Alcohol degrading compositions and uses thereof

Abstract

The present invention provides an alcohol degrading composition comprising one or more strains of the genus Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmotic pressure carbohydrate. Also provided herein are methods of using the compositions.

Description

[0001] The present invention provides an alcohol degradation composition, which includes one or more species of Bacillus, rice bran, L-cysteine ​​and a high molecular weight low osmotic pressure carbohydrate. Also provided herein is a method of using the composition. Background Art

[0002] The fermentation of sugars into ethanol is one of the earliest biotechnologies employed by humans. The intoxicating effects of ethanol consumption have been known to humans since ancient times. Ethanol has been used by humans as a narcotic component of alcoholic beverages since prehistoric times. Dried residues on 9,000-year-old pottery found in China indicate that Neolithic people consumed alcoholic beverages. Today, many cultures around the world allow social drinking. It is considered a legitimate way to celebrate special occasions or to relax after a hard day at work. Moderate drinking is often seen as a harmless act.

[0003] People derive many benefits from social drinking. That's why the activity has remained popular for thousands of years. Alcohol is often described as a social lubricant. People tend to feel more relaxed and less shy after a drink or two. There are many social occasions based around drinking. Some studies even suggest that moderate drinking may offer certain health benefits. It's these beneficial aspects that ensure alcohol's continued popularity.

[0004] However, even people who drink in moderation can experience alcohol-related problems. Alcohol is a toxin that can harm the body even in small amounts. People who regularly drink above safe limits are at increased risk for health problems, including but not limited to certain cancers, cardiovascular events, high blood pressure, drunk driving accidents, and alcohol abuse and addiction. For some individuals, drinking any alcohol is unsafe.

[0005] Alcohol intoxication, also called drunkenness or alcohol poisoning, is the adverse behavioral and physical effects that occur after recent alcohol consumption. At low doses, symptoms may include mild sedation and poor coordination. At high doses, slurred speech, difficulty walking, and vomiting may occur. Extreme doses may cause respiratory depression, coma, or death. Complications may include seizures, aspiration pneumonia, injury (including suicide), and hypoglycemia.

[0006] Alcohol is metabolized primarily in the liver, which is why the liver is particularly susceptible to damage. Binge drinking significantly increases the risk of alcoholic fatty liver disease, an early, reversible consequence of excessive alcohol consumption. Long-term drinking alters fat metabolism in the liver, and excess fat accumulates in the liver. Other effects on the liver include long-term inflammation (alcoholic hepatitis). This can lead to scar tissue and, ultimately, cirrhosis.

[0007] New compositions, supplements, and / or therapies are needed to reduce the undesirable effects associated with alcohol intake. Summary of the invention

[0008] The present invention is based on the unexpected discovery that L-cysteine ​​can be used to increase the degradation of alcohol by one or more species of Bacillus. The inventors have unexpectedly discovered that L-cysteine ​​can be used to increase the degradation of alcohol by one or more species of Bacillus, particularly when combined with high molecular weight low osmotic pressure carbohydrates (such as dextrins). The inventors have shown that L-cysteine ​​can be used to increase the degradation of alcohol by one or more species of Bacillus in the digestive tract (gut), particularly when combined with high molecular weight low osmotic pressure carbohydrates (such as dextrins). Advantageously, the inventors have developed novel compositions to reduce the uptake of alcohol by the blood and, therefore, reduce the undesirable effects associated with alcohol intake.

[0009] The inventors have unexpectedly shown that the compositions described herein speed up the body's processing of alcohol by accelerating alcohol degradation, particularly in the digestive tract. Normally, about 80% of ingested alcohol resides 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 (thereby reducing the amount of alcohol processed by the liver). The inventors have shown that taking the compositions described herein prior to alcohol intake significantly reduces blood alcohol levels and breath alcohol levels after alcohol intake compared to placebo.

[0010] Thus, in one aspect, an alcohol degrading composition is provided that includes one or more species of Bacillus, rice bran, L-cysteine, and a high molecular weight low osmotic pressure carbohydrate.

[0011] Studies have shown that high molecular weight low osmotic pressure carbohydrates (e.g., dextrin) and / or L-cysteine ​​form a microenvironment in the digestive tract, so that the microbial consortium of the composition provided herein discharges an enzyme cascade targeting short carbon chains (e.g., ethanol / alcohol) after intestinal resuscitation, thereby preferentially targeting these substrates. The targeted enzyme preferentially acts on the alcohol that stays in the intestine and breaks it down into carbon dioxide and water, bypassing the liver to convert alcohol into acetaldehyde and acetic acid / acetate (which are hangover metabolites, otherwise formed by the liver converting alcohol). Therefore, the composition described herein accelerates the body's processing of alcohol (away from the liver).

[0012] After resuscitation in the intestine, the Bacillus (and its endospores) in the composition scan the biochemical conditions of its microenvironment and begin to discharge unique bioactive substances to optimize the conditions for its survival and reproduction, such as pH, conductivity, and electrolytes. Nutrients and substrates are essential for survival and subsequent reproduction. When alcohol / ethanol / ethyl alcohol is present in the microenvironment, enzymes targeting alcohol are discharged to decompose alcohol into carbon-containing fragments. Carbon that cannot be used as nutrients by microorganisms or adjacent tissue cells will be biochemically metabolized into water and carbon dioxide, which can escape the body system without causing any biological consequences / symptoms. High molecular weight low osmotic pressure carbohydrates (e.g., dextrins) and / or L-cysteine ​​provided in the composition described herein enhance this environmental scan and the selective discharge of bioactive substances to optimize enzymatic conditions.

[0013] Advantageously, compositions provided herein can be formulated as acid-resistant tablets or capsules. Known such preparations are resistant to gastric acid and only dissolve when they reach the duodenum. Then, the species of the Bacillus genus of the compositions can be released to settle in the upper part of the intestinal tract, where they can stay for about a day and then be eliminated from the body through feces. The strains of compositions as described herein are selected to preferentially and effectively metabolize ethanol into CO2 and water, thereby reducing the further reabsorption of alcohol by the intestinal tract. Therefore, it is expected that the alcohol absorbed by the body is less, and the damage caused by alcohol degradation products to the organs is also reduced.

[0014] As described above, in one aspect, the present invention provides an alcohol degradation composition comprising one or more species of Bacillus, rice bran, L-cysteine, and a high molecular weight low osmotic pressure carbohydrate.

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

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

[0017] Appropriately,

[0018] a) the Bacillus subtilis species may be selected from the group consisting of: Bacillus subtilis strain DFM 0326 (LMGP-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900); and / or

[0019] c) The Bacillus coagulans species may be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0020] Suitably, the high molecular weight low osmotic pressure carbohydrate may be dextrin.

[0021] Suitably, the alcohol may be ethyl alcohol (ethanol).

[0022] Suitably, the composition may further comprise one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus MT 03, Bacillus atrophaeus and Pediococcus pentosaceus.

[0023] Suitably, the composition may comprise at least about 10% w / w L-cysteine.

[0024] Suitably, the composition may comprise at least about 10,000 cfu / g of bacteria of the genus Bacillus.

[0025] Suitably, the composition may comprise at least about 67% w / w rice bran.

[0026] Suitably, the composition may comprise at least about 0.5% w / w high molecular weight low osmotic pressure carbohydrate.

[0027] Suitably, the composition may further comprise one or more of the following: vitamin B12, magnesium salt of fatty acid, calcium phosphate, potassium phosphate, silicon dioxide and cellulose, optionally wherein the magnesium salt of fatty acid is magnesium stearate.

[0028] Suitably, the composition may be formulated as an acid-resistant tablet or capsule. Suitably, the acid-resistant tablet or capsule may comprise a film coating, wherein the film coating comprises hydroxypropylmethylcellulose (HPMC).

[0029] Suitably, in some examples, the one or more species of the genus Bacillus are not genetically modified.

[0030] The present invention also provides use of the alcohol degradation composition as described herein for degrading alcohol.

[0031] The present invention further provides the use of L-cysteine ​​for increasing the degradation of alcohol by one or more species of Bacillus.

[0032] Suitably, L-cysteine ​​may be combined with a high molecular weight low osmotic pressure carbohydrate, optionally wherein the high molecular weight low osmotic pressure carbohydrate is dextrin.

[0033] Suitably, L-cysteine ​​may be combined with rice bran.

[0034] Suitably, the one or more species of the genus Bacillus may be selected from Bacillus subtilis and Bacillus coagulans, optionally wherein the composition comprises Bacillus subtilis and Bacillus coagulans.

[0035] Appropriately,

[0036] a) the Bacillus subtilis species may be selected from the group consisting of: Bacillus subtilis strain DFM 0326 (LMGP-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900); and / or

[0037] c) The Bacillus coagulans species may be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0038] Suitably, the alcohol may be ethyl alcohol (ethanol).

[0039] Suitably, the use may be for degrading alcohol in a subject. Suitably, the use may be for metabolizing alcohol in the digestive tract of a subject, optionally wherein the use is for metabolizing alcohol in the intestinal tract of a subject, more optionally wherein the use is for metabolizing alcohol in the small intestine of a subject.

[0040] Suitably, the use may be for reducing the absorption of alcohol into the blood of a subject.

[0041] Suitably, the use may be for reducing breath or blood alcohol concentration in a subject.

[0042] The present invention further provides a composition as described herein for use as a medicament.

[0043] The present invention further provides a composition as described herein for use in degrading alcohol in a subject.

[0044] The present invention also provides a composition as described herein for use in preventing and / or treating alcohol-induced organ damage in a subject. Suitably, the organ may be the liver and / or pancreas.

[0045] Suitably, the composition may be used to prevent and / or treat a disease, disorder or ailment selected from the group consisting of: alcohol-induced fatty liver, alcohol-induced hepatitis, liver cirrhosis, alcohol-induced cancer, cardiovascular disease, obesity, neuropathy, neurodegenerative disease, 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.

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

[0047] Provided are methods of degrading alcohol in a subject comprising administering to the subject a composition described herein.

[0048] The present invention further provides a method for 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 pancreas.

[0049] Suitably, the method may be used to prevent and / or treat a disease, disorder or ailment selected from the group consisting of: alcohol-induced fatty liver, alcohol-induced hepatitis, liver cirrhosis, alcohol-induced cancer, cardiovascular disease, obesity, neuropathy, neurodegenerative disease, 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.

[0050] Suitably, the composition may be administered prior to alcohol ingestion.

[0051] The present invention provides an alcohol degradation composition, which includes one or more species of Bacillus, rice bran, L-cysteine ​​and a high molecular weight low osmotic pressure carbohydrate. Also provided herein is a method of using the composition.

[0052] In each aspect and embodiment of the invention as described herein, unless the context dictates otherwise, rice bran can be replaced with any suitable cereal (e.g., cereal grains). In these aspects and embodiments, suitable cereals can be any suitable cereal bran. Suitable cereals and suitable cereal brans are discussed elsewhere herein.

[0053] Throughout the description and claims of this specification, the words “comprise” and “comprising” and variations thereof mean “including but not limited to”, and they are not intended to (and do not) exclude other parts, additives, components, integers or steps.

[0054] Throughout the description and claims of this specification, the singular encompasses the plural, unless the context requires otherwise. In particular, where the indefinite article is used, the specification is to be understood as contemplating plurality as well as singularity, unless the context requires otherwise.

[0055] Features, integers, characteristics, compounds, chemical moieties or groups described in conjunction with a particular aspect, embodiment or example of the invention are to be understood to be applicable to any other aspect, embodiment or example described herein unless incompatible therewith.

[0056] Various aspects of the invention are described in further detail below.

[0057] Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure

[0058] Several Bacillus strains described in this application are deposited in the Belgian Collaborative Collection of Microorganisms (BCCM) (LMG), which is an international depository institution located at Universiteit Gent, KLLedeganckstraat 35, 9000 Gent, Belgium. These 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

[0059] The embodiments of the present invention will be further described below with reference to the accompanying drawings, in which:

[0060] Figure 1 The mean blood alcohol concentration after ingestion of 0.3 g / kg body weight is shown (n=24).

[0061] Figure 2 The mean reduction in blood alcohol absorption by AB001 is shown.

[0062] Figure 3 Shown are the mean breath alcohol concentrations after ingestion of 0.3 g / kg body weight (n=24).

[0063] Figure 4 Mean reductions in breath alcohol levels by AB001 are shown.

[0064] Figure 5 Shown are mean blood alcohol concentrations after ingestion of 2 x 0.3 g / kg body weight with a light breakfast in between (30 min, n=24).

[0065] Figure 6 The mean reduction in blood alcohol absorption by AB001 is shown.

[0066] Figure 7 Shown are mean breath alcohol concentrations after ingestion of 2 x 0.3 g / kg body weight with a light breakfast in between (30 min, n=24).

[0067] Figure 8 Data generated from individuals (74 males and females, aged 26 to 66 years) ingesting 60cc of wine (14%) in 1 hour are shown. The individuals were given the following composition at 600mg / dose: fermented rice bran 414mg, L-cysteine ​​120mg, dextrin 10mg, vitamin B12 0.90mcg, excipient 26mg, HPMC capsule.

[0068] Fig. 9Data are shown for subjects (84 individuals, 56 males, and 28 females, aged 26 to 72 years) who ingested 60 cc of wine (14%) over 1 hour.

[0069] Composition: fermented rice bran 69%, L-cysteine ​​20%, dextrin 2%, vitamin B12 0.00002%,

[0070] Excipient 9%, HPMC capsule.

[0071] Fig.10 Data are shown for subjects (87 males and females, aged 26 to 66 years) who ingested 60 cc of wine (14%) over 1 hour. Subjects were given 750 mg / dose of

[0072] Composition: fermented rice bran 518mg, L-cysteine ​​150mg, dextrin 15mg, vitamin B12 0.90mcg, excipient 67mg, HPMC capsule, and determine the reaction time.

[0073] Fig.11 Data are shown for subjects (62 males and females, aged 26 to 66 years) who ingested 60 cc of wine (14%) over 1 hour.

[0074] Composition: fermented rice bran 69%, L-cysteine ​​20%, dextrin 2%, vitamin B12 0.00002%,

[0075] Excipient 9%, HPMC capsule. Compared to the "expected awake time" according to the iBAC manual, the time is shortened to 0.05‰ (according to sc.edu*

[0076] (*https: / / sc.edu / about / offices_and_divisions / fraternity_and_sorority_life / do cuments / bac-charts1617.pdf).

[0077] Fig.12 Changes in plasma bilirubin levels are shown; data were generated from an in vivo alcohol study in mice. IC = intact control group, fed a standard rodent diet, CMD = placebo group, fed a high fat and high carbohydrate diet (Western Diet) mixed with 10% ethanol and maltodextrin. PB = probiotic group, fed a high fat and high carbohydrate diet (Western Diet) mixed with 10% ethanol and AB001.

[0078] Fig.13 Shown are changes in body weight during an in vivo alcohol study in mice.

[0079] Fig.14 An overview of experimental design for in vivo alcohol studies in mice.

[0080] The patents, scientific and technical literature cited herein establish the knowledge available to those skilled in the art at the time of filing. The entire disclosures of issued patents, published and pending patent applications, and other publications cited herein are incorporated herein by reference to the same extent as if each was specifically and individually indicated to be incorporated by reference. In the event of any inconsistency, the present disclosure will control.

[0081] Various aspects of the invention are described in further detail below. DETAILED DESCRIPTION

[0082] The present invention is based on the unexpected discovery that L-cysteine ​​can be used to increase the degradation of alcohol by one or more species of Bacillus. The inventors unexpectedly found that L-cysteine ​​can increase the degradation of alcohol by one or more species of Bacillus, particularly when combined with high molecular weight low osmotic pressure carbohydrates (such as dextrins). The data provided herein show that L-cysteine, particularly when combined with high molecular weight low osmotic pressure carbohydrates (such as dextrins), can be used to increase the degradation of alcohol by one or more species of Bacillus in the digestive tract. Advantageously, the inventors have developed a novel composition to reduce the blood uptake of alcohol and thus reduce the undesirable effects associated with alcohol intake.

[0083] Thus, provided herein are alcohol degrading compositions comprising one or more species of Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmotic pressure carbohydrate.

[0084] The compositions provided herein may be referred to as "MYRKL" and / or "AB001." In addition, the compositions provided herein may be referred to as "Pinch," unless the context otherwise defines "Pinch" (see Example 1).

[0085] As used herein, "alcohol" refers to a class of organic compounds characterized by one or more hydroxyl ("OH") groups attached to the carbon atoms of an alkyl group (hydrocarbon chain). Alcohols can be considered as organic derivatives of water (H2O) in which one of the hydrogen atoms is replaced by an alkyl group (usually represented by R in organic structures). For example, in ethanol (or ethylalcohol), the alkyl group is an ethyl group, -CH2CH3. Depending on how the carbon of the alkyl group is attached to the hydroxyl group, alcohols can be classified as primary, secondary, or tertiary alcohols. Most alcohols are colorless liquids or solids at room temperature. Low molecular weight alcohols have a high solubility in water; as the molecular weight increases, their solubility in water becomes lower, and their boiling point, vapor pressure, density, and viscosity increase. Those skilled in the art can easily identify alcohols using conventional methods in the art. Non-limiting examples of alcohols include methanol and ethanol.

[0086] As will be clear to those skilled in the art, "alcohol degradation compositions" as referred to herein are compositions that degrade alcohols. In other words, as used herein, "alcohol degradation compositions" are compositions that decompose (e.g., biochemically decompose) alcohols. In the context of the present invention, the degradation (e.g., decomposition) of a substance (such as an alcohol) involves converting the substance into one or more other different substances. In addition, as will be understood by those skilled in the art, as used herein, "alcohol degradation" refers to the decomposition of alcohols, and as used herein, "alcohol degradation" refers to the decomposition of alcohols. As will be clear to those skilled in the art, the compositions described herein may be used in vitro or in vivo.

[0087] Alcohol can be degraded (e.g. decomposed) in a variety of different ways. In the context of the present invention, biochemical degradation is particularly relevant. Thus, in one example, alcohol can be biochemically degraded (e.g. decomposed). As known to those skilled in the art, biochemical decomposition of a substance can involve enzyme catalyzed reactions. Thus, in one example, alcohol can be enzymatically degraded.

[0088] In the body, alcohol is metabolized through several processes or pathways. The most common of these pathways involve two enzymes – alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). These enzymes help break down alcohol molecules so that they can be eliminated from the body. After alcohol is ingested, most of the ethanol in the body is broken down in the liver by ADH. First, ADH metabolizes alcohol into acetaldehyde, which is a highly toxic substance and a known carcinogen. Then, in a second step, acetaldehyde is further metabolized by acetaldehyde dehydrogenase into another less active byproduct, acetate, which is then broken down into water and carbon dioxide for easier elimination. Acetate is mainly broken down into carbon dioxide and water in tissues other than the liver. Alcohol dehydrogenase generates free oxygen radicals that affect genes. The enzymes cytochrome P450 2E1 (CYP2E1) and catalase also break down alcohol into acetaldehyde. However, CYP2E1 is only active after a person drinks a large amount of alcohol, and catalase metabolizes only a small portion of the alcohol in the body. Small amounts of alcohol are also removed by interacting with fatty acids to form compounds called fatty acid ethyl esters (FAEE). These compounds have been shown to cause damage to the liver and pancreas.

[0089] Advantageously, the compositions described herein promote the degradation (e.g., decomposition) of alcohol in the digestive tract into carbon dioxide and water, while bypassing the liver to convert alcohol into harmful metabolites, including acetaldehyde and, in turn, acetic acid, which are believed to be hangover metabolites formed by the liver's conversion of alcohol. The compositions described herein can promote the degradation of alcohol in the digestive tract into carbon dioxide and water via intermediate metabolites (other than acetaldehyde and / or acetic acid).

[0090] As used herein, "metabolism" is a term used to describe all biochemical reactions involved in maintaining the viability of cells and organisms. For example, metabolism includes all biochemical reactions involved in converting one molecule into another (to essentially maintain the viability of the cell or organism). Metabolism includes processes for cell growth, reproduction, response to the environment, survival mechanisms, support, and maintenance of cellular structure and integrity. The biochemical reactions involved in metabolism utilize various enzymes.

[0091] In one example, alcohol can be metabolized (i.e., alcohol can be degraded by metabolism). Therefore, in one example, an alcohol metabolism composition is provided, which includes one or more strains of Bacillus, rice bran, L-cysteine, and a high molecular weight low osmotic pressure carbohydrate (e.g., dextrin). As known to those skilled in the art, metabolism can be enzymatic, and therefore, in some examples, alcohol can be enzymatically metabolized.

[0092] Metabolism can be divided into two categories: catabolism and anabolism. Catabolism includes 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 decomposition of organic or inorganic substances (such as proteins, sugars, fatty acids, etc.). Anabolism includes a series of biochemical reactions that build or synthesize molecules from smaller units, usually requiring energy (ATP) input in the process. Therefore, catabolism refers to the destructive biochemical reactions that occur in an organism, while metabolism refers to the entire biochemical reactions in an organism, which can be either constructive or destructive.

[0093] In some instances, the degradation of alcohol by metabolism can be considered catabolism. Thus, in some instances, alcohol can be catabolized (i.e., alcohol can be degraded by catabolism). In another instance, alcohol can be enzymatically catabolized.

[0094] In some instances, alcohol is degraded in a subject. As a non-limiting example, alcohol can be enzymatically decomposed, metabolized, or catabolized in a subject. When alcohol is degraded in a subject (e.g., particularly in the duodenum and / or small intestine), this can be referred to as digestion. In some instances, alcohol can be degraded by biochemical digestion.

[0095] In one example, the alcohol is ethyl alcohol (also known as ethanol).

[0096] Ethanol is an organic compound. It is a simple alcohol with a chemical formula of C2H6O. Its molecular formula can also be written as CH3-CH2-OH or C2H5OH (ethyl group is connected to hydroxyl group), and is usually abbreviated as EtOH. Ethanol is a volatile, flammable, colorless liquid with a typical wine smell and spicy taste. It is an active ingredient in psychoactive drugs, recreational drugs and alcoholic beverages. Therefore, in one example, alcohol is included in alcoholic beverages. Non-limiting examples of alcoholic beverages include beer, wine and spirits (such as vodka).

[0097] Thus, in one example, provided herein is an ethanol degradation composition comprising one or more species of Bacillus, rice bran, L-cysteine, and a high molecular weight, low osmotic pressure carbohydrate (eg, dextrin).

[0098] In another example, provided herein is an ethanol metabolism composition comprising one or more species of Bacillus, rice bran, L-cysteine, and a high molecular weight low osmotic pressure carbohydrate (eg, dextrin).

[0099] As discussed elsewhere herein, the alcohol degradation compositions provided herein include one or more strains of the genus Bacillus. For example, the composition may include two or more strains of the genus Bacillus. In another example, the composition may include three or more strains of the genus Bacillus. In yet another example, the composition may include four or more strains of the genus Bacillus. In yet another example, the composition may include five or more strains of the genus Bacillus. In yet another example, the composition may include six or more strains of the genus Bacillus. In another example, the composition may include seven or more strains of the genus Bacillus.

[0100] As is known in the art, a genus consists of several species. Thus, the genus "Bacillus" includes all species within the genus "Bacillus" known to those skilled in the art, including, but 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 stearothermophilus, Bacillus subtilis, Bacillus Velezii, Bacillus MT 03. Bacillus atrophaeus and Bacillus thuringiensis. It is recognized that the genus Bacillus continues to undergo taxonomic reorganization. Therefore, the genus is intended to include species that have been reclassified, including but not limited to organisms such as B. stearothermophilus (now called "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 Alicyclobacillus, Amphibacillus, Aneurinibacillus, Anoxybacillus, Brevibacillus, Filobacillus, Gracilibacillus, Halobacillus, Paenibacillus, Salibacillus, Thermobacillus, Ureibacillus, and Virgibacillus.

[0101] Species in the genus Bacillus are gram-positive bacteria classified as members of the family Bacillaceae, the order Bacilales, the class Bacilli. As used herein, "Bacillus sp." refers to a species in the genus "Bacillus."

[0102] Bacillus species found to be particularly important in the context of the present invention include B. subtilis and B. coagulans. As described in the examples below, these bacteria are abundant in the compositions of the present invention and are particularly effective in degrading (e.g., metabolizing) ethanol into carbon dioxide and water, especially in the digestive tract.

[0103] Thus, in one example, the one or more species of the genus Bacillus are selected from Bacillus subtilis and Bacillus coagulans.

[0104] In another example, the compositions provided herein include Bacillus subtilis and Bacillus coagulans.

[0105] According to the present invention, any suitable strain of Bacillus subtilis and / or Bacillus coagulans may be used. A person skilled in the art will be able to readily 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.

[0106] The Bacillus subtilis strain deposited under LMG-P Accession No. 32899 may be referred to herein as "DFM 0326" or "strain DFM 0326". Bacillus subtilis strain DFM 0326 (deposited under LMG-P Accession No. 32899) was deposited on November 22, 2022, at the Belgian Cooperative Collection of Microorganisms (BCCM) under the Budapest Treaty of 1977, Laboratory of Microbiology - (LMG),Universiteit Gent,KLLedeganckstraat 35,9000Gent,Belgium.

[0107] 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 on November 22, 2022, at the Belgian Cooperative Collection of Microorganisms (BCCM) under the Budapest Treaty of 1977, Laboratory of Microbiology - (LMG),Universiteit Gent,KLLedeganckstraat 35,9000Gent,Belgium.

[0108] 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 on December 14, 2022, at the Belgian Cooperative Collection of Microorganisms (BCCM) under the Budapest Treaty of 1977, Laboratory of Microbiology - (LMG),Universiteit Gent,KLLedeganckstraat 35,9000Gent,Belgium.

[0109] Thus, in some examples, the Bacillus 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 Bacillus coagulans species can be Bacillus coagulans strain DFM0705 (LMG P-32921).

[0110] Thus, in examples where the composition includes Bacillus subtilis and Bacillus coagulans, the Bacillus subtilis species can be Bacillus subtilis strain DFM 0326 (LMG P-32899), and the Bacillus coagulans species can be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0111] In another example, when the composition includes Bacillus subtilis and Bacillus coagulans, the Bacillus subtilis species can be Bacillus subtilis strain DFM 1015 (LMG P-32900), and the Bacillus coagulans species can be Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0112] In some examples, the compositions of the present invention may include a combination of Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900).

[0113] In another example where the composition includes Bacillus subtilis and Bacillus coagulans, the composition can include Bacillus 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). It is noteworthy that the composition used in the examples provided herein includes Bacillus subtilis strain DFM 0326 (LMG P-32899), Bacillus subtilis strain DFM1015 (LMG P-32900) and Bacillus coagulans strain DFM 0705 (LMG P-32921).

[0114] Thus, the compositions of the present invention may include 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).

[0115] The inventors have also identified several other bacterial species that are particularly relevant to the compositions described herein. Thus, in one example, the composition may further include one or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus Velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus. In another example, the composition may further include two or more, three or more, four or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus Velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

[0116] In another example, the composition can further include Bacillus amyloliquefaciens, Bacillus velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

[0117] The bacterial strains included in the alcohol degradation compositions provided herein are identified as being able to preferentially and efficiently metabolize ethanol into carbon dioxide and water. Advantageously, the inventors have shown that ingestion of the compositions described herein prior to alcohol intake significantly reduces blood alcohol levels and breath alcohol levels after alcohol intake compared to a placebo, thereby demonstrating that the compositions described herein reduce further absorption of alcohol by the intestine after alcohol intake.

[0118] Compositions provided herein include one or more strains of Bacillus of suitable amount or concentration.Therefore, the amount or concentration of one or more strains of Bacillus can be described by the number (cfu / g) of colony forming units (cfu) of reference per gram of composition or the total number (in other words, cfu of every effective dose) of colony forming units (cfu) of every dosage composition.It will be clear to those skilled in the art, and as described in more detail elsewhere herein, dosage can include one or more dosage units (e.g., 2 dosage units).In the example of using multiple dosage units to provide effective dose, cfu / dosage corresponds to the total cfu of multiple dosage units.

[0119] In one example, the composition described herein includes about 10,000 cfu / g of Bacillus bacteria to about 1×10 8 cfu / g of Bacillus bacteria.

[0120] In one example, the compositions described herein include at least about 1×10 8 cfu / g of Bacillus bacteria. In another example, the composition described herein includes at least about 1×10 7 cfu / g of Bacillus bacteria. In another example, the composition described herein includes at least about 1×10 6 cfu / g of Bacillus bacteria. In another example, the composition described herein includes at least about 1×10 5 cfu / g of Bacillus bacteria.

[0121] In one example, the compositions described herein include at least about 10,000 cfu / g (i.e., at least about 1.0×10 4 cfu / g) of Bacillus bacteria.

[0122] In another example, the compositions described herein include at least about 11,000 cfu / g (i.e., at least about 1.1×10 4 cfu / g) of Bacillus. In another example, the composition described herein includes at least about 12,000 cfu / g (i.e., at least about 1.2×10 4 cfu / g) of Bacillus bacteria.

[0123] In another example, the compositions described herein include at least about 13,000 cfu / g (i.e., at least about 1.3×10 4 cfu / g) of Bacillus bacteria.

[0124] In another example, the compositions described herein include at least about 14,000 cfu / g (i.e., at least about 1.4×10 4cfu / g) of Bacillus. In another example, the composition described herein includes at least about 15,000 cfu / g (i.e., at least about 1.5×10 4 cfu / g) of Bacillus bacteria.

[0125] In one example, the composition described herein includes about 1×10 8 cfu / g of Bacillus bacteria. In another example, the composition described herein includes about 1×10 7 cfu / g of Bacillus bacteria. In another example, the composition described herein includes about 1×10 6 cfu / g of Bacillus bacteria. In another example, the composition described herein includes about 1×10 5 cfu / g of Bacillus bacteria.

[0126] In one example, the composition described herein comprises about 10,000 cfu / g (ie, about 1.0×10 4 cfu / g) of Bacillus bacteria.

[0127] In another example, the composition described herein comprises about 11,000 cfu / g (ie, about 1.1×10 4 cfu / g) of Bacillus. In another example, the composition described herein includes about 12,000 cfu / g (ie, about 1.2×10 4 cfu / g) of Bacillus bacteria.

[0128] In another example, the composition described herein comprises about 13,000 cfu / g (ie, about 1.3×10 4 cfu / g) of Bacillus bacteria.

[0129] In another example, the composition described herein comprises about 14,000 cfu / g (ie, about 1.4×10 4 cfu / g) of Bacillus. In another example, the composition described herein includes about 15,000 cfu / g (ie, about 1.5×10 4 cfu / g) of Bacillus bacteria.

[0130] Those skilled in the art can easily determine the amount or concentration of bacteria present in the composition using conventional methods known in the art. For example, the total viable count (TVC) of Bacillus viable cells can be determined by a given culture method based on a specific Bacillus culture medium (such as Chrome Select agar). Alternative methods are known in the art.

[0131] In one example, the composition described herein includes about 5,000 cfu of Bacillus bacteria per dose to about 1×10 8 cfu of Bacillus bacteria / dose.

[0132] In one example, the compositions described herein include at least about 1×10 8 cfu of Bacillus bacteria / dose. In another example, the composition described herein includes at least about 1×10 7 cfu of Bacillus bacteria / dose. In another example, the composition described herein includes at least about 1×10 6 cfu of Bacillus bacteria / dose.

[0133] In yet another example, the compositions described herein include at least about 1×10 5 cfu of Bacillus bacteria / dose.

[0134] In one example, the compositions described herein include at least about 5,000 cfu (i.e., at least about 0.5×10 4 cfu) of Bacillus bacteria / dose.

[0135] In another example, the compositions described herein include at least about 10,000 cfu (i.e., at least about 1.0×10 4 cfu) of Bacillus spp. / dose. In another example, the compositions described herein include at least about 11,000 cfu (i.e., at least about 1.1×10 4 cfu) of Bacillus spp. / dose. In another example, the composition described herein includes at least about 12,000 cfu (i.e., at least about 1.2×10 4 cfu) of Bacillus spp. / dose. In another example, the compositions described herein include at least about 13,000 cfu (i.e., at least about 1.3×10 4 cfu) of Bacillus spp. / dose. In another example, the compositions described herein include at least about 14,000 cfu (i.e., at least about 1.4×10 4 cfu) of Bacillus spp. / dose. In another example, the compositions described herein include at least about 15,000 cfu (i.e., at least about 1.5×10 4 cfu) of Bacillus bacteria / dose.

[0136] In one example, the composition described herein includes about 1×10 8 cfu of Bacillus bacteria / dose. In another example, the composition described herein includes about 1×10 7cfu of Bacillus bacteria / dose. In another example, the composition described herein includes about 1×10 6 cfu of Bacillus bacteria / dose.

[0137] In yet another example, the composition described herein includes about 1×10 5 cfu of Bacillus bacteria / dose.

[0138] In one example, the composition described herein includes about 5,000 cfu (ie, about 0.5×10 4 cfu) of Bacillus spp. / dose. In one example, the composition described herein includes about 10,000 cfu (ie, about 1.0×10 4 cfu) of Bacillus spp. / dose. In another example, the composition described herein includes about 11,000 cfu (ie, about 1.1×10 4 cfu) of Bacillus bacteria / dose. In another example, the composition described herein includes about 12,000 cfu (ie, about 1.2×10 4 cfu) of Bacillus sp. / dose. In another example, the composition described herein includes about 13,000 cfu (ie, about 1.3×10 4 cfu) of Bacillus spp. / dose. In another example, the composition described herein includes about 14,000 cfu (ie, about 1.4×10 4 cfu) of Bacillus spp. / dose. In another example, the composition described herein includes about 15,000 cfu (ie, about 1.5×10 4 cfu) of Bacillus bacteria / dose.

[0139] It will be clear to those skilled in the art that the amount or concentration of one or more species of Bacillus in the composition may consist of any single species of Bacillus or any combination of species of Bacillus. For example, the amount or concentration of one or more species of Bacillus in the composition may consist entirely of one species of Bacillus (e.g., the concentration may consist entirely of Bacillus subtilis or entirely of Bacillus coagulans). Alternatively, the amount or concentration of one or more species of Bacillus in the composition may consist of two or more, three or more, four or more, or five or more species of Bacillus (e.g., the concentration may consist of Bacillus subtilis and Bacillus coagulans). Thus, in one example, the amount or concentration of one or more species of Bacillus in the composition refers to the amount or concentration of the combination of Bacillus species present.

[0140] In some examples, the compositions provided herein include a suitable concentration of bacteria, wherein a certain proportion of the concentration is composed of one or more species of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans). In one example, the composition described herein includes about 10,000 cfu / g (i.e., about 1.0×10 4 cfu / g) to about 1×10 8 cfu / g of bacteria. In one example, the composition described herein includes at least about 1×10 8 cfu / g of bacteria. In another example, the composition described herein includes at least about 1×10 7 cfu / g of bacteria. In another example, the composition described herein includes at least about 1×10 6 cfu / g of bacteria. In another example, the composition described herein includes at least about 1×10 5 cfu / g of bacteria. In one example, the composition described herein includes at least about 10,000 cfu / g (i.e., at least about 1.0×10 4 cfu / g) of bacteria. In another example, the composition described herein includes at least about 11,000 cfu / g (i.e., at least about 1.1×10 4 In another example, the composition described herein includes at least about 12,000 cfu / g (i.e., at least about 1.2×10 4 In another example, the composition described herein includes at least about 13,000 cfu / g (i.e., at least about 1.3×10 4 In another example, the composition described herein includes at least about 14,000 cfu / g (i.e., at least about 1.4×10 4 In another example, the composition described herein includes at least about 15,000 cfu / g (i.e., at least about 1.5×10 4 cfu / g) of bacteria. In one example, the composition described herein includes about 1×10 8 cfu / g of bacteria. In another example, the composition described herein includes about 1×10 7 cfu / g of bacteria. In another example, the composition described herein includes about 1×10 6 cfu / g of bacteria. In another example, the composition described herein includes about 1×10 5 cfu / g of bacteria. In one example, the composition described herein includes about 10,000 cfu / g (ie, about 1.0×10 4cfu / g) of bacteria. In another example, the composition described herein includes about 11,000 cfu / g (ie, about 1.1×10 4 cfu / g) of bacteria. In another example, the composition described herein includes about 12,000 cfu / g (ie, about 1.2×10 4 cfu / g) of bacteria. In another example, the composition described herein includes about 13,000 cfu / g (ie, about 1.3×10 4 In another example, the composition described herein includes about 14,000 cfu / g (ie, about 1.4×10 4 cfu / g) of bacteria. In another example, the composition described herein includes about 15,000 cfu / g (ie, about 1.5×10 4 cfu / g) of bacteria.

[0141] In some examples, the compositions provided herein include a suitable amount of bacteria, wherein a certain proportion of the amount consists of one or more species of the genus Bacillus (eg, Bacillus subtilis and / or Bacillus coagulans).

[0142] In one example, the compositions described herein include about 5,000 cfu of bacteria per dose to about 1×10 8 cfu of bacteria / dose. In one example, the composition described herein includes at least about 1×10 8 cfu of bacteria / dose. In another example, the composition described herein includes at least about 1×10 7 cfu of bacteria / dose. In another example, the composition described herein includes at least about 1×10 6 cfu of bacteria / dose. In another example, the composition described herein includes at least about 1×10 5 cfu of bacteria / dose. In one example, the compositions described herein include at least about 5,000 cfu (i.e., at least about 0.5×10 4 cfu) of bacteria per dose. In another example, the compositions described herein include at least about 10,000 cfu (i.e., at least about 1.0×10 4 cfu) of bacteria per dose. In another example, the compositions described herein include at least about 11,000 cfu (i.e., at least about 1.1×10 4 cfu) of bacteria per dose. In another example, the compositions described herein include at least about 12,000 cfu (i.e., at least about 1.2×10 4 cfu) of bacteria per dose. In another example, the compositions described herein include at least about 13,000 cfu (i.e., at least about 1.3×104 cfu) of bacteria per dose. In another example, the compositions described herein include at least about 14,000 cfu (i.e., at least about 1.4×10 4 cfu) of bacteria per dose. In another example, the compositions described herein include at least about 15,000 cfu (i.e., at least about 1.5×10 4 cfu) of bacteria / dose. In one example, the composition described herein includes about 1×10 8 cfu of bacteria / dose. In another example, the composition described herein includes about 1×10 7 cfu of bacteria / dose. In another example, the composition described herein includes about 1×10 6 cfu of bacteria / dose. In another example, the composition described herein includes about 1×10 5 cfu of bacteria / dose. In one example, the composition described herein includes about 5,000 cfu (ie, about 0.5×10 4 cfu) of bacteria per dose. In one example, the composition described herein includes about 10,000 cfu (ie, about 1.0×10 4 cfu) of bacteria per dose. In another example, the composition described herein includes about 11,000 cfu (ie, about 1.1×10 4 cfu) of bacteria per dose. In another example, the composition described herein includes about 12,000 cfu (ie, about 1.2×10 4 cfu) of bacteria per dose. In another example, the composition described herein includes about 13,000 cfu (ie, about 1.3×10 4 cfu) of bacteria per dose. In another example, the composition described herein includes about 14,000 cfu (ie, about 1.4×10 4 cfu) of bacteria per dose. In another example, the composition described herein includes about 15,000 cfu (ie, about 1.5×10 4 cfu) of bacteria / dose.

[0143] As will be clear to the skilled person, the amount or concentration of bacteria, wherein a certain proportion consists of one or more species of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans), may further include any suitable individual species or any combination of species. For example, the amount or concentration of bacteria, wherein a certain proportion consists of one or more species of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans), may further include a certain proportion of one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

[0144] In one example, one or more species of the genus Bacillus are genetically modified.

[0145] 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 indirectly manipulated genomes by controlling reproduction and selecting offspring with desired characteristics, however, 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.

[0146] In other examples, the one or more species of the genus Bacillus are not genetically modified. In other words, the one or more species of the genus Bacillus can be naturally occurring.

[0147] One or more 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) wherein the group includes two or more different microorganisms (e.g., two or more bacteria, which may be from the same species (e.g., two or more different strains) or different species (e.g., two or more different species).

[0148] The microbial consortium may be a naturally occurring microbial consortium (e.g., a consortium naturally produced during the fermentation of a grain, such as rice bran). In other words, one or more species of Bacillus may become part of the composition due to the presence of the fermented grain, such as rice bran (and its associated naturally occurring microbial consortium) in the composition. Thus, one or more species of Bacillus may be a natural component of the fermented grain, such as rice bran.

[0149] The present inventors have discovered 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 used in the examples provided herein, in particular fermented rice bran. Thus, Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900) and Bacillus coagulans strain DFM 0705 (LMGP-32921) can be part of the compositions described herein because of the presence of fermented grains, such as rice bran (and its associated naturally occurring microbial consortium) in the compositions.

[0150] In another example, one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus Velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be (part of) a naturally occurring microbial consortium, e.g., a consortium naturally produced during the fermentation of a grain, such as rice bran. In other words, due to the presence of a fermented grain, such as rice bran (and its associated naturally occurring microbial consortium) in the composition, one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus Velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be part of the composition. Thus, one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus Velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be a natural component of a fermented grain, such as rice bran.

[0151] In another example, one or more species of Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans) and one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus Velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus can be (part of) a naturally occurring microbial consortium (e.g., a community naturally occurring during the fermentation of a grain (such as rice bran)). In other words, due to the presence of fermented grains, such as rice bran (and its associated naturally occurring microbial consortium) in the composition, one or more species of Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans) and one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus Velez, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus can be part of the composition. Thus, one or more species of Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans) and one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus velezensii, Bacillus MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be natural components of fermented grains such as rice bran.

[0152] It will be clear to those skilled in the art that the present invention is not limited to naturally occurring microbial consortia. Thus, the microbial consortia discussed above may also be artificially generated, for example by combining one or more bacterial isolates. In one example, therefore, one or more species of Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans) may be added to the composition alone.

[0153] Thus, the alcohol degradation composition may also include a grain, such as rice bran (e.g., fermented rice bran), as discussed in more detail elsewhere herein. For example, fermented rice bran may be a natural source of one or more species of Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans) present in the composition.

[0154] The present inventors have unexpectedly discovered that L-cysteine ​​can be used to increase the degradation of alcohol by one or more species of Bacillus, particularly when combined with a high molecular weight, low osmotic pressure carbohydrate such as dextrin.

[0155] Thus, the alcohol degrading compositions described herein include L-cysteine ​​in combination with one or more species of Bacillus (eg, where the bacteria are added to the composition as a bacterial supplement or a natural product (eg, as part of fermented rice bran)).

[0156] L-cysteine ​​(L-cys) is a non-essential amino acid and is therefore one of the building blocks required for protein synthesis. It 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 reactivity of amino acids and therefore for many of their biological functions in humans. L-cysteine ​​occupies a key position in the sulfur metabolism of all organisms and is used for the synthesis of proteins, glutathione, biotin, lipoic acid, methionine and other sulfur-containing metabolites. In addition, 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 intestinal bacteria. The amino acid L-cysteine ​​is not only of biological importance, but also of economic importance. For example, it is used as a food additive (especially in the baking industry), as a starting material for cosmetics and for the preparation of active pharmaceutical ingredients (especially N-acetylcysteine ​​and S-carboxymethylcysteine).

[0157] It will be clear to those skilled in the art that L-cysteine ​​referred to herein refers to any suitable form of the amino acid L-cysteine. Thus, the term "L-cysteine" encompasses free form L-cysteine ​​as well as L-cysteine ​​salts.

[0158] In the context of the present invention, in one example, L-cysteine ​​may be in free form, a salt thereof, or a mixture thereof.

[0159] Examples of salts include, for example, sulfates, hydrochlorides, carbonates, ammonium salts, sodium salts, and potassium salts. In one example, L-cysteine ​​is a crystalline fraction of >0.1 mm.

[0160] L-cysteine ​​is available from a number of suppliers and can be readily obtained by one skilled in the art. In addition, one skilled in the art will be able to readily detect the presence of L-cysteine ​​in a substance (e.g., a composition as described herein) using methods known in the art. For example, L-cysteine ​​crystals can be macroscopically detected in the composition as white particles. HPLC (high performance liquid chromatography) performed on an Inertsil ODs-3 column is an established method for detecting L-cysteine.

[0161] L-cysteine ​​can be obtained industrially by hydrolyzing animal materials (such as poultry feathers or pig hair). In contrast, synthetic L-cys can be obtained from fermentation of genetically modified E. coli or Pseudomonas thiazolinophilum. Thus, in some instances, L-cysteine ​​is of animal origin. In other instances, L-cysteine ​​is of synthetic origin.

[0162] In one example, the L-cysteine ​​is of plant origin.

[0163] In some examples, the compositions described herein can include an L-cysteine ​​derivative instead of, or in addition to, L-cysteine.

[0164] L-cysteine ​​derivatives are well known to those skilled in the art. N-acetylcysteine ​​(NAC) is the N-acetylated form of the amino acid L-cysteine ​​and is therefore an example of an L-cysteine ​​derivative. Therefore, in some instances, the compositions described herein may include N-acetylcysteine ​​(NAC). NAC is readily available in the art.

[0165] L-cysteine ​​is present in the alcohol degradation composition described herein with a suitable concentration or amount. Therefore, the amount or concentration of L-cysteine ​​can be described with reference to the %w / w of the composition or the total weight (e.g., mgs) of each dosage composition (in other words, the weight of each effective dose). It will be clear to those skilled in the art, and as described in more detail elsewhere herein, a dosage may include one or more dosage units (e.g., 2 dosage units). In instances where an effective dose is provided using multiple dosage units, the weight of each dosage corresponds to the total weight of L-cysteine ​​in the multiple dosage units.

[0166] In one example, the composition includes about 10% w / w L-cysteine ​​to about 40% w / w L-cysteine.

[0167] In another example, the composition includes about 15% w / w L-cysteine ​​to about 35% w / w L-cysteine. In another example, the composition includes about 20% w / w L-cysteine ​​to about 30% w / w L-cysteine.

[0168] In one example, the composition includes at least about 10% w / w L-cysteine.

[0169] In another example, the composition includes at least about 15% w / w of L-cysteine. In yet another example, the composition includes at least about 20% w / w of L-cysteine. In another example, the composition includes at least about 25% w / w of L-cysteine. In another example, the composition includes at least about 30% w / w of L-cysteine. In yet another example, the composition includes at least about 35% w / w of L-cysteine. In yet another example, the composition includes at least about 40% w / w of L-cysteine.

[0170] In some examples, the composition includes about 10% w / w L-cysteine.

[0171] In another example, the composition includes about 15% w / w of L-cysteine. In another example, the composition includes about 20% w / w of L-cysteine. In yet another example, the composition includes about 25% w / w of L-cysteine. In another example, the composition includes about 30% w / w of L-cysteine. In another example, the composition includes about 35% w / w of L-cysteine. In yet another example, the composition includes about 40% w / w of L-cysteine.

[0172] In one example, the composition includes about 38 mg of L-cysteine ​​per dose to about 200 mg of L-cysteine ​​per dose.

[0173] In one example, the composition includes at least about 38 mg of L-cysteine ​​per dose.

[0174] In one example, the composition includes at least about 50 mg of L-cysteine ​​per dose. In one example, the composition includes at least about 75 mg of L-cysteine ​​per dose. In one example, the composition includes at least about 100 mg of L-cysteine ​​per dose.

[0175] In one example, the composition includes at least about 150 mg of L-cysteine ​​per dose.

[0176] In one example, the composition includes at least about 160 mg of L-cysteine ​​per dose. In one example, the composition includes at least about 180 mg of L-cysteine ​​per dose.

[0177] In one example, the composition includes about 38 mg of L-cysteine ​​per dose.

[0178] In one example, the composition includes about 50 mg of L-cysteine ​​per dose. In one example, the composition includes about 75 mg of L-cysteine ​​per dose. In one example, the composition includes about 100 mg of L-cysteine ​​per dose.

[0179] In one example, the composition includes about 150 mg of L-cysteine ​​per dose.

[0180] In one example, the composition includes about 160 mg of L-cysteine ​​per dose. In one example, the composition includes about 180 mg of L-cysteine ​​per dose.

[0181] The data presented herein demonstrate that the addition of L-cysteine ​​to a composition comprising a high molecular weight, low osmotic pressure carbohydrate (e.g., dextrin) and one or more species of Bacillus results in the reprogramming of the bacteria such that they degrade alcohol more efficiently compared to the rate of alcohol degradation in the absence of L-cysteine.

[0182] Thus, the alcohol degrading compositions described herein include L-cysteine ​​in combination with one or more species of Bacillus and a high molecular weight, low osmotic pressure carbohydrate (eg, dextrin).

[0183] As used herein, "high molecular weight low osmotic pressure carbohydrate" refers to a carbohydrate having a molecular weight of about 500,000 g / mol to about 700,000 g / mol, wherein the osmotic pressure of the carbohydrate is low. One skilled in the art will be able to readily identify suitable carbohydrates having low osmotic pressure using routine tests known in the art. For the avoidance of doubt, as used herein, a low osmotic pressure carbohydrate is a carbohydrate having a glycogen recovery rate that is about 50% higher than maltodextrin.

[0184] High molecular weight low osmotic pressure carbohydrate is present in alcohol degradation composition as described herein with suitable concentration or amount.Therefore, the amount or concentration of high molecular weight low osmotic pressure carbohydrate can be described with reference to the %w / w of composition or the gross weight (e.g. mgs) of each dosage composition (in other words, the weight of each effective dose).It will be clear to those skilled in the art, and as described in more detail elsewhere herein, dosage can include one or more dosage units (e.g. 2 dosage units).In the example that effective dose is provided using multiple dosage units, the weight of each dosage corresponds to the gross weight of high molecular weight low osmotic pressure carbohydrate in multiple dosage units.

[0185] In one example, the composition includes about 0.5% w / w to about 5% w / w of a high molecular weight low osmotic pressure carbohydrate.

[0186] In another example, the composition includes about 0.5% w / w to about 3% w / w of a high molecular weight low osmotic pressure carbohydrate. In one example, the composition includes about 0.5% w / w to about 2% w / w of a high molecular weight low osmotic pressure carbohydrate.

[0187] In one example, the composition includes at least about 0.5% w / w high molecular weight low osmotic pressure carbohydrate.

[0188] In another example, the composition includes at least about 1% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes at least about 1.5% w / w of high molecular weight low osmotic pressure carbohydrates. In yet another example, the composition includes at least about 2% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes at least about 2.5% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes at least about 3% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes at least about 3.5% w / w of high molecular weight low osmotic pressure carbohydrates. In yet another example, the composition includes at least about 4% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes at least about 4.5% w / w of high molecular weight low osmotic pressure carbohydrates. In yet another example, the composition includes at least about 5% w / w of high molecular weight low osmotic pressure carbohydrates.

[0189] In one example, the composition includes about 0.5% w / w of a high molecular weight low osmotic pressure carbohydrate.

[0190] In another example, the composition includes about 1% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes about 1.5% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes about 2% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes about 2.5% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes about 3% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes about 3.5% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes about 4% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes about 4.5% w / w of high molecular weight low osmotic pressure carbohydrates. In another example, the composition includes about 5% w / w of high molecular weight low osmotic pressure carbohydrates.

[0191] In one example, the composition includes about 2 mg to about 50 mg of the high molecular weight low osmotic pressure carbohydrate per dose.

[0192] In one example, the composition includes at least about 2 mg of a high molecular weight low osmotic pressure carbohydrate per dose.

[0193] In one example, the composition includes at least about 2 mg of a high molecular weight low osmotic pressure carbohydrate per dose.

[0194] In one example, the composition includes at least about 4 mg of a high molecular weight low osmotic pressure carbohydrate per dose.

[0195] In one example, the composition includes at least about 10 mg of high molecular weight low osmotic pressure carbohydrates / dose. In one example, the composition includes at least about 15 mg of high molecular weight low osmotic pressure carbohydrates / dose. In one example, the composition includes at least about 20 mg of high molecular weight low osmotic pressure carbohydrates / dose. In one example, the composition includes at least about 25 mg of high molecular weight low osmotic pressure carbohydrates / dose. In one example, the composition includes at least about 30 mg of high molecular weight low osmotic pressure carbohydrates / dose. In one example, the composition includes at least about 35 mg of high molecular weight low osmotic pressure carbohydrates / dose. In one example, the composition includes at least about 40 mg of high molecular weight low osmotic pressure carbohydrates / dose. In one example, the composition includes at least about 45 mg of high molecular weight low osmotic pressure carbohydrates / dose.

[0196] In one example, the composition includes about 2 mg of a high molecular weight low osmotic pressure carbohydrate per dose.

[0197] In one example, the composition includes about 4 mg of a high molecular weight low osmotic pressure carbohydrate per dose.

[0198] In one example, the composition includes about 10 mg of high molecular weight low osmotic pressure carbohydrate / dose. In one example, the composition includes about 15 mg of high molecular weight low osmotic pressure carbohydrate / dose. In one example, the composition includes about 20 mg of high molecular weight low osmotic pressure carbohydrate / dose. In one example, the composition includes about 25 mg of high molecular weight low osmotic pressure carbohydrate / dose. In one example, the composition includes about 30 mg of high molecular weight low osmotic pressure carbohydrate / dose. In one example, the composition includes about 35 mg of high molecular weight low osmotic pressure carbohydrate / dose. In one example, the composition includes about 40 mg of high molecular weight low osmotic pressure carbohydrate / dose. In one example, the composition includes about 45 mg of high molecular weight low osmotic pressure carbohydrate / dose.

[0199] In one example, the high molecular weight low osmotic pressure carbohydrate is dextrin.

[0200] Dextrin is a general term applied to a variety of 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 the hydrolysis of starch or glycogen. "Dextrin" refers to a glucose polymer produced by the hydrolysis of starch (or glycogen) that includes glucose units linked together primarily by α-1,4 bonds. In addition to α-1,4 bonds, a certain proportion of α-1,6 bonds may be present in a particular dextrin, the amount of which depends on the starch starting material. Since the biodegradation rate of α-1,6 bonds is generally lower than that of α-1,4 bonds, it is preferred that, for many applications, the percentage of α-1,6 bonds is less than 10%, more preferably less than 5%. In some instances, therefore, dextrins are mixtures of polymers of D-glucose units linked by α-(1->4) or α-(1->6) glycosidic bonds.

[0201] Dextrins can be produced from starch by using enzymes such as amylase, such as in human digestion and in malting and saccharification, or by applying dry heat (pyrolysis or baking) under acidic conditions. The latter process is used in industry. Dextrins produced by heating are also called pyrodextrins. Typically, dextrins are produced by hydrolyzing starch obtained from various natural products such as wheat, rice, corn, maize and cassava.

[0202] Dextrins are typically white, yellow or brown powders that are partially or completely soluble in water to produce optically active solutions of low viscosity. Dextrins are available from a variety of suppliers and are readily available to the skilled artisan. One skilled in the art will be able to readily identify dextrins that are suitable for use in the context of the present invention. One skilled in the art will be able to readily detect the presence of dextrins in a substance (e.g., a composition as described herein) using methods known in the art. For example, most dextrins can be detected using an iodine solution.

[0203] The term "dextrin" encompasses pyrodextrin, digestible dextrin, and hydrogenated products thereof, including derivatives thereof. The term "dextrin derivative" herein means those obtained by chemically or enzymatically treating dextrin, and encompasses, in addition to the above-mentioned polydextrose, for example, branched dextrin obtained by allowing glycosyltransferase to act on dextrin, and cyclodextrin obtained by allowing cyclodextrin-producing enzyme to act on starch.

[0204] In some examples, the dextrin is enzyme treated.

[0205] In one example, the dextrin, which is a high molecular weight, low osmotic pressure carbohydrate, is a cluster dextrin (also known as a highly branched cyclic dextrin). Cluster dextrins are maltodextrins that have a high molecular weight, but a narrow weight distribution, are soluble, and their osmotic pressure is close to zero. Typical large molecular weight carbohydrates have lower solubility than cluster dextrins. On the other hand, low molecular weight carbohydrates exhibit higher osmotic pressures, as do pure glucose solutions. Along with other digestible contents commonly found in sports drinks, this slows their entry into the small intestine. Cluster dextrins enter the small intestine faster, and endurance is improved faster. Solubility is at the heart of cluster dextrin function. High molecular weight cluster dextrins also degrade slowly, balancing insulin secretion and lipid breakdown. Cluster dextrins are produced by Glico Nutrition.

[0206] In some examples, the dextrin, as well as the high molecular weight low osmotic pressure carbohydrate, is derived from wheat or corn (eg, in some examples, the dextrin is wheat dextrin or corn dextrin).

[0207] In some examples, the dextrin is enzyme-treated wheat or corn.

[0208] In one example, the dextrin is derived from wheat (eg, 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).

[0209] In another example, the dextrin is derived from corn (eg, corn dextrin).

[0210] In a particular example, the dextrin is hydrolyzed corn dextrin (eg, Vitargo).

[0211] In some examples, dextrin is present in a suitable concentration or amount in the alcohol degrading compositions described herein.

[0212] In one example, the composition includes about 0.5% w / w to about 5% w / w dextrin.

[0213] In another example, the composition includes about 0.5% w / w to about 3% w / w dextrin. In another example, the composition includes about 0.5% w / w to about 2% w / w dextrin.

[0214] In one example, the composition includes at least about 0.5% w / w dextrin.

[0215] In another example, the composition includes at least about 1% w / w of dextrin. In another example, the composition includes at least about 1.5% w / w of dextrin. In yet another example, the composition includes at least about 2% w / w of dextrin. In another example, the composition includes at least about 2.5% w / w of dextrin. In another example, the composition includes at least about 3% w / w of dextrin. In another example, the composition includes at least about 3.5% w / w of dextrin. In yet another example, the composition includes at least about 4% w / w of dextrin. In another example, the composition includes at least about 4.5% w / w of dextrin. In yet another example, the composition includes at least about 5% w / w of dextrin.

[0216] In one example, the composition includes about 0.5% w / w dextrin.

[0217] In another example, the composition includes about 1% w / w dextrin. In another example, the composition includes about 1.5% w / w dextrin. In yet another example, the composition includes about 2% w / w dextrin. In another example, the composition includes about 2.5% w / w dextrin. In another example, the composition includes about 3% w / w dextrin. In another example, the composition includes about 3.5% w / w dextrin. In yet another example, the composition includes about 4% w / w dextrin. In another example, the composition includes about 4.5% w / w dextrin. In yet another example, the composition includes about 5% w / w dextrin.

[0218] In one example, the composition includes about 2 mg to about 50 mg of dextrin per dose.

[0219] In one example, the composition includes at least about 2 mg of dextrin per dose.

[0220] In one example, the composition includes at least about 4 mg of dextrin per dose.

[0221] In one example, the composition includes at least about 5 mg of dextrin per dose. In one example, the composition includes at least about 10 mg of dextrin per dose. In one example, the composition includes at least about 15 mg of dextrin per dose. In one example, the composition includes at least about 20 mg of dextrin per dose. In one example, the composition includes at least about 25 mg of dextrin per dose. In one example, the composition includes at least about 30 mg of dextrin per dose. In one example, the composition includes at least about 35 mg of dextrin per dose. In one example, the composition includes at least about 40 mg of dextrin per dose. In one example, the composition includes at least about 45 mg of dextrin per dose.

[0222] In one example, the composition includes about 2 mg of dextrin per dose.

[0223] In one example, the composition includes about 4 mg of dextrin per dose.

[0224] In one example, the composition includes about 10 mg of dextrin per dose. In one example, the composition includes about 15 mg of dextrin per dose. In one example, the composition includes about 20 mg of dextrin per dose. In one example, the composition includes about 25 mg of dextrin per dose. In one example, the composition includes about 30 mg of dextrin per dose. In one example, the composition includes about 35 mg of dextrin per dose. In one example, the composition includes about 40 mg of dextrin per dose. In one example, the composition includes about 45 mg of dextrin per dose.

[0225] In one example, the composition described herein includes L-cysteine ​​and dextrin. L-cysteine ​​and dextrin can be present in the alcohol degradation composition described herein at any suitable concentration. Suitable concentrations or amounts of L-cysteine ​​and dextrin are described elsewhere herein and are equally applicable to the composition comprising L-cysteine ​​and dextrin described herein. Illustrative examples of suitable concentrations or amounts are provided below.

[0226] In one example, the composition includes 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 examples, the composition may also include about 50% w / w to about 90% w / w rice bran (e.g., fermented rice bran) and / or about 10,000 cfu / g of Bacillus bacteria to about 15,000 cfu / g of Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0227] In one example, the composition described herein includes at least about 0.5% w / w dextrin and at least about 10% w / w L-cysteine. For example, the composition 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 Example 1 Test 7B. In each of these examples, the composition 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0228] In one example, the composition described herein includes at least about 0.5% w / w dextrin and at least about 20% w / w L-cysteine. For example, the composition 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 Example 1 Test 6B. In each of these examples, the composition 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0229] In one example, the composition described herein includes at least about 0.5% w / w dextrin and at least about 30% w / w L-cysteine. For example, the composition 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 Example 1 Test 5B. In each of these examples, the composition 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., Bacillus subtilis and / or Bacillus 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., Bacillus subtilis and / or Bacillus coagulans).

[0230] In one embodiment, the composition described herein includes at least about 5% w / w dextrin and at least about 20% w / w L-cysteine. For example, the composition described herein may include about 5% w / w dextrin and about 20% w / w L-cysteine. This example corresponds to the composition tested in Example 1 Test 8B. In each of these examples, the composition 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0231] In one example, the composition described herein includes at least about 3% w / w of dextrin and at least about 30% w / w of L-cysteine. For example, the composition described herein may include about 3% w / w of dextrin and about 30% w / w of L-cysteine. In each of these examples, the composition may also include at least about 67% w / w of rice bran (e.g., at least about 67% w / w of fermented rice bran) and / or at least 10,000 cfu / g of bacteria of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans). For example, in each of these examples, the composition may include about 67% w / w of rice bran (e.g., about 67% w / w of fermented rice bran) and / or 10,000 cfu / g of bacteria of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0232] In one example, the composition includes about 2 mg to about 50 mg of dextrin / dose and about 38 mg to about 200 mg of L-cysteine / dose. In each of these examples, the composition may also include about 300 mg to about 600 mg of rice bran / dose (e.g., fermented rice bran / dose) and / or about 5,000 cfu of Bacillus bacteria / dose to about 1×10 8 cfu of Bacillus bacteria / dose (e.g. Bacillus subtilis and / or Bacillus coagulans).

[0233] In one example, the composition described herein includes at least about 2 mg of dextrin / dose and at least about 38 mg of L-cysteine / dose. For example, the composition described herein can include about 2 mg of dextrin / dose and about 38 mg of L-cysteine / dose. This example corresponds to the composition tested in Example 1 Test 7B. In each of these examples, the composition can also include at least about 300 mg of rice bran / dose (e.g., at least about 300 mg of fermented rice bran / dose) and / or at least 5,000 cfu of bacteria / dose of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans). For example, in each of these examples, the composition can include about 300 mg of rice bran / dose (e.g., about 300 mg of fermented rice bran / dose) and / or 5,000 cfu of bacteria / dose of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0234] In one example, the composition described herein includes at least about 2 mg of dextrin and at least about 76 mg of L-cysteine / dose. For example, the composition described herein can include about 2 mg of dextrin / dose and about 76 mg of L-cysteine / dose. This example corresponds to the composition tested in Example 1 Test 6B. In each of these examples, the composition can also include at least about 300 mg of rice bran / dose (e.g., at least about 300 mg of fermented rice bran / dose) and / or at least 5,000 cfu of bacteria / dose of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans). For example, in each of these examples, the composition can include about 300 mg of rice bran / dose (e.g., about 300 mg of fermented rice bran / dose) and / or 5,000 cfu of bacteria / dose of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0235] In one example, the composition described herein includes at least about 2 mg of dextrin / dose and at least about 114 mg of L-cysteine / dose. For example, the composition described herein can include about 2 mg of dextrin / dose and about 114 mg of L-cysteine / dose. This example corresponds to the composition tested in Example 1 Test 5B. In each of these examples, the composition can also include at least about 300 mg of rice bran / dose (e.g., at least about 300 mg of fermented rice bran / dose) and / or at least 5,000 cfu of bacteria / dose of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans). For example, in each of these examples, the composition can include about 300 mg of rice bran / dose (e.g., about 300 mg of fermented rice bran / dose) and / or 5,000 cfu of bacteria / dose of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0236] In one example, the composition described herein includes at least about 20 mg of dextrin / dose and at least about 76 mg of L-cysteine / dose. For example, the composition described herein can include about 20 mg of dextrin / dose and about 76 mg of L-cysteine / dose. This example corresponds to the composition tested in Example 1 Test 8B. In each of these examples, the composition can also include at least about 300 mg of rice bran / dose (e.g., at least about 300 mg of fermented rice bran / dose) and / or at least 5,000 cfu of bacteria / dose of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans). For example, in each of these examples, the composition can include about 300 mg of rice bran / dose (e.g., about 300 mg of fermented rice bran / dose) and / or 5,000 cfu of bacteria / dose of the genus Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0237] Studies have shown that high molecular weight low osmotic pressure carbohydrates (e.g., dextrin) and / or L-cysteine ​​create a microenvironment at the cellular level, so that the microbial consortium of the composition provided herein discharges an enzyme cascade targeting short carbon chains (e.g., ethanol / alcohol) after intestinal resuscitation, thereby preferentially targeting these substrates. As discussed above, generally, about 80% of the ingested alcohol stays in the small intestine for a considerable period of time before being absorbed by the blood. The targeted enzymes act only on the alcohol in the intestine and break it down into carbon dioxide and water, bypassing the process of converting alcohol into acetaldehyde and acetic acid in the liver, i.e., the hangover metabolites formed by the liver converting alcohol.

[0238] In particular, when Bacillus cells and their endospores in the duodenum and small intestine are revived, the cells scan the biochemical conditions of their microenvironment and begin to excrete unique bioactive substances to optimize the conditions for their survival and reproduction, such as pH, conductivity, electrolytes. Nutrients and substrates are essential for survival and subsequent reproduction. When alcohol / ethanol / ethyl alcohol is present in the microenvironment, enzymes targeting alcohol are excreted to break down the alcohol into carbon-containing fragments. Carbon that cannot be used as nutrients by microorganisms or adjacent tissue cells will be biochemically metabolized into water and carbon dioxide, which can escape the body system without causing any biological consequences / symptoms. Studies have shown that high molecular weight low osmotic pressure carbohydrates (such as dextrins) and / or L-cysteine ​​enhance this environmental scanning and selective excretion of bioactive substances to optimize enzymatic conditions.

[0239] As described elsewhere herein, the alcohol degradation compositions described herein may include cereals (e.g., cereal grains), such as rice bran. Cereals are grasses planted (grown) for the edible components of their cereal grains (botany, a kind of fruit of a caryopsis), consisting of endosperm, germ, and bran. The term cereal may also refer to the cereal grains themselves (particularly "cereal grains") produced thereby. Cereal grains are seeds from grasses (such as wheat, millet, rice, barley, oats, rye, triticale, sorghum, and maize (corn)).

[0240] In some examples, the alcohol degradation compositions described herein may include a cereal (e.g., cereal grain) selected from the group consisting of wheat, millet, rice, barley, oats, rye, triticale, sorghum, and maize (corn). Those skilled in the art can readily identify cereals (e.g., cereal grains) suitable for use in the compositions described herein.

[0241] Bran (bran), also called mill bran, is the hard outer layer of the grain kernel. It includes the aleurone layer and the pericarp. Corn (maize) bran also includes the pedicel (tip cap). Bran, along with the germ, is a component of whole grains and is typically produced as a by-product of milling during the production of refined grains. Bran is present in grain kernels including rice, corn (maize), wheat, oats, barley, rye, and millet.

[0242] Thus, in some examples, the alcohol degradation compositions described herein may include cereal bran. In some examples, the alcohol degradation 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.

[0243] In some examples, the alcohol degrading compositions described herein can include oat bran.

[0244] In some examples, the alcohol degrading compositions described herein can include rice bran.

[0245] Rice bran is a by-product of the rice milling process. Typically rice milling produces about 15% w / w broken rice grains, about 10% w / w rice bran, about 20% rice husks, and about 55% w / w whole rice grains. The composition of rice bran (by weight percentage) is typically 11-13% water, 18-21% crude fat and oil, 14-16% crude protein, 8-10% crude fiber, 9-12% ash, and 33-36% carbohydrates. Rice bran has naturally occurring lipases that hydrolyze oil into glycerol and free fatty acids, giving the product a rancid odor and taste. As used herein, "rice bran" refers to the hard outer layer of rice, including the aleurone layer and pericarp. It is an integral part of the whole rice along with the germ, and as mentioned above, it is typically produced as a by-product of milling during the production of refined rice.

[0246] Alcohol degradation compositions as described herein can include rice bran in any suitable form. Suitable forms include raw rice bran, recently ground (unhydrolyzed) full-fat rice bran, low-fat rice bran, defatted rice bran, fermented rice bran, stabilized rice bran, etc. Raw rice bran is the rice bran obtained after grinding. Low-fat rice bran and defatted rice bran are obtained from full-fat rice bran by methods such as solvent extraction. The fat content of full-fat rice bran is about 14-18% by weight, and the fat content of low-fat and defatted rice bran is about 3-14% and less than 3% (based on weight) respectively.

[0247] In one example, the rice bran is formulated as raw rice bran, recently ground (unhydrolyzed) full fat rice bran, low fat rice bran, defatted rice bran, fermented rice bran, and / or stabilized rice bran.

[0248] In another more preferred embodiment, the rice bran is formulated as fermented rice bran and / or stabilized rice bran.

[0249] In another example, the rice bran is fermented rice bran. The rice bran undergoes a natural / spontaneous fermentation process by naturally occurring microbial strains, typically soil-bound strains such as Bacillus and Pediococcus.

[0250] As used herein, "fermented rice bran" refers to rice bran that has undergone a fermentation process. Fermented rice bran contains probiotics, which stabilize the microflora of the small intestine.

[0251] As used herein, "stabilized rice bran" refers to rice bran that has been heated for a short period of time, such as by passing it through a high temperature and high pressure extruder. The heating stabilizes the rice bran. In other words, therefore, "stabilized rice bran" is heat-treated rice bran. For example, after milling, the rice bran can be stabilized under conditions of heating at 130 degrees Celsius for less than 10 seconds. In some instances, the stabilized rice bran is a dietary fiber. Generally, the stabilized rice bran is a dietary fiber that can be broken down in the colon. As a dietary fiber, the stabilized rice bran is a prebiotic that interacts with the colonic microbiome.

[0252] The microbial content in fermented rice bran may have a prebiotic and stabilizing effect on the small intestinal microbiota, and rice bran, as a dietary fiber, stabilizes colonic conditions. Another mechanism of action may be the reduction of intestinal oxidative stress, which normalizes intestinal mucosal barrier function and may lead to reduced alcohol absorption.

[0253] Rice bran (e.g., fermented rice bran) is present in an alcohol degradation (e.g., alcohol metabolism) composition as described herein in a suitable amount or concentration as described below. Therefore, the amount or concentration of rice bran can be described with reference to the % w / w of the composition or the total weight (e.g., mgs) of each dose of the composition (in other words, the weight per effective dose). It will be clear to those skilled in the art, and as described in more detail elsewhere herein, a dose may include one or more dosage units (e.g., 2 dosage units). In instances where an effective dose is provided using multiple dosage units, the weight per dosage corresponds to the total weight of rice bran in the multiple dosage units.

[0254] In one example, the composition includes about 50% w / w to about 90% w / w rice bran.

[0255] In another example, the composition comprises about 60% w / w to about 80% w / w rice bran. In another example, the composition comprises about 73% w / w to about 79% w / w rice bran.

[0256] In one example, the composition comprises at least about 50% w / w rice bran. In another example, the composition comprises at least about 55% w / w rice bran. In one example, the composition comprises at least about 60% w / w rice bran. In another example, the composition comprises at least about 65% w / w rice bran. In one example, the composition comprises at least about 73% w / w rice bran. In one example, the composition comprises at least about 75% w / w rice bran. In one example, the composition comprises at least about 79% w / w rice bran. In another example, the composition comprises at least about 85% w / w rice bran. In one example, the composition comprises at least about 90% w / w rice bran.

[0257] In one example, the composition includes about 50% w / w rice bran. In another example, the composition includes about 55% w / w rice bran. In one example, the composition includes about 60% w / w rice bran. In another example, the composition includes about 65% w / w rice bran. In one example, the composition includes about 73% w / w rice bran. In one example, the composition includes about 75% w / w rice bran. In one example, the composition includes about 79% w / w rice bran. In another example, the composition includes about 85% w / w rice bran. In one example, the composition includes about 90% w / w rice bran.

[0258] In certain examples, the composition includes at least about 67% w / w rice bran.

[0259] For example, the composition may include about 67% w / w rice bran.

[0260] 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.

[0261] In another example, the composition includes at least about 79% w / w rice bran. For example, the composition can include about 79% w / w rice bran.

[0262] In another example, the composition includes at least about 79.5% w / w rice bran. For example, the composition can include about 79.5% w / w rice bran.

[0263] In one example, the composition includes at least about 300 mg of rice bran (eg, fermented rice bran) per dose. As described elsewhere herein, the dose may be formulated as two capsules.

[0264] In one example, the composition includes at least about 300 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes at least about 350 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes at least about 400 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes at least about 450 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes at least about 500 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes at least about 550 mg of rice bran (e.g., fermented rice bran) per dose.

[0265] In one example, the composition includes about 300 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes about 350 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes about 400 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes about 450 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes about 500 mg of rice bran (e.g., fermented rice bran) per dose. In one example, the composition includes about 550 mg of rice bran (e.g., fermented rice bran) per dose.

[0266] As described elsewhere herein, an alcohol degradation composition is provided, which includes one or more species of Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans), rice bran (e.g., fermented rice bran), L-cysteine, and a high molecular weight, low osmotic pressure carbohydrate (e.g., dextrin). One or more species of Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans), rice bran (e.g., fermented rice bran), L-cysteine, and a high molecular weight, low osmotic pressure carbohydrate (e.g., dextrin) may be present in any suitable amount or concentration in the alcohol degradation composition described herein. Suitable amounts and concentrations of one or more species of Bacillus (e.g., Bacillus subtilis and / or Bacillus coagulans), rice bran (e.g., fermented rice bran), L-cysteine, and a high molecular weight, low osmotic pressure carbohydrate (e.g., dextrin) are described elsewhere herein. Illustrative examples of suitable concentrations are provided below.

[0267] In one example, the composition includes about 0.5% w / w to 5% w / w dextrin, about 10% w / w to 40% w / w L-cysteine, about 50% w / w to 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., Bacillus subtilis and / or Bacillus coagulans).

[0268] In one example, the composition described herein includes 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0269] In one example, the composition described herein includes 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0270] In one example, the composition described herein includes 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0271] In one example, the composition described herein includes 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0272] In one example, the composition described herein includes 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 Bacillus bacteria (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0273] In one example, the composition includes about 2 mg to about 50 mg of dextrin / dose, about 38 mg to about 200 mg of L-cysteine / dose, about 300 mg to about 600 mg of rice bran / dose (e.g., fermented rice bran / dose), and about 5,000 cfu of Bacillus bacteria / dose to about 1×10 8 cfu of Bacillus bacteria / dose (e.g. Bacillus subtilis and / or Bacillus coagulans).

[0274] In one example, the composition described herein includes at least about 2 mg of dextrin / dose, at least about 38 mg of L-cysteine / dose, at least about 300 mg of rice bran / dose (e.g., at least about 300 mg of fermented rice bran / dose), and at least 5,000 cfu of Bacillus bacteria / dose (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0275] In one example, the composition described herein includes at least about 2 mg of dextrin, 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 5,000 cfu of Bacillus bacteria per dose (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0276] In one example, the composition described herein includes at least about 2 mg of dextrin / dose, at least about 114 mg of L-cysteine / dose, at least about 300 mg of rice bran / dose (e.g., at least about 300 mg of fermented rice bran / dose), and at least 5,000 cfu of Bacillus bacteria / dose (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0277] In one example, the composition described herein includes at least about 20 mg of dextrin / dose, at least about 76 mg of L-cysteine / dose, at least about 300 mg of rice bran / dose (e.g., at least about 300 mg of fermented rice bran / dose), and at least 5,000 cfu of Bacillus bacteria / dose (e.g., Bacillus subtilis and / or Bacillus coagulans).

[0278] A composition of 79.5% w / w fermented rice bran (including one or more species of the genus Bacillus), 0.5% w / w dextrin, and 20.0% w / w L-cysteine ​​was evaluated to be particularly effective in digesting alcohol in the intestine, about 50% faster than the liver, as described in the Examples below. Thus, in a particular example, the composition described herein includes about 79.5% w / w fermented rice bran (including one or more species of the genus Bacillus), about 0.5% w / w dextrin, and about 20.0% w / w L-cysteine.

[0279] The alcohol degradation compositions described herein may include one or more additional components, such as one or more additional ingredients. For example, the compositions described herein may further include emulsifiers, fillers and / or inactive ingredients. Those skilled in the art will readily understand the meaning of "emulsifiers," "fillers," and "inactive ingredients" in the context of the compositions provided herein. Non-limiting examples of additional components include vitamin B12, magnesium salts of fatty acids (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose).

[0280] The additional components described herein may be in any suitable form. Suitable forms will be readily recognized by those skilled in the art.

[0281] Thus, in one example, the alcohol degradation composition described herein may further include one or more of the following: vitamin B12, magnesium salts of fatty acids (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose). In another example, the alcohol degradation composition described herein may further include two or more of the following: vitamin B12, magnesium salts of fatty acids (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose). In another example, the alcohol degradation composition described herein may further include three or more of the following: vitamin B12, magnesium salts of fatty acids (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose). In another example, the alcohol degradation composition described herein may further include four or more of the following: vitamin B12, magnesium salts of fatty acids (e.g., magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (e.g., microcrystalline cellulose).

[0282] In one example, the alcohol degradation composition further includes vitamin B12, magnesium salt of fatty acid (eg, magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide, and cellulose (eg, microcrystalline cellulose).

[0283] Examples of magnesium salts of fatty acids include magnesium stearate. Thus, in one example, the compositions described herein may further include magnesium stearate. Magnesium stearate is the magnesium salt of the fatty acid stearic acid. Magnesium salts of fatty acids (e.g., magnesium stearate) may be excipients, inactive ingredients, and / or may be used as lubricants for production machinery. Magnesium stearate is a GRAS listed ingredient.

[0284] In some instances, vitamin B12 is added for regulatory purposes.

[0285] In some instances, magnesium salts (e.g., magnesium stearate), calcium salts, and / or potassium salts are inactive ingredients (e.g., they have no clinical effect). For example, magnesium salts (e.g., magnesium stearate), calcium salts, and / or potassium salts may be added as filling aids (e.g., fillers) to help capsule filling machines work effectively.

[0286] In one example, the composition described herein further includes microcrystalline cellulose. Microcrystalline cellulose can be used as an emulsifier, a filling aid and / or an inactive ingredient. Microcrystalline cellulose (and maltodextrin) can be used as a bulking excipient when punching tablets and as a flow agent when making capsule formulations. In some instances, the composition described herein further includes maltodextrin.

[0287] In one example, the composition includes about 5% w / w to about 50% w / w of microcrystalline cellulose. In another example, the composition includes about 5% w / w to about 35% w / w of microcrystalline cellulose. In another example, the composition includes about 5% w / w to about 20% w / w of microcrystalline cellulose. In another example, the composition includes about 5% w / w to about 15% w / w of microcrystalline cellulose. In another example, the composition includes about 5% w / w to about 8% w / w of microcrystalline cellulose.

[0288] In one example, the composition includes at least about 5% w / w of microcrystalline cellulose. In one example, the composition includes at least about 8% w / w of microcrystalline cellulose. In another example, the composition includes at least about 10% w / w of microcrystalline cellulose. In another example, the composition includes at least about 15% w / w of microcrystalline cellulose. In yet another example, the composition includes at least about 20% w / w of microcrystalline cellulose. In another example, the composition includes at least about 25% w / w of microcrystalline cellulose. In another example, the composition includes at least about 30% w / w of microcrystalline cellulose. In yet another example, the composition includes at least about 35% w / w of microcrystalline cellulose. In another example, the composition includes at least about 40% w / w of microcrystalline cellulose. In another example, the composition includes at least about 45% w / w of microcrystalline cellulose. In another example, the composition includes at least about 50% w / w of microcrystalline cellulose.

[0289] In one example, the composition includes about 5% w / w of microcrystalline cellulose. In one example, the composition includes about 8% w / w of microcrystalline cellulose. In another example, the composition includes about 10% w / w of microcrystalline cellulose. In another example, the composition includes about 15% w / w of microcrystalline cellulose. In another example, the composition includes about 20% w / w of microcrystalline cellulose. In another example, the composition includes about 25% w / w of microcrystalline cellulose. In yet another example, the composition includes about 30% w / w of microcrystalline cellulose. In another example, the composition includes about 35% w / w of microcrystalline cellulose. In another example, the composition includes about 40% w / w of microcrystalline cellulose. In another example, the composition includes about 45% w / w of microcrystalline cellulose. In another example, the composition includes about 50% w / w of microcrystalline cellulose.

[0290] In one example, the compositions described herein include at least about 30 mg of microcrystalline cellulose per dose. As described elsewhere herein, the dose can be formulated as two capsules.

[0291] In one example, the compositions described herein include at least about 40 mg of microcrystalline cellulose per dose. In one example, the compositions described herein include at least about 50 mg of microcrystalline cellulose per dose. In one example, the compositions described herein include at least about 60 mg of microcrystalline cellulose per dose. In one example, the compositions described herein include at least about 70 mg of microcrystalline cellulose per dose. In one example, the compositions described herein include at least about 80 mg of microcrystalline cellulose per dose. In one example, the compositions described herein include at least about 90 mg of microcrystalline cellulose per dose. In one example, the compositions described herein include at least about 100 mg of microcrystalline cellulose per dose.

[0292] In one example, the composition described herein further includes magnesium stearate. Magnesium stearate can be used as an emulsifier, a filling aid and / or an inactive ingredient.

[0293] In one example, the composition includes about 0.2% w / w to about 1.5% w / w of magnesium stearate. In another example, the composition includes about 0.5% w / w to about 1.4% w / w of magnesium stearate. In another example, the composition includes about 0.6% w / w to about 1.3% w / w of magnesium stearate.

[0294] In one example, the composition includes at least about 0.2% w / w of magnesium stearate. In another example, the composition includes at least about 0.3% w / w of magnesium stearate. In another example, the composition includes at least about 0.4% w / w of magnesium stearate. In yet another example, the composition includes at least about 0.5% w / w of magnesium stearate. In another example, the composition includes at least about 0.6% w / w of magnesium stearate. In another example, the composition includes at least about 0.7% w / w of magnesium stearate. In yet another example, the composition includes at least about 0.8% w / w of magnesium stearate. In another example, the composition includes at least about 0.9% w / w of magnesium stearate. In another example, the composition includes at least about 1.0% w / w of magnesium stearate. In another example, the composition includes at least about 1.1% w / w of magnesium stearate. In another example, the composition includes at least about 1.2% w / w magnesium stearate. In another example, the composition includes at least about 1.3% w / w magnesium stearate. In another example, the composition includes at least about 1.4% w / w magnesium stearate. In another example, the composition includes at least about 1.5% w / w magnesium stearate.

[0295] In one example, the composition includes about 0.2% w / w of magnesium stearate. In another example, the composition includes about 0.3% w / w of magnesium stearate. In another example, the composition includes about 0.4% w / w of magnesium stearate. In yet another example, the composition includes about 0.5% w / w of magnesium stearate. In another example, the composition includes about 0.6% w / w of magnesium stearate. In another example, the composition includes about 0.7% w / w of magnesium stearate. In yet another example, the composition includes about 0.8% w / w of magnesium stearate. In another example, the composition includes about 0.9% w / w of magnesium stearate. In another example, the composition includes about 1.0% w / w of magnesium stearate. In another example, the composition includes about 1.1% w / w of magnesium stearate. In another example, the composition includes about 1.2% w / w of magnesium stearate. In another example, the composition includes about 1.3% w / w magnesium stearate. In another example, the composition includes about 1.4% w / w magnesium stearate. In another example, the composition includes about 1.5% w / w magnesium stearate.

[0296] In one example, the compositions described herein include at least about 4 mg of magnesium stearate per dose. As described elsewhere herein, the dose can be formulated as two capsules.

[0297] In one example, the compositions described herein include at least about 5 mg of magnesium stearate per dose. In one example, the compositions described herein include at least about 6 mg of magnesium stearate per dose. In one example, the compositions described herein include at least about 7 mg of magnesium stearate per dose. In one example, the compositions described herein include at least about 8 mg of magnesium stearate per dose. In one example, the compositions described herein include at least about 9 mg of magnesium stearate per dose. In one example, the compositions described herein include at least about 10 mg of magnesium stearate per dose.

[0298] In one example, the composition described herein further includes silicon dioxide. Silicon dioxide can be used as an emulsifier, a filling aid and / or an inactive ingredient.

[0299] In one example, the composition includes about 0.5% w / w to about 4% w / w silicon dioxide. In another example, the composition includes about 0.7% w / w to about 3% w / w silicon dioxide. In another example, the composition includes about 0.9% w / w to about 2% w / w silicon dioxide.

[0300] In one example, the composition includes at least about 0.5% w / w silicon dioxide. In another example, the composition includes at least about 1% w / w silicon dioxide. In another example, the composition includes at least about 1.5% w / w silicon dioxide. In yet another example, the composition includes at least about 2% w / w silicon dioxide. In another example, the composition includes at least about 2.5% w / w silicon dioxide. In another example, the composition includes at least about 3% w / w silicon dioxide. In yet another example, the composition includes at least about 3.5% w / w silicon dioxide. In another example, the composition includes at least about 4% w / w silicon dioxide.

[0301] In one example, the composition includes about 0.5% w / w silicon dioxide. In another example, the composition includes about 1% w / w silicon dioxide. In another example, the composition includes about 1.5% w / w silicon dioxide. In yet another example, the composition includes about 2% w / w silicon dioxide. In another example, the composition includes about 2.5% w / w silicon dioxide. In another example, the composition includes about 3% w / w silicon dioxide. In yet another example, the composition includes about 3.5% w / w silicon dioxide. In another example, the composition includes about 4% w / w silicon dioxide.

[0302] In one example, the compositions described herein include at least about 4 mg of silicon dioxide per dose. As described elsewhere herein, the dose may be formulated as two capsules.

[0303] In one example, the compositions described herein include at least about 5 mg of silicon dioxide per dose. In one example, the compositions described herein include at least about 6 mg of silicon dioxide per dose. In one example, the compositions described herein include at least about 7 mg of silicon dioxide per dose. In one example, the compositions described herein include at least about 8 mg of silicon dioxide per dose.

[0304] In one example, the composition described herein further includes vitamin B12. For regulatory purposes, vitamin B12 may be included in the composition described herein. In one example, the composition includes at least 15% of the recommended daily intake (RDI), i.e., 0.38mcg to 2.4mcg (EU) and 2.5mcg (for USA).

[0305] In one example, the compositions described herein include at least about 0.76 μg (mcg) of vitamin B12 per dose. In one example, the compositions described herein include at least about 0.9 μg (mcg) of vitamin B12 per dose.

[0306] The composition can be formulated into any suitable form. For example, it can be in the form of a tablet or a capsule. In one example, the composition is formulated as an acid-resistant tablet or capsule. Generally, "capsule" refers to empty capsules and filled capsules, while "shell" refers specifically to empty capsules, unless the context otherwise requires.

[0307] In some instances, the compositions described herein are included within a capsule (e.g., within a shell). In some instances, the compositions described herein are included within an acid-resistant capsule (e.g., within an acid-resistant shell). It will be clear to those skilled in the art that when referring to the % w / w of an ingredient present in a composition, this does not take into account any weight attributed to the capsule (thus only the % w / w of the composition within the capsule is considered).

[0308] In one example, the acid-resistant tablet or capsule includes a film coating, wherein the film coating includes hydroxypropyl methylcellulose (HPMC). HPMC is a semisynthetic, inert, viscoelastic polymer used in various applications. For example, HPMC can be used as an excipient in oral tablets and capsule formulations, wherein, depending on the grade, it acts as a release control agent to delay the release of the drug compound into the digestive tract. In tablets, HPMC can also be used as a component of a binder and / or tablet coating.

[0309] In one example, the composition described herein is comprised within a (capsule) shell, wherein the shell comprises hydroxypropylmethylcellulose (HPMC).

[0310] Those skilled in the art will understand the meaning of "acid-resistant" in the context of the present invention, particularly in the context of the ingestible compositions described herein. For example, the compositions described herein can be formulated as acid-resistant tablets or capsules, or can be included in acid-resistant capsules (e.g., acid-resistant shells) that dissolve once they reach the duodenum, allowing microbial cells and spores to be released and deposited in the upper part of the intestinal tract.

[0311] In one example, the composition is present in a capsule, wherein the capsule includes about 80 mg to about 100 mg of HPMC. For example, the capsule may include at least about 80 mg of HPMC. In one example, the capsule includes at least about 90 mg of HPMC. In one example, the capsule includes at least about 100 mg of HPMC. In one example, the capsule includes about 80 mg of HPMC. In one example, the capsule includes about 90 mg of HPMC. In another example, the capsule includes about 100 mg of HPMC.

[0312] Typically, HPMC is present as a film coating on the outer surface of the capsules described herein.

[0313] Compositions as described herein can be in unit dosage form. When compositions as described herein are in unit dosage form, one tablet or capsule can be administered, and this constitutes a dosage, or two tablets or capsules can be administered, and this constitutes a dosage. Those skilled in the art can determine suitable dosage and regimen according to the following examples. Therefore, in one example, the dosage of compositions according to the present invention includes multiple small tablets or capsules (e.g., two).

[0314] As used herein, the term "dosage form" refers to an amount of a drug that is taken at one time, optionally at fixed intervals. This is also referred to herein as a "dose".

[0315] In an embodiment, the invention provides solid unit dosage forms for oral administration.

[0316] In a specific example, the dosage of the composition described herein includes: about 300 mg of fermented rice bran, about 38 mg of L-cysteine, about 30 mg of microcrystalline cellulose, about 4 mg of magnesium stearate, about 4 mg of silicon dioxide, about 2 mg of dextrin, about 0.76 μg (mcg) of vitamin B12 and about 5,000 cfu of Bacillus. In this specific example, the dosage can be formulated as two tablets or capsules. In other words, the amount of the component can represent the total amount of the component present in the dosage (i.e., in two tablets or capsules). This corresponds to the composition used in Example 1 Test 7B. Therefore, the technician will understand that at least each of these components, with at least these amounts, provides an effective dosage according to the present invention. Thus, in one example, a dosage of the composition described herein includes at least about 300 mg of fermented rice bran, at least about 38 mg of L-cysteine, at least about 30 mg of microcrystalline cellulose, at least about 4 mg of magnesium stearate, at least about 4 mg of silicon dioxide, at least about 2 mg of dextrin, at least about 0.76 μg (mcg) of vitamin B12, and at least about 5,000 cfu of Bacillus bacteria.

[0317] In a specific example, the dosage of the composition described herein includes: 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 Bacillus. In this specific example, the dosage can be formulated as two tablets or capsules. In other words, the amount of the component can represent the total amount of the component present in the dosage (i.e., in two tablets or capsules). Therefore, the technician will understand that at least each of these components, with at least these amounts, provides an effective dosage according to the present invention. Thus, in one example, a dosage of the composition described herein includes 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 Bacillus bacteria.

[0318] Typically, HPMC is present as a film coating on the outer surface of the capsules described herein.

[0319] The compositions described herein may be used as (or as a part of) a dietary supplement, a nutraceutical, a food composition, a medical food, or a medicament.

[0320] As used herein, the term "dietary supplement" or "food supplement" refers to a composition that is consumed in addition to the daily diet or between meals.

[0321] As used herein, the term "food composition" refers to any type of composition that can be eaten and / or drunk without causing symptoms of toxicity in a subject that eats or drinks the respective composition.

[0322] Therefore, provided herein is the use of the composition described herein for degrading alcohol. The term "degrading alcohol" is described elsewhere herein and is equally applicable herein.

[0323] The composition can be used to degrade alcohol in a subject (e.g., can be used in vivo). The subject can be any suitable subject, for example, the subject can be a human. The subject can be a person who plans to drink or has drunk alcohol.

[0324] In one example, the composition can be used to metabolize alcohol in the digestive tract of a subject. The term "metabolize alcohol" is described elsewhere herein and is equally applicable herein. In one example, the composition can be used to metabolize alcohol in the intestinal tract of a subject. In a specific example, the composition can be used to metabolize alcohol in the small intestine of a subject. More particularly, the composition can be used to metabolize alcohol in the duodenum of a subject.

[0325] In one example, the composition can be used to reduce the blood absorption of alcohol in a subject. One skilled in the art can determine the reduction of blood absorption of alcohol in the presence of a composition provided herein (compared to when the composition is not used) using methods known in the art (e.g., the methods described in the Examples section below).

[0326] When the composition is used to degrade alcohol in a subject, it can be used to reduce the breath or blood alcohol concentration of the subject. Those skilled in the art can use methods known in the art (such as the method described in the following examples) to determine the reduction of breath or blood alcohol concentration in the presence of a composition provided herein (compared to when the composition is not used). For example, those skilled in the art can use methods known in the art (such as the method described in the following examples) about 30 minutes after alcohol intake (drinking), in the presence of a composition provided herein (compared to when the composition is not used), easily determine the reduction of breath or blood alcohol concentration.

[0327] Use of L-cysteine ​​for increasing alcohol degradation

[0328] Provided herein is the use of L-cysteine ​​for increasing alcohol degradation by one or more strains of the genus Bacillus. L-cysteine ​​can be used to increase alcohol degradation in vitro or in vivo. For example, when L-cysteine ​​is used as (or as part of) a dietary supplement, a nutrient, a medical food, or a drug, it can be used to increase alcohol degradation by one or more strains of the genus Bacillus.

[0329] The terms "L-cysteine", "alcohol degrading" and "one or more species of the genus Bacillus" are defined elsewhere herein, as well as examples of what these terms encompass. These definitions and aspects apply equally here.

[0330] One skilled in the art will be able to determine increased alcohol degradation in the presence of L-cysteine ​​(compared to when L-cysteine ​​is not used) using methods known in the art, such as those described in the Examples section below.

[0331] In a specific example, L-cysteine ​​can be used to increase alcohol degradation of one or more species of Bacillus selected from Bacillus subtilis and Bacillus coagulans. As described elsewhere herein, the one or more species of Bacillus can include Bacillus subtilis. Alternatively, the one or more species of Bacillus can include Bacillus coagulans. In an example, the one or more species of Bacillus can include Bacillus subtilis and Bacillus coagulans. The characteristics of these species are provided elsewhere herein, which are equally applicable to this aspect.

[0332] Suitable concentrations, amounts, ratios, etc. of one or more species of the genus Bacillus are described elsewhere herein and are equally applicable here.

[0333] In one embodiment, when the alcohol is ethanol, L-cysteine ​​can be used to increase the degradation of the alcohol by one or more species of the genus Bacillus.

[0334] In one example, when L-cysteine ​​is used to increase alcohol degradation by one or more species of Bacillus, it can be used in combination with a high molecular weight low osmotic pressure carbohydrate such as dextrin. In addition, or alternatively, L-cysteine ​​can be combined with rice bran.

[0335] In one example, when L-cysteine ​​is used as (or as part of) a dietary supplement, nutraceutical, or medical food (e.g., when it is part of a composition described herein), it can be used to increase the degradation of alcohol by one or more species of Bacillus.

[0336] Treatments and uses

[0337] As described elsewhere herein, the compositions described herein can be used to degrade alcohol in vitro or in vivo. Thus, the compositions described herein can be used as medicaments.

[0338] In one example, the compositions described herein can be used as a drug for degrading alcohol in a subject. The compositions provided herein may be particularly useful, for example, for preventing and / or treating organ damage caused by alcohol in a subject. For example, the compositions provided herein can be used to prevent and / or treat liver and / or pancreatic damage caused by alcohol in a subject.

[0339] As used herein, "organ damage caused by alcohol" includes acute and chronic alcohol-induced organ damage. Typically, alcohol-induced damage includes inflammation and / or inflammatory conditions, which lead to visceral organ and tissue dysfunction, resulting in severe secondary and sometimes life-threatening diseases. Since the liver is the main site of ethanol metabolism, alcohol abuse causes the greatest degree of tissue damage to the liver. For example, long-term excessive drinking leads to a variety of liver lesions, among which the most typical are fatty degeneration, hepatitis, and fibrosis / cirrhosis. Fatty degeneration is the earliest response to alcohol abuse, characterized by the deposition of fat in hepatocytes. Fatty degeneration can progress to steatohepatitis, which is a more serious inflammatory liver injury. Liver disease at this stage can lead to the development of fibrosis, during which extracellular matrix proteins are excessively deposited. The fibrotic reaction begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive scarring of the liver, vascular changes, and ultimately liver failure.

[0340] Other alcohol-induced injuries include acute and chronic pancreatitis. Pancreatitis is inflammation of the pancreas, resulting in retroperitoneal organ damage and dysfunction. The etiologies of pancreatitis vary, with alcohol and gallstones being the most common. Acute pancreatitis (AP) is a necrotizing inflammatory disease caused by destruction of exocrine cells by infiltrating inflammatory cells. Diagnostic criteria are usually the patient's presentation with characteristic symptoms, elevated lipase levels, and significant imaging findings. Acute pancreatitis either resolves with complete regeneration of the pancreas, causes transient organ failure, or progresses to systemic inflammation and multiorgan failure. Chronic pancreatitis (CP) is thought to be the result of recurrent episodes of acute pancreatitis, leading to pancreatic insufficiency, steatorrhea, diabetes, pancreatic calcification, and fibrosis. Alcohol renders the pancreas vulnerable to damage from otherwise benign factors. Therefore, one of the main strategies to prevent recurrences is to provide patients with counseling and strategies to abstain from alcohol (and smoking).

[0341] The compositions provided herein can be used to prevent and / or treat a disease, disorder or ailment selected from the group consisting of: fatty liver caused by alcohol, hepatitis caused by alcohol, cirrhosis, cancer caused by alcohol, cardiovascular disease, obesity, neuropathy, neurodegenerative disease, hangover symptoms, flushing syndrome, headache and / or acetaldehyde poisoning. In one example, the compositions provided herein can be used to prevent and / or treat a disease, disorder or ailment selected from the group consisting of: fatty liver caused by alcohol, hepatitis caused by alcohol, cirrhosis and cancer caused by alcohol.

[0342] 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.

[0343] Examples of cancers caused by alcohol are well known in the art and include liver cancer, pancreatic cancer, breast cancer, esophageal cancer, and oropharyngeal cancer. As used herein, the term "oropharyngeal cancer" refers to cancers that originate from the mouth, throat, larynx, or upper esophagus. In the early stages of cancer in this area, its source can be determined. However, many times, cancers in this area are discovered at an advanced invasive stage and their source cannot be determined. Therefore, cancers that originate from this source are collectively referred to as "oropharyngeal cancer." Those skilled in the art will be able to easily identify cancers associated with different parts of the body as described above.

[0344] As used herein, the term "neuropathy" refers to any disease or abnormality of the neurons of the nervous system. In particular, "neuropathy" refers to a disorder of the peripheral nervous system that affects nerves anywhere except the brain and spinal cord. A non-limiting example of a neuropathy is alcoholic polyneuropathy, which is characterized by numbness, abnormal sensations that occur spontaneously or in response to external stimuli (called dysesthesias and allodynias), and a characteristic form of pain (called neuropathic pain or neuralgia).

[0345] As used herein, the term "neurodegenerative disease" refers to any neurological disease or abnormality caused by neuronal degeneration, including neuronal death and loss of neurotransmitter function. Non-limiting examples of neurodegenerative diseases are Alzheimer's disease (e.g., late-onset Alzheimer's disease) and Parkinson's disease. As used herein, the term "late-onset Alzheimer's disease" refers to the onset of Alzheimer's disease in the elderly (particularly those aged 65 and above).

[0346] In one example, the neurodegenerative disease is Alzheimer's disease, optionally the neurodegenerative disease is late-onset Alzheimer's disease.

[0347] As used herein, "hangover" refers to the general discomfort that people who drink (e.g., drink and / or ingest) alcohol (excessively) usually feel when waking up. In other words, hangover is the result of body poisoning caused by consuming (excessive) alcohol. Hangover is a series of symptoms that occur the next day after drinking too much, and if the person smokes too much, the situation may become worse. The body protects itself from poisoning and secretes enzymes that metabolize and excrete toxins. However, when alcohol intake is excessive, the body's ability to metabolize alcohol decreases, and hangover symptoms occur. "Hangover symptoms" include headache (caused by vasodilation caused by histamine accumulation), red eyes, occasional memory loss, vomiting, possible flatulence, extreme thirst (derived from the body's reaction to dehydration caused by alcohol), abdominal and muscle pain (causing a sense of weakness, and sometimes diarrhea). In particular, headache is common in all hangover patients, and this is due to the effect of certain vasodilators (such as histamine) in the human body causing vasodilation.

[0348] As used herein, the term "hot flush syndrome" refers to the flushing that occurs after drinking alcohol. Hot flushes are associated with erythema (redness caused by dilated capillaries) that appear on the face, neck, and shoulders after drinking alcohol. Hot flushes after drinking alcohol are usually accompanied by a series of symptoms: dizziness, nausea, headache, rapid pulse, occasional extreme sleepiness, and occasional swelling and itching of the skin. These symptoms are collectively referred to as "hot flush syndrome" or "Asian flush."

[0349] The compositions provided herein can degrade alcohol in the digestive tract (intestinal tract) of the subject, thereby reducing the amount of alcohol absorbed by the blood. Therefore, the compositions provided herein can degrade alcohol before alcohol is transported to the liver. Therefore, the compositions provided herein can be used to protect the liver and related organs from liver damage caused by alcohol.

[0350] The compositions provided herein are administered to a subject at any time point before, during (e.g., simultaneously with alcohol intake or between alcohol intake, e.g., between the first drinking and the second drinking) or after alcohol intake, and can effectively degrade alcohol. From the perspective of effect, it is preferred to ingest the agent before or during alcohol intake, and most preferably at least one hour before alcohol intake. In some instances, the composition is used for administration before or simultaneously with alcohol intake.

[0351] In some instances, the composition (e.g., an effective amount of a composition described herein) is ingested at least five hours prior to the intake of alcohol. In some instances, the composition (e.g., an effective amount of a composition described herein) is ingested at least four hours prior to the intake of alcohol. In some instances, the composition (e.g., an effective amount of a composition described herein) is ingested at least three hours prior to the intake of alcohol. In some instances, the composition (e.g., an effective amount of a composition described herein) is ingested at least two hours prior to the intake of alcohol.

[0352] In one example, a composition (eg, an effective amount of a composition described herein) is ingested at least one hour prior to ingestion of alcohol.

[0353] In one example, a composition (eg, an effective amount of a composition described herein) is ingested at least 30 minutes prior to ingestion of alcohol.

[0354] In one example, a composition (eg, an effective amount of a composition described herein) is ingested at least 15 minutes prior to ingestion of alcohol.

[0355] In the case of using AB001 to prevent alcohol ingestion due to occasional drinking, it may be beneficial to take two doses before drinking alcohol, with a 2-hour interval between the two doses and the last dose taken at least 2 hours before ingestion of alcohol.

[0356] In some examples, a composition (eg, an effective amount of a composition described herein) is ingested at least 1 day prior to ingestion of alcohol.

[0357] In one example, a composition described herein (e.g., a dose of a composition described herein) is taken daily. In some examples, a composition (e.g., an effective amount of a composition described herein) is taken daily 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 prior to alcohol intake. For example, one dose (e.g., 2 capsules or tablets of a composition described herein) may be taken daily 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 prior to alcohol intake. For example, one dose (e.g., 2 capsules or tablets of a composition described herein) may be taken daily 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days prior to alcohol intake.

[0358] In a specific example, one dose (e.g., 2 capsules or tablets of a composition described herein) may be taken daily 7 days prior to alcohol intake. In other words, a composition described herein (e.g., an effective amount of a composition described herein, such as a dosage of a composition described herein) may be taken daily 1 week prior to alcohol intake.

[0359] In one example, a composition (eg, an effective amount of a composition described herein) is ingested at least 15 minutes prior to ingestion of alcohol.

[0360] In some examples, the composition (eg, an effective amount of a composition described herein) is ingested simultaneously with alcohol. In other words, the composition (eg, an effective amount of a composition described herein) is ingested at the same time as alcohol.

[0361] In other examples, the composition (e.g., an effective amount of a composition described herein) is ingested after (e.g., subsequently to) the intake of alcohol. For example, the composition (e.g., an effective amount of a composition described herein) can be ingested after the intake of a first alcoholic beverage. In another example, the composition (e.g., an effective amount of a composition described herein) can be ingested after the intake of a first alcoholic beverage but before the intake of a second alcoholic beverage, and so on, for example, the composition (e.g., an effective amount of a composition described herein) can be ingested after the intake of a second alcoholic beverage but before the intake of a third alcoholic beverage.

[0362] In some instances, the composition (e.g., an effective amount of a composition described herein) is ingested at least five hours after the ingestion of alcohol. In some instances, the composition (e.g., an effective amount of a composition described herein) is ingested at least four hours after the ingestion of alcohol. In some instances, the composition (e.g., an effective amount of a composition described herein) is ingested at least three hours after the ingestion of alcohol. In some instances, the composition (e.g., an effective amount of a composition described herein) is ingested at least two hours after the ingestion of alcohol.

[0363] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least one hour after ingestion of alcohol.

[0364] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 30 minutes after ingestion of alcohol.

[0365] In one example, the composition (eg, an effective amount of a composition described herein) is ingested at least 15 minutes after ingestion of alcohol.

[0366] It will be clear to those skilled in the art that the compositions described herein can be administered to a subject at any time point before, during or after alcohol intake. As described above, from the perspective of effect, it is preferred to take the agent before or during alcohol intake, most preferably at least one hour before alcohol intake.

[0367] As used herein, "ingestion" refers to the absorption (e.g., consumption) of a substance by an organism. Thus, as used herein, "alcohol intake" refers to the act or process by which alcohol is absorbed into an organism (e.g., a subject, preferably a human). In the context of the present invention, alcohol is preferably taken in orally, wherein the subject is a human. "Alcohol intake" and "drinking" are used interchangeably herein.

[0368] The composition can be taken orally in the form of an aqueous solution, tablet, capsule, granule, etc. In addition, the composition can be added to an alcoholic beverage (or other alcohol source) before it is taken. For example, the composition can be added as an additional ingredient during the production of the alcoholic beverage.

[0369] Suitable intake amounts of the compositions disclosed herein depend on the quality of the alcohol that is (to be) ingested.

[0370] Also provided herein are pharmaceutical preparations comprising the compositions of the present invention. As will be apparent to those skilled in the art, pharmaceutical preparations are preparations suitable for administration to a subject to degrade alcohol. Pharmaceutical preparations can be administered to a subject for the prevention and / or treatment of a disease, disorder or ailment selected from the group consisting of: fatty liver caused by alcohol, hepatitis caused by alcohol, cirrhosis, cancer caused by alcohol, cardiovascular disease, obesity, neuropathy, neurodegenerative disease, hangover symptoms, flushing syndrome, headache and / or acetaldehyde poisoning. As used herein, pharmaceutical preparations include an effective dose of the compositions of the present invention.

[0371] The compositions described herein are used to be administered to a subject (preferably a person) in an effective amount (effective dose). "Effective amount" refers to the amount that produces a desired (therapeutic or non-therapeutic) response alone or together with other doses. The effective amount to be used will depend on, for example, the treatment (or non-therapeutic) purpose, the route of administration, and the condition of the subject. For example, for a given subject, the appropriate dose of the composition of the present invention can be determined by a doctor (or a person administering the composition), while considering various factors known to change the effect of the composition of the present invention, such as alcohol intake, body weight, sex, diet, administration time and route, other drugs and other relevant clinical factors. Dosage and dosage regimen can vary according to the specific condition, illness or symptom or overall condition of the subject. The effective dose can be determined by in vitro or in vivo methods.

[0372] The compositions described herein are advantageously presented in dosage units. For example, the compositions can be presented in the form of capsules or tablets. Other suitable dosage units are described elsewhere herein.

[0373] An "effective amount" may include administration of one or more dosage units. For example, an effective amount may be achieved by administration of one or two capsules or tablets. When an effective amount includes multiple dosage units, the dosage units may be administered together, or may be taken at intervals throughout the day.

[0374] Those skilled in the art can easily determine alternative appropriate effective amounts and dosage forms using routine experiments based on the following examples.

[0375] As used herein, the terms "treating" and "treatment" refer to the administration of a composition to a subject (e.g., a symptomatic subject suffering from an undesirable condition, disorder, affliction or disease) to affect a reduction in the severity and / or frequency of symptoms, to eliminate symptoms and / or their underlying causes, and / or to promote improvement or remediation of damage, and / or to prevent an undesirable condition, disorder, affliction or disease in an asymptomatic subject susceptible to, or suspected of having or at risk of having, a particular undesirable condition, disorder, affliction or disease.

[0376] As used herein, the term "prevent" means to avoid the occurrence or recurrence of

[0377] Symptoms and / or their underlying causes, damages, adverse conditions, illnesses, ailments and / or diseases. For example, in the context of the present invention, "prevention" may be avoiding the occurrence of one or more symptoms associated with a hangover.

[0378] As discussed elsewhere herein, the subject can be any suitable subject, for example, the subject can be a human. The subject can be a human who plans to drink or has consumed alcohol.

[0379] As used herein, "pharmaceutical composition" refers to a composition with pharmacological activity or other direct effects to alleviate, treat or prevent diseases, and / or its finished dosage form or preparation, and for human use. Pharmaceutical compositions or pharmaceutical preparations are usually produced under Good Manufacturing Practice (GMP) conditions. Pharmaceutical compositions or preparations can be sterile or non-sterile. If non-sterile, such pharmaceutical compositions or preparations generally meet the microbiological quality standards and standards of non-sterile drug products described in the United States Pharmacopoeia (USP) or the European Pharmacopoeia (EP). Therefore, compositions as described herein can be formulated as pharmaceutical compositions. In some instances, pharmaceutical compositions are non-sterile.

[0380] Unless otherwise defined herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. For example, Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2nd ed., John Wiley and Sons, NY (1994); and Hale and Marham, Harper & Co., 1996.

[0381] Collins Biological Dictionary, Harper Perennial, NY (1991) provides a general dictionary of many terms used in the present invention for those skilled in the art. Although any method and material similar or equivalent to the method and material described herein can be used to practice the present invention, described herein are preferred methods and materials. Therefore, the terms defined below will be described more fully by reference to the entire specification. In addition, as used herein, unless the context clearly indicates otherwise, the singular terms "a", "an" and "the" include plural references. Unless otherwise indicated, nucleic acids are written from left to right in the 5' to 3' direction; amino acid sequences are written from left to right in the amino to carboxyl direction. It should be understood that the present invention is not limited to the specific methods, protocols and reagents described, because these may vary, depending on the context in which they are used by those skilled in the art.

[0382] Aspects of the invention are demonstrated by the following non-limiting examples.

[0383] Example

[0384] Example 1 - Development of the compositions described herein

[0385] background

[0386] The inventors had previously developed food-grade quality fermented rice bran for evaluation purposes. A safety study was initiated using a case study design. Approximately 1,400 people took the product regularly over a long period of time. No side effects / adverse reactions were reported. However, signs of an anti-hangover effect were reported. The inventors sought to further investigate this effect.

[0387] experiment

[0388] Tissue tests confirmed the anti-hangover effect of fermented rice bran in a controlled manner. Eight men in their 30s to 50s each drank four pints of beer (4.2%) within an hour and a half for the first time. The average 30 minutes after drinking was 1.24‰, and 5.5 hours ≤ 0.20‰.

[0389] Two weeks later, the same group went through the same procedure but took 0.75g of fermented rice bran powder before drinking. Averaged 0.91‰ 30 minutes after drinking, and ≤0.20‰ 4.0 hours after drinking. Digestion of alcohol is 25% faster than in the liver. Measured by a breathalyser.

[0390] A more comprehensive test was then conducted, including both sexes, and participants with a wider range of age and weight. All tests were crossover designs, with either iBAC or Breathalyzer, the same group without and with fermented rice bran (referred to herein as "Pinch", please note that "Pinch" as used herein may also include other ingredients such as dextrin and / or L-cysteine ​​as described below). Participants enjoyed tea / coffee and a cheese roll before drinking 60cl of red wine (13.5%) within four hours. Breathalyzer measurements were taken every hour starting 15 minutes after drinking, with an endpoint of ≤0.20‰. The test results are shown below. The composition of the fermented rice bran powder used for each test is also shown below. The data are summarized in Figures 8 to 11 middle.

[0391] Test 1

[0392] Test 1a

[0393] 16 participants, 11 males and 5 females, aged 24 to 68 years, weighing 46 to 92 kg, did not use Pinch

[0394] 15 minutes: average 0.97‰

[0395] 1 hour: average 0.89‰

[0396] 2 hours: average 0.52‰

[0397] 3 hours: average 0.42‰

[0398] 4 hours: average 0.29‰

[0399] 5 hours: average 0.16‰

[0400] Test 1b, Pinch = fermented rice bran only

[0401] Thirteen participants, 9 males and 4 females, aged 24 to 68 years, weighing 46 to 92 kg, used Pinch

[0402] 15 minutes: average 1.03‰

[0403] 1 hour: average 0.78‰

[0404] 2 hours: average 0.41‰

[0405] 3 hours: average 0.22‰

[0406] 4 hours: average 0.07‰

[0407] Test 2

[0408] Test 2a

[0409] 14 participants, 10 males and 4 females, aged 22 to 62 years, weighing 46 to 87 kg, did not use Pinch

[0410] 15 minutes: average 0.91‰

[0411] 1 hour: average 0.80‰

[0412] 2 hours: average 0.52‰

[0413] 3 hours: average 0.44‰

[0414] 4 hours: average 0.24‰

[0415] 5 hours: average 0.11‰

[0416] Test 2b, Pinch = fermented rice bran + 5% dextrin

[0417] Fourteen participants, 10 males and 4 females, aged 22 to 62 years, weighing 46 to 87 kg, used Pinch

[0418] 15 minutes: average 0.93‰

[0419] 1 hour: average 0.72‰

[0420] 2 hours: average 0.36‰

[0421] 3 hours: average 0.19‰

[0422] 4 hours: average 0.03

[0423] Test 3

[0424] Test 3a

[0425] 17 participants, 12 males and 5 females, aged 20 to 59 years, weighing 42 to 97 kg, did not use Pinch

[0426] 15 minutes: average 1.04‰

[0427] 1 hour: average 0.90‰

[0428] 2 hours: average 0.61‰

[0429] 3 hours: average 0.42‰

[0430] 4 hours: average 0.21‰

[0431] 5 hours: average 0.11‰

[0432] Test 3b, Pinch = fermented rice bran + 2% dextrin

[0433] Thirteen participants, 9 males and 4 females, aged 20 to 48 years, weighing 46 to 84 kg, used Pinch

[0434] 15 minutes: average 0.96‰

[0435] 1 hour: average 0.76‰

[0436] 2 hours: average 0.34‰

[0437] 3 hours: average 0.18‰

[0438] 4 hours: average 0.08‰

[0439] Test 4

[0440] Test 4a

[0441] 18 participants, 11 males and 7 females, aged 20 to 69 years, weighing 42 to 125 kg, did not use Pinch

[0442] 15 minutes: average 0.96‰

[0443] 1 hour: average 0.87‰

[0444] 2 hours: average 0.62‰

[0445] 3 hours: average 0.39‰

[0446] 4 hours: average 0.20‰

[0447] 5 hours: average 0.08‰

[0448] Test 4b, Pinch = fermented rice bran + 0.5% dextrin

[0449] Fifteen participants, 10 males and 5 females, aged 24 to 64 years, weighing 42 to 125 kg, used Pinch

[0450] 15 minutes: average 0.96‰

[0451] 1 hour: average 0.76‰

[0452] 2 hours: average 0.35‰

[0453] 3 hours: average 0.16‰

[0454] 4 hours: average 0.04‰

[0455] Test 5

[0456] Test 5a

[0457] 17 participants, 11 males and 6 females, aged 28 to 64 years, weighing 43 to 125 kg, did not use Pinch

[0458] 15 minutes: average 0.92‰

[0459] 1 hour: average 0.81‰

[0460] 2 hours: average 0.65‰

[0461] 3 hours: average 0.44‰

[0462] 4 hours: average 0.23‰

[0463] 5 hours: average 0.06‰

[0464] Test 5b, Pinch = fermented rice bran + 0.5% dextrin + 30% L-cysteine

[0465] Sixteen participants, 11 males and 5 females, aged 28 to 64 years, weighing 43 to 125 kg, used Pinch

[0466] 15 minutes: average 0.98‰

[0467] 1 hour: average 0.71‰

[0468] 2 hours: average 0.32‰

[0469] 3 hours: average 0.05‰

[0470] Test 6

[0471] Test 6a

[0472] 14 participants, 8 males and 6 females, aged 22 to 69 years, weighing 41 to 125 kg, did not use Pinch

[0473] 15 minutes: average 0.92‰

[0474] 1 hour: average 0.84‰

[0475] 2 hours: average 0.61‰

[0476] 3 hours: average 0.42‰

[0477] 4 hours: average 0.27‰

[0478] 5 hours: average 0.08‰

[0479] Test 6b, Pinch = fermented rice bran + 0.5% dextrin + 20% L-cysteine

[0480] Sixteen participants, 11 males and 5 females, aged 28 to 62 years, weighing 43 to 125 kg, used Pinch

[0481] 15 minutes: average 0.98‰

[0482] 1 hour: average 0.65‰

[0483] 2 hours: average 0.28‰

[0484] 3 hours: average 0.06‰

[0485] Test 7

[0486] Test 7a

[0487] 16 participants, 8 males and 8 females, aged 21 to 65 years, weighing 42 to 125 kg, did not use Pinch

[0488] 15 minutes: average 1.03‰

[0489] 1 hour: average 0.90‰

[0490] 2 hours: average 0.73‰

[0491] 3 hours: average 0.52‰

[0492] 4 hours: average 0.28‰

[0493] 5 hours: average 0.10‰

[0494] Test 7b, Pinch = fermented rice bran + 0.5% dextrin + 10% L-cysteine

[0495] Fifteen participants, 10 males and 5 females, aged 21 to 65 years, weighing 42 to 125 kg, used Pinch

[0496] 15 minutes: average 0.96‰

[0497] 1 hour: average 0.68‰

[0498] 2 hours: average 0.31‰

[0499] 3 hours: average 0.17‰

[0500] 4 hours: average 0.03‰

[0501] Test 8

[0502] Test 8a

[0503] 14 participants, 9 males and 5 females, aged 26 to 65 years, weighing 44 to 125 kg, did not use Pinch

[0504] 15 minutes: average 0.93‰

[0505] 1 hour: average 0.78‰

[0506] 2 hours: average 0.63‰

[0507] 3 hours: average 0.48‰

[0508] 4 hours: average 0.24‰

[0509] 5 hours: average 0.07‰

[0510] Test 8b, Pinch = fermented rice bran + 5% dextrin + 20% L-cysteine

[0511] Twelve participants, 8 males and 4 females, aged 26 to 65 years, weighing 44 to 125 kg, used Pinch

[0512] 15 minutes: average 0.96‰

[0513] 1 hour: average 0.75‰

[0514] 2 hours: average 0.44‰

[0515] 3 hours: average 0.21‰

[0516] 4 hours: average 0.03‰

[0517] Microbial characteristics

[0518] Using Sanger DNA sequencing, the main bacterial strains found in the used compositions were identified as species of Bacillus subtilis and species of Bacillus coagulans. Other genera / species identified were Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus MT 03, Bacillus atrophaeus and Pediococcus pentosaceus.

[0519] Dextrin and L-Cysteine

[0520] Dextrin is available from a variety of suppliers. Dextrins from three different suppliers were tested and confirmed to be effective (data not shown). The preferred dextrin for use herein is hydrolyzed corn dextrin (eg, Vitargo).

[0521] L-cysteine ​​is also available from multiple suppliers. L-cysteine ​​from three different suppliers was tested and confirmed to be effective (data not shown). The preferred L-cysteine ​​used herein is of plant origin.

[0522] in conclusion

[0523] The results show that fermented rice bran including two major strains of Bacillus, namely Bacillus subtilis and Bacillus coagulans, has a substantial alcohol digestion effect, 25-30% faster than the digestion of alcohol by the liver alone. In addition, the above results show that dextrin further accelerates the rate of alcohol digestion, about 35-40% faster than liver digestion. Using 0.5 to 5% dextrin, the difference in additional effects observed was minimal. From a clinical perspective, a composition of 79.5% w / w fermented rice bran (including at least 10,000 cfu / g of bacteria of the genus Bacillus), 0.5% w / w dextrin and 20.0% w / w L-cysteine ​​was evaluated as the optimal mixture for intestinal digestion of alcohol, about 50% faster than liver digestion of alcohol. Therefore, a combination of 0.5% w / w dextrin and 20.0% w / w L-cysteine ​​was used in the following Examples 2 and 3. Thus, the composition used in Examples 2 and 3 includes 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 cfu of Bacillus bacteria.

[0524] Mode of action

[0525] Without being bound by this hypothesis, the present inventors believe that dextrin and / or L-cysteine ​​create a microenvironment at the cellular level that allows the microbial consortium to expel an enzyme cascade that targets short carbon chains (e.g., ethanol / alcohols) after intestinal resuscitation - resulting in preferential targeting / preferential use of ethanol / alcohols as substrates.

[0526] Normally, about 80% of ingested alcohol stays in the small intestine for quite some time before being absorbed into the bloodstream. The targeted enzyme acts only on alcohol in the intestine and breaks it down into carbon dioxide and water, bypassing the liver's process of converting alcohol into acetaldehyde and acetic acid, the hangover metabolites.

[0527] Example 2 - Dietary Supplement Comparative Trial PERA-ATX-001: Evaluation of Bacteria-Based Nutritional Supplements Clinical study on the effect of (AB001) on intestinal ethanol absorption

[0528] Research Summary

[0529]

[0530]

[0531] Table 1: Summary of PERA-ATX-001 study.

[0532] Introduction

[0533] As described elsewhere herein, the inventors have developed an alcohol degradation composition (AB001) to help avoid problems associated with alcohol intake. It consists of naturally fermented rice bran, Bacillus subtilis and Bacillus coagulans, L-cysteine ​​and dextrin. It also includes magnesium stearate and calcium and potassium phosphates. The supplement is made with an acid-resistant capsule HPMC that dissolves once it reaches the duodenum. The culture is released and precipitates in the upper part of the intestine, where they remain for about a day before being excreted from the body through feces. The bacterial strains included in the composition are selected to preferentially and efficiently metabolize ethanol into CO2 and water, thereby reducing further absorption of alcohol by the intestine. As a result, it is expected that the body absorbs less alcohol and that damage to organs caused by alcohol degradation products is also reduced.

[0534] The aim of this study was to evaluate the reduction of alcohol absorption in blood and breath alcohol levels in healthy subjects when they consumed a certain amount of alcohol after one week of dietary supplementation with AB001 or placebo. In addition, cognitive function one hour after alcohol ingestion and the tolerability of both interventions were explored.

[0535] Patients and methods

[0536] Study population

[0537] A prospective, double-blind, randomized, crossover study is planned to be conducted in 24 healthy adult volunteers who must not suffer from any disease that could affect alcohol digestion or tolerance (e.g., gastrointestinal or metabolic disorders, alcohol addiction, allergies, etc.).

[0538] Research Plan

[0539] The study was conducted in accordance with international and local ethical and scientific standards. The protocol was approved by the responsible ethical review committee ( The study was approved by the German Federal Hospital for Infectious Diseases (Bundesamt für Verbraucherschutz und Lebensmittelsicherheit) in Rheinland-Pfalz, Mainz, Germany and released to the responsible national authorities (Bundesamt für Verbraucherschutz und Lebensmittelsicherheit). Before participation, participants signed a written informed consent. Thereafter, blood was drawn for safety analysis and to determine potential exclusion criteria, and participants were randomized into two study arms (Visit 1).

[0540] The subjects were asked to participate in two experimental procedures (visits 2 and 3) after taking two placebo or AB001 capsules each day for one week. After arriving at the research center, the subjects had a light breakfast, and then they consumed 0.3 g of alcohol / kg body weight of high-alcohol spirits (vodka). Breath tests (gas chromatography) were performed at a central laboratory (Labor Augsburg, Augsburg, Germany) at 0 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, and 360 min. Alcotest 3820, Safety AG, L1beck, Germany) and blood was drawn to measure alcohol. Before and 60 min after drinking, participants were asked to perform a digital connection test. The time required to complete the test was recorded. The experiment was run for at least 120 min until no alcohol was found in the breath test at two consecutive time points.

[0541] After the second experimental session (Visit 3), the patient was withdrawn from the study.

[0542] Statistical analysis

[0543] The area under the curve (AUC) of blood alcohol levels over time is used to calculate the reduction in alcohol absorption by AB001. Typically, this can be done in two ways:

[0544] A. AUC can be calculated for each participant individually by using the following formula for each time point Tk:

[0545] AUC(0-180)=∑_(k=0)^180(C[k+1]-C[k]) / 2*([k+1]-[k]

[0546] Where T[k] and T[k+1] are two consecutive time points, C[k+1] and C[k] are the alcohol concentrations measured upon reaching the respective time points, and T[k+1]-T[k] is the time interval between the measurements. This was done for each individual and for both treatment groups. A two-sided Student's T-test was used to calculate the p-value for the differences between the groups (5% error, 80% power, type 1).

[0547] B. Optionally, calculate the mean ± STD of the blood alcohol results for each time point and calculate the area under the curve for each treatment. Calculate the contribution of each time point to the AUC and calculate the p value for the difference between groups using a two-sided Student's T test (5% error, 80% power, type 1).

[0548] The calculated results for blood alcohol content 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).

[0549] result

[0550] Deviation from the plan

[0551] No protocol deviations occurred in this trial. However, the sponsor informed the site that the treatment pack for subject 13 was mixed up and the correct order of refills was verum (Box 1) followed by placebo (Box 2). Patients 21 to 24 reported a possible similar problem. This information was confirmed by the respective results after unblinding, and the patients were therefore included in the reverse randomization sequence in the final analysis.

[0552] patient

[0553] According to the plan, 24 healthy subjects were enrolled in the study (13 males, 11 females, mean age: 25.4±7.7 years (range: 18-55 years), BMI: 23.6±2.5 kg / m 2 (Range: 19.1kg / m 2 -29.1kg / m 2 Tables 2 and 3 provide a list of patients and individual patient characteristics as well as blood pressure and alcohol intake.

[0554]

[0555]

[0556] Table 2: Patient characteristics.

[0557]

[0558]

[0559] Table 3: Blood pressure, body weight and alcohol intake (32% vodka) at different visits.

[0560] Statistical analysis population

[0561] All patients were studied according to the protocol and included in the safety and efficacy analyses.

[0562] Efficacy Results

[0563] Overall, IRB-approved alcohol intake (0.3 g / kg body weight) was low (47 mL to 89 mL of 32% alcohol spirits), and 6 subjects (25%) did not reach a measurable blood alcohol concentration under either intervention. Of the remaining participants, 4 subjects did not exceed a blood alcohol concentration of 0.1‰ after using verum or placebo (17% of the test population). In the placebo experiment, no detectable breath alcohol concentration was seen in 3 subjects at all. Breath alcohol levels above 0.1‰ were detected in 18 subjects in this group. The highest alcohol concentrations observed occurred in the placebo experiment, at 0.33‰ (breath) and 0.27‰ (blood), respectively (verum: 0.30‰ and 0.21‰).

[0564] Blood alcohol results

[0565] Figure 1 Mean blood concentrations after one week of regular nutritional supplementation (study product or placebo, 2 capsules / day) are provided.

[0566] No measurable alcohol levels were detected in the blood for more than 180 min in any single experiment. AUC for placebo experiments 血液(0-180min) The calculation was 8.5±0.6o / oo*min, and the verum experiment was 2.5±0.2*min (-70.3%; p<0.005, see Figure 2 ).

[0567] Breath alcohol results

[0568] Figure 3 Mean breath alcohol concentrations after one week of regular nutritional supplementation (study product or placebo, 2 capsules / day) and ingestion of 0.3 g / kg body weight of alcohol are presented.

[0569] No measurable levels of alcohol were detected in breath for more than 180 min in any single experiment. AUC calculated from mean concentrations in the placebo experiment 呼气(0-180min) The verum test was 14.0o / oo*mL, and the verum test was 9.7o / oo*mL (-30.7%, p<0.005, see Figure 4 ).

[0570] Digital connection test

[0571] Alcohol intake did not affect patients' cognitive function, as assessed by measuring the time required to complete a standardized digital connection test. Individual results are shown in Table 4.

[0572]

[0573] Table 4: Time requirements for digital connection tests at baseline (0 min) and after 60 min

[0574] There was no difference in the time required to complete cognitive function tests between verum and placebo, both before and one hour after ingestion.

[0575] Security Analysis

[0576] Nutritional supplementation was well tolerated, and no adverse events or serious adverse events were reported in this trial. It can be concluded that nutritional supplementation had no side effects in this trial.

[0577] In addition, no clinically relevant deviations from normal values ​​were observed in the safety biochemistry panels performed before and after the study.

[0578] Discussion and Conclusion

[0579] As shown herein, blood alcohol absorption was significantly reduced by more than 70% after one week of AB001 supplementation compared to placebo. The measurable alcohol in the breath was also significantly reduced, but to a lesser extent (~30%). It is well known that breath and blood alcohol are highly correlated, but breath alcohol measurements are more susceptible to physiological changes (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 generally be more determined by alcohol absorbed early in the upper gastrointestinal tract (i.e., buccal mucosa and stomach). This may explain why the effects measured in the blood test are more obvious than in the breath test.

[0580] Of note, in 10 cases (42%), the amount of alcohol consumed (0.3 g / kg body weight) did not result in a measurable, relevant alcohol concentration in the blood. The amount of alcohol to be consumed in this study was determined by the IRB during the study approval process.

[0581] In conclusion, regular supplementation with AB001 for one week resulted in a substantial reduction in blood alcohol uptake and, therefore, a greater than 70% reduction in alcohol uptake in systemic metabolism. Therefore, regular intake of AB001 as a nutritional supplement may help prevent liver and other organ damage known to be associated with regular alcohol intake and may reduce the negative medical and economic impacts of social drinking on individuals and society.

[0582] References for Example 2

[0583] Jones AW. Medicolegal Alcohol Determination–Blood–or breath alcohol concentration. Forensic Sci. Rev. 12:23-47, 2000.

[0584] Example 3 - Dietary Supplement Comparative Trial PERA-ATX-002: Evaluation of Single-Dose Nutritional Supplements A prospective randomized study of the effects of (AB001) on alcohol absorption in healthy subjects

[0585] Research Summary

[0586]

[0587]

[0588] Table 5: Summary of PERA-ATX-002 study.

[0589] As mentioned above, the inventors have developed an alcohol degradation supplement (AB001) to help avoid problems associated with alcohol intake. It consists of naturally fermented rice bran, Bacillus subtilis and Bacillus coagulans, L-cysteine ​​and dextrin. It also includes magnesium stearate and calcium and potassium phosphates. The supplement is made of acid-resistant capsules HPMC that dissolve once it reaches the duodenum. The cultures are released and precipitated in the upper part of the intestine, where they stay for about a day and are then excreted from the body through feces. The bacterial strains are selected to preferentially and efficiently metabolize ethanol into CO2 and water, thereby reducing further absorption of alcohol by the intestine. Therefore, it is expected that the body absorbs less alcohol and that the damage caused to the organs by alcohol degradation products is also reduced.

[0590] Example 2 provides the first randomized placebo-controlled double-blind crossover study, in which 24 healthy subjects (13 males, 11 females, age: 25.4±7.7yrs, BMI: 23.6±2.5kg / m2) were randomized to take AB001 or placebo, 2 capsules / day, one week before the alcohol exposure experiment. On the day of the experiment, they ate a light breakfast and drank a moderate amount of spirits (0.3g / kg body weight). In order to determine the blood alcohol level, a breath alcohol test and blood draw were performed for up to 6 hours. The area under the curve was calculated to determine the alcohol absorption rate. After using AB001, the blood alcohol level was significantly reduced by 70.3% (compared with placebo, p<0.005), (breath test: -30.7%; compared with placebo, p<0.005). No difference was found in the cognitive function test performed 60min after alcohol intake (22.4±7.7sec vs.22.7±5.6sec,ns). No adverse events or serious adverse events were reported in this study.

[0591] The purpose of the study in Example 3 is to continue scientific research on the performance of AB001 and answer the following questions:

[0592] 1. What results would be expected if a single dose of AB001 was taken directly before alcohol ingestion, rather than a 7-day supplementation as in previous studies?

[0593] 2. Are the observed inhibitory effects maintained at higher doses of alcohol?

[0594] Patients and methods

[0595] Study population

[0596] A prospective, double-blind, randomized, crossover study is planned to be conducted in 24 healthy adult volunteers who must not suffer from any disease that could affect alcohol digestion or tolerance (e.g., gastrointestinal or metabolic disorders, alcohol addiction, allergies, etc.; see the study protocol for detailed inclusion and exclusion criteria).

[0597] Research Plan

[0598] The study was conducted in accordance with international and local ethical and scientific standards. The protocol was approved by the responsible ethical review committee ( Rheinland-Pfalz, Mainz, Germany) and published to the responsible national authorities (Bundesamt für Verbraucherschutz und Lebensmittelsicherheit).

[0599] Prior to participation, participants signed written informed consent. Thereafter, blood was drawn for safety analysis and to determine potential exclusion criteria, and participants were randomized into two study arms (Visit 0).

[0600] The enrolled subjects were asked to participate in two experimental procedures (visits 1 and 2). Arriving at the study center in the morning after an overnight fast, they were randomly assigned to receive either placebo or AB001 supplementation. One hour after ingestion of the study product, participants consumed the first glass of high-alcohol spirits (vodka; 0.3 g / kg body weight, time point 0 min) and ate a light breakfast consisting of a roll, ham or jam, and tea or coffee. Thereafter, they consumed the second glass of spirits (vodka; 0.3 g / kg body weight, time point 30 min). Blood was drawn to determine plasma alcohol concentration, and breathalyzer assessment was performed after 0, 15, 30, 45, 60, 75, 90, 120, 180, 240, 300, 360, and 420 min to determine breath alcohol concentration. Participants remained at the study center throughout the entire procedure. A standardized lunch was provided 4 hours later. In addition, participants underwent a cognitive function test (digit connection test, NCT-A) at time points 0 and 60 min. Information on adverse events was recorded. The experiment was terminated early if no alcohol was detected in the breath at two consecutive time points after the second alcohol ingestion.

[0601] The second experiment was performed 3 to 5 days later following the same experimental protocol. After the second experiment (Visit 2), the patient was withdrawn from the study.

[0602] Statistical analysis

[0603] The area under the curve (AUC) of blood alcohol levels over time is used to calculate the reduction in alcohol absorption by AB001. Typically, this can be done in two ways:

[0604] A. AUC can be calculated for each participant individually by using the following formula for each time point Tk:

[0605] AUC(0-180)=∑_(k=0)^180(C[k+1]-C[k]) / 2*([k+1]-[k]

[0606] Where T[k] and T[k+1] are two consecutive time points, C[k+1] and C[k] are the alcohol concentrations measured upon reaching the respective time points, and T[k+1]-T[k] is the time interval between the measurements. This was done for each individual and for both treatment groups. A two-sided Student's T-test was used to calculate the p-value for the differences between the groups (5% error, 80% power, type 1).

[0607] B. Optionally, calculate the mean ± STD of the blood alcohol results for each time point and calculate the area under the curve for each treatment. Calculate the contribution of each time point to the AUC and calculate the p value for the difference between groups using a two-sided Student's T test (5% error, 80% power, type 1).

[0608] The calculated results for blood alcohol content were p = 0.014 (A) and p = 0.000019 (B), and the calculated results for breath alcohol content were p = 0.0448 (A) and p = 0.000074 (B), respectively (see Results section below).

[0609] result

[0610] Deviation from the plan

[0611] No protocol deviations occurred in this trial.

[0612] patient

[0613] According to the plan, 24 healthy subjects were enrolled in the study (12 males, 12 females, mean age: 28.3±10.8 years (range: 20-56 years), BMI: 23.5±5.7 kg / m 2 (Range: 16.9kg / m 2 -31.1kg / m 2 Tables 6 and 7 provide a list of patients and individual patient characteristics as well as blood pressure and alcohol intake.

[0614]

[0615] Table 6: Patient characteristics.

[0616]

[0617]

[0618] Table 7: Blood pressure, pulse and alcohol intake (32% vodka) at different visits.

[0619] Statistical analysis population

[0620] All patients were studied according to the protocol and included in the safety and efficacy analyses.

[0621] Efficacy Results

[0622] Typically, IRB-approved alcohol intake (2 × 0.3 g / kg body weight) resulted in measurable blood alcohol levels in all subjects. The highest alcohol concentrations observed were in the placebo trials, 0.88o / oo (breath) and 0.91o / oo (blood), respectively (AB001: 0.77o / oo and 0.72o / oo).

[0623] Blood alcohol results

[0624] Figure 5Mean blood concentrations after nutritional supplementation with 2 capsules of the study product or placebo one hour before the experiment are provided.

[0625] AUC in placebo trials 血液(0-420min) The calculated value was 116 ± 32 0 / 00*min, and the AB001 experiment was 104 ± 24 0 / 00*min (-10.1%; p < 0.05, see Figure 6 ).

[0626] Breath alcohol results

[0627] Figure 7 Mean breath alcohol concentrations after nutritional supplementation with 2 capsules of the study product or placebo one hour before the experiment are provided.

[0628] AUC in placebo trials 呼气(0-420min) The calculation was 98±29o / oo*min, and the AB001 experiment was 91±25o / oo*min (-7.2%, p<0.05).

[0629] Digital connection test

[0630] Alcohol intake did not affect patients' cognitive function, as assessed by measuring the time required to complete a standardized digital connection test. Individual results are shown in Table 8.

[0631]

[0632]

[0633] Table 8: Time requirements for digital connection tests at baseline (0 min) and after 60 min.

[0634] Individual subjects had mild impairments in performance after alcohol ingestion that were statistically significant in the AB001 trial (p<0.05) and nearly statistically significant in the placebo trial (p=0.057).

[0635] Security Analysis

[0636] The nutritional supplement was well tolerated. Two adverse events were reported in this trial.

[0637] At Screening and Visit 3 prior to ingestion of AB001, Subject 6 (female, 27 years old) reported a case of mild anemia. Mild anemia was diagnosed based on the following laboratory results (Screening / Visit 3—Reference Ranges):

[0638] Red blood cells: 3.74 / 3.64 Mio / μL (reference range: 3.9–5.2 Mio / μL)

[0639] Hemoglobin: 11 / 2 / 11.0 g / dL (reference range: 12-16 g / dL

[0640] Hematocrit: 34 / 33% (reference range: 36%-46%)

[0641] At screening, the investigators rated these findings as “not clinically significant” and therefore the subjects could be included. The subjects were advised to follow up with their family physicians about this condition after the trial. The investigators classified this event as “unrelated” to the study intervention.

[0642] At Visit 3 prior to taking AB001, Subject 9 (male, 30 years old) reported a moderate headache (migraine). The subject reported this as a known ongoing event, which was treated, in practice, with 200 mg of ibuprofen. The Investigator classified this event as "unrelated" to the study intervention.

[0643] In addition, no serious adverse events were reported in this trial.

[0644] It can be concluded that the intake of nutritional supplements was not associated with any adverse effects in this trial. In addition, no other clinically relevant deviations from normal values ​​were observed in the safety biochemistry panels performed before and after the study.

[0645] Discussion and Conclusion

[0646] In Example 2 (PERA-ATX-001), supplementation with AB001 for one week significantly reduced blood alcohol absorption by more than 70% compared to placebo when 0.3 g / kg alcohol was consumed after a light breakfast. Measurable alcohol in breath was also significantly reduced, but to a lesser degree (~30%).

[0647] In this example, it was observed that taking a single dose of AB001, 2 x 0.3 g / kg alcohol each time, one hour before drinking, with a 30-min interval between two drinks and a light meal during the period, could also effectively reduce blood and breath alcohol. In particular, compared with placebo, the use of AB001 significantly reduced the amount of alcohol in the blood by about 10%, and the amount of alcohol in the breath by 7%.

[0648] In conclusion, a single dose of AB001 taken within 1 h before drinking reduced intestinal alcohol absorption, resulting in a significant reduction in blood and breath alcohol levels of approximately 10% and 7%, respectively.

[0649] Example 4 - In vivo alcohol studies

[0650] In vivo studies were conducted as described below. It demonstrates the efficacy of fermented rice bran and natural health-beneficial Bacillus species. The composition described in Examples 2 and 3 (also referred to herein as AB001) was used. The study demonstrated that taking AB001 reduced the production of bilirubin in male plasma during and after 10% alcohol drinking and a high-fat, high-carbohydrate diet. For the female group, when the out-of-range values ​​were excluded from the raw data, the results showed that CMD (placebo group) increased bilirubin by 3.7 times (Av. 1.68 mg / dl) compared to IC (control group) (Av. 0.46 mg / dl), while PB (probiotic group) increased bilirubin by 1.8 times (Av. 0.82 mg / dl), i.e., compared to CMD, preventing bilirubin from rising. Using a similar analysis, for the male group, when the out-of-range values ​​were excluded from the raw data, the results showed that CMD and PB reduced bilirubin (to 0.44 to 0.45), respectively, compared to 0.91 mg / dl for IC. This suggests that AB001 consumption did not adversely affect bilirubin levels. Fig.12 .

[0651] In vivo studies also showed that AB001 (ie, the composition of Examples 2 and 3) also prevented excessive weight gain in animals exposed to a high fat and high carbohydrate diet (western diet). Fig.13 ).

[0652] Fig.14 An overview of the experimental design for the in vivo alcohol study is shown. Animal studies used 90 mice (C57BL / 6JRj; Javier Labs; France), grouped by sex, 8 weeks old when arriving at the experimental facility and acclimatized (5 days). The mice were grouped and fed as follows:

[0653] 1) The intact group had access to water and was fed a standard rodent diet (standard rodent pellet diet; Lactamin; Vadstena; Sweden). This group is referred to herein as the "IC" group.

[0654] 2) The placebo group drank 10% ethanol aqueous solution and was fed a mixture of 12% maltodextrin and a Western high-fat, high-carbohydrate diet (D12492M diet, Research Diets, New Brunswick, NJ 08901, USA). This group is referred to herein as the "CMD" group.

[0655] 3) DFM products, drinking 10% ethanol solution, and feeding a mixture of 12% DFM products and a Western high-fat, high-carbohydrate diet (D12492M diet, Research Diets, New Brunswick, NJ 08901, USA). This group is referred to herein as the "PB" group. As used herein, DFM refers to a composition of the present invention, in this case AB001, as described in Examples 2 and 3.

[0656] For six weeks, mice were placed on a 12-hour day-night cycle. Five mice were housed in IVC cages with beta-chip bedding. During the adaptation period and the study, drinking water was supplied in bottles (free access to water). Animal weight, food intake, and water intake were measured weekly. Differences in body weight, food intake, and water intake were calculated at the beginning and last day of the experiment.

[0657] Blood and tissue samples were collected from anesthetized animals. Liver and spleen were collected postmortem by intracardiac injection of pentobarbital (Allfatal, Omnidea). Plasma was collected from blood to measure bilirubin levels. The left lobe of the liver was sampled and stored in 10% neutral formalin solution for 24 hours for morphological analysis. For fat content of the liver, samples were stored at -80°C.

[0658] Statistical analysis was performed using Prism version 9.1.0 (GraphPad Software, Inc, San Diego, CA, USA) to distinguish whether significant differences between samples were found or observed. If p ≤ 0.05, the groups were considered to be statistically different.

[0659] abbreviation

[0660]

[0661]

[0662] Table 9: Abbreviations used in Examples 2 and 3.

[0663] The reader is advised to pay attention to all papers and documents related to the present application filed concurrently or previously with the present specification, which are open to public inspection with the present specification, and the contents of all these papers and documents are incorporated herein by reference.

[0664] All features disclosed in this specification (including any accompanying claims, abstract and drawings) and / or all steps of any disclosed method or process may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive.

[0665] Each feature disclosed in this specification (including any accompanying claims, abstracts and drawings) may be replaced by an optional feature having the same, equivalent or similar purpose, unless expressly stated otherwise. Therefore, unless expressly stated otherwise, each feature disclosed is only an example of a series of equivalent or similar features.

[0666] The present invention is not limited to the details of any foregoing embodiments. The present invention extends to any novel feature or any novel combination of features disclosed in this specification (including any accompanying claims, abstract and drawings), or any novel step or any novel combination of any disclosed method or process.

Claims

1. An alcohol degradation composition comprising one or more species of Bacillus, rice bran, L-cysteine ​​and a high molecular weight low osmotic pressure carbohydrate.

2. The composition according to claim 1, wherein The one or more species of Bacillus are selected from Bacillus subtilis and Bacillus coagulans.

3. The composition according to claim 2, wherein The composition includes Bacillus subtilis and Bacillus coagulans.

4. A composition according to any one of claims 2 or 3, wherein: a) the Bacillus subtilis species is selected from the group consisting of Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMGP-32900); and / or c) The Bacillus coagulans species is Bacillus coagulans strain DFM 0705 (LMGP-32921).

5. A composition according to any one of the preceding claims, wherein The high molecular weight low osmotic pressure carbohydrate is dextrin.

6. A composition according to any one of the preceding claims, wherein The alcohol is ethanol.

7. A composition according to any one of the preceding claims, wherein The composition further comprises one or more species selected from the group consisting of Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.

8. A composition according to any one of the preceding claims, wherein The composition includes at least about 10% w / w L-cysteine.

9. A composition according to any one of the preceding claims, wherein The composition includes at least about 10,000 cfu / g of bacteria of the genus Bacillus.

10. A composition according to any one of the preceding claims, wherein The composition comprises at least about 67% w / w rice bran.

11. A composition according to any one of the preceding claims, wherein The composition includes at least about 0.5% w / w of a high molecular weight low osmotic pressure carbohydrate.

12. A composition according to any one of the preceding claims, wherein The composition further comprises one or more of the following: vitamin B12, magnesium salt of fatty acid, calcium phosphate, potassium phosphate, silicon dioxide and cellulose, optionally wherein the magnesium salt of fatty acid is magnesium stearate.

13. A composition according to any one of the preceding claims, wherein The composition is formulated as acid-resistant tablets or capsules.

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. A composition according to any one of the preceding claims, wherein The one or more species of the genus Bacillus are not genetically modified.

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

17. Use of L-cysteine ​​for increasing the degradation of alcohol by one or more species of the genus Bacillus.

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

19. The use according to claim 17 or 18, wherein The L-cysteine ​​is combined with rice bran.

20. The use according to any one of claims 17 to 19, wherein The one or more species of Bacillus are selected from Bacillus subtilis and Bacillus coagulans, and optionally wherein the composition comprises Bacillus subtilis and Bacillus coagulans.

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

22. The use according to any one of claims 17 to 21, wherein The alcohol is ethanol.

23. The use according to any one of claims 16 to 22, wherein The use is for degrading alcohol in a subject.

24. The use according to claim 23, wherein The use is for metabolizing alcohol in the digestive tract of the subject, optionally wherein the use is for metabolizing alcohol in the intestinal tract of the subject, more optionally wherein the use is for metabolizing alcohol in the small intestine of the subject.

25. The use according to claim 23 or 24, wherein The use is for reducing the blood absorption of alcohol by the subject.

26. The use according to any one of claims 23 to 25, wherein The use is for reducing breath or blood alcohol concentration in the subject.

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

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

29. Use of the composition according to any one of claims 1 to 15 for preventing and / or treating alcohol-induced organ damage in a subject.

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

31. A composition for use according to any one of claims 27 to 30, wherein The composition is used to prevent and / or treat a disease, disorder or condition selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, liver 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 the group consisting of liver cancer, pancreatic cancer, breast cancer, esophageal cancer, and oropharyngeal cancer.

33. A composition for use according to any one of claims 27 to 32, wherein The composition is intended for administration prior to alcohol ingestion.

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

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 of claim 35, wherein: The organ is the liver and / or the pancreas.

37. The method according to any one of claims 34 to 36, for preventing and / or treating a disease, disorder or ailment selected from the group consisting of alcohol-induced fatty liver, alcohol-induced hepatitis, liver cirrhosis, alcohol-induced cancer, cardiovascular disease, obesity, neuropathy, neurodegenerative disease, hangover symptoms, flushing syndrome, headache and / or acetaldehyde poisoning.

38. The method of claim 37, wherein: The cancer is selected from the group consisting of liver cancer, pancreatic cancer, breast cancer, esophageal cancer, and oropharyngeal cancer.

39. The method according to any one of claims 34 to 38, wherein: The composition is administered prior to or during alcohol intake.

Images