WO2017179354A1 - 認知機能改善用組成物 - Google Patents
認知機能改善用組成物 Download PDFInfo
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- WO2017179354A1 WO2017179354A1 PCT/JP2017/010083 JP2017010083W WO2017179354A1 WO 2017179354 A1 WO2017179354 A1 WO 2017179354A1 JP 2017010083 W JP2017010083 W JP 2017010083W WO 2017179354 A1 WO2017179354 A1 WO 2017179354A1
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- oxidation reaction
- cognitive function
- reaction product
- hop oxidation
- hop
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- 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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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to a composition for improving cognitive function.
- the maintenance, improvement, and improvement of cognitive functions are required by a wide range of generations from young to old. Maintenance, improvement, and improvement of memory and learning skills are important not only for students and adults studying for exams and qualification exams, but also for daily work and life. Moreover, since the decline in memory and concentration in the elderly is related to the quality of life, it is required to prevent, maintain, improve and improve the cognitive function.
- Non-patent Document 1 Korean Patent Application 1
- hop which is the origin of bitter components in beer
- various health functions such as sedation and stomach effect are known.
- an extract obtained from this hop is blended in a certain amount or more with respect to food or drink, a unique and intense bitter taste may be produced, which may impair the palatability.
- Patent Document 1 It has been reported that the lipid metabolism improving function can be maintained while suppressing (Patent Document 1).
- Patent Document 1 there has been no report on the relationship between hop-derived components and their oxidized products and cognitive functions.
- the present inventors have now found that hop oxidation reaction products are effective in maintaining, improving, improving cognitive functions, and the like.
- the present invention is based on this finding.
- an object of the present invention is to provide a composition that is effective for maintaining, improving, and improving cognitive function.
- a composition for maintaining, enhancing and / or improving cognitive function comprising a hop oxidation reaction product.
- the hop oxidation reaction product is an S-fraction.
- composition according to [6] above comprising S-fraction in an amount of 1 to 200 mg per dose in terms of dry mass.
- Any of the above [1] to [7] for use in the treatment, prevention or amelioration of a disease or symptom for which maintenance, enhancement and / or improvement of cognitive function is effective in the treatment, prevention or amelioration The composition as described.
- a cognitive function improving agent For the production of a composition or food for maintaining, enhancing and / or improving cognitive function, or for producing a cognitive function maintaining agent, a cognitive function improving agent and a cognitive function improving agent Use of hop oxidation products.
- a hop oxidation reaction product and a composition containing the same as a cognitive function maintenance agent, a cognitive function enhancer, or a cognitive function improver Use of a hop oxidation reaction product and a composition containing the same for use in maintaining, enhancing and / or improving cognitive function.
- a disease in which maintenance, enhancement, and / or improvement of cognitive function is effective for its treatment, prevention, or improvement comprising ingesting or administering to a subject an effective amount of a hop oxidation reaction product How to treat, prevent and ameliorate symptoms.
- a composition for the treatment, prevention and improvement of diseases and conditions for which maintenance, enhancement and / or improvement of cognitive function is effective in the treatment, prevention or improvement thereof or Use of a hop oxidation reaction product for the manufacture of a therapeutic, prophylactic or ameliorating agent for diseases and symptoms for which maintenance, enhancement and / or improvement of cognitive function is effective in the treatment, prevention or improvement thereof.
- a hop oxidation reaction product and a composition containing the same as a therapeutic agent, preventive agent, and ameliorating agent for diseases and symptoms in which maintenance, enhancement and / or improvement of cognitive function is effective in the treatment, prevention or improvement thereof Use [16] A hop oxidation reaction product and a composition comprising the same for use in the treatment, prevention and amelioration of diseases and conditions in which maintenance, enhancement and / or improvement of cognitive function is effective in the treatment, prevention or amelioration thereof.
- a composition containing a hop oxidation reaction product that can exhibit functions such as maintaining, improving, and improving cognitive function. Since the hop oxidation reaction product uses a hop-derived component that humans have taken as food for many years, the present invention is advantageous in that it can be used as a functional material safe for mammals including humans.
- FIG. 5 is a diagram showing a schedule of human tests in Example 2.
- 6 is a diagram showing an example of a letter-number-Sequencing Test question sheet in Example 2.
- FIG. 6 is a graph showing the result of Trail Making Test in Example 2.
- 10 is a graph showing the result of Pattern Recognition Memory in Example 2.
- 10 is a graph showing the results of Spatial Working Memory (within errors) in Example 2.
- Indicates p ⁇ 0.05 (t-test). 10 is a graph showing the results of Spatial Working Memory (between errors) in Example 2.
- FIG. 10 is a diagram showing a time rate (Discrimination index) of searching for a novel object of a mouse in Example 4.
- FIG. 10 is a diagram illustrating a search time ratio of searching for a novel object of a mouse in Example 4.
- 10 is a graph showing the total number of mice entering (arm ⁇ ⁇ ⁇ ⁇ entry) in Example 5. It is the graph showing the spontaneous alternation behavior fluctuation rate (spontaneous alteration) of the mouse
- FIG. FIG. 10 is a diagram showing a time rate (Discrimination index) for searching for a novel object of a mouse in Example 5.
- FIG. 10 is a diagram illustrating a search time ratio of searching for a novel object of a mouse in Example 5.
- the hop oxidation reaction product means a product obtained by oxidizing a hop or a processed product thereof (hop pellet, hop extract, etc.).
- the hop oxidation reaction product provided by the present invention can be obtained, for example, by oxidizing a hop by contacting it with oxygen in the air.
- the hop oxidation reaction product can be produced, for example, by oxidizing hops according to the method described in Patent Document 1.
- the oxidation treatment is preferably performed by heating the hops in air.
- heating temperature is not specifically limited, A preferable upper limit is 100 degreeC and a more preferable upper limit is 80 degreeC.
- the heating temperature is set to 100 ° C. or lower, it is advantageous in promoting oxidation preferentially over isomerization.
- the minimum of preferable heating temperature is 60 degreeC. When the heating temperature is set to 60 ° C. or higher, it is advantageous for allowing the oxidation reaction to proceed efficiently.
- the reaction period is not particularly limited, and can be appropriately determined depending on the type of hop and the reaction temperature.
- the form of the hop when it is subjected to the oxidation reaction is not particularly limited as long as it can contact oxygen in the air, but the reaction time can be shortened preferably by making it into powder form.
- the hop may be in any form as long as it contains a lupulin part, and is harvested and dried, harvested and dried, compressed, crushed, or pelletized. However, it is preferably in the form of hop pellets.
- hop pellets Commercially available hop pellets may be used, for example, hop spikelets compressed into pellets (Type 90 pellets), pellets with selectively enriched lupurin (Type 45 pellets), or isomerization treatment Hop pellets (for example, Isomerized Pellets (HopSteiner)) and the like.
- a hop extract oxidation reaction product generated by subjecting the hop extract to oxidation treatment may be provided as a hop oxidation reaction product in the present invention.
- the hop extract oxidation reaction product can be produced, for example, by oxidizing the hop extract according to the method described in Patent Document 1.
- Hops contain acidic resin components such as ⁇ -acid (humulones), ⁇ -acid (luprons), and iso- ⁇ -acid (isohumulones).
- humulones are used in the meaning including humulone, adhumulone, cohumulone, posthumulone, and prehumulone.
- luprons are used in the meaning including lupron, adolpron, colpron, post-lupron and plepron.
- isohumulones refers to isohumulone, isoadhumulone, isocohumulone, isoposthumulone, isoprehumulone, Rho-isohumulone, Rho-isoadhumulone, Rho-isocohumulone, Rho-isoposthumulone, Rho-isoprehumulone, tetrahydroisohumulone, Tetrahydroisoadhumulone, Tetrahydroisocohumulone, Tetrahydroisoprehumulone, Tetrahydroisoposthumulone, Hexahydroisohumulone, Hexahydroisoadhumulone, Hexahydroisocohumulone, Hexahydroisocohumulone And hexahydroisoprehumulone.
- Isohumulones have cis and trans stereoisomers, and unless otherwise specified, they are used to include both.
- the contents of ⁇ -acid, ⁇ -acid and iso- ⁇ -acid are reduced, and the contents of components other than these are increased.
- the ratio of the peak areas of ⁇ acid, ⁇ acid and iso ⁇ acid to the HPLC total peak area of the oxidation reaction product Is 20% or less, preferably 10% or less.
- Components other than ⁇ -acid, ⁇ -acid and iso- ⁇ -acid contained in the oxidation reaction product of the present invention can be easily detected by well-known analytical means such as HPLC.
- a hop oxidation reaction product prepared by the same procedure as in Example 1 of Patent Document 1 contains components other than ⁇ acid, ⁇ acid, and iso ⁇ acid, and a peak corresponding to this component (this In the specification, “S-fraction (S-Fr)”) may exhibit physiological activity.
- S-fraction (S-Fr) peaks in the range indicated by arrows (excluding ⁇ acid and ⁇ acid peaks) correspond to the S-fraction.
- the hop oxidation reaction product preferably contains ⁇ acid oxide, iso ⁇ acid oxide and ⁇ acid oxide, and as such oxide, for example, “tricyclooxyisohumulones” are contained.
- “tricyclooxyisohumulones” means tricyclooxyisocohumulone A (TCOIcoH A: see formula 1 below, IUPAC name: (3aS, 5aS, 7S, 8aS) -3,3a- dihydroxy-7- (1-hydroxy-1-methylethyl) -6,6-dimethyl-2- (2-methylpropanoyl) -5a, 6,7,8-tetrahydro-3aH, 5H-cyclopenta [c] pentalene-1, 4-dione), tricyclooxyisohumulone A (TCOIH A: see formula 2 below, IUPAC name: (3aS, 5aS, 7S, 8aS) -3,3a-dihydroxy-7- (1-hydroxy-1 -methylethyl)
- oxides other than “tricyclooxyisohumulones” contained in the hop oxidation reaction product include scorpiomymurinol A and scorpiocohumulinol A.
- the hop oxidation reaction product may be provided as an aqueous medium extract.
- the aqueous medium is not particularly limited as long as it is usually used for food production, but is preferably water or ethanol, more preferably water.
- the extraction temperature is not particularly limited, but is preferably 60 ° C. or lower, and more preferably 50 to 60 ° C. in consideration of extraction efficiency.
- the hop oxidation reaction product used in the present invention is a total amount of tricyclooxyisohumulone A and tricyclooxyisocohumulone A, scorpiooffmurinol A and scorpiokov. It can be characterized by a ratio to the total amount of murinol A (in terms of dry mass), for example, an aqueous medium extract of a hop oxidation reaction product with this ratio in the range 1-30, preferably in the range 2-20 An aqueous medium extract of the hop oxidation reaction product can be used.
- the hop oxidation reaction product used in the present invention can be characterized by the content ratio (in terms of dry mass) of TCOIHs in the S-fraction.
- the content ratio is 5 to 15% by mass, preferably 5 to 12%.
- a hop oxidation reaction product preferably an aqueous medium extract of the hop oxidation reaction product
- the S-fraction of the hop oxidation reaction product is mainly composed of the components of the arrow A1 fraction shown in FIG. 1, the matured described in Biosci., Biotechnol., Biochem., 2015 (79): 1684-1694
- the content can be measured by the same measurement method as hop bitter acids.
- the Brix value of the aqueous medium extract of the hop oxidation reaction product is not particularly limited, but is, for example, 3 or less, preferably 1.5 to 3.
- the aqueous medium extract of the hop oxidation reaction product may remove insoluble components by decantation or filter paper.
- the aqueous medium extract of the hop oxidation reaction product may also be subjected to activated carbon treatment.
- composition of the present invention may contain one or more other components intended to maintain, enhance and / or improve cognitive function, in addition to the hop oxidation reaction product.
- Components intended to maintain, improve and / or improve cognitive function include, for example, omega-3 series fatty acids such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), ginkgo biloba extract, resveratrol, curcumin Examples include polyphenols, lecithin, isohumulone, peptides, and vitamins that prevent abnormal metabolism of homocysteine, which is a risk factor for Alzheimer's disease.
- the hop oxidation reaction product (preferably, the S-fraction) has the effect of maintaining, improving and improving the cognitive function including the memory function. Therefore, the hop oxidation reaction product can be used as an active ingredient of a composition for maintaining, improving and / or improving cognitive function, and also maintains a cognitive function, a cognitive function improving method, and a cognitive function improving method. Can be used for Further, the hop oxidation reaction product can be used as an active ingredient of a cognitive function maintenance agent, a cognitive function improvement agent, and a cognitive function improvement agent.
- “cognitive function” is used to include a memory function and an attention / concentration function.
- the “memory function” means a function including a spatial cognitive function, a working memory function, a working memory function, an episode memory function, a visual memory function, and a learning function.
- the working memory includes a language working memory, a working working memory, and a spatial working memory.
- “maintaining memory function” includes preventing deterioration of memory function.
- “Improving memory function” includes, for example, enhancing the memory function from the current level, promoting the establishment of medium- to long-term memory, and thus promoting the growth of the brain.
- “improvement of memory function” includes, for example, recovery of a memory function that has once declined or a symptom having a sign of decline. Examples of maintenance, improvement and / or improvement of the memory function include enhancement of the memory function and suppression of decrease in the memory function.
- “maintenance of attention / concentration function” includes, for example, suppressing reduction in attention and concentration caused by aging in the elderly and the like. “Improvement of attention / concentration function” includes, for example, improving temporary attention / concentration function and promoting maintenance / improvement of medium- to long-term attention / concentration function. Furthermore, “improvement of attention / concentration function” includes, for example, recovery of a function that has once decreased due to aging or other factors, or a function having a sign of decrease. Examples of the maintenance, improvement and / or improvement of the attention / concentration function include enhancement of the attention / concentration function and suppression of deterioration of the attention / concentration function.
- the method for maintaining cognitive function, the method for improving cognitive function, and the method for improving cognitive function of the present invention are carried out by ingesting or administering an effective amount of a hop oxidation reaction product to a human or non-human animal.
- a method for maintaining cognitive function, a method for improving cognitive function, and cognition comprising ingesting or administering an effective amount of a hop oxidation reaction product to a subject in need thereof.
- a function improvement method is provided.
- the subject of ingestion or administration is a mammal including a human, preferably a human.
- the present invention also provides the use of a hop oxidation reaction product for the manufacture of compositions and foods for maintaining, enhancing and / or improving cognitive function.
- the present invention further provides the use of a hop oxidation reaction product for the production of a cognitive maintenance agent, a cognitive improvement agent, and a cognitive improvement agent.
- a hop oxidation reaction product and a composition containing the same as a cognitive function maintenance agent, cognitive function enhancer or cognitive function improver there is further provided use of a hop oxidation reaction product and a composition containing the same for use in maintaining, enhancing and / or improving cognitive function.
- hop oxidation reaction product in the present invention may be used in humans and non-human animals, and is intended for both therapeutic use and non-therapeutic use.
- non-therapeutic means not including the act of operating, treating, or diagnosing a human (that is, a medical act on a human), and specifically, receiving a doctor or doctor's instructions It means that the person does not include a method of performing surgery, treatment or diagnosis on humans.
- the hop oxidation reaction product can also be used for the treatment, prevention or improvement of diseases and symptoms for which the maintenance, improvement and / or improvement of cognitive function is effective for the treatment, prevention or improvement.
- the hop oxidation reaction product can be used as a therapeutic agent, preventive agent, or ameliorating agent for these diseases and symptoms, and can also be used in a method for treating, preventing, or improving these diseases and symptoms.
- the therapeutic method, the preventive method, and the ameliorating method of the present invention can be performed by administering an effective amount of a hop oxidation reaction product to a mammal including a human in need of treatment, prevention, or improvement. That is, according to the present invention, maintenance, enhancement and / or improvement of cognitive function comprising ingesting or administering an effective amount of a hop oxidation reaction product to a subject in need thereof.
- the subject of ingestion or administration is a mammal including a human, preferably a human.
- a therapeutic composition a preventive composition, and an improved composition for diseases and symptoms for which maintenance, enhancement and / or improvement of cognitive function is effective in the treatment, prevention or improvement thereof.
- hop oxidation products are preferably pharmaceutical compositions.
- a hop oxidation reaction product for the manufacture of a therapeutic agent, preventive agent and ameliorating agent for diseases and symptoms in which maintenance, enhancement and / or improvement of cognitive function is effective in the treatment, prevention or improvement thereof Use of is provided.
- the present invention further includes a hop oxidation reaction product as a therapeutic agent, preventive agent and ameliorating agent for diseases and symptoms whose maintenance, enhancement and / or improvement of cognitive function is effective for the treatment, prevention or improvement thereof, and the same Use of the composition is provided.
- hop oxidation reaction products for use in the treatment, prevention and amelioration of diseases and conditions for which the maintenance, enhancement and / or improvement of cognitive function is effective in the treatment, prevention or amelioration thereof and the like A composition is provided.
- composition for maintaining, improving and / or improving the cognitive function of the present invention and the cognitive function maintaining agent, improving agent and / or improving agent of the present invention and the therapeutic agent, prophylactic agent and improving agent of the present invention are pharmaceuticals. It can be provided in the form of a quasi-drug, food, feed (including pet food) and the like, and can be carried out according to the following description. Moreover, the cognitive function maintenance method, the cognitive function improvement method, the cognitive function improvement method, and the treatment method, prevention method, and improvement method of the present invention can be performed according to the following description. Furthermore, the use of the invention can also be carried out according to the description below.
- composition and agent of the present invention and the hop oxidation reaction product which are the active ingredients of the present invention, can be orally administered to humans and non-human animals.
- Oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. These preparations can be formulated using a pharmaceutically acceptable carrier by a technique usually performed in the art.
- Pharmaceutically acceptable carriers include excipients, binders, diluents, additives, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, etc. Is mentioned.
- the hop oxidation reaction product which is an active ingredient of the present invention
- the food product can be provided as it is as a food product, or can be provided by containing it in a food product.
- the food provided in this manner is a food containing an effective amount of a hop oxidation reaction product.
- “containing an effective amount” of a hop oxidation reaction product means that a hop oxidation reaction product (preferably, an S-fraction) within a range described later when an amount normally consumed in each food is ingested. ) Refers to the content that can be ingested.
- Food means health food, functional food, nutritional supplement, supplement, health functional food (eg, food for specified health use, functional nutrition food, functional indication food), food for special use (eg, food for infants) , Food for pregnant women, food for sick people).
- composition and agent of the present invention and the hop oxidation reaction product have the effect of maintaining, improving and / or improving cognitive function, they can be provided by being included in foods taken daily or in foods taken as supplements. .
- the composition and agent of the present invention and the hop oxidation reaction product can be provided in a unit package form in which the amount taken per meal is predetermined.
- the unit packaging form per serving include a form in which a certain amount is specified by a pack, packaging, can, bottle, or the like.
- the intake per meal can be determined according to the intake per hop oxidation reaction product, which will be described later.
- the food item of the present invention may be provided together with a document or the like on which the explanation items regarding the intake amount are displayed on the package or the explanation items are described.
- the food of the present invention may be marked with a cognitive function maintenance, enhancement and / or improvement effect.
- the food of the present invention may be given the following partial or full display.
- “maintenance, improvement and / or improvement of cognitive function” is used in the meaning including the following indications.
- Maintain, enhance, improve, improve, enhance, support, maintain memory ability ⁇ Maintain, enhance, enhance, improve, enhance, support, maintain cognitive function ⁇ Maintain attention Enhance, Improve, Improve, Enhance, Support, Maintain ⁇ Continue to Concentrate, Enhance, Improve, Enhance, Support, Maintain ⁇ Help to maintain memory, decrease Prevent ⁇ Inadvertently prevent, forgetfulness ⁇ Improve memory retention, improve memory accuracy ⁇ Suppress the decline in memory associated with aging
- the food of the present invention can be provided by adding a hop oxidation reaction product to a daily intake food or a food intake as a supplement.
- the hop oxidation reaction product is preferably a health food or a functional food.
- one or more other components intended to maintain, enhance and / or improve cognitive function may be further added to the food of the present invention containing a hop oxidation reaction product. Examples of the component intended to maintain, enhance and / or improve cognitive function include those described above.
- the form of “food” is not particularly limited, and may be, for example, a beverage form, a semi-liquid form or a gel form.
- Examples of supplements include tablets produced by tableting after adding excipients, binders and the like to dry powder of hop oxidation reaction products, and capsules enclosed in capsules.
- Foods provided in the present invention include foods and drinks containing carbohydrates such as rice, noodles, breads and pasta; Western confectionery such as cookies and cakes; Japanese confectionery such as buns and sheepskin; candy, gums, yogurt and Various confectionery such as pudding and frozen desserts; whiskey, bourbon, spirits, liqueur, wine, fruit liquor, sake, sake, shochu, beer, non-alcoholic beer with alcohol content of 1% or less, sparkling liquor, other miscellaneous sake , Alcoholic beverages such as strawberry high; beverages with fruit juice, beverages with vegetable juice, beverages with fruit juice and vegetable juice, soft drinks, carbonated beverages, milk, soy milk, milk beverages, drink-type yogurt, drink-type jelly, coffee, Cocoa, tea drink, energy drink, sports drink, mineral water, near water, non-alcohol
- Non-alcoholic beverages such as beer-taste beverages; processed products using eggs, processed products of seafood and livestock meat (including organs such as liver) (including delicacy), and the like, but are not limited thereto It is not a thing.
- Tea beverages include fermented tea, semi-fermented tea and non-fermented tea, for example, black tea, green tea, barley tea, brown rice tea, sencha tea, gyokuro tea, roasted tea, oolong tea, turmeric tea, puer tea, rooibos tea. , Rose tea, chrysanthemum tea, ginkgo leaf tea, herb tea (for example, mint tea, jasmine tea).
- fruits used in fruit juice-containing beverages and fruit and vegetable juice-containing beverages include apples, mandarin oranges, grapes, bananas, pears, peaches, mangoes, acais, blueberries, and ume.
- vegetables used in vegetable juice-containing beverages, fruit juices, and vegetable juice-containing beverages include tomato, carrot, celery, pumpkin, cucumber, and watermelon.
- the hop oxidation reaction product which is an active ingredient of the present invention uses a hop-derived component that humans have taken as food for many years, it has low toxicity, and mammals (for example, humans, mice, rats, Rabbits, dogs, cats, cows, horses, pigs, monkeys, etc.).
- the intake or dosage of the hop oxidation reaction product can be determined depending on the sex, age and weight of the recipient, symptoms, administration time, dosage form, administration route, combined drugs and the like.
- Examples of the intake and dose (in terms of dry mass) of adult hop oxidation reaction product in the present invention are 8 to 1700 mg (preferably 160 to 1000 mg), and S-fraction adult (50 kg) )
- the intake and dose (in terms of dry mass) per dose is 1 to 200 mg (preferably 20 to 120 mg).
- the intake and dose (in terms of dry mass) of hop oxidation reaction product per adult (50 kg) is, for example, 160 to 1000 mg
- S-fraction adult intake (50 kg) per dose and dose (in terms of dry mass) is, for example, 20 to 120 mg.
- Adults of hop oxidation products to maintain, improve, and improve cognitive function in people with cognitive decline including those with dementia, suspected mild cognitive impairment, and those with mild cognitive impairment) 50kg
- the intake and dose (converted to dry mass) per time is, for example, 8 to 1700 mg
- the intake and dose (converted to dry weight) per adult (50 kg) of S-fraction is For example, 1 to 200 mg.
- the hop oxidation reaction product may be ingested or administered in several doses depending on the subject.
- intake or administration in the above amount is performed once a week (preferably once every 3 days) for 1 month (preferably 3 months, more preferably 6 months). More preferably, it can be continued every day).
- the ratio (%) of the peak values of ⁇ acid, ⁇ acid, and iso ⁇ acid in the total area value (mAU ⁇ min) of all peaks detected at a detection wavelength of 270 nm was calculated.
- areas where solvent peaks and negative peaks due to injection shock occur were excluded from analysis.
- the HPLC chromatogram upon analysis of the product was as shown in FIG.
- Example 1 Preparation of Hop Oxidation Reaction Product (1) Hop Oxidation Treatment Step Hops of Haratauperle seed (HPE seed) were pulverized with a pellet mill, and the obtained hop pulverized product was stirred at 120 ° C. at 120 ° C. while stirring. Heated for about an hour. The obtained heated hop (aged hop pellet) was added to water so as to have a solid content concentration of 5 w / v%, and extraction treatment was performed at 50 ° C. for 30 minutes. The obtained extract was subjected to solid-liquid separation by decantation to obtain a solid-liquid separation liquid (Brix about 2).
- hop oxidation reaction products include scorpiohumurinol A, scorpiocohumulinol A, tricyclooxyisohumulone A, tricyclooxyisocohumulone A as ⁇ acid oxide, iso ⁇ acid oxide or ⁇ acid oxide.
- the ratio of the total amount of tricyclooxyisohumulone A and tricyclooxyisocohumulone A to the total amount of scorpiohumurinol A and scorpiocohumulinol A ((tricyclooxyisohumulone A + tricyclooxyisocohumulone A) / (Scolpiofumlinol A + Scorpio kofumlinol A)) was as follows. Lot 1: 3.2 Lot 2: 6.8 Lot 3: 12.1
- the ratio of the total amount of tricyclooxyisohumulone and tricyclooxyisocohumulone to the total amount of scorpionofurinol and scorpiocohumulinol is about 2 to 20. I understood.
- Example 2 Confirmation test of effect of hop oxidation reaction product intake on cognitive function (1)
- (1) Preparation of placebo and test food
- the hard capsules used for each food were unified in color and shape so that they could not be distinguished by appearance.
- one test food contains 17.5 mg of S-Fr in terms of dry mass.
- Test conditions Ten healthy male and female non-smokers 40 years of age or older were randomly assigned to the placebo group and the test food group, 5 persons each. Two placebos per day were used in the placebo group, and two test foods were used per day in the test food group (S-Fr was 35 mg in terms of dry mass in 2 test foods).
- the test schedule is as shown in FIG. Specifically, on the first day of the test, the cognitive function was evaluated without taking each food. On the third day of the test, each food was ingested and the cognitive function was evaluated after 1 hour. On the fourth day of the test, only the food was ingested. On the fifth day of the test, each food was ingested and the cognitive function was evaluated after 1 hour. In addition, during the test period, intake of food and drink containing hops was prohibited, and intake of food and drink containing caffeine was prohibited before the cognitive function evaluation on Tests 1, 3, and 5.
- TMT Cognitive function evaluation method PART A of Trail Making Test
- LNS Letter-Number Sequencing Test
- CANTAB of CAMBRIDGE COGNITION
- PRM Pattern Recognition Memory
- SWM Spatial Working Memory
- PAL Paired Associates Learning
- the order of evaluation was TMT, PRM, SWM, PAL, and LNS.
- the cognitive function evaluation was performed in the morning and started after resting for 10 minutes after entering the evaluation room. Details of each evaluation method are as follows. Both evaluation methods are widely accepted methods for evaluating cognitive function.
- TMT TMT is a method for evaluating visual search, processing speed, and duration of attention. Specifically, paper on which numbers from 1 to 25 were printed was used, the numbers were connected in order from 1 and ended when 25 was reached, and the time required until the end was measured. The faster the time, the faster the processing speed and the greater the attention and concentration.
- PRM PRM is a method for evaluating visual pattern recognition memory. Specifically, using a tablet PC, the subject first memorized 10 patterns randomly displayed on the screen. After all the patterns are displayed, two types of patterns (one pattern each displayed and one not displayed) are displayed in the center of the screen, so the subject touches the pattern displayed first. I let you. If the pattern displayed earlier can be touched, the answer is correct, and the larger the number of correct answers, the higher the visual pattern recognition memory, that is, the higher the visual memory.
- (Iii) SWM SWM is a method for evaluating working memory in space. Specifically, since 12 boxes are displayed on the screen using a tablet PC, the subject touched the boxes and opened them in order. Only one of the twelve boxes contained a blue square, and until the blue square was found, it was one turn and repeated a total of 12 turns. Once you find a box that contains a blue rectangle, the same box will not contain a blue rectangle on subsequent turns. If you touch the same box more than once in one turn, it counts as with errors, and if you touch a box that had a blue square in the past in 12 turns, it counts as between errors. did. The smaller the number of within errors and between errors, the higher the working memory of the space.
- (Iv) PAL PAL is a method for evaluating visual space recognition memory and learning ability. Specifically, using a tablet PC, 12 boxes are displayed on the screen, and one type of pattern is hidden in each of them. Each box was displayed with a random opening pattern, and the subject memorized the pattern and the location of the box where it was. Since all the patterns are displayed one by one in the center of the screen after all the boxes have been opened, the subject was allowed to touch the box containing the pattern. The process was continued until all 12 patterns were correctly answered, and the number of mistakes was measured as the number of errors. The smaller the number of errors, the higher the spatial recognition memory and learning ability.
- V LNS LNS is a method for evaluating the working memory of a language.
- the test supervisor read out the numbers and alphabets randomly arranged, memorized them, and rearranged the order in the head, and pronounced them in the order of numbers and alphabets. If you can pronounce it in the correct order, the answer will be correct, and the higher the number of correct answers, the higher the working memory of the language.
- An example of the question sheet used is shown in FIG. 3 (what the test supervisor reads out is shown on the left of the question sheet and the answer is shown on the right of the question sheet).
- Table 3 shows the background data of subjects in each group. It was confirmed that there was no age and gender bias among the groups.
- the results of the first evaluation are used as reference values, and the results of the second and third evaluations are shown as change values from the results of the first evaluation in FIG. According to FIG. 4, it was confirmed that the time required for completion in the test food group was shorter in both the second and third evaluations than in the placebo group. From this, it was shown that attention and concentration improved by ingestion of hop oxidation reaction products.
- the results of the first evaluation are used as reference values, and the results of the second and third evaluations are shown as change values from the results of the first evaluation in FIG. According to the results of FIG. 5, it was confirmed that the number of correct answers was larger in the test food group than in the placebo group in both the second and third evaluations. From this, it was shown that visual memory is improved by ingestion of hop oxidation reaction products.
- the results of the first evaluation are used as reference values, and the results of the second and third evaluations are shown in FIG. 6 and FIG. 7 as changes from the results of the first evaluation.
- FIGS. 6 and 7 it was confirmed that both the errors in the test food group (FIG. 6) and the number of errors in the between errors (FIG. 7) were smaller in the second and third evaluations than in the placebo group. It was. From this, it was shown that the working memory of the space improves by ingesting the hop oxidation reaction product.
- the results of the first evaluation are used as reference values, and the results of the second and third evaluations are shown as change values from the results of the first evaluation in FIG. According to the results of FIG. 8, it was confirmed that the number of errors in the test food group was smaller in both the second and third evaluations than in the placebo group.
- the results of the first evaluation are used as reference values, and the results of the second and third evaluations are shown as change values from the results of the first evaluation in FIG. According to the results of FIG. 9, it was confirmed that the number of correct answers was larger in the test food group than in the placebo group in both the second and third evaluations. This indicates that the intake of hop oxidation products improves the working memory of the language.
- Example 3 Confirmation test of effect of hop oxidation reaction product intake on cognitive function (2)
- effects on short-term memory and spatial memory were evaluated.
- Cognitive function evaluation method Y-maze test
- Y-maze test When the mouse is put into a certain space, if a route originally selected immediately before is remembered, a route different from the immediately previous route is selected for a new search desire. Therefore, when a mouse is put into a Y-shaped maze having three arms having the same width, length, etc., it normally enters an arm different from the arm that has just entered.
- the Y-maze test is a test that uses the properties of mice to evaluate short-term memory and spatial memory, which are indicators of cognitive function.
- the order of the moved arm was recorded when the mouse was put in the tip of any arm of the Y-shaped maze and allowed to search freely for 8 minutes.
- spontaneous alternation behavior a case where different arms are selected three times in succession and entered is called spontaneous alternation behavior.
- the total number of intrusions into the arm and the number of spontaneous alternation actions in time were counted, and the voluntary alternation behavior fluctuation rate (%) was calculated using the following formula (1).
- a higher voluntary alternation behavior variation rate indicates that short-term memory is retained.
- FIG. 11 shows the total number of approaches
- FIG. 12 shows the voluntary alternation behavior fluctuation rate. From the results of FIGS. 11 and 12, no change in the total number of intrusions due to the administration of the hop oxidation reaction product is observed, that is, the administration of the hop oxidation reaction product does not affect the amount of behavior (FIG. 11). It was confirmed that the product administration group had a higher rate of voluntary alternation behavior than the non-administration group, that is, short-term memory was retained by the hop oxidation reaction product (FIG. 12). From these results, it was shown that the hop oxidation reaction product containing S-Fr can improve the cognitive function.
- Example 4 Confirmation test of effect of hop oxidation reaction product intake on cognitive function (3)
- effects on long-term memory and episode memory were evaluated.
- Cognitive function evaluation method new object recognition test
- a mouse When a mouse originally recognizes it as a novel object, it approaches and performs a search action such as confirming its shape and smelling it. At this time, a search action is not performed on the stored object, or the search is performed for a shorter time than the novel object.
- the novel object recognition test uses this property.
- Two blocks X and Y of the same size as a golf ball are installed in a place 4cm away from the adjacent corner of the container (floor 38.5cm x 38.5cm, height 40cm). To do. The mouse was placed in this container and subjected to a free search for 10 minutes. After completion, the mouse was returned to the breeding cage. This is an acquisition attempt.
- the mouse When the interval between the acquisition trial and the test trial is short, the mouse exhibits a long time searching action with a novel object (golf ball Z in this test), and its preference is increased with the interval between the acquisition trial and the test trial. Attenuate. Therefore, it is generally considered that the behavioral change with respect to novelty reflects “memory of object shape at the time of acquisition”.
- the search time for substances at the time of acquisition trial and the search time for new substances at the time of test trial were measured, and the Discrimination index (DI) was calculated by the following equation (2).
- the Discrimination index was high, and a dose-dependent tendency was observed for this effect. It was shown that administration of the hop oxidation reaction product containing S-Fr preserved the memory of the shape of the object during the acquisition trial, that is, enhanced long-term memory.
- the search time for a novel object (novel) and a non-new object (familiar) at the time of a test trial was measured, and the search time ratio (exploration time (%)) was calculated by the following equations (3) and (4) (FIG. 15). .
- the search time ratio for novel objects tended to increase depending on the dose.
- Example 5 Confirmation test of effect of hop oxidation reaction product intake on cognitive function (4)
- short-term memory and spatial memory in an Alzheimer's disease model were evaluated.
- An oligomer hypothesis has been proposed that amyloid ⁇ , which is one of the causative substances of Alzheimer's disease, forms a soluble oligomer in the brain and exhibits neurotoxicity.
- ADDL A ⁇ -derived diffusible ligands
- ADDL A ⁇ -derived diffusible ligands
- mice administered with ADDLs can be used as a model for cognitive decline and diseases caused by accumulation of waste products in the brain, especially Alzheimer type dementia (Shunaga Iwata, Takaomi Nishimichi (2010) “ Solving the mystery of Alzheimer's disease ”, Chugai Medical, pp. 173-180).
- Amyloid ⁇ 1-42 (Peptide Laboratories) was dissolved in hexafluoroisopropanol (HFIP, Wako) to 1 mM. The solution was allowed to stand at room temperature for 30 minutes, and then HFIP was removed by evaporation, and dissolved in dimethyl sulfoxide (DMSO, manufactured by Wako) to 5 mM. The solution was diluted to 100 ⁇ M in phosphate buffer (PBS) and allowed to stand at 4 ° C. for 24 hours to polymerize amyloid ⁇ . The solution was centrifuged at 10,000 rpm for 15 minutes, and the supernatant was obtained as an ADDL solution.
- HFIP hexafluoroisopropanol
- DMSO dimethyl sulfoxide
- hop oxidation reaction product Y-shaped maze test
- the hop oxidation reaction product is S-Fr, resulting in a dry mass conversion of 0 (diluted solvent) and 1, 10 mg / kg body weight. As such, it was forcibly administered orally into the stomach.
- the hop oxidation reaction product was prepared by the same procedure as in Example 3 (2).
- the cognitive function of the mouse was evaluated by the same Y-shaped maze test as in Example 3 (1) 60 minutes after a single administration.
- FIG. 16 shows the total number of approaches
- FIG. 17 shows the voluntary alternation behavior fluctuation rate.
- variation of the total number of invasion by hop oxidation reaction product administration is not recognized, ie, a hop oxidation reaction product administration does not affect behavior amount (FIG. 16), but a hop oxidation reaction product administration group
- the voluntary alternation behavior fluctuation rate was higher, that is, it was confirmed that cognitive functions such as short-term memory were retained by the hop oxidation reaction product.
- the effect tended to depend on the dose of S-Fr (FIG. 17).
- mice showed a high Discrimination index in the group in which the hop oxidation product was administered intragastrically. It was shown that administration of the hop oxidation reaction product containing S-Fr preserved the memory of the shape of the object during the acquisition trial, that is, enhanced long-term memory.
- the search time ratio (exploration time (%)) was calculated in the same manner as in Example 4 (FIG. 19). It was found that the search time ratio for novel objects tended to increase by administration of the hop oxidation reaction product containing S-Fr.
- the hop oxidation reaction product containing S-Fr is associated with a decrease in cognitive function, memory retention, retention and regeneration due to accumulation of waste products in the brain even when ingested for a short period. It has been shown to improve the decline and even improve dementia such as Alzheimer's disease.
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Abstract
Description
[1]ホップ酸化反応産物を含んでなる、認知機能の維持、向上および/または改善のための組成物。
[2]認知機能が記憶機能である、上記[1]に記載の組成物。
[3]認知機能が注意・集中機能である、上記[1]に記載の組成物。
[4]食品組成物である、上記[1]~[3]のいずれかに記載の組成物。
[5]1回摂取に適した単位包装形態である、上記[1]~[4]のいずれかに記載の組成物。
[6]ホップ酸化反応産物がS-フラクションである、上記[1]~[5]のいずれかに記載の組成物。
[7]S-フラクションを乾燥質量換算で1回当たりの摂取量で1~200mgで含んでなる、上記[6]に記載の組成物。
[8]認知機能の維持、向上および/または改善がその治療、予防または改善に有効である疾患または症状の治療、予防または改善に用いるための、上記[1]~[7]のいずれかに記載の組成物。
[9]有効量のホップ酸化反応産物を、対象に摂取させるか、あるいは投与することを含んでなる、認知機能の維持方法、認知機能の向上方法および認知機能の改善方法。
[10]認知機能の維持、向上および/または改善のための組成物または食品の製造のための、または、認知機能の維持剤、認知機能の向上剤および認知機能の改善剤の製造のための、ホップ酸化反応産物の使用。
[11]認知機能の維持剤、認知機能の向上剤または認知機能の改善剤としての、ホップ酸化反応産物およびそれを含む組成物の使用。
[12]認知機能の維持、向上および/または改善に用いるための、ホップ酸化反応産物およびそれを含む組成物。
[13]有効量のホップ酸化反応産物を、対象に摂取させるか、あるいは投与することを含んでなる、認知機能の維持、向上および/または改善がその治療、予防または改善に有効である疾患および症状の治療方法、予防方法および改善方法。
[14]認知機能の維持、向上および/または改善がその治療、予防または改善に有効である疾患および症状の治療用組成物、予防用組成物および改善用組成物の製造のための、または、認知機能の維持、向上および/または改善がその治療、予防または改善に有効である疾患および症状の治療剤、予防剤および改善剤の製造のための、ホップ酸化反応産物の使用。
[15]認知機能の維持、向上および/または改善がその治療、予防または改善に有効である疾患および症状の治療剤、予防剤および改善剤としての、ホップ酸化反応産物およびそれを含む組成物の使用
[16]認知機能の維持、向上および/または改善がその治療、予防または改善に有効である疾患および症状の治療、予防および改善に用いるための、ホップ酸化反応産物およびそれを含む組成物。
本発明において、ホップ酸化反応産物とは、ホップまたはその加工物(ホップペレット、ホップエキス等)を酸化処理して得られるものをいう。本発明により提供されるホップ酸化反応産物は、例えば、ホップを空気中の酸素に接触させて酸化することにより得ることができる。
より、その含有量を測定することができる。
後記実施例に示されるように、ホップ酸化反応産物(好ましくは、S-フラクション)は記憶機能をはじめとする認知機能の維持、向上および改善作用を有する。従って、ホップ酸化反応産物は認知機能の維持、向上および/または改善のための組成物の有効成分として使用することができるとともに、認知機能の維持方法、認知機能の向上方法および認知機能の改善方法に使用することができる。また、ホップ酸化反応産物は認知機能の維持剤、認知機能の向上剤および認知機能の改善剤の有効成分として使用することができる。本発明において「認知機能」は記憶機能および注意・集中機能を含む意味で用いられる。
・記憶力を持続する、高める、向上させる、改善する、増強する、サポートする、維持する
・認知機能を持続する、高める、向上させる、改善する、増強する、サポートする、維持する
・注意力を持続する、高める、向上させる、改善する、増強する、サポートする、維持する
・集中力を持続する、高める、向上させる、改善する、増強する、サポートする、維持する
・記憶力の維持に役立つ、低下を防止する
・うっかりを防止する、物忘れを防止する
・記憶の定着を向上させる、記憶の精度を高める
・加齢に伴う記憶の低下を抑制する
ホップとしては、ペレット状のハラタウペルレ種(HPE種)を用いた。このホップをミルで粉砕し、80℃で24時間まで加熱反応時間を保持した。得られた生成物について以下のように前処理を実施した後、HPLC分析に供した。
採取した生成物を10%w/vとなるようエタノールに添加し、50℃で1時間抽出を行った。得られた抽出液をエタノールで10倍に希釈した。
[HPLC構成装置]
ホンプ:LC-10ADvp×3(SHIMADZU)
デガッサー:DGU-20A5(SHIMADZU)
システムコントローラー:CBM-20A(SHIMADZU)
オートサンプラー:SIL-20ACHT(SHIMADZU)
カラムオーブン:CTO-20AC(SHIMADZU)
フォトダイオードアレー検出器:SPD-M20A(SHIMADZU)
波形解析ソフトウェア:LCSolution(SHIMADZU)
カラム:Alltima C18 2.1mm I.D. x100mm 粒子径3μm
流速:0.6mL/min
溶出溶媒A:水/リン酸、1000/0.2, (v/v) + EDTA(free) 0.02%(w/v)
溶出溶媒B:アセトニトリル
溶出溶媒C:水
注入量:3μL
カラム温度:40℃
検出波長:270nm(酸化反応産物、イソα酸、α酸、β酸)
グラジエントプログラム:
(1)ホップの酸化処理工程
ハラタウペルレ種(HPE種)のホップをペレットミルで粉砕し、得られたホップ粉砕物を大気下で攪拌しながら60℃で120時間程度加熱した。得られた加熱済みホップ(熟成ホップペレット)に、固形分濃度5w/v%となるように水に添加し、50℃で30分間抽出処理を行った。得られた抽出液をデカンテーションにより固液分離し、固液分離液(Brix 約2)を得た。
上記(1)で得られた固液分離液に、活性炭(Y180C、味の素ファインケミカル社製;対固液分離液0.5w/v%)およびポリビニルポリピロリドン(ポリクラール10、ISPジャパン社製;対固液分離液0.4w/v%)を添加して2時間静置した。得られた混合液に濾過助剤(珪藻土)を添加し、濾過処理を行い、濾液(Brix値 約1.5)を得た。得られた濾液をホップ酸化反応産物水抽出物として以下の実施例で使用した。
上記(2)で得られた濾液(ホップ酸化反応産物水抽出液)について、以下の条件にて
HPLC-MSMS分析を行い、ホップ酸化反応産物に含まれる各種成分の含有量を測定した。なお、ホップ酸化反応産物には、α酸酸化物、イソα酸酸化物またはβ酸酸化物として、スコルピオフムリノールA、スコルピオコフムリノールA、トリシクロオキシイソフムロンA、トリシクロオキシイソコフムロンAが含まれることが知られている(Biosci.,Biotechnol.,Biochem.,2015 (79):1684-1694、J.,Agric.,Food Chem., 2015:63:10181-10191)。また、分析に際して使用した標準品はJ.,Agric.,Food Chem., 2015:63:10181-10191およびJ. Nat. Prod. 2014, 77, 1252-1261に記載の方法に準じて調製した。
カラム:Unison UK-C18 100×2mm i.d. 粒子径3μm
流速:0.25mL/分
カラム温度:40℃
移動相A:1%ギ酸含有水
移動相B::1%ギ酸含有アセトニトリル
注入量:3μL
グラジエント:0→30分、15→31%B
30→40分、31→80%B
40→43分、80%B
以降は、洗浄および平衡化工程
質量分析装置:AB SCIEX 4000Q Trap
イオンソース:ESI-ネガティブイオンモード
イオンスプレー電圧:-4500V
分析パラメータ:
ロット1:3.2
ロット2:6.8
ロット3:12.1
(1)プラセボおよび被験食品の調製
1粒あたり結晶セルロースのみを257mg充填したハードカプセル(1号サイズ)をプラセボとした。1粒あたり結晶セルロース100mgと実施例1(2)で得られたホップ酸化反応産物水抽出物の乾燥物153mgとを充填したハードカプセルを被験食品とした。各食品に使用したハードカプセルは色および形状を統一し外見で区別がつかないようにした。ここで、被験食品1粒にはS-Frが乾燥質量換算で17.5mg含有される。
40歳以上の健常な非喫煙者の男女10名を被験者として、ランダムにプラセボ群と被験食品群に5名ずつ割り付けた。プラセボ群にはプラセボを1日当たり2粒、被験食品群には被験食品を1日当たり2粒用いた(被験食品2粒中、S-Frは乾燥質量換算で35mg)。試験のスケジュールは図2に記載の通りである。具体的には、試験1日目は各食品を摂取させずに認知機能評価を行った。試験3日目は各食品を摂取させ、1時間後に認知機能評価を行った。試験4日目は各食品の摂取のみを行った。試験5日目は各食品を摂取させ、1時間後に認知機能評価を行った。なお、試験期間中はホップを含む飲食品の摂取を禁止し、試験1、3、5日目の認知機能評価前にはカフェインを含有する飲食品の摂取を禁止した。
認知機能評価としてTrail Making TestのPART A(以後、TMT)、Letter-Number Sequencing Test(以後、LNS)およびCAMBRIDGE COGNITION社のCANTABを用いた。CANTABは複数の認知機能評価が可能なソフトウェアであり、その中でPattern Recognition Memory(以後、PRM)、Spatial Working Memory(以後、SWM)、Paired Associates Learning(以後、PAL)を用いた。評価の順番は、TMT、PRM、SWM、PAL、LNSの順とした。認知機能評価は午前中に実施し、評価を行う部屋に入室後10分間安静にした後に開始した。各評価方法の詳細は以下の通りである。いずれの評価方法も認知機能を評価する上で広く認められた方法である。
TMTは視覚探索や処理速度、注意の持続を評価する方法である。具体的には、1から25までの数字が印刷された紙を用い、1から順番に数字を線で繋ぎ、25に到達した時点で終了とし、終了までに要した時間を測定した。時間が早いほど処理速度が速く、注意力・集中力が持続したことを表す。
PRMは視覚のパターン認識記憶を評価する方法である。具体的には、タブレット型PCを用い、被験者にまず画面上にランダムに表示される10種類の模様を暗記させた。全ての模様が表示された後に、画面中央に2種類の模様(先ほど表示された模様と表示されていない模様が1種類ずつ)が表示されるため、被験者には先に表示された模様をタッチさせた。先に表示された模様をタッチできれば正解となり、正解数が多いほど視覚のパターン認識記憶、すなわち、視覚記憶が高いことを表す。
SWMは空間のワーキングメモリーを評価する方法である。具体的には、タブレット型PCを用い、画面上に12個のボックスが表示されるため、被験者はボックスをタッチしてこれらを順に開いた。12個のボックスの内1つにのみ青色の四角形が入っており、青色の四角形を見つけるまでを1ターンとし、合計で12ターン繰り返した。一度青色の四角形が入っていたボックスを見つけると、それ以降のターンには同じボックスには青色の四角形は入っていない。1回のターンにて2回以上同じボックスをタッチした場合にはwithin errorsとしてカウントし、12回のターンの中で過去に青色の四角形が入っていたボックスをタッチした場合にはbetween errorsとしてカウントした。within errorsおよびbetween errorsの数が少ないほど空間のワーキングメモリーが高いことを表す。
PALは視覚空間認識記憶と学習能を評価する方法である。具体的には、タブレット型PCを用い、画面上に12個のボックスが表示され、それぞれに1種類ずつの模様が隠されている。ボックスは1つずつランダムに開き模様が表示され、被験者に模様とそれが入っていたボックスの場所を暗記させた。全てのボックスが開き終わった後に画面中央に模様が1つずつ表示されるため、被験者にその模様が入っていたボックスをタッチさせた。12個の模様全てに正解するまで継続し、間違えた数をエラー数として測定した。エラー数が少ないほど空間認識記憶と学習能が高いことを表す。
LNSは言語のワーキングメモリーを評価する方法である。試験監督者がランダムに並べられた数字およびアルファベットを読み上げ、被験者にこれを暗記させた上で、頭の中で順番を並べ替えて、数字、アルファベットの順番に発音させた。正しい順番通りに発音することが出来れば正解となり、正解数が多いほど言語のワーキングメモリーが高いことを表す。なお、使用した質問用紙の一例を図3に示す(試験監督者が読み上げるものが質問用紙左に、その回答が質問用紙右に示されている。)。
本実施例では短期記憶および空間記憶に関する効果を評価した。
(1)認知機能の評価方法(Y字迷路試験)
マウスをある空間に投入すると、本来、直前に選択したルートを覚えている場合には、新規探索欲求のために、その直前のルートとは異なるルートを選択する性質がある。そのため、幅、長さ等が等価の3本のアームを持つY字迷路にマウスを入れた場合、通常は直前に進入したアームとは異なるアームに進入する。Y字迷路試験は、マウスのその性質を利用し、認知機能の指標となる短期記憶および空間記憶の評価に利用する試験である。
6週齢雄のCD-1マウス(日本SLC社より入手)に、ホップ酸化反応産物をS-Frとして乾燥質量換算で0(希釈溶媒)、1、3、10mg/kg体重となるように胃内強制投与した。投与したS-Frを含むホップ酸化反応産物は、投与直前に実施例1(2)で得られたホップ酸化反応産物抽出物の乾燥物に蒸留水を添加することにより調製したものである。投与40分後、記憶障害を誘発するために0.85mg/kg体重のスコポラミン塩酸塩(SIGMA社製)を腹腔内投与し、健忘モデルマウスを作成した。スコポラミン(SCP)の腹腔内投与20分後、Y字迷路試験を実施した(図10)。なお、各群10匹で実験を行い、平均、標準誤差を求めた。
本実施例では長期記憶およびエピソード記憶に関する効果を評価した。
(1)認知機能の評価方法(新奇物体認識試験)
マウスは本来新奇物体と認識すると接近し、形状の確認、匂いを嗅ぐなどの探索行動を行う。このとき、記憶している物体に対しては探索行動をとらないか、新奇物体に比べて短い時間しか探索しない。この性質を利用するのが新奇物体認識試験である。
各群10匹の6週齢雄のCD-1マウスに、ホップ酸化反応産物をS-Frとして乾燥質量換算で0(希釈溶媒)、1、3mg/kg体重となるように胃内へ強制投与した。上記ホップ酸化反応産物は実施例3(2)と同様の手順で調製した。投与60分後に獲得試行を行った。24時間後に各個体に、獲得試行時と同用量のホップ酸化反応産物を強制胃内投与し60分後にテスト試行を行った。結果は図14に示される通りであった。
本実施例ではアルツハイマー病モデルにおける短期記憶および空間記憶を評価した。
(1)アルツハイマー病モデルの作成
アルツハイマー病の原因物質の一つであるアミロイドβは、脳内で可溶性オリゴマーを形成し神経毒性を示すというオリゴマー仮説が提唱されている。アミロイドβオリゴマーの一種であるADDL(Aβ-derived diffusible ligands)はシナプスの可塑性を阻害するリガンドとして同定され、ADDLを脳室内に投与することで認知機能低下作用を示す。そのため、ADDLを投与したマウスは、脳内で老廃物が蓄積して生じる認知機能の低下および疾患、中でもアルツハイマー型認知症のモデルとして用いることができる(岩田修永、西道隆臣(2010)『アルツハイマー病の謎を解く』、中外医学社、173~180頁)。
(i)Y字迷路試験
アルツハイマー病モデルマウスに、ホップ酸化反応産物をS-Frとして乾燥質量換算で0(希釈溶媒)、1、10mg/kg体重となるように胃内へ強制経口投与した。上記ホップ酸化反応産物は実施例3(2)と同様の手順で調製したものである。単回投与60分後にマウスの認知機能は実施例3(1)と同様のY字迷路試験にて評価した。
アルツハイマー病モデルマウスに、ホップ酸化反応産物をS-Frとして乾燥質量換算で0(希釈溶媒)、10mg/kg体重となるように胃内へ経口投与した。上記ホップ酸化反応産物は実施例3(2)と同様の手順で調製した。投与60分後に実施例4(1)と同様の新奇物体認識試験における獲得試行を行った。24時間後に各個体に、獲得試行時と同用量のホップ酸化反応産物を強制胃内投与し60分後にテスト試行を行った。結果は図18に示される通りであった。
Claims (10)
- ホップ酸化反応産物を含んでなる、認知機能の維持、向上および/または改善のための組成物。
- 認知機能が記憶機能である、請求項1に記載の組成物。
- 認知機能が注意・集中機能である、請求項1に記載の組成物。
- 食品組成物である、請求項1~3のいずれか一項に記載の組成物。
- 1回摂取に適した単位包装形態である、請求項1~4のいずれか一項に記載の組成物。
- ホップ酸化反応産物がS-フラクションである、請求項1~5のいずれか一項に記載の組成物。
- S-フラクションを乾燥質量換算で1回当たりの摂取量で1~200mgで含んでなる、請求項6に記載の組成物。
- 認知機能の維持、向上および/または改善がその治療、予防または改善に有効である疾患または症状の治療、予防または改善に用いるための、請求項1~7のいずれか一項に記載の組成物。
- 有効量のホップ酸化反応産物を、対象に摂取させるか、あるいは投与することを含んでなる、認知機能の維持方法、認知機能の向上方法および認知機能の改善方法。
- 認知機能の維持、向上および/または改善のための組成物または食品の製造のための、または、認知機能の維持剤、認知機能の向上剤および認知機能の改善剤の製造のための、ホップ酸化反応産物の使用。
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019181058A1 (ja) * | 2018-03-23 | 2019-09-26 | キリン株式会社 | 精神機能の低下抑制用組成物 |
JP2020083835A (ja) * | 2018-11-28 | 2020-06-04 | キリンホールディングス株式会社 | 精神疲労抑制用組成物 |
JP2020080771A (ja) * | 2018-11-28 | 2020-06-04 | キリンホールディングス株式会社 | 疲労対象の注意機能および判断機能の低下抑制用組成物 |
JP2020150848A (ja) * | 2019-03-20 | 2020-09-24 | 小林製薬株式会社 | 経口組成物 |
JP2020158412A (ja) * | 2019-03-25 | 2020-10-01 | キリンホールディングス株式会社 | 認知機能改善用組成物 |
WO2021131570A1 (ja) * | 2019-12-25 | 2021-07-01 | サントリーホールディングス株式会社 | 認知機能の低下抑制又は改善用組成物 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5070512A (ja) * | 1973-10-29 | 1975-06-12 | ||
WO2012081675A1 (ja) * | 2010-12-15 | 2012-06-21 | キリンホールディングス株式会社 | ホップ酸化反応産物、その製造法および用途 |
WO2013191264A1 (ja) * | 2012-06-20 | 2013-12-27 | キリン株式会社 | ホップ酸化反応産物抽出物含有発泡性飲料 |
JP2015224194A (ja) * | 2014-05-26 | 2015-12-14 | キリン株式会社 | 認知症の予防、及び治療のための医薬、食品、組成物 |
JP2015224193A (ja) * | 2014-05-26 | 2015-12-14 | キリン株式会社 | 記憶学習機能を向上する医薬、食品、組成物 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6199287B2 (ja) * | 2012-06-20 | 2017-09-20 | キリン株式会社 | 酸化処理に付したホップの水性媒体抽出物を含有する飲料 |
JP6163084B2 (ja) * | 2013-11-11 | 2017-07-12 | キリン株式会社 | 認知症の予防、治療及び/又は認知機能を改善する組成物、及びこれを用いた医薬、食品 |
KR101685616B1 (ko) * | 2014-07-11 | 2016-12-13 | 한국생명공학연구원 | 환삼덩굴 추출물을 유효성분으로 포함하는 퇴행성 뇌질환의 예방 또는 치료용 조성물 |
-
2017
- 2017-03-14 AU AU2017249813A patent/AU2017249813B2/en active Active
- 2017-03-14 US US16/092,970 patent/US20190117715A1/en not_active Abandoned
- 2017-03-14 JP JP2018511935A patent/JP6994457B2/ja active Active
- 2017-03-14 EP EP17782172.5A patent/EP3443973A4/en active Pending
- 2017-03-14 WO PCT/JP2017/010083 patent/WO2017179354A1/ja active Application Filing
-
2021
- 2021-10-29 JP JP2021177177A patent/JP2022017430A/ja active Pending
-
2022
- 2022-05-02 US US17/734,177 patent/US20220257680A1/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5070512A (ja) * | 1973-10-29 | 1975-06-12 | ||
WO2012081675A1 (ja) * | 2010-12-15 | 2012-06-21 | キリンホールディングス株式会社 | ホップ酸化反応産物、その製造法および用途 |
WO2013191264A1 (ja) * | 2012-06-20 | 2013-12-27 | キリン株式会社 | ホップ酸化反応産物抽出物含有発泡性飲料 |
JP2015224194A (ja) * | 2014-05-26 | 2015-12-14 | キリン株式会社 | 認知症の予防、及び治療のための医薬、食品、組成物 |
JP2015224193A (ja) * | 2014-05-26 | 2015-12-14 | キリン株式会社 | 記憶学習機能を向上する医薬、食品、組成物 |
Non-Patent Citations (4)
Title |
---|
ANO Y ET AL.: "Iso-alpha-acids, bitter components of beer, prevent inflammation and cognitive decline induced in a mouse model of Altzheimer's disease", J BIOL CHEM., vol. 292, no. 9, 3 March 2017 (2017-03-03), pages 3720 - 3728, XP055429585, ISSN: 1067-8816 * |
LU YH. ET AL.: "DNA strand-scission by phloroglucinols and lignans from heartwood of Garcinia subelliptica Merr And Justicia plants", PHYTOCHEMISTRY, vol. 69, no. 1, 2008, pages 225 - 233, XP022392524, ISSN: 0031-9422 * |
NORIO SASAOKA ET AL.: "Oral Administration of Hop Flower Extracts Mitigates Alzheimer Phenotypes in Mice", BIO IND., vol. 31, no. 12, 2014, pages 34 - 39, XP9513323, ISSN: 0910-6545 * |
TOBE H ET AL.: "The neuroprotective effect of isohumulone on swine brain cells ", BULLETIN OF KOCHI NATIONAL COLLEGE OF TECHNOLOGY, 1 January 2011 (2011-01-01), pages 59 - 63, XP055579661, ISSN: 0454-1170 * |
Cited By (12)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2022017430A (ja) | 2022-01-25 |
US20220257680A1 (en) | 2022-08-18 |
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