WO2020002971A1 - Use of co2 generating agent for the treatment of alcohol addiction - Google Patents
Use of co2 generating agent for the treatment of alcohol addiction Download PDFInfo
- Publication number
- WO2020002971A1 WO2020002971A1 PCT/IB2018/054718 IB2018054718W WO2020002971A1 WO 2020002971 A1 WO2020002971 A1 WO 2020002971A1 IB 2018054718 W IB2018054718 W IB 2018054718W WO 2020002971 A1 WO2020002971 A1 WO 2020002971A1
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- WIPO (PCT)
- Prior art keywords
- alcohol
- oral composition
- impulse control
- addiction
- control disorder
- Prior art date
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- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 1
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- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
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- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
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- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
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- 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
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
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- 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 invention relates to a composition for well-being, for treating hepatic trouble, for improving liver condition, but also for treating human alcohol addiction.
- “Drug addiction” is a chronic relapsing disorder, characterized by compulsion and craving to seek and take the drug, loss of control over drug intake, and emergence of negative emotional states when access to the drug is discontinued (Koob and Le Moal, 1997, 2008). Essentially, the path leading to addiction follows a course of social drug-taking, related with the hedonic effects of the drug (positive reinforcement) and known as drug recreational use. By increasing dosages, the recreational use may lead to perceiving the“need” or
- the World Health Organization defines substance addiction as using a substance repeatedly, despite knowing and experiencing harmful effects.
- Substance addiction is a chronic, relapsing disease characterized by a loss of control over drug use, compulsive drug seeking and craving for a substance, use that persists despite negative consequences, and physical and/or psychological dependence on the substance.
- Substance addiction typically follows a course of tolerance, withdrawal, compulsive drug taking behavior, drug seeking behavior, and relapse.
- Substance abuse and addiction are public health issues with significant social and economic impact on both the addict and society by playing a major role in violent crime and the spread of infectious diseases.
- Addictive substances include alcohol, caffeine, nicotine, cannabis (marijuana) and cannabis derivatives, opiates and other morphine-like opioid agonists such as heroin, phencyclidine and phencyclidine-like compounds, sedative ipnotics such as benzodiazepines and barbiturates and psychostimulants such as cocaine, amphetamines and amphetamine-related drugs such as dextroamphetamine and methylamphetamine.
- Substance addiction is a chronic, relapsing disease characterized by a loss of control over drug use, compulsive drug seeking and craving for a substance, use that persists despite negative consequences, and physical and/or psychological dependence on the substance.
- Substance addiction typically follows a course of tolerance, withdrawal, compulsive drug taking behavior, drug seeking behavior, and relapse.
- Substance abuse and addiction are public health issues with significant social and economic impact on both the addict and society by playing a major role in violent crime and the spread of infectious diseases.
- Addictive substances include alcohol, caffeine, nicotine, cannabis (marijuana) and cannabis derivatives, opiates and other morphine-like opioid agonists such as heroin, phencyclidine and phencyclidine-like compounds, sedative ipnotics such as benzodiazepines and barbiturates and psychostimulants such as cocaine, amphetamines and amphetamine-related drugs such as dextroamphetamine and methylamphetamine.
- Alcohol is one of the most commonly abused substances at a global level.
- Elevated alcohol consumption is in fact associated with costly, adverse social consequences, such as disruption of families, crime, traumatic accidents, and lost productivity. Additionally, alcoholism leads to serious liver and cardiovascular disease and generates dependence resulting in severe mental disorders, social problems and adverse consequences including the division of families, tragic accidents and the reduction of work performance.
- WHO alcohol consumption is responsible for 20-30% of oesophageal and liver cancer, liver cirrhosis, homicides, epilepsy, and motor vehicle accidents worldwide. Globally, alcohol abuse leads to about 1.8 million deaths per year.
- the European Status Report on Alcohol and Health 2010, the total tangible cost of alcohol to the European ETnion was estimated to be Euro 125 billion, equivalent to 1.3% of the gross domestic product. Actual spending on alcohol -related problems accounts for 66 billion of this, while potential production not realized due to absenteeism, unemployment and premature mortality accounts for a further 59 billion.
- Compulsive behaviour towards the consumption of alcohol is a core symptom of the disorder.
- several approaches have been investigated to help alcoholic patients to not only control alcohol drinking but also alcohol cravings and relapse (Monti et ah, 1993; Volpicelli et al. 1992; O'Brien et al. 1997).
- Medications such as naltrexone, acamprosate, ondansetron, disulfuram, gamma hydroxybutyrate (GHB), and topiramate have been tested for their potential therapeutic effect on alcohol abuse belong to several classes (Volpicelli et al. 1992; O'Brien et al. 1997).
- naltrexone acamprosate, and disulfuram
- naltrexone the non-selective opioid antagonist naltrexone
- naltrexone the pharmacological gold standard.
- condition stimuli were listed among the main causes of relapse.
- specific stress conditions such as loss of work and economic difficulties, or stimuli predictive of the presence of alcohol previously associated with its use, such as a bottle of the preferred wine and a bar-like environment, may strongly facilitate relapse in detoxified former alcoholics.
- the present invention meets these needs by providing methods and nutraceutical compositions useful in treating and preventing addiction, including addiction to addictive substances and practice of behaviours associated with impulse control disorders, as well as reducing relapse use of addictive substances and relapse practice of behaviours associated with impulse control disorders.
- the present invention is directed to a composition and a method for treating alcohol substance addiction or an impulse control disorder or reducing the likelihood of relapse use of an alcohol substance or practice of a behavior associated with an alcohol impulse control disorder by administering to a subject in need thereof a composition including an effective amount of enteric resistant active agent suitable for generating for at least l2hours, in which the composition is effective to treat the substance addiction or impulse control disorder or reduce the likelihood of relapse use of the addictive substance or practice of the behavior associated with the impulse control disorder.
- the invention relates thus to an oral composition at least suitable for treating human alcohol addiction or an alcoholic impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, said composition comprising enteric resistant active agent suitable for generating for at least l2hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas expulsion from the stomach through the esophagus.
- enteric resistant active agent suitable for generating for at least l2hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas expulsion from the stomach through the esophagus.
- the invention further relates to an oral composition for treating human alcohol addiction or an alcoholic impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, said composition comprising a growth medium appropriate for aldehyde producing bacteria, especially for aldehyde producing bacteria naturally present in the stomach, said growth media comprising advantageously a gelled phase.
- a carrier especially a gas retaining/releasing means associated to/with a coating comprising a gelling agent and ethanol, especially comprising a sugar gelling agent and ethanol
- composition of the invention is also advantageous for other health purposes, such as formation of acetic acid into the stomach, treating addiction against various addictive substances, such as cannabis, cocaine, etc., satiety,
- the oral composition of the invention is more specifically :
- Oral Composition for well-being at least suitable for treating human alcohol addiction or an alcoholic impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, said composition comprising at least:
- An amount of not pasteurized vinegar with an acetic acid content of more than 4% by volume, or extract thereof possibly as a dry component, such as a dry powder, a dry powder issued from the filtration of the vinegar producing medium
- the dry weight ratio between the amount of Enteric resistant flake particles with a thickness of less than 500pm, a dry density of less than 2, a flake side surface of 3 to 30mm 2 and a maximum length of less than lOmm , and the dry weight of not pasteurized vinegar with an acetic acid content of more than 4% by volume or extract thereof is comprised between 1 : 3 and 10 : 1.
- the oral composition further comprising an amount of hepato protective agent or agents
- the dry weight ratio between the amount of hepato protective agent or agents, and the dry weight of not pasteurized vinegar with an acetic acid content of more than 4% by volume or extract thereof is comprised between 1 : 25 and 10 : 1.
- the hepato protective agent is selected among the group consisting of
- cichoric acid and salt thereof glycine betaine, ester and salt thereof, ferrulic acid and salt thereof, sinapic acid and salt thereof, chlorogenic acid and salt thereof, coumaric acid and salt thereof, melatonin, glutathione, vitamins, beta carotene, N acetylcysteine, S Adenosyl Methionine, methionine, silybin, isosilybin, silydianin and silychristin, and mixture thereof.
- the hepato protective agent is also an osmoprotective agent and/or an
- antioxidant agent and/or an oxyradical scavenger.
- the said enteric resistant active agent is formed by active flake particles having a particle surface provided with gas retaining/releasing means selected from pits, cavities and open pores.
- the said flake particles have a thickness from lOpm up to 200pm.
- the said flake particles are selected so that when mixed into sparkling water or sparkling wine or champaign, the particles are moving up and down into the medium. •
- the composition is substantially free from acetic acid.
- the particles are mixed with not pasteurized vinegar, preferably not
- pasteurized apple vinegar then filtered and dried at temperature below 60°C, one or more other agents, such as hepato protective agent, osmo protective agents, flavoring agents, etc. being advantageously added to the filtrate before its drying
- the oral composition comprising aldehyde producing bacteria and/or with a growth medium appropriate for aldehyde producing bacteria, especially for aldehyde producing bacteria naturally present in the stomach, said growth media comprising advantageously a gelled phase.
- the oral composition is in the form of a dosage form, advantageously as a bag, said unit dosage form comprising preferably 100 to 500mg enteric resistant flake particles with a thickness of less than 500pm, and having a particle size defining a side surface of 3 to 30mm 2 , and 50 to 500mg of Not pasteurized Vinegar or extract thereof.
- the oral composition is
- the oral composition can also comprise some flavoring agents, including any of the many non-toxic natural or artificial flavoring agents known in the art.
- the flavoring agents used may include one or more of a variety of natural or artificial herb and/or fruit flavors, including mint, peppermint, aniseed, orange, lemon, lime, blueberry, cherry, apply, berry, pineapple, banana, grape, strawberry, watermelon, and kiwi flavorings, among others.
- the flavoring agents may include one or more of natural or artificial vanilla, chocolate, peanut butter, cola, root beer, cream soda, pistachio, honey, marshmallow, butterscotch, and caramel flavorings, among others.
- Appropriate acidity regulators can also be present in the composition.
- Such regulators may include nontoxic bases, nontoxic acids, or nontoxic buffering agents, or any combination thereof, provided that the resulting food formulation exhibits the desired acidity after preparation.
- Suitable bases include, but are not limited to, alkali metal or alkaline earth metal carbonates, or alkali metal or alkaline earth metal bicarbonate salts.
- Suitable edible acids include, but are not limited to, citric acid, malic acid, fumaric acid, ascorbic acid, and/or tartaric acid, among others.
- Buffering agents may include, but are not limited to, salts such as sodium or potassium citrate, sodium or potassium lactate, sodium monophosphate, disodium phosphate, or dicalcium phosphate, among others.
- Red no. 2 an example of a variety of natural or artificial food colorings that are non toxic and known in the art, including for example Red no. 2 (amaranth), Red no. 3 (erythrosine), Red no. 4 (Ponceau SX), DC Red no. 22 (eosine), Red no. 28 (phloxine), Red no. 40 (Allura Red; or disodium salt of 6-hydroxy-
- a single component of a food formulation may function as both a coloring agent and a flavoring agent, for example caramel.
- the oral composition comprising or being associated to a growth medium for aldehyde producing bacteria, especially Acetobacter aceti, most preferably Acetobacter aceti naturally present in the stomach.
- aldehyde producing bacteria especially to Acetobacter aceti bacteria.
- the oral composition further comprising an additional therapeutic agent, advantageously an antidepressant.
- the enteric resistant active agent is suitable for accelerating the oxidation of alcohol in the stomach, and/or the formation of acetic acid in the stomach.
- the enteric resistant active agent is of natural origin.
- the oral composition comprises glycine betaine and/or Taraxacum
- the oral composition being in a dry form or in an aqueous form with
- the not pasteurized vinegar is from vegetable origin, advantageously from grapes and apple. Said not pasteurized vinegar is in liquid form or in a dried form, such as a dry powder.
- said enteric resistant active agent is suitable for generating for at least 12 hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas bubbling within the stomach.
- Said enteric active agent is suitable for the growth of acetobacter bacteria’s present in the stomach or present in the oral composition to be administered, especially acetobacter aceti present in the oral composition,
- said enteric resistant active agent is suitable for lowering the C02 gas
- stomach content for at least 12 hours, advantageously at least 24 hours, preferably for at least 3 days.
- the said enteric resistant active agent is formed by active flake particles having advantageously a density higher than 1 (such as comprised between 1.1 and 2, especially between 1.2 and 1.8), a particle surface comprised between 3 and 50mm 2 , especially between 3 and 20mm 2 (advantageously between 3mm 2 and l8mm 2 , preferably between 5mm 2 and l5mm 2 ), and gas retaining/releasing means selected from pits, cavities and open pores (pores with a diameter for example between lOOnm and 600nm).
- active flake particles having advantageously a density higher than 1 (such as comprised between 1.1 and 2, especially between 1.2 and 1.8), a particle surface comprised between 3 and 50mm 2 , especially between 3 and 20mm 2 (advantageously between 3mm 2 and l8mm 2 , preferably between 5mm 2 and l5mm 2 ), and gas retaining/releasing means selected from pits, cavities and open pores (pores with a diameter for example between lOOnm and 600nm).
- said flake particles have a thickness of less than 2mm, advantageously of less than lmm, preferably from lOpm up to 500pm.
- the said enteric resistant active agent is a gas retaining/releasing means adapted for collecting C02 gases dissolved within the enteric medium.
- the gas retaining/releasing means is adapted for collecting C02 gases dissolved within the enteric medium, whereby lowering its apparent density below the enteric medium density.
- the gas retaining/releasing means is adapted for collecting C02 gases
- the oral composition comprises aldehyde producing bacteria (such as acetic acid producing bacteria, especially for patients with low aldehyde producing bacteria) and/or with a growth medium (such as alcohol or wine containing growth medium) appropriate for aldehyde producing bacteria, especially for aldehyde producing bacteria naturally present in the stomach, said growth media comprising advantageously a gelled phase.
- aldehyde producing bacteria are growing on the support and increases the aldehyde (for example vinegar) producing bacteria content within the stomach
- the gas retaining/releasing means is associated with a coating comprising a gelling agent and ethanol, especially comprising a sugar or gum gelling agent and ethanol.
- the gelling agent can be xanthan gum.
- the gelling agent can comprise a cellulose ether, vinyl alcohol, vinyl pyrrolidone, natural gum, acrylic polymer, polyoxyethylene - polyoxypropylene copolymer and mixtures thereof.
- the cellulose ether is advantageously selected from the group consisting of hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, methyl cellulose, hydroxypropyl ethylcellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxycellulose and mixtures thereof.
- the vinyl alcohol is preferably polyvinyl alcohol.
- the vinyl pyrrolidone is preferably polyvinylpyrrolidones.
- the natural gum is advantageously selected from the group consisting of karaya gum, locust bean gum, guar gum, gelan gum, xanthan gum, gum arabic, tragacanth carrageenan, pectin, agar, alginic acid, sodium alginate and mixtures thereof.
- the acrylic polymer is preferably selected from the group consisting of methacrylates, polyacrylates copolymers and mixtures thereof.
- the polyoxyethylene- polyoxypropylene copolymer is advantageously poloxamer.
- the oral composition comprising from lOOmg up to 5g (advantageously from 200mg up to lOOOmg, preferably from 500mg up to 800mg) of enteric resistant active agent suitable for generating for at least l2hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas expulsion from the stomach through the esophagus.
- the dosage form can be in the form of capsule or tablets, with an enteric degradable binding or capsule, or suspension.
- the oral composition further comprising an additional therapeutic agent, advantageously an antidepressant.
- the antidepressant is bupropion or sibutramine.
- Antidepressants are drugs used to treat depression.
- the three neurotransmitters believed to be involved in depression are serotonin, dopamine, and norepinephrine. Certain types of antidepressants increase the levels of one or more of these neurotransmitters in the brain by blocking their reabsorption.
- SSRIs selective serotonin reuptake inhibitors
- SNRIs tricyclic and tetracyclic serotonin and norepinephrine reuptake inhibitors
- NRIs norepinephrine reuptake inhibitors
- NDRIs norepinephrine and dopamine reuptake inhibitors
- MAOIs monoamine oxidase inhibitors
- SSRIs include, e.g., cericlamine, citalopram, clomipramine, cyanodothiepin, dapoxetine, duloxetine, escitalopram, femoxetine, fluoxetine, fluvoxamine, ifoxetine, imipramine, indalpine, indeloxazine, litoxetine, lofepramine, mianserine, milnacipran, mirtazapine, nefazadone, nortriptyline, paroxetine, sertraline, sibutramine, tomoxetine, trazodone, venlafaxine, and zimeldine.
- SNRIs include, e.g., amoxapine, atomoxetine, bicifadine, desipramine, desvenlafaxine, duloxetine, maprotiline, milnacipran, nefazodone, reboxetine, sibutramine, and venlafaxine.
- Nisoxetine, nortriptyline, reboxetine, talsupram, and tomoxetine are all examples of NRIs.
- NDRIs include, e.g., bupropion, hydroxybupropion, and tesofensine.
- Azaspirones include, e.g., buspirone, gepirone, ipsapirone, tandospirone, and tiaspirone.
- Buspirone is an anxiolytic (partial agonist at 5-HT1 autoreceptors) that may be provided with an antidepressant such as an SSRI.
- MAOIs include, e.g., amiflamine, brofaromine, clorgyline, alpha- ethyltryptamine, iproclozide, iproniazid, isocarboxazid, mebanazine, moclobemide, nialamide, pargyline, phenelzine, pheniprazine, pirlindole, safrazine, selegiline, toloxatone, and tranlcypromine.
- amiflamine, brofaromine e.g., amiflamine, brofaromine, clorgyline, alpha- ethyltryptamine, iproclozide, iproniazid, isocarboxazid, mebanazine, moclobemide, nialamide, pargyline, phenelzine, pheniprazine, pirlindole, safrazine, selegiline,
- antidepressants include, e.g., amesergide, amineptine, benactyzine, bupropion, clozapine, fezolamine, levoprotiline, lithium, medifoxamine, mianserin, minaprine, olanzapine, oxaflozane, oxitriptan, rolipram, teniloxazine, tofenacin, trazodone, tryptophan, and viloxazine.
- amesergide amineptine, benactyzine, bupropion, clozapine, fezolamine, levoprotiline, lithium, medifoxamine, mianserin, minaprine, olanzapine, oxaflozane, oxitriptan, rolipram, teniloxazine, tofenacin, trazodone, tryptophan, and viloxazine
- the enteric resistant active agent is suitable for accelerating the oxidation of alcohol in the stomach, and/or the formation of acetic acid in the stomach.
- the enteric resistant active agent is of natural origin (such as pod or coat of seeds, such as of common bean or phaseolus vulgaris or white beans).
- the oral composition comprises glycine betaine (for example from 25mg up to 800mg).
- the oral composition further comprising Acetobacter, especially acetobacter aceti, especially from a vinegar process.
- Acetobacter especially acetobacter aceti, especially from a vinegar process.
- said drying is advantageously operated at low temperature.
- the liquid vinegar is filtered, and the filtrate is dried at low temperature, such as at a temperature of less than 50°C.
- a process for drying is disclosed in W02014021719A1.
- the invention relates also to a method of treating alcohol addiction or an alcohol impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, comprising administering to a subject in need thereof an oral composition according to the invention comprising an effective amount of enteric resistant active agent suitable for generating for at least l2hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas expulsion from the stomach through the esophagus, wherein the composition is effective to treat the alcohol addiction or alcohol impulse control disorder or reduce the likelihood of relapse use of alcohol or practice of the behavior associated with the alcohol impulse control disorder.
- the invention further relates to a method of treating alcohol addiction or an alcohol impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcohol impulse control disorder, comprising administering to a subject in need thereof a composition according to the invention comprising an effective amount of enteric resistant active agent effective to treat the alcohol addiction or impulse control disorder or reduce the likelihood of relapse use of the alcohol or practice of the behavior associated with the impulse control disorder.
- “treat,” and similar word such as“treatment,”“treating” etc. is an approach for obtaining beneficial or desired results, including and preferably clinical results.
- Treatment can involve optionally either the reducing or amelioration of a disease or condition, (e.g., addiction, relapse use, withdrawal), or the delaying of the progression of the disease or condition (e.g., addiction relapse use, withdrawal).
- a disease or condition e.g., addiction, relapse use, withdrawal
- the delaying of the progression of the disease or condition e.g., addiction relapse use, withdrawal.
- “prevent,” and similar word such as“prevention,”“preventing” etc. is an approach for preventing the onset or recurrence of a disease or condition, (e.g., addiction, relapse use, withdrawal) or preventing the occurrence or recurrence of the symptoms of a disease or condition, or optionally an approach for delaying the onset or recurrence of a disease or condition or delaying the occurrence or recurrence of the symptoms of a disease or condition.
- Preventing also includes inhibiting the onset or recurrence of a disease or condition, or one or more symptoms thereof, and reducing the likelihood of onset or recurrence of a disease or condition, or one or more symptoms thereof.
- Alcoholism is defined as a chronic relapsing disease. Therefore, studies on alcohol addiction are aimed not only at identifying remedies suitable to decrease alcohol consumption but also for alcohol seeking prevention. Activation of the brain stress system is thought to play a pivotal role in alcohol addiction, and stress is a major factor triggering relapse in abstinent alcoholics (Koob, 2008). Yohimbine, an a-2 adrenoceptor antagonist, increases cell firing and release of brain noradrenalin, and acts as a pharmacologic stressor (Abercrombie et al, 1988; Aghajanian and
- Yohimbine is known to increase anxiety-like symptoms related to alcohol abuse in humans (Charney et al, 1983; Umhau et al, 2011) and in rats, and importantly this drug has been shown to reinstate alcohol seeking following extinction in rats trained to self-administer alcohol (Le et al, 2005; Marinelli et al, 2007). This
- pharmacological stressor can therefore be used to investigate the effect of the composition of the invention on reinstatement of alcohol seeking behavior, as further described in the examples below.
- addiction is used to describe a recurring compulsion by an individual to engage in some specific activity, despite harmful consequences to the individual's health, mental state or social life.
- addictive behavior is often reserved for substance addictions, but as used herein with respect to the compositions and treatments of the present invention also refers to other compulsions, such as problem gambling, compulsive overeating and other impulse control disorders.
- Factors that have been suggested as causes of addiction include genetic,
- Addiction is now narrowly defined as“uncontrolled, compulsive use.” If there is no harm being suffered by, or damage done to, the patient or another party, then clinically it may be considered compulsive, but to the definition of some it is not categorized as“addiction”. In practice, the two kinds of addiction (physiological dependence and psychological dependence) are not always easy to distinguish. Addictions often have both physical and psychological components.
- Physical dependence refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation.
- addictive agents for which a user may develop a physical dependence include nicotine, opioids, barbiturates, benzodiazepines, alcohol, i.e., ethyl alcohol, GHB, and methaqualone.
- addictive agents includes any and all agents to which a subject can become addicted, either physically or psychologically, or both.
- addictions to be treated by the methods and compositions of the present invention include addiction to chemical entities, such as drugs, e.g., ethyl alcohol, nicotine, or cocaine, as well as addiction to other behaviors, e.g., pathological gambling, pathological overeating, pathological use of electronic devices, e.g., smart phones, pathological use of electronic video games, pathological use of electronic communication devices, pathological use of cellular telephones, addiction to pornography, sex addiction, obsessive compulsive disorder, compulsive spending, binge eating disorder, food addiction, anorexia, bulimia, intermittent explosive disorder, kleptomania, pyromania, trichotillomania, compulsive overexercising, and compulsive overworking.
- Addiction to addictive agents to be treated with the methods and compositions of the present invention include addictive recreational drugs, as well as addictive medications.
- addictive agents include, but are not limited to, alcohol, e.g., ethyl alcohol, gamma hy dr oxybutyrate (GHB), caffeine, nicotine, cannabis (marijuana) and cannabis derivatives, opiates and other morphine-like opioid agonists such as heroin, phencyclidine and phencyclidine-like compounds, sedative ipnotics such as benzodiazepines, methaqualone, mecloqualone, etaqualone and barbiturates and psychostimulants such as cocaine, amphetamines and
- amphetamine-related drugs such as dextroamphetamine and methylamphetamine.
- Other examples include LSD, psilocybin, ecstasy and other hallucinogens.
- addictive medications include, e.g., benzodiazepines, barbiturates, and pain medications including alfentanil, allylprodine, alphaprodine, anileridine benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, desomorphine, dextromoramide, dezocine, diampromide,
- dihydrocodeine dihydromorphine, dimenoxadol, dimepheptanol,
- Addiction to two or more addictive agents or addictive behaviors is referred to as polyaddiction, and may also be treated in accordance with the present invention.
- the subject treated in accordance with the present invention may be any animal, including a mammal, and, particularly, a human.
- the subject is suffering from or at risk for addiction to any physically addictive agent or addictive or compulsive behavior, including, e.g., any of those described below.
- the subject is addicted to alcohol, cocaine, nicotine, marijuana, an opiate or other opioid agonist or methamphetamine or other psychostimulant, or phencyclidine and phencyclidine derivatives.
- a subject is considered at risk of addiction or relapse to use of an addictive agent or practice of an addictive or compulsive behavior when the subject has previously been addicted to the same or a different addictive agent or addictive or compulsive behavior.
- the subject is considered at risk of addiction or relapse to use of an addictive agent or practice of an addictive or compulsive behavior when the subject is psychologically addicted to an addictive agent or addictive or compulsive behavior, even if the subject is no longer physically addicted.
- the subject is addicted to or at risk of becoming addicted to a therapeutic agent provided to the patient to treat a disease or disorder, e.g., a pain medication.
- the subject may be at risk of abusing an addictive therapeutic agent, such as a pain medication.
- Abusing an addictive therapeutic agent in certain embodiments, is understood to indicate using the agent for a reason different than or in addition to its prescribed use.
- a subject may be provided with both an addictive therapeutic agent alone or in combination with an additional therapeutic agent.
- a subject suffering from pain, or at risk of pain may be provided with an opioid agonist, to both provide analgesia and prevent or treat addiction to the opioid agonist.
- Alcoholism like many other addictions, is a chronic relapsing disorder
- extrahypothalamic CRF within the bed nucleus of the stria terminalis and median raphe nucleus is likely to mediate stress-induced reinstatement of drug- seeking behaviour (Erb et al 1998; Shaham et al. 1995; Le et al. 2000).
- the present invention further includes unit dosage forms of pharmaceutical compositions comprising the active agent and possibly another therapeutic agent.
- Each unit dosage form comprises a therapeutically effective amount of a pharmaceutical composition of the present invention, when used in the
- a unit dosage form may include a
- therapeutically effective amount in a single tablet, or a unit dosage form may include a therapeutically effective amount in two or more tablets, such that the prescribed amount comprises a therapeutically effective amount.
- Phaseolus vulgaris beans have been broken so as to form large pod particles with a particle size of about 5 - lOmm 2 , and powder particles issued form the core of the Phaseolus vulgaris.
- the large pod particles and particles have been sterilized (heat treated).
- the pod particles with a size larger than 5mm 2 have been recovered from the broken beans.
- Bags were prepared for containing dry unit dosage form, ready to be mixed with water or sparkling water, before oral administered to a patient.
- the dry mixture was prepared by mixing the following ingredients :
- Phaseolus vulgaris bean particles were added to liquid not pasteurized apple vinegar (with an acetic acid content of 5% by volume). After mixing, the mixture was filtered. The filtrate was mixed with glycine betaine, before being dried at low temperature (less than 50°C). The dry filtrate comprised about 50-70% by weight Phaseolus vulgaris, about 20 to 40% by weight of not pasteurized apple vinegar, and about 5 to 30% by weight glycine betaine.
- the so dried filtrate (comprising bean pods) was used for preparing a dry mixture to be placed in unit dosage bags. To lkg of said dried filtrate, the following compounds were added:
- Each bag comprised a dry dosage form of lg to 3g, with a dry bean pod content of about 200 to 500mg.
- the dose to be administered can be selected in function of the addiction trouble to be treated and the severity thereof.
- Said formulation was prepared as in Formulation 1, except that the formulation 1 was mixed with 5 to lOml water, so as to prepare ready to be administered unit dosage form.
- Formulation 3
- Phaseolus vulgaris bean particles were added to liquid not pasteurized apple vinegar (with an acetic acid content of 5% by volume). Thereafter, the following ingredients were added:
- Each bag comprised an aqueous dosage form in the form of a suspension (volume of 5 to lOml) comprising a dry matter content of lg to 3g, with a dry bean pod content of about 200 to 500mg.
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Abstract
Composition for treating human alcohol addiction or an alcoholic impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, said composition comprising enteric resistant active agent suitable for generating for at least 12 hours, advantageously for at least 24hours, a C02 gas expulsion from the stomach through the esophagus.
Description
USE OF C02 GENERATING AGENT FOR THE TREATMENT OF ALCOHOL ADDICTION
The invention relates to a composition for well-being, for treating hepatic trouble, for improving liver condition, but also for treating human alcohol addiction.
BACKGROUND OF THE INVENTION
As taught in US 2014/0072662,“Drug addiction is a chronic relapsing disorder, characterized by compulsion and craving to seek and take the drug, loss of control over drug intake, and emergence of negative emotional states when access to the drug is discontinued (Koob and Le Moal, 1997, 2008). Essentially, the path leading to addiction follows a course of social drug-taking, related with the hedonic effects of the drug (positive reinforcement) and known as drug recreational use. By increasing dosages, the recreational use may lead to perceiving the“need” or
“craving” for the drug that in turn may move in a pattern of escalating compulsive use. This transition ultimately drives to a dependence state, where the continued drug use is rather aimed to prevent the withdrawal syndrome (negative
reinforcement).” The World Health Organization (WHO) defines substance addiction as using a substance repeatedly, despite knowing and experiencing harmful effects. Substance addiction is a chronic, relapsing disease characterized by a loss of control over drug use, compulsive drug seeking and craving for a substance, use that persists despite negative consequences, and physical and/or psychological dependence on the substance. Substance addiction typically follows a course of tolerance, withdrawal, compulsive drug taking behavior, drug seeking behavior, and relapse. Substance abuse and addiction are public health issues with significant social and economic impact on both the addict and society by playing a major role in violent crime and the spread of infectious diseases. Addictive substances include alcohol, caffeine, nicotine, cannabis (marijuana) and cannabis derivatives, opiates and other
morphine-like opioid agonists such as heroin, phencyclidine and phencyclidine-like compounds, sedative ipnotics such as benzodiazepines and barbiturates and psychostimulants such as cocaine, amphetamines and amphetamine-related drugs such as dextroamphetamine and methylamphetamine.
As stated in said document,“the World Health Organization (WHO) defines substance addiction as using a substance repeatedly, despite knowing and experiencing harmful effects. Substance addiction is a chronic, relapsing disease characterized by a loss of control over drug use, compulsive drug seeking and craving for a substance, use that persists despite negative consequences, and physical and/or psychological dependence on the substance. Substance addiction typically follows a course of tolerance, withdrawal, compulsive drug taking behavior, drug seeking behavior, and relapse. Substance abuse and addiction are public health issues with significant social and economic impact on both the addict and society by playing a major role in violent crime and the spread of infectious diseases. Addictive substances include alcohol, caffeine, nicotine, cannabis (marijuana) and cannabis derivatives, opiates and other morphine-like opioid agonists such as heroin, phencyclidine and phencyclidine-like compounds, sedative ipnotics such as benzodiazepines and barbiturates and psychostimulants such as cocaine, amphetamines and amphetamine-related drugs such as dextroamphetamine and methylamphetamine.
Alcohol is one of the most commonly abused substances at a global level.
Particularly in Europe, about 58 million adults (16%) are classified as heavy drinkers, of which about 23 million (6%) are alcoholics. Europeans spend Euro 100 billion on alcoholic beverages annually, which is reflected by the high rate of alcohol consumption per capita of 10 litres of pure alcohol per year. Similarly, the alcohol consumption in North America in the last decade averaged 8.5 litres per year (Spanagel, 2009). Excessive alcohol drinking is a condition that in the Einited States affects more than 12% of the population at some point in their life (Hasin et al, 2007). Consuming and abusing these huge amounts of alcohol clearly drives to detrimental consequences with enormous socio-economic and health impacts on the world population. Elevated alcohol consumption is in fact associated with costly,
adverse social consequences, such as disruption of families, crime, traumatic accidents, and lost productivity. Additionally, alcoholism leads to serious liver and cardiovascular disease and generates dependence resulting in severe mental disorders, social problems and adverse consequences including the division of families, tragic accidents and the reduction of work performance. According to the WHO, alcohol consumption is responsible for 20-30% of oesophageal and liver cancer, liver cirrhosis, homicides, epilepsy, and motor vehicle accidents worldwide. Globally, alcohol abuse leads to about 1.8 million deaths per year. According to the European Status Report on Alcohol and Health 2010, the total tangible cost of alcohol to the European ETnion was estimated to be Euro 125 billion, equivalent to 1.3% of the gross domestic product. Actual spending on alcohol -related problems accounts for 66 billion of this, while potential production not realized due to absenteeism, unemployment and premature mortality accounts for a further 59 billion.
Compulsive behaviour towards the consumption of alcohol is a core symptom of the disorder. In recent years several approaches have been investigated to help alcoholic patients to not only control alcohol drinking but also alcohol cravings and relapse (Monti et ah, 1993; Volpicelli et al. 1992; O'Brien et al. 1997). Medications such as naltrexone, acamprosate, ondansetron, disulfuram, gamma hydroxybutyrate (GHB), and topiramate have been tested for their potential therapeutic effect on alcohol abuse belong to several classes (Volpicelli et al. 1992; O'Brien et al. 1997). Few of these pharmacotherapeutics, such as naltrexone, acamprosate, and disulfuram, have been proven to be of a certain utility and approved for the treatment of alcoholism. Among these medications, the non-selective opioid antagonist naltrexone is currently considered the pharmacological gold standard. However, despite some promising results none of these medications, including naltrexone, is of sufficient efficacy in alcoholism and prognosis remains poor.
Currently available pharmacotherapies for alcohol addiction are only moderately successful, continue to be viewed with considerable scepticism outside the scientific community and have not become widely adopted as treatments (Heilig et al, 2011). Indeed, the clinical diagnosis of alcoholism follows well established criteria as
reported in the Diagnostic and Statistical Manual of Mental Disorders [currently in its fourth edition, (DSM IV), see table 1], contributing to eliminate some of the subjective judgment involved in making diagnoses. However, approximately three- quarters of those in the general population who meet diagnostic criteria for alcoholism never receive treatment (Hasin et al, 2007). Therefore, new therapeutic approaches for treatment of alcoholism are needed.
In the past, treatment for substance addictions focused on behavioural therapy, but dependence on many of these highly addictive substances is hard to break. In particular, addictions to alcohol, cocaine, and heroin are considered chronic, relapsing disorders. Also, concurrent abuse of multiple substances, such as nicotine, heroin, cocaine and alcohol, is common.
The associated medical, social and occupational difficulties that develop during the course of addiction do not disappear after detoxification and changes in brain due to addictive drugs endure long after the patient stops taking them, accounting for high risks of relapse (O'Brien and McLellan, 1996). Clinical evidence indicates that 40% to 60% of patients treated for drug dependence return to active substance use within a year following treatment discharge (McLellan et al, 2000).
The long-lasting, chronic nature of many addictions and high rates of recidivism present a considerable challenge for the treatment of drug and alcohol addiction, such that understanding of the neurobiological basis of relapse has emerged as a central issue in addiction research. Emotional and environmental factors
(conditioning stimuli) were listed among the main causes of relapse. For example, it is known that specific stress conditions such as loss of work and economic difficulties, or stimuli predictive of the presence of alcohol previously associated with its use, such as a bottle of the preferred wine and a bar-like environment, may strongly facilitate relapse in detoxified former alcoholics.
People suffering from Alcohol addiction are generally also suffering from liver troubles.
Clearly, there is a need in the art for new methods for treating and preventing addiction and the relapse use of addictive agents. The present invention meets these
needs by providing methods and nutraceutical compositions useful in treating and preventing addiction, including addiction to addictive substances and practice of behaviours associated with impulse control disorders, as well as reducing relapse use of addictive substances and relapse practice of behaviours associated with impulse control disorders.
SUMMARY OF THE INVENTION
The present invention is directed to a composition and a method for treating alcohol substance addiction or an impulse control disorder or reducing the likelihood of relapse use of an alcohol substance or practice of a behavior associated with an alcohol impulse control disorder by administering to a subject in need thereof a composition including an effective amount of enteric resistant active agent suitable for generating for at least l2hours, in which the composition is effective to treat the substance addiction or impulse control disorder or reduce the likelihood of relapse use of the addictive substance or practice of the behavior associated with the impulse control disorder.
The invention relates thus to an oral composition at least suitable for treating human alcohol addiction or an alcoholic impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, said composition comprising enteric resistant active agent suitable for generating for at least l2hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas expulsion from the stomach through the esophagus. This long time efficiency of the particles resistant in the acid gastric medium is appropriate for preventing recidivism risk.
The invention further relates to an oral composition for treating human alcohol addiction or an alcoholic impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, said composition comprising a growth medium appropriate for aldehyde producing bacteria, especially for aldehyde producing bacteria naturally present in the stomach, said growth media comprising advantageously a gelled
phase. Advantageously, it comprises a carrier, especially a gas retaining/releasing means associated to/with a coating comprising a gelling agent and ethanol, especially comprising a sugar gelling agent and ethanol
While not being bound to any theory, it is expected that a better treatment of alcohol addiction is due to the better release of C02 gas dissolved into the gastric medium and/or a better oxidation of alcohol, and/or acetic acid comprised in the particles and/or a better growth of acetobacter aceti on the support resistant in the acid gastric medium and/or the up and down movement of the support within the gastric medium, whereby C02 is release, while oxygen is loaded before the downwards movement of the support in the gastric medium. While still not being bound to any theory, it is expected that some acetaldehyde is released in the stomach, whereby generating an Antabuse effect.
The composition of the invention is also advantageous for other health purposes, such as formation of acetic acid into the stomach, treating addiction against various addictive substances, such as cannabis, cocaine, etc., satiety,
The oral composition of the invention is more specifically :
Oral Composition for well-being, at least suitable for treating human alcohol addiction or an alcoholic impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, said composition comprising at least:
An amount of Enteric resistant flake particles with a thickness of less than 500pm, a dry density of less than 2 (advantageously comprised between 0.8 and 1.8, such as comprised between 1 and 1.5), a flake side surface of 3 to 30mm2 (the surface being measured in a plane, namely as a side of the flattened flake) and a maximum length of less than lOmm, and
An amount of not pasteurized vinegar with an acetic acid content of more than 4% by volume, or extract thereof (possibly as a dry component, such as
a dry powder, a dry powder issued from the filtration of the vinegar producing medium),
Whereby the dry weight ratio between the amount of Enteric resistant flake particles with a thickness of less than 500pm, a dry density of less than 2, a flake side surface of 3 to 30mm2 and a maximum length of less than lOmm , and the dry weight of not pasteurized vinegar with an acetic acid content of more than 4% by volume or extract thereof is comprised between 1 : 3 and 10 : 1.
The said composition has advantageously one or more of the following details or characteristics:
• The oral composition further comprising an amount of hepato protective agent or agents,
Whereby the dry weight ratio between the amount of hepato protective agent or agents, and the dry weight of not pasteurized vinegar with an acetic acid content of more than 4% by volume or extract thereof is comprised between 1 : 25 and 10 : 1.
• The hepato protective agent is selected among the group consisting of
cichoric acid and salt thereof, glycine betaine, ester and salt thereof, ferrulic acid and salt thereof, sinapic acid and salt thereof, chlorogenic acid and salt thereof, coumaric acid and salt thereof, melatonin, glutathione, vitamins, beta carotene, N acetylcysteine, S Adenosyl Methionine, methionine, silybin, isosilybin, silydianin and silychristin, and mixture thereof.
• The hepato protective agent is also an osmoprotective agent and/or an
antioxidant agent and/or an oxyradical scavenger.
• The said enteric resistant active agent is formed by active flake particles having a particle surface provided with gas retaining/releasing means selected from pits, cavities and open pores.
• The said flake particles have a thickness from lOpm up to 200pm.
• The said flake particles are selected so that when mixed into sparkling water or sparkling wine or champaign, the particles are moving up and down into the medium.
• The composition is substantially free from acetic acid.
• The particles are mixed with not pasteurized vinegar, preferably not
pasteurized apple vinegar, then filtered and dried at temperature below 60°C, one or more other agents, such as hepato protective agent, osmo protective agents, flavoring agents, etc. being advantageously added to the filtrate before its drying
• The oral composition comprising aldehyde producing bacteria and/or with a growth medium appropriate for aldehyde producing bacteria, especially for aldehyde producing bacteria naturally present in the stomach, said growth media comprising advantageously a gelled phase.
• The oral composition is in the form of a dosage form, advantageously as a bag, said unit dosage form comprising preferably 100 to 500mg enteric resistant flake particles with a thickness of less than 500pm, and having a particle size defining a side surface of 3 to 30mm2, and 50 to 500mg of Not pasteurized Vinegar or extract thereof. The oral composition is
advantageously in the form of a dry mixture of the different components. It could also be in the form of a aqueous suspension.
• The oral composition can also comprise some flavoring agents, including any of the many non-toxic natural or artificial flavoring agents known in the art. In particular, the flavoring agents used may include one or more of a variety of natural or artificial herb and/or fruit flavors, including mint, peppermint, aniseed, orange, lemon, lime, blueberry, cherry, apply, berry, pineapple, banana, grape, strawberry, watermelon, and kiwi flavorings, among others. Alternatively, or in addition, the flavoring agents may include one or more of natural or artificial vanilla, chocolate, peanut butter, cola, root beer, cream soda, pistachio, honey, marshmallow, butterscotch, and caramel flavorings, among others.
• Appropriate acidity regulators can also be present in the composition. Such regulators may include nontoxic bases, nontoxic acids, or nontoxic buffering agents, or any combination thereof, provided that the resulting food formulation exhibits the desired acidity after preparation. Suitable bases
include, but are not limited to, alkali metal or alkaline earth metal carbonates, or alkali metal or alkaline earth metal bicarbonate salts. Suitable edible acids include, but are not limited to, citric acid, malic acid, fumaric acid, ascorbic acid, and/or tartaric acid, among others. Buffering agents may include, but are not limited to, salts such as sodium or potassium citrate, sodium or potassium lactate, sodium monophosphate, disodium phosphate, or dicalcium phosphate, among others.
• Appropriate coloring agents possibly present in the composition may
include any of a variety of natural or artificial food colorings that are non toxic and known in the art, including for example Red no. 2 (amaranth), Red no. 3 (erythrosine), Red no. 4 (Ponceau SX), DC Red no. 22 (eosine), Red no. 28 (phloxine), Red no. 40 (Allura Red; or disodium salt of 6-hydroxy-
5 [(2 -m ethoxy-5 -methyl-4-sulfophenyl) azo]-2-naphthalenesulfonic acid), Yellow no. 5 (tartrazine; trisodium 5 -hydroxy- l-(4-sulfonatophenyl) (4- sulfonatophenylazo)-H-pyrazole-3-carboxylate), DC Yellow no. 1
(quinoline yellow SS), Yellow no. 6 (Sunset Yellow FCF; or disodium salt of 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid)), DC Yellow no. 10 (Quinoline Yellow WS), Green no. 3 (Fast Green FCF), DC Green no. 5 (Alizarine Cyanine Green F), DC Green no. 6 (Quinizarine Green SS), Blue no. 1 (Brilliant Blue FCF), Blue no. 2 (Indigo Carmine), annatto, anthocyanins, beet extracts, beta-carotene, caramel,
carmine/cochineal, paprika oleoresin, and turmeric, among others. It should be apparent that a single component of a food formulation may function as both a coloring agent and a flavoring agent, for example caramel.
• The oral composition comprising or being associated to a growth medium for aldehyde producing bacteria, especially Acetobacter aceti, most preferably Acetobacter aceti naturally present in the stomach.
• The oral composition comprising or being associated to acid working
aldehyde producing bacteria, especially to Acetobacter aceti bacteria.
• The oral composition further comprising an additional therapeutic agent, advantageously an antidepressant.
• The enteric resistant active agent is suitable for accelerating the oxidation of alcohol in the stomach, and/or the formation of acetic acid in the stomach.
• The enteric resistant active agent is of natural origin.
• The oral composition comprises glycine betaine and/or Taraxacum
officinale extract and/or Milkk thistle extract.
• The oral composition being in a dry form or in an aqueous form with
suspended solid particles.
• The not pasteurized vinegar is from vegetable origin, advantageously from grapes and apple. Said not pasteurized vinegar is in liquid form or in a dried form, such as a dry powder.
• said enteric resistant active agent is suitable for generating for at least 12 hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas bubbling within the stomach.
• Said enteric active agent is suitable for the growth of acetobacter bacteria’s present in the stomach or present in the oral composition to be administered, especially acetobacter aceti present in the oral composition,
• said enteric resistant active agent is suitable for lowering the C02 gas
stomach content for at least 12 hours, advantageously at least 24 hours, preferably for at least 3 days.
• the said enteric resistant active agent is formed by active flake particles having advantageously a density higher than 1 (such as comprised between 1.1 and 2, especially between 1.2 and 1.8), a particle surface comprised between 3 and 50mm2, especially between 3 and 20mm2 (advantageously between 3mm2 and l8mm2, preferably between 5mm2 and l5mm2), and gas retaining/releasing means selected from pits, cavities and open pores (pores with a diameter for example between lOOnm and 600nm).
• said flake particles have a thickness of less than 2mm, advantageously of less than lmm, preferably from lOpm up to 500pm.
• the said enteric resistant active agent is a gas retaining/releasing means adapted for collecting C02 gases dissolved within the enteric medium.
• the gas retaining/releasing means is adapted for collecting C02 gases dissolved within the enteric medium, whereby lowering its apparent density below the enteric medium density.
• the gas retaining/releasing means is adapted for collecting C02 gases
dissolved within the enteric medium, and for generating a C02 bubbling within the enteric medium.
• The oral composition comprises aldehyde producing bacteria (such as acetic acid producing bacteria, especially for patients with low aldehyde producing bacteria) and/or with a growth medium (such as alcohol or wine containing growth medium) appropriate for aldehyde producing bacteria, especially for aldehyde producing bacteria naturally present in the stomach, said growth media comprising advantageously a gelled phase. In this case, aldehyde producing bacteria are growing on the support and increases the aldehyde (for example vinegar) producing bacteria content within the stomach
• The gas retaining/releasing means is associated with a coating comprising a gelling agent and ethanol, especially comprising a sugar or gum gelling agent and ethanol. The gelling agent can be xanthan gum. The gelling agent can comprise a cellulose ether, vinyl alcohol, vinyl pyrrolidone, natural gum, acrylic polymer, polyoxyethylene - polyoxypropylene copolymer and mixtures thereof. The cellulose ether is advantageously selected from the group consisting of hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxyethyl methylcellulose, methyl cellulose, hydroxypropyl ethylcellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxycellulose and mixtures thereof.
The vinyl alcohol is preferably polyvinyl alcohol. The vinyl pyrrolidone is preferably polyvinylpyrrolidones. The natural gum is advantageously selected from the group consisting of karaya gum, locust bean gum, guar gum, gelan gum, xanthan gum, gum arabic, tragacanth carrageenan, pectin, agar, alginic acid, sodium alginate and mixtures thereof. The acrylic polymer is preferably selected from the group consisting of methacrylates,
polyacrylates copolymers and mixtures thereof. The polyoxyethylene- polyoxypropylene copolymer is advantageously poloxamer.
• The oral composition comprising from lOOmg up to 5g (advantageously from 200mg up to lOOOmg, preferably from 500mg up to 800mg) of enteric resistant active agent suitable for generating for at least l2hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas expulsion from the stomach through the esophagus.
• The oral composition comprising an enteric degradable dosage form
comprising loose particles of enteric resistant active agent or bound particles suitable to be converted into loose particles in the stomach (with or without disintegrant agent). The dosage form can be in the form of capsule or tablets, with an enteric degradable binding or capsule, or suspension.
• The oral composition further comprising an additional therapeutic agent, advantageously an antidepressant. In a particular embodiment, the antidepressant is bupropion or sibutramine. Antidepressants are drugs used to treat depression. The three neurotransmitters believed to be involved in depression are serotonin, dopamine, and norepinephrine. Certain types of antidepressants increase the levels of one or more of these neurotransmitters in the brain by blocking their reabsorption. Several different classes of antidepressants have been identified, including selective serotonin reuptake inhibitors (SSRIs), tricyclic and tetracyclic serotonin and norepinephrine reuptake inhibitors (SNRIs), norepinephrine reuptake inhibitors (NRIs), norepinephrine and dopamine reuptake inhibitors (NDRIs), azaspirones, monoamine oxidase inhibitors (MAOIs), and atypical antidepressants.
SSRIs include, e.g., cericlamine, citalopram, clomipramine, cyanodothiepin, dapoxetine, duloxetine, escitalopram, femoxetine, fluoxetine, fluvoxamine, ifoxetine, imipramine, indalpine, indeloxazine, litoxetine, lofepramine, mianserine, milnacipran, mirtazapine, nefazadone, nortriptyline, paroxetine, sertraline, sibutramine, tomoxetine, trazodone, venlafaxine, and zimeldine.
Amitriptyline, amoxapine, butriptyline, clomipramine, demexiptiline, desipramine, dibenzepin, dimetacrine, dothiepin, doxepin, imipramine, iprindole, lofepramine, maprotiline, melitracen, metapramine, mianserin, mirtazpine, nortriptyline, propizepine, protriptyline, quinupramine, setiptiline, tianeptine, and trimipramine are all tricyclic and tetracyclic antidepressants. SNRIs include, e.g., amoxapine, atomoxetine, bicifadine, desipramine, desvenlafaxine, duloxetine, maprotiline, milnacipran, nefazodone, reboxetine, sibutramine, and venlafaxine. Nisoxetine, nortriptyline, reboxetine, talsupram, and tomoxetine are all examples of NRIs. NDRIs include, e.g., bupropion, hydroxybupropion, and tesofensine. Azaspirones include, e.g., buspirone, gepirone, ipsapirone, tandospirone, and tiaspirone. Buspirone is an anxiolytic (partial agonist at 5-HT1 autoreceptors) that may be provided with an antidepressant such as an SSRI. Specific MAOIs include, e.g., amiflamine, brofaromine, clorgyline, alpha- ethyltryptamine, iproclozide, iproniazid, isocarboxazid, mebanazine, moclobemide, nialamide, pargyline, phenelzine, pheniprazine, pirlindole, safrazine, selegiline, toloxatone, and tranlcypromine. Atypical
antidepressants include, e.g., amesergide, amineptine, benactyzine, bupropion, clozapine, fezolamine, levoprotiline, lithium, medifoxamine, mianserin, minaprine, olanzapine, oxaflozane, oxitriptan, rolipram, teniloxazine, tofenacin, trazodone, tryptophan, and viloxazine.
• the enteric resistant active agent is suitable for accelerating the oxidation of alcohol in the stomach, and/or the formation of acetic acid in the stomach.
• the enteric resistant active agent is of natural origin (such as pod or coat of seeds, such as of common bean or phaseolus vulgaris or white beans).
• The oral composition comprises glycine betaine (for example from 25mg up to 800mg).
• The oral composition further comprising Acetobacter, especially acetobacter aceti, especially from a vinegar process. For the drying of vinegar, said drying is advantageously operated at low temperature. Most preferably the
liquid vinegar is filtered, and the filtrate is dried at low temperature, such as at a temperature of less than 50°C. A process for drying is disclosed in W02014021719A1.
• The drying of vinegar is advantageously carried out in presence of the flakes or pods, and of the osmo protecting agent.
• Any combinations of one or more details and characteristics disclosed here above.
The invention relates also to a method of treating alcohol addiction or an alcohol impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, comprising administering to a subject in need thereof an oral composition according to the invention comprising an effective amount of enteric resistant active agent suitable for generating for at least l2hours, advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas expulsion from the stomach through the esophagus, wherein the composition is effective to treat the alcohol addiction or alcohol impulse control disorder or reduce the likelihood of relapse use of alcohol or practice of the behavior associated with the alcohol impulse control disorder.
The invention further relates to a method of treating alcohol addiction or an alcohol impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcohol impulse control disorder, comprising administering to a subject in need thereof a composition according to the invention comprising an effective amount of enteric resistant active agent effective to treat the alcohol addiction or impulse control disorder or reduce the likelihood of relapse use of the alcohol or practice of the behavior associated with the impulse control disorder.
As used herein, unless the context makes clear otherwise,“treat,” and similar word such as“treatment,”“treating” etc., is an approach for obtaining beneficial or desired results, including and preferably clinical results. Treatment can involve optionally either the reducing or amelioration of a disease or condition, (e.g.,
addiction, relapse use, withdrawal), or the delaying of the progression of the disease or condition (e.g., addiction relapse use, withdrawal).
As used herein, unless the context makes clear otherwise,“prevent,” and similar word such as“prevention,”“preventing” etc., is an approach for preventing the onset or recurrence of a disease or condition, (e.g., addiction, relapse use, withdrawal) or preventing the occurrence or recurrence of the symptoms of a disease or condition, or optionally an approach for delaying the onset or recurrence of a disease or condition or delaying the occurrence or recurrence of the symptoms of a disease or condition. Preventing also includes inhibiting the onset or recurrence of a disease or condition, or one or more symptoms thereof, and reducing the likelihood of onset or recurrence of a disease or condition, or one or more symptoms thereof.
Alcoholism is defined as a chronic relapsing disease. Therefore, studies on alcohol addiction are aimed not only at identifying remedies suitable to decrease alcohol consumption but also for alcohol seeking prevention. Activation of the brain stress system is thought to play a pivotal role in alcohol addiction, and stress is a major factor triggering relapse in abstinent alcoholics (Koob, 2008). Yohimbine, an a-2 adrenoceptor antagonist, increases cell firing and release of brain noradrenalin, and acts as a pharmacologic stressor (Abercrombie et al, 1988; Aghajanian and
VanderMaelen, 1982; Holmberg et al, 1962; Le et al, 2005; Lee et al, 2004).
Yohimbine is known to increase anxiety-like symptoms related to alcohol abuse in humans (Charney et al, 1983; Umhau et al, 2011) and in rats, and importantly this drug has been shown to reinstate alcohol seeking following extinction in rats trained to self-administer alcohol (Le et al, 2005; Marinelli et al, 2007). This
pharmacological stressor can therefore be used to investigate the effect of the composition of the invention on reinstatement of alcohol seeking behavior, as further described in the examples below.
The term addiction is used to describe a recurring compulsion by an individual to engage in some specific activity, despite harmful consequences to the individual's health, mental state or social life. The term“addiction” is often reserved for
substance addictions, but as used herein with respect to the compositions and treatments of the present invention also refers to other compulsions, such as problem gambling, compulsive overeating and other impulse control disorders. Factors that have been suggested as causes of addiction include genetic,
biological/pharmacological and social factors.
The medical community now makes a careful theoretical distinction between physical or physiological dependence (characterized by symptoms of withdrawal) and psychological dependence (sometimes referred to simply as addiction).
Addiction is now narrowly defined as“uncontrolled, compulsive use.” If there is no harm being suffered by, or damage done to, the patient or another party, then clinically it may be considered compulsive, but to the definition of some it is not categorized as“addiction”. In practice, the two kinds of addiction (physiological dependence and psychological dependence) are not always easy to distinguish. Addictions often have both physical and psychological components.
Physical dependence (or drug dependence) refers to a state resulting from habitual use of a drug, where negative physical withdrawal symptoms result from abrupt discontinuation. Examples of addictive agents for which a user may develop a physical dependence include nicotine, opioids, barbiturates, benzodiazepines, alcohol, i.e., ethyl alcohol, GHB, and methaqualone.
As used herein with respect to the disorders to be treated by the methods and compositions of the present invention, addictive agents includes any and all agents to which a subject can become addicted, either physically or psychologically, or both. As noted above, addictions to be treated by the methods and compositions of the present invention include addiction to chemical entities, such as drugs, e.g., ethyl alcohol, nicotine, or cocaine, as well as addiction to other behaviors, e.g., pathological gambling, pathological overeating, pathological use of electronic devices, e.g., smart phones, pathological use of electronic video games, pathological use of electronic communication devices, pathological use of cellular telephones, addiction to pornography, sex addiction, obsessive compulsive disorder, compulsive spending, binge eating disorder, food addiction, anorexia, bulimia, intermittent
explosive disorder, kleptomania, pyromania, trichotillomania, compulsive overexercising, and compulsive overworking.
Addiction to addictive agents to be treated with the methods and compositions of the present invention include addictive recreational drugs, as well as addictive medications. Examples of addictive agents include, but are not limited to, alcohol, e.g., ethyl alcohol, gamma hy dr oxybutyrate (GHB), caffeine, nicotine, cannabis (marijuana) and cannabis derivatives, opiates and other morphine-like opioid agonists such as heroin, phencyclidine and phencyclidine-like compounds, sedative ipnotics such as benzodiazepines, methaqualone, mecloqualone, etaqualone and barbiturates and psychostimulants such as cocaine, amphetamines and
amphetamine-related drugs such as dextroamphetamine and methylamphetamine. Other examples include LSD, psilocybin, ecstasy and other hallucinogens.
Examples of addictive medications include, e.g., benzodiazepines, barbiturates, and pain medications including alfentanil, allylprodine, alphaprodine, anileridine benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, desomorphine, dextromoramide, dezocine, diampromide,
dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol,
dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacylmorphan, lofenitanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, OXYCONTIN®, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propiram, propoxyphene sufentanil, tramadol, tilidine, salts thereof, mixtures of any of the foregoing, mixed m-agonists/antagonists, and the like.
While a subject may be addicted to a single addictive agent or behavior, frequently, a subject is addicted to two or more addictive agents or behaviors. Addiction to two
or more addictive agents or addictive behaviors is referred to as polyaddiction, and may also be treated in accordance with the present invention.
The subject treated in accordance with the present invention may be any animal, including a mammal, and, particularly, a human.
In particular embodiments, the subject is suffering from or at risk for addiction to any physically addictive agent or addictive or compulsive behavior, including, e.g., any of those described below. In particular embodiments, the subject is addicted to alcohol, cocaine, nicotine, marijuana, an opiate or other opioid agonist or methamphetamine or other psychostimulant, or phencyclidine and phencyclidine derivatives.
In particular embodiments, a subject is considered at risk of addiction or relapse to use of an addictive agent or practice of an addictive or compulsive behavior when the subject has previously been addicted to the same or a different addictive agent or addictive or compulsive behavior. In certain embodiment, the subject is considered at risk of addiction or relapse to use of an addictive agent or practice of an addictive or compulsive behavior when the subject is psychologically addicted to an addictive agent or addictive or compulsive behavior, even if the subject is no longer physically addicted.
In certain embodiments, the subject is addicted to or at risk of becoming addicted to a therapeutic agent provided to the patient to treat a disease or disorder, e.g., a pain medication. In a related embodiment, the subject may be at risk of abusing an addictive therapeutic agent, such as a pain medication. Abusing an addictive therapeutic agent, in certain embodiments, is understood to indicate using the agent for a reason different than or in addition to its prescribed use. In such a situation, a subject may be provided with both an addictive therapeutic agent alone or in combination with an additional therapeutic agent. For example, a subject suffering from pain, or at risk of pain, may be provided with an opioid agonist, to both provide analgesia and prevent or treat addiction to the opioid agonist.
Alcoholism, like many other addictions, is a chronic relapsing disorder
characterized by high recidivism rates. Two major factors triggering relapse behaviour are stress and environmental conditioning experiences (O'Brien et al.
1997; Monti et al. 1993; Shaham et al. 1995), which probably facilitate relapse to alcohol-seeking via distinct brain mechanisms. For example, activation of the mesolimbic dopamine system via an opioid-dependent mechanism (or via direct alterations in dopamine transmission in the basolateral nucleus of amygdala) seems to mediate the effect of drug-associated cues (Liu and Wiess 2002; Ciccocioppo et al. 2001), and, extrahypothalamic CRF within the bed nucleus of the stria terminalis and median raphe nucleus is likely to mediate stress-induced reinstatement of drug- seeking behaviour (Erb et al 1998; Shaham et al. 1995; Le et al. 2000).
The present invention further includes unit dosage forms of pharmaceutical compositions comprising the active agent and possibly another therapeutic agent. Each unit dosage form comprises a therapeutically effective amount of a pharmaceutical composition of the present invention, when used in the
recommended amount. For example, a unit dosage form may include a
therapeutically effective amount in a single tablet, or a unit dosage form may include a therapeutically effective amount in two or more tablets, such that the prescribed amount comprises a therapeutically effective amount.
Tests on volunteers and formulations
Formulation 1
Phaseolus vulgaris beans have been broken so as to form large pod particles with a particle size of about 5 - lOmm2, and powder particles issued form the core of the Phaseolus vulgaris. The large pod particles and particles have been sterilized (heat treated).
The pod particles with a size larger than 5mm2 have been recovered from the broken beans.
When placing the pod particles within a water glass with citric acid or acetic acid and with some oil, some particles are sinking while some others are floating. No movement of particles was observed.
When further adding to said water glass some sparkling water or Champaign, an upwards and downwards movement of pod particles was observed. The particles moving up and down within the sparkling water medium were recovered. When using powder particles, the powder particles are sinking.
Bags were prepared for containing dry unit dosage form, ready to be mixed with water or sparkling water, before oral administered to a patient. The dry mixture was prepared by mixing the following ingredients :
• Phaseolus vulgaris bean particles
• Extract of apple vinegar (not pasteurized),
• Citric acid
· Glycine betaine
• Peppermint
• Microcrystalline cellulose E460
• Milkk thistle
• Flavoring agent
· Sorbitol
Phaseolus vulgaris bean particles were added to liquid not pasteurized apple vinegar (with an acetic acid content of 5% by volume). After mixing, the mixture was filtered. The filtrate was mixed with glycine betaine, before being dried at low temperature (less than 50°C). The dry filtrate comprised about 50-70% by weight Phaseolus vulgaris, about 20 to 40% by weight of not pasteurized apple vinegar, and about 5 to 30% by weight glycine betaine.
The so dried filtrate (comprising bean pods) was used for preparing a dry mixture to be placed in unit dosage bags.
To lkg of said dried filtrate, the following compounds were added:
50 to l50g Milkk thissle extract
80 to 300g Taraxacum officinale
- 200 to 500 g peppermint
500 to lOOOg microcrystalline cellulose
100 to 250g citric acid
20 to lOOg Flavoring agent
300 to lOOOg sorbitol
- Possibly sugar or aspartame, if necessary or required.
Each bag comprised a dry dosage form of lg to 3g, with a dry bean pod content of about 200 to 500mg.
Some volunteers have taken once a day dry dosage form comprising about 300mg Phaseolus vulgaris pod for 15 days. No side effects were observed.
After day 3, It was observed that when the volunteers have taken one wine glass they had no or less addiction for taking a further wine glass. When taking however said second wine glass, they had some specific sensations, like belching, bloating, acid taste, nausea, etc., sensation convincing the volunteers not to further taken a glass wine.
Said sensations were still acting two days after the end of administration of the bean pod particles, when the volunteers took a glass wine. The dose to be administered can be selected in function of the addiction trouble to be treated and the severity thereof.
It has to be noted the administration of a dose of acetobacter aceti as such had no effect or very limited effect during the time (less than 1 hour), while the drinking of a vinegar dose had no effect at all.
Formulation 2
Said formulation was prepared as in Formulation 1, except that the formulation 1 was mixed with 5 to lOml water, so as to prepare ready to be administered unit dosage form. Formulation 3
Phaseolus vulgaris bean particles were added to liquid not pasteurized apple vinegar (with an acetic acid content of 5% by volume). Thereafter, the following ingredients were added:
Milkk thissle extract
- Glycine betaine
Taraxacum officinale extract
peppermint
- Microcrystalline cellulose
citric acid
- Flavoring agent
lOOOg sorbitol
- Possibly sugar or aspartame, if necessary or required.
Each bag comprised an aqueous dosage form in the form of a suspension (volume of 5 to lOml) comprising a dry matter content of lg to 3g, with a dry bean pod content of about 200 to 500mg.
Claims
1. Oral Composition for well-being, at least suitable for treating human alcohol addiction or an alcoholic impulse control disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, said composition comprising at least:
An amount of Enteric resistant flake particles with a thickness of less than 500pm, a dry density of less than 2, a flake side surface of 3 to 30mm2 and a maximum length of less than 10mm, and
An amount of not pasteurized vinegar with an acetic acid content of more than 4% by volume, or extract thereof,
Whereby the dry weight ratio between the amount of Enteric resistant flake particles with a thickness of less than 500pm, a dry density of less than 2, a flake side surface of 3 to 30mm2 and a maximum length of less than 10mm , and the dry weight of not pasteurized vinegar with an acetic acid content of more than 4% by volume or an extract thereof is comprised between 1 : 3 and 10 : 1.
2. The oral composition of claim 1, further comprising an amount of hepato protective agent or agents,
Whereby the dry weight ratio between the amount of hepato protective agent or agents, and the dry weight of not pasteurized vinegar with an acetic acid content of more than 4% by volume or extract thereof is comprised between 1 : 25 and 10 : 1.
3. The oral composition of claim 2, in which the hepato protective agent is selected among the group consisting of cichoric acid and salt thereof, glycine betaine, ester and salt thereof, ferrulic acid and salt thereof, sinapic acid and salt thereof, chlorogenic acid and salt thereof, coumaric acid and salt thereof, melatonin, glutathione, vitamins, beta carotene, N
acetylcysteine, S Adenosyl Methionine, methionine, silybin, isosilybin, silydianin and silychristin, and mixture thereof.
4. The oral composition of claim 2 or 3, in which the hepato protective agent is also an osmoprotective agent and/or an antioxidant agent and/or an oxyradical scavenger.
5. The oral composition of any one of the preceding claims, whereby the said enteric resistant active agent is formed by active flake particles having a particle surface provided with gas retaining/releasing means selected from pits, cavities and open pores.
6. The oral composition of the preceding claim, in which said flake particles have a thickness from lOpm up to 200pm.
7. The oral composition of any one of the preceding claims, comprising
aldehyde producing bacteria and/or with a growth medium appropriate for aldehyde producing bacteria, especially for aldehyde producing bacteria naturally present in the stomach, said growth media comprising
advantageously a gelled phase.
8. The oral composition of any one of the preceding claims, in the form of a dosage form, advantageously as a bag, said unit dosage form comprising preferably 100 to 500mg enteric resistant flake particles with a thickness of less than 500pm, and having a particle size defining a side surface of 3 to 30mm2, and 50 to 500mg of Not pasteurized Vinegar or extract thereof
9. The oral composition of any one of the preceding claims, comprising or being associated to a growth medium for aldehyde producing bacteria, especially Acetobacter aceti, most preferably Acetobacter aceti naturally present in the stomach.
10. The oral composition of any one of the preceding claims, comprising or being associated to acid working aldehyde producing bacteria, especially to Acetobacter aceti bacteria.
11. The oral composition of any one of the preceding claims further comprising an additional therapeutic agent, advantageously an antidepressant.
12. The oral composition of any one of the preceding claims, in which the
enteric resistant active agent is suitable for accelerating the oxidation of alcohol in the stomach, and/or the formation of acetic acid in the stomach.
13. The oral composition of any one of the preceding claims, in which the enteric resistant active agent is of natural origin.
14. The oral composition of any one of the preceding claims, which comprises glycine betaine and/or Taraxacum officinale extract and/or Milkk thistle extract.
15. The oral composition of any one of the preceding claims being in a dry form or in an aqueous form with suspended particles.
16. The oral composition of any one of the preceding claims, in which the not pasteurized vinegar is from vegetable origin, advantageously from grapes and apple.
17. A method of treating alcohol addiction or an alcohol impulse control
disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcoholic impulse control disorder, comprising administering to a subject in need thereof an oral composition according to any one of the preceding claims comprising an effective amount of enteric resistant active agent suitable for generating for at least l2hours,
advantageously for at least 24hours, preferably for at least 3 days, or even more preferably for at least 7 days, a C02 gas expulsion from the stomach through the esophagus, wherein the composition is effective to treat the alcohol addiction or alcohol impulse control disorder or reduce the likelihood of relapse use of alcohol or practice of the behavior associated with the alcohol impulse control disorder.
18. A method of treating alcohol addiction or an alcohol impulse control
disorder or reducing the likelihood of relapse use of alcohol or practice of a behavior associated with an alcohol impulse control disorder, comprising administering to a subject in need thereof a composition according to any one of the claims 1 to 16 comprising an effective amount of enteric resistant active agent effective to treat the alcohol addiction or impulse control disorder or reduce the likelihood of relapse use of the alcohol or practice of the behavior associated with the impulse control disorder.
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PCT/IB2018/054718 WO2020002971A1 (en) | 2018-06-26 | 2018-06-26 | Use of co2 generating agent for the treatment of alcohol addiction |
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PCT/IB2018/054718 WO2020002971A1 (en) | 2018-06-26 | 2018-06-26 | Use of co2 generating agent for the treatment of alcohol addiction |
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US5324516A (en) * | 1991-12-19 | 1994-06-28 | Dossan Technical Center | Galenic composition for decreasing blood alcohol concentration |
US20020102315A1 (en) * | 1999-03-12 | 2002-08-01 | Vladimir Leko | Herbal composition and medicament against diabetes mellitus type II manufactured thereof |
US20100183796A1 (en) * | 2009-01-19 | 2010-07-22 | Kiyosumi Hattori | Food made of bean peel as raw material and method for producing food material thereof |
WO2014021719A1 (en) | 2012-08-01 | 2014-02-06 | Purac Biochem B.V. | Preparation of a powdered vinegar |
US20140072662A1 (en) | 2012-07-06 | 2014-03-13 | Omeros Corporation | Andrographis Paniculata Compositions and Methods for Treatment of Addictions |
US9168274B1 (en) * | 2013-01-09 | 2015-10-27 | Jonathan Gropper | Method to reduce intoxication from ethanol in humans |
WO2018126303A1 (en) * | 2017-01-05 | 2018-07-12 | Philippe Kriwin | Composition for treating alcohol addiction |
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Publication number | Priority date | Publication date | Assignee | Title |
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US5324516A (en) * | 1991-12-19 | 1994-06-28 | Dossan Technical Center | Galenic composition for decreasing blood alcohol concentration |
US20020102315A1 (en) * | 1999-03-12 | 2002-08-01 | Vladimir Leko | Herbal composition and medicament against diabetes mellitus type II manufactured thereof |
US20100183796A1 (en) * | 2009-01-19 | 2010-07-22 | Kiyosumi Hattori | Food made of bean peel as raw material and method for producing food material thereof |
US20140072662A1 (en) | 2012-07-06 | 2014-03-13 | Omeros Corporation | Andrographis Paniculata Compositions and Methods for Treatment of Addictions |
WO2014021719A1 (en) | 2012-08-01 | 2014-02-06 | Purac Biochem B.V. | Preparation of a powdered vinegar |
US9168274B1 (en) * | 2013-01-09 | 2015-10-27 | Jonathan Gropper | Method to reduce intoxication from ethanol in humans |
WO2018126303A1 (en) * | 2017-01-05 | 2018-07-12 | Philippe Kriwin | Composition for treating alcohol addiction |
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