WO2024143060A1 - 脳神経細胞保護用組成物 - Google Patents

脳神経細胞保護用組成物 Download PDF

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WO2024143060A1
WO2024143060A1 PCT/JP2023/045395 JP2023045395W WO2024143060A1 WO 2024143060 A1 WO2024143060 A1 WO 2024143060A1 JP 2023045395 W JP2023045395 W JP 2023045395W WO 2024143060 A1 WO2024143060 A1 WO 2024143060A1
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composition
docosahexaenoic acid
acid
lutein
brain
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PCT/JP2023/045395
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English (en)
French (fr)
Japanese (ja)
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賢 森田
俊明 末安
啓甫 安本
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サントリーホールディングス株式会社
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Priority to CN202380089042.4A priority Critical patent/CN120417894A/zh
Priority to JP2024567649A priority patent/JPWO2024143060A1/ja
Publication of WO2024143060A1 publication Critical patent/WO2024143060A1/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
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A23L33/115—Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12—Fatty acids or derivatives thereof
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • A61K31/6615—Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7024—Esters of saccharides
    • 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
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the inventors conducted extensive research to solve the above problems and discovered that by combining lutein and/or its fatty acid ester with a docosahexaenoic acid compound in a specific ratio range, brain nerve cells are protected more effectively (synergistically) than when only lutein and/or its fatty acid ester or only docosahexaenoic acid compounds are used, which led to the completion of the present invention.
  • the composition for protecting brain nerve cells of the present invention contains the following components (A) and (B): (A) lutein and/or its fatty acid ester; (B) a docosahexaenoic acid compound, and the weight ratio ((B)/(A)) of component (A) (converted into lutein) to component (B) (converted into docosahexaenoic acid) is 10 to 120.
  • the composition of the present invention contains lutein and/or its fatty acid ester and a docosahexaenoic acid compound as active ingredients.
  • compositions of the present invention comprise lutein and/or its fatty acid esters.
  • Lutein is a type of carotenoid.
  • Lutein and/or its fatty acid ester are contained in plants and can be prepared by extracting from plants.
  • Lutein fatty acid ester is contained in green and yellow vegetables such as spinach, kale, broccoli, pumpkin, carrot, paprika, etc.; fruits such as orange, peach, papaya, prune, mango, avocado, raspberry, rosehip, etc.; and marigold petals.
  • docosahexaenoic acid compounds extracted and/or purified from raw materials such as natural products containing docosahexaenoic acid compounds may be used, or the raw materials may be used as they are to contain the docosahexaenoic acid compounds in the composition.
  • raw materials containing docosahexaenoic acid compounds include edible oils and fats such as oils and fats extracted from fish oil, meat, and dairy products.
  • the amount in terms of lutein or similar expressions means the amount of lutein when component (A) is lutein, and means the value obtained by multiplying the number of moles of the ester by the molecular weight of lutein when component (A) is a fatty acid ester of lutein.
  • the amount of lutein and/or its fatty acid ester can be measured by HPLC (high performance liquid chromatography).
  • the amount calculated as docosahexaenoic acid or a similar expression means the amount when component (B) is free DHA. When component (B) is not free DHA, it means the amount calculated as free DHA after liberating DHA by saponification or enzyme treatment.
  • the amount of free DHA can be measured by gas chromatography (GC).
  • GC gas chromatography
  • Amelioration of a condition or disease includes recovering a subject from a condition or disease, alleviating the symptoms of a condition or disease, slowing or preventing the progression of a condition or disease, etc. Amelioration includes at least partial amelioration.
  • the compositions of the present invention may be applied in either therapeutic or non-therapeutic applications, the latter being a concept that does not include medical procedures, i.e., surgery, treatment or diagnosis of humans.
  • composition of the present invention may contain any additives and any components other than component (A) and component (B) as long as the effects of the present invention are not impaired.
  • additives and components may be selected depending on the form of the composition, and those that can generally be used in foods and beverages, pharmaceuticals, quasi-drugs, feed, etc. may be used.
  • Optional components include zeaxanthin and/or its fatty acid esters, arachidonic acid compounds, eicosapentaenoic acid compounds, and the like.
  • the composition of the present invention preferably further contains zeaxanthin and/or its fatty acid ester, an arachidonic acid compound, and an eicosapentaenoic acid compound.
  • the composition of the present invention may contain lutein and/or its fatty acid ester, a docosahexaenoic acid compound, zeaxanthin and/or its fatty acid ester, an arachidonic acid compound, and an eicosapentaenoic acid compound as active ingredients.
  • Zeaxanthin is a type of carotenoid.
  • Zeaxanthin and/or its fatty acid esters are contained in vegetables such as paprika and spinach, chicken eggs, marigold petals, etc., and can be prepared, for example, by extraction from plants.
  • the composition of the present invention may contain a plant-derived raw material rich in zeaxanthin and/or its fatty acid esters. Zeaxanthin and/or its fatty acid esters may also be used as commercially available products.
  • the salt of arachidonic acid examples include calcium salt and sodium salt.
  • the compound containing arachidonic acid as a constituent fatty acid is preferably a compound selected from the group consisting of triglycerides in which some or all of the constituent fatty acids are arachidonic acid, diglycerides in which some or all of the constituent fatty acids are arachidonic acid, monoglycerides in which the constituent fatty acid is arachidonic acid, phospholipids in which some or all of the constituent fatty acids are arachidonic acid, glycolipids in which some or all of the constituent fatty acids are arachidonic acid, and alcohol esters of arachidonic acid.
  • arachidonic acid compounds triglycerides, diglycerides and phospholipids in which some or all of the constituent fatty acids are arachidonic acid are more preferred, triglycerides and diglycerides in which some or all of the constituent fatty acids are arachidonic acid are even more preferred, and triglycerides in which some or all of the constituent fatty acids are arachidonic acid are particularly preferred.
  • microorganisms examples include those belonging to the genera Mortierella, Conidiobolus, Pythium, Phytophthora, Penicillium, Cladosporium, Mucor, Fusarium, Aspergillus, Rhodotorula, Entomophthora, Echinosporangium, and Saprolegnia.
  • arachidonic acid compounds extracted and/or purified from raw materials such as natural products containing arachidonic acid compounds may be used, or the raw materials may be used as they are to contain the arachidonic acid compounds in the composition.
  • raw materials containing arachidonic acid compounds include edible oils and fats such as oils and fats produced by microorganisms, and oils and fats extracted from eggs, meat, and seafood. There are no limitations on the method for producing arachidonic acid compounds using microorganisms, and known methods, such as the method described in JP 2016-172770 A, can be used.
  • eicosapentaenoic acid compound eicosapentaenoic acid (free eicosapentaenoic acid, hereinafter also referred to as EPA), its salts and derivatives thereof can be used.
  • the eicosapentaenoic acid compound may be used alone or in combination of two or more.
  • the derivative of eicosapentaenoic acid for example, a compound having a structure in which eicosapentaenoic acid is bonded and a compound that can separate eicosapentaenoic acid by hydrolysis can be used.
  • a compound containing eicosapentaenoic acid in the constituent fatty acid can be mentioned.
  • the eicosapentaenoic acid compound may be used alone or in combination of two or more.
  • the eicosapentaenoic acid compound is preferably selected from the group consisting of free eicosapentaenoic acid, salts thereof, and compounds containing eicosapentaenoic acid as a constituent fatty acid.
  • salts of eicosapentaenoic acid include calcium salts and sodium salts.
  • the compound containing eicosapentaenoic acid as a constituent fatty acid is preferably a compound selected from the group consisting of triglycerides in which some or all of the constituent fatty acids are eicosapentaenoic acid, diglycerides in which some or all of the constituent fatty acids are eicosapentaenoic acid, monoglycerides in which the constituent fatty acid is eicosapentaenoic acid, phospholipids in which some or all of the constituent fatty acids are eicosapentaenoic acid, glycolipids in which some or all of the constituent fatty acids are eicosapentaenoic acid, and alcohol esters of eicosapentaenoic acid.
  • eicosapentaenoic acid compounds triglycerides, diglycerides and phospholipids in which some or all of the constituent fatty acids are eicosapentaenoic acid are more preferred, triglycerides and diglycerides in which some or all of the constituent fatty acids are eicosapentaenoic acid are even more preferred, and triglycerides in which some or all of the constituent fatty acids are eicosapentaenoic acid are particularly preferred.
  • the eicosapentaenoic acid compound is not limited by its form or production method, and may be a chemically synthesized product, or may be derived from a natural product or a genetically modified organism (Escherichia coli, yeast, plant, etc.).
  • Examples of the eicosapentaenoic acid compound derived from a natural product include those derived from fish and shellfish, algae, fungi (Labyrinthula, etc.), and plants (Marchantia polymorpha, etc.) that have the ability to produce EPA.
  • it is preferable that the eicosapentaenoic acid compound is derived from fish and shellfish.
  • eicosapentaenoic acid compounds extracted and/or purified from raw materials such as natural products containing eicosapentaenoic acid compounds may be used, or the raw materials may be used as they are to contain eicosapentaenoic acid compounds in the composition.
  • Raw materials containing eicosapentaenoic acid compounds include, for example, edible oils and fats such as oils and fats extracted from fish oil, eggs, meat, dairy products and algae.
  • fish oil containing eicosapentaenoic acid compounds it is preferable to use fish oil concentrated so that the content of eicosapentaenoic acid compounds (eicosapentaenoic acid equivalent) is 5% by weight or more, preferably 10% by weight or more, more preferably 20% by weight or more.
  • eicosapentaenoic acid compounds extracted and/or purified from fish oil containing eicosapentaenoic acid compounds may be used, or the fish oil may be used as it is.
  • the cognitive function is preferably memory function. Cognitive functions such as memory function can be evaluated, for example, by the Cognitrax test.
  • Cognitrax is a cognitive function test designed for Japanese people based on CNS vital Signs developed by CNS Vital Signs, Inc. in the United States (Gualtieri CT. et al. Reliability and validity of a computerized neurocognitive test battery, CNS Vital Signs. Arch Clin Neuropsychol 21(7):623-643(2006)).
  • the compositions of the invention can be used to improve overall memory as assessed, for example, by the Cognitrax test.
  • various foods and drinks can be made by blending components that can be used in foods and drinks (e.g., food ingredients, food additives used as necessary, etc.) with component (A) and component (B).
  • the foods and drinks are not particularly limited, and examples thereof include general foods and drinks, health foods, health drinks, functional foods, foods for specified health uses, dietary supplements, foods and drinks for sick people, etc.
  • the above health foods, functional foods, foods for specified health uses, dietary supplements, etc. can be used in various formulation forms, such as fine granules, tablets, granules, powders, capsules, chewable tablets, dry syrups, syrups, liquids, beverages, and liquid diets.
  • the dosage form may be a dosage form suitable for administration.
  • oral administration for example, oral solid preparations such as tablets, coated tablets, fine granules, granules, powders, pills, capsules, dry syrups, and chewables; oral liquid preparations such as oral liquids and syrups.
  • parenteral administration for example, injections, drips, ointments, lotions, patches, suppositories, nasal preparations, and pulmonary preparations (inhalants) may be used.
  • the pharmaceutical product may be a pharmaceutical product for non-human animals.
  • the administration (ingestion) form of the pharmaceutical or quasi-drug may be oral or parenteral (percutaneous, transmucosal, enteral, injection, etc.) administration. From the viewpoint of more fully obtaining the effects of the present invention, the administration form of the pharmaceutical or quasi-drug is preferably oral.
  • the carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in pharmaceuticals or quasi-drugs, and examples of such carriers, additives, etc. include one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc.
  • the feed can be prepared by mixing components (A) and (B) with components that can be used in feed.
  • feed include livestock feed for cows, pigs, chickens, sheep, horses, etc.; small animal feed for rabbits, guinea pigs, rats, mice, etc.; and pet food for dogs, cats, small birds, etc.
  • the manufacturing method is not particularly limited, and it can be manufactured by a general method using component (A) and component (B).
  • the contents of component (A) and component (B) in the composition of the present invention can be appropriately set depending on the form of the composition, etc.
  • the total content of lutein and/or its fatty acid esters in the composition of the present invention is, for example, preferably 0.01% by weight or more, more preferably 0.1% by weight or more, and preferably 9% by weight or less.
  • the total content of lutein and/or its fatty acid esters (in terms of lutein) in the composition is preferably 0.01 to 9 wt %, more preferably 0.1 to 9 wt %.
  • the total content of docosahexaenoic acid compounds in the composition of the present invention is, for example, preferably 1 wt % or more, more preferably 10 wt % or more, and preferably 80 wt % or less in the composition.
  • the total content of docosahexaenoic acid compounds (calculated as docosahexaenoic acid) in the composition is preferably 1 to 80% by weight, more preferably 10 to 80% by weight.
  • the total content (in terms of arachidonic acid) in the composition is, for example, preferably 2% by weight or more, more preferably 4% by weight or more, and preferably 40% by weight or less, more preferably 32% by weight or less.
  • the total content of arachidonic acid compounds (in terms of arachidonic acid) in the composition is preferably 2 to 40% by weight, more preferably 4 to 32% by weight.
  • the content of arachidonic acid can be measured by gas chromatography (GC).
  • the composition of the present invention can be ingested or administered in a manner appropriate for its form.
  • the composition of the present invention is preferably administered or ingested orally.
  • the intake amount (which can also be called the dosage amount) of the composition of the present invention is not particularly limited as long as it is an amount (effective amount) that provides a brain nerve cell protective effect, and may be appropriately set depending on the administration form, administration method, subject body weight, etc.
  • the total dosage of lutein and/or its fatty acid esters is, in terms of lutein, preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and even more preferably 80 mg or less per 60 kg body weight per day.
  • the total dosage of docosahexaenoic acid compounds is, in terms of docosahexaenoic acid, preferably 10 mg or more, more preferably 100 mg or more, and preferably 2,000 mg or less, more preferably 1,000 mg or less per 60 kg body weight per day.
  • the total dosage of lutein and/or its fatty acid esters is, in terms of lutein, preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per 60 kg body weight per day for a human (adult).
  • the total dosage of docosahexaenoic acid compounds is, in terms of docosahexaenoic acid, preferably 10 to 2,000 mg, more preferably 100 to 2,000 mg, and even more preferably 100 to 1,000 mg per 60 kg body weight per day for a human (adult). It is preferable to ingest or administer the above amount one or more times a day, for example, once a day, or in divided doses (for example, 2 to 3 times a day).
  • the above-mentioned amounts of lutein and/or its fatty acid ester and docosahexaenoic acid compound are orally ingested or administered to a human.
  • the composition of the present invention can be used to allow a human (adult) to ingest or administer the above amounts of lutein and/or its fatty acid ester and docosahexaenoic acid compound per 60 kg of body weight per day.
  • the total dosage of lutein and/or its fatty acid esters is the total amount of lutein and/or its fatty acid esters when two or more kinds of lutein and/or its fatty acid esters are used, and the total dosage of docosahexaenoic acid compounds is the total amount of docosahexaenoic acid compounds when two or more kinds of docosahexaenoic acid compounds are used.
  • the total dosage of zeaxanthin and/or its fatty acid esters when orally administered or ingested by a human (adult) is preferably 0.1 mg or more, more preferably 0.5 mg or more, and preferably 50 mg or less, more preferably 30 mg or less, and even more preferably 20 mg or less, per 60 kg of body weight per day, in terms of zeaxanthin.
  • the total dosage of zeaxanthin and/or its fatty acid esters is preferably 0.1 to 50 mg, more preferably 0.1 to 30 mg, and even more preferably 0.5 to 20 mg, per 60 kg of body weight per day, in terms of zeaxanthin, for a human (adult).
  • the total dosage of the eicosapentaenoic acid compound is, in terms of eicosapentaenoic acid, preferably 10 to 500 mg, more preferably 20 to 400 mg, and even more preferably 30 to 300 mg per 60 kg of body weight per day for a human (adult).
  • the present invention also includes the use of lutein and/or its fatty acid ester and a docosahexaenoic acid compound to produce a composition for protecting brain nerve cells.
  • the weight ratio of the docosahexaenoic acid compound (converted to docosahexaenoic acid) to the lutein and/or its fatty acid ester (converted to lutein) is 10 to 120.
  • lutein and/or its fatty acid ester and docosahexaenoic acid compound, and the ratio thereof, etc. are the same as those of the composition of the present invention described above.
  • the lutein and/or its fatty acid ester, and the docosahexaenoic acid compound one type may be used, or two or more types may be used.
  • the above uses are preferably in humans or non-human mammals, more preferably in humans.
  • a numerical range expressed by a lower limit and an upper limit includes the lower limit and the upper limit.
  • a range expressed by "1 to 2" means 1 or more and 2 or less, including 1 and 2.
  • the upper limit and the lower limit may be in any combination. All academic and patent literature cited herein is hereby incorporated by reference.
  • SH-SY5Y was put to sleep using medium 1 and cultured in a CO2 incubator (37°C, 5% CO2 , ambient O2 , humidified).
  • the medium was replaced with fresh medium 2 once every 2 to 3 days.
  • the medium was replaced with the above-mentioned medium 3 once every 2 to 3 days.
  • On the 14th day it was replaced with medium 4 to which Rotenone (Sigma-Aldrich Co.) was added so as to have a final concentration of 0.2 ⁇ M, and cultured for 48 hours.
  • Table 1 shows the LDH release level values in each Example and Comparative Example, and the rate of change from Comparative Example 1 (the difference in LDH release level compared to Comparative Example 1). Also shown is the sum of the rate of change from Comparative Example 1 for the combinations of Comparative Examples corresponding to the combinations of DHA and lutein used in Examples 1 to 4. 1 shows the rates of change in Examples 1 to 4 and Comparative Example 6. In addition, the sum of the rates of change from Comparative Example 1 for the combinations of DHA and lutein used in Examples 1 to 4 and the combinations of Comparative Examples corresponding to each combination is also shown. In FIG.
  • Example 5 We investigated the effects of a combination of arachidonic acid, DHA, EPA, lutein, and zeaxanthin on memory function in elderly individuals with cognitive decline. The memory function was examined using the above-mentioned Cognitrax (provided by Health Solutions Co., Ltd.).
  • the subjects were healthy men and women aged 55 to 79 years who complained of forgetfulness. Before the start of the study, the subjects underwent a cognitive function test, MoCA-J (Japanese version of Montreal Cognitive Assessment).

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PCT/JP2023/045395 2022-12-26 2023-12-19 脳神経細胞保護用組成物 WO2024143060A1 (ja)

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