WO2023234166A1 - 抗てんかん用組成物 - Google Patents

抗てんかん用組成物 Download PDF

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Publication number
WO2023234166A1
WO2023234166A1 PCT/JP2023/019470 JP2023019470W WO2023234166A1 WO 2023234166 A1 WO2023234166 A1 WO 2023234166A1 JP 2023019470 W JP2023019470 W JP 2023019470W WO 2023234166 A1 WO2023234166 A1 WO 2023234166A1
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Prior art keywords
bifidobacterium
epileptic
culture
composition
seizures
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English (en)
French (fr)
Japanese (ja)
Inventor
利明 石井
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Morinaga Milk Industry Co Ltd
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Morinaga Milk Industry Co Ltd
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Priority to JP2024524796A priority Critical patent/JPWO2023234166A1/ja
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants

Definitions

  • Epilepsy is a condition that causes repeated epileptic seizures.
  • "Epileptic seizures” are seizures caused by abnormal electrical activity of nerve cells in the brain, and the nervous system such as motor nerves, sensory nerves, autonomic nerves, consciousness, or higher brain functions suddenly becomes abnormally activated. It is caused by doing this. Therefore, “epileptic seizures” correspond to each nervous system, and some parts of the body become stiff (caused by abnormalities in motor nerves), numbness in the hands and feet, and ringing in the ears (caused by abnormalities in sensory nerves). It causes a variety of symptoms, including palpitations and nausea (caused by abnormalities in the autonomic nervous system), loss of consciousness, and difficulty speaking (caused by abnormalities in higher brain function).
  • the prevalence of epilepsy is said to be 0.5 to 1%, and according to Non-Patent Document 1, it is a disease with a relatively high prevalence. Furthermore, epilepsy can occur in any age group, from infants to the elderly.
  • Diagnosis of epilepsy can include neurological examination and blood tests. Brain abnormalities can be detected using electroencephalogram (EEG), high-density EEG, computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET). :positron emission tomography) It is detected by scans, single photon emission computed tomography (SPECT), and neuropsychological tests to assess thinking, memory, and speech abilities. Analysis techniques include statistical parametric mapping (SPM), curry analysis, and magnetoencephalography (MEG).
  • EEG electroencephalogram
  • CEG computed tomography
  • MRI magnetic resonance imaging
  • PET positron emission tomography
  • SPM statistical parametric mapping
  • MEG magnetoencephalography
  • antiepileptic drugs do not eliminate the cause of epilepsy, but rather make epileptic seizures less likely to occur. However, for some cases of epilepsy, even if two antiepileptic drugs are tried alone or in combination at sufficient blood concentrations to have no side effects, antiepileptic drugs that are appropriate for the epilepsy may not be used for a certain period of time (specifically It is known that seizures may not be controlled for a period of one year or more or for a period of three times the longest pre-treatment seizure interval, whichever is longer), and this is considered drug-resistant epilepsy. being called. According to Non-Patent Document 2, 20 to 30% of epilepsy patients fall under this drug-induced epilepsy.
  • drugs used for drug therapy are pharmaceuticals, they are not easy to use and are generally prone to side effects.
  • Side effects of antiepileptic drugs include an idiosyncratic acute initial reaction to the drug that involves an allergic mechanism, and a dose-dependent suppressive effect on the nervous system (specifically, dizziness, nystagmus, double vision, drowsiness, nausea, or (loss of appetite, etc.) and chronic side effects (specifically, weight gain, hirsutism or hair loss, urinary stones, cerebellar atrophy, etc.) that occur during long-term use are known.
  • a dose-dependent suppressive effect on the nervous system specifically, dizziness, nystagmus, double vision, drowsiness, nausea, or (loss of appetite, etc.
  • chronic side effects specifically, weight gain, hirsutism or hair loss, urinary stones, cerebellar atrophy, etc.
  • Non-Patent Document 3 shows that children who followed a ketogenic diet for one year showed a reduction in epilepsy symptoms. This is reported.
  • the ketogenic diet is a diet characterized by high fat and low carbohydrate content, it may lead to hypoglycemia, dyslipidemia, or growth disorders.
  • One of the objects of the present invention is to provide an antiepileptic composition effective for preventing, treating, or alleviating epileptic seizures.
  • the antiepileptic composition according to any one of [1] to [7] which contains one or both of the Bifidobacterium bacterium and its culture as an active ingredient.
  • [9] Use of one or both of a Bifidobacterium bacterium and a culture thereof in the manufacture of a composition for administration to a subject in need of prevention, treatment, or alleviation of epileptic seizures.
  • a Bifidobacterium bacterium and a culture thereof in the manufacture of a composition for administration to a subject in need of prevention, treatment, or alleviation of epileptic seizures.
  • an antiepileptic composition that is effective in preventing, treating, or alleviating epileptic seizures.
  • the effects described here are not necessarily limited, and may be any effects described in this specification.
  • the administration schedule of Pentylenetetrazole (PTZ) and Bifidobacterium breve MCC1274 strain (FERM BP-11175) in a test example is shown.
  • a graph showing the relationship between the number of administrations of PTZ and the average convulsion score in the administration group and non-administration group of Bifidobacterium breve MCC1274 strain (FERM BP-11175) is shown.
  • the anti-epileptic composition of the present invention is an anti-epileptic composition containing one or both of a Bifidobacterium bacterium and a culture thereof as an active ingredient.
  • the active ingredient of the antiepileptic composition of the present invention is one or both of a Bifidobacterium bacterium and a culture thereof.
  • Bifidobacterium bacteria targeted by the present invention include Bifidobacterium breve, Bifidobacterium lactis, Bifidobacterium longum, and Bifidobacterium longum.
  • Bifidobacterium infantis Bifidobacterium adolescentis, Bifidobacterium bifidum, and Bifidobacterium animalis. These Bifidobacterium species may be used alone or in any combination of two or more species.
  • Preferred examples include, but are not limited to, Bifidobacterium breve, Bifidobacterium longum, and Bifidobacterium infantis. More preferred are Bifidobacterium longum and Bifidobacterium breve. More preferably, one or both of Bifidobacterium breve MCC1274 strain (FERM BP-11175) and a culture thereof. One or both of Bifidobacterium and its culture are used for producing the antiepileptic composition of the present invention. It is preferable that the bacteria of the genus Bifidobacterium and the culture thereof are live bacteria.
  • Bifidobacterium breve is a type of bacteria belonging to the genus Bifidobacterium. Bifidobacterium breve lives mainly in the large intestines of infants and young children, and among the bacterial species belonging to the genus Bifidobacterium, Bifidobacterium longum subsp. infantis ), it is known as an infant-type Bifidobacterium bacterium.
  • the anti-epileptic composition of the present invention contains either or both of a Bifidobacterium bacterium and a culture containing a Bifidobacterium bacterium, which mainly resides in large numbers in the large intestine of infants. Therefore, it is extremely safe, and there is little need to worry about side effects even when administered continuously for a long period of time, making it very useful. Furthermore, it is highly safe when used in combination with other drugs.
  • examples of Bifidobacterium breve include Bifidobacterium breve MCC1274 strain (FERM BP-11175), Bifidobacterium breve M-16V (NITE BP-02622), and the like.
  • MCC means Morinaga Culture Collection (Morinaga Milk Industry Co., Ltd.).
  • strains identified by the strain names listed above are not limited to the strains themselves that have been deposited and registered with designated institutions under the strain names (hereinafter also referred to as "deposited strains” for convenience of explanation).
  • Substantially equivalent bacterial strains are also included. That is, for example, the present invention is not limited to the strain deposited with the above-mentioned depository institution under the deposit number Bifidobacterium breve strain MCC1274 (FERM BP-11175), but also includes strains substantially equivalent thereto.
  • a strain that is substantially equivalent to the deposited strain may be, for example, a derivative strain that uses the deposited strain as a parent strain.
  • Derivative strains include strains bred from the deposited strain or naturally occurring strains from the deposited strain.
  • Examples of the derived strains include the following strains.
  • Bacterial strains determined to be the same by the Randomly Amplified Polymorphic DNA (RAPD) method or the Pulsed-field gel electrophoresis (PFGE) method FAO/WHO (2006) Probiotics in Food: Health and Nutritional Properties and Guidelines for Evaluation. Report of a Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria, Cordoba, Argentina, 1-4 October 2001 [and] Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food, London, Ontario, Canada, 30 April-1 May 2002.
  • RAPD Randomly Amplified Polymorphic DNA
  • PFGE Pulsed-field gel electrophoresis
  • MCC1274 is located at the Patent Organism Depositary Center, National Institute of Advanced Industrial Science and Technology (Chuo 6, 1-1-1 Higashi, Tsukuba City, Ibaraki Prefecture, 305-8566, Japan (currently IPOD), Patent Organism Depositary Center, National Institute of Advanced Industrial Science and Technology, Japan).
  • NITE-IPOD Room 120, 2-5-8 Kazusa Kamatari, Kisarazu, Chiba 292-0818, Japan, has been deposited with the accession number IPOD FERM BP-11175 since August 25, 2009. .
  • M-16V was transferred to the National Institute of Technology and Evaluation, Patent Microorganism Depositary (Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, 292-0818, Japan) from January 26, 2018, to NITE. It has been deposited under accession number BP-02622. These bacteria are generally available from the above-mentioned repositories.
  • Bifidobacterium breve strain MCC1274 can be easily obtained by culturing a distributed strain of Bifidobacterium breve FERM BP-11175.
  • the culturing method is not particularly limited, and the culturing can be carried out under appropriate conditions depending on the properties of the bacterium.
  • the culture temperature is usually 25 to 50°C, preferably 35 to 42°C.
  • the culture is preferably performed under anaerobic conditions, and for example, the culture can be performed while aerating an anaerobic gas such as carbon dioxide gas. Alternatively, it may be cultured under microaerobic conditions such as liquid static culture.
  • the medium for culturing Bifidobacterium breve strain MCC1274 is not particularly limited, and any medium commonly used for culturing bacteria belonging to the genus Bifidobacterium can be used.
  • a carbon source for example, sugars such as glucose, galactose, lactose, arabinose, mannose, sucrose, starch, starch hydrolyzate, and blackstrap molasses can be used depending on their assimilation properties.
  • a nitrogen source for example, ammonia, ammonium salts such as ammonium sulfate, ammonium chloride and ammonium nitrate, and nitrates can be used.
  • the inorganic salts for example, sodium chloride, potassium chloride, potassium phosphate, magnesium sulfate, calcium chloride, calcium nitrate, manganese chloride, ferrous sulfate, etc. can be used.
  • organic ingredients such as peptone, soybean flour, defatted soybean meal, meat extract, and yeast extract may be used.
  • the obtained culture may be used as is, it may be diluted or concentrated, and the bacterial cells recovered from the culture may be used.
  • the antiepileptic composition of the present invention not only Bifidobacterium breve MCC1274 strain but also a culture or culture supernatant containing Bifidobacterium breve MCC1274 strain can be used as an active ingredient.
  • the culture is preferably one in which Bifidobacterium breve MCC1274 strain is cultured and propagated, and then as much as possible other than bacterial bodies is removed, and one consisting essentially only of bacterial bodies is more preferable.
  • substantially consisting only of bacterial bodies means that 95% by mass or more of the total mass of the culture is composed of bacterial bodies in terms of wet mass.
  • the culture supernatant is the culture solution obtained when culturing Bifidobacterium breve MCC1274 strain, or its supernatant solution, and the culture supernatant is preferably sterilized by filtering. .
  • the culture of Bifidobacterium bacteria may contain other components in addition to Bifidobacterium cells, as long as they do not interfere with the effects of the present invention. Good too.
  • examples of such components include components such as the medium used for culture, and components such as buffers used for recovery, separation, or washing of the culture.
  • the antiepileptic composition of the present invention may consist only of the above-mentioned active ingredient, or may be a composition containing the above-mentioned active ingredient and any other ingredient other than the above-mentioned active ingredient.
  • the optional components are not particularly limited, and additives conventionally included in pharmaceuticals can be included.
  • additives include antioxidants, excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, and diluents, as well as formulation carriers described below.
  • the product form of the anti-epileptic composition of the present invention is not particularly limited, but forms such as foods and medicines described below are preferred.
  • the subject to whom the anti-epileptic composition of the present invention is administered is a subject in need of prevention, treatment or alleviation of epileptic seizures.
  • the subject is usually a human, but it is also possible to administer to mammals other than humans, for example, pet animals such as dogs and cats, and livestock such as cows, sheep, and pigs. Below, a case where the subject is a human will be explained.
  • the subject in need of prevention, treatment or alleviation of epileptic seizures is preferably one of the following (1) to (4).
  • Subjects with a history of head trauma, stroke, brain tumor, Alzheimer's disease, etc., or brain diseases Subjects whose family members have epilepsy (3) Subjects who have been diagnosed with epilepsy (4) Subjects who have had an epileptic seizure subject of something
  • treatment refers to completely or partially inhibiting a disease, disorder, or condition, eg, halting its onset over a period of time.
  • therapy refers to therapeutic treatment.
  • prevention refers to preventing a disease, disorder, or condition from occurring in a patient who may be predisposed to, but has not yet been diagnosed with, the disease, disorder, or condition.
  • Prevention refers to preventive measures.
  • the term "alleviation” refers to the complete or partial alleviation of a disease, disorder or condition in a patient who has been diagnosed as having a predisposition to the disease, disorder and/or condition, e.g. , refers to causing regression of a disease, disorder, and/or condition. It also means reducing the frequency of seizures associated with a disease, disorder, or condition.
  • ⁇ Epileptic seizure> The seizure types seen in epilepsy are broadly classified by the International Federation of Epilepsy into focal seizures, generalized seizures, and seizures of unknown origin, and are subcategorized into focal seizures with preserved consciousness, focal impaired consciousness seizures, and focal motor onset seizures. It is classified into onset seizures, focal nonmotor onset seizures, focal onset bilateral tonic-clonic seizures, generalized motor seizures, generalized nonmotor seizures, motor seizures of unknown origin, nonmotor onset seizures of unknown origin, and unclassifiable seizures.
  • the composition according to the present invention is provided for the prevention, treatment, or alleviation of epileptic seizures, but the targeted seizure types are not particularly limited.
  • prevention, treatment, and alleviation of epileptic seizures mean prevention of onset of seizures, disappearance of seizures, and reduction in the frequency of onset of seizures before and after administration of the antiepileptic composition of the present invention, respectively. .
  • Administration routes for the antiepileptic composition of the present invention include, for example, oral administration, tube administration (nasally, gastrostomy, intestinal fistula, etc.), intraperitoneal administration, intramuscular administration, transmucosal administration, intranasal administration, and rectal administration. Examples include internal administration, but oral administration is particularly preferred.
  • the content of Bifidobacterium bacteria in the anti-epileptic composition of the present invention is not particularly limited, but the content of Bifidobacterium bacteria is such that the amount of Bifidobacterium bacteria can be easily ingested per day to exhibit effective anti-epileptic effects.
  • it contains bacteria of the genus P. genus.
  • the content of Bifidobacterium bacteria in the antiepileptic composition is preferably 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU/g, more preferably 1 ⁇ 10 8 to 1 ⁇ 10 per gram of the composition. 11 CFU/g, more preferably 1 ⁇ 10 9 to 5 ⁇ 10 10 CFU/g, but more preferably.
  • the antiepileptic composition of the present invention containing Bifidobacterium bacteria may be administered once per day, or may be administered in two or more divided doses per day.
  • the anti-epileptic composition of the present invention may be administered at any time during the day, but is preferably administered, for example, before meals, after meals, or before going to bed.
  • the anti-epileptic composition of the present invention containing Bifidobacterium bacteria may be administered once, but preferably once a week or more, and preferably once every 3 days or more. is more preferable, it is even more preferable that the drug is administered once or more every two days, and it is most preferable that the drug is administered continuously every day. For example, it is preferable to administer it daily for three weeks or more.
  • ⁇ Evaluation method> The effectiveness of the antiepileptic compositions described herein in preventing, treating, or alleviating epileptic seizures can be evaluated based on animal models such as mouse or rabbit or monkey models.
  • animal models such as mouse or rabbit or monkey models.
  • animal models that can be used to evaluate the anti-epileptic compositions described herein include the Kindling mouse model by administration of pentylenetetrazole, which can also be used to evaluate the effects of drugs, etc. It is being In addition, as an evaluation item for antiepileptic effects in animal models, for example, convulsion scores are used (Giovambattista De Sarro, Neuropharmacology 39 (2000) 2147-2161).
  • treating epileptic seizures may mean reducing the convulsion score to 0, and alleviating epileptic seizures may mean reducing the convulsion score.
  • Prevention of epileptic seizures may also mean suppressing an increase in convulsion scores in subjects who are predisposed to having epileptic seizures compared to a group that does not take the anti-epileptic composition.
  • treating epileptic seizures may mean preventing epileptic seizures from occurring for two years or more, and alleviating epileptic seizures means shortening the duration of seizures and reducing seizure frequency.
  • epileptic seizures which may mean reduction in severity, reduction in the severity of symptoms, and elimination of some seizure types, is the use of anti-epileptic drugs in subjects who have not been diagnosed with epilepsy but are predisposed to having epileptic seizures. It may also mean reducing the incidence of epilepsy compared to a group not receiving the composition.
  • the anti-epileptic composition of the present invention may be a pharmaceutical and contains either or both of a Bifidobacterium bacterium and a Bifidobacterium bacterium culture.
  • the subject to be administered, the active ingredient Bifidobacterium bacteria, and the culture of Bifidobacterium bacteria are the same as in the antiepileptic composition of the present invention described above.
  • the medicine according to the present invention can be prepared by adding the anti-epileptic composition of the present invention to a known medicine, or a new medicine can be prepared by mixing the anti-epileptic composition into the raw material of the medicine. You can also.
  • the medicines of the present technology include those in which the anti-epileptic composition of the present invention is used as a medicine, and those in which the anti-epileptic composition of the present invention is added to existing medicines.
  • the antiepileptic composition of the present invention When using the antiepileptic composition of the present invention as a medicine, it may be used as it is, after being concentrated, or after being processed into a solid, granule, or powder form.
  • the antiepileptic composition of the present invention can be formulated into a desired dosage form as appropriate depending on the administration method, such as oral administration or parenteral administration.
  • the dosage form is not particularly limited, but for oral administration, for example, solid preparations such as powders, granules, tablets, troches, and capsules; liquid preparations such as solutions, syrups, suspensions, and emulsions; can be converted into
  • parenteral administration it can be formulated into suppositories, sprays, inhalants, ointments, patches, injections, and the like.
  • formulation can be carried out by a known method as appropriate depending on the dosage form.
  • a pharmaceutical carrier When formulating, a pharmaceutical carrier may be added as appropriate.
  • components such as excipients, pH adjusters, coloring agents, and flavoring agents that are commonly used in formulation can be used.
  • components having the effect of preventing, treating, or alleviating diseases and symptoms that are known or will be discovered in the future may be used in combination depending on the purpose.
  • various organic or inorganic carriers can be used depending on the dosage form.
  • carriers for solid preparations include excipients, binders, disintegrants, lubricants, stabilizers, and flavoring agents.
  • excipient examples include sugar derivatives such as lactose, sucrose, glucose, mannitol and sorbitol; starch derivatives such as corn starch, potato starch, ⁇ -starch, dextrin and carboxymethyl starch; crystalline cellulose and hydroxypropyl cellulose. , cellulose derivatives such as hydroxypropyl methylcellulose, carboxymethylcellulose and carboxymethylcellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate and magnesium aluminate metasilicate; phosphate derivatives such as calcium phosphate; Examples include carbonate derivatives such as calcium carbonate; and sulfate derivatives such as calcium sulfate.
  • sugar derivatives such as lactose, sucrose, glucose, mannitol and sorbitol
  • starch derivatives such as corn starch, potato starch, ⁇ -starch, dextrin and carboxymethyl starch
  • binder examples include, in addition to the excipients described above, gelatin; polyvinylpyrrolidone; macrogol, and the like.
  • disintegrant examples include, in addition to the excipients described above, chemically modified starch or cellulose derivatives such as croscarmellose sodium, sodium carboxymethyl starch, and crosslinked polyvinylpyrrolidone.
  • lubricant examples include talc; stearic acid; stearic acid metal salts such as calcium stearate and magnesium stearate; colloidal silica; waxes such as beegum and gay wax; boric acid; glycol; carboxylic acid such as fumaric acid and adipic acid. Acids; carboxylic acid sodium salts such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; starch derivatives, etc. Can be mentioned.
  • the stabilizer examples include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; sorbic acid and the like.
  • the flavoring agent examples include sweeteners, acidulants, fragrances, and the like.
  • carriers used in the case of liquid preparations for oral administration include solvents such as water, flavoring agents, and the like.
  • anti-epileptic composition of the present invention can be used in combination with drugs that are known or will be discovered in the future and have an anti-epileptic effect.
  • the content of Bifidobacterium bacteria in the medicine of this technology is not particularly limited, but it contains Bifidobacterium bacteria in an amount that can be easily ingested in a daily dose to exhibit an effective antiepileptic effect. It is preferable to do so.
  • the content of Bifidobacterium bacteria in the medicine is preferably 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU/g, more preferably 1 ⁇ 10 8 to 1 ⁇ 10 11 CFU/g, per 1 g of medicine. More preferably, it is 1 ⁇ 10 9 to 5 ⁇ 10 10 CFU/g.
  • the daily dosage of Bifidobacterium bacteria in the pharmaceutical of the present technology is preferably at least 1 ⁇ 10 6 CFU/kg body weight/day or more.
  • the daily dose may be administered once a day, or may be divided into two or more doses per day.
  • Administration routes include, for example, oral administration, tube administration (nasally, gastrostomy, intestinal fistula, etc.), intraperitoneal administration, intramuscular administration, transmucosal administration, intranasal administration, and intrarectal administration.
  • oral administration is preferred.
  • the subject of administration is usually a human, but the present invention also includes mammals other than humans, such as pet animals such as dogs and cats, and livestock such as cows, sheep, and pigs.
  • the anti-epileptic composition of the present invention may be a food and contains either or both of a Bifidobacterium bacterium and a Bifidobacterium bacterium culture.
  • the subjects to be ingested, the active ingredients of Bifidobacterium bacteria, and the culture of Bifidobacterium bacteria are the same as in the antiepileptic composition of the present invention described above.
  • Foods in the present invention include foods and drinks.
  • Food and beverages include tablets, liquid foods, and feed (including for pets), regardless of their form such as liquid, paste, solid, or powder, as well as flour products, instant foods, processed agricultural products, and marine products.
  • dairy products include fermented milk, milk drinks, lactic acid bacteria drinks, sweetened condensed milk, skim milk powder, sweetened milk powder, modified milk powder, cream, cheese, butter, and ice creams.
  • dairy products include fermented milk, milk drinks, lactic acid bacteria drinks, sweetened condensed milk, skim milk powder, sweetened milk powder, modified milk powder, cream, cheese, butter, and ice creams.
  • flour products include bread, macaroni, spaghetti, noodles, cake mixes, fried flour, and bread crumbs.
  • instant foods include instant noodles, cup noodles, retort/cooked foods, cooked canned foods, microwave foods, instant soups/stews, instant miso soup/suimono, canned soups, freeze/dried foods, and other instant foods. Can be mentioned.
  • processed agricultural products include canned agricultural products, canned fruits, jams and marmalades, pickles, boiled beans, dried agricultural products, and cereals (processed grain products).
  • processed marine products include canned marine products, fish meat hams and sausages, seafood paste products, marine delicacies, and boiled fish meat.
  • processed livestock products include canned livestock products, pastes, and livestock hams and sausages.
  • fats and oils examples include butter, margarines, and vegetable oils.
  • Examples of basic seasonings include soy sauce, miso, sauces, processed tomato seasonings, mirin, and vinegar.
  • Examples of complex seasonings and foods include cooking mixes, curry ingredients, sauces, dressings, noodle soups, spices, and other complex seasonings.
  • frozen foods examples include raw frozen foods, semi-cooked frozen foods, and cooked frozen foods.
  • sweets examples include caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice sweets, bean sweets, dessert sweets, and other sweets.
  • beverages include carbonated drinks, natural fruit juices, fruit juice drinks, soft drinks with fruit juice, pulp drinks, fruit drinks with fruit particles, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powder drinks, and concentrated drinks. , sports drinks, nutritional drinks, alcoholic drinks, and other beverages.
  • dairy products are particularly preferred as the anti-epileptic food of the present invention, and fermented milk is particularly preferred.
  • fermented milk is particularly preferred.
  • the content of Bifidobacterium bacteria in the food of the present invention is not particularly limited, but the content of Bifidobacterium bacteria is such that the amount of Bifidobacterium bacteria can be easily ingested per day to exhibit effective antiepileptic effects. It is preferable to contain.
  • the food provided by the present invention can be used in the same manner as described for the above-mentioned pharmaceuticals, and can also be used for purposes other than anti-epileptic effects.
  • the content of Bifidobacterium bacteria in the food is the same as the Bifidobacterium bacteria contained in the medicine. As such, it can be applied to the target of the above-mentioned medicine.
  • the content of Bifidobacterium bacteria in food is preferably 1 x 10 6 to 1 x 10 12 CFU/g, more preferably 1 x 10 8 to 1 x 10 11 CFU/g, per 1 g of food. More preferably, it contains 1 ⁇ 10 9 to 5 ⁇ 10 10 CFU/g.
  • the daily intake of Bifidobacterium bacteria in the food of the present invention is preferably at least 1 ⁇ 10 6 CFU/kg body weight/day or more.
  • the consumer may consume the daily amount of Bifidobacterium bacteria once a day, or may divide the intake into two or more times per day.
  • routes of intake include oral intake and tube intake (nasally, gastrostomy, intestinal fistula, etc.), and oral intake is particularly preferred.
  • Ingestants are usually humans, but the present invention also includes mammals other than humans, such as pet animals such as dogs and cats, and livestock such as cows, sheep, and pigs.
  • the food according to the invention is also suitable for subjects (e.g., humans or other mammals) that do not have "morbid” or "abnormal” symptoms, conditions, or diseases, i.e., "healthy”. or to a subject (e.g., a human or other mammal) in a "normal” state, to maintain a "healthy” or “normal” state. Furthermore, it can be applied to "healthy people concerned about epilepsy symptoms" in order to maintain a "healthy" or "normal” state.
  • the Bifidobacterium bacterium and its culture are a component of a pharmaceutical composition or a food ingredient, the Bifidobacterium bacterium and its culture Their pharmacological effects are basically the same. Therefore, the amount and method of application of the food can be adjusted as appropriate, based on the Bifidobacterium bacterium and its culture itself, depending on the expected effect.
  • the food related to the present invention is a health food, a functional food, an enteral nutritional food, a food for special use, a food with health claims, a food for specified health uses, a food with nutritional function claims, a food with functional claims, or Examples include foods such as quasi-drugs. Specifically, it may be a food that is ingested for purposes such as "may reduce the risk of developing epilepsy." In this case as well, the amount and method of application of the food can be adjusted as appropriate based on the Bifidobacterium bacterium and its culture itself, depending on the expected effect. .
  • the present invention also provides a method for preventing, treating, or alleviating epileptic seizures using the above-mentioned antiepileptic composition, or its active ingredients, Bifidobacterium bacteria and its culture. provide.
  • the present invention also provides a non-therapeutic administration method of administering the above-mentioned antiepileptic composition, or one or both of its active ingredients, a Bifidobacterium bacterium and a culture thereof.
  • the anti-epileptic composition, one or both of the Bifidobacterium bacterium and its culture, and the dosage, frequency and timing of administration are as described above.
  • an effective amount of a Bifidobacterium bacterium or a culture thereof is used in the method of preventing, treating or alleviating epileptic seizures.
  • the present application includes the following embodiments.
  • Composition for use [2] The anti-epileptic composition is orally administered to the subject at a concentration of 1 ⁇ 10 6 to 1 ⁇ 10 12 CFU/g of Bifidobacterium breve MCC1274 strain (FERM BP-11175) per day.
  • the anti-epileptic composition according to [1] which contains the active ingredient in an amount of .
  • Bifidobacterium breve strain MCC1274 (FERM BP-11175) or a culture thereof for use in the prevention, treatment or alleviation of epileptic seizures.
  • Non-containing method comprising administering an effective amount of one or both of Bifidobacterium breve strain MCC1274 (FERM BP-11175) and its culture to a subject in need of prevention, treatment or alleviation of epileptic seizures. Therapeutic Administration Methods.
  • mice were divided into two groups (14 mice in the non-administration group and 12 mice in the administration group), and one group (administration group) was suspended in physiological saline to a concentration of 1.3 x 10 10 cfu/mL.
  • Bifidobacterium breve MCC1274 strain [FERM BP-11175] (hereinafter referred to as B.
  • breve MCC1274 strain) was orally administered (3.25 x 10 9 cfu/0.25 mL/mouse) every other day on days when PTZ was not administered ( Figure 1 ).
  • the other group (non-administration group) included B.
  • mice was orally administered.
  • Mouse behavior was observed for 30 minutes after PTZ administration, and the degree of convulsion was scored according to the following evaluation method.
  • a new anti-epileptic composition can be provided.
  • the anti-epileptic composition of the present invention has excellent safety and can be continuously administered over a long period of time because its active ingredient is a culture containing one or both of a Bifidobacterium bacterium and a culture thereof. It is very useful because there is little need to worry about side effects.

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JP2019172661A (ja) * 2018-03-28 2019-10-10 森永乳業株式会社 ストレス緩和用組成物並びに該ストレス緩和用組成物を用いた医薬品組成物及び飲食品組成物
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