US20220354931A1 - Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith - Google Patents
Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith Download PDFInfo
- Publication number
- US20220354931A1 US20220354931A1 US17/557,046 US202117557046A US2022354931A1 US 20220354931 A1 US20220354931 A1 US 20220354931A1 US 202117557046 A US202117557046 A US 202117557046A US 2022354931 A1 US2022354931 A1 US 2022354931A1
- Authority
- US
- United States
- Prior art keywords
- composition
- alcohol
- dehydrogenase
- aldh
- liver
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 61
- 208000024891 symptom Diseases 0.000 title abstract description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 94
- 241001465754 Metazoa Species 0.000 claims abstract description 24
- 239000002207 metabolite Substances 0.000 claims abstract description 24
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 claims description 71
- 108010021809 Alcohol dehydrogenase Proteins 0.000 claims description 61
- 210000004185 liver Anatomy 0.000 claims description 56
- 241000283690 Bos taurus Species 0.000 claims description 25
- 241000283073 Equus caballus Species 0.000 claims description 21
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 claims description 15
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 14
- 102000007698 Alcohol dehydrogenase Human genes 0.000 claims description 13
- 239000002775 capsule Substances 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 9
- JVFMQNJSQVWUKH-UHFFFAOYSA-N galline Chemical compound C1=CC=[Ga]C=C1 JVFMQNJSQVWUKH-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 6
- 238000009825 accumulation Methods 0.000 claims description 5
- 241000272522 Anas Species 0.000 claims description 4
- 239000008280 blood Substances 0.000 claims description 4
- 210000004369 blood Anatomy 0.000 claims description 4
- 238000013270 controlled release Methods 0.000 claims description 4
- 239000006187 pill Substances 0.000 claims description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
- 239000002702 enteric coating Substances 0.000 claims description 2
- 238000009505 enteric coating Methods 0.000 claims description 2
- AZHSSKPUVBVXLK-UHFFFAOYSA-N ethane-1,1-diol Chemical compound CC(O)O AZHSSKPUVBVXLK-UHFFFAOYSA-N 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 abstract description 50
- 108090000790 Enzymes Proteins 0.000 abstract description 50
- 241000282414 Homo sapiens Species 0.000 abstract description 20
- 230000015556 catabolic process Effects 0.000 abstract description 11
- 238000007254 oxidation reaction Methods 0.000 abstract description 5
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 abstract description 2
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 abstract description 2
- 230000002269 spontaneous effect Effects 0.000 abstract description 2
- 230000001839 systemic circulation Effects 0.000 abstract description 2
- 235000019441 ethanol Nutrition 0.000 description 72
- 238000000338 in vitro Methods 0.000 description 28
- 230000002255 enzymatic effect Effects 0.000 description 24
- 239000000284 extract Substances 0.000 description 18
- 229940040511 liver extract Drugs 0.000 description 16
- 241000283074 Equus asinus Species 0.000 description 15
- 241000287828 Gallus gallus Species 0.000 description 11
- 241001494479 Pecora Species 0.000 description 11
- 235000013330 chicken meat Nutrition 0.000 description 11
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 230000008859 change Effects 0.000 description 10
- 241000272525 Anas platyrhynchos Species 0.000 description 9
- 241000282898 Sus scrofa Species 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 235000019687 Lamb Nutrition 0.000 description 8
- 239000006227 byproduct Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 241000272814 Anser sp. Species 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 206010001605 Alcohol poisoning Diseases 0.000 description 4
- 208000007848 Alcoholism Diseases 0.000 description 4
- 102100033816 Aldehyde dehydrogenase, mitochondrial Human genes 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 108010009513 Mitochondrial Aldehyde Dehydrogenase Proteins 0.000 description 4
- 206010028813 Nausea Diseases 0.000 description 4
- 239000000287 crude extract Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 230000008693 nausea Effects 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 206010000087 Abdominal pain upper Diseases 0.000 description 3
- 206010002942 Apathy Diseases 0.000 description 3
- 206010008531 Chills Diseases 0.000 description 3
- 206010009696 Clumsiness Diseases 0.000 description 3
- 206010019133 Hangover Diseases 0.000 description 3
- 208000008454 Hyperhidrosis Diseases 0.000 description 3
- 206010033557 Palpitations Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 208000002173 dizziness Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000004149 ethanol metabolism Effects 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 230000009931 harmful effect Effects 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 239000013589 supplement Substances 0.000 description 3
- 230000035900 sweating Effects 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000035922 thirst Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 101710088194 Dehydrogenase Proteins 0.000 description 2
- 101100398650 Mus musculus Lamb1 gene Proteins 0.000 description 2
- 201000007930 alcohol dependence Diseases 0.000 description 2
- 208000025746 alcohol use disease Diseases 0.000 description 2
- 235000013334 alcoholic beverage Nutrition 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960005489 paracetamol Drugs 0.000 description 2
- 230000002974 pharmacogenomic effect Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- RYKKQQUKJJGFMN-HVDRVSQOSA-N 4,5-bis(hydroxymethyl)-2-methylpyridin-3-ol;(2s)-5-oxopyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC(=O)N1.CC1=NC=C(CO)C(CO)=C1O RYKKQQUKJJGFMN-HVDRVSQOSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000022309 Alcoholic Liver disease Diseases 0.000 description 1
- 102100040069 Aldehyde dehydrogenase 1A1 Human genes 0.000 description 1
- 101710150756 Aldehyde dehydrogenase, mitochondrial Proteins 0.000 description 1
- 241000272808 Anser Species 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 101100129922 Caenorhabditis elegans pig-1 gene Proteins 0.000 description 1
- 101100520057 Drosophila melanogaster Pig1 gene Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010016825 Flushing Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000283903 Ovis aries Species 0.000 description 1
- 238000001069 Raman spectroscopy Methods 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000004807 desolvation Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 231100000206 health hazard Toxicity 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 231100000334 hepatotoxic Toxicity 0.000 description 1
- 244000038280 herbivores Species 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- -1 liver damage Chemical compound 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 235000020912 omnivore Nutrition 0.000 description 1
- 244000054334 omnivore Species 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
- A61K38/443—Oxidoreductases (1) acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/44—Oxidoreductases (1)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/54—Mixtures of enzymes or proenzymes covered by more than a single one of groups A61K38/44 - A61K38/46 or A61K38/51 - A61K38/53
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/0004—Oxidoreductases (1.)
- C12N9/0008—Oxidoreductases (1.) acting on the aldehyde or oxo group of donors (1.2)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y102/00—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2)
- C12Y102/01—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2) with NAD+ or NADP+ as acceptor (1.2.1)
- C12Y102/0101—Acetaldehyde dehydrogenase (acetylating) (1.2.1.10)
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
- C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
- C12Y101/01001—Alcohol dehydrogenase (1.1.1.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y102/00—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2)
- C12Y102/01—Oxidoreductases acting on the aldehyde or oxo group of donors (1.2) with NAD+ or NADP+ as acceptor (1.2.1)
- C12Y102/01003—Aldehyde dehydrogenase (NAD+) (1.2.1.3)
Definitions
- the present invention relates to a dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith, and, more particularly, to assisted enzyme-based breakdown of alcohol within the human body.
- ethanol ingested beverage alcohol
- the primary enzymes in the human body involved in ethanol metabolism are Alcohol Dehydrogenase (“ADH”) and Aldehyde Dehydrogenase (“ALDH”).
- ADH Alcohol Dehydrogenase
- ALDH Aldehyde Dehydrogenase
- the main pathway of ethanol metabolism involves its oxidation to acetaldehyde, a reaction that is catalysed by ADH and co-enzyme NAD+.
- acetaldehyde is oxidized to acetic acid. This metabolism is illustrated as FIG. 1 .
- the mechanism through which ADH and ALDH influences alcoholism risk is thought to involve local elevation of acetaldehyde levels, resulting either from a more rapid ethanol oxidation or from a slower acetaldehyde oxidation.
- Acetaldehyde is a toxic substance whose accumulation leads to highly adverse reactions that include facial flushing, nausea, rapid heart rate and veisalgia, and symptoms associated therewith ( FIG. 1 ).
- NAFLD Non-Alcoholic Fatty Liver Disease
- a composition including two exogenous enzymes from animals for consumption by human beings before and/or after consuming alcohol to prevent, treat and/or alleviate veisalgia and/or symptoms associated therewith arising from or caused by consumption of alcohol or production of alcohol in the body in patients with NAFLD, wherein a first enzyme of the two exogenous enzymes is capable of converting alcohol into a first metabolite while a second enzyme thereof is capable of converting the first metabolite into a second metabolite which is excretable to systemic circulation after an oxidation reaction of the alcohol in the presence of the two exogenous enzymes and NAD + /NADH, and wherein the first enzyme to the second enzyme is in a molar ratio of 1:3-51 in the composition in order to avoid local elevation of the first metabolite in the human being after consumption of alcohol.
- the first enzyme is alcohol dehydrogenase and the second enzyme is aldehyde dehydrogenase.
- the first enzyme to the second enzyme in the composition is in a molar ratio in the range of approximately 1:3 to approximately 1:51 (while our experiments have been conducted only up to a ratio of 1:51, variations in the sourced bovine liver material may increase the ratio by as much as 10% to 1:56).
- the local elevation of the first metabolite leads to veisalgia symptoms.
- the first metabolite is acetaldehyde.
- the second metabolite is acetate.
- the symptoms associated with veisalgia comprise fatigue, apathy, concentration problems, clumsiness, confusion, thirst, sweating, shivering, stomach pain, nausea, dizziness and heart pounding.
- the aldehyde dehydrogenase is represented by an amino acid sequence of SEQ ID NO: 1.
- the animals from which the two exogenous enzymes are comprise bovine, ovine, equine and galline.
- the exogenous enzymes are from livers of bovine, ovine, equine and galline.
- the at least two different exogeneous enzymes can be sourced from the same or two different origins of animal.
- the at least two different exogeneous enzymes are sourced from the same original of animal, and the animal is selected from bovine, ovine, equine, or galline.
- the at least two different exogeneous enzymes are sourced from different origins of animal, and the animal is selected from bovine, ovine, equine, galline, anas, or any combination thereof.
- the at least two different exogeneous enzymes are more abundant in livers than other body parts of the animal.
- the composition of the present invention is consumed orally by the subject before and/or after the alcohol consumption.
- the at least two different exogeneous enzymes can be in solid form.
- composition can also be formulated into a controlled-release system, and further include an enteric coating encapsulating the at least two different exogeneous enzymes to form an enteric capsule, tablet and/or pill.
- Another aspect of the present invention provides a method for lowering alcohol content and/or preventing accumulation of one of metabolites of the alcohol causing veisalgia and symptoms associated therewith in a subject, including consuming the composition of the present invention by the subject before and/or after consuming alcohol.
- the composition can be formulated in an enteric capsule, tablet, and/or pill which enables a controlled-release system of delivering the at least two different exogeneous enzymes to a target site of the subject.
- the at least two different exogeneous enzymes are delivered to blood streams via gastrointestinal tract of the subject.
- the at least two different exogeneous enzymes can be in solid form.
- FIG. 1 schematically illustrates the general mechanism of how ADH and ALDH2 metabolize alcohol in a human body.
- FIG. 2 shows the result of in vitro enzymatic activity of the present composition from extract of cows' liver in terms of the change in concentration of alcohol and its by-products or metabolites over time.
- FIG. 3 shows the result of in vitro enzymatic activity of the present composition from extract of lambs' liver in terms of the change in concentration of alcohol and its by-products or metabolites over time.
- FIG. 4 shows the result of in vitro enzymatic activity of the present composition from extract of sheep' liver in terms of the change in concentration of alcohol and its by-products or metabolites over time.
- FIG. 5 shows the result of in vitro enzymatic activity of the present composition from extract of horse liver in terms of the change in concentration of alcohol and its by-products or metabolites over time.
- FIG. 6 shows the result of in vitro enzymatic activity of the present composition from extract of donkey liver in terms of the change in concentration of alcohol and its by-products or metabolites over time.
- FIG. 7 shows the result of in vitro enzymatic activity of the present composition from extract of chicken liver in terms of the change in concentration of alcohol and its by-products or metabolites over time.
- FIG. 8 shows the result of in vitro enzymatic activity from an extract of duck liver in terms of the change in concentration of alcohol and its by-products or metabolites over time showing no increase in acetate due to the liver not containing ALDH.
- FIG. 9 shows the result of in vitro enzymatic activity from an extract of pig liver in terms of the change in concentration of alcohol and its by-products or metabolites over time showing no increase in acetate due to the liver not containing ALDH.
- FIG. 10 shows the result of in vitro enzymatic activity of the contents of ADH and ALDH from cows' liver extract during heating of the extract.
- FIG. 11 shows the result of in vitro enzymatic activity of the contents of ADH and ALDH from horse liver extract during heating of the extract.
- FIG. 12 shows the result of in vitro enzymatic activity of the contents of ADH and ALDH from donkey liver extract during heating of the extract.
- FIG. 13 shows the basic criteria of a survey to the effect of the present composition of this invention on the severity of veisalgia by using Alcohol Hangover Severity Scale (AHSS).
- AHSS Alcohol Hangover Severity Scale
- I.M. intramuscular I.V.—intravenous NAFLD—non-alcoholic fatty liver disease
- any numerical value or range presented with the term “about’, “approximately”, or alike, is understood by a skilled artisan to refer to also include those values near a recited value or near the upper and lower limits of a recited range.
- “about 40 [units]” may mean within ⁇ 25% of 40 (e.g., from 30 to 50), within ⁇ 20%, ⁇ 15%, ⁇ 10%, ⁇ 9%, ⁇ 8%, ⁇ 7%, ⁇ 7%, ⁇ 5%, ⁇ 4%, ⁇ 3%, ⁇ 2%, ⁇ 1%, less than ⁇ 1%, or any other value or range of values therein or therebelow.
- the terms “about” and “approximately” are used herein interchangeably throughout the present application.
- all values within a given range may be an endpoint for the range encompassed thereby (e.g., the range 50-80 includes the ranges with endpoints such as 55-80, 50-75, etc.).
- the terms “about” and “approximately,” when used in connection with a numeric value or a range of values which is provided to characterize a particular solid form e.g., a specific temperature or temperature range, such as, for example, that describing a melting, dehydration, desolvation or glass transition temperature; a mass change, such as, for example, a mass change as a function of temperature or humidity; a solvent or water content, in terms of, for example, mass or a percentage; or a peak position, such as, for example, in analysis by IR, Raman spectroscopy or XRPD; and to indicate that the value or range of values may deviate to an extent deemed reasonable to one of ordinary skill in the art while still describing the particular solid form.
- the terms “about” and “approximately,” when used in this context, indicate that the numeric value or range of values may vary within 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1.5%, 1%, 0.5%, or 0.25% of the recited value or range of values.
- a tilde i.e., “ ⁇ ⁇ ”
- preceding a numerical value or range of values indicates “about” or “approximately”.
- Enzymes are macromolecular biological catalysts, which can accelerate chemical reactions in the human body. Almost all metabolic processes in cells need enzyme catalysis in order to occur at rates fast enough to sustain life. Enzymes are known to catalyse more than 5,000 biochemical reactions. Most enzymes are proteins, and the specificity comes from their unique three-dimensional structures. As many enzymes are naturally produced by the human body, they are safe to use as supplements that may be ingested.
- the present invention focuses on two enzymes for alcohol metabolism, namely Alcohol Dehydrogenase (“ADH”) and Aldehyde Dehydrogenase (“ALDH”).
- ADH is an enzyme found primarily in the liver and stomach that converts ethanol to acetaldehyde, a toxin which is then further broken down by ALDH to acetate, which can be converted to carbon dioxide and water.
- ALDH Aldehyde Dehydrogenase
- compositions may be effective in reducing or preventing NAFLD.
- ADH and ALDH were tested, in vitro, to determine activity on ethanol substrates.
- the ADH and ALDH were sourced from mammal or ayes livers, a plentiful natural source for the starting material that can contribute to production of a low-cost oral supplement.
- the enzymes tested use a molar ratio of ADH and ALDH ranging from approximately 1:3 to approximately 1:51, to enable the second step of the enzymatic alcohol degradation process to be the dominant enzymatic reaction.
- the rationale for developing such a formulation is to prevent the accumulation of acetaldehyde, which is the major cause of veisalgia and symptoms associated therewith. Using this formulation, acetaldehyde, the breakdown product from alcohol in the first step of enzymatic process, is effectively degraded to acetic acid and eventually water and carbon dioxide.
- the ADH and ALDH from the livers of nine animals including cow, lamb, sheep, pig, horse, donkey, chicken, duck and goose were tested, in vitro, to determine activity on alcohol and aldehyde substrates in order to find out the molar ratio of ADH:ALDH from their liver extract. Pig, duck and goose livers were found not to contain ALDH.
- Table 1 summarizes the in vitro test results of the molar ratio of ADH:ALDH in each animal.
- the enzymes extracted from the livers of the nine animals were tested in vitro and only six of them including cows, lamb, sheep, horse, donkey and chicken were found to contain both ADH and ALDH. From the test results, the range of the molar ratio of ADH:ALDH among these six animals is from approximately 1:3 to approximately 1:51.
- liver extract from cows, lamb, sheep, horse, donkey and chicken are illustrated in Table 1, FIG. 2 to FIG. 7 respectively.
- livers of herbivores contained both ADH and ALDH; for omnivores that eat both plant and animal matter, their livers contained only ADH but did not have ALDH.
- the present invention produces a high-quality therapeutic enzyme remedy in an enteric capsule form to enhance degradation of alcohol in the human body, in order to relieve veisalgia and symptoms associated therewith for both casual and frequent alcohol drinkers.
- It is a freeze-dried powder from extract of bovine, ovine, equine or galline liver, or a mixture of extracts from different animals, by proprietary extraction and isolation methods that produce a product safe for human consumption and effective for alcohol degradation.
- ADH and ALDH enzymes are successfully extracted from livers of different origin, including cow, lamb, sheep, horse, donkey or chicken. The extracts were freeze-dried and stored as dried powder.
- the present invention uses an inventive extraction method.
- the inventive extraction includes precise control of the heating and cooling of the extract from mammalian or ayes livers. It is found that when the extract from livers was heated to 40° C., an extract with the highest content of ADH, together with ADH and ALDH enzymes contents in the molar ratio range from approximately 1:3 to approximately 1:51, can be obtained.
- the in vitro enzymatic activity of contents of ADH and ALDH from the liver extract of cows, horse and donkey in this heating process are illustrated in FIG. 10 to FIG. 12 .
- the therapeutic enzyme of the present invention could not be produced from the livers of pig, duck or goose. From an in vitro study of the present invention, ALDH was not present in the liver extract from pig, duck or goose, where ALDH is one of the main components in the present composition.
- the extracted enzymes may be packaged with antioxidants in enteric capsules.
- Antioxidants along with other optional excipients, can protect the enzymes from degradation in order to maintain a longer shelf-life with maximum efficacy.
- Oral supplements according to the present invention may be used in the following manner:
- ALD Alcoholic Liver Disease
- NAFLD non-alcoholic fatty liver disease
- the subjects were successfully recruited and were asked to complete the same questionnaire twice during the 1-month test period.
- the subjects drank 150 ml to 550 ml of an alcoholic beverage with an alcohol content ranging from 15% to 55% along with food.
- the questionnaire was completed on the next day 8-12 hours after the alcohol consumption, where one questionnaire for each subject was completed under their normal alcohol intake practice, and the other was completed with taking the freeze-dried powder from cow's liver extract encapsulated in enteric capsule before alcohol consumption. Twelve symptoms including fatigue, apathy, concentration problems, clumsiness, confusion, thirst, sweating, shivering, stomach pain, nausea, dizziness and heart pounding were used to evaluate the severity of veisalgia for all subjects
- the subjects were asked to indicate to what extent they experienced the 12 symptoms mentioned above after they woke up. It can be seen that 2 subjects did not develop veisalgia and/or any symptoms associated therewith, no matter with or without taking the above mentioned composition during the test period; 22 subjects developed veisalgia and/or symptoms associated therewith, in the absence of the above mentioned composition, but veisalgia or the associated symptoms was/were relieved after taking the above mentioned composition; 1 subject developed veisalgia and the associated symptoms, whether or not the above mentioned composition was taken. From the AHSS survey, about 88% of the subjects had a positive response towards to the above-mentioned composition, with significant relief of their veisalgia and the associated symptoms after the alcohol consumption.
- the subjects were asked to indicate to what extent they experienced the 12 symptoms mentioned above after they woke up. It can be seen that 8 subjects developed veisalgia and/or symptoms associated therewith, in the absence of the above-mentioned composition, but veisalgia or the associated symptoms was/were relieved after taking the above-mentioned composition; 1 subject developed mild veisalgia and the associated symptoms, whether or not the above-mentioned composition was taken. From the AHSS survey, about 89% of the subjects had a positive response towards to the above-mentioned composition, with significant relief of their veisalgia and the associated symptoms after the alcohol consumption.
- the compositions may be effective in reducing or preventing NAFLD.
- the enzyme compositions of the present invention may be used as an oral or injectable medication which can rapidly remove alcohol in emergency situations of acute alcohol intoxication.
- the present composition can reduce and prevent the severity of acute alcohol intoxication by efficiently converting alcohol to non-harmful substances before body tissues and organs, for instance, liver, uptake harmful levels of alcohol from blood.
- recombinant DNA technology by introducing mammalian expression vectors carrying genes of human h-ADH and h-ALDH into safe and well-studied mammalian cell lines may be employed. These mammalian-cells-expressed target enzymes are further isolated and purified by chromatographic techniques.
- the present invention is useful to produce clinical grade h-ADH and h-ALDH for effective intravenous (“I.V.”) or intramuscular (“I.M.”) infusion of therapeutic enzyme remedies for emergency use in hospitals and clinics.
- the human genome includes 19 ALDH genes.
- ALDH1 is primarily found in the liver and may be used in the enzyme extract version of the present invention.
- Another ALDH is ALDH2 which is found in the mitochondria.
- ALDH2 may be selected as the ALDH used in the present invention; its sequence is represented by SEQ ID NO: 1:
- Recombinant ALDH such as ALDH2 is commercially available from suppliers such as Sigma Aldrich. Examples of recombinant techniques to product ALD and ALDH are described in Nene et al., J. Biomed. Sci. 2017, 24: 3, published 5 Jan. 2017, the disclosure of which is incorporated by reference herein.
- the active ingredients in the formulation of the present invention may be incorporated into an oral formulation that may be administered as a dietary supplement product.
- a potential health benefit of this product is to relieve veisalgia and the associated symptoms for casual and frequent alcohol drinkers. The product should be taken before consuming alcohol.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
Abstract
A composition includes two exogenous enzymes from animals for consumption by human beings to prevent, treat and/or alleviate veisalgia and/or symptoms associated therewith arising from or caused by consumption or spontaneous production of alcohol through a dual-enzyme based breakdown of the alcohol, wherein a first enzyme of the two exogenous enzymes is capable of converting alcohol into a first metabolite while a second enzyme thereof is capable of converting the first metabolite into a second metabolite which is excretable to systemic circulation after an oxidation reaction of the alcohol in the presence of the two exogenous enzymes and NAD+/NADH, and wherein the first enzyme to the second enzyme is in a molar ratio of 1:3-51 in the composition in order to avoid an elevation in the level of the first metabolite in the human being.
Description
- This application is a continuation-in-part of the U.S. non-provisional patent application Ser. No. 17/308,995 filed May 5, 2021 and issued under the U.S. Pat. No. 11,208,631 on Dec. 28, 2021, and the disclosure of which is incorporated herein by reference in its entirety.
- The present invention relates to a dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith, and, more particularly, to assisted enzyme-based breakdown of alcohol within the human body.
- The effect of ingested beverage alcohol (ethanol) on different organs in human body, including the brain/Central Nervous System, liver & pancreas, depends on the ethanol concentration intake and the duration of exposure. Both of these variables are affected by the absorption of ethanol into the blood stream and tissues as well as by ethanol metabolism5. The primary enzymes in the human body involved in ethanol metabolism are Alcohol Dehydrogenase (“ADH”) and Aldehyde Dehydrogenase (“ALDH”). The main pathway of ethanol metabolism involves its oxidation to acetaldehyde, a reaction that is catalysed by ADH and co-enzyme NAD+. In a second reaction catalyzed by ALDH and co-enzyme NAD+, acetaldehyde is oxidized to acetic acid. This metabolism is illustrated as
FIG. 1 . The mechanism through which ADH and ALDH influences alcoholism risk is thought to involve local elevation of acetaldehyde levels, resulting either from a more rapid ethanol oxidation or from a slower acetaldehyde oxidation. Acetaldehyde is a toxic substance whose accumulation leads to highly adverse reactions that include facial flushing, nausea, rapid heart rate and veisalgia, and symptoms associated therewith (FIG. 1 ). - Recently, many people use over-the-counter pain relievers, like aspirin or acetaminophen, to relieve veisalgia and symptoms associated therewith. It is important to recognize that the combination of alcohol and acetaminophen can be toxic to the liver. Furthermore, there is no medication for acute alcohol intoxication. Haemodialysis is the only option in emergency cases, especially in the US, where the medicine Metadoxin has not been approved by the FDA. Consequently, the development of innovative preventive measures which can effectively minimize the risk of potential health hazards brought about by drinking alcohol has become a very important strategy to lessen the burden on the overall economy. There is a huge void in the healthcare market for a product which is effective, safe and convenient for daily use as a prophylaxis measure for casual and frequent alcohol drinkers and patients suffering from alcohol use disorder.
- As seen from the various alcohol ingestion-related problems, there is a need in the art to enhance the breakdown of alcohol in the human body. Enhanced breakdown of alcohol and alcohol metabolism products would reduce long-term harmful effects from alcohol such as liver damage, and short-term effects such as veisalgia and alcohol poisoning. Thus, there is a need in the art for compositions that can enhance the breakdown of alcohol in the human body that are low-cost and have minimal side effects.
- In addition, certain populations may experience spontaneous production of alcohol in the gut, leading to a common condition known as Non-Alcoholic Fatty Liver Disease (“NAFLD”). A composition that would metabolize such spontaneously accumulated alcohol would relieve the suffering of large numbers of persons with this ailment.
- In one aspect, there is provided a composition including two exogenous enzymes from animals for consumption by human beings before and/or after consuming alcohol to prevent, treat and/or alleviate veisalgia and/or symptoms associated therewith arising from or caused by consumption of alcohol or production of alcohol in the body in patients with NAFLD, wherein a first enzyme of the two exogenous enzymes is capable of converting alcohol into a first metabolite while a second enzyme thereof is capable of converting the first metabolite into a second metabolite which is excretable to systemic circulation after an oxidation reaction of the alcohol in the presence of the two exogenous enzymes and NAD+/NADH, and wherein the first enzyme to the second enzyme is in a molar ratio of 1:3-51 in the composition in order to avoid local elevation of the first metabolite in the human being after consumption of alcohol.
- In one embodiment, the first enzyme is alcohol dehydrogenase and the second enzyme is aldehyde dehydrogenase.
- In another embodiment, the first enzyme to the second enzyme in the composition is in a molar ratio in the range of approximately 1:3 to approximately 1:51 (while our experiments have been conducted only up to a ratio of 1:51, variations in the sourced bovine liver material may increase the ratio by as much as 10% to 1:56).
- In other embodiment, the local elevation of the first metabolite leads to veisalgia symptoms.
- In yet another embodiment, the first metabolite is acetaldehyde.
- In other embodiment, the second metabolite is acetate.
- In also another embodiment, the symptoms associated with veisalgia comprise fatigue, apathy, concentration problems, clumsiness, confusion, thirst, sweating, shivering, stomach pain, nausea, dizziness and heart pounding.
- In an embodiment, the aldehyde dehydrogenase is represented by an amino acid sequence of SEQ ID NO: 1.
- In an embodiment, the animals from which the two exogenous enzymes are comprise bovine, ovine, equine and galline.
- In other embodiment, the exogenous enzymes are from livers of bovine, ovine, equine and galline.
- The at least two different exogeneous enzymes can be sourced from the same or two different origins of animal.
- More specifically, the at least two different exogeneous enzymes are sourced from the same original of animal, and the animal is selected from bovine, ovine, equine, or galline.
- Alternatively, the at least two different exogeneous enzymes are sourced from different origins of animal, and the animal is selected from bovine, ovine, equine, galline, anas, or any combination thereof.
- The at least two different exogeneous enzymes are more abundant in livers than other body parts of the animal.
- In certain exemplary embodiments, the composition of the present invention is consumed orally by the subject before and/or after the alcohol consumption.
- The at least two different exogeneous enzymes can be in solid form.
- The composition can also be formulated into a controlled-release system, and further include an enteric coating encapsulating the at least two different exogeneous enzymes to form an enteric capsule, tablet and/or pill.
- Another aspect of the present invention provides a method for lowering alcohol content and/or preventing accumulation of one of metabolites of the alcohol causing veisalgia and symptoms associated therewith in a subject, including consuming the composition of the present invention by the subject before and/or after consuming alcohol.
- As described hereinabove, the composition can be formulated in an enteric capsule, tablet, and/or pill which enables a controlled-release system of delivering the at least two different exogeneous enzymes to a target site of the subject.
- The at least two different exogeneous enzymes are delivered to blood streams via gastrointestinal tract of the subject.
- As described hereinabove, the at least two different exogeneous enzymes can be in solid form.
- There is provided at least 89% of a population of the same subject is absent of veisalgia and symptoms associated therewith after consuming an effective amount of the composition prior to or after consumption of alcohol.
-
FIG. 1 schematically illustrates the general mechanism of how ADH and ALDH2 metabolize alcohol in a human body. -
FIG. 2 shows the result of in vitro enzymatic activity of the present composition from extract of cows' liver in terms of the change in concentration of alcohol and its by-products or metabolites over time. -
FIG. 3 shows the result of in vitro enzymatic activity of the present composition from extract of lambs' liver in terms of the change in concentration of alcohol and its by-products or metabolites over time. -
FIG. 4 shows the result of in vitro enzymatic activity of the present composition from extract of sheep' liver in terms of the change in concentration of alcohol and its by-products or metabolites over time. -
FIG. 5 shows the result of in vitro enzymatic activity of the present composition from extract of horse liver in terms of the change in concentration of alcohol and its by-products or metabolites over time. -
FIG. 6 shows the result of in vitro enzymatic activity of the present composition from extract of donkey liver in terms of the change in concentration of alcohol and its by-products or metabolites over time. -
FIG. 7 shows the result of in vitro enzymatic activity of the present composition from extract of chicken liver in terms of the change in concentration of alcohol and its by-products or metabolites over time. -
FIG. 8 shows the result of in vitro enzymatic activity from an extract of duck liver in terms of the change in concentration of alcohol and its by-products or metabolites over time showing no increase in acetate due to the liver not containing ALDH. -
FIG. 9 shows the result of in vitro enzymatic activity from an extract of pig liver in terms of the change in concentration of alcohol and its by-products or metabolites over time showing no increase in acetate due to the liver not containing ALDH. -
FIG. 10 shows the result of in vitro enzymatic activity of the contents of ADH and ALDH from cows' liver extract during heating of the extract. -
FIG. 11 shows the result of in vitro enzymatic activity of the contents of ADH and ALDH from horse liver extract during heating of the extract. -
FIG. 12 shows the result of in vitro enzymatic activity of the contents of ADH and ALDH from donkey liver extract during heating of the extract. -
FIG. 13 shows the basic criteria of a survey to the effect of the present composition of this invention on the severity of veisalgia by using Alcohol Hangover Severity Scale (AHSS). - The following abbreviations and their corresponding long expressions are used herein interchangeably:
- I.M.—intramuscular
I.V.—intravenous
NAFLD—non-alcoholic fatty liver disease - Throughout the present application, any numerical value or range presented with the term “about’, “approximately”, or alike, is understood by a skilled artisan to refer to also include those values near a recited value or near the upper and lower limits of a recited range. For example, “about 40 [units]” may mean within ±25% of 40 (e.g., from 30 to 50), within ±20%, ±15%, ±10%, ±9%, ±8%, ±7%, ±7%, ±5%, ±4%, ±3%, ±2%, ±1%, less than ±1%, or any other value or range of values therein or therebelow. Also, the terms “about” and “approximately” are used herein interchangeably throughout the present application.
- Further, the term “approximately” is to cover minor variations to the composition that do not affect the activity of the overall composition. That is, minor changes that produce the same effects as the claimed composition are intended to be included in the scope of the appended claims.
- For numerical ranges provided for certain quantities, it should be understood that these ranges also cover subranges therein. For example, the range “from 50 to 80” includes all possible ranges therein (e.g., 51-79, 52-78, 53-77, 54-76, 55-75, 70-70, etc.).
- Furthermore, all values within a given range may be an endpoint for the range encompassed thereby (e.g., the range 50-80 includes the ranges with endpoints such as 55-80, 50-75, etc.).
- As used herein and unless otherwise specified, the terms “about” and “approximately,” when used in connection with a numeric value or a range of values which is provided to characterize a particular solid form, e.g., a specific temperature or temperature range, such as, for example, that describing a melting, dehydration, desolvation or glass transition temperature; a mass change, such as, for example, a mass change as a function of temperature or humidity; a solvent or water content, in terms of, for example, mass or a percentage; or a peak position, such as, for example, in analysis by IR, Raman spectroscopy or XRPD; and to indicate that the value or range of values may deviate to an extent deemed reasonable to one of ordinary skill in the art while still describing the particular solid form. For example, in particular embodiments, the terms “about” and “approximately,” when used in this context, indicate that the numeric value or range of values may vary within 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1.5%, 1%, 0.5%, or 0.25% of the recited value or range of values. As used herein, a tilde (i.e., “˜˜”) preceding a numerical value or range of values indicates “about” or “approximately”.
- Further, it is understood that, when active ingredient ranges are applied to human populations, there is a wide range of body weights that receive approximately the same dosage. Therefore, the amount of active ingredient per kg of body weight has a natural range when a dose of, for example, 100 mg is applied to patients with weights ranging from 50 kg to over 100 kg. Therefore, the experimental results shown in the present disclosure can naturally be extrapolated over the ranges described as “approximate” and “about” as set forth above.
- 1. Mechanism of the Present Invention:
- Enzymes are macromolecular biological catalysts, which can accelerate chemical reactions in the human body. Almost all metabolic processes in cells need enzyme catalysis in order to occur at rates fast enough to sustain life. Enzymes are known to catalyse more than 5,000 biochemical reactions. Most enzymes are proteins, and the specificity comes from their unique three-dimensional structures. As many enzymes are naturally produced by the human body, they are safe to use as supplements that may be ingested.
- The present invention focuses on two enzymes for alcohol metabolism, namely Alcohol Dehydrogenase (“ADH”) and Aldehyde Dehydrogenase (“ALDH”). ADH is an enzyme found primarily in the liver and stomach that converts ethanol to acetaldehyde, a toxin which is then further broken down by ALDH to acetate, which can be converted to carbon dioxide and water. These two enzymes were studied using in vitro assays, proving that the corresponding enzymatic activity is highly potent, and could potentially be used to enhance the degradation of alcohol in the human body for alcohol drinkers to prevent as well as treat and/or alleviate veisalgia and symptoms associated therewith. These enzymes may also be used to treat those whose faulty microbiomes are overproducing ethanol from non-alcohol-based food and beverages leading to non-alcoholic fatty liver disease (“NAFLD”). Thus, the compositions may be effective in reducing or preventing NAFLD.
- In one aspect, ADH and ALDH were tested, in vitro, to determine activity on ethanol substrates. The ADH and ALDH were sourced from mammal or ayes livers, a plentiful natural source for the starting material that can contribute to production of a low-cost oral supplement.
- The enzymes tested use a molar ratio of ADH and ALDH ranging from approximately 1:3 to approximately 1:51, to enable the second step of the enzymatic alcohol degradation process to be the dominant enzymatic reaction. The rationale for developing such a formulation is to prevent the accumulation of acetaldehyde, which is the major cause of veisalgia and symptoms associated therewith. Using this formulation, acetaldehyde, the breakdown product from alcohol in the first step of enzymatic process, is effectively degraded to acetic acid and eventually water and carbon dioxide.
- 2. Formulations Used in the Present Invention
- The ADH and ALDH from the livers of nine animals including cow, lamb, sheep, pig, horse, donkey, chicken, duck and goose were tested, in vitro, to determine activity on alcohol and aldehyde substrates in order to find out the molar ratio of ADH:ALDH from their liver extract. Pig, duck and goose livers were found not to contain ALDH.
-
-
- The cow liver is sourced from Australia in frozen form. The in vitro enzymatic activity results from liver of cows (from dry powder of cows' liver extract when the concentration is about 50 mg/ml) for ADH is on average 3.25 Unit and for ALDH is on average 91.31 Unit. The molar ratio of ADH:ALDH is rounded up to 1:28.
-
-
- The lamb liver is sourced from Australia in frozen form. The in vitro enzymatic activity results from liver of lamb (from dry powder of lamb liver extract when concentration is about 50 mg/ml) for ADH is on average 1.60 Unit and for ALDH is on average 63.09 Unit. The molar ratio of ADH:ALDH is rounded up to 1:39.
-
-
- The sheep liver is sourced from Australia in frozen form. The in vitro enzymatic activity results from the livers of sheep (from dry powder of sheep liver extract when concentration is about 50 mg/ml) for ADH is on average 0.80 Unit and for ALDH is on average 40.65 Unit. The molar ratio of ADH:ALDH is rounded up to 1:51.
-
-
- The pig liver is sourced from local markets in Hong Kong and is fresh. Pig liver was determined to only have the ADH enzyme without the ALDH enzyme. The in vitro enzymatic activity results from the liver of pigs (from dry powder of pig liver extract when concentration is about 50 mg/ml) for ADH is 3.51 Unit. As seen in
FIG. 9 , there is no increase in acetate due to the liver not containing ALDH.
- The pig liver is sourced from local markets in Hong Kong and is fresh. Pig liver was determined to only have the ADH enzyme without the ALDH enzyme. The in vitro enzymatic activity results from the liver of pigs (from dry powder of pig liver extract when concentration is about 50 mg/ml) for ADH is 3.51 Unit. As seen in
-
-
- The horse liver is sourced from China in frozen form. The in vitro enzymatic activity results from the livers of horses (from supernatant of crude extract of horse liver) for ADH is 9.04 Unit and for ALDH is 42.67 Unit. The molar ratio of ADH:ALDH is rounded up to 1:5.
-
-
- The donkey liver is sourced from China in fresh form. The in vitro enzymatic activity results from livers of donkeys (from supernatant of crude extract of donkey liver) for ADH is 9.87 Unit and for ALDH is 184.00 Unit. The molar ratio of ADH:ALDH is rounded up to 1:19.
-
-
- The chicken liver is sourced from local markets in Hong Kong in fresh form. The in vitro enzymatic activity results from livers of chickens (from supernatant of crude extract of chicken liver) for ADH is 2.96 Unit and for ALDH is 8.09 Unit. The molar ratio of ADH:ALDH is rounded up to 1:3.
-
-
- The duck liver is sourced from local markets in Hong Kong in fresh form. Duck liver was determined to have only ADH enzyme without ALDH enzyme. The in vitro enzymatic activity results from livers of ducks (from supernatant of crude extract of duck liver) for ADH is 1.32 Unit. As seen in
FIG. 8 , there is no increase in acetate due to the liver not containing ALDH.
- The duck liver is sourced from local markets in Hong Kong in fresh form. Duck liver was determined to have only ADH enzyme without ALDH enzyme. The in vitro enzymatic activity results from livers of ducks (from supernatant of crude extract of duck liver) for ADH is 1.32 Unit. As seen in
-
-
- The goose liver is sourced from Hungary in frozen form. The goose liver is foie gras and contains too much fat in the liver, as a result, in vitro test of ADH & ALDH enzymes cannot be done.
- Table 1 summarizes the in vitro test results of the molar ratio of ADH:ALDH in each animal.
-
TABLE 1 Ratio Animal ADH:ALDH Cows 1:28 Lamb 1:39 Sheep 1:51 Pig 1:0 Horse 1:5 Donkey 1:19 Chicken 1:3 Duck 1:0 Goose 0:0 - The enzymes extracted from the livers of the nine animals were tested in vitro and only six of them including cows, lamb, sheep, horse, donkey and chicken were found to contain both ADH and ALDH. From the test results, the range of the molar ratio of ADH:ALDH among these six animals is from approximately 1:3 to approximately 1:51.
- The in vitro enzymatic activity of liver extract from cows, lamb, sheep, horse, donkey and chicken are illustrated in Table 1,
FIG. 2 toFIG. 7 respectively. - From the results, it can be concluded that the livers of herbivores contained both ADH and ALDH; for omnivores that eat both plant and animal matter, their livers contained only ADH but did not have ALDH.
- In one aspect, the present invention produces a high-quality therapeutic enzyme remedy in an enteric capsule form to enhance degradation of alcohol in the human body, in order to relieve veisalgia and symptoms associated therewith for both casual and frequent alcohol drinkers. It is a freeze-dried powder from extract of bovine, ovine, equine or galline liver, or a mixture of extracts from different animals, by proprietary extraction and isolation methods that produce a product safe for human consumption and effective for alcohol degradation.
- Using extraction and isolation methods, ADH and ALDH enzymes are successfully extracted from livers of different origin, including cow, lamb, sheep, horse, donkey or chicken. The extracts were freeze-dried and stored as dried powder.
- From the in-house stability test of the freeze-dried powder from bovine and ovine liver extract, it shows very good stability when stored more than 12 months at room temperature and dry humidity.
- The present invention uses an inventive extraction method. The inventive extraction includes precise control of the heating and cooling of the extract from mammalian or ayes livers. It is found that when the extract from livers was heated to 40° C., an extract with the highest content of ADH, together with ADH and ALDH enzymes contents in the molar ratio range from approximately 1:3 to approximately 1:51, can be obtained. The in vitro enzymatic activity of contents of ADH and ALDH from the liver extract of cows, horse and donkey in this heating process are illustrated in
FIG. 10 toFIG. 12 . - Therefore, the therapeutic enzyme of the present invention could not be produced from the livers of pig, duck or goose. From an in vitro study of the present invention, ALDH was not present in the liver extract from pig, duck or goose, where ALDH is one of the main components in the present composition.
- Optionally, the extracted enzymes may be packaged with antioxidants in enteric capsules. Antioxidants, along with other optional excipients, can protect the enzymes from degradation in order to maintain a longer shelf-life with maximum efficacy.
- Oral supplements according to the present invention may be used in the following manner:
- 1. To enhance alcohol metabolism in the human body in order to relieve veisalgia and symptoms associated therewith.
- 2. To degrade alcohol to prevent Alcoholic Liver Disease (“ALD”) and non-alcoholic fatty liver disease (NAFLD).
- Two surveys were conducted by selecting subjects fulfilling the basic criteria shown in
FIG. 11 to evaluate the effect of the present composition of this invention on the severity of veisalgia by using Alcohol Hangover Severity Scale (AHSS). - Survey 1—Test of freeze-dried powder from cows' liver extract (ADH:ALDH 1:28) encapsulated in enteric capsule:
- Twenty-five subjects were successfully recruited and were asked to complete the same questionnaire twice during the 1-month test period. The subjects drank 150 ml to 550 ml of an alcoholic beverage with an alcohol content ranging from 15% to 55% along with food. The questionnaire was completed on the next day 8-12 hours after the alcohol consumption, where one questionnaire for each subject was completed under their normal alcohol intake practice, and the other was completed with taking the freeze-dried powder from cow's liver extract encapsulated in enteric capsule before alcohol consumption. Twelve symptoms including fatigue, apathy, concentration problems, clumsiness, confusion, thirst, sweating, shivering, stomach pain, nausea, dizziness and heart pounding were used to evaluate the severity of veisalgia for all subjects
- The subjects were asked to indicate to what extent they experienced the 12 symptoms mentioned above after they woke up. It can be seen that 2 subjects did not develop veisalgia and/or any symptoms associated therewith, no matter with or without taking the above mentioned composition during the test period; 22 subjects developed veisalgia and/or symptoms associated therewith, in the absence of the above mentioned composition, but veisalgia or the associated symptoms was/were relieved after taking the above mentioned composition; 1 subject developed veisalgia and the associated symptoms, whether or not the above mentioned composition was taken. From the AHSS survey, about 88% of the subjects had a positive response towards to the above-mentioned composition, with significant relief of their veisalgia and the associated symptoms after the alcohol consumption.
- Survey 2—Test of freeze-dried powder from donkey liver extract (ADH:ALDH 1:19) encapsulated in enteric capsule:
- Nine subjects were successfully recruited and were asked to complete the same questionnaire twice during the 1-month test period. The subjects drank 100 ml to 300 ml of alcoholic beverage with alcohol content ranging from 50% to 53% with food. The questionnaire was completed on the next day 8-12 hours after alcohol consumption, where one questionnaire for each subject was completed under their normal alcohol intake practice, and the other was completed after taking the freeze-dried powder from donkey liver extract encapsulated in enteric capsule before alcohol consumption. Twelve symptoms including fatigue, apathy, concentration problems, clumsiness, confusion, thirst, sweating, shivering, stomach pain, nausea, dizziness and heart pounding were used to evaluate the severity of veisalgia for all subjects
- The subjects were asked to indicate to what extent they experienced the 12 symptoms mentioned above after they woke up. It can be seen that 8 subjects developed veisalgia and/or symptoms associated therewith, in the absence of the above-mentioned composition, but veisalgia or the associated symptoms was/were relieved after taking the above-mentioned composition; 1 subject developed mild veisalgia and the associated symptoms, whether or not the above-mentioned composition was taken. From the AHSS survey, about 89% of the subjects had a positive response towards to the above-mentioned composition, with significant relief of their veisalgia and the associated symptoms after the alcohol consumption.
- As determined from the plots in
FIG. 2 toFIG. 7 , the equilibrium mid-point of ethanol and acetate from the in vitro tests were determined. The equilibrium mid-points are listed in Table 2. -
TABLE 2 Ratio Equilibrium mid Animal ADH:ALDH point (seconds) Cows 1:28 88 Lamb 1:39 100 Sheep 1:51 102 Horse 1:5 75 Donkey 1:19 73 Chicken 1:3 95 - From the data in Table 2, it can be seen that even though the ratios of ADH:ALDH vary from 1:3 to 1:51 from the 6 animals (cows, lamb, sheep, horse, donkey and chicken), each ADH:ALDH ratio demonstrates a similar equilibrium mid-point for ethanol and acetate. That is, the in vitro experiments indicate that all ratios are effective on breaking down alcohol, and then acetaldehyde, into their respective metabolites, at approximately the same rate without the accumulation of the first metabolites. Further, the results of the two surveys set forth above show substantially similar reductions in veisalgia symptoms for ADH:ALDH of 1:19 and 1:28. Therefore, based on the similar equilibrium midpoints and the human survey results, it has been determined that the breakdown of metabolites is efficacious over the entire range from 1:3 to at least 1:51. Consequently, the different ratios of ADH:ALDH in the range from 1:3 to 1:51 in the composition will be efficacious in reducing veisalgia symptoms. Further, based on these same metabolic mechanisms, the compositions may be effective in reducing or preventing NAFLD.
- At higher doses, the enzyme compositions of the present invention may be used as an oral or injectable medication which can rapidly remove alcohol in emergency situations of acute alcohol intoxication. The present composition can reduce and prevent the severity of acute alcohol intoxication by efficiently converting alcohol to non-harmful substances before body tissues and organs, for instance, liver, uptake harmful levels of alcohol from blood.
- For injectable formulations and optionally for oral formulations, recombinant DNA technology by introducing mammalian expression vectors carrying genes of human h-ADH and h-ALDH into safe and well-studied mammalian cell lines may be employed. These mammalian-cells-expressed target enzymes are further isolated and purified by chromatographic techniques. The present invention is useful to produce clinical grade h-ADH and h-ALDH for effective intravenous (“I.V.”) or intramuscular (“I.M.”) infusion of therapeutic enzyme remedies for emergency use in hospitals and clinics.
- The human genome includes 19 ALDH genes. ALDH1 is primarily found in the liver and may be used in the enzyme extract version of the present invention. Another ALDH is ALDH2 which is found in the mitochondria. ALDH2 may be selected as the ALDH used in the present invention; its sequence is represented by SEQ ID NO: 1:
- MSAAATQAVP APNQQPEVFC NQIFINNEWH DAVSRKTFPT VNPSTGEVIC QVAEGDKEDV DKAVKAARAA FQLGSPWRRM DASHRGRLLN RLADLIERDR TYLAALETLD NGKPYVISYL VDLDMVLKCL RYYAGWADKY HGKTIPIDGD FFSYTRHEPV GVCGQIIPWN FPLLMQAWKL GPALATGNVV VMKVAEQTPL TALYVANLIK EAGFPPGVVN IVPGFGPTAG AAIASHEDVD KVAFTGSTEI GRVIQVAAGS SNLKRVTLEL GGKSPNIIMS DADMDWAVEQ AHFALFFNQG QCCCAGSRTF VQEDIYDEFV ERSVARAKSR VVGNPFDSKT EQGPQVDETQ FKKILGYINT GKQEGAKLLC GGGIAADRGY FIQPTVFGDV QDGMTIAKEE IFGPVMQILK FKTIEEVVGR ANNSTYGLAA AVFTKDLDKA NYLSQALQAG TVWVNCYDVF GAQSPFGGYK MSGSGRELGE YGLQAYTEVK TVTVKVPQKN S
- Recombinant ALDH such as ALDH2 is commercially available from suppliers such as Sigma Aldrich. Examples of recombinant techniques to product ALD and ALDH are described in Nene et al., J. Biomed. Sci. 2017, 24: 3, published 5 Jan. 2017, the disclosure of which is incorporated by reference herein.
- The active ingredients in the formulation of the present invention may be incorporated into an oral formulation that may be administered as a dietary supplement product. A potential health benefit of this product is to relieve veisalgia and the associated symptoms for casual and frequent alcohol drinkers. The product should be taken before consuming alcohol.
- The disclosures of each of the following references are incorporated by reference herein.
- 1. Thomas D. Hurley, Howard J. Edenberg, Ting-Kai Li. Pharmacogenomics of Alcoholism. In: Pharmacogenomics: The Search for Individualized Therapies, Germany Wiley-VCH, Weinheim, Chapter 21, p. 417-441.
- 2. Nene et al., J. Aldehyde dehydrogenase 2 activation and coevolution of its εPKC-mediated phosphorylation sites. Biomed. Sci. 2017, 24: 3.
Claims (19)
1. A composition for converting ethanol to acetaldehyde and subsequently converting the acetaldehyde to acetate, said composition comprising alcohol dehydrogenase and aldehyde dehydrogenase in a molar ratio of approximately 1:3 to 1:51.
2. (canceled)
3. The composition of claim 1 , wherein the alcohol dehydrogenase and aldehyde dehydrogenase are sourced from the same or two different animal origins.
4. The composition of claim 3 , wherein the alcohol dehydrogenase and aldehyde dehydrogenase are sourced from the same animal origin, and the animal is selected from bovine, ovine, equine, or galline.
5. The composition of claim 3 , wherein the alcohol dehydrogenase and aldehyde dehydrogenase are sourced from different animal origin, and the animal is selected from bovine, ovine, equine, galline, anas, or any combination thereof.
6. The composition of claim 3 , wherein the alcohol dehydrogenase and aldehyde dehydrogenase are more abundant in livers than other body parts of the animal.
7. The composition of claim 1 , wherein the composition is to be consumed orally by the subject before and/or after ethanol consumption.
8. The composition of claim 1 , wherein the alcohol dehydrogenase and aldehyde dehydrogenase are in solid form.
9. The composition of claim 1 , wherein the composition is a controlled-release system, and further comprises an enteric coating encapsulating the alcohol dehydrogenase and aldehyde dehydrogenase to form an enteric capsule, tablet and/or pill.
10. (canceled)
11. A method for lowering ethanol content and/or preventing accumulation of one of metabolites of the ethanol in a subject, the method comprising consuming the composition of claim 1 by the subject before and/or after consuming ethanol.
12. The method of claim 11 , wherein the composition is orally consumed by the subject before and/or after ethanol alcohol consumption.
13. The method of claim 11 , wherein the composition is formulated in an enteric capsule, tablet, and/or pill which enables a controlled-release system of delivering the alcohol dehydrogenase and aldehyde dehydrogenase to a target site of the subject.
14. The method of claim 13 , wherein the alcohol dehydrogenase and aldehyde dehydrogenase are delivered to blood streams via gastrointestinal tract of the subject.
15. (canceled)
16. (canceled)
17. The method of claim 11 , wherein the alcohol dehydrogenase and aldehyde dehydrogenase are in solid form.
18. (canceled)
19. (canceled)
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17/557,046 US11471514B1 (en) | 2021-05-05 | 2021-12-21 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
CN202210141982.0A CN114887041A (en) | 2021-05-05 | 2022-02-16 | Dual enzyme composition for preventing, treating and/or alleviating hangover and its related symptoms |
PCT/CN2022/090852 WO2022233288A1 (en) | 2021-05-05 | 2022-05-04 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
KR1020237041971A KR20240008330A (en) | 2021-05-05 | 2022-05-04 | Dual-enzyme compositions for preventing, treating and/or alleviating hangovers and related symptoms |
TW111116880A TW202243688A (en) | 2021-05-05 | 2022-05-04 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
EP22798629.6A EP4333988A1 (en) | 2021-05-05 | 2022-05-04 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
US17/947,195 US11795441B2 (en) | 2021-05-05 | 2022-09-19 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
CN202211467926.2A CN116270985A (en) | 2021-12-21 | 2022-11-22 | Dual enzyme composition for preventing, treating and/or alleviating hangover and symptoms associated therewith |
US18/465,961 US20240216479A1 (en) | 2021-05-05 | 2023-09-12 | Encapsulation of dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17/308,995 US11208631B1 (en) | 2021-05-05 | 2021-05-05 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
US17/557,046 US11471514B1 (en) | 2021-05-05 | 2021-12-21 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/308,995 Continuation-In-Part US11208631B1 (en) | 2021-05-05 | 2021-05-05 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/947,195 Continuation-In-Part US11795441B2 (en) | 2021-05-05 | 2022-09-19 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
Publications (2)
Publication Number | Publication Date |
---|---|
US11471514B1 US11471514B1 (en) | 2022-10-18 |
US20220354931A1 true US20220354931A1 (en) | 2022-11-10 |
Family
ID=82714723
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/557,046 Active US11471514B1 (en) | 2021-05-05 | 2021-12-21 | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
Country Status (6)
Country | Link |
---|---|
US (1) | US11471514B1 (en) |
EP (1) | EP4333988A1 (en) |
KR (1) | KR20240008330A (en) |
CN (1) | CN114887041A (en) |
TW (1) | TW202243688A (en) |
WO (1) | WO2022233288A1 (en) |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN100391448C (en) | 2003-11-19 | 2008-06-04 | 奥加生物药业(I.P.1)有限公司 | Materials and methods for improving alcohol metabolism and alleviating the effects of hangovers |
US20050271754A1 (en) | 2004-06-07 | 2005-12-08 | Cochrane Patrick W | Composition for prevention or treatment of an alcohol hangover |
US20050271739A1 (en) | 2004-06-08 | 2005-12-08 | Wang Xiang H | Methods and compositions for accelerating alcohol metabolism |
KR101925096B1 (en) | 2018-05-02 | 2018-12-04 | 아미코젠주식회사 | A manufacturing method of hangover-eliminating enzyme powder and a composition for relieving hangover comprising thereof |
US11208631B1 (en) | 2021-05-05 | 2021-12-28 | Alcolear Limited | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith |
-
2021
- 2021-12-21 US US17/557,046 patent/US11471514B1/en active Active
-
2022
- 2022-02-16 CN CN202210141982.0A patent/CN114887041A/en active Pending
- 2022-05-04 KR KR1020237041971A patent/KR20240008330A/en active Search and Examination
- 2022-05-04 WO PCT/CN2022/090852 patent/WO2022233288A1/en active Application Filing
- 2022-05-04 EP EP22798629.6A patent/EP4333988A1/en active Pending
- 2022-05-04 TW TW111116880A patent/TW202243688A/en unknown
Also Published As
Publication number | Publication date |
---|---|
TW202243688A (en) | 2022-11-16 |
EP4333988A1 (en) | 2024-03-13 |
CN114887041A (en) | 2022-08-12 |
WO2022233288A1 (en) | 2022-11-10 |
KR20240008330A (en) | 2024-01-18 |
US11471514B1 (en) | 2022-10-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Al Hafid et al. | Phenylketonuria: a review of current and future treatments | |
Ostojic et al. | Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans | |
Ayad et al. | Impact of feeding yeast culture on milk yield, milk components, and blood components in Algerian dairy herds. | |
JP2826808B2 (en) | Functional food with brain function improvement, learning ability enhancement and memory enhancement effect | |
US20160310545A1 (en) | Probiotic compositions and methods for inducing and supporting weight loss | |
JPH06315347A (en) | Food composition using bile acid salt activation lipase | |
US11208631B1 (en) | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith | |
KR20190015718A (en) | Compositions of probiotics and digestive enzymes and methods for their preparation | |
US9585852B2 (en) | Agmatine containing dietary supplements, nutraceuticals and foods | |
JP5592640B2 (en) | Antistress agent containing lactic acid bacteria fermented royal jelly, method for producing the same, hypothalamus-pituitary-adrenocortical activity inhibitor, and sympathetic-adrenal medullary activity inhibitor | |
Huntley et al. | Xylose metabolism in the pig | |
Doster | Bovine atypical interstitial pneumonia | |
Edwards et al. | Immunogenic inhibition of prominent ruminal bacteria as a means to reduce lipolysis and biohydrogenation activity in vitro | |
Aspiras et al. | Hepatoprotective effect of Fermented Water Kefir on Sprague-Dawley rats (Rattus norvegicus) induced with sublethal dose of Acetaminophen | |
Lee et al. | Intravenous administration of L-tryptophan stimulates gastrointestinal hormones and melatonin secretions: study on beef cattle | |
Løkken et al. | No effect of oral ketone ester supplementation on exercise capacity in patients with McArdle disease and healthy controls: a randomized placebo‐controlled cross‐over study | |
WO2022164890A2 (en) | Bacteria producing gamma-aminobutyric acid (gaba) and uses of the bacteria | |
Blau | Sapropterin dihydrochloride for phenylketonuria and tetrahydrobiopterin deficiency | |
CN105769928B (en) | Application of clostridium butyricum in preparation for preventing and treating or assisting in treating hyperglycemia | |
US11471514B1 (en) | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith | |
US11795441B2 (en) | Dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith | |
US20230364169A1 (en) | Use of antrodia cinnamomea for increasing alcohol metabolism or/and hangover | |
US20240216479A1 (en) | Encapsulation of dual-enzyme composition for preventing, treating and/or alleviating veisalgia and symptoms associated therewith | |
CN116270985A (en) | Dual enzyme composition for preventing, treating and/or alleviating hangover and symptoms associated therewith | |
Xie et al. | In vitro and in vivo studies of soybean peptides on milk production, rumen fermentation, ruminal bacterial community, and blood parameters in lactating dairy cows |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FEPP | Fee payment procedure |
Free format text: ENTITY STATUS SET TO UNDISCOUNTED (ORIGINAL EVENT CODE: BIG.); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
FEPP | Fee payment procedure |
Free format text: ENTITY STATUS SET TO SMALL (ORIGINAL EVENT CODE: SMAL); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |