JP2018038396A - Food-and-drink composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a food-and-drink composition that contains an ω-3 fatty acid, the composition being better in preventing and/or improving the degradation of cerebral functions.SOLUTION: This invention relates to a food-and-drink composition, comprising 0.1-1,000 pts.wt of an ω-3 fatty acid based on 1 pt.wt of a compound expressed by formula (I). The compound of formula (I) is at least one chosen from nobiletin, tangeretin, luteolin, and quercetin. The ω-3 fatty acid is chosen from α-linoleic acid, eicosatrienoic acid, eicosatetraenoic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid. The food-and-drink composition contains a compound of formula (1) and the ω-3 fatty acid [R-Rare each independently H, OH, Calkyl, or Calkoxy].SELECTED DRAWING: None

Description

［式中、ここで、式中、Ｒ^１〜Ｒ^７は、各々独立して、Ｈ、ＯＨ、Ｃ_１−６アルキル又はＣ_１−６アルコキシである］の化合物及びω−３脂肪酸を含有する飲食品組成物に関する。本発明の組成物は、脳機能の低下を予防及び／又は改善するために使用することができる。 The present invention relates to a compound of formula (I):

Wherein R ^{1 to} R ⁷ are each independently H, OH, C _1-6 alkyl or C _1-6 alkoxy, and a ω-3 fatty acid. It is related with the food-drinks composition. The composition of this invention can be used in order to prevent and / or improve the fall of brain function.

  In today's aging society, the number of patients with dementia is increasing and becoming a social problem. However, radical treatment and prevention methods for Alzheimer's disease and cerebrovascular disease, which are said to be the main cause of dementia, have not yet been established. Therefore, in the present age when the risk of developing dementia is increasing, finding a method for preventing or delaying the onset of dementia has become an important issue. In addition, a state having mild cognitive impairment that is not dementia but difficult to say is called mild cognitive impairment (MCI), and there is concern that it will increase in the future.

  Memory consists of three processes: memory encoding, retention, and recall. Learning and memory disorders, which are the core symptoms of Alzheimer's disease, particularly impair memory retention and recall processes. It is believed that One of the causes is understood to be neurodegeneration due to polymerization and accumulation of amyloid β (Aβ), which reduces the function of the NMDA receptor. In psychology and brain science, the function that supports human memory, thinking, and prediction is called "working memory." In Japanese, this is also called work memory, and it is a function that assigns priorities and thinks about plans while judging work information to be entered one after another. However, it is also known that if there is too much information to be remembered or if you do something else at the same time, it will temporarily exceed the capacity and you will forget it.

  On the other hand, flavonoids are pigments, bitterness and pungent components contained in plants, and are one of polyphenols. Flavonoids, one of the flavonoids, have different characteristics and actions depending on the type and are widely used for supplements.

  As one of the flavones, nobiletin is known to have a neurite elongation action on nerve cells (Patent Document 1). In addition, an extract of citrus peel containing nobiletin and the like that improves central neurodegenerative diseases accompanied by learning / memory disorders and movement disorders is known (Patent Document 2).

  The ω-3 fatty acid is one of the categories of unsaturated fatty acids, and generally refers to those having a carbon-carbon double bond at the ω-3 position. Docosahexaenoic acid (DHA), which is abundant in herring and sardine fish oil, is a kind of omega-3 fatty acid, and it is possible to enhance brain function with a brain function improving composition containing a mixture of DHA and phospholipid as an active ingredient. Known (Patent Document 3).

  However, it is not known that the brain function improving effect by ω-3 fatty acid is enhanced by using the compound of formula (I) and ω-3 fatty acid in combination.

JP 2002-060340 A JP 2014-111664 A Japanese Patent Laid-Open No. 7-17855

  The problem to be solved by the present invention is to provide a food / beverage composition containing ω-3 fatty acid, which is more excellent for preventing and / or improving a decrease in brain function. .

  Moreover, the subject which this invention tends to solve is solving the problem (odor, capsule crack) of the food-drinks composition containing omega-3 fatty acid.

  Furthermore, the present inventors have found that omega-3 fatty acids have neurocytotoxicity and active oxygen generation promoting action, and solve these problems, that is, in a food and beverage composition containing omega-3 fatty acids. It was also an object of the present invention to provide a food / beverage composition that can suppress the neurocytotoxicity and active oxygen generation promoting action of ω-3 fatty acids and has a neuroprotective action.

  That is, the present invention relates to the following.

  As a result of intensive studies, the present inventors have found that the combination of the compound of formula (I) and the ω-3 fatty acid has a remarkable neuroprotective action, and completed the present invention.

  According to the present invention, it is possible to provide a food or beverage composition containing a compound of the above formula (I) and a ω-3 fatty acid having a remarkable neuroprotective action. The food / beverage product composition of the present invention can be suitably used for preventing and / or improving a decrease in brain function. Further, by blending the compound of the above formula (I) together with the ω-3 fatty acid, it is possible to solve the problems of the food / beverage composition containing the ω-3 fatty acid, such as odor and capsule cracking.

  The present invention is described in detail below.

<Composition>
One aspect of the present invention is a composition such as a food or beverage composition containing the compound of formula (I) and an ω-3 fatty acid.

［式中、ここで、式中、Ｒ^１〜Ｒ^７は、各々独立して、Ｈ、ＯＨ、Ｃ_１−６アルキル又はＣ_１−６アルコキシである］の化合物は、その立体異性体、位置異性体、及びそれらの塩を含む。また、前記式（Ｉ）の化合物は、植物、動物、微生物等の天然物から抽出されたものや化学合成品を用いることができ、例えば、柑橘系の皮から得ることができる。天然物からの抽出物は、その原料種類、産地及び製造方法は特に限定されない。 <Compound of Formula (I)>
In the present invention, the formula (I):

Wherein the compounds R ^{1 to} R ⁷ are each independently H, OH, C _1-6 alkyl or C _1-6 alkoxy, wherein the stereoisomer, position Including isomers, and salts thereof. The compound of the formula (I) can be extracted from natural products such as plants, animals, microorganisms, and chemically synthesized products. For example, it can be obtained from citrus peel. Extracts from natural products are not particularly limited in terms of raw material type, production area and production method.

In the present invention, the compound of the formula (I) is represented by the formula:
R ¹ is H, OH, C _1-6 alkyl or C _1-6 alkoxy, preferably H, OH or C _1-6 alkoxy, more preferably H, OH or methoxy;
R ² is H, OH, C _1-6 alkyl or C _1-6 alkoxy, preferably H, OH or C _1-6 alkoxy, more preferably H, OH or methoxy;
R ³ is H, OH, C _1-6 alkyl or C _1-6 alkoxy, preferably H, OH or C _1-6 alkoxy, more preferably H, OH or methoxy;
R ⁴ is H, OH, C _1-6 alkyl or C _1-6 alkoxy, preferably H, OH or C _1-6 alkoxy, more preferably H, OH or methoxy;
R ⁵ is H, OH, C _1-6 alkyl or C _1-6 alkoxy, preferably H, OH or C _1-6 alkoxy, more preferably H, OH or methoxy;
R ⁶ is H, OH, C _1-6 alkyl or C _1-6 alkoxy, preferably H, OH or C _1-6 alkoxy, more preferably H, OH or methoxy;
R ⁷ is H, OH, C _1-6 alkyl or C _1-6 alkoxy, preferably H, OH or C _1-6 alkoxy, more preferably H, OH or methoxy.

  In the present invention, the compound of the formula (I) is, for example, polymethoxyflavone (3,5,6,7,8,3 ′, 4′-heptamethoxyflavone; nobiletin, 3,5,6,7,3 ', 4'-hexamethoxyflavone; tangeretin, sinensetin, 3,5,7,3', 4'-pentamethoxyflavone; 5,6,7,4'-tetramethoxyflavone, 5,7,3 ', 4 '-Tetramethoxyflavone, 5-hydroxy-3,7,3', 4'-tetramethoxyflavone; 5,7,4'-trimethoxyflavone, 5-hydroxy-3,7,4'-trimethoxyflavone; 5,7-dimethoxyflavone, 5-hydroxy-3,7-dimethoxyflavone), methoxyflavone (5-hydroxy-7-methoxyflavone) or flavone (luteoline, quercetin) ), And preferably nobiletin, tangeretin, luteolin, quercetin, and most preferably nobiletin is tangeretin. The compounds of formula (I) can be used in combination of one or more.

の構造を有するポリメトキシフラボンである。 Nobiletin includes the following:

This is a polymethoxyflavone having the structure:

の構造を有するポリメトキシフラボンである。 Tangeretin is:

This is a polymethoxyflavone having the structure:

の構造を有するポリメトキシフラボンである。 5,7-Dimethoxyflavone is:

This is a polymethoxyflavone having the structure:

の構造を有するフラボンである。 Luteolin is the following:

It is a flavone having the following structure.

の構造を有するフラボンである。 Quercetin is the following:

It is a flavone having the following structure.

  In the present invention, the salt of the compound of the formula (I) is not particularly limited as long as it is a physiologically acceptable salt. For example, a salt with an alkali metal salt, an alkaline earth metal salt, an organic base, etc. And salts with sodium, potassium, calcium, magnesium, ammonium, or diethanolamine, ethylenediamine, and the like. These salts can be obtained, for example, by converting a sulfate group or a carboxyl group present in fucoidan or the like into a salt by a known method. Furthermore, ammonia, methylamine, dimethylamine, trimethylamine, dicyclohexylamine, tris (hydroxymethyl) aminomethane, N, N-bis (hydroxyethyl) piperazine, 2-amino-2-methyl-1-propanol, ethanolamine, Examples include salts of amines such as N-methylglucamine and L-glucamine; and salts with basic amino acids such as lysine, δ-hydroxylysine and arginine. Also, for example, salts of mineral acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid; methanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, acetic acid, propionic acid, tartaric acid, fumaric acid, maleic acid, Malic acid, oxalic acid, succinic acid, citric acid, benzoic acid, mandelic acid, cinnamic acid, lactic acid, glycolic acid, glucuronic acid, ascorbic acid, nicotinic acid, salts with organic acids such as salicylic acid; or aspartic acid, glutamic acid And salts with acidic amino acids and the like.

  In the present invention, the compound of the formula (I) and the salt thereof can use each component contained in various plant extracts. For example, as an example of nobiletin, a dry powder obtained from a plant extract obtained by the following method can be used. That is, dried immature fruits of citrus fruits such as seeker, Daidai, and pheasant are pulverized, and 70% ethanol is added to the pulverized fruits. Extraction for 50 to 100 ° C, preferably 80 to 100 ° C, more preferably 90 to 100 ° C for 0.5 to 72 hours, preferably 1 to 24 hours, more preferably 1.5 to 10 hours To do. The extract is passed through a silica gel column, washed with water (room temperature) or the like, and then the compound (I) and its salt are eluted with 20 to 50, 30 to 40% ethanol or the like. The eluate is dehydrated using vacuum drying and hot air drying. The obtained dried product is crushed to obtain a nobiletin-containing extract. The nobiletin-containing extract usually contains 1 to 80% by weight, preferably 3 to 60% by weight, particularly preferably 5 to 30% by weight of the compound of formula (I) and a salt thereof. In the present invention, as the compound of formula (I) and its salt, commercially available products may be used as appropriate.

  In the present invention, the compound of the above formula (I) or a salt thereof is, for example, 0.00001 to 60% by weight, 0.0001 to 50% by weight, 0.001 to 30% by weight with respect to the total amount of the composition of the present invention. %, Preferably 0.005 to 20% by weight, more preferably 0.005 to 10% by weight, particularly preferably 0.01 to 2% by weight, most preferably 0.05 to 0.5% by weight. Can do.

  In the present invention, nobiletin and tangeretin are most preferable as the compound of the formula (I) or a salt thereof. Therefore, for example, nobiletin and tangeretin are used as the compound of the formula (I) or a salt thereof with respect to the total amount of the composition of the present invention. Both can be used at 0.005 to 30% by weight, preferably 0.02 to 5% by weight, and most preferably 0.1 to 2% by weight. The composition of the present invention may contain both nobiletin and tangeretin as a synthetic product as the compound of formula (I) or a salt thereof, and may contain nobiletin and tangeretin in the nobiletin-containing extract. In the composition of the present invention, as a compound of the formula (I) or a salt thereof, for example, 0.01-10 parts by weight of tangeretin, preferably 1 part by weight of nobiletin, 0.1 parts by weight of nobiletin. It can be used in an amount of 0.3 to 1 part by weight of tangeretin based on 1 to 2 parts by weight, particularly preferably 1 part by weight of nobiletin.

<Ω-3 fatty acid>
In the present invention, the ω-3 fatty acid is a fatty acid having a carbon-carbon double bond at the ω-3 position, and includes stereoisomers, positional isomers, and salts thereof. Moreover, what was extracted from natural products, such as a plant, an animal, and microorganisms, and a chemically synthesized product can be used for omega-3 fatty acid, for example, it can obtain from fish oils, such as a tuna, a skipjack, and a sardine. Extracts from natural products are not particularly limited in terms of raw material type, production area and production method.

  In the present invention, the ω-3 fatty acid is, for example, α-linolenic acid (ALA), eicosatrienoic acid (ETE), eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA). And docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) is particularly preferable for obtaining the effects of the present invention. One or more omega-3 fatty acids can be used in combination. For example, when docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are used in combination, 1 part by weight of docosahexaenoic acid (DHA) is used. Eicosapentaenoic acid (EPA) 0.001-50 parts by weight, preferably 0.01-20 parts by weight, more preferably 0.05-1 part by weight, more preferably 0.1-0.6 parts by weight, especially Preferably it can be used in a proportion of 0.1 to 0.3 parts by weight.

  In the present invention, the omega-3 fatty acid or a salt thereof is, for example, 0.1 to 90% by weight, preferably 0.5 to 60% by weight, more preferably 1 to 50% by weight, based on the total amount of the composition of the present invention. %, Particularly preferably 10 to 30% by weight, most preferably 15 to 25% by weight.

<Other active ingredients>
In the present invention, the composition of the present invention can use other physiologically active substances or health food materials as other active ingredients. Examples of other active ingredients include phosphatidylcholine, phosphatidylserine, curcumin, γ-aminobutyric acid, niacin, calcium pantothenate, vitamin B12, vitamin B6, vitamin B2, vitamin B1, ginkgo biloba, ferulic acid, γ oryzanol, pyrroloquinoline. Quinone (PQQ), catechin, resveratrol, sphingolipid, rice oil, egg yolk, soybean, cinnamon, orange peel, tachibana peel, berries, meringo, green juice, healthy vinegar, healthy tea, royal jelly, aloe, blueberry, propolis, Isoflavone, Noni, Nucleic acid, Garlic, Turmeric, Enzyme, Ginseng, Millet, Natto, Germinated brown rice, Maca, Meshimakobu, Grape seed, Spirulina, Tomorrow, Fucoidan, Oyster, Horse oil, Mulberry leaves, Salacia, Hanabiratake, Tabashi Carrot, blackcurrant, swordfish, kikui Mo, collagen, chlorella, glucosamine, chitosan, carnitine, CoQ10, ceramide, octacosanol and the like.

  In the present invention, the other active ingredient is, for example, 0.01 to 50% by weight, preferably 0.05 to 20% by weight, more preferably 0.1 to 10% by weight, based on the total amount of the composition of the present invention. Most preferably, it can be used at 0.3 to 5% by weight.

<Weight ratio of the compound of formula (I) and ω-3 fatty acid in the composition>
The composition of the present invention contains, for example, 0.1 to 1,000 parts by weight of ω-3 fatty acid with respect to 1 part by weight of the compound of formula (I). From the viewpoint of the protective action against the neurotoxicity of ω-3 fatty acid, that is, from the viewpoint of the effect of improving brain function, 0.1 to 5,000 ω-3 fatty acid is added to 1 part by weight of the compound of formula (I). The content is preferably 0.1 to 1,000, more preferably 0.5 to 1,000 parts by weight, still more preferably 1 to 600 parts by weight, and particularly preferably 10 to 300 parts by weight.

  The composition of the present invention may further contain appropriate active ingredients and additives that can be used for foods and drinks, functional indication foods, specified health foods, quasi drugs, pharmaceuticals, etc. Depending on the formulation method used, it can be appropriately formulated.

  When the omega-3 fatty acid in the composition is derived from fish oil, the odor may be a problem. However, the composition of the present invention has the expectation that the odor can be remarkably suppressed by blending the above formula (I) compound such as nobiletin together with the ω-3 fatty acid in the appropriate amount. An effect that cannot be achieved. Furthermore, when a composition containing a ω-3 fatty acid is encapsulated in a capsule or the like, the capsule may crack. However, the composition of the present invention cannot be expected to suppress capsule cracking by blending the above formula (I) compound such as nobiletin with ω-3 fatty acid in the appropriate amount. There is an effect.

<Formulation>
In the present invention, the composition of the present invention can be administered orally or parenterally, for example, as solid preparations such as tablets, capsules, granules, powders; or liquid preparations such as syrups and injections. For solid preparations, excipients, lubricants, binders, disintegrants; for liquid preparations, use solvents, solubilizers, suspending agents, tonicity agents, buffers, soothing agents, etc. be able to. If necessary, additives such as preservatives, antioxidants, colorants, sweeteners and the like can be used.

  Examples of excipients include sugar alcohols such as D-sorbitol, mannitol, and xylitol, sugars such as glucose, sucrose, lactose, and fructose, crystalline cellulose, carmellose sodium, croscarmellose sodium, calcium hydrogen phosphate, wheat starch, Rice starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titanium oxide, magnesium aluminate metasilicate, talc, kaolin, olive oil and the like.

  Examples of the binder include cellulose derivatives such as methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, polyvinyl alcohol, acrylic polymer, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, and alginic acid. Examples thereof include sodium and propylene glycol alginate.

  Examples of the disintegrant include starch, low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, and partially pregelatinized starch. Preferable examples of the solvent include water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil and the like.

  Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, and white beeswax.

  Examples of the solubilizer include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like.

  Preferable examples of the suspending agent / emulsifier include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glyceryl monostearate; Hydrophilic polymers such as alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose; eg shellac wax, beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, cyclic Examples include waxes such as lanolin, lanolin wax, candelilla wax, mole, montan wax, shellac wax, and rice wax. That.

  Examples of isotonic agents include sodium chloride, glycerin, D-mannitol and the like. Preferable examples of the buffer include buffer solutions such as phosphate, acetate, carbonate, citrate and the like. Preferable examples of the soothing agent include benzyl alcohol. Preferable examples of the preservative include paraoxybenzoates, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid and the like. Preferable examples of the antioxidant include sulfite and ascorbic acid.

  When making the composition of this invention into a solid formulation, a normal method can be used. For example, a method of pulverizing and sizing the extruded granulated product that is molded by kneading the composition and passing through a screen, and stirring granulation by adding kneading water to the composition and molding by a vertical granulator Examples include a method of pulverizing and sieving using a comil, a method of compressing the preparation composition with a roller compactor, pulverizing and sieving with a roll granulator, and a method of drying a fluidized bed after stirring granulation Is done. For example, in the case of producing by direct compression, after mixing the composition, it may be directly put into a tableting machine for tableting.

<Food>

  The composition of the present invention can be used as a food or drink composition, and can be provided by being included in a food or functional food. Examples of such foods or functional foods include cooked rice; various kinds of noodles including soba, udon, harusame, Chinese noodles, instant noodles, cup noodles; soft drinks, carbonated drinks, nutrition drinks, fruit drinks, lactic acid drinks, sports drinks Beverages such as Carrero, stew, various soups; Ice cream, ice sorbet, shaved ice and other frozen desserts; Strawberries, cookies, candy, gum, chocolate, tablet confectionery, snacks, biscuits, jellies, jams, creams, and other baked goods Sweets such as kamaboko, hampen, processed food such as ham, sausage; dairy products such as processed milk and fermented milk; fats and oils such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing Processed foods; seasonings such as sauces, dressings, miso, soy sauce, sauces; soups Stew, salad, delicatessen, sprinkle, pickles; health and nutrition supplement other various forms is illustrated.

  Furthermore, supplements (dispersed, granules, soft capsules, hard capsules, tablets, chewable tablets, quick disintegrating tablets, syrups, liquids, etc.) containing the composition of the present invention may be prepared.

  Moreover, the composition of this invention can also be contained with respect to animal baits, such as a pet.

  Additives are added to the food as needed. Examples of such additives include glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, corn syrup, lactose, mannitol, dextrin, citric acid, sodium citrate, tartaric acid, malic acid, succinic acid, lactic acid L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerol, propylene glycol, glycerol fatty acid ester, polyglycerol fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, Examples include agar, vitamin C, vitamin B, vitamin E, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, surfactants, pigments, fragrances, and preservatives.

<Use of composition of the present invention>
The composition of the present invention can be used for foods and drinks that are allowed to display various symptoms. Here, in the present invention, foods and beverages permitted to display symptoms for improvement / prevention are foods and beverages having medicinal effects that are permitted / designated by the government or public organizations. These are labeled foods, health functional foods such as specified health foods, and special purpose foods. Although names and rules vary depending on circumstances, times, and systems in each country, those that are essentially the same are included in the present invention.

  In the present invention, the blending amount of the composition of the present invention is not particularly limited, and the purpose of application (type of target disease or symptom, etc.), application target site, sex and age of the user, food and drink, functional indication food , Specific health foods, quasi-drugs, or pharmaceutical forms, their administration or intake method, frequency, preference, etc.

  In the present invention, the compounding amount of the composition of the present invention into a food or drink, functional indication food, specified health food, quasi-drug, or pharmaceutical is not particularly limited, but the composition of the present invention per day for an adult The dose can be used, for example, at 0.01 to 20 g, preferably 0.1 to 10 g, more preferably 0.5 to 5 g, and most preferably 1 to 3 g.

  In the present invention, when the composition of the present invention is used, the daily dose or daily dose of the compound of the formula (I) is, for example, 0.005 to 4,000 mg, preferably 0.1 ˜3,000 mg, more preferably 0.5 to 1,000 mg, still more preferably 1 to 800 mg, particularly preferably 2 to 300 mg, and most preferably 3 to 60 mg. In addition, the daily dose or daily dose of the compound of the formula (I) is, for example, 0.01 to 2,000 mg, preferably 0.05 to 1,000 mg, more preferably 0.1 to 500 mg, More preferably 0.2 to 200 mg, most preferably 0.5 to 50 mg can be used.

  In the present invention, when the composition of the present invention is used, the dose of omega-3 fatty acid per adult or per day is, for example, 1 to 5,000 mg, preferably 10 to 1,000 mg, more preferably Can be used at 40-500 mg, most preferably 40-300 mg.

  The dosage form of the composition of the present invention is not particularly limited in terms of formulation. For example, functional foods such as supplements, energy drinks, confectionery such as gummi, candy, gum, crackers, biscuits, foods such as ice cream, jelly, yokan, bread, tea steamed, curry, milk beverages, soft drinks, Beverages such as soup, and seasonings such as dressing and ponzu are exemplified as food and drink compositions that can be eaten and consumed.

  In addition, the composition of the present invention is preferably taken as a functional food from the viewpoint of the effect of the present invention to prevent and / or improve a decrease in brain function, and among functional foods, a functional display food, Functional nutrition foods, dietary supplements, and foods for specified health use may be mentioned, but functional indication foods are preferable in that the following uses can be clearly indicated.

  In addition, the composition of the present invention is preferably a composition such as a tablet, granule, capsule or the like from the viewpoint that the odor which is a problem of a preparation containing ω-3 fatty acid is improved. Examples of capsules include hard capsules and soft capsules, and soft capsules are more preferable from the viewpoint of easy swallowing.

<Brain function>
One aspect of the present invention is a composition comprising a compound of formula (I) and an omega-3 fatty acid for preventing and / or improving a decrease in “brain function”.

  The composition of the present invention can be used to prevent and / or improve the decrease in “brain function”.

  In the present invention, “brain function” includes “cognitive function”, “memory, taste, orientation, understanding, calculation, learning, language, judgment, working memory, memory function, execution function, attention function, language function” and the like. Including. Among them, the attention function is the basis for various cognitive activities in daily life. When the attention function acts appropriately and is mobilized, the function can appropriately pass its role.

  In the present invention, “reduced brain function” means that brain function declines, “cognitive function”, “memory, taste, orientation, understanding, calculation, learning, language, judgment, working memory”, “memory function” , Execution function, attention function, language function "and the like. “Decrease in brain function” is caused by brain diseases such as aging, mental stress, nutritional balance, overwork, lack of sleep, drug addiction, dementia, brain tumor, and chronic subdural hematoma.

  In the present invention, “preventing and / or improving a decrease in brain function” means, for example, a preventive or ameliorating action of symptoms or diseases caused by a decrease in brain function associated with aging, a decrease in cognitive ability, memory, preference , Orientation, understanding, calculation, learning, language, reduced accuracy of judgment, memory / learning ability, emotional disorders (eg depression), intellectual disorders (eg dementia, specifically Alzheimer's) Prevention / improvement of type dementia, cerebrovascular dementia), prevention of forgetfulness, prevention of carelessness, prevention of blurring, maintenance / improvement of memory, maintenance / improvement of concentration, maintenance / improvement of attention, refreshing head, head It means that it has an effect of rejuvenating and rejuvenating.

  In the present invention, “decrease in cognitive function” means that cognitive ability declines, and includes, for example, a decline in cognitive ability.For example, the person's name cannot be remembered or what he / she has forgotten to do. Forgetful things are forgotten.

  In the present invention, “reduced memory” means that memory capacity declines, and includes, for example, decreased memory capacity. In addition, “prevention and / or improvement of memory loss” means prevention or suppression, treatment or improvement of the above-mentioned memory loss, and includes maintenance of memory.

  In the present invention, the “decrease in working memory” means that the working memory declines. For example, the function of assigning priorities and determining plans while judging work information that is entered one after another is reduced. This means that, for example, if there is too much information to be remembered or if you do something else at the same time, the capacity will be temporarily exceeded and you will be forgotten.

  In the present invention, “decrease in attention function” means that attention function declines. For example, “not concentrating”, “unrecognizable”, “faint”, “approach to things” Are not long-lasting ”and“ cannot do two or more things at the same time ”.

  In the present invention, the product according to the composition of the present invention, the packaging of the product, the information related to the product, or the advertisement related to the product (for example, transaction documents, instruction manuals, attached documents, mail order catalogs, Internet sites, etc.) Can be labeled as “prevent (or inhibit) and / or improve (or treat) a decrease in brain function” and “prevent and / or improve a decrease in brain function” For example, “Cognitive functions such as memory, preferences, orientation, understanding, calculation, learning, language, judgment, execution, attention, etc. are maintained”, “Supporting attention functions that are part of cognitive functions ”,“ Enhancing the accuracy of memory ”,“ supporting the storage of information such as numbers, words, figures, and situations that are part of the cognitive function ”,“ supporting the storage of information ”,“ memory (daily life) Actions and sizes ”And“ maintains the memory that is part of the cognitive function (the ability to remember words, images of objects and position information) ”,“ memory that is part of the cognitive function (perception) "Improving the accuracy of recalling recognized things" can be displayed, and a display similar to those can be displayed.

<Other aspects>

  One aspect of the present invention is a preventive and / or ameliorating agent for reducing brain function, comprising the compound of formula (I) and an omega-3 fatty acid as active ingredients.

  One aspect of the present invention is a neuroprotective agent comprising the compound of formula (I) and an omega-3 fatty acid as active ingredients.

  One aspect of the present invention is a method for preventing and / or ameliorating brain function decline, comprising administering an effective amount of the compound of formula (I) and ω-3 fatty acid.

  In one embodiment of the present invention, 0.1 to 1,000 parts by weight, 0.1 to 500 parts by weight, and 0.5 to 500 parts by weight of omega-3 fatty acid are added to 1 part by weight of the compound of formula (I). The odor of omega-3 fatty acid is characterized by being blended at a ratio of preferably 1.0 to 400 parts by weight, more preferably 1.0 to 300 parts by weight, and still more preferably 1.0 to 60 parts by weight. How to suppress or reduce.

  Hereinafter, the present invention will be specifically described with reference to Examples, Formulation Examples, etc., but the present invention is not limited to the following Examples.

  Test Example 1: Cytotoxicity test 1

<Sample preparation>
As nobiletin (NB), “nobiletin synthetic product (98%)” (manufactured by Wako) was used.
As the DHA, “4,7,10,13,16,19-docosahexaenoic acid (98%)” (manufactured by Nacalai Tesque) was used.
Nobiletin and DHA were added to DMSO and stirred, and each sample was prepared to be a test example containing each component as shown in Table 1 when the medium was added.

<Test method>
Rat adrenal medullary pheochromocytoma-derived cell line PC12 cells were seeded at 5.0 × 10 ³ / cell (flat bottom 96-well polyerlysine-coated plate) at 37 ° C. under 5% CO ₂ condition. Incubated overnight.
After overnight culture, the above medium was removed, a DMEM medium containing each of the examples (nobiletin and / or DHA) was added, and further cultured for 72 hours.
After culturing for 72 hours, 5 mg / mL MTT solution was added at 10 μL / cell and cultured for 6 hours. After culturing for 6 hours, 100 μL / well of 10% SDS solution was added, and the absorbance at 570 nm was measured with a plate reader (manufactured by Perkin Elmer). The cell viability in each example was calculated as a relative value when the absorbance of a control to which nobiletin and DHA were not added was taken as 100. The results are also shown in Table 1.

<Results and discussion>
When a certain amount of DHA was added to the cell line, the cell viability was reduced to 80% or less (Comparative Example 1-0). The cell viability recovered in a concentration-dependent manner by co-adding nobiletin there (Examples 1-1 to 1-4). When the ginkgo biloba extract was used, the cell viability decreased rather (Reference Example 1-1). It was confirmed that nobiletin improves the cytotoxicity of DHA in a concentration-dependent manner.

Test Example 2: Reactive oxygen (ROS) generation test under oxidative stress <Sample preparation>
Nobiletin (98%) (manufactured by Wako Co., Ltd.) was used as nobiletin (NB).
As DHA, 4,7,10,13,16,19-docosahexaenoic acid (98%) (manufactured by Nacalai Tesque) was used.
Nobiletin and DHA were added to DMSO and stirred, and each sample was prepared so as to be a test example containing each component as shown in Table 2 when the medium was added.

<Assay method>
PC12 cells were seeded at 1.0 × 10 ⁴ / cell (flat bottom 96-well black plate for fluorescence measurement) and cultured at 37 ° C. under 5% CO ₂ for 48 hours.
After culturing for 48 hours, the medium was changed to a serum-free medium containing 100 μM DCFH-DA (2 ′, 7′-Dichlorodihydrofluorine diacetate), and cultured under conditions of 37 ° C. and 5% CO 2 for 1 hour.
After culturing for 1 hour, the above medium was removed, a DMEM medium containing each of the examples and the like (nobiletin and DHA) was added, and the mixture was further cultured at 37 ° C. under 5% CO ₂ for 30 minutes.
After culturing for 30 minutes, 150 μM H ₂ O ₂ was added as oxidative stress, and the fluorescence intensity (480/530 nm) 20 minutes after the addition was measured. The measured value was defined as the amount of generated active oxygen (ROS). The average value was substituted into the following formula and calculated as the inhibition rate of ROS generation relative to the control to which nobiletin and DHA were not added. The results are shown in Table 2 below.

ROS generation inhibition rate (%) = (average value of control−average value of each example) / average value of control) × 100

<Results and discussion>
By adding H ₂ O ₂ , active oxygen was generated in the medium. With respect to the generation of active oxygen under oxidative stress, generation suppression was not observed when DHA was added (Comparative Example 2-0), and even when nobiletin was added, the generation suppression rate remained at about 40% (Comparative Example 2- 1-2-4). On the other hand, it was confirmed that the addition rate of nobiletin and DHA significantly increased the active oxygen generation inhibition rate (Examples 2-1 to 2-12).

  Test Example 3: Odor improvement test

<Sample preparation>
As nobiletin (NB), “nobiletin high content extract (containing nobiletin 58%)” (manufactured by Rohto Pharmaceutical Co., Ltd.) was used. As DHA, life's Omega 60 (Lot No. VY00147014) made by DSM Nutrition Japan Co., Ltd. and DHA-46MK (LotNo. 151111) Maruha Nichiro Co., Ltd. were used, and DHA / EPA = 225 mg. / 45 mg was used after adjusting.
Sampling was performed according to the following formulation, and the mixture was placed in a glass vial with a screw cap (capacity 30 mL, manufactured by Nichiden Rika Glass Co., Ltd.). A composition as a specimen was prepared so as to contain each component as shown in Table 3.

<Test method>
Sensory evaluation of the odor immediately after mixing of the test substance and the odor after storing at 60 ° C. for 24 hours was performed. The sensory evaluation was performed by VAS method for five subjects. For details of the VAS method, on the 10 cm straight line, set the intensity of the odor felt in each test object to 0 when “not smell bad at all” is 0, and when 100 is “bad smell that can't be confused”. Used to draw a line. The average value of the numerical values of five subjects was used as the numerical value of the sample. The average value was substituted into the following formula, and the reduction rate of unpleasant odor with respect to Comparative Example 3-0 was calculated. However, regarding Comparative Examples 1 and 2, the average value of five subjects was used as the value.
[formula]
Odor reduction rate (%) = (Average value of Comparative Example 3-0−Average value of each Example) / Average value of Comparative Example 3-0 × 100

<Results and discussion>
DHA / EPA has an unpleasant odor peculiar to fish oil, and increased its strong odor in a short time by storing under high temperature conditions. It was confirmed that the strong odor of DHA / EPA immediately after mixing and after storage at 60 ° C. for 24 hours was suppressed by NB (Examples 3-1 to 3-8).

Test Example 4: Cytotoxicity test 2
<Sample preparation>
As nobiletin (NB), “nobiletin synthetic product (98%)” (manufactured by Wako) was used. As the DHA, “4,7,10,13,16,19-docosahexaenoic acid (98%)” (manufactured by Nacalai Tesque) was used. As the EPA, “Icosapentanoic Acid” (manufactured by Cayman) was used.
Nobiletin (NB), DHA, and EPA were prepared in DMSO, and each sample was prepared to be a test example containing each component as shown in Table 4 when the medium was added.

<Test method>
Rat adrenal medullary pheochromocytoma-derived cell line PC12 cells were seeded at 5.0 × 10 ³ / cell (flat bottom 96-well polyerlysine-coated plate) at 37 ° C. under 5% CO ₂ condition. Incubated overnight.
After overnight culture, the above medium was removed, a DMEM medium containing each of the examples (nobiletin and / or DHA) was added, and further cultured for 24 hours.
After culturing for 24 hours, the cell viability was calculated according to the protocol using Cell Counting Kit-8 (manufactured by Dojindo). The cell viability in each example and the like was calculated as a relative value (%) when the absorbance (AD450) of a control without any addition of nobiletin, DHA, or EPA was defined as 100. The results are also shown in Table 4.

<Results and discussion>
When a certain amount of DHA or EPA was added to the cell line, the cell viability was reduced to 80% or less (Comparative Examples 4-5 and 4-6). The cell viability was sufficiently recovered by co-adding nobiletin (Example). It was confirmed that nobiletin markedly improved cytotoxicity by DHA and EPA.

Test Example 5: Human test for memory and concentration <Adjustment of soft capsule>
Nobiletin-containing extract (containing 5% nobiletin and 3% tangeretin) (manufactured by Rohto Pharmaceutical Co., Ltd.) as nobiletin, and life's Omega 60 (Lot No. VY00147014) manufactured by DSM Nutrition Japan, Inc. as DHA and EPA, And DHA-46MK (LotNo.151111161) made by Maruha Nichiro Co., Ltd. was mixed and filled into a soft capsule (350 mg per capsule). It adjusted so that it might become 1 mg of nobiletin, 0.6 mg of tangeretin, 225 mg of DHA, and 45 mg of EPA per 3 soft capsules.

<Test method>
The test was carried out for those in their thirties. Three soft capsules were ingested daily for 5 consecutive days. The following two evaluations were performed immediately before the continuous intake or 30 minutes after the intake on the fifth day. As the first evaluation, a memory test was performed (15 words are randomly displayed on the screen every 1.5 seconds. After 15 words are displayed, the stored words are entered in the answer column. Evaluate the number of correct answers). As a second evaluation, a VAS questionnaire was conducted. (Details of the VAS method are as follows: “I don't think at all” is 0 and “I think very much” is 100 on a 10 cm line for each of the following evaluation items. The strength was drawn with a pen.As evaluation items, mental fatigue, physical fatigue, irritability, dullness, moodiness, concentration, depression, motivation, relaxation of tension, and improvement of sleepiness were evaluated.

<Results and discussion>
In the short-term memory test, the number of correct answers after ingestion increased by 50% compared to before ingestion (4.7 before ingestion and 7 after ingestion). Furthermore, in the VAS questionnaire, improvement was observed after ingestion compared to before ingestion (18% mental fatigue, 17.4% physical fatigue, 31% irritability, 28.6% dullness, motivation 3.7%, tension improved by 44%, sleepiness improved by 27.8%).

Test Example 6: Clinical trial <Adjustment of soft capsule>
Nobiletin-containing extract (containing 5% nobiletin) (manufactured by Rohto Pharmaceutical Co., Ltd.) as nobiletin, and life's Omega 60 (Lot No. VY00147014) manufactured by DSM Nutrition Japan Co., Ltd., and DHA- as DHA and EPA 46MK (LotNo. 151111) manufactured by Maruha Nichiro Co., Ltd. was mixed and filled into a soft capsule (300 mg per capsule). It adjusts so that it may become 1 mg of nobiletin, 225 mg of DHA, and 45 mg of EPA per 4 soft capsules. As a placebo control, a soft capsule without nobiletin, DHA, EPA is prepared.

<Test method>
The test will be conducted on healthy middle-aged men and women (60 people) who are worried about forgetting things. Take 4 capsules daily for 12 weeks. As a rule, take 2 capsules (grains) before breakfast and 2 capsules (grains) before dinner. Compared to the placebo control, the following three assessments are performed before and after continuous ingestion. Forgetfulness level (NRS), subjective state assessment (NRS), N-style mental state scale for the elderly (NM scale). Calculate and evaluate descriptive statistics of the amount of change from before ingestion to the week after ingestion.

[Prescription example]
The composition of the present invention will be described more specifically with reference to formulation examples, but the present invention is not limited to these formulation examples. The content of the components shown in the following formulation examples indicates the dose per day or once per adult.

The following formulations were prepared using a food and beverage composition comprising nobiletin and DHA / EPA;
Specifically, in the following prescription examples 1 to 19, a nobiletin-containing extract (manufactured by Rohto Pharmaceutical Co., Ltd., containing 30% nobiletin) and DHA and EPA are mixed until they are mixed uniformly, and the nobiletin and DHA / EPA-containing composition is mixed. Obtained. As DHA and EPA, those obtained by mixing Maruha Nichiro (DHA content 38% by weight, EPA content 4.2% by weight) and DSM (DHA content 30% by weight, EPA content 15% by weight) were used.

  Examples of prescription are given below.

Formulation Example 1: Tablets Nobiletin and DHA / EPA-containing composition 1 g, powdered reduced maltose starch syrup 35 g, sucrose behenic acid ester 3 g, and fine silicon dioxide 1 g are mixed and tableted with a tableting machine to give 4 mg of nobiletin And 830 mg of DHA and 166 mg of EPA are obtained.

Formulation Example 2: Soft capsule 1 g of composition containing nobiletin and DHA / EPA, 30 g of Kollidon 30, 30 g of CAVAMAX W6 FOOD, 130 g of olive oil, 63 g of beeswax, and 63 g of Poem S100 are filled into a soft capsule with a filling machine. Thus, a soft capsule containing 24 mg of nobiletin, 813 mg of DHA, and 163 mg of EPA is obtained.

Formulation Example 3: Hard Capsules Nobiletin 40 mg, DHA 800 mg, and EPA 320 mg hard capsules are obtained by filling 1 g of the composition containing nobiletin and DHA / EPA as it is with a filling machine.

Formulation Example 4: Gummy 100% orange juice is heated to 60 ° C., 15 g of gelatin and 10 g of sugar are added and mixed until the gelatin is completely dissolved. Thereto, 1 g of nobiletin and DHA / EPA-containing composition is added and mixed thoroughly. After pouring into a silicon container and removing the rough heat, the mixture is allowed to stand for 30 minutes in a refrigerator, whereby 85 mg of nobiletin, 763 mg of DHA, and 153 mg of EPA are obtained.

Formulation Example 5: Straw 100 g of sugar, 25 g of lemon juice, and 25 g of water are heated in a pan and mixed until it becomes a fox color. Thereto, 1 g of nobiletin and DHA / EPA-containing composition is added and mixed thoroughly. After pouring into a silicon container and removing the rough heat, it is allowed to stand in the refrigerator for 15 minutes to obtain a koji mixture containing 143 mg of nobiletin, 714 mg of DHA and 143 mg of EPA.

Formulation Example 6: Cracker 25 g of salted butter is dissolved and mixed well at room temperature, and 75 g of strong powder and 30 g of milk are mixed well until there is no roughness. Thereto, 1 g of nobiletin and DHA / EPA-containing composition is added and mixed thoroughly. After thinly extending the dough, cut and mold it. By firing the molded product at 200 ° C. for 15 minutes, a cracker containing nobiletin 270 mg, DHA 608 mg, and EPA 122 mg is obtained.

Formulation Example 7: Biscuit 100 g of weak flour, 20 g of strong flour, 50 g of sugar and 1 g of baking powder are added to 40 g of salted butter and mixed well until the whole becomes familiar. 30 g of milk and 1 g of a composition containing nobiletin and DHA / EPA are added thereto and mixed thoroughly. The obtained dough is put together and wrapped in wrap, allowed to stand at −20 ° C. for 1 hour, then cut and molded. By firing the molded product at 160 ° C. for 20 minutes, biscuits containing nobiletin 455 mg, DHA 455 mg, and EPA 91 mg mg are obtained.

Formulation Example 8: Ice cream 200 g of fresh cream, 50 g of egg yolk, and 60 g of granulated sugar are mixed well. There, 1 g of nobiletin and a DHA / EPA containing composition are dissolved. 80 g of coconut oil is added and mixed well, and then homogenized with a homogenizer. This is sterilized at 85 ° C. for 15 seconds, rapidly cooled to 5 ° C. or less, then added with 2 g of vanilla fragrance, mixed well, and then aged at 5 ° C. overnight. This was frozen in an overrun 30% with a continuous ice cream freezer, filled into a cup at an outlet temperature of -5 ° C, and rapidly frozen at -40 ° C to obtain ice cream containing nobiletin 625 mg, DHA 313 mg, and EPA 63 mg. It is done.

Formulation Example 9: Jelly 5 g of gelatin, 200 g of orange juice, and 40 g of granulated sugar are mixed well. This is heated to 85 ° C. and sufficiently dissolved, and then 0.5 g of nobiletin and DHA / EPA-containing composition are added and mixed well. Here, 0.2 g of orange fragrance preparation is added and mixed well, then filled into a cup, cooled and gelled to obtain a jelly containing 2 mg of nobiletin, 415 mg of DHA, and 40 mg of EPA.

Formulation Example 10: Yokan 4 g of agar is dissolved in 600 mL of water at 60 ° C. Add 500g of strain and mix well. After lightly boiling, add 0.5g of nobiletin and DHA / EPA containing composition, add 20g of sugar and 0.1g of salt, and mix well. By filling this into a vat and allowing it to cool and gel, a mixture containing 12 mg of nobiletin, 406 mg of DHA and 81 mg of EPA is obtained.

Formulation Example 11: Milk drink Nobiletin and DHA / EPA-containing composition 0.5 g of milk is mixed to a total of 1000 g, and homogenized by a homogenizer, so that milk drink containing nobiletin 20 mg, DHA 400 mg, and EPA 80 mg Is obtained.

Formulation Example 12: Yogurt Beverage By mixing 500 g of yogurt, 50 g of glucose liquid sugar, 0.5 g of nobiletin and DHA / EPA-containing composition with a total of 1000 g of water and homogenizing with a homogenizer, 42 mg of nobiletin and A fermented milk drink containing 381 mg of DHA and 300 mg of EPA is obtained.

Formulation Example 13: Bread 146 g of hot water at about 30 ° C., in which 250 g of strong wheat flour, 7 g of dry yeast, 15 g of white sucrose, 3 g of salt and 0.5 g of nobiletin and DHA / EPA-containing composition are mixed, and kneaded until it is smoothly mixed. . There, 5 g of butter is dissolved at room temperature and mixed well. The obtained dough is put together in a bowl with oil, and primary fermentation is performed at 30 ° C. for about 1 hour. Then degas from the dough and place in a mold with oil. Cover and perform secondary fermentation at 30 ° C for about 1 hour. Place the mold with the lid in the oven preheated at 190 ° C and bake for 30 minutes. Once baked, it can be quickly removed from the mold and cooled on a net or the like to obtain 71 mg of nobiletin, 357 mg of DHA, and 71 mg of EPA.

Formulation Example 14: Dressing 5 g of salt, 20 g of grain vinegar, and 10 g of wine vinegar are stirred until there is no undissolved residue. To this, 40 g of olive olive oil, 0.5 g of nobiletin and a DHA / EPA-containing composition are added and thoroughly stirred to obtain a dressing containing nobiletin 135 mg, DHA 304 mg, and EPA 61 mg.

Formulation Example 15: Ponzu vinegar 5 g of salt, 20 g of grain vinegar, and 10 g of wine vinegar are stirred until there is no undissolved residue. To this, 40 g of olive olive oil, 0.5 g of nobiletin and DHA / EPA-containing composition are added and sufficiently stirred to obtain ponzu vinegar containing 227 mg of nobiletin, 227 mg of DHA, and 45 mg of EPA.

Formulation Example 16: Chawanmushi 150 g of raw whole egg, 500 g of soup stock, 5 g of sake, 5 g of nobiletin and 5 g of DHA / EPA-containing composition are mixed well and filled into a cup. By heating this at 90 ° C. for 15 minutes in a steamer, 18 mg of nobiletin, 4151 mg of DHA, and 830 mg of EPA are obtained.

Formulation Example 17: Sprinkle By mixing 5 g of salted tea granule, 10 g of bonito granule seasoning, 5 g of kelp granule seasoning, 1 g of fried laver, 1 g of sesame seeds, 1 g of dried cherry shrimp, 0.5 g of nobiletin and DHA / EPA-containing composition, Sprinkling with 313 mg of nobiletin, 156 mg of DHA and 31 mg of EPA is obtained.

Formulation Example 18: Instant soup Into 500 g of water, 10 g of granulated bird gala seasoning, 5 g of soy sauce, 4 g of sesame oil, 5 g of nobiletin and DHA / EPA-containing composition are boiled. Turn 100g of beaten egg into it and stop heating. The obtained soup is cooled and then subjected to lyophilization to obtain instant soup containing nobiletin 2273 mg, DHA 2273 mg, and EPA 455 mg.

Formulation Example 19: Retort curry After 4.5 g of coconut oil, 4.5 g of rapeseed oil, and 7.5 g of wheat flour are heated and mixed at 140 ° C., 4.2 g of curry powder and 1.5 g of sodium chloride are added and mixed well. 5.4 g of sugar, 12 g of chopped onion, 2.4 g of granulated beef extract, 1 g of Worcester sauce, 1 g of soy sauce, 5 g of a composition containing nobiletin and DHA / EPA, and 120 g of water are added and heated and mixed at 90 ° C. for 15 minutes. Add 8g of beef, 8g of potatoes and 6g of carrots, put them in a retort pouch, and fill and seal. A retort curry containing 3125 mg of nobiletin, 1563 mg of DHA, and 313 mg of EPA is obtained by performing a retort treatment at 121 ° C for 30 minutes.

The following formulations were also prepared using nobiletin and DHA / EPA;
Specifically, in the following formulation examples 20 to 23, nobiletin-containing extract (manufactured by Rohto Pharmaceutical Co., Ltd., containing 5% nobiletin, 4% tangeretin) and DHA, DHA / EPA-containing fish oil (manufactured by DSM, A DHA content of 30% by weight and an EPA content of 15% by weight) were used.

Formulation Example 20: Granules Nobiletin extract 0.5g, DHA / EPA-containing fish oil 10g, acidulant 5g, sweetener (sucralose) 30g by granulating with a granulator, nobiletin 25mg, tangeretin 20mg, DHA 3000mg, EPA 1500mg The blended granules (45.5 g) are obtained.

Formulation Example 21: Drink agent By mixing 0.1 g of nobiletin extract and 5 g of DHA / EPA-containing fish oil and filling the bottle, a drink (5 mL) containing 5 mg of nobiletin, 4 mg of tangeretin, and 1500 mg of DHA and 750 mg of EPA is obtained. .

Formulation Example 22: Stick jelly Nobiletin extract 0.05 g, DHA / EPA-containing fish oil 15 g, sugar 5 g, concentrated apple juice 2 g, gelling agent (thickening polysaccharide) mixed with warming and cooled Thus, 2.5 mg of nobiletin, 2 mg of tangeretin, and 4500 mg of DHA and 2250 mg of EPA, a stick jelly (25 g) is obtained.

Formulation Example 23: Sugar-coated tablets 0.3 g of nobiletin extract, 20 g of DHA / EPA-containing fish oil, and 50 g of dextrin are mixed and compressed into tablets. Further, by sugar coating, a sugar-coated tablet (75 g) containing 15 mg of nobiletin, 12 mg of tangeretin, 6000 mg of DHA, and 3000 mg of EPA is obtained.

  In Formulation Examples 1 to 23, a desired formulation can be formulated by appropriately adjusting the type and blending amount of nobiletin, tangeretin, ω-3 fatty acid, other blending components, and the like.

  The composition containing the compound of formula (I) and omega-3 fatty acid of the present invention can be used for preventing and / or improving the decrease in brain function.

Claims (9)

Formula (I):

A food and beverage composition containing a compound of the formula: wherein R ^{1 to} R ⁷ are each independently H, OH, C _1-6 alkyl or C _1-6 alkoxy, and ω-3 fatty acid. .   The food-drinks composition of Claim 1 which contains 0.1-1,000 weight part of (omega) -3 fatty acid with respect to 1 weight part of compounds of a formula (I).   The food or beverage composition according to claim 1 or 2, wherein the compound of the formula (I) is at least one selected from the group consisting of nobiletin, tangerine, luteolin, and quercetin.   The ω-3 fatty acid is α-linolenic acid (ALA), eicosatrienoic acid (ETE), eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA) The food-drinks composition as described in any one of Claims 1-3 which is at least one selected from the group which consists of.   The food-drinks composition as described in any one of Claims 1-4 for preventing and / or improving the fall of a brain function.   The food-drinks composition as described in any one of Claims 1-5 which contains 0.1-3,000 mg of compounds of Formula (I) as a daily dose.   The food-drinks composition as described in any one of Claims 1-5 which contains 1-5,000 mg of omega-3 fatty acid as a daily dose.   The food-drinks composition as described in any one of Claims 1-7 with which the capsule was filled. Formula (I):

[Wherein R ^{1 to} R ⁷ are each independently H, OH, C _1-6 alkyl or C _1-6 alkoxy] with respect to 1 part by weight of polymethoxyflavone represented by ω A method for suppressing or reducing odor, which comprises blending 3 fatty acids in a proportion of 0.1 to 1,000 parts by weight.