WO2016142580A1 - Composition pour prévenir les symptômes de la gueule de bois - Google Patents

Composition pour prévenir les symptômes de la gueule de bois Download PDF

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Publication number
WO2016142580A1
WO2016142580A1 PCT/FI2016/050135 FI2016050135W WO2016142580A1 WO 2016142580 A1 WO2016142580 A1 WO 2016142580A1 FI 2016050135 W FI2016050135 W FI 2016050135W WO 2016142580 A1 WO2016142580 A1 WO 2016142580A1
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composition
cysteine
composition according
hangover symptoms
preventing hangover
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PCT/FI2016/050135
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English (en)
Inventor
Semi KORPELA
Osmo Suovaniemi
Kari SYRJÄNEN
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Biohit Oyj
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Priority to CN201680026252.9A priority Critical patent/CN107835684A/zh
Publication of WO2016142580A1 publication Critical patent/WO2016142580A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • 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
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention concerns a non-toxic oral pharmaceutical composition for use in preventing the development of hangover symptoms.
  • hangover is typical physically and psychically stressing syndrome and condition.
  • the alcohol hangover is characterized by headache, tremulousness, nausea, diarrhea and fatigue combined with decreased occupational, cognitive or visual-spatial skill performance. Additionally, symptoms comprise tiredness, thirst because of dehydration, sweating and quiver. Not much is known about the pathophysiology of hangover. It is, however, known that the level of alcohol intoxication relates to the degree of hangover, not always related to the amount of alcohol intake (Ylikahri et al., 1974).
  • acetaldehy de-associated carcinomas stomach and esophagus.
  • Concentrations of acetaldehyde in the upper digestive tract and in the stomach can be effectively reduced in connection with alcohol drinking and smoking by a very simple approach; L-cysteine capsule or lozenge (Salaspuro et al., 2002; Linderborg et al., 2011).
  • hangover symptoms impair or prevent performance to work, thus leading to increased absence, raises the risk of accidents and thus reduces remarkably public health and economy.
  • hangover typically leads to continued drinking, which in a long term increases the alcohol consumption and generates alcoholic dependency. Taken together, reducing and preventing hangover would benefit both public health and public economy.
  • Alcohol is oxidized to acetaldehyde by cytoplasmic alcohol dehydrogenase (ADH) enzyme.
  • ADH cytoplasmic alcohol dehydrogenase
  • acetaldehyde is oxidized to acetic acid by mitochondrial and cytoplasmic aldehyde dehydrogenase (ALDH) enzymes.
  • Acetic acid is then transported from the liver to the muscles and adipose tissue where it is further broken down into carbon dioxide and water.
  • acetaldehyde concentrations in blood and tissues are regulated by a delicate balance betweenalcohoi and ALDH enzymes.
  • acetaldehyde is much more toxic than ethanol. Furthermore, acetaldehyde derived from alcoholic beverages has been classified as a Group 1 carcinogen for humans by the International Agency for Research on Cancer (IAI C/ ⁇ HO)(iARC 2012).
  • the inventors have surprisingly found that a pharmaceutical composition eliminating or significantly reducing the amount of acetaldehyde carried to or formed in different body sites will prevent hangover symptoms, which could provide a link between hangover and alcohol consumption.
  • the first metabolite of alcohol is acetaldehyde.
  • the alcohol is evenly distributed in the liquid phase of the organs. Hence, after alcohol intake and as long as there is any alcohol left in the organs, the alcohol content in the blood, saliva, gastric juice and intestinal contents remain equal.
  • Acetaldehyde is formed from the alcohol,
  • Microbes particularly in the digestive tract, are capable of oxidizing alcohol to acetaldehyde.
  • acetaldehyde contents of a microbial origin (18 - 143 ⁇ ) have been measured in human saliva.
  • acetaldehyde builds up in the saliva as an intermediate product of the microbial metabolism (Homann et al, Carcinogenesis (1997) 18: 1739 - 1743).
  • acetaldehyde is formed from ethyl alcohol as a consequence of the hepatic metabolism and, locally in the digestive tract via alcohol dehydrogenase of microbial origin (Salaspuro et al, (1996) Ann Med 28: 195 - 200). Saliva readily distributes from the mouth to the other areas of the upper digestive tract, whereby areas of increased exposure to acetaldehyde in the saliva include the mouth, pharynx, oesophagus and stomach. Consequently, the effects of acetaldehyde may extend to the whole upper digestive tract area.
  • acetaldehyde is also formed in the large intestine, because the bacteria representing the normal intestinal flora are capable of converting ethanol into acetaldehyde (Jokelainen et al, (1996) Gut 39: 100 - 104). In the intestines, also
  • endogenous ethanol can be found, i.e., ethanol formed in the intestines under oxygen-free conditions as the effect of microbes. Acetaldehyde is formed, when this ethanol comes into contact with oxygen near the mucous membrane.
  • carcinogenic acetaldehyde can be produced also endogenously by the oral microbes from various foodstuffs with high sugar or carbohydrate content. This will result in an increased acetaldehydecontent also in the stomach, especially in subjects suffering from an achlorhydric (acid- free) stomach.
  • compositions which can be used to prevent hangover symptoms.
  • compositions for use in the prevention of hangovers which compositions also mask the taste of the active agents.
  • the present invention concerns a non-toxic solid pharmaceutical composition for oral administration, containing one or more agent from the group of L-cysteine, D-cysteine and N-acetyl-cysteine, combined with one or more pharmaceutical additives, which regulate the release rate of the active agents. More specifically, the composition of the present invention is characterized by what is stated in the characterizing part of Claim 1.
  • the present invention provides an effective composition and a method for use in preventing hangover.
  • the compositions are effective in releasing the active agents in the mouth or in the stomach, and binding acetaldehyde, in particular, when they are consumed in connection with eating, drinking or smoking, i.e., just before, during or immediately after eating, drinking or smoking.
  • These compositions can be used also in a regular basis, e.g. at 6 to 8-hour intervals.
  • the composition comprises one or more carriers that regulate the release of the active substances, thus giving a continuous effect.
  • the present invention concerns a non-toxic solid pharmaceutical composition for oral administration, containing one or more cysteine compound from the group of L-cysteine, D-cysteine and N-acetyl-cysteine as active compounds, combined with one or more carriers, the composition being intended for use in preventing hangover symptoms.
  • cyste compound is intended to mean an amino acid cysteine, such as L- or D-cysteine, or a derivative or salt thereof, particularly N-acetyl-cysteine.
  • the function of this main active agent is based on the local effect obtainable through the chemical reaction of this cysteine compound with acetaldehyde in the gastrointestinal tract.
  • the composition further contains diamine oxidase (i.e. histaminase) as an active agent for degrading excess histamine.
  • the active agents consist of amino acids selected from L-cysteine, D-cysteine, N-acetyl-cysteine, preferably being L-cysteine.
  • one or more vitamins or a similar nutritious supplement is further included in the composition.
  • This supplementary agent can be, for example, a taurine compound or a common water-soluble vitamin, such as vitamin C, B l s B 2 , B 3 , B 6 , B 9 , or Bi2, due to the contents of reactive functional groups of these compounds, or a salt thereof, or any combination of the previous.
  • the composition may be formulated into, for example, a tablet, a capsule, a granule, or a powder, or optionally into a tablet or a capsule filled with said powder or granules.
  • the composition may be formulated into a monolithic or multi-particular preparation.
  • the composition for release in a foodstuff or a drink (including water and any beverages) is preferably formulated into and added to said foodstuff or drink in the form of a powder or granules.
  • the composition for administration into and release in the mouth or in the stomach of the subject is preferably administered as a capsule, tablet or lozenge, most suitably as a capsule enclosing the active agents and additives in a granulated form.
  • the function of the cysteine or the N-acetyl-cysteine is based on the neutralization of acetaldehyde formed during consumption of alcohol, smoking, or of alcohol- or acetaldehyde-containing foodstuff or drinks, including foodstuff and drinks that contain materials that are capable of forming alcohol or acetaldehyde prior to or just after consumption, such as certain bacteria, yeasts or carbohydrates.
  • the above mentioned optional vitamins and supplements function by potentially amplifying the acetaldehyde-binding effect of the cysteine compound.
  • the function of the diamine oxidase is based on its enzymatic activity in degrading histamine, whereby reducing the contribution of histamine in the development of hangover symptoms.
  • the composition of the present invention comprises an effective amount of one or more agent from the group of L-cysteine, D-cysteine and N-acetyl-cysteine, as well as optionally of one or more agent selected from cystine, glutathione and methionine.
  • the glutathione can be present in the composition in either oxidized or reduced form.
  • the reduced form is used, since this will provide an increased local effect, while the oxidized form can be targeted to the systemic route of action.
  • an effective amount of diamine oxidase, a taurine compound or a common water-soluble vitamin can be included in the composition.
  • An "effective amount” means an amount capable of binding or inactivating an amount of acetaldehyde present in a foodstuff, alcohol or other drink, or formed during the consumption of foodstuff, alcohol or other drink, or after eating, drinking or smoking, or at least keeping the acetaldehyde content essentially lower than without the use of the composition.
  • an effective amount means an amount capable of degrading an excess of histamine present in the foodstuffs or temporarily formed in the subject.
  • composition means that the acetaldehyde content should be kept at a level that is at least 20%, preferably over 40%, and most preferably over 60%> lower than without using the composition according to the description of the invention.
  • the mentioned acetaldehyde is mainly formed in the saliva of the subject. Due to the deposition of acetaldehyde into the aerodigestive tract, the acetaldehyde also reaches the oesophagus and stomach via normal wash-out of saliva. Further, the alcohol reaching the blood circulation will be spread throughout the body and into the organs, where it can cause harm as such or when metabolized into acetaldehyde. Thus, the harm is, at least in part, systemic.
  • Such a harmful content of acetaldehyde in the mouth, oesophagus, stomach or intestines , and to a small extent in the other organs, can be formed as a result of consuming alcoholic drinks, particularly strong alcoholic drinks, or ingestion of foodstuffs containing alcohol or acetaldehyde, in particular among people having atrophic gastritis or an achlorhydric (acid-free) stomach.
  • Alcohol drinks are ethanol-containing drinks, their ethanol content varying between 0.7% and 84% by volume.”
  • Alcohol foodstuffs refer to all foodstuffs containing at least 0.7% of ethanol. Such foodstuffs can be, for example, fermented juices or preserves, or foodstuffs preserved with small amounts of alcohol, pastries, jellies, and mousse seasoned with liqueur or corresponding products containing alcohol.
  • Acetaldehyde-containing foodstuffs refer to all foodstuffs containing measurable amounts of acetaldehyde. Acetaldehyde is contained in foodstuffs, wherein ethanol has been generated in connection with fermentation, such as beer, cider, wine, home-brewed beer, and other alcoholic drinks, as well as many juices. In certain foodstuffs, such as some milk products, acetaldehyde is used for preservation purposes and to add flavor, or acetaldehyde is formed in the product as a consequence of microbial activity. For example, sugary juices or sugar-containing foodstuffs in general, provide a food substrate for such microbes.
  • acetaldehyde is formed, for example, in fermented milk products, such as yoghurt.
  • fermented milk products such as yoghurt.
  • the microbes used to make yoghurt produce acetaldehyde in the yoghurt.
  • sherry and Calvados contain particularly high
  • compositions according to the invention can be of benefit even in connection with consuming light alcoholic drinks or foodstuffs, these drinks or foodstuffs containing only small amounts of alcohol.
  • "In connection with consuming alcoholic drinks” herein refers to the period of time that begins when the subject starts intake alcoholic drinks and ends when there is no more alcohol in the blood. However, this term, as such, is not intended to restrict the invention to a reaction of the alcohol in the blood.
  • compositions of the invention can be beneficial also "in connection with consuming drinks", where the drinks contain components capable of forming alcohol or acetaldehyde in the body, or containing only small amounts of alcohol (thus not forming a measurable alcohol content in the blood), the time period can optionally be interpreted to begin 10 to 0 minutes before the subject drinking and ending about 10 minutes after drinking.
  • connection with eating herein refers to the period of time starting 10 minutes before the subject eating and ending 10 minutes after finishing eating.
  • the composition can, for example, be mixed with the foodstuff or it can be administered before or after eating.
  • the composition of the present invention contains, as active agents, one or more agents from the group of L-cysteine, D-cysteine and N-acetyl-cysteine, as a combination with one or more agents selected from cystine, glutathione and methionine, in any of the forms previously described, the composition optionally including further active agents.
  • the composition further contains diamine oxidase (i.e. histaminase) as an active agent for degrading excess histamine.
  • a taurine compound or a common water-soluble vitamin is included in the composition.
  • composition further comprises one or more pharmaceutical additives, preferably including one or more non-toxic carriers that provide controlled release of said compounds in the desired area(s) of the body.
  • Controlled release herein refers to the local release of the cysteine compound during a time period of more than 30 minutes, preferably 0.5 to 8 hours, and most suitably in 2 to 4 hours, after administration.
  • the products formed by the binding of acetaldehyde to the active agents are inert, safe and non-toxic for the human.
  • the scope of the invention also includes the salts of these compounds, specifically pharmaceutically acceptable salts, in particular water-soluble salts. It is of further advantage to add to the compositions of the present invention at least one of the substances selected from the group comprising chromium, vitamin B12, A-, D-, E, -C- vitamins, niacin, biotin, thiamine, B2-, B5-, B6-vitamins and folic acid and trace elements, such as chromium, manganese, selenium, zinc and iron, and anti-microbials that decrease acetaldehyde formation, as these further improve the desired effect.
  • Another useful compound to be added to the composition of the invention which can amplify the acetaldehyde-binding effect of the composition, is lecithin.
  • lecithin Another useful compound to be added to the composition of the invention, which can amplify the acetaldehyde-binding effect of the composition.
  • a unit dose of the composition according to the invention can be in the form of, for example, a powder, a tablet, a capsule, a lozenge or a chewing gum.
  • the possibly used tablet can be in a form of a monolithic or multi-particular preparation, while the possibly used capsule can contain the active agents and the additives in, e.g. powder or granule form.
  • the compositions of the invention are formulated into capsules containing the active agents as well as one or more suitable additives, most suitably in granulated form.
  • the granules, tablets and capsules can be covered by a water-soluble film, which effectively covers or masks the taste of the active agents.
  • the compositions intended for release in foodstuff or drinks, prior to consumption can be formulated into for example, powders, which are easily mixed into the foodstuff or drink.
  • the additives typically include agents that mask the taste of the active agents, such as sweeteners or flavourings.
  • compositions intended for release in the mouth can be formulated into for example tablets or other preparations, which can be placed between the cheek or the lip and the gum, or preparations that are sucked or chewed in the mouth.
  • the unit doses for release in the mouth can be prepared by simply mixing the solid substances, optionally moistened by ethanol, and formulating them into a suitable form, e.g. by pressing into tablets.
  • the compositions intended for release in the stomach can be formulated into for example tablets or capsules to be swallowed.
  • the content of the active agents in the composition can vary between 0.2 to 2 w-% of cysteine and 0.2 to 2 w-% of cystine, glutathione or methionine, or a combination thereof.
  • the composition also includes a gum base, in a content of 90 to 99 w-% of the composition, preferably in an amount of 500 to 1500 mg per unit dose.
  • the content of active agents in the composition can vary between 5 to 40 w-% of cysteine and 0 to 20 w-%> of cystine, glutathione or methionine, or a combination thereof.
  • the composition also includes one or more diluting agent or filler, in a content of 85 to 98 w-% of the composition, preferably in an amount of 50 to 750 mg per unit dose.
  • the content of active agents in the composition can vary between 5 to 40 w-%> of cysteine and 0 to 20 w-%> of cystine, glutathione or methionine, or a combination thereof.
  • the composition also includes one or more bulking agents, in a content of 85 to 98 w-%> of the composition, preferably in an amount of 50 to 750 mg per unit dose.
  • the release of the active compounds in the conditions of the mouth usually takes place in amounts of 15 to 25 mg per hour. In the stomach, the rate of release is generally 40 to 80 mg per hour.
  • One to two preparations according to the invention can be administered at a time and the administration can be repeated at 2 to 10-hour intervals, most preferably at 4 to 8-hour intervals. In case of chewing gums, a longer interval of 6 to 10 hours can be used, since one gum, after chewing, can be tucked in between the cheek and gums, and chewed again later to release more active agents.
  • the composition can be formulated to release its active agents in a controlled manner in the mouth or in the stomach.
  • the composition is to release the active agents in the mouth, and comprises, for the purpose of controlling the release, a carrier, usually in the form of a polymer, that does not dissolve or dissolves only poorly in the mouth (hereafter called "a carrier/polymer that does not dissolve in the mouth”).
  • a carrier usually in the form of a polymer, that does not dissolve or dissolves only poorly in the mouth (hereafter called "a carrier/polymer that does not dissolve in the mouth”).
  • the polymer not dissolving in the mouth can be any pharmaceutically acceptable additive, such as metacrylate polymer, for example Eudragit RS or S, or ethyl cellulose (EC).
  • metacrylate polymer for example Eudragit RS or S, or ethyl cellulose (EC).
  • the carrier can also be selected from those forming a gel that adheres to the mucous membranes in the mouth.
  • Such carriers are generally selected from pharmaceutically acceptable polymers. More specifically, the carrier can be selected from the group comprising various chitosans, alginates, such as sodium alginate, aluminium hydroxide, sodium hydrogen carbonate, sodium carboxymethyl cellulose, and sodium hydrogen carbonate.
  • composition can comprise, for example:
  • Sweeteners such as sugars and sugar alcohols
  • the sugars can comprise, for example, saccharose, fructose or glucose or mixtures thereof.
  • the sugar alcohols can comprise mannitol, sorbitol, maltitol, lactitol, isomaltose, or xylitol or mixtures thereof.
  • a preferable sweetener comprises mannitol, and its amount in the composition can be quite large; accordingly, it simultaneously functions as a diluent.
  • the flavourings can comprise, for example, spearmint, peppermint, menthol, citrus fruit, eucalyptus or aniseed or a mixture thereof.
  • the composition can also comprise other ingredients, such as substances that prevent unpleasant oral smell, substances that function as breath fresheners and/or prevent dental caries, or the preparation can comprise vitamins.
  • the composition can also comprise substances that increase salivation.
  • composition can comprise, as a further additive, a bulking agent, preferably an inert agent, particularly in a content of 20-70 w-%, preferably 40 to 60 w-%, most preferably about 50 w-%.
  • a bulking agent preferably an inert agent, particularly in a content of 20-70 w-%, preferably 40 to 60 w-%, most preferably about 50 w-%.
  • the inert bulking agent can be for example dicalcium hydrogen phosphate,
  • MMC microcrystalline cellulose
  • a typical preparation/unit dose (such as one tablet) for release in the mouth can comprise or consist of the following: Cysteine
  • Lubricant(s) (0.5 to 3% by weight)
  • the tablets can be prepared by mixing a powdery mass and compressing it into sucking tablets by any well-known methods.
  • cysteine or cystine or glutathione or methionine is increased, the amount of diluent(s)/sweetener(s) and flavourings can also be increased, as the taste of the cysteine preferably is disguised.
  • a typical preparation/unit dose can be formulated into a chewing gum, and essentially comprises or consists of the following:
  • Gum base (comprising e.g. sweeteners)
  • the gum base can be formed from medicated chewing gum (Morjaria, Y. et ah, Drug Delivery Systems & Sciences, vol. 4, No. 1, 2004) or natural or synthetic elastomers, softeners, waxes or lipids.
  • medicated chewing gum Memjaria, Y. et ah, Drug Delivery Systems & Sciences, vol. 4, No. 1, 2004
  • natural or synthetic elastomers, softeners, waxes or lipids Natural gum bases, including crude rubber and smoked natural rubber, are permitted by the FDA. However, modern gum bases are mostly synthetic and include styrene-butadiene rubber, polyethylene and polyvinyl acetate.
  • the gum base generally constitutes 15 to 40 w-% of a chewing gum.
  • the remaining portion includes mainly medicating agents, sugars, sweeteners, softeners, flavourings and colouring agents.
  • Pharmagum is a compressible new gum system. It is a mixture of polyol(s) and/or sugars with a gum base. A formulation that contains Pharmagum gums can be compressed into a gum tablet by using conventional tablet presses. The manufacturing method is quick and inexpensive.
  • the amount of gum base in the preparation, comprising sweeteners, can be 50 to 500 mg, preferably 500 to 1500 mg.
  • Pharmagum S contains rubber base and sorbitol
  • Pharmagum M contains rubber base, mannitol, and isomaltose.
  • the composition can be prepared by mixing a powdered mass and compressing it into chewable pieces.
  • the preparation can be a buccal tablet comprising:
  • the non-ionized macro molecules include, e.g., methylcellulose (MC), hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG).
  • the ionizing polymers include, e.g., sodium carboxymethyl cellulose (NaCMC), alginic acid, sodium alginate, chitosan, polycarbofile (NoveonTM) and carbomer
  • the non-ionized macro molecules generally constitute 40 to 80 w-% of a buccal tablet, whereas the ionizing polymers generally constitute 20 to 60 w-% of such a tablet.
  • the preparation can also be a sublingual tablet essentially comprising or consisting of the following:
  • the diluents include, e.g., lactose, calcium phosphates, starch, carboxymethyl cellulose, hydroxymethyl cellulose.
  • the sweetener can be, for example, mannitol or xylitol.
  • the diluents generally constitute 90 to 98 w-% of a sublingual tablet.
  • the composition is formulated to release the active agents in the stomach, and comprises, for the purpose of controlling the release, a carrier, such as a polymer, that does not dissolve or dissolves only poorly in the stomach (here called simply "a carrier/polymer that does not dissolve in the stomach").
  • a carrier such as a polymer
  • the composition is, for this purpose, preferably formulated by pressing it into tablets or by enclosing the composition into capsules.
  • the composition can be covered by a water insoluble film.
  • a carrier not dissolving in the stomach can be a polymer, such as metacrylate polymer, for example Eudragit RS or S, or ethyl cellulose.
  • Such polymers are preferably present in a content of 10-50 w-%, more preferably 20 to 40 w-%, and most suitably 20 to 30 w-% of the entire composition.
  • the carrier can also form a gel in the stomach that floats in the contents of the stomach, or the composition can be formulated into a liquid preparation taken orally (mixture), the physical structure of which preferably is a gel.
  • the carrier of the composition can attach to the mucous membrane of the stomach, thus causing the entire preparation, including active agent, to attach to the mucous membrane.
  • the composition can also comprise a bulking agent, preferably an inert agent, such as dicalcium hydrogen phosphate, microcrystalline cellulose (MCC), or another
  • the composition comprises matrix granules not dissolving in the stomach.
  • a composition can comprise for example:
  • the polymer not dissolving in the stomach can in the above composition be any commonly used additive, such as metacrylate polymer, for example Eudragit RS or S, or ethyl cellulose (EC).
  • the inert bulking agent may be for example dicalcium hydrogen phosphate, microcrystalline cellulose (MCC), or other corresponding non-swelling agent.
  • the solid substances are mixed and moistened by ethanol.
  • the moistened mixture is granulated by using in pharmaceutical industry well known methods and devices.
  • the dried granules can be used as such or distributed into dosages, for example into capsules.
  • the composition comprises matrix tablets not dissolving in stomach.
  • a composition can comprise for example: Cysteine Cystine/ glutathione/methionine
  • the polymer not dissolving in stomach may in the above composition be any in
  • the inert bulking agent can be, for example, dicalcium hydrogen phosphate, microcrystalline cellulose (MCC), or another corresponding non-swelling agent.
  • MMC microcrystalline cellulose
  • the solid substances are mixed and the mixture is granulated by using, for example, ethanol or a hydrophilic polymer solution.
  • the granules are pressed into tablets using methods and devices well known in the pharmaceutical industry.
  • the release of the active compound(s) is here based on the diffusion of the water- soluble effective compound(s) from the pores formed to the tablet matrix.
  • the composition comprises one or more porous film forming agents for coating the preparation, such as ethyl cellulose or hydroxypropyl methylcellulose, or a combination thereof.
  • porous film forming agents for coating the preparation such as ethyl cellulose or hydroxypropyl methylcellulose, or a combination thereof.
  • a combination of ethyl cellulose and hydroxypropyl methylcellulose is used, such as a combination with a relative amount of EC to HPMC being 3/2 to 7/3.
  • composition covered by a porous film can comprise, for example:
  • Porous film forming agent(s)
  • a water-soluble bulking agent can, in such a composition, be for example lactose or some other water-soluble bulking agent commonly used in the pharmaceutical industry.
  • the solid substances are mixed and the mixture is pressed into tablets using methods and devices well-known in the pharmaceutical industry.
  • the porous film can be prepared from a water-soluble polymer, such as hydroxypropyl methyl cellulose (HPMC), or a water- insoluble polymer, such as ethyl cellulose (EC), preferably from a mixture of such polymers.
  • HPMC hydroxypropyl methyl cellulose
  • EC ethyl cellulose
  • the relative amount of the film forming substances, for example EC and HPMC is preferably 2-5 parts water-insoluble polymer and 1-2 parts water-soluble polymer.
  • the water-soluble polymer dissolves and pores are formed in the remaining water insoluble polymer.
  • the release of the effective compound(s) is here based on the diffusion of the water-soluble effective compound(s) from the pores formed in the film.
  • the film forming substances effectively mask also the taste of the active agent(s).
  • the composition is formulated with the help of two or more additives into a controlled-release formulation consisting of granules containing one or more active compounds, the granules being contained in a capsule, whereby at least one additive forms the capsule and at least one additive functions as a binder in the granules.
  • the binders are selected from polymers, such as hydroxypropylmethyl cellulose, polypropylene, Carbopol or methacrylate, preferably polymers with a solution pH of 6-7, and most preferably from methacrylate derivatives, which are known by the trade names Eudragit L, Eudragit S, and Eudragit RS.
  • the granules are separately coated with a polymeric film formed using porous film forming agents, such as ethyl cellulose (EC) and hydroxyl propyl methylcellulose (HPMC), preferably a mixture of these, more preferably a mixture, where the relative amount of EC to HPMC is 1/1 to 5/1, particularly 2/1 to 5/1, and most suitably 3/2 to 7/3.
  • porous film forming agents such as ethyl cellulose (EC) and hydroxyl propyl methylcellulose (HPMC), preferably a mixture of these, more preferably a mixture, where the relative amount of EC to HPMC is 1/1 to 5/1, particularly 2/1 to 5/1, and most suitably 3/2 to 7/3.
  • the composition is a non-toxic, solid and oral pharmaceutical composition for use in preventing hangover symptoms, the composition comprising one or more cysteine compounds from the group of L-cysteine, D-cysteine and N-acetyl- cysteine as active agents; optionally B12-vitamin; and one or more additives, including one or more non-toxic carriers that provide slowly controlled release of the active agents during a period of more than 30 minutes, preferably 0.5 to 8 hours and most suitably in 2 to 4 hours.
  • L-cysteine is used as the active agent, Eudragit® RS-PO as a binder and
  • the active agent consists 50 to 500 mg, preferably 100 to 300 mg and most suitably about 250 mg of L-cysteine.
  • the composition comprises a vitamin combination consisting of Bi-, B 2 -, B 6 -, B 9 - and Bi 2 -vitamins.
  • the composition comprises 250 mg of L-cysteine, 100 mg of Eudragit® RS-PO, 200 mg of CaHP0 4 , 73.5 mg of hydroxyl- propylmethyl-cellulose, 1.5 mg of titanium dioxide, 1.1 mg of Bi -vitamin (thiamine), 1.4 mg of B 2 -vitamin (riboflavin), 16 mg of B3-vitamin (niacin), 1.4 mg of B6-vitamin (pyridoxine), 200 ⁇ g of Bg-vitamin (folic acid) and 2.5 ⁇ g of Bi 2 -vitamin (cobalamin).
  • composition comprising effective amount of cysteine administered into the foodstuff or drink soon to be consumed by a subject, or directly to the subject, in a suitable amount, which can contain, for example, 5 to 40 w-% of cysteine, most suitably directly to the subject prior or in connection with the subject consuming alcohol-containing drinks or foodstuff, or acetaldehyde-containing drinks or foodstuff.
  • the preparation has a shape that makes it easy to keep in the mouth or to swallow.
  • the composition for release of active agents in the stomach is in the form of a preparation having a diameter of at least 7 mm, preferably 8 to 15 mm, more preferably 11 to 15 mm. This assists the preparation to stay in the stomach sufficient time for the controlled release of the active agents.
  • the present invention provides preparations and methods, which can be used to prevent the development of hangover symptoms.
  • hangover is prevented by using a method of treatment that comprises the following stages:
  • composition of the present invention to be self- administered before consuming alcoholic drinks or foodstuff, or acetaldehyde- containing drinks or foodstuff,
  • the stages a) to c) are repeated as many times as feels necessary.
  • the method is characterized by administering the composition to the subject in step b) by placing 1 or 2 preparations formulated from the composition in the mouth or swallowing them.

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Abstract

La présente invention concerne une composition pharmaceutique solide non-toxique pour l'administration par voie orale destinée à être utilisée pour prévenir les symptômes de la gueule de bois, la composition contenant un ou plusieurs composés de cystéine sélectionnés dans le groupe constitué de L-cystéine, D-cystéine et N-acétyl-cystéine, combinés avec un ou plusieurs additifs, et éventuellement une combinaison de vitamines B.
PCT/FI2016/050135 2015-03-06 2016-03-07 Composition pour prévenir les symptômes de la gueule de bois WO2016142580A1 (fr)

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CN201680026252.9A CN107835684A (zh) 2015-03-06 2016-03-07 预防宿醉症状的组合物

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FI20155150 2015-03-06
FI20155150A FI127823B (en) 2015-03-06 2015-03-06 A composition for preventing the symptoms of a hangover

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017212113A1 (fr) 2016-06-06 2017-12-14 Catapult Cat Oy Combinaison de l-cystéine, d'acide ascorbique et de vitamine b3 destinée à traiter la xylostomiase
CN108671232A (zh) * 2018-07-09 2018-10-19 珠海中科先进技术研究院有限公司 一种能够降低体内乙醛浓度的组合制剂及其制备方法与用途
EP3391895A1 (fr) 2017-04-18 2018-10-24 Ecillax S.r.l. Compositions utiles pour le traitement de symptômes associés à l'abus d'alcool
US11317645B2 (en) 2018-01-29 2022-05-03 Joseph M. Fisher Compositions and methods for delaying and reducing blood alcohol concentration
WO2023187097A1 (fr) * 2022-03-31 2023-10-05 De Faire Medical Ab Compositions de dégradation d'alcool et leurs utilisations

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101125170A (zh) * 2007-07-26 2008-02-20 程开生 解酒用胃内漂浮组合物
CN101862332A (zh) * 2009-04-20 2010-10-20 兰章华 防治过量饮酒对人体损伤的组合物及其制备方法和用途
DE102011013224A1 (de) * 2011-03-07 2012-09-13 Roman Gerdes Orthomolekulares Mittel gegen die Folgen von Alkoholkonsum

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100391448C (zh) * 2003-11-19 2008-06-04 奥加生物药业(I.P.1)有限公司 提高乙醇代谢和减轻宿醉效应的物质和方法
FI20060501L (fi) * 2006-05-22 2007-11-23 Biohit Oyj Koostumus ja menetelmä asetaldehydin sitomiseksi vatsassa
FI129157B (fi) * 2012-05-28 2021-08-13 Biohit Oyj Koostumus käytettäväksi vakavien päänsärkyjen esiintymistiheyden pienentämiseksi tai niiden vähentämiseksi
FI20135097L (fi) * 2013-02-01 2014-08-02 Biohit Oyj Koostumus aldehydien sitomiseen suussa

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101125170A (zh) * 2007-07-26 2008-02-20 程开生 解酒用胃内漂浮组合物
CN101862332A (zh) * 2009-04-20 2010-10-20 兰章华 防治过量饮酒对人体损伤的组合物及其制备方法和用途
DE102011013224A1 (de) * 2011-03-07 2012-09-13 Roman Gerdes Orthomolekulares Mittel gegen die Folgen von Alkoholkonsum

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017212113A1 (fr) 2016-06-06 2017-12-14 Catapult Cat Oy Combinaison de l-cystéine, d'acide ascorbique et de vitamine b3 destinée à traiter la xylostomiase
EP3391895A1 (fr) 2017-04-18 2018-10-24 Ecillax S.r.l. Compositions utiles pour le traitement de symptômes associés à l'abus d'alcool
US11317645B2 (en) 2018-01-29 2022-05-03 Joseph M. Fisher Compositions and methods for delaying and reducing blood alcohol concentration
CN108671232A (zh) * 2018-07-09 2018-10-19 珠海中科先进技术研究院有限公司 一种能够降低体内乙醛浓度的组合制剂及其制备方法与用途
WO2023187097A1 (fr) * 2022-03-31 2023-10-05 De Faire Medical Ab Compositions de dégradation d'alcool et leurs utilisations

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FI20155150A (fi) 2016-09-07
FI127823B (en) 2019-03-15

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