WO2023187097A1 - Alcohol degrading compositions and uses thereof - Google Patents

Alcohol degrading compositions and uses thereof Download PDF

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Publication number
WO2023187097A1
WO2023187097A1 PCT/EP2023/058370 EP2023058370W WO2023187097A1 WO 2023187097 A1 WO2023187097 A1 WO 2023187097A1 EP 2023058370 W EP2023058370 W EP 2023058370W WO 2023187097 A1 WO2023187097 A1 WO 2023187097A1
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Prior art keywords
composition
alcohol
bacillus
dose
rice bran
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PCT/EP2023/058370
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English (en)
French (fr)
Inventor
Johan De Faire
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De Faire Medical AB
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De Faire Medical AB
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Priority to AU2023246874A priority Critical patent/AU2023246874A1/en
Priority to US18/851,739 priority patent/US20250213626A1/en
Priority to EP23717428.9A priority patent/EP4499048A1/en
Priority to JP2024557929A priority patent/JP2025511131A/ja
Priority to KR1020247035468A priority patent/KR20240167863A/ko
Priority to CA3246845A priority patent/CA3246845A1/en
Priority to CN202380039669.9A priority patent/CN119343134A/zh
Publication of WO2023187097A1 publication Critical patent/WO2023187097A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
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    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/718—Starch or degraded starch, e.g. amylose, amylopectin
    • A—HUMAN NECESSITIES
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    • A61K31/716—Glucans
    • A61K31/721—Dextrans
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
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    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
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    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
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    • A61P25/00—Drugs for disorders of the nervous system
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    • A—HUMAN NECESSITIES
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Definitions

  • the present invention provides an alcohol degrading composition comprising one or more bacterial species of the Bacillus genus, rice bran, L-cysteine and a high molecular weight low osmolality carbohydrate. Methods of using the composition are also provided herein.
  • Alcohol is often described as a social lubricant. People tend to feel more relaxed after a drink or two and a bit less self-conscious. There are many social occasions that are based around alcohol consumption. Some studies even suggest that drinking in moderation may bring certain health benefits. It is these beneficial aspects of alcohol that ensure its continued popularity.
  • Alcohol is a toxin that can cause damage to the body even in small doses.
  • Those who drink regularly above the safe limits are at increased risk of health problems, including but not limited to certain cancers, cardiovascular events, high blood pressure, accidents while under the influence, and progression to alcohol abuse and addiction. For some individuals, it is not safe for them to drink any alcohol at all.
  • Alcohol intoxication also known as drunkenness or alcohol poisoning
  • Symptoms at lower doses may include mild sedation and poor coordination.
  • At higher doses there may be slurred speech, trouble walking, and vomiting.
  • Extreme doses may result in a respiratory depression, coma, or death.
  • Complications may include seizures, aspiration pneumonia, injuries including suicide, and low blood sugar.
  • Alcohol is mostly metabolized in the liver, which is why the liver is particularly at risk of damage.
  • Drinking heavily significantly increases the risk of alcoholic fatty liver, an early and reversible consequence of excessive alcohol intake.
  • Chronic drinking alters the liver’s metabolism of fats, 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 finally liver cirrhosis.
  • the invention is based on the surprising finding that L-cysteine can be used to increase alcohol degradation by one or more bacterial species of the Bacillus genus.
  • the inventors have surprisingly discovered that L-cysteine can be used to increase alcohol degradation by one or more bacterial species of the Bacillus genus particularly when combined with a high molecular weight low osmolality carbohydrate, such as dextrin.
  • the inventors have shown that L-cysteine can be used to increase alcohol degradation by one or more bacterial species of the Bacillus genus in the gut, particularly when combined with a high molecular weight low osmolality carbohydrate, such as dextrin.
  • the inventors have developed a novel composition to reduce uptake of alcohol into the blood and, therefore, to reduce the undesirable effects associated with alcohol ingestion.
  • compositions described herein accelerate the body’s processing of alcohol by accelerating alcohol degradation, particularly in the gut.
  • alcohol degradation particularly in the gut.
  • about 80% of alcohol that is ingested resides in the small intestine before being absorbed to the blood.
  • the compositions described herein advantageously reduce the amount of alcohol absorption from the gut into the blood (and thus reduce the amount of alcohol that is processed by the liver).
  • uptake of the compositions described herein prior to alcohol ingestion significantly reduces blood alcohol levels and breath alcohol levels after alcohol ingestion, as compared to placebo.
  • an alcohol degrading composition comprising one or more bacterial species of the Bacillus genus, rice bran, L-cysteine and a high molecular weight low osmolality carbohydrate is provided.
  • a high molecular weight low osmolality carbohydrate e.g. dextrin
  • L-cysteine create a micro-environment in the gut that makes the microbial consortium of the compositions provided herein, upon resuscitation in the intestinal tract, excrete an enzyme cascade targeted towards short carbon chains, e.g. ethanol/alcohol, resulting in preferential targeting of these substrates.
  • the targeted enzymes preferentially act on the alcohol residing in the intestinal tract and break it down into carbon dioxide and water, bypassing the liver process of converting alcohol into acetaldehyde and acetic acid/acetate (which are hangover metabolites that would otherwise be formed by the liver’s conversion of alcohol).
  • the compositions described herein thus accelerate the body’s processing of alcohol (away from the liver).
  • the Bacillus spp. of the composition Upon resuscitation in the intestinal tract, the Bacillus spp. of the composition (and their endospores) scan the biochemical conditions of their micro-environment and start to excrete a unique selection of bio-active substances to optimise the conditions, e.g. pH, conductivity, electrolytes, for their survival and multiplication. Nutrients and substrates are essential for survival and subsequent multiplication.
  • alcohol/ethanol/ethyl alcohol is present in the micro-environment, alcohol-targeted enzymes are excreted to break down alcohol into fragments containing carbon. Carbon that cannot be used by the microbes, or neighbouring tissue cells, as a nutrient will be biochemically metabolised into water and carbon dioxide that can escape the body system without causing any biological consequences/symptoms.
  • the high molecular weight low osmolality carbohydrate (e.g. dextrin) and/or L-cysteine provided in the compositions described herein enhance this environmental scan and selective excretion of bio-active substances for optimised enzymatic conditions.
  • compositions provided herein may be formulated as an acid resistant tablet or capsule.
  • Such formulations are known to resist the acid in the stomach, only to dissolve once reaching the duodenum.
  • the Bacillus spp. of the composition can then be released to settle in the upper part of the intestinal tract where they can reside for about one day before being eliminated from the body through the feces.
  • the bacterial spp. of the composition described herein were selected to preferably and effectively metabolize ethyl alcohol into CO2 and water, thus reducing the further resorption of alcohol from the intestinal tract. As a consequence, less alcohol is expected to be absorbed by the body, and damage of organs through alcohol degradation products is expected to be diminished.
  • the invention provides an alcohol degrading composition comprising one or more bacterial species of the Bacillus genus, rice bran, L-cysteine and a high molecular weight low osmolality carbohydrate.
  • the one or more bacterial species of the Bacillus genus may be selected from B. subtilis and B. coagulans.
  • the composition may comprise B. subtilis and B. coagulans.
  • a) the B. subtilis species may be selected from the group consisting of: Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900); and/or c) the B. coagulans species may be Bacillus coagulans strain DFM 0705 (LMG P-32921).
  • the high molecular weight low osmolality carbohydrate may be dextrin.
  • the alcohol may be ethyl alcohol (ethanol).
  • the composition may further comprise one or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.
  • Bacillus amyloliquefaciens Bacillus velezensis
  • Bacillus sp MT 03 Bacillus atrophaeus
  • Pediococcus pentosaceus selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.
  • the composition may comprise at least about 10% w/w of L-cysteine.
  • the composition may comprise at least about 10,000 cfu/g of bacteria of the Bacillus genus.
  • the composition may comprise at least about 67% w/w of rice bran.
  • the composition may comprise at least about 0.5% w/w of high molecular weight low osmolality carbohydrate.
  • the composition may further comprise one or more of: vitamin B12, a fatty acid magnesium salt, calcium phosphate, potassium phosphate, silicon dioxide and cellulose, optionally wherein the fatty acid magnesium salt is magnesium stearate.
  • the composition may be formulated as an acid resistant tablet or capsule.
  • the acid resistant tablet or capsule may comprise a film coating, wherein the film coating comprises hydroxypropyl methylcellulose (HPMC).
  • HPMC hydroxypropyl methylcellulose
  • the one or more bacterial species of the Bacillus genus is not genetically modified.
  • the invention also provides the use of an alcohol degrading composition as described herein, for degrading alcohol.
  • the invention further provides the use of L-cysteine for increasing alcohol degradation by one or more bacterial species of the Bacillus genus.
  • the L-cysteine may be combined with a high molecular weight low osmolality carbohydrate, optionally wherein the high molecular weight low osmolality carbohydrate is dextrin.
  • the L-cysteine may be combined with rice bran.
  • the one or more bacterial species of the Bacillus genus may be selected from B. subtilis and B. coagulans, optionally wherein the composition comprises B. subtilis and B. coagulans.
  • a) the B. subtilis species may be selected from the group consisting of: Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900); and/or c) the B. coagulans species may be Bacillus coagulans strain DFM 0705 (LMG P-32921).
  • the alcohol may be ethyl alcohol (ethanol).
  • the use may be for degrading alcohol in a subject.
  • the use may be for metabolising alcohol in the gut of the subject, optionally wherein the use is for metabolising alcohol in the intestine of the subject, more optionally wherein the use is for metabolising alcohol in the small intestine of the subject.
  • the use may be for reducing absorption of alcohol into the blood of the subject.
  • the use may be for reducing breath or blood alcohol concentration in the subject.
  • the invention further provides a composition as described herein for use as a medicament.
  • the invention further provides a composition described herein for use in degrading alcohol in a subject.
  • a composition described herein for use in preventing and/or treating alcohol-induced organ damage in a subject is also provided.
  • the organ may be the liver and/or the pancreas.
  • the composition may be for use in preventing and/or treating a disease, condition or illness selected from the group consisting of: alcohol induced fatty liver, alcohol induced hepatitis, liver cirrhosis, alcohol induced cancer, cardio-vascular conditions, obesity, neuropathy, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache and/or intoxication by acetaldehyde.
  • a disease, condition or illness selected from the group consisting of: alcohol induced fatty liver, alcohol induced hepatitis, liver cirrhosis, alcohol induced cancer, cardio-vascular conditions, obesity, neuropathy, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache and/or intoxication by acetaldehyde.
  • the cancer may be selected from: liver cancer, pancreatic cancer, breast cancer, esophageal cancer and oropharyngolaryngeal cancer.
  • the composition may be for administration before alcohol ingestion.
  • a method of degrading alcohol in a subject comprising administering a composition described herein to the subject is provided.
  • the invention further provides a method of preventing and/or treating alcohol-induced organ damage in a subject, comprising administering a composition described herein to the subject.
  • the organ may be the liver and/or the pancreas.
  • the method may be for preventing and/or treating a disease, condition or illness selected from the group consisting of: alcohol induced fatty liver, alcohol induced hepatitis, liver cirrhosis, alcohol induced cancer, cardio-vascular conditions, obesity, neuropathy, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache and/or intoxication by acetaldehyde.
  • a disease, condition or illness selected from the group consisting of: alcohol induced fatty liver, alcohol induced hepatitis, liver cirrhosis, alcohol induced cancer, cardio-vascular conditions, obesity, neuropathy, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache and/or intoxication by acetaldehyde.
  • the cancer may be selected from: liver cancer, pancreatic cancer, breast cancer, esophageal cancer and oropharyngolaryngeal cancer.
  • the composition may be administered before alcohol ingestion.
  • the present invention provides an alcohol degrading composition comprising one or more bacterial species of the Bacillus genus, rice bran, L-cysteine and a high molecular weight low osmolality carbohydrate. Methods of using the composition are also provided herein.
  • rice bran may be replaced with any suitable cereal (e.g. cereal grain) unless the context provides otherwise.
  • a suitable cereal may be any suitable cereal bran. Suitable cereals and suitable cereal brans are discussed elsewhere herein.
  • Figure 2 shows mean reduction of alcohol absorption into the blood by AB001 .
  • Figure 4 shows mean reduction in breath alcohol levels by AB001 .
  • Figure 6 shows mean reduction of alcohol absorption into the blood by AB001.
  • Figure 8 shows data generated from individuals (74 men and women age 26 to 66) having ingested 60 cc of wine (14%) consumed in 1 h.
  • the individuals were given the following composition at 600 mg/dose: Fermented rice bran 414 mg, L-cysteine 120 mg, dextrin 10 mg, Vitamin B12 0.90 mcg, Excipients 26 mg, HPMC capsules.
  • Figure 9 shows data generated from individuals (84 men, 56, and women, 28, age 26 to 72) having ingested 60 cc of wine (14%) consumed in 1 h.
  • the individuals were given the following composition: Fermented rice bran 69%, L-cysteine 20%, dextrin 2%, Vitamin B12 0.00002%, Excipients 9%, HPMC capsules, at the indicated dosages.
  • Figure 10 shows data generated from individuals (87 men and women age 26 to 66) having ingested 60 cc of wine (14%) consumed in 1 h.
  • the individuals were given the following composition, at 750 mg/dose: Fermented rice bran 518 mg, L-cysteine 150 mg, dextrin 15mg, Vitamin B120.90mcg, Excipients 67 mg, HPMC capsules, and response time was determined.
  • Figure 11 shows data generated from individuals (62 men and women age 26 to 66) having ingested 60 cc of wine (14%) consumed in 1 h.
  • the individuals were given the following Composition: Fermented rice bran 69%, L-cysteine 20%, dextrin 2%, Vitamin B12 0.00002%, Excipients 9%, HPMC capsules.
  • Time-cut in % to 0.05 %o compared to “predicted time to soberness” according to iBAC manual (acc. to sc.edu* (*https://sc.edu/about/offices_and_divisions/fraternity_and_sorority_life/documents/bac- charts1617.pdf).
  • Figure 12 shows changes in bilirubin content in plasma; data generated from an in vivo alcohol study in mice.
  • IC Intact Control group with standard rodent fed
  • CMD Placebo Group
  • PB Probiotic Group
  • Figure 13 shows body weight change during the in vivo alcohol study in mice.
  • Figure 14 provides an overview of the experimental design for the in vivo alcohol study in mice.
  • the invention is based on the surprising finding that L-cysteine can be used to increase alcohol degradation by one or more bacterial species of the Bacillus genus.
  • the inventors have surprisingly discovered that L-cysteine can increase alcohol degradation by one or more bacterial species of the Bacillus genus particularly when combined with a high molecular weight low osmolality carbohydrate, such as dextrin.
  • the data presented herein demonstrates that L-cysteine, particularly when combined with a high molecular weight low osmolality carbohydrate, such as dextrin, can be used to increase alcohol degradation by one or more bacterial species of the Bacillus genus in the gut.
  • the inventors have developed a novel composition to reduce uptake of alcohol into the blood and, therefore, to reduce the undesirable effects associated with alcohol ingestion.
  • an alcohol degrading composition comprising one or more bacterial species of the Bacillus genus, rice bran, L-cysteine and a high molecular weight low osmolality carbohydrate is provided herein.
  • the composition provided herein may be referred to as “MYRKL” and/or “AB001”. Additionally, the composition provided herein may be referred to as “Pinch” unless the context defines “Pinch” otherwise (see Example 1).
  • alcohol refers to any of a class of organic compounds characterized by one or more hydroxyl (—OH) groups attached to a carbon atom of an alkyl group (hydrocarbon chain). Alcohols may be considered as organic derivatives of water (H2O) in which one of the hydrogen atoms has been replaced by an alkyl group, typically represented by R in organic structures. For example, in ethanol (or ethyl alcohol) the alkyl group is the ethyl group, — CH2CH3. Alcohols may be classified as primary, secondary, or tertiary, according to which carbon of the alkyl group is bonded to the hydroxyl group. Most alcohols are colourless liquids or solids at room temperature.
  • Alcohols of low molecular weight are highly soluble in water; with increasing molecular weight, they become less soluble in water, and their boiling points, vapour pressures, densities, and viscosities increase.
  • Non-limiting examples of alcohol include methanol and ethanol.
  • an “alcohol degrading composition”, as referred to herein, is a composition which degrades alcohol.
  • an “alcohol degrading composition”, as used herein, is a composition which breaks down (e.g. biochemically breaks down) alcohol.
  • degradation e.g. breakdown
  • a substance such as alcohol
  • alcohol degrading refers to the breaking down of alcohol
  • alcohol degradation refers to the breakdown of alcohol.
  • the composition described herein can be used in vitro or in vivo.
  • Alcohol may be degraded (e.g. broken down) in several different ways. Particularly relevant in the context of the present invention is biochemical degradation. Accordingly, in one example, alcohol may be degraded (e.g. broken down) biochemically. As would be known to the skilled person, the biochemical break down of a substance may involve enzyme catalyzed reactions. Thus, in one example, alcohol may be degraded enzymatically.
  • alcohol dehydrogenase ADH
  • aldehyde dehydrogenase ADH
  • ADH aldehyde dehydrogenase
  • acetaldehyde is further metabolized by acetaldehyde dehydrogenase to another, less active byproduct called acetate, which then is broken down into water and carbon dioxide for easy elimination.
  • Acetate is broken down to carbon dioxide and water mainly in tissues other than the liver.
  • Alcoholdehydrogenase generates free oxygen radicals that affect the genes.
  • the enzymes cytochrome P450 2E1 (CYP2E1) and catalase also break down alcohol to acetaldehyde.
  • CYP2E1 only is active after a person has consumed large amounts of alcohol, and catalase metabolizes only a small fraction of alcohol in the body. Small amounts of alcohol also are removed by interacting with fatty acids to form compounds called fatty acid ethyl esters (FAEEs). These compounds have been shown to contribute to damage to the liver and pancreas.
  • FAEEs fatty acid ethyl esters
  • compositions described herein promote the degradation (e.g. break down) of alcohol into carbon dioxide and water in the gut, whilst by-passing the liver’s conversion of alcohol into noxious metabolites, including acetaldehyde and in turn acetic acid, which are considered as hangover metabolites that are formed by the liver’s conversion of alcohol.
  • the compositions described herein may promote the degradation of alcohol into carbon dioxide and water in the gut via intermediary metabolites that are not acetaldehyde and/or acetic acid.
  • Metabolism is a term used to describe all biochemical reactions involved in maintaining the living state of cells and organisms.
  • metabolism includes all the biochemical reactions involved in converting one molecule into another (to essentially maintain the living state of a cell or an organism).
  • Metabolism includes processes for cell growth, reproduction, response to the environment, survival mechanisms, sustenance, and maintenance of cell structure and integrity.
  • the biochemical reactions involved in metabolism utilize various enzymes.
  • alcohol may be metabolized (i.e. alcohol may be degraded via metabolism).
  • an alcohol metabolizing composition comprising one or more bacterial species of the Bacillus genus, rice bran, L-cysteine and a high molecular weight low osmolality carbohydrate (e.g. dextrin) is provided.
  • metabolism may be enzymatic thus, in some examples, alcohol may be metabolized enzymatically.
  • Metabolism may be categorized into two: 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.
  • catabolism may be used to refer to all biochemical or enzymatic reactions involved in the breakdown of organic or inorganic materials such as proteins, sugars, fatty acids, etc.
  • Anabolism includes a sequence of biochemical reactions that constructs or synthesizes molecules from smaller units, usually requiring the input of energy (ATP) in the process.
  • Catabolism thus refers to destructive biochemical reactions which occur in an organism whereas metabolism refers to the whole set of biochemical reactions in the organism, which can be either constructive or destructive.
  • alcohol may be catabolized (i.e alcohol may be degraded via catabolism). In a further example, alcohol may be catabolized enzymatically.
  • alcohol is degraded in a subject.
  • alcohol may be broken down enzymatically, metabolized or catabolized in a subject. Where alcohol degradation occurs in a subject (e.g. particularly in the duodenum and/or small intestine) this may be referred to digestion. In some examples, alcohol may be degraded by biochemical digestion.
  • the alcohol is ethyl alcohol (also known as ethanol).
  • Ethanol is an organic chemical compound. It is a simple alcohol with the chemical formula C2H6O. Its formula can be also written as CH3-CH2-OH or C2H5OH (an ethyl group linked to a hydroxyl group), and is often abbreviated as EtOH. Ethanol is a volatile, flammable, colorless liquid with a characteristic wine-like odor and pungent taste. It is a psychoactive drug, recreational drug, and the active ingredient in alcoholic drinks. Accordingly, in one example, the alcohol is comprised within an alcoholic drink. Non-limiting examples of alcoholic drinks include beer, wine and spirits (e.g. vodka).
  • an ethanol degrading composition comprising one or more bacterial species of the Bacillus genus, rice bran, L-cysteine and a high molecular weight low osmolality carbohydrate (e.g. dextrin) is provided herein.
  • an ethanol metabolizing composition comprising one or more bacterial species of the Bacillus genus, rice bran, L-cysteine and a high molecular weight low osmolality carbohydrate (e.g. dextrin) is provided herein.
  • the alcohol degrading composition provided herein comprises one or more bacterial species of the Bacillus genus.
  • the composition may comprise two or more bacterial species of the Bacillus genus.
  • the composition may comprise three or more bacterial species of the Bacillus genus.
  • the composition may comprise four or more bacterial species of the Bacillus genus.
  • the composition may comprise five or more bacterial species of the Bacillus genus. In a further example, the composition may comprise six or more bacterial species of the Bacillus genus. In another example, the composition may comprise seven or more bacterial species of the Bacillus genus.
  • a genus is made up of several species.
  • the genus "Bacillus” thus includes all species within the genus “Bacillus,” known to those of skill 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 velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Bacillus thuringiensis.
  • the genus Bacillus continues to undergo taxonomical reorganization.
  • the genus include species that have been reclassified, including but not limited to such organisms as B. stearothermophilus, which is now named "Geobacillus stearothermophilus.”
  • the production of resistant endospores in the presence of oxygen is considered the defining feature of the genus Bacillus, although this characteristic also applies to the recently named Alicyclobacillus, Amphibacillus, Aneurinibacillus, Anoxybacillus, Brevibacillus, Filobacillus, Gracilibacillus, Halobacillus, Paenibacillus, Salibacillus, Thermobacillus, Ureibacillus, and Virgibacillus.
  • Bacillus species refers to a species within the genus "Bacillus”.
  • Bacillus species found to be particularly important in the context of the present invention include Bacillus subtilis (B. subtilis) and Bacillus coagulans (B. coagulans). As described in the examples below, these bacteria are abundant in the composition of the invention and are particularly effective at degrading (e.g. metabolizing) ethyl alcohol into carbon dioxide and water, especially within the gut.
  • the one or more bacterial species of the Bacillus genus is selected from B. subtilis and B. coagulans.
  • the composition provided herein comprises B. subtilis and B. coagulans.
  • B. subtilis strains and/or B. coagulans strains may be used in accordance with the present invention.
  • a person skilled in the art would readily be able to 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.
  • a Bacillus subtilis strain deposited under LMG-P accession number 32899 may be referred to herein as “DFM 0326” or “strain DFM 0326”.
  • Bacillus subtilis strain DFM 0326 (deposited under LMG-P accession number 32899) was deposited at the Belgian Coordinated Collections of Micro-organisms (BCCM), Laboratorium voor Microbiologie - Bacterienverzameling (LMG), Universiteit Gent, K.L. Ledeganckstraat 35, 9000 Gent, Belgium under The Budapest Treaty of 1977 on 22 November 2022.
  • a 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 at the Belgian Coordinated Collections of Micro-organisms (BCCM), Laboratorium voor Microbiologie - Bacterienverzameling (LMG), Universiteit Gent, K.L. Ledeganckstraat 35, 9000 Gent, Belgium under The Budapest Treaty of 1977 on 22 November 2022.
  • a 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 at the Belgian Coordinated Collections of Micro-organisms (BCCM), Laboratorium voor Microbiologie - Bacterienverzameling (LMG), Universiteit Gent, K.L. Ledeganckstraat 35, 9000 Gent, Belgium under The Budapest Treaty of 1977 on 14 December 2022.
  • the B. subtilis species may be selected from the group consisting of: Bacillus subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900); and/or the B. coagulans species may be Bacillus coagulans strain DFM 0705 (LMG P-32921).
  • the B. subtilis species may be Bacillus subtilis strain DFM 0326 (LMG P-32899) and the B. coagulans species may be Bacillus coagulans strain DFM 0705 (LMG P-32921).
  • the B. subtilis species may be Bacillus subtilis strain DFM 1015 (LMG P-32900) and the B. coagulans species may be Bacillus coagulans strain DFM 0705 (LMG P-32921).
  • composition according to the invention may comprise the B. subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900) in combination.
  • the composition may comprise the B. subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900) and the B. coagulans species strain DFM 0705 (LMG P- 32921).
  • the compositions used in the examples provided herein comprise the B. subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900) and the B. coagulans strain DFM 0705 (LMG P-32921).
  • composition according to the present invention may comprise Bacillus subtilis strain DFM 0326 (LMG P-32899), Bacillus subtilis strain DFM 1015 (LMG P-32900) and Bacillus coagulans strain DFM 0705 (LMG P-32921).
  • the composition may further comprise one or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.
  • composition may further comprise two or more, or three or more, or four or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.
  • composition may further comprise Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.
  • the bacterial strains included in the alcohol degrading composition provided herein were identified to preferably and effectively metabolize ethyl alcohol into carbon dioxide and water.
  • the inventors have shown that uptake of the compositions described herein prior to alcohol ingestion significantly reduces blood alcohol levels and breath alcohol levels after alcohol ingestion, as compared to placebo, thereby demonstrating that the compositions described herein reduce further absorption of alcohol from the intestinal tract following alcohol ingestion.
  • the composition provided herein comprises an appropriate amount or concentration of the one or more bacterial species of the Bacillus genus.
  • a dose may include one or more dosage units (e.g. 2 dosage units).
  • the cfu/dose corresponds to the total cfu over the plurality of dosage units.
  • the composition described herein comprises about 10,000 cfu/g of bacteria of the Bacillus genus to about 1 x 10 8 cfu/g of bacteria of the Bacillus genus.
  • the composition described herein comprises at least about 1 x 10 8 cfu/g of bacteria of the Bacillus genus. In another example, the composition described herein comprises at least about 1 x 10 7 cfu/g of bacteria of the Bacillus genus. In another example, the composition described herein comprises at least about 1 x 10 6 cfu/g of bacteria of the Bacillus genus. In a further example, the composition described herein comprises at least about 1 x 10 5 cfu/g of bacteria of the Bacillus genus.
  • the composition described herein comprises at least about 10,000 cfu/g (i.e. at least about 1 .0 x 10 4 cfu/g) of bacteria of the Bacillus genus.
  • the composition described herein comprises at least about 11 ,000 cfu/g (i.e. at least about 1.1 x 10 4 cfu/g) of bacteria of the Bacillus genus. In a further example, the composition described herein comprises at least about 12,000 cfu/g (i.e. at least about 1.2 x 10 4 cfu/g) of bacteria of the Bacillus genus.
  • composition described herein comprises at least about 13,000 cfu/g (i.e. at least about 1.3 x 10 4 cfu/g) of bacteria of the Bacillus genus.
  • the composition described herein comprises at least about 14,000 cfu/g (i.e. at least about 1.4 x 10 4 cfu/g) of bacteria of the Bacillus genus. In another example, the composition described herein comprises at least about 15,000 cfu/g (i.e. at least about 1.5 x 10 4 cfu/g) of bacteria of the Bacillus genus.
  • the composition described herein comprises about 1 x 10 8 cfu/g of bacteria of the Bacillus genus. In another example, the composition described herein comprises about 1 x 10 7 cfu/g of bacteria of the Bacillus genus. In another example, the composition described herein comprises about 1 x 10 6 cfu/g of bacteria of the Bacillus genus. In a further example, the composition described herein comprises about 1 x 10 5 cfu/g of bacteria of the Bacillus genus.
  • the composition described herein comprises about 10,000 cfu/g (i.e. about 1.0 x 10 4 cfu/g) of bacteria of the Bacillus genus.
  • the composition described herein comprises about 11,000 cfu/g (i.e. about 1.1 x 10 4 cfu/g) of bacteria of the Bacillus genus. In a further example, the composition described herein comprises about 12,000 cfu/g (i.e. about 1.2 x 10 4 cfu/g) of bacteria of the Bacillus genus.
  • composition described herein comprises about 13,000 cfu/g (i.e. about 1.3 x 10 4 cfu/g) of bacteria of the Bacillus genus.
  • the composition described herein comprises about 14,000 cfu/g (i.e. about 1.4 x 10 4 cfu/g) of bacteria of the Bacillus genus. In a further example, the composition described herein comprises about 15,000 cfu/g (i.e. about 1.5 x 10 4 cfu/g) of bacteria of the Bacillus genus.
  • TVC total viable count
  • Bacillus live cells for example can be determined by established cultivation methods based on specific Bacillus media, such Chrome Select agar. Alternative methods are known in the art.
  • the composition described herein comprises about 5,000 cfu of bacteria of the Bacillus genus/dose to about 1 x 10 8 cfu of bacteria of the Bacillus genus/dose.
  • the composition described herein comprises at least about 1 x 10 8 cfu of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises at least about 1 x 10 7 cfu of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises at least about 1 x 10 6 cfu of bacteria of the Bacillus genus/dose.
  • the composition described herein comprises at least about 1 x 10 5 cfu of bacteria of the Bacillus genus/dose. In one example, the composition described herein comprises at least about 5,000 cfu (i.e. at least about 0.5 x 10 4 cfu) of bacteria of the Bacillus genus/dose.
  • the composition described herein comprises at least about 10,000 cfu (i.e. at least about 1.0 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises at least about 11 ,000 cfu (i.e. at least about 1.1 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In a further example, the composition described herein comprises at least about 12,000 cfu (i.e. at least about 1.2 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises at least about 13,000 cfu (i.e.
  • composition described herein comprises at least about 1 .3 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises at least about 14,000 cfu (i.e. at least about 1.4 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises at least about 15,000 cfu (i.e. at least about 1 .5 x 10 4 cfu) of bacteria of the Bacillus genus/dose.
  • the composition described herein comprises about 1 x 10 8 cfu of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises about 1 x 10 7 cfu of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises about 1 x 10 6 cfu of bacteria of the Bacillus genus/dose.
  • composition described herein comprises about 1 x 10 5 cfu of bacteria of the Bacillus genus/dose.
  • the composition described herein comprises about 5,000 cfu (i.e. about 0.5 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In one example, the composition described herein comprises about 10,000 cfu (i.e. about 1.0 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises about 11 ,000 cfu (i.e. about 1.1 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In a further example, the composition described herein comprises about 12,000 cfu (i.e. about 1.2 x 10 4 cfu) of bacteria of the Bacillus genus/dose.
  • the composition described herein comprises about 13,000 cfu (i.e. about 1.3 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In another example, the composition described herein comprises about 14,000 cfu (i.e. about 1.4 x 10 4 cfu) of bacteria of the Bacillus genus/dose. In a further example, the composition described herein comprises about 15,000 cfu (i.e. about 1.5 x 10 4 cfu) of bacteria of the Bacillus genus/dose.
  • the amount or concentration of the one or more bacterial species of the Bacillus genus in the composition may be made up from any individual species of the Bacillus genus or any combination of species of the Bacillus genus.
  • the amount or concentration of the one or more bacterial species of the Bacillus genus in the composition may be made up from entirely one Bacillus species (e.g. the concentration may be made up from entirely B. subtilis or entirely B. coagulans).
  • the amount or concentration of the one or more bacterial species of the Bacillus genus in the composition may be made up from two or more, three or more, four or more, or five or more bacterial species of the Bacillus genus (e.g.
  • the concentration may be made up from B. subtilis and B. coagulans). Accordingly, in one example, the amount or concentration of the one or more bacterial species of the Bacillus genus in the composition refers to the amount or concentration of the combination of the Bacillus species present.
  • the composition provided herein comprises an appropriate concentration of bacteria, wherein a proportion of the concentration is made up from one or more bacterial species of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition described herein comprises about 10,000 cfu/g (i.e. about 1.0 x 10 4 cfu/g) of bacteria to about 1 x 10 8 cfu/g of bacteria.
  • the composition described herein comprises at least about 1 x 10 8 cfu/g of bacteria.
  • the composition described herein comprises at least about 1 x 10 7 cfu/g of bacteria.
  • the composition described herein comprises at least about 1 x 10 6 cfu/g of bacteria. In a further example, the composition described herein comprises at least about 1 x 10 5 cfu/g of bacteria. In one example, the composition described herein comprises at least about 10,000 cfu/g (i.e. at least about 1.0 x 10 4 cfu/g) of bacteria. In another example, the composition described herein comprises at least about 11 ,000 cfu/g (i.e. at least about 1.1 x 10 4 cfu/g) of bacteria. In a further example, the composition described herein comprises at least about 12,000 cfu/g (i.e.
  • the composition described herein comprises at least about 1.2 x 10 4 cfu/g) of bacteria. In another example, the composition described herein comprises at least about 13,000 cfu/g (i.e. at least about 1.3 x 10 4 cfu/g) of bacteria. In another example, the composition described herein comprises at least about 14,000 cfu/g (i.e. at least about 1.4 x 10 4 cfu/g) of bacteria. In another example, the composition described herein comprises at least about 15,000 cfu/g (i.e. at least about 1.5 x 10 4 cfu/g) of bacteria. In one example, the composition described herein comprises about 1 x 10 8 cfu/g of bacteria.
  • the composition described herein comprises about 1 x 10 7 cfu/g of bacteria. In another example, the composition described herein comprises about 1 x 10 6 cfu/g of bacteria. In a further example, the composition described herein comprises about 1 x 10 5 cfu/g of bacteria. In one example, the composition described herein comprises about 10,000 cfu/g (i.e. about 1.0 x 10 4 cfu/g) of bacteria. In another example, the composition described herein comprises about 11 ,000 cfu/g (i.e. about 1.1 x 10 4 cfu/g) of bacteria. In a further example, the composition described herein comprises about 12,000 cfu/g (i.e.
  • the composition described herein comprises about 1.2 x 10 4 cfu/g) of bacteria. In another example, the composition described herein comprises about 13,000 cfu/g (i.e. about 1.3 x 10 4 cfu/g) of bacteria. In another example, the composition described herein comprises about 14,000 cfu/g (i.e. about 1.4 x 10 4 cfu/g) of bacteria. In a further example, the composition described herein comprises about 15,000 cfu/g (i.e. about 1.5 x 10 4 cfu/g) of bacteria.
  • the composition provided herein comprises an appropriate amount of bacteria, wherein a proportion of the amount is made up from one or more bacterial species of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • Bacillus genus e.g. B. subtilis and/or B. coagulans.
  • the composition described herein comprises about 5,000 cfu of bacteria/dose to about 1 x 10 8 cfu of bacteria/dose. In one example, the composition described herein comprises at least about 1 x 10 8 cfu of bacteria/dose. In another example, the composition described herein comprises at least about 1 x 10 7 cfu of bacteria/dose. In another example, the composition described herein comprises at least about 1 x 10 6 cfu of bacteria/dose. In a further example, the composition described herein comprises at least about 1 x 10 5 cfu of bacteria/dose. In one example, the composition described herein comprises at least about 5,000 cfu (i.e. at least about 0.5 x 10 4 cfu) of bacteria/dose.
  • the composition described herein comprises at least about 10,000 cfu (i.e. at least about 1.0 x 10 4 cfu) of bacteria/dose. In another example, the composition described herein comprises at least about 11 ,000 cfu (i.e. at least about 1.1 x 10 4 cfu) of bacteria/dose. In a further example, the composition described herein comprises at least about 12,000 cfu (i.e. at least about 1.2 x 10 4 cfu) of bacteria/dose. In another example, the composition described herein comprises at least about 13,000 cfu (i.e. at least about 1.3 x 10 4 cfu) of bacteria/dose.
  • the composition described herein comprises at least about 14,000 cfu (i.e. at least about 1.4 x 10 4 cfu) of bacteria/dose. In another example, the composition described herein comprises at least about 15,000 cfu (i.e. at least about 1.5 x 10 4 cfu) of bacteria/dose. In one example, the composition described herein comprises about 1 x 10 8 cfu of bacteria/dose. In another example, the composition described herein comprises about 1 x 10 7 cfu of bacteria/dose. In another example, the composition described herein comprises about 1 x 10 6 cfu of bacteria/dose. In a further example, the composition described herein comprises about 1 x 10 5 cfu of bacteria/dose.
  • the composition described herein comprises about 5,000 cfu (i.e. about 0.5 x 10 4 cfu) of bacteria/dose. In one example, the composition described herein comprises about 10,000 cfu (i.e. about 1.0 x 10 4 cfu) of bacteria/dose. In another example, the composition described herein comprises about 11 ,000 cfu (i.e. about 1.1 x 10 4 cfu) of bacteria/dose. In a further example, the composition described herein comprises about 12,000 cfu (i.e. about 1.2 x 10 4 cfu) of bacteria/dose. In another example, the composition described herein comprises about 13,000 cfu (i.e.
  • composition described herein comprises about 1.3 x 10 4 cfu) of bacteria/dose. In another example, the composition described herein comprises about 14,000 cfu (i.e. about 1.4 x 10 4 cfu) of bacteria/dose. In a further example, the composition described herein comprises about 15,000 cfu (i.e. about 1.5 x 10 4 cfu) of bacteria/dose.
  • the amount or concentration of bacteria may further comprise any appropriate individual species or any combination of species.
  • the amount or concentration of bacteria may further comprise any appropriate individual species or any combination of species.
  • the amount or concentration of bacteria may further comprise any appropriate individual species or any combination of species.
  • coagulans may further comprise a proportion of one or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus.
  • the one or more bacterial species of the Bacillus genus is genetically modified.
  • “genetic modification” and “genetic engineering” refer to the direct manipulation (e.g. modification) of one or more genes, for example, using recombinant DNA technology.
  • humans have manipulated genomes indirectly by controlling breeding and selecting offspring with desired traits however genetic engineering involves direct manipulation (e.g. modification) of one or more genes.
  • a gene from another species may be added to an organism's genome to give it a desired phenotype.
  • the one or more bacterial species of the Bacillus genus is not genetically modified. In other words, the one or more bacterial species of the Bacillus genus may be naturally occurring.
  • the one or more bacterial species of the Bacillus genus may be present within a microbial consortium.
  • “Microbial consortium”, as used herein, refers to a group of microbes (e.g. bacteria) wherein the group comprises two or more distinct microbes (e.g. two of more bacteria which may be from the same species (e.g. two or more distinct strains) or distinct species(e.g. two or more distinct species).
  • the microbial consortium may be a naturally occurring microbial consortium (e.g. a consortium that is naturally produced during fermentation of a cereal, such as rice bran).
  • a naturally occurring microbial consortium e.g. a consortium that is naturally produced during fermentation of a cereal, such as rice bran.
  • the one or more bacterial species of the Bacillus genus may be part of the composition by virtue of the presence of a fermented cereal, such as rice bran (with its associated naturally produced microbial consortium) in the composition.
  • the one or more bacterial species of the Bacillus genus may therefore be a natural component of a fermented cereal, such as rice bran.
  • 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 (in particular, the fermented rice bran) used in the examples provided herein. Accordingly, the B. subtilis strain DFM 0326 (LMG P-32899) and Bacillus subtilis strain DFM 1015 (LMG P-32900), and the B. coagulans strain DFM 0705 (LMG P-32921) may be part of the composition described herein by virtue of the presence of a fermented cereal, such as rice bran (with its associated naturally produced microbial consortium), in the composition.
  • a fermented cereal such as rice bran (with its associated naturally produced microbial consortium
  • the one or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be (part of) a naturally occurring microbial consortium (e.g. a consortium that is naturally produced during fermentation of a cereal, such as rice bran).
  • a naturally occurring microbial consortium e.g. a consortium that is naturally produced during fermentation of a cereal, such as rice bran.
  • the one or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be part of the composition by virtue of the presence of a fermented cereal, such as rice bran (with its associated naturally produced microbial consortium) in the composition.
  • the one or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may therefore be a natural component of a fermented cereal, such as rice bran.
  • the one or more bacterial species of the Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the one or more bacterial species selected from the group consisting of: Bacillus amyloliquefaciens, Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus may be (part of) a naturally occurring microbial consortium (e.g. a consortium that is naturally produced during fermentation of a cereal, such as rice bran).
  • the one or more bacterial species of the Bacillus genus e.g. B. subtilis and/or B.
  • Bacillus amyloliquefaciens Bacillus velezensis, Bacillus sp MT 03, Bacillus atrophaeus, and Pediococcus pentosaceus
  • Bacillus amyloliquefaciens Bacillus velezensis
  • Bacillus sp MT 03 Bacillus atrophaeus
  • Pediococcus pentosaceus may be part of the composition by virtue of the presence of a fermented cereal, such as rice bran (with its associated naturally produced microbial consortium) in the composition.
  • the one or more bacterial species of the Bacillus genus e.g. B. subtilis and/or B.
  • Bacillus amyloliquefaciens Bacillus velezensis
  • Bacillus sp MT 03 Bacillus atrophaeus
  • Pediococcus pentosaceus may therefore be a natural component of a fermented cereal, such as rice bran.
  • the invention is not limited to naturally occurring microbial consortia. Accordingly, the microbial consortia discussed above may also be generated artificially, for example by combining one or more bacterial isolates together. In one example, the one or more bacterial species of the Bacillus genus (e.g. B.subtilis and/or B. coagulans) may therefore be added to the composition individually.
  • Bacillus genus e.g. B.subtilis and/or B. coagulans
  • the alcohol degrading composition may therefore also include a cereal such as rice bran (e.g. fermented rice bran) as discussed in more detail elsewhere herein.
  • rice bran e.g. fermented rice bran
  • the fermented rice bran may be the natural source of the one or more bacterial species of the Bacillus genus (e.g. B.subtilis and/or B. coagulans) present within the composition.
  • L-cysteine can be used to increase alcohol degradation by one or more bacterial species of the Bacillus genus particularly when combined with a high molecular weight low osmolality carbohydrate, such as dextrin.
  • the alcohol degrading composition described herein thus comprises L-cysteine in combination with the one or more bacterial species of the Bacillus genus (e.g. wherein the bacteria are added to the composition as a bacterial supplement or as a natural product e.g. as part of fermented rice bran).
  • L-cysteine (L-cys) is a non-essential amino acid and thus is one of the building blocks required for the synthesis of proteins. It contains sulphur in the form of a thiol group (-SH) at the end of its side chain.
  • the -SH group is responsible for the high reactive capacity of the amino acid, and therefore is responsible for many of its biological functions in human beings.
  • L-cysteine occupies a key position in sulfur metabolism in all organisms and is used in the synthesis of proteins, glutathione, biotin, lipoic acid, methionine and other sulfur-containing metabolites.
  • L-cysteine serves as a precursor for the biosynthesis of coenzyme A.
  • L-cysteine The biosynthesis of L-cysteine has been studied in detail in bacteria, especially in enterobacteria.
  • the amino acid L-cysteine is not only of biological importance but is also of economic importance. It is used, for example, as a food additive (in particular in the baking industry), as a starting material in cosmetics, and as a starting material for the preparation of active pharmaceutical ingredients (in particular N-acetyl-cysteine and S-carboxymethy l-cysteine).
  • L-cysteine refers to the amino acid L-cysteine in any suitable form.
  • L-cysteine therefore encompasses L- cysteine in free form as well as L-cysteine salts.
  • L-cysteine in the context of the present invention, in one example L-cysteine can be in the free form, a salt thereof, or a mixture thereof.
  • the salt include, for example, sulfate, hydrochloride, carbonate, ammonium salt, sodium salt, and potassium salt.
  • the L-cysteine is a crystal fraction of >0.1 mm.
  • L-cysteine is available from several suppliers and can be readily sourced by the skilled person. Furthermore, the skilled person would readily be able to detect the presence of L-cysteine in a substance (e.g. in a composition described herein) using methods known in the art. For instance, L-Cysteine crystals may be macroscopically detected in the composition described herein as white particles. HPLC, High-Performance Liquid Chromatography, on an Inertsil ODs-3 column is an established method for detection of L-cysteine.
  • L-cysteine may be obtained industrially by hydrolysis of animal materials, such as poultry feathers or hog hair.
  • synthetic L-cys may be obtained from fermentation of genetically modified E. coli or Pseudomonas thiazolinophilum. Accordingly, in some examples, L-cysteine is of animal origin. In other examples, L-cysteine is of synthetic origin.
  • L-cysteine is of vegetable origin.
  • composition described herein may comprise an L-cysteine derivative instead of or in addition to L-cysteine.
  • N-acetyl cysteine is an N-acetylated form of the amino acid L-cysteine thus is an example of an L-cysteine derivative. Accordingly, in some examples the composition described herein may comprise N- acetylcysteine (NAC). NAC is readily available in the art.
  • L-cysteine is present in the alcohol degrading composition described herein at an appropriate concentration or amount.
  • the amount or concentration of L-cysteine may therefore be described by reference to the % w/w of composition or by the total weight (e.g. mgs) per dose of composition (in other words the weight per effective dose).
  • a dose may include one or more dosage units (e.g. 2 dosage units).
  • the weight per dose corresponds to the total weight of L-cysteine over the plurality of dosage units.
  • the composition comprises about 10% w/w of L-cysteine to about 40% w/w of L-cysteine. In another example, the composition comprises about 15% w/w of L-cysteine to about 35% w/w of L-cysteine. In another example, the composition comprises about 20% w/w of L- cysteine to about 30% w/w of L-cysteine.
  • the composition comprises at least about 10% w/w of L-cysteine.
  • the composition comprises at least about 15% w/w of L-cysteine. In a further example, the composition comprises at least about 20% w/w of L-cysteine. In another example, the composition comprises at least about 25% w/w of L-cysteine. In another example, the composition comprises at least about 30% w/w of L-cysteine. In a further example, the composition comprises at least about 35% w/w of L-cysteine. In a further example, the composition comprises at least about 40% w/w of L-cysteine.
  • the composition comprises about 10% w/w of L-cysteine.
  • the composition comprises about 15% w/w of L-cysteine. In another example, the composition comprises about 20% w/w of L-cysteine. In a further example, the composition comprises about 25% w/w of L-cysteine. In another example, the composition comprises about 30% w/w of L-cysteine. In another example, the composition comprises about 35% w/w of L-cysteine. In a further example, the composition comprises about 40% w/w of L- cysteine.
  • the composition comprises about 38 mg of L-cysteine/dose to about 200 mg of L-cysteine/dose.
  • the composition comprises at least about 38 mg of L-cysteine/dose.
  • the composition comprises at least about 50 mg of L-cysteine/dose. In one example, the composition comprises at least about 75 mg of L-cysteine/dose. In one example, the composition comprises at least about 100 mg of L-cysteine/dose.
  • the composition comprises at least about 150 mg of L-cysteine/dose.
  • the composition comprises at least about 160 mg of L-cysteine/dose. In one example, the composition comprises at least about 180 mg of L-cysteine/dose.
  • the composition comprises about 38 mg of L-cysteine/dose. In one example, the composition comprises about 50 mg of L-cysteine/dose. In one example, the composition comprises about 75 mg of L-cysteine/dose. In one example, the composition comprises about 100 mg of L-cysteine/dose.
  • the composition comprises about 150 mg of L-cysteine/dose.
  • the composition comprises about 160 mg of L-cysteine/dose. In one example, the composition comprises about 180 mg of L-cysteine/dose.
  • L-cysteine to a composition comprising a high molecular weight low osmolality carbohydrate (e.g. dextrin) and one or more bacterial species of the Bacillus genus results in re-programing of the bacteria so that they more efficiently degrade alcohol compared to the rate of alcohol degradation in the absence of L- cysteine.
  • a high molecular weight low osmolality carbohydrate e.g. dextrin
  • Bacillus genus results in re-programing of the bacteria so that they more efficiently degrade alcohol compared to the rate of alcohol degradation in the absence of L- cysteine.
  • the alcohol degrading composition described herein therefore comprises L-cysteine in combination with the one or more bacterial species of the Bacillus genus and a high molecular weight low osmolality carbohydrate (e.g. dextrin).
  • a “high molecular weight low osmolality carbohydrate” refers to a carbohydrate with a molecular weight of about 500,000 g/mol to about 700,000 g/mol wherein the osmolality of the carbohydrate is low.
  • a person of skill in the art would readily be able to identify appropriate carbohydrates with a low osmolality using routine tests known in the art.
  • a low osmolality carbohydrate is a carbohydrate that has about 50% greater glycogen recovery than maltodextrin.
  • the high molecular weight low osmolality carbohydrate is present in the alcohol degrading composition described herein at an appropriate concentration or amount.
  • the amount or concentration of the high molecular weight low osmolality carbohydrate may therefore be described by reference to the % w/w of composition or by the total weight (e.g. mgs) per dose of composition (in other words the weight per effective dose).
  • a dose may include one or more dosage units (e.g. 2 dosage units).
  • the weight per dose corresponds to the total weight of the high molecular weight low osmolality carbohydrate over the plurality of dosage units.
  • the composition comprises about 0.5% w/w to about 5% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises about 0.5% w/w to about 3% w/w of high molecular weight low osmolality carbohydrate. In one example, the composition comprises about 0.5% w/w to about 2% w/w of high molecular weight low osmolality carbohydrate.
  • the composition comprises at least about 0.5% w/w of high molecular weight low osmolality carbohydrate.
  • the composition comprises at least about 1 % w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises at least about 1.5% w/w of high molecular weight low osmolality carbohydrate. In a further example, the composition comprises at least about 2% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises at least about 2.5% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises at least about 3% w/w of high molecular weight low osmolality carbohydrate.
  • the composition comprises at least about 3.5% w/w of high molecular weight low osmolality carbohydrate. In a further example, the composition comprises at least about 4% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises at least about 4.5% w/w of high molecular weight low osmolality carbohydrate. In a further example, the composition comprises at least about 5% w/w of high molecular weight low osmolality carbohydrate.
  • the composition comprises about 0.5% w/w of high molecular weight low osmolality carbohydrate.
  • the composition comprises about 1% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises about 1.5% w/w of high molecular weight low osmolality carbohydrate. In a further example, the composition comprises about 2% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises about 2.5% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises about 3% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises about 3.5% w/w of high molecular weight low osmolality carbohydrate.
  • the composition comprises about 4% w/w of high molecular weight low osmolality carbohydrate. In another example, the composition comprises about 4.5% w/w of high molecular weight low osmolality carbohydrate. In a further example, the composition comprises about 5% w/w of high molecular weight low osmolality carbohydrate. In one example, the composition comprises about 2 mg to about 50 mg of high molecular weight low osmolality carbohydrate/dose.
  • the composition comprises at least about 2 mg of high molecular weight low osmolality carbohydrate/dose.
  • the composition comprises at least about 2 mg of high molecular weight low osmolality carbohydrate/dose.
  • the composition comprises at least about 4 mg of high molecular weight low osmolality carbohydrate/dose.
  • the composition comprises at least about 10 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises at least about 15 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises at least about 20 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises at least about 25 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises at least about 30 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises at least about 35 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises at least about 40 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises at least about 45 mg of high molecular weight low osmolality carbohydrate/dose.
  • the composition comprises about 2 mg of high molecular weight low osmolality carbohydrate/dose.
  • the composition comprises about 4 mg of high molecular weight low osmolality carbohydrate/dose.
  • the composition comprises about 10 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises about 15 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises about 20 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises about 25 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises about 30 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises about 35 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises about 40 mg of high molecular weight low osmolality carbohydrate/dose. In one example, the composition comprises about 45 mg of high molecular weight low osmolality carbohydrate/dose.
  • the high molecular weight low osmolality carbohydrate is dextrin.
  • Dextrin is a generic term applied to a variety of products obtained by heating a starch in the presence of small amounts of moisture and an 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) which comprises glucose units linked together by means mainly of a-1 ,4 linkages. In addition to a-1 ,4 linkages, there may be a proportion of a-1 ,6 linkages in a particular dextrin, the amount depending on the starch starting material.
  • a-1 ,6 linkages Since the rate of biodegradability of a-1 ,6 linkages is typically less than that for a-1 ,4 linkages, it is preferred that, for many applications, the percentage of a-1 ,6 linkages is less than 10% and more preferably less than 5%.
  • dextrins are thus mixtures of polymers of D-glucose units linked by alpha-(1->4) or alpha-(1->6) glycosidic bonds.
  • Dextrins can be produced from starch using enzymes like amylases, as during digestion in the human body and during malting and mashing, or by applying dry heat under acidic conditions (pyrolysis or roasting). The latter process is used industrially. Dextrins produced by heat are also known as pyrodextrins. Typically, dextrins are produced by the hydrolysis of starch obtained from various natural products such as wheat, rice, corn, maize and tapioca.
  • Dextrins are typically white, yellow, or brown powder that are partially or fully water-soluble, yielding optically active solutions of low viscosity. Dextrins are available from several suppliers and can be readily sourced by the skilled person. The skilled person would readily be able to identify suitable dextrins for use in the context of the present invention. The skilled person would readily be able to detect the presence of dextrin in a substance (e.g. in a composition described herein) using methods known in the art. For example, most dextrins can be detected with iodine solution.
  • the term “dextrin” encompasses pyrodextrins, digestible dextrins, and hydrogenated products thereof, including derivatives thereof.
  • the term “dextrin derivative” herein means those obtained by chemically or enzymatically processing dextrins, and encompasses, for example, branched dextrins obtained by causing a glycosyltransferase to act on a dextrin, and cyclodextrins obtained by causing a cyclodextrin producing enzyme to act on a starch, in addition to the above-described polydextrose.
  • dextrin is enzymatically processed.
  • the dextrin and thus, the high molecular weight low osmolality carbohydrate, is cluster dextrin (also referred to as highly branched cyclic dextrin).
  • Cluster dextrin is a maltodextrin which has a high molecular weight, but narrow weight distribution, is soluble, and its osmotic pressure is near zero. Typical macromolecular carbohydrates are less soluble than Cluster Dextrin.
  • low molecular carbohydrates exhibit higher osmotic pressure, as does pure glucose solution. Along with other digestible contents typically found in sports drinks, this slows their descent to the small intestine.
  • Cluster Dextrin is faster to the small intestine and faster to ramp-up endurance. Solubility is at the heart of Cluster Dextrin’s functioning. High molecular weight Cluster Dextrin also degrades slowly, balancing insulin secretion with lipid breakdown.
  • Cluster dextrin is manufactured by Glico Nutrition.
  • the dextrin, and thus, the high molecular weight low osmolality carbohydrate is derived from wheat or corn (e.g. in some examples the dextrin is wheat dextrin or corn dextrin).
  • the dextrin is enzymatically processed wheat or corn.
  • the dextrin is derived from wheat (e.g. wheat dextrin).
  • the dextrin may be a wheat dextrin powder (such as Surbex Nutri-Fiber Wheat Dextrin Powder which is a soluble non viscous fiber).
  • the dextrin is derived from corn (e.g. corn dextrin).
  • the dextrin is hydrolysed corn dextrin (e.g. Vitargo).
  • dextrin is present in the alcohol degrading composition described herein at an appropriate concentration or amount.
  • the composition comprises about 0.5% w/w to about 5% w/w of dextrin.
  • the composition comprises about 0.5% w/w to about 3% w/w of dextrin.
  • the composition comprises about 0.5% w/w to about 2% w/w of dextrin. In one example, the composition comprises at least about 0.5% w/w of dextrin.
  • the composition comprises at least about 1 % w/w of dextrin. In another example, the composition comprises at least about 1.5% w/w of dextrin. In a further example, the composition comprises at least about 2% w/w of dextrin. In another example, the composition comprises at least about 2.5% w/w of dextrin. In another example, the composition comprises at least about 3% w/w of dextrin. In another example, the composition comprises at least about 3.5% w/w of dextrin. In a further example, the composition comprises at least about 4% w/w of dextrin. In another example, the composition comprises at least about 4.5% w/w of dextrin. In a further example, the composition comprises at least about 5% w/w of dextrin.
  • the composition comprises about 0.5% w/w of dextrin.
  • the composition comprises about 1% w/w of dextrin. In another example, the composition comprises about 1.5% w/w of dextrin. In a further example, the composition comprises about 2% w/w of dextrin. In another example, the composition comprises about 2.5% w/w of dextrin. In another example, the composition comprises about 3% w/w of dextrin. In another example, the composition comprises about 3.5% w/w of dextrin. In a further example, the composition comprises about 4% w/w of dextrin. In another example, the composition comprises about 4.5% w/w of dextrin. In a further example, the composition comprises about 5% w/w of dextrin.
  • the composition comprises about 2 mg to about 50 mg of dextrin/dose.
  • the composition comprises at least about 2 mg of dextrin/dose.
  • the composition comprises at least about 4 mg of dextrin/dose.
  • the composition comprises at least about 5 mg of dextrin/dose. In one example, the composition comprises at least about 10 mg of dextrin/dose. In one example, the composition comprises at least about 15 mg of dextrin/dose. In one example, the composition comprises at least about 20 mg of dextrin/dose. In one example, the composition comprises at least about 25 mg of dextrin/dose. In one example, the composition comprises at least about 30 mg of dextrin/dose. In one example, the composition comprises at least about 35 mg of dextrin/dose. In one example, the composition comprises at least about 40 mg of dextrin/dose. In one example, the composition comprises at least about 45 mg of dextrin/dose. In one example, the composition comprises about 2 mg of dextrin/dose.
  • the composition comprises about 4 mg of dextrin/dose.
  • the composition comprises about 10 mg of dextrin/dose. In one example, the composition comprises about 15 mg of dextrin/dose. In one example, the composition comprises about 20 mg of dextrin/dose. In one example, the composition comprises about 25 mg of dextrin/dose. In one example, the composition comprises about 30 mg of dextrin/dose. In one example, the composition comprises about 35 mg of dextrin/dose. In one example, the composition comprises about 40 mg of dextrin/dose. In one example, the composition comprises about 45 mg of dextrin/dose.
  • the composition described herein comprises L-cysteine and dextrin.
  • L- cysteine and dextrin may be present in the alcohol degrading composition described herein at any appropriate concentration.
  • Appropriate concentrations or amounts of L-cysteine and dextrin are described elsewhere herein and apply equally to a composition described herein comprising both L-cysteine and dextrin. Illustrative examples of appropriate concentrations or amounts are provided below.
  • the composition comprises about 0.5% w/w to 5% w/w of dextrin and about 10% w/w of L-cysteine to about 40% w/w of L-cysteine.
  • the composition may also comprise about 50% w/w to about 90% w/w of rice bran (e.g. fermented rice bran) and/or about 10,000 cfu/g of bacteria of the Bacillus genus to about 15,000 cfu/g of bacteria of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition described herein comprises at least about 0.5% w/w of dextrin and at least about 10% w/w of L-cysteine.
  • the composition described herein may comprise about 0.5% w/w of dextrin and about 10% w/w of L-cysteine.
  • This example corresponds with a composition as tested in example 1 , test 7B.
  • the composition may also comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • rice bran e.g. about 67% w/w of fermented rice bran
  • bacteria of the Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 0.5% w/w of dextrin and at least about 20% w/w of L-cysteine.
  • the composition described herein may comprise about 0.5% w/w of dextrin and about 20% w/w of L-cysteine.
  • This example corresponds with a composition as tested in example 1 , test 6B.
  • the composition may also comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • rice bran e.g. about 67% w/w of fermented rice bran
  • bacteria of the Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 0.5% w/w of dextrin and at least about 30% w/w of L-cysteine.
  • the composition described herein may comprise about 0.5% w/w of dextrin and about 30% w/w of L-cysteine.
  • This example corresponds with a composition as tested in example 1 , test 5B.
  • the composition may also comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • rice bran e.g. about 67% w/w of fermented rice bran
  • bacteria of the Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 5% w/w of dextrin and at least about 20% w/w of L-cysteine.
  • the composition described herein may comprise about 5% w/w of dextrin and about 20% w/w of L-cysteine.
  • This example corresponds with a composition as tested in example 1 , test 8B.
  • the composition may also comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • rice bran e.g. about 67% w/w of fermented rice bran
  • bacteria of the Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 3% w/w of dextrin and at least about 30% w/w of L-cysteine.
  • the composition described herein may comprise about 3% w/w of dextrin and about 30% w/w of L-cysteine.
  • the composition may also comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise 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 Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition comprises about 2 mg to about 50 mg of dextrin/dose and about 38 mg to about 200 mg of L-cysteine/dose.
  • the composition may also comprise about 300 mg to about 600 mg of rice bran/dose (e.g.
  • fermented rice bran/dose and/or about 5,000 cfu of bacteria of the Bacillus genus/dose to about 1 x10 8 cfu of bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • Bacillus genus/dose e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 2 mg of dextrin/dose and at least about 38 mg of L-cysteine/dose.
  • the composition described herein may comprise about 2 mg of dextrin/dose and about 38 mg of L- cysteine/dose.
  • This example corresponds with a composition as tested in example 1 , test 7B.
  • the composition may also comprise 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 of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise about 300 mg of rice bran/dose (e.g. about 300 mg of fermented rice bran/dose) and/or 5,000 cfu of bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • rice bran/dose e.g. about 300 mg of fermented rice bran/dose
  • bacteria of the Bacillus genus/dose e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 2 mg of dextrin and at least about 76 mg of L-cysteine/dose.
  • the composition described herein may comprise about 2 mg of dextrin/dose and about 76 mg of L-cysteine/dose.
  • This example corresponds with a composition as tested in example 1 , test 6B.
  • the composition may also comprise 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 of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise about 300 mg of rice bran/dose (e.g. about 300 mg of fermented rice bran/dose) and/or 5,000 cfu of bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • rice bran/dose e.g. about 300 mg of fermented rice bran/dose
  • bacteria of the Bacillus genus/dose e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 2 mg of dextrin/dose and at least about 114 mg of L-cysteine/dose.
  • the composition described herein may comprise about 2 mg of dextrin/dose and about 114 mg of L- cysteine/dose.
  • This example corresponds with a composition as tested in example 1 , test 5B.
  • the composition may also comprise 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 of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise about 300 mg of rice bran/dose (e.g. about 300 mg of fermented rice bran/dose) and/or 5,000 cfu of bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition described herein comprises at least about 20 mg of dextrin/dose and at least about 76 mg of L-cysteine/dose.
  • the composition described herein may comprise about 20 mg of dextrin/dose and about 76 mg of L- cysteine/dose. This example corresponds with a composition as tested in example 1 , test 8B.
  • the composition may also comprise 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 of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition may comprise about 300 mg of rice bran/dose (e.g. about 300 mg of fermented rice bran/dose) and/or 5,000 cfu of bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the high molecular weight low osmolality carbohydrate (e.g. dextrin) and/or L-cysteine create a micro-environment on a cellular level that makes the microbial consortium of the compositions provided herein, upon resuscitation in the intestinal tract, excrete an enzyme cascade targeted towards short carbon chains, e.g. ethanol/alcohol, resulting in preferential targeting of these substrates.
  • an enzyme cascade targeted towards short carbon chains e.g. ethanol/alcohol
  • the targeted enzymes act only on the alcohol in the tract and break it down into carbon dioxide and water, bypassing the liver process of converting alcohol into acetaldehyde and acetic acid, i.e. hangover metabolites formed by the liver’s conversion of alcohol.
  • the cells scan the biochemical conditions of their micro-environment and start to excrete a unique selection of bio-active substances to optimise the conditions, e.g. pH, conductivity, electrolytes, for their survival and multiplication. Nutrients and substrates are essential for survival and subsequent multiplication.
  • alcohol/ethanol/ethyl alcohol is present in the micro-environment, alcohol-targeted enzymes are excreted to break down alcohol into fragments containing carbon.
  • Carbon that cannot be used by the microbes, or neighbouring tissue cells, as a nutrient will be biochemically metabolised into water and carbon dioxide that can escape the body system without causing any biological consequences/symptoms. It is suggested that high molecular weight low osmolality carbohydrate (e.g. dextrin) and/or L-cysteine enhance this environmental scan and selective excretion of bio-active substances for optimised enzymatic conditions.
  • high molecular weight low osmolality carbohydrate e.g. dextrin
  • L-cysteine enhance this environmental scan and selective excretion of bio-active substances for optimised enzymatic conditions.
  • the alcohol degrading composition described herein may include a cereal (e.g. a cereal grain) such as rice bran.
  • a cereal is any grass cultivated (grown) for the edible components of its grain (botanically, a type of fruit called a caryopsis), composed of endosperm, germ, and bran.
  • the term cereal may also refer to the resulting grain itself (specifically "cereal grain”).
  • Cereal grains are the seeds that come from grasses such as wheat, millet, rice, barley, oats, rye, triticale, sorghum, and maize (corn).
  • the alcohol degrading composition described herein may include a cereal (e.g. a cereal grain) selected from the group consisting of: wheat, millet, rice, barley, oats, rye, triticale, sorghum, and maize (corn).
  • a cereal e.g. a cereal grain
  • a suitable cereal e.g. cereal grain
  • Bran also known as miller's bran, is the hard outer layers of cereal grain. It comprises aleurone and pericarp. Corn (maize) bran also includes the pedicel (tip cap). Along with germ, bran is an integral part of whole grains, and is often produced as a byproduct of milling in the production of refined grains. Bran is present in cereal grain, including rice, corn (maize), wheat, oats, barley, rye and millet.
  • the alcohol degrading composition described herein may comprise cereal bran.
  • the alcohol degrading composition described herein may comprise a cereal bran selected from the group consisting of: rice bran, corn (maize) bran, wheat bran, oat bran, barley bran, rye bran and millet bran.
  • the alcohol degrading composition described herein may comprise oat bran.
  • the alcohol degrading composition described herein may comprise rice bran.
  • Rice bran is a by-product of the rice milling process. Generally rice milling yields about 15% w/w broken kernels, about 10% w/w rice bran, about 20% hulls and about 55% w/w whole kernels.
  • the composition of rice bran (in percent by weight) is generally 11-13% of water, 18- 21% of crude fat and oil, 14-16% crude protein, 8-10% of crude fiber, 9-12% of ash and 33- 36% of carbohydrate.
  • Rice bran has naturally occurring lipases that hydrolyze the oil into glycerol and free fatty acids which give the product a rancid smell and taste.
  • “rice bran” refers to the hard outer layer of rice which comprises aleurone and pericarp. Along with germ, it is an integral part of whole rice, and, as mentioned above, is often produced as a by-product of milling in the production of refined rice.
  • the alcohol degrading composition described herein may comprise rice bran in any suitable form. Suitable forms include raw rice bran, recently milled (unhydrolyzed) full-fat rice bran, low-fat rice bran, defatted rice bran, fermented rice bran, stabilized rice bran and so forth.
  • Raw rice bran is rice bran as obtained after milling.
  • Low-fat rice bran and defatted rice bran are derived from full-fat rice bran by solvent extraction or the like.
  • Full-fat rice bran has a fat content of about 14-18% by weight and low fat and defatted rice bran have about 3-14% and less than 3% fat, respectively, on a weight basis.
  • the rice bran is formulated as raw rice bran, recently milled (unhydrolyzed) full-fat rice bran, low-fat rice bran, defatted rice bran, fermented rice bran and/or stabilized rice bran.
  • the rice bran is formulated as fermented rice bran and/or stabilized rice bran.
  • the rice bran is fermented rice bran.
  • Rice bran undergoes a natural/spontaneous fermentation process by naturally occurring microbial strains, typically soil-bound strains, e.g. Bacillus and Pediococcus.
  • Fermented rice bran refers to rice bran which has undergone a fermentation process. Fermented rice bran contains probiotic microbes that stabilise the microbiome of the small intestine.
  • stabilized rice bran refers to rice bran which has been heated for a short period of time, for example by passing it through a high temperature high pressure extruder. The heat stabilizes the rice bran.
  • “stabilized rice bran” is thus heat treated rice bran.
  • rice bran may be stabilized after milling is being by heating it at 130 degrees Celsius for less than 10 seconds.
  • stabilized rice bran is a dietary fibre.
  • stabilized rice bran is a dietary fibre that can be catabolized in the colon.
  • stabilised rice bran is a prebiotic interacting with the microbiome of colon.
  • the microbial contents of fermented rice bran may have a probiotic and stabilising effect on the microbiome of the small intestine and that the rice bran, being a dietary fibre, stabilises the conditions of colon.
  • Another mechanism of action maybe a reduction of intestinal oxidative stress, which normalizes the barrier function of the intestinal mucosa and may result in less alcohol absorption.
  • Rice bran e.g. fermented rice bran
  • the alcohol degrading (e.g. alcohol metabolizing) composition described herein in an appropriate amount or concentration as described below.
  • the amount or concentration of rice bran may therefore be described by reference to the % w/w of composition or by the total weight (e.g. mgs) per dose of composition (in other words the weight per effective dose).
  • a dose may include one or more dosage units (e.g. 2 dosage units).
  • the weight per dose corresponds to the total weight of rice bran over the plurality of dosage units.
  • the composition comprises about 50% w/w to about 90% w/w of rice bran.
  • the composition comprises about 60% w/w to about 80% w/w of rice bran. In another example, the composition comprises about 73% w/w to about 79% w/w of rice bran.
  • the composition comprises at least about 50% w/w of rice bran. In another example, the composition comprises at least about 55% w/w of rice bran. In one example, the composition comprises at least about 60% w/w of rice bran. In a further example, the composition comprises at least about 65% w/w of rice bran. In one example, the composition comprises at least about 73% w/w of rice bran. In one example, the composition comprises at least about 75% w/w of rice bran. In one example, the composition comprises at least about 79% w/w of rice bran. In a further example, the composition comprises at least about 85% w/w of rice bran. In one example, the composition comprises at least about 90% w/w of rice bran.
  • the composition comprises about 50% w/w of rice bran. In another example, the composition comprises about 55% w/w of rice bran. In one example, the composition comprises about 60% w/w of rice bran. In a further example, the composition comprises about 65% w/w of rice bran. In one example, the composition comprises about 73% w/w of rice bran. In one example, the composition comprises about 75% w/w of rice bran. In one example, the composition comprises about 79% w/w of rice bran. In a further example, the composition comprises about 85% w/w of rice bran. In one example, the composition comprises about 90% w/w of rice bran.
  • the composition comprises at least about 67% w/w of rice bran.
  • the composition may comprise about 67% w/w of rice bran.
  • the composition comprises at least about 73 %w/w of rice bran.
  • the composition may comprise about 73% w/w of rice bran.
  • the composition comprises at least about 79 %w/w of rice bran.
  • the composition may comprise about 79% w/w of rice bran.
  • the composition comprises at least about 79.5 %w/w of rice bran.
  • the composition may comprise about 79.5% w/w of rice bran.
  • the composition comprises at least about 300mg of rice bran (e.g. fermented rice bran) per dose.
  • a dose may be formulated as two capsules.
  • the composition comprises at least about 300mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises at least about 350mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises at least about 400mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises at least about 450mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises at least about 500mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises at least about 550mg of rice bran (e.g. fermented rice bran) per dose.
  • the composition comprises at least about 300mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises at least about 350mg of rice bran (e.g. fermented rice bran) per dose. In one
  • the composition comprises about 300mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises about 350mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises about 400mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises about 450mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises about 500mg of rice bran (e.g. fermented rice bran) per dose. In one example, the composition comprises about 550mg of rice bran (e.g. fermented rice bran) per dose.
  • rice bran e.g. fermented rice bran
  • an alcohol degrading composition comprising one or more bacterial species of the Bacillus genus (e.g. B subtilis and/or B. coagulans), rice bran (e.g. fermented rice bran), L-cysteine and a high molecular weight low osmolality carbohydrate (e.g. dextrin) is provided.
  • the one or more bacterial species of the Bacillus genus e.g. B subtilis and/or B. coagulans
  • rice bran e.g. fermented rice bran
  • L-cysteine a high molecular weight low osmolality carbohydrate
  • dextrin may be present in the alcohol degrading composition described herein at any appropriate amount or concentration.
  • Appropriate amounts and concentrations of the one or more bacterial species of the Bacillus genus (e.g. B subtilis and/or B. coagulans), rice bran (e.g. fermented rice bran), L-cysteine and the high molecular weight low osmolality carbohydrate (e.g. dextrin) are described elsewhere herein. Illustrative examples of appropriate concentrations are provided below.
  • the composition comprises about 0.5% w/w to 5% w/w of dextrin, about 10% w/w of L-cysteine to about 40% w/w of L-cysteine, about 50% w/w to about 90% w/w of rice bran (e.g. fermented rice bran) and about 10,000 cfu/g of bacteria of the Bacillus genus to about 15,000 cfu/g of bacteria of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • the composition described herein comprises at least about 0.5% w/w of dextrin, at least about 10% w/w of L-cysteine, at least about 67% w/w of rice bran (e.g. at least about 67% w/w of fermented rice bran) and at least 10,000 cfu/g of bacteria of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 0.5% w/w of dextrin, at least about 20% w/w of L-cysteine, at least about 67% w/w of rice bran (e.g. at least about 67% w/w of fermented rice bran) and at least 10,000 cfu/g of bacteria of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 0.5% w/w of dextrin, at least about 30% w/w of L-cysteine, at least about 67% w/w of rice bran (e.g. at least about 67% w/w of fermented rice bran) and at least 10,000 cfu/g of bacteria of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 5% w/w of dextrin, at least about 20% w/w of L-cysteine, at least about 67% w/w of rice bran (e.g. at least about 67% w/w of fermented rice bran) and at least 10,000 cfu/g of bacteria of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition described herein comprises at least about 3% w/w of dextrin, at least about 30% w/w of L-cysteine, at least about 67% w/w of rice bran (e.g. at least about 67% w/w of fermented rice bran) and at least 10,000 cfu/g of bacteria of the Bacillus genus (e.g. B. subtilis and/or B. coagulans).
  • Bacillus genus e.g. B. subtilis and/or B. coagulans
  • the composition comprises 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 bacteria of the Bacillus genus/dose to about 1 x10 8 cfu of bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition described herein comprises 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 bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition described herein comprises at least about 2 mg of dextrin, 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 bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition described herein comprises 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 bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • the composition described herein comprises 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 bacteria of the Bacillus genus/dose (e.g. B. subtilis and/or B. coagulans).
  • composition of 79.5% w/w fermented rice bran (including one or more bacterial species of the Bacillus genus), 0.5% w/w dextrin and 20.0% w/w L-cysteine was assessed to be particularly effective at digesting alcohol in the intestinal tract, having about 50% faster than liver digestion of alcohol, as described in the examples below.
  • the composition described herein comprises about 79.5% w/w fermented rice bran (including one or more bacterial species of the Bacillus genus), about 0.5% w/w dextrin and about 20.0% w/w L-cysteine.
  • the alcohol degrading composition described herein may include one or more additional components e.g. one or more additional ingredients.
  • the composition described herein may further comprise emulsifying agents, filling agents and/or non-active ingredients.
  • additional components include vitamin B12, fatty acid magnesium salts (e.g. magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide and cellulose (e.g. microcrystalline cellulose).
  • the alcohol degrading composition described herein may further comprise one or more of: vitamin B12, a fatty acid magnesium salt (e.g. magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide and cellulose (e.g. microcrystalline cellulose).
  • the alcohol degrading composition described herein may further comprise two or more of: vitamin B12, a fatty acid magnesium salt (e.g. magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide and cellulose (e.g. microcrystalline cellulose).
  • the alcohol degrading composition described herein may further comprise three or more of: vitamin B12, a fatty acid magnesium salt (e.g.
  • the alcohol degrading composition described herein may further comprise four or more of: vitamin B12, a fatty acid magnesium salt (e.g. magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide and cellulose (e.g. microcrystalline cellulose).
  • the alcohol degrading composition described further comprises vitamin B12, a fatty acid magnesium salt (e.g. magnesium stearate), calcium phosphate, potassium phosphate, silicon dioxide and cellulose (e.g. microcrystalline cellulose).
  • a fatty acid magnesium salt e.g. magnesium stearate
  • calcium phosphate e.g. magnesium stearate
  • potassium phosphate e.g. potassium phosphate
  • silicon dioxide e.g. microcrystalline cellulose
  • fatty acid magnesium salts include magnesium stearate. Accordingly, in one example, the composition described herein may further comprise magnesium stearate.
  • Magnesium stearate is the magnesium salt of the fatty acid stearic acid.
  • Magnesiums salts of fatty acids e.g. magnesium stearate
  • Magnesium stearte is a GRAS-listed ingedient.
  • vitamin B12 is added for regulatory purposes.
  • magnesium salts e.g. magnesium stearate
  • calcium salts and/or potassium salts are non-active ingredients (e.g. they have no clinical effects).
  • magnesium salts e.g. magnesium stearate
  • calcium salts and/or potassium salts may be added as filling aids (e.g. filling agents) which help capsule filling machines work effectively.
  • the composition described herein further comprises microcrystalline cellulose.
  • Microcrystalline cellulose may be used as an emulsifying agent, filling aid and/or a non-active ingredient.
  • Microcrystalline cellulose (and also maltodextrin) may be used as a cake-forming excipient when punching tablets and as a fluidity agent when making capsule formulations.
  • the composition described herein further comprises maltodextrin.
  • the composition comprises about 5% w/w to about 50% w/w of microcrystalline cellulose. In another example, the composition comprises about 5% w/w to about 35% w/w of microcrystalline cellulose. In another example, the composition comprises about 5% w/w to about 20% w/w of microcrystalline cellulose. In another example, the composition comprises about 5% w/w to about 15% w/w of microcrystalline cellulose. In another example, the composition comprises about 5% w/w to about 8% w/w of microcrystalline cellulose.
  • the composition comprises at least about 5%w/w of microcrystalline cellulose. In one example, the composition comprises at least about 8% w/w of microcrystalline cellulose. In another example, the composition comprises at least about 10%w/w of microcrystalline cellulose. In another example, the composition comprises at least about 15%w/w of microcrystalline cellulose. In a further exam pie, the composition comprises at least about 20%w/w of microcrystalline cellulose. In another example, the composition comprises at least about 25%w/w of microcrystalline cellulose. In another example, the composition comprises at least about 30%w/w of microcrystalline cellulose. In yet a further example, the composition comprises at least about 35%w/w of microcrystalline cellulose. In another example, the composition comprises at least about 40%w/w of microcrystalline cellulose. In another example, the composition comprises at least about 45%w/w of microcrystalline cellulose. In another example, the composition comprises at least about 50%w/w of microcrystalline cellulose.
  • the composition comprises about 5%w/w of microcrystalline cellulose. In one example, the composition comprises about 8%w/w of microcrystalline cellulose. In another example, the composition comprises about 10%w/w of microcrystalline cellulose. In another example, the composition comprises about 15%w/w of microcrystalline cellulose. In a further example, the composition comprises about 20%w/w of microcrystalline cellulose. In another example, the composition comprises about 25%w/w of microcrystalline cellulose. In yet a further example, the composition comprises about 30%w/w of microcrystalline cellulose. In another example, the composition comprises about 35%w/w of microcrystalline cellulose. In another example, the composition comprises about 40%w/w of microcrystalline cellulose. In another example, the composition comprises about 45%w/w of microcrystalline cellulose. In another example, the composition comprises about 50%w/w of microcrystalline cellulose.
  • the composition described herein comprises at least about 30 mg of microcrystalline cellulose per dose.
  • a dose may be formulated in two capsules.
  • the composition described herein comprises at least about 40 mg of microcrystalline cellulose per dose. In one example, the composition described herein comprises at least about 50 mg of microcrystalline cellulose per dose. In one example, the composition described herein comprises at least about 60 mg of microcrystalline cellulose per dose. In one example, the composition described herein comprises at least about 70 mg of microcrystalline cellulose per dose. In one example, the composition described herein comprises at least about 80 mg of microcrystalline cellulose per dose. In one example, the composition described herein comprises at least about 90 mg of microcrystalline cellulose per dose. In one example, the composition described herein comprises at least about 100 mg of microcrystalline cellulose per dose.
  • the composition described herein further comprises magnesium stearate.
  • Magnesium stearate may be used as an emulsifying agent, filling aid and/or a non-active ingredient.
  • the composition comprises about 0.2% w/w to about 1.5% w/w of magnesium stearate. In another example, the composition comprises about 0.5% w/w to about 1.4% w/w of magnesium stearate. In another example, the composition comprises about 0.6% w/w to about 1 .3% w/w of magnesium stearate.
  • the composition comprises at least about 0.2 %w/w of magnesium stearate. In another example, the composition comprises at least about 0.3%w/w of magnesium stearate. In another example, the composition comprises at least about 0.4% w/w of magnesium stearate. In a further example, the composition comprises at least about 0.5% w/w of magnesium stearate. In another example, the composition comprises at least about 0.6% w/w of magnesium stearate. In another example, the composition comprises at least about 0.7% w/w of magnesium stearate. In yet a further example, the composition comprises at least about 0.8% w/w of magnesium stearate. In another example, the composition comprises at least about 0.9% w/w of magnesium stearate.
  • the composition comprises at least about 1.0% w/w of magnesium stearate. In another example, the composition comprises at least about 1.1 % w/w of magnesium stearate. In another example, the composition comprises at least about 1.2% w/w of magnesium stearate. In another example, the composition comprises at least about 1.3% w/w of magnesium stearate. In another example, the composition comprises at least about 1.4% w/w of magnesium stearate. In another example, the composition comprises at least about 1.5% w/w of magnesium stearate.
  • the composition comprises about 0.2% w/w of magnesium stearate. In another example, the composition comprises about 0.3% w/w of magnesium stearate. In another example, the composition comprises about 0.4% w/w of magnesium stearate. In a further example, the composition comprises about 0.5% w/w of magnesium stearate. In another example, the composition comprises about 0.6% w/w of magnesium stearate. In another example, the composition comprises about 0.7% w/w of magnesium stearate. In yet a further example, the composition comprises about 0.8% w/w of magnesium stearate. In another example, the composition comprises about 0.9% w/w of magnesium stearate.
  • the composition comprises about 1.0% w/w of magnesium stearate. In another example, the composition comprises about 1.1 % w/w of magnesium stearate. In another example, the composition comprises about 1.2% w/w of magnesium stearate. In another example, the composition comprises about 1.3% w/w of magnesium stearate. In another example, the composition comprises about 1.4% w/w of magnesium stearate. In another example, the composition comprises about 1.5% w/w of magnesium stearate.
  • the composition described herein comprises at least about 4 mg of magnesium stearate per dose.
  • a dose may be formulated in two capsules.
  • the composition described herein comprises at least about 5 mg of magnesium stearate per dose. In one example, the composition described herein comprises at least about 6 mg of magnesium stearate per dose. In one example, the composition described herein comprises at least about 7 mg of magnesium stearate per dose. In one example, the composition described herein comprises at least about 8 mg of magnesium stearate per dose. In one example, the composition described herein comprises at least about 9 mg of magnesium stearate per dose. In one example, the composition described herein comprises at least about 10 mg of magnesium stearate per dose.
  • composition described herein further comprises silicon dioxide.
  • Silicon dioxide may be used as an emulsifying agent, filling aid and/or a non-active ingredient.
  • the composition comprises about 0.5% w/w to about 4% w/w of silicon dioxide. In another example, the composition comprises about 0.7% w/w to about 3% w/w of silicon dioxide. In another example, the composition comprises about 0.9% w/w to about 2% w/w of silicon dioxide.
  • the composition comprises at least about 0.5% w/w of silicon dioxide. In another example, the composition comprises at least about 1% w/w of silicon dioxide. In another example, the composition comprises at least about 1.5% w/w of silicon dioxide. In a further example, the composition comprises at least about 2% w/w of silicon dioxide. In another example, the composition comprises at least about 2.5% w/w of silicon dioxide. In another example, the composition comprises at least about 3% w/w of silicon dioxide. In yet a further example, the composition comprises at least about 3.5% w/w of silicon dioxide. In another example, the composition comprises at least about 4% w/w of silicon dioxide. In one example, the composition comprises about 0.5% w/w of silicon dioxide.
  • the composition comprises about 1 % w/w of silicon dioxide. In another example, the composition comprises about 1.5% w/w of silicon dioxide. In a further example, the composition comprises about 2% w/w of silicon dioxide. In another example, the composition comprises about 2.5% w/w of silicon dioxide. In another example, the composition comprises about 3% w/w of silicon dioxide. In yet a further example, the composition comprises about 3.5% w/w of silicon dioxide. In another example, the composition comprises about 4% w/w of silicon dioxide.
  • the composition described herein comprises at least about 4 mg of silicon dioxide per dose.
  • a dose may be formulated in two capsules.
  • the composition described herein comprises at least about 5 mg of silicon dioxide per dose. In one example, the composition described herein comprises at least about 6 mg of silicon dioxide per dose. In one example, the composition described herein comprises at least about 7 mg of silicon dioxide per dose. In one example, the composition described herein comprises at least about 8 mg of silicon dioxide per dose.
  • the composition described herein further comprises vitamin B12.
  • Vitamin B12 may be included in the composition described herein for regulatory purposes.
  • the composition comprises at least 15% of recommended daily intake (RDI), i.e. 0.38 mcg up to 2.4 mcg (Ell) and 2.5 mcg for USA.
  • RDI recommended daily intake
  • the composition described herein comprises at least about 0.76 pg (mcg) of vitamin B12 per dose. In one example, the composition described herein comprises at least about 0.9 pg (mcg) of vitamin B12 per dose.
  • composition may be formulated in any appropriate form.
  • it may be in the form of a tablet or capsule.
  • the composition is formulated as an acid resistant tablet or capsule.
  • capsule refers to both empty and filled capsules whereas “shell” specifically refers to an empty capsule unless the context requires otherwise.
  • the composition described herein is comprised within a capsule (e.g. within a shell). In some examples, the composition described herein is comprised within an acid resistant capsule (e.g. within an acid resistant shell). As would be clear to a person of skill in the art, when reference is made to a % w/w of an ingredient present within the composition, this does not take into account any weight attributed to the capsule (and thus only takes into account the % w/w of the composition within the capsule).
  • the acid resistant tablet or capsule comprises a film coating, wherein the film coating comprises hydroxypropyl methylcellulose (HPMC).
  • HPMC is a semisynthetic, inert, viscoelastic polymer used in various applications.
  • HPMC may be used as an excipient in oral tablet and capsule formulations, where, depending on the grade, it functions as controlled release agent to delay the release of a medicinal compound into the digestive tract.
  • HPMC may also be used as a binder and/or as a component of tablet coatings.
  • composition described herein is comprised within a (capsule) shell wherein the shell comprises hydroxypropyl methylcellulose (HPMC).
  • HPMC hydroxypropyl methylcellulose
  • composition described herein may be formulated as an acid resistant tablet or capsule or may be comprised within an acid resistant capsule (e.g. an acid resistant shell) which is dissolved once reaching the duodenum, allowing the microbial cells and spores to be released and settle in the upper part of the intestinal tract.
  • an acid resistant capsule e.g. an acid resistant shell
  • the composition present within a capsule wherein the capsule comprises about 80 mg to about 100 mg of HPMC.
  • the capsule may comprise at least about 80 mg of HPMC.
  • the capsule comprises at least about 90 mg of HPMC.
  • the capsule comprises at least about 100 mg of HPMC.
  • the capsule comprises about 80 mg of HPMC.
  • the capsule comprises about 90 mg of HPMC.
  • the capsule comprises about 100 mg of HPMC.
  • HPMC is present as a film coating at the exterior surface of the capsule described herein.
  • composition described herein may be in unit dosage form. Where the composition described herein is in unit dosage form, it may be that one tablet or capsule is administered and this constitutes a dose, alternatively it may be that two tablets or capsules are administered and this constitutes a dose. Suitable dosages and regimens can be determined by a person skilled in the art, based on the examples below. Accordingly, in one example, a dose of the composition according to the present invention includes a plurality of small tablets or capsules (e.g. two).
  • dose form refers to an amount of medication to be taken at one time, optionally in regular intervals. This is also referred to as a “dose” herein.
  • the invention provides a solid unit dose form for oral administration.
  • a dose of the composition described herein comprises: about 300 mg of fermented rice bran, about 38mg 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 pg (mcg) vitamin B12 and about 5,000 cfu bacteria from the Bacillus genus.
  • the dose may be formulated as two tablets or capsules.
  • the amounts of the components may represent a total amount of the component present in the dose (i.e. in the two tablets or capsules). This corresponds to the composition that is used in Example 1 , test 7B.
  • dose of the composition described herein comprises: at least about 300 mg of fermented rice bran, at least about 38mg 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 pg (mcg) vitamin B12 and at least about 5,000 cfu bacteria from the Bacillus genus.
  • a dose of the composition described herein comprises: about 552 mg of fermented rice bran, about 150mg 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 pg (mcg) vitamin B12 and about 100,000 cfu bacteria from the Bacillus genus.
  • the dose may be formulated as two tablets or capsules.
  • the amounts of the components may represent a total amount of the component present in the dose (i.e. in the two tablets or capsules). A skilled person would thus understand that at least each of these components, in at least these amounts, provide an effective dose in accordance with the invention.
  • dose of the composition described herein comprises: at least about 552 mg of fermented rice bran, at least about 150mg 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 pg (mcg) vitamin B12 and at least about 100,000 cfu bacteria from the Bacillus genus.
  • HPMC is present as a film coating at the exterior surface of the capsule described herein.
  • the composition described herein may be used as (or used as part of) a dietary supplement, a nutraceutical, a food composition, a medical food, or a medicament.
  • dietary supplement or “food supplement” as used herein, refers to a composition which is consumed in addition to the daily meals or in between.
  • composition refers to any kind of composition which is eatable and/or drinkable without causing toxic symptoms in the subject eating or drinking the respective composition.
  • compositions described herein for degrading alcohol are provided herein.
  • degrading alcohol is described elsewhere herein and applies equally here.
  • the composition may be used for degrading alcohol in a subject (e.g. the use may be in vivo).
  • the subject may be any suitable subject, for example, the subject may be human.
  • the subject may be a human that is intending to consume or has consumed alcohol.
  • the composition may be used for metabolising alcohol in the gut of the subject.
  • the term “metabolising alcohol” is described elsewhere herein and applies equally here.
  • the composition may be used for metabolising alcohol in the intestine of the subject.
  • the composition may be used for metabolising alcohol in the small intestine of the subject. More specifically, the composition may be used for metabolising alcohol in the duodenum of the subject.
  • the composition may be used for reducing absorption of alcohol into the blood of the subject.
  • a person of skill in the art would be able to determine a reduction in absorption of alcohol into the blood in the presence of the 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).
  • the composition When the composition is used to degrade alcohol in a subject, it may be used for reducing breath or blood alcohol concentration in the subject.
  • a person of skill in the art would be able to determine a reduction in breath or blood alcohol concentration in the presence of the 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).
  • a person of skill in the art would readily be able to determine a reduction in breath or blood alcohol concentration in the presence of the 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) about 30 minutes after alcohol ingestion (alcohol consumption).
  • L-cysteine for increasing alcohol degradation by one or more bacterial species of the Bacillus genus is provided herein.
  • L-cysteine may be used in vitro or in vivo for increasing alcohol degradation.
  • L-cysteine may be used for increasing alcohol degradation by one or more bacterial species of the Bacillus genus when it is used as (or used as part of) a dietary supplement, a nutraceutical, a medical food or a medicament.
  • L-cysteine “alcohol degradation” and “one or more bacterial species of the Bacillus genus” are defined elsewhere herein, with examples of what is encompassed by these terms. These definitions and aspects apply egually here.
  • a person of skill in the art would 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 (e.g. the methods described in the examples section below).
  • L-cysteine may be used for increasing alcohol degradation by one or more bacterial species of the Bacillus genus selected from B. subtilis and B. coagulans.
  • the one or more bacterial species of the Bacillus genus may comprise B. subtilis.
  • the one or more bacterial species of the Bacillus genus may comprise B. coagulans.
  • the one or more bacterial species of the Bacillus genus may comprise B. subtilis and B. coagulans.
  • Suitable concentrations, amounts, proportions etc of the one or more bacterial species of the Bacillus genus are described elsewhere herein and apply egually to this aspect.
  • L-cysteine may be used for increasing alcohol degradation by one or more bacterial species of the Bacillus genus, when the alcohol is ethyl alcohol.
  • the L-cysteine may be combined with a high molecular weight low osmolality carbohydrate, such as dextrin, when it is used for increasing alcohol degradation by one or more bacterial species of the Bacillus genus.
  • the L-cysteine may be combined with rice bran.
  • L-cysteine may be used for increasing alcohol degradation by one or more bacterial species of the Bacillus genus when it is used as (or used as part of) a dietary supplement, a nutraceutical or a medical food (e.g. when it is part of a composition that is described herein).
  • composition described herein may be used in vitro or in vivo for degrading alcohol.
  • the compositions described herein may therefore be used as a medicament.
  • compositions described herein may be used as a medicament for degrading alcohol in a subject.
  • the compositions provided herein may be particularly advantageous, for example, for preventing and/or treating alcohol-induced organ damage in a subject.
  • the compositions provided herein may be useful for preventing and/or treating alcohol-induced damage to the liver and/or pancreas of a subject.
  • Alcohol induced organ damage includes both acute and chronic alcohol induced organ damage.
  • Alcohol induced damage comprises inflammation and/or inflammatory conditions which cause malfunction of internal organs and tissues, leading to severe secondary and sometimes life-threatening diseases.
  • the liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism.
  • chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis.
  • Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes.
  • Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins.
  • the fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure.
  • pancreatitis is defined as inflammation of the pancreas, leading to damage and dysfunction of the retroperitoneal organ.
  • pancreatitis There are various etiologies of pancreatitis, the most common being alcohol and gallstones.
  • Acute pancreatitis (AP) is a necro-inflammatory disease resulting from exocrine cell destruction by infiltrating inflammatory cells.
  • the diagnostic criteria are typically when a patient presents with characteristic symptoms, elevated lipase levels, and distinct imaging findings. Acute pancreatitis will either resolve with the pancreas fully regenerating, lead to transient organ failure, or progress to cause systemic inflammation and multi-organ failure.
  • CP Chronic pancreatitis
  • Alcohol predisposes the pancreas to damage from otherwise benign agents.
  • one of the main strategies to prevent recurrent attacks involve providing alcohol (and smoking) cessation counseling and strategies to patients.
  • compositions provided herein may be useful for preventing and/or treating a disease, condition or illness selected from the group consisting of: alcohol induced fatty liver, alcohol induced hepatitis, liver cirrhosis, alcohol induced cancer, cardio-vascular conditions, obesity, neuropathy, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache and/or intoxication by acetaldehyde.
  • the compositions provided herein may be useful for preventing and/or treating a disease, condition or illness selected from the group consisting of: alcohol induced fatty liver, alcohol induced hepatitis, liver cirrhosis, and alcohol induced cancer.
  • Alcohol induced fatty liver is also referred to herein as alcoholic fatty liver.
  • alcohol induced hepatitis is also referred to herein as alcoholic hepatitis.
  • Examples of alcohol induced cancers are well known in the art, and include liver cancer, pancreatic cancer, breast cancer, esophageal cancer and oropharyngolaryngeal cancer.
  • neuropathy refers to any disease or abnormality of the neurons of the nervous system.
  • “In particular "neuropathy” means a disorder of the peripheral nervous system, affecting nerves anywhere except brain and the spinal cord.
  • a non-limiting example for neuropathy is alcoholic polyneuropahy which is characterized by numbness, abnormal sensations called dysesthesias and allodynias that occur either spontaneously or in reaction to external stimuli, and a characteristic form of pain, called neuropathic pain or neuralgia.
  • neurodegenerative disease refers to any disease or abnormality of the of the nervous system caused by deterioration of neurons, which include death of neurons and functional loss of neurotransmitters.
  • Non-limiting examples for a neurodegenerative disease are Alzheimer's disease (e.g. late-onset Alzheimer's Disease) and Parkinson's disease.
  • late-onset Alzheimer's Disease refers to the onset of Alzheimer's Disease in elderly people, in particular in people being 65 years old and older.
  • the neurodegenerative disease is Alzheimer's Disease, optionally the neurodegenerative disease is late-onset Alzheimer's Disease.
  • hangover refers to general discomfort generally suffered on waking by a person who has drunk (e.g. consumed and/or ingested) alcohol (to excess).
  • hangover is the result of intoxication of the organism, caused by the ingestion of (an excessive amount) of alcohol.
  • Hangover is the appearance of a series of symptoms on the day after having drunk alcohol excessively and can become worse if the person smokes excessively.
  • the organism protects itself from intoxication and secretes enzymes that metabolise and excrete the toxins.
  • the ingestion of alcohol is excessive the capacity of the organism to metabolise it is less and the symptoms of hangover appear.
  • “Hangover symptoms” include a headache, produced by dilation of blood vessels caused by the accumulation of histamine, red eyes, occasional memory loss, vomiting, possible flatulence, intense thirst, which originates as a response of the body to dehydration caused by the alcohol, abdominal and muscular pain, which results in a feeling of weakness and in some cases, diarrhoea.
  • headache is common in all people suffering from hangover and results from dilation of the blood vessels due to the effect of some vasodilator substances (such as histamine) in the person.
  • Flushing syndrome refers to the flushing as a consequence of drinking alcohol. Flushing is associated with the erythema (reddening caused by dilation of capillaries) of the face, neck, and shoulder, after consumption of alcohol. Flushing after alcohol consumption is often associated with a range of symptoms: dizziness, nausea, headaches, an increased pulse, occasional extreme drowsiness, and occasional skin swelling and itchiness. There symptoms are collectively called “Flushing syndrome” or "Asian flush”.
  • compositions provided herein are able to degrade alcohol in the gut (intestine) of a subject, thereby reducing the amount of alcohol that is absorbed into the blood.
  • the compositions provided herein can therefore degrade alcohol before the alcohol is transported to the liver.
  • the compositions provided herein can therefore be used to protect the liver and associated organs from alcohol induced liver damage.
  • compositions provided herein are effective at degrading alcohol when they are administered to a subject at any point before, during (e.g. simultaneously with alcohol ingestion or between ingestion of alcohol e.g. between a first alcoholic drink and a second alcoholic drink), or after ingestion of alcohol.
  • the agent is preferably ingested before or during ingestion of alcohol, most preferably at least one hour before ingestion of alcohol.
  • the composition is for administration before or simultaneously with alcohol ingestion.
  • the composition (e.g. an effective amount of the composition described herein) is ingested at least five hours before ingestion of alcohol. In some examples, the composition (e.g. an effective amount of the composition described herein) is ingested at least four hours before ingestion of alcohol. In some examples, the composition (e.g. an effective amount of the composition described herein) is ingested at least three hours before ingestion of alcohol. In some examples, the composition (e.g. an effective amount of the composition described herein) is ingested at least two hours before ingestion of alcohol.
  • the composition e.g. an effective amount of the composition described herein
  • the composition e.g. an effective amount of the composition described herein
  • the composition e.g. an effective amount of the composition described herein
  • AB001 In case of using AB001 to protect from alcohol ingested by occasional drinking, it may be beneficial to take two doses prior to drinking with a 2-hour time difference between them, and the last dose taken at least 2 hours prior to the ingestion of alcohol.
  • the composition e.g. an effective amount of the composition described herein
  • the composition described herein (e.g. a dose of the composition described herein) is taken daily.
  • the composition e.g. an effective amount of the composition described herein
  • one dose e.g. 2 capsules or tablets of the composition described herein
  • one dose e.g.
  • 2 capsules or tablets of the composition described herein may be taken daily for 2 days, 3 days, 4 days, 5 days, 6 days or 7 days preceding alcohol ingestion.
  • one dose e.g. 2 capsules or tablets of the composition described herein
  • 7 days preceding alcohol ingestion e.g. 2 capsules or tablets of the composition described herein
  • the composition described herein e.g. an effective amount of the composition described herein, such as a dose of the composition described herein
  • the composition e.g. an effective amount of the composition described herein
  • the composition e.g. an effective amount of the composition described herein
  • the composition is ingested simultaneously with alcohol.
  • the composition e.g. an effective amount of the composition described herein
  • the composition (e.g. an effective amount of the composition described herein) is ingested after (e.g. following) alcohol ingestion.
  • the composition e.g. an effective amount of the composition described herein
  • the composition e.g. an effective amount of the composition described herein
  • the composition (e.g. an effective amount of the composition described herein) is ingested at least five hours after ingestion of alcohol. In some examples, the composition (e.g. an effective amount of the composition described herein) is ingested at least four hours after ingestion of alcohol. In some examples, the composition (e.g. an effective amount of the composition described herein) is ingested at least three hours after ingestion of alcohol. In some examples, the composition (e.g. an effective amount of the composition described herein) is ingested at least two hours after ingestion of alcohol.
  • the composition e.g. an effective amount of the composition described herein
  • the composition (e.g. an effective amount of the composition described herein) is ingested at least 30 minutes after ingestion of alcohol. In one example, the composition (e.g. an effective amount of the composition described herein) is ingested at least 15 minutes after ingestion of alcohol.
  • composition described herein may be administered to a subject at any point before, during, or after ingestion of alcohol.
  • the agent is preferably ingested before or during ingestion of alcohol, most preferably at least one hour before ingestion of alcohol.
  • Alcohol ingestion refers to the taking in (e.g. consumption) of a substance by an organism. Accordingly, as used herein, “alcohol ingestion” refers to the act or process of taking alcohol into an organism (e.g. a subject, preferably a human). In the context of the present invention, alcohol is preferably ingested via the mouth where the subject is human. “Alcohol ingestion” and “alcohol consumption” may be used interchangeably herein.
  • the composition may be orally ingested in the form of an aqueous solution, a tablet, a capsule, a granule, or the like.
  • the composition may be added to an alcoholic beverage (or other source of alcohol) before it is ingested.
  • the composition may be added as an additional ingredient during the production of an alcoholic beverage.
  • An appropriate ingestion amount of the composition disclosed herein depends on the mass of alcohol that is (to be) ingested.
  • a pharmaceutical formulation is also provided herein, comprising the composition of the invention.
  • a pharmaceutical formulation is a formulation that is suitable for administration to a subject for degrading alcohol.
  • the pharmaceutical formulation may be for administration to a subject for preventing and/or treating a disease, condition or illness selected from the group consisting of: alcohol induced fatty liver, alcohol induced hepatitis, liver cirrhosis, alcohol induced cancer, cardio-vascular conditions, obesity, neuropathy, neurodegenerative diseases, hangover symptoms, flushing syndrome, headache and/or intoxication by acetaldehyde.
  • a pharmaceutical formulation, as used herein comprises an effective dose of the composition of the invention.
  • compositions described herein are for administration to a subject (preferably a human) in an effective amount (in an effective dose).
  • An “effective amount” is an amount that alone, or together with further doses, produces the desired (therapeutic or non-therapeutic) response.
  • the effective amount to be used will depend, for example, upon the therapeutic (or non- therapeutic) objectives, the route of administration, and the condition of the subject.
  • a suitable dosage of the composition of the invention for a given subject can be determined by a physician (or the person administering the composition), taking into consideration various factors known to modify the action of the composition of the invention for example amount of alcohol ingestion, body weight, sex, diet, time and route of administration, other medications and other relevant clinical factors.
  • the dosages and schedules may be varied according to the particular condition, disorder or symptom the overall condition of the subject. Effective dosages may be determined by either in vitro or in vivo methods.
  • compositions described herein are advantageously presented in dosage units.
  • the composition may be presented in the form of a capsule or a tablet.
  • Other suitable dosage units are described elsewhere herein.
  • an “effective amount” may comprise administration of one or more dosage units.
  • an effective amount may be achieved by administration of one or two capsules or tablets.
  • the dosage units may be administered together, or they may be taken at spaced intervals during the day.
  • treating refers to the administration of a composition to a subject (e.g., a symptomatic subject afflicted with an adverse condition, disorder, illness or disease) so as to affect a reduction in severity and/or frequency of a symptom, eliminate a symptom and/or its underlying cause, and/or facilitate improvement or remediation of damage, and/or preventing an adverse condition, disorder, illness or disease in an asymptomatic subject who is susceptible to a particular adverse condition, disorder, illness or disease, or who is suspected of developing or at risk of developing the condition, disorder, illness or disease.
  • a subject e.g., a symptomatic subject afflicted with an adverse condition, disorder, illness or disease
  • prevention means the avoidance of the occurrence or re-occurrence a symptom and/or its underlying cause, damage, an adverse condition, disorder, illness and/ or disease.
  • prevention in the context of the present invention may be avoiding the appearance of one or more of the symptoms related to hangover.
  • the subject may be any suitable subject, for example, the subject may be human.
  • the subject may be a human that is intending to consume or has consumed alcohol.
  • a “pharmaceutical composition” refers to a composition having pharmacological activity or other direct effect in the mitigation, treatment, or prevention of disease, and/or a finished dosage form or formulation thereof and is for human use.
  • a pharmaceutical composition or pharmaceutical preparation is typically produced under good manufacturing practices (GMP) conditions.
  • GMP good manufacturing practices
  • Pharmaceutical compositions or preparations may be sterile or non-sterile. If non-sterile, such pharmaceutical compositions or preparations typically meet the microbiological specifications and criteria for non-sterile pharmaceutical products as described in the U.S. Pharmacopeia (USP) or European Pharmacopoeia (EP). Accordingly, the composition described herein may be formulated as a pharmaceutical composition. In some examples, the pharmaceutical composition is non-sterile.
  • nucleic acids are written left to right in 5' to 3' orientation; amino acid sequences are written left to right in amino to carboxy orientation, respectively. It is to be understood that this invention is not limited to the particular methodology, protocols, and reagents described, as these may vary, depending upon the context they are used by those of skill in the art.
  • the inventors have previously developed a food grade quality of fermented rice bran for evaluation purposes.
  • a safety study was initiated applying a case study design. Around 1 ,400 people have taken the product on a regular long-term basis. No side effects/adverse reactions have been reported. However, indications of anti-hangover effects were reported. The inventors sought to investigate this effect further.
  • a test was organised to confirm the anti-hangover effects of fermented rice bran in a controlled way. Eight individuals, men in their 30s to 50s, had four pints of beer each (4.2%) in one and a half hours at a first occasion. Average 1.24 %o 30 minutes post drinking and 5.5 hours to ⁇ 0.20%o.
  • Dextrin is available from several suppliers. Dextrin from three different suppliers was tested and confirmed to work (data not shown). The preferred dextrin that was used herein was hydrolysed corn dextrin (e.g. Vitargo).
  • L-Cysteine is also available from several suppliers. L-cysteine from three different suppliers was tested and confirmed to work (data not shown). The preferred L-cysteine that was used herein was of vegetable origin.
  • fermented rice bran comprising two dominant Bacillus strains, i.e. subtilis and coagulans, has a basic alcohol digesting effect of 25 - 30% faster than the alcohol digestion by the liver only. Additionally, the results above show that dextrin speeds up the alcohol digestion further, approximately 35 - 40% faster than liver digestion. A very marginal difference of added effects using 0.5 to 5% dextrin was observed.
  • a composition of 79.5% w/w fermented rice bran (comprising at least 10,000 cfu/g of bacteria of the Bacillus genus), 0.5% w/w dextrin and 20.0% w/w L-cysteine was assessed to be the optimal mixture for digesting alcohol in the intestinal tract from a clinical perspective, having about 50% faster than liver digestion of alcohol.
  • a combination of 0.5% w/w dextrin and 20.0% w/w L-cysteine was therefore used examples 2 and 3 below.
  • composition used in examples 2 and 3 therefore comprised, per dose (of 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 dioxides (4 mg), 0.00012% w/w vitamin B12 (0.0009 mg) and at least 1x 10 5 cfu of bacteria of the Bacillus genus.
  • both dextrin and/or L- cysteine create a micro-environment on a cellular level that makes the microbial consortium, upon resuscitation in the intestinal tract, excrete an enzyme cascade targeted towards short carbon chains, e.g. ethanol/alcohol - resulting in preferential targeting/ preferential use of ethanol/alcohol as a substrate.
  • Example 2 Dietary Supplement Comparative Trial PERA-ATX-001 : Clinical Study to Assess the Impact of a Bacterial- based Nutritional Supplement (AB001) on Ethyl Alcohol Absorption in the Intestinal Tract
  • an alcohol degrading composition (AB001) to help avoid problems associated with alcohol ingestion. It is composed 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 comes in acid resistant capsules, HPMC, which are dissolved once reaching the duodenum. The cultures are released and settle in the upper part of the intestinal tract where they stay for about one day before being eliminated from the body through the feces. The bacterial strains included in the composition were selected to preferably and effectively metabolize ethyl alcohol into CO2 and water, thus reducing the further absorption of alcohol from the intestinal tract.
  • the enrolled subjects were asked to participate in two experimental procedures (visits 2 and 3) after one week each of regular administration of two capsules per day of placebo or AB001 . After arrival at the study site, the subjects ate a light breakfast, and thereafter they ingested 0.3 g alcohol/kg bodyweight of a high alcoholic spirit (vodka).
  • a breath test (Drager Alcotest 3820, Drager Safety AG, Lubeck, Germany) and a blood draw for measurement of alcohol in a central laboratory (Labor Augsburg, Augsburg, Germany, gaschromatography) at timepoints 0 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 180 min, 240 min, 300 min, and 360 min were done. Prior to drinking the alcohol and after 60 min, the participants were asked to perform a number connection test. The time required for completion of the test was documented. The experiment was run for at least 120 min, and until no alcohol was seen in the breath test at two consecutive timepoints.
  • AUC area under the curve
  • the AUC can be calculated for each participant individually by employing the following formula to each timepoint Tk:
  • the mean ⁇ STD of the blood alcohol results for each timepoint was calculated and the area under the curve was calculated for each treatment.
  • the contribution of each timepoint to the AUC was calculated and two-sided student's T-Test was used to calculate the p-value (5 % error, 80 % power, type 1) for differences between the groups.
  • Table 2 Patient characteristics.
  • Table 3 Blood pressure, weight and amount of alcohol (32 % vodka) ingested at the different visits.
  • the AUCBiood(0-i80 min) was calculated to be 8.5 ⁇ 0.6 o/oo*min from the placebo experiments and 2.5 ⁇ 0.2*min from the verum experiments (-70.3 %; p ⁇ 0.005, see Figure 2).
  • the AUCBreath(o-i8o min) as calculated from the mean concentrations was 14.0 o/oo*mL from the placebo experiments and 9.7 o/oo*mL from the verum experiments (- 30.7 %, p ⁇ 0.005, see Figure 4).
  • the nutritional supplement was well tolerated, and there were no adverse events or serious adverse events reported in this trial. It can be concluded that the nutritional supplement has had no side effects in this trial. In addition, there were no clinically relevant deviations from normal values observed in the safety biochemistry panels taken before and after the study.
  • an alcohol degrading supplement (AB001) to help avoid problems associated with alcohol ingestion. It is composed 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 comes in acid resistant capsules, HPMC, which are dissolved once reaching the duodenum. The cultures are released and settle in the upper part of the intestinal tract where they stay for about one day before being eliminated from the body through the feces.
  • the bacterial strains were selected to preferably and effectively metabolize ethyl alcohol into CO2 and water, thus reducing the further absorption of alcohol from the intestinal tract. In consequence, less alcohol is expected to be absorbed by the body, and damage of organs through alcohol degradation products is expected to be diminished.
  • Example 2 provides a first randomized placebo-controlled double-blind crossover study wherein 24 healthy subjects (13 male, 11 female, age: 25.4 ⁇ 7.7 yrs, BMI: 23.6 ⁇ 2.5 kg/m 2 ) were randomized to take 2 capsules/day of AB001 or placebo for one week prior to an alcohol exposure experiment. On the experimental day, they ingested a light breakfast and drank a moderate glass of spirit (0.3 g/kg body weight). Breath alcohol tests and blood draws for determination of blood alcohol levels were performed for up to 6 hours. Areas under the curves were calculated to determine alcohol absorption rates. A significant reduction of blood alcohol levels by 70.3 % (p ⁇ 0.005 vs.
  • Example 3 The purpose of the study of Example 3 was to continue the scientific investigation of the performance of AB001 and to answer the following questions:
  • the enrolled subjects were asked to participate in two experimental procedures (visits 1 and 2). After arrival at the study site in the morning after an overnight fast, they were randomized to receive either placebo or the AB001 supplement.
  • a high alcoholic spirit (vodka; 0.3 g/kg body weight, timepoint 0 min) and consumed a light breakfast with rolls, ham or jam and with tea or coffee. Thereafter, they drank a second glass of alcohol (vodka; 0.3 g/kg bodyweight, timepoint 30 min).
  • the second experiment was performed 3 to 5 days later following the same experimental protocol. After the second experiment (visit 2), the patients were dismissed from the study.
  • the area under the curve (AUG) of blood alcohol levels over time were used to calculate the reduction in alcohol absorption by AB001 . In general, this can be done by two ways:
  • the AUG can be calculated for each participant individually by employing the following formula to each timepoint Tk:
  • the mean ⁇ STD of the blood alcohol results for each timepoint was calculated and the area under the curve was calculated for each treatment.
  • the contribution of each timepoint to the AUC was calculated and two-sided student's T-Test was used to calculate the p-value (5 % error, 80 % power, type 1) for differences between the groups.
  • the AUCBiood(0-420min) was calculated to be 116 ⁇ 32 o/oo*min from the placebo experiments and 104 ⁇ 24 0/00*min from the AB001 experiments (-10.1 %; p ⁇ 0.05, see Figure 6).
  • the AUCBreath(o-42o min) as calculated from the mean concentrations was 98 ⁇ 29 o/oo*min from the placebo experiments and 91 ⁇ 25 o/oo*min from the AB001 experiments (-7.2 %, p ⁇ 0.05).
  • Example 2 PERA-ATX-001
  • a substantial reduction of alcohol absorption into the blood by more than 70 % was observed after one week of AB001 supplementation as compared to placebo, when drinking 0.3 g/kg of alcohol after a light breakfast.
  • the reduction of measurable alcohol in the breath was also reduced significantly but to a lower extent (by ⁇ 30 %).
  • uptake of a single dose of AB001 taken only one hour prior to drinking 2 x 0.3 g/kg of alcohol with 30 min time interval between the shots, and during which a light meal was ingested, was also effective at reducing alcohol in the blood and breath.
  • the amount of alcohol in the blood was significantly reduced by about 10 % and breath alcohol was significantly reduced by 7 % with AB001 as compared to placebo.
  • uptake of a single dose of AB001 within 1 h prior to drinking reduces the amount of alcohol absorption in the intestinal tract leading to a significant reduction of alcohol in the blood and breath alcohol by about 10 % and 7 % respectively.
  • Intact group drank water and fed with standard rodent diet (standard rodent pelleted feed; Lactamin; Vadstena; Sweden). This group is referred to as the “IC” group herein.
  • CMD Placebo group drank a solution of 10% ethanol in water and fed with 12% maltodextrin mixed with the western high-fat high-carb diet (D12492M diet, Research Diets, New Brunswick, NJ 08901 , USA). This group is referred to as the “CMD” group herein.
  • DFM as used herein refers to the composition of the invention, in this case AB001 , as described in Examples 2 and 3.
  • mice had a cycle of 12 hours day/night. Every 5 individuals were kept in IVC cages with beta chip bedding. The drinking solutions were supplied in bottles (ad libitum) during the adaptation period and during the study. Animal body weight, feed and water consumption were measured weekly. The difference on the body weight, feed and water consumption was calculated at the beginning and final experimental day.
  • the samples were stored at -80 °C.

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