Composition for improving cognitive function, food, medicine, and composition kit containing the same, and method for producing the composition

Abstract

To provide a cognitive function improving composition that can be easily absorbed by a living body and easily demonstrate effects, a food, a pharmaceutical, and composition kit including the same, and a production method of the composition.SOLUTION: There are provided: a cognitive function improving composition containing hesperidin and tea polyphenol; a food, a pharmaceutical and a composition kit including the same; and a production method of the composition.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving cognitive function, a food product, a drug product, and a composition kit containing the composition, and a method for producing the composition. [Background technology]

[0002] Flavanone glycosides are found in large amounts in citrus fruits such as mandarins and are known to have lipid antioxidant properties, etc. Among them, hesperidin is a flavanone glycoside that has been recognized for its effects of strengthening blood vessels, lowering blood pressure, reducing cholesterol and triglycerides, and improving blood flow.

[0003] As an example of an invention utilizing hesperidin, the invention of Patent Document 1 involves conjugating glucose to a portion of hesperidin, which has low water solubility and is difficult to process, and then enzymatically treating the hesperidin to make it water soluble.

[0004] Regarding the effects and efficacy of compositions containing hesperidin, for example, according to Patent Document 2, it has been confirmed that drinking enzyme-treated hesperidin improves the quality of sleep.

[0005] According to Non-Patent Document 1, drinking enzyme-treated hesperidin (170 mg as aglycone) significantly restored the blood flow and skin surface temperature of the hands that had decreased due to cold stimulation compared to the placebo group.

[0006] Patent Document 3, filed by the present inventors, discloses a composition containing flavanone glycosides and tea polyphenols. Patent Document 3 also discloses a method for producing this composition, which includes a process for preparing a mixed and kneaded product by kneading a raw material containing the flavanone glycosides and a raw material containing the tea polyphenols to obtain a mixed and kneaded product, and an extraction process for immersing the mixed and kneaded product in an extraction solvent.

[0007] Patent Document 4, filed by the present inventors, discloses a composition containing hesperidin and tea polyphenols for improving sensitivity to cold, alleviating stiff shoulders, recovering from fatigue, or improving sleep, as well as a food, drug, and composition kit containing the composition, and a method for producing the composition. This technology aims to obtain the above-mentioned composition, etc., which is easily absorbed by the body and is likely to have the effects of improving the various physical conditions mentioned above. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] Japanese Patent Application Publication No. 3-7593 [Patent Document 2] Japanese Patent Application Laid-Open No. 2010-064992 [Patent Document 3] International Publication No. 2014 / 136681 [Patent Document 4] Patent No. 6826347 Public Relations [Non-patent literature]

[0009] [Non-Patent Document 1] Journal of the Japanese Society of Nutrition and Food Science, Vol. 61, No. 5, 233-239 (2008) Summary of the Invention [Problem to be solved by the invention]

[0010] In recent years, the number of elderly people involved in social and economic activities has been increasing, but physical abilities decline with age. In particular, declines in cognitive functions such as attention, judgment, and memory can significantly impede daily life. In addition to aging, cognitive decline can also occur due to various illnesses. Therefore, maintaining, preventing, and improving cognitive function are important issues in Japan.

[0011] Regarding the effects of hesperidin that have been known up to now, as shown in the above-mentioned prior art, several effects on the body have been predicted. However, in the prior art, the absorbability and effects in the body relative to the amount ingested are limited, and therefore the effects have not been fully confirmed.

[0012] The present inventors have used a composition containing hesperidin and tea polyphenols, which are easily absorbed by the body and exhibit their effects, as described in Patent Document 4, and have been examining the effects of this composition on the body.

[0013] The present invention has been made in consideration of the above-mentioned circumstances, and aims to provide a composition that is easily absorbed by the body and can effectively improve cognitive function, a food, a drug, a composition kit containing the same, and a method for producing the composition. [Means for solving the problem]

[0014] Embodiments of the present invention have the following aspects. A first aspect of the present invention is a composition for improving cognitive function, which contains hesperidin and tea polyphenols.

[0015] A second aspect of the present invention relates to a composition for improving cognitive function according to the first aspect, which further comprises an association of hesperidin and tea polyphenols.

[0016] A third aspect of the present invention relates to the composition for improving cognitive function according to the second aspect, wherein the association of hesperidin with the tea polyphenols has a structure in which the hydrophobic portion of the hesperidin is incorporated into the tea polyphenols through association.

[0017] A fourth aspect of the present invention is a composition for improving cognitive function according to any one of the first to third aspects, which comprises a mixed and rolled product obtained by mixing and rolling a mandarin orange containing the hesperidin and tea containing the tea polyphenols, and which comprises 10 to 50% by mass of mandarin orange mixed with the total mass of the rolled product.

[0018] A fifth aspect of the present invention relates to the composition for improving cognitive function according to the fourth aspect, wherein the mandarin orange comprises an unripe mandarin orange, and the tea comprises fresh green tea leaves.

[0019] A sixth aspect of the present invention relates to a composition for improving cognitive function according to any one of the first to fifth aspects, wherein the composition contains 20 to 60 mg of hesperidin per 1000 mg of the total mass of the composition.

[0020] A seventh aspect of the present invention is a composition for improving cognitive function according to any one of the first to sixth aspects, wherein the tea polyphenols are contained in an amount of 75 to 200 mg per 1000 mg of the total mass of the composition.

[0021] Aspect 8 of the present invention relates to a composition for improving cognitive function according to any one of aspects 1 to 7, wherein the tea polyphenols are contained in a mass ratio of the hesperidin to the hesperidin of 2:1 to 1:4.

[0022] A ninth aspect of the present invention is a food product comprising the composition for improving cognitive function according to any one of the first to eighth aspects.

[0023] A tenth aspect of the present invention is a pharmaceutical agent comprising the composition for improving cognitive function according to any one of the first to eighth aspects.

[0024] An eleventh aspect of the present invention is a composition kit including 28 to 90 compositions for improving cognitive function according to any one of the first to eighth aspects.

[0025] A twelfth aspect of the present invention is a method for producing a composition for improving cognitive function according to any one of the first to eighth aspects, comprising a rolling step of mixing and rolling the raw material a containing hesperidin and the raw material b containing tea polyphenols to obtain a mixed and rolled product.

[0026] Aspect 13 of the present invention is a method for producing a composition for improving cognitive function according to aspect 12, wherein the rolled product preparation step uses mandarin orange as raw material a and tea as raw material b, and mixes and rolls the raw material a in an amount of 10 to 50% by mass relative to the total mass of the mixed rolled product.

[0027] A fourteenth aspect of the present invention is a method for producing a composition for improving cognitive function according to the thirteenth aspect, wherein the mandarin orange of the raw material a is an unripe mandarin orange, and the tea of ​​the raw material b is fresh green tea leaves.

[0028] A fifteenth aspect of the present invention is a method for producing a composition for improving cognitive function according to any one of aspects 12 to 14, wherein the kneaded product preparation step further comprises, after mixing and kneading raw materials a and b, blowing hot air at a temperature of 80 to 120°C for 10 to 60 minutes and drying the mixed kneaded product to a moisture content of 5% by mass relative to the total mass of the mixed kneaded product. A sixteenth aspect of the present invention is a method for producing a composition for improving cognitive function according to any one of aspects 12 to 15, wherein the kneaded product preparation step comprises mixing raw material a and raw material b in a ratio of 1:2 to 1:4, and kneading the mixture for 15 to 30 minutes. [Effects of the Invention]

[0029] According to the present invention, it is possible to obtain a composition that is easily absorbed by the body and is effective in improving cognitive function, as well as a food, drug, and composition kit containing the composition, and a method for producing the composition. DETAILED DESCRIPTION OF THE INVENTION

[0030] The cognitive function improving composition of the present invention, the food, drug, and composition kit containing the same, and the method for producing the composition will be described below with reference to embodiments, although the present invention is not limited to the following embodiments.

[0031] (Embodiment) The composition for improving cognitive function of this embodiment (hereinafter also simply referred to as "the composition of this embodiment") contains hesperidin (hereinafter, component (A)) and tea polyphenols (hereinafter, component (B)).

[0032] <Component (A): Hesperidin> Component (A) is hesperidin. Hesperidin is a type of flavanone glycoside. Flavanone glycosides are glycosides in which sugar is bound to a flavonoid having a flavanone skeleton, and examples include hesperidin, narirutin, naringin, and neohesperidin. Of these, hesperidin is a glycoside of the flavanone hesperetin. Component (A) is contained in raw materials of citrus fruits such as unripe mandarins, etc. These raw materials may contain the above-mentioned flavanone glycosides other than hesperidin.

[0033] <(B) Ingredient: Tea polyphenols> Component (B) is tea polyphenols. Tea polyphenols generally refer to polyphenols contained in tea leaves or polyphenols extracted from tea leaves. Examples of tea polyphenols include catechin, protocyanidin, flavonol glycosides, and black tea polyphenols. More specifically, fresh green tea leaves contain gallic acid, theasinensin B, epigallocatechin, caffeine, theasinensin A, epicatechin, epigallocatechin gallate, epicatechin gallate, naringin, theaflavin, and the like. Component (B) is contained in raw materials such as non-fermented tea leaves such as green tea, and fermented tea leaves such as black tea and oolong tea. The source of component (B) may be a refined product such as catechin, protocyanidin, flavonol glycoside, or black tea polyphenol, or an extract such as black tea extract or green tea extract. Among non-fermented tea leaves, fresh green tea leaves are preferred because they are rich in tea polyphenol components and, after undergoing the rolling process described below, also contain the catechins and other components contained in fermented tea. In this embodiment, fresh green tea leaves are used.

[0034] The composition of the present embodiment may contain the above-mentioned components and may also contain optional components described below. Depending on the components, the composition may be prepared in various forms, such as a solid form such as a powder or tablet, or a liquid.

[0035] <Association> The cognitive function improving composition of this embodiment preferably contains an aggregate of the above-mentioned hesperidin (component (A)) and the above-mentioned tea polyphenol (component (B)). Here, the aggregate refers to a compound formed by bonding multiple compounds through intermolecular forces (e.g., hydrophobic bonds or hydrogen bonds).

[0036] In the composition of this embodiment, hesperidin and tea polyphenols are associated with each other by rolling or other operations during the manufacturing process described below. As a result, hesperidin becomes particularly effective for improving cognitive function through association with tea polyphenols. Specifically, this is thought to be due to the increased water solubility of hesperidin, which is normally poorly soluble and difficult to absorb, as well as other synergistic effects such as increased absorbability into the body.

[0037] Furthermore, in this embodiment, it is particularly preferable that the association of hesperidin with the tea polyphenols has a structure in which the hydrophobic portion of the hesperidin is incorporated by the tea polyphenols through association.

[0038] In general, component (A) has poor solubility in water because its hydrophobic moieties (e.g., the hesperetin moiety in hesperidin) tightly associate to form crystals. However, when raw materials containing hesperidin and tea polyphenols are mixed and kneaded, water-soluble catechins and tea polyphenols produced by the oxidative polymerization of catechins incorporate the hydrophobic moieties of flavonoids through association (a stacking effect) due to their amphiphilic nature. In other words, when hesperidin and tea polyphenols coexist, the tea polyphenols separate the hydrophobic associations between hesperidin and form an aggregate with hesperidin. The formed aggregate of tea polyphenols and hesperidin is highly soluble in water. Furthermore, this form is thought to enhance hesperidin's absorption into the body.

[0039] The formation of such an association between hesperidin and tea polyphenols can be confirmed by, for example, 1H-NMR analysis, which shows that the chemical shift of the ring portion of hesperidin is negative compared to other hydrophilic portions such as the sugar portion (Glc-1,6) of hesperidin, thereby confirming that the hydrophobic B-ring and C-ring portions of hesperidin are covered.

[0040] Such an aggregate of hesperidin and tea polyphenols enhances the cognitive function improving effect of this embodiment. Conventional techniques have attempted to increase the water solubility of hesperidin by enzymatic extraction and reactions such as glycosyltransferase, but these require the ingestion of relatively large amounts of hesperidin, such as 0.5 to 50 g or 500 mg to 2000 mg. This may be due to the insufficient absorption of hesperidin per weight, which may require the ingestion of large amounts to exert its physiological activity. In this embodiment, as described below, by ingestion of a composition containing 20 to 60 mg of hesperidin, various physical constitutions, particularly cognitive function, are immediately improved.

[0041] (Intake amount) The composition of this embodiment preferably contains 20 to 60 mg of hesperidin per serving. Specifically, when used for the purpose of improving cognitive function, the desired effect can be achieved by taking the above-mentioned amount per serving. As a guideline, a sufficient effect can be achieved by taking 20 mg of the hesperidin contained in the composition of this embodiment per serving. There is no particularly desirable upper limit to the intake amount, but setting the upper limit at 60 mg as a guideline is appropriate from the perspective of cost and the intake form described below.

[0042] The total weight of the composition of this embodiment can be selected as appropriate, so long as the hesperidin content per intake of the composition is within the above-mentioned range. However, as a guideline, it is preferable that the composition contains 20 to 60 mg of hesperidin per 1000 mg of total weight of the composition. Per 1000 mg of intake or per 1000 mg of total weight of the composition, it is more preferable that the composition contains 20 to 50 mg, even more preferable that the composition contains 22 to 40 mg, and particularly preferable that the composition contains 30 to 40 mg. Ingesting 20 mg of hesperidin per 1000 mg of total weight of the composition provides a sufficient effect of improving physical constitution. While there is no particularly desirable upper limit for the intake amount, setting the upper limit at 60 mg as a guideline is appropriate from the perspective of cost and the intake form described below.

[0043] The composition of this embodiment preferably contains 75 to 200 mg of tea polyphenols per serving. By including 75 mg or more, the hesperidin of this embodiment can be effectively absorbed. When used for the purpose of improving cognitive function, the desired effect can be achieved by ingesting the above-mentioned amount per serving. While there is no particularly desirable upper limit for the intake amount, setting the upper limit at 200 mg is an appropriate amount in terms of the amount of hesperidin, costs, and the intake form described below.

[0044] The total weight of the composition of this embodiment can be selected as appropriate, so long as the tea polyphenol content per intake of the composition is within the above-mentioned range. However, as a guideline, it is preferable that the composition contains 75 to 200 mg of tea polyphenols per 1000 mg of total weight. It is even more preferable that the tea polyphenol content per intake or per 1000 mg of total weight of the composition is 25 to 40 mg. A range of 20 to 60 mg per 1000 mg of total weight of the composition is an appropriate amount from the perspectives of sufficient effect, cost, and the intake form described below.

[0045] The composition of the present embodiment preferably contains tea polyphenols to hesperidin in a mass ratio of 2:1 to 1:4. In the composition of this embodiment, the mass ratio of tea polyphenols to hesperidin is approximately 1 to 1.6 times that of hesperidin in the aggregate of hesperidin and tea polyphenols. Analysis by the present inventors has shown that aggregates are often formed at a ratio of approximately 1 to 2 molecules of tea polyphenols to 1 molecule of hesperidin. However, it is presumed that this wide range is due to the fact that tea polyphenols contain components with a wide range of molecular weights, all of which may associate with hesperidin. In view of this, in the composition of this embodiment, if the hesperidin:tea polyphenol ratio is greater than 2:1, hesperidin can exert its physiological activity, and if the hesperidin:tea polyphenol ratio is up to about 1:4, the tea polyphenol content is not excessively high and hesperidin can exert its physiological activity. The composition of the present embodiment preferably contains hesperidin and tea polyphenols in a mass ratio of 1.5:1 to 1:2, and more preferably 1:1 to 1:1.25.

[0046] (optional ingredient) The composition of the present embodiment may contain optional components other than components (A) and (B) depending on, for example, the dosage form and the like. For example, a solid composition may contain a binder such as starch in order to improve granulation or moldability.

[0047] (for cognitive function improvement) The composition of this embodiment can be a composition for improving cognitive function. Here, cognitive function broadly refers to the functions of an organism collecting, perceiving, remembering, and judging external information, as well as the functions related thereto. Specifically, it refers to the functions of obtaining information through the senses, such as the five senses (sight, hearing, smell, touch, and taste), vestibular sense (balance), and proprioception, as well as the functions of processing such information, and functions related thereto. More specifically, cognitive function includes functions such as attention, judgment, and memory.

[0048] Cognitive function here refers to the cognitive functions possessed by living organisms in general, and particularly those possessed by humans. Cognitive function improvement broadly refers to the improvement of these functions, but in particular refers to the recovery of cognitive function in subjects with declined cognitive function to a state prior to decline. Factors that cause cognitive function decline include various diseases as well as aging.

[0049] Specific indicators of cognitive decline and improvement (recovery) include, for example, the results of the MMSE test, the TMT (Trail Making Test), the Benton Visual Retention Test, or the Standard Verbal Paired Associate Learning Test.

[0050] The MMSE test is a type of method widely used as a screening test for dementia. It involves administering a test on multiple test items, calculating the total score, and comparing it with the score for a perfect score. The test items include, for example, 11 items: time orientation (5 points), place orientation (5 points), immediate word recall (3 points), calculation (5 points), delayed recall (3 points), object naming (2 points), sentence repetition (1 point), verbal command (3 points), written command (1 point), sentence writing (1 point), and figure copying (1 point), totaling a maximum score of 30 points. This embodiment is particularly effective in improving cognitive function in the calculation item of the MMSE test.

[0051] As an effect of this embodiment, it is preferable that the total score of the MMSE test out of a total of 30 points improves by an average of 0.4 points or more 12 weeks after starting to take 20 to 60 mg of the composition for improving cognitive function of this embodiment per day. Furthermore, it is preferable that the score for the calculation section of the MMSE test (out of 5 points) improves by an average of 0.25 points or more 12 weeks after starting intake of 20 to 60 mg of the composition for improving cognitive function of this embodiment per day. Furthermore, the score for the above calculation items is preferably 4.90 or more, and more preferably 4.95 or more, 12 weeks after the start of intake.

[0052] Additionally, various TMT tests can be used as indicators for the TMT test, but for example, the Trail Making Test Japanese version (TMT-J) may be used. TMT-J is a test method that can comprehensively measure a wide range of aspects, including attention, working memory, spatial search, processing speed, perseveration, and impulsivity. The TMT-J test consists of TMT-J Part A, in which participants connect numbers in order from 1 to 26, and TMT-J Part B, in which participants connect numbers and the Japanese alphabet alternately. In both cases, the time it takes to connect the letters is measured, and a reduction in the time is evaluated as improvement. In this embodiment, improvements are observed in both TMT-J Part A and TMT-J Part B.

[0053] As an effect of this embodiment, the change in the time required (in seconds) for the TMT-J Part A test is preferably reduced by 15.0 or more, more preferably by 20.0 or more, and particularly preferably by 25.0 or more. Furthermore, as an effect of this embodiment, the amount of change in the time (number of seconds) required for the TMT-J Part B test is preferably reduced by 20.0 or more, and more preferably reduced by 24.0 or more.

[0054] In conventional techniques, hesperidin was not sufficiently absorbed into the body, but when the composition of the present embodiment is administered, the effect on the body, as described below, is sufficiently large that it is thought to lead to improvement in cognitive function. The present inventors have investigated the activity of hesperidin, and in particular, have investigated the ecological efficacy and effects of a composition containing hesperidin and tea polyphenols, which is easily absorbed by the body and exhibits its effects. As a result, they have discovered that a composition containing hesperidin and tea polyphenols has a previously unknown effect of improving cognitive function, which led to the completion of the present invention.

[0055] The composition of the present embodiment may have functions such as improving sensitivity to cold, improving stiff shoulders, recovering from fatigue, improving sleep, etc., in addition to improving cognitive function. Specifically, by including the composition of the present embodiment, the composition also has these functions.

[0056] (food) The food product of this embodiment contains the composition of this embodiment. The target food is not particularly limited, and examples thereof include gel foods obtained by adding thickening polysaccharides, gelatin, or the like to the beverage of the present embodiment described above and cooling the mixture. Other examples include processed foods and confectioneries.

[0057] The food product of this embodiment also includes beverages. The beverage of this embodiment contains the composition of this embodiment. For example, an extract can be obtained by immersing the composition of this embodiment in water or another solvent, for example, an alcohol such as ethanol, or another organic solvent, and then heating the resulting mixture at a desired temperature, or by immersing the rolled mixture in a solvent such as water at a desired temperature. That is, the beverage of this embodiment can be obtained in the same manner as conventionally known methods for drinking tea. In particular, since the physiologically active components of the composition of this embodiment are highly water-soluble, even if the composition is served in a dry state, the physiologically active components can be re-dissolved in water by extracting them with water, making them more easily absorbed. Alternatively, the composition of the present embodiment in a liquid or solid form may be added to any beverage (for example, soft drinks, alcoholic beverages).

[0058] (drug) The drug of this embodiment contains the composition of this embodiment. Here, the drug includes pharmaceuticals, quasi-drugs, etc.

[0059] The content of the composition of this embodiment in the drug is determined appropriately taking into consideration the dosage form of the drug, etc. For example, the content of the composition of the present embodiment in a pharmaceutical product may be the same as or greater than that of a composition contained in food, etc. A single dose may be an amount that allows 500 to 2000 mg of hesperidin to be ingested.

[0060] (Composition kit) The composition of this embodiment can also be in the form of a kit containing the composition. For example, the kit can contain 28 to 90 packets, each containing an amount of the composition for one intake. Although the composition of this embodiment can achieve some improvement in physical constitution within one hour to one day even when taken in the above-mentioned amount only once, particularly significant effects such as improved cognitive function can be achieved by taking, for example, one packet per day continuously for at least four weeks, preferably at least eight weeks. Therefore, compositions for improving cognitive function in particular can be provided in the form of a kit containing at least 28 packets (a four-week supply), preferably at least 56 packets (an eight-week supply). While there is no particular upper limit, sufficient effects can be achieved by taking 90 packets (a three-month supply) continuously as a guideline, so a kit containing up to 90 packets may be used for continuous intake. For example, a kit set may contain 56 to 70 packets (an eight- to ten-week supply) to achieve sufficient effects. Furthermore, the kit may contain 28 to 90 of the above-mentioned foods or medicines.

[0061] (Manufacturing method) The method for producing the composition of the present embodiment is determined appropriately depending on the dosage form, etc. For example, the (A) component and the (B) component may be dispersed in water and mixed to obtain a liquid composition of the present embodiment, or the liquid composition of the present embodiment may be dried by freeze-drying or the like to obtain a solid composition of the present embodiment.

[0062] Alternatively, for example, the composition of the present embodiment can be obtained from a raw material containing component (A) (hereinafter, sometimes referred to as raw material a) and a raw material containing component (B) (hereinafter, sometimes referred to as raw material b).

[0063] An example of a production method for obtaining the composition of this embodiment from raw materials a and b will be described below. The method for producing the composition of this embodiment includes a step of kneading raw materials a and b to obtain a kneaded mixture (kneaded mixture preparation step, kneading step). This kneaded mixture may be used as the composition of this embodiment, or an additional step may be added to the kneaded mixture. For example, a fermentation step may be added to ferment the kneaded mixture. Alternatively, a step of extracting components from the kneaded mixture (extraction step) may be added, and the product (water extract, hot water extract) that has undergone this extraction step may be used as the composition of this embodiment.

[0064] <Mushroom preparation process> The rolling / kneading step is a step of obtaining a rolling / kneading mixture of raw materials a and b. First, raw material a is sliced ​​or crushed into small pieces by a conventionally known technique, and the small pieces of raw material a are mixed with raw material b and kneaded (kneading operation) to obtain a mixed kneaded product.

[0065] Raw material a may be any fruit containing component (A), such as mandarin oranges, oranges, iyokan, ponkan, pomelo, hyuganatsu, hassaku, daidai, natsumikan, grapefruit, yuzu, kabosu, or trifoliate orange. Of these, mandarin oranges are preferred, with unripe mandarin oranges being more preferred. Functional components such as hesperidin and methoxyflavones are found in high concentrations in unripe mandarin oranges, and unripe mandarin oranges are preferred because they have not traditionally been used as effectively as mature mandarin oranges. Thinned mandarin oranges, which are fruit that will not be harvested but have been removed before maturity, are particularly preferred, as they allow for effective use of thinned mandarin oranges. Raw material a may be fresh produce or a dried product, and a dried product is preferable. If the raw material a is a dried product, moisture is less likely to be squeezed out during the rolling operation, and the (A) component in raw material a is less likely to be washed away.

[0066] Raw material b is tea leaves, and may be fresh tea leaves, fermented tea leaves, or pre-withered tea leaves. Fresh green tea leaves are preferred because they are rich in tea polyphenols that interact with hesperidin in this embodiment. It is preferable that raw material b is withered in advance before mixing with raw material a. The withered raw material b is less likely to lose moisture during the rolling operation, and the (B) component in raw material b is less likely to be washed away. The moisture content of the withered raw material b is, for example, preferably 45 to 65% by mass, and may be 45 to 60% by mass.

[0067] The rolling method is not particularly limited, and for example, raw material b may be rolled for a given time, and then raw material a may be added and rolled, or raw materials a and b may be charged in advance and then rolled. For example, a tea manufacturing machine or a device such as a pressure vessel may be used for the rolling operation.

[0068] The mass ratio of raw material b / raw material a (hereinafter sometimes referred to as the b / a ratio) is determined taking into consideration the moisture content of raw material a and raw material b. For example, if raw material a is fresh fruit or vegetable and raw material b is fresh tea leaves, the b / a ratio is preferably 1 to 10, more preferably 2 to 8, even more preferably 2 to 6, particularly preferably 2 to 4, and even more particularly preferably 3 to 4. If the b / a ratio is less than the above lower limit, the solubility of the resulting composition of the present embodiment in water may be reduced. However, even if the b / a ratio exceeds the above upper limit, the solubility of the composition of the present embodiment in water may not be further improved. Furthermore, for example, when tea is used as raw material b and unripe mandarin oranges as raw material a, the unripe mandarin oranges may be added in an amount of 10 to 50% by weight relative to the amount of tea. Furthermore, the unripe mandarin oranges may be added in an amount of 21 to 30% by weight relative to the amount of tea.

[0069] The temperature of the raw material in the kneading operation is, for example, 20 to 40° C. The time for the kneading operation is, for example, preferably 10 to 60 minutes, more preferably 15 to 30 minutes, and even more preferably 15 to 25 minutes.

[0070] Alternatively, the rolling operation can be carried out by simultaneously applying a higher temperature and / or a higher pressure instead of the physical rolling operation using a tea processing machine or the like at 20 to 40°C as described above. For example, the raw material can be pressurized at a temperature of 80°C or higher, preferably 120°C or higher, for the same period of time as described above, preferably 10 to 20 minutes. This operation is preferable because it increases the water solubility. This operation can be carried out using the pressure vessel, such as an autoclave.

[0071] The above-described mixed and rolled product may be used as the composition of this embodiment. Furthermore, a fermentation step (fermentation step) may be added after the rolling preparation step. In particular, when raw material b is not fermented tea, a fermentation step may be added to the composition. The composition of this embodiment does not necessarily require a fermentation step because the rolling step sufficiently increases the water solubility of the composition, causing oxidation of the catechins contained in the tea leaves to produce components equivalent to black tea polyphenols. However, a fermentation step may be carried out to obtain a composition containing more fermented components. In the fermentation operation, the mixed rolled product is piled up to a thickness of several centimeters and left to stand in an environment such as a fermentation room at a temperature of 20 to 27°C and a humidity of 30 to 60% RH. The fermentation time is, for example, 0 to 4 hours. Note that fermentation of raw material a or raw material b may start simultaneously with the start of the rolling operation. In that case, taking into consideration that fermentation occurs earlier, the fermentation time may be, for example, 0 to 1 hour.

[0072] In addition, the rolling process may include a drying operation after the rolling process (or after the fermentation process if a fermentation process is included). By including the drying operation, oxidases (such as polyphenol oxidase) in the rolling process can be inactivated, the moisture content can be reduced, and the quality stability of the rolling process can be improved. The drying operation is carried out, for example, by putting the raw material into a continuous dryer and blowing hot air at a temperature of 80 to 120° C. into it so that the exhaust temperature is 50 to 60° C. The drying operation time is not particularly limited and is, for example, 10 to 60 minutes. The moisture content of the mixed and rolled product after the drying operation is preferably, for example, 5% by mass or less.

[0073] <Extraction process> The composition of this embodiment may be further subjected to an extraction step to obtain an extracted composition. As will be described later, the extracted composition will be referred to as a water extract, a hot water extract, or the like depending on the solvent used for extraction. The extraction step is a step of further extracting an extract composition from the mixed rolled product obtained in the rolled product preparation step. The extraction step may, for example, be a method in which the mixed and rolled product is immersed in an extraction solvent and heated at a given temperature to extract the composition of the present embodiment into the extraction solvent, thereby obtaining a liquid composition of the present embodiment.

[0074] Examples of extraction solvents include water, organic solvents (for example, lower alcohols having 1 to 6 carbon atoms), and mixtures thereof. The temperature conditions in the extraction step are not particularly limited, and a temperature of 20 to 100°C is preferred, for example. As a guideline, an extract composition extracted with water at room temperature or lower (0 to 40°C) is called a water extract, and an extract composition extracted with water at a higher temperature (40 to 100°C) (hot water) is called a hot water extract. Extraction with hot water is preferred because it increases the amount of extracted components. Higher hot water temperatures are more preferred because they increase the amount extracted, but a temperature of 60 to 100°C will ensure that the components that provide the effects of the present application are sufficiently extracted. The extraction time is not particularly limited, and is preferably, for example, 3 to 30 minutes.

[0075] After the extraction step, the liquid composition of the present embodiment may be dried to form a solid composition of the present embodiment. Examples of drying methods include freeze-drying. [Example]

[0076] The present embodiment will be described below with reference to examples, but the present invention is not limited to the following examples.

[0077] (Production of Composition) 30 kg of green tea leaves (raw material b) were withered to obtain 15 kg of raw material b with a moisture content of 50% by mass. 15 kg of withered raw material b was mixed with 10 kg of sliced ​​unripe mandarin oranges (raw material a) and rolled using a tea processing machine to obtain a mixed rolled product (rolling operation). The rolling time was 20 minutes, and the rolling temperature was 35°C. The mixed and kneaded product was dried by exposing it to air at 100° C. for 30 minutes (drying operation). The elution rate was calculated by the following formula (1). The obtained composition was designated as Example 1.

[0078] Dissolution rate (mass%) = [dissolution amount per mandarin orange] ÷ [amount of hesperidin in dried raw material A (100 mg)] × 100 (1) [In formula (1), the amount of elution per mandarin orange is the amount of elution (amount (mg) of component (A) eluted from the mixed, rolled product) determined in the extraction test described below, multiplied by 4 in Example 1.]

[0079] (Extraction test) (hot water extraction) 100 mg of the composition of Example 1 was immersed in 100 mL of water at 100°C, and then left at room temperature until the water temperature reached approximately room temperature, thereby obtaining a hot water extract (Example 2). In addition, a hot water extract (Comparative Example 1) was also obtained by hot water extraction of 100 mg of raw material a alone, instead of the composition of Example 1. The resulting extract was filtered through a 0.45 μm membrane filter, and the amount of hesperidin in the filtrate was measured using ultra-high performance liquid chromatography (UFLC) (HPLC, manufactured by Shimadzu Corporation). Three measurements were performed for each sample, and the amount of hesperidin eluted was calculated from the obtained area. The HPLC analysis conditions were as follows: The amount of hesperidin contained in the dried material a (100 mg) was 20.8 mg.

[0080] [Analysis conditions] Column: Shim-pack C18 (3.0 × 50 mm, Shimadzu Corporation). Mobile phase A: CH3CN:10 mM phosphoric acid = 20:80 (volume ratio). Mobile phase B: CH3CN:10 mM phosphoric acid = 30:70 (volume ratio). Gradient composition: Mobile phase A:mobile phase B = 100:0 (volume basis) linearly over 7 minutes, and mobile phase A:mobile phase B = 0:100 (volume basis). Flow rate: 0.6mL / min. Column temperature: 40°C. Detection wavelength: 280nm.

[0081] As a result of the test, the elution rate of hesperidin relative to the amount of hesperidin in the raw material from the hot water extract of Example 2 was 45.2±2.7%. In contrast, the elution rate of hesperidin from the hot water extract of Comparative Example 1 was 9.6±1.2%.

[0082] (cognitive function improvement test) The subjects were middle-aged and elderly people who were enrolled in the University of Nagasaki's clinical trial network and experienced cognitive decline but were otherwise healthy. Each subject was given a test drink containing 1.2 g of the composition of Example 1 (containing 36.7 mg of hesperidin) dissolved in water and ingested daily with dinner for 12 weeks. The following tests were performed on the day the intake began (week 0), 6 weeks after the intake began, and 12 weeks after the intake began.

[0083] This study was a randomized, double-blind, placebo-controlled, parallel-group comparative study. Prior to the study, a screening test was conducted using a modified Japanese version of the Montreal Cognitive Assessment (MoCA-J), a test used to screen for mild cognitive impairment. After that, taking into consideration age and MoCA-J score, subjects were randomly assigned to a test food group (22 subjects) (containing 36.7 mg of hesperidin) and a placebo food group (21 subjects) (containing 0 mg of hesperidin). Measurement values ​​are shown as mean ± standard error. Comparisons between different foods were performed using unpaired t-tests or Mann-Whitney U tests, and comparisons with the baseline were performed using paired t-tests or Wilcoxon signed-rank tests. All tests were two-sided, with a statistical significance level of p < 0.05.

[0084] (1) Mini-Mental State Examination (MMSE) As mentioned above, the test consisted of 11 items, including time orientation (5 points), place orientation (5 points), immediate word recall (3 points), calculation (5 points), delayed recall (3 points), object naming (2 points), sentence repetition (1 point), verbal commands (3 points), written commands (1 point), sentence writing (1 point), and figure copying (1 point), with a total possible score of 30 points.

[0085] Table 1 shows the results of the MMSE test, which is an indicator of the improvement in cognitive function due to the composition of Example 1. Here, mean ± standard error *P < 0.05 (significantly different compared to placebo food). After 12 weeks of intake, the test food group showed significantly higher scores than the placebo group, especially in the calculation item, which involved subtracting 7 from 100 in order and repeating this process four times. That is, it was shown that cognitive function was improved by drinking one packet of the composition of Example 1 (containing 36.7 mg of hesperidin) per day for 12 weeks.

[0086] [Table 1]

[0087] (2)Trail Making Test Japanese version (TMT-J) exam As mentioned above, the TMT-J test consisted of two tests: TMT-J Part A, in which participants had to connect numbers in order from 1 to 26, and TMT-J Part B, in which participants had to connect numbers and the Japanese syllabary alternately. For the TMT-J Part A test, participants used a horizontal A4 sheet of paper with 26 circles, each approximately 1 cm in diameter, written randomly. Each circle had a number from 1 to 26 written on it, and participants had to connect the circles in numerical order with a line in pencil, measuring the time required in seconds. For the TMT-J Part B test, participants used a horizontal A4 sheet of paper with 25 circles, each approximately 1 cm in diameter, written randomly. Each circle had either a number from 1 to 13 or the hiragana characters "a-shi" written on it, and participants had to connect the circles in the order of number and hiragana with a line in the order "1 → a → 2 → i → 3 → u," measuring the time required in seconds.

[0088] Table 2 shows the results of the time required for TMT-J Part A, which is an index of the improvement of cognitive function due to the composition of Example 1, and the amount of change. Here, mean ± standard error *P < 0.05 (significant difference compared to placebo food) #p < 0.05 (significant difference compared to the start date of intake). The time required to complete the test was reduced over time in both the test food and placebo groups from the start of intake until 12 weeks later, and was significantly reduced in both groups after 12 weeks compared to the start date. Furthermore, after 12 weeks, the test food group showed significantly lower values ​​than the placebo group. When the change in time required was calculated, after 12 weeks, the values ​​in the test food group were significantly lower than those in the placebo group.

[0089] [Table 2]

[0090] Table 3 shows the results of the time required for TMT-J Part B and the amount of change, which are indicators of the improvement of cognitive function by the composition of Example 1. Here, the mean value ± standard error was set to p<0.05 (significant difference compared to the intake start date). The time required for both the placebo and test food groups decreased over time, and was significantly shorter 12 weeks after initiation of intake than at the start of intake. The time required for the test food group after 12 weeks of intake tended to be shorter than that for the placebo group (p = 0.10). No significant difference was observed in the amount of change in time required between the groups. In particular, it was shown that cognitive function was improved by taking one packet of the composition of Example 1 (containing 36.7 mg of hesperidin) once a day for 12 weeks.

[0091] [Table 3]

[0092] Although several embodiments of the present invention have been described above, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. These embodiments and their modifications are included within the scope and spirit of the invention, as well as within the scope of the invention and its equivalents as defined in the claims. [Industrial Applicability]

[0093] According to the present invention, it is possible to obtain a composition for improving cognitive function that is easily absorbed by the body and is highly effective, a food product, a drug, a composition kit containing the same, and a method for producing the composition.

Claims

1. A composition for improving cognitive function containing hesperidin and tea polyphenols, The improvement in cognitive function is an improvement in attention, working memory, spatial search, processing speed, perseveration, or impulsivity; A composition for improving cognitive function, comprising as an active ingredient a mixed rolled product of the mandarin orange containing hesperidin and tea containing the tea polyphenol, A composition for improving cognitive function, comprising 10 to 50% by mass of mandarin oranges relative to the total mass of the mixed rolled product.

2. 2. The composition for improving cognitive function according to claim 1, comprising an aggregate of said hesperidin and said tea polyphenol.

3. 3. The composition for improving cognitive function according to claim 2, wherein the association of hesperidin and tea polyphenol has a structure in which the hydrophobic portion of hesperidin is incorporated into the tea polyphenol by association.

4. The composition for improving cognitive function according to claim 1, wherein the mandarin orange comprises an unripe mandarin orange and the tea comprises fresh green tea leaves.

5. 3. The composition for improving cognitive function according to claim 1, wherein the composition contains 20 to 60 mg of hesperidin per 1000 mg of total mass of the composition.

6. The composition for improving cognitive function according to claim 1 or 2, wherein the tea polyphenols are contained in an amount of 75 to 200 mg per 1000 mg of the total mass of the composition.

7. The composition for improving cognitive function according to claim 1 or 2, containing the tea polyphenols in a mass ratio of 2:1 to 1:4 relative to the hesperidin.

8. A food for improving cognitive function, comprising the composition for improving cognitive function according to claim 1 or 2.

9. A drug for improving cognitive function, comprising the composition for improving cognitive function according to claim 1 or 2.

10. A composition kit for improving cognitive function, comprising 28 to 90 compositions for improving cognitive function according to claim 1 or 2.

11. 3. A method for producing a composition for improving cognitive function according to claim 1, comprising a kneaded product preparation step of mixing and kneading the raw material a containing hesperidin and the raw material b containing tea polyphenols to obtain a mixed kneaded product.

12. The rolling preparation step uses mandarin oranges as the raw material a and tea as the raw material b, and mixes and rolls the raw material a in an amount of 10 to 50% by mass with respect to the total mass of the mixed rolling product. A method for producing a composition for improving cognitive function according to claim 11.

13. The method for producing a composition for improving cognitive function according to claim 12, wherein the mandarin orange of raw material a is an unripe mandarin orange, and the tea of ​​raw material b is fresh green tea leaves.

14. 12. The method for producing a composition for improving cognitive function according to claim 11, wherein the rolling preparation step further comprises, after the operation of mixing and rolling the raw material a and the raw material b, blowing hot air at a temperature of 80 to 120°C for 10 to 60 minutes and drying the mixed and rolled product so that the moisture content is 5% by mass with respect to the total mass of the mixed and rolled product.

15. The method for producing a composition for improving cognitive function according to claim 11, wherein the rolling and kneading step comprises mixing raw material a and raw material b in a ratio of 1:2 to 1:4 and rolling the mixture for 15 to 30 minutes.

16. The composition for improving cognitive function according to claim 1 or 2, wherein the improvement in cognitive function is a reduction in the time required for a Trail Making Test.

17. The composition for improving cognitive function according to claim 16, wherein the improvement in cognitive function is a reduction of 15.0 or more in the time required for the TMT-J Part A test, or a reduction of 20.0 or more in the time required for the TMT-J Part B test.

Images