B. coagulans.

3. The composition according to claim 1, wherein the composition comprises B. subtilis and B. coagulans.

4. a) The B. subtilis species is selected from the group consisting of Bacillus subtilis DFM 0326 strain (LMG P-32899) and Bacillus subtilis DFM 1015 strain (LMG P-32900), and / or c) The composition according to claim 2, wherein the B. coagulans species is Bacillus coagulans DFM 0705 strain (LMG P-32921).

5. The composition according to claim 1, wherein the high molecular weight, low osmolality carbohydrate is dextrin.

6. The composition according to claim 1, wherein the alcohol is ethyl alcohol.

7. The composition according to claim 1, further comprising one or more bacterial species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus species MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

8. The composition according to claim 1, wherein the composition comprises at least 10% (by weight / by weight) of L-cysteine.

9. The composition according to claim 1, wherein the composition comprises at least 10,000 cfu / g of bacteria of the genus Bacillus.

10. The composition according to claim 1, wherein the composition comprises at least 67% (by weight / by weight) of rice bran.

11. The composition according to claim 1, wherein the composition comprises at least 0.5% (by weight) of a high molecular weight, low osmolality carbohydrate.

12. The composition according to claim 1, wherein the composition further comprises one or more of vitamin B12, a magnesium fatty acid salt, calcium phosphate, potassium phosphate, silicon dioxide, and cellulose.

13. The composition according to claim 1, wherein the composition is formulated as an acid-resistant tablet or capsule.

14. The composition according to claim 13, wherein the acid-resistant tablet or capsule comprises a film coating, wherein the film coating comprises hydroxypropyl methylcellulose (HPMC).

15. The composition according to claim 1, wherein one or more bacterial species of the genus Bacillus are not genetically modified.

16. Use of the alcohol decomposition composition according to any one of claims 1 to 15 for decomposing alcohol.

17. Use of L-cysteine ​​to enhance alcohol decomposition by one or more bacterial species of the genus Bacillus.

18. The use according to claim 17, wherein the L-cysteine ​​is combined with a high molecular weight, low osmolality carbohydrate.

19. The use according to claim 17, wherein the L-cysteine ​​is combined with rice bran.

20. The use according to claim 17, wherein the one or more bacterial species of the genus Bacillus is at least one selected from the group consisting of B. subtilis and B. coagulans.

21. a) The B. subtilis species is selected from the group consisting of Bacillus subtilis DFM 0326 strain (LMG P-32899) and Bacillus subtilis DFM 1015 strain (LMG P-32900), and / or c) The use according to claim 20, wherein the B. coagulans species is Bacillus coagulans DFM 0705 strain (LMG P-32921).

22. The use according to claim 17, wherein the alcohol is ethyl alcohol.

23. The use according to any one of claims 17 to 22, wherein the use is for breaking down alcohol in the subject.

24. The use according to claim 23, wherein the use is for metabolizing alcohol in the gastrointestinal tract of the subject.

25. The use according to claim 23, wherein the use is for the purpose of reducing the absorption of alcohol into the blood of the subject.

26. The use according to claim 23, wherein the use is for the purpose of reducing the breath alcohol concentration or blood alcohol concentration in the subject.

27. A composition according to any one of claims 1 to 15 for use as a pharmaceutical.

28. A composition according to any one of claims 1 to 15 for use in the decomposition of alcohol in a test subject.

29. A composition according to any one of claims 1 to 15 for use in the prevention and / or treatment of alcohol-induced organ damage in a subject.

30. The composition for use according to claim 29, wherein the organ is the liver and / or pancreas.

31. The composition for use according to claim 27, wherein the composition is for use in the prevention and / or treatment of a disease, condition, or illness selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, cirrhosis, alcohol-induced cancer, cardiovascular disease, obesity, neuropathy, neurodegenerative disease, hangover symptoms, flushing syndrome, headache, and / or acetaldehyde poisoning.

32. The composition for use according to claim 31, wherein the cancer is selected from liver cancer, pancreatic cancer, breast cancer, esophageal cancer, and oral pharyngeal / laryngeal cancer.

33. The composition for use according to claim 27, wherein the composition is intended to be administered before alcohol consumption.

34. A method for decomposing alcohol in a subject, comprising administering a composition according to any one of claims 1 to 15 to the subject.

35. A method for preventing and / or treating alcohol-induced organ damage in a subject, comprising administering to the subject a composition according to any one of claims 1 to 15.

36. The method according to claim 35, wherein the organ is the liver and / or pancreas.

37. The method according to claim 34, for preventing and / or treating a disease, condition, or illness selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, cirrhosis, alcohol-induced cancer, cardiovascular disease, obesity, neuropathy, neurodegenerative disease, hangover symptoms, flushing syndrome, headache, and / or acetaldehyde poisoning.

38. The method according to claim 37, wherein the cancer is selected from liver cancer, pancreatic cancer, breast cancer, esophageal cancer, and oral pharyngeal cancer.

39. The method according to claim 34, wherein the composition is administered before alcohol consumption.

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