Composition for improving brain function

Abstract

To provide a composition for improving brain functions that has excellent action of improving brain functions.SOLUTION: A composition for improving brain functions contains tripeptide composed of Leu-Arg-Ala. The brain function improvement may be cognitive function improvement.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for improving brain function, which contains a specific peptide as an active ingredient. [Background technology]

[0002] It is known that peptides consisting of specific sequences exert various functions when orally ingested. For example, as disclosed in Patent Documents 1 and 2, tripeptides consisting of Leu-Arg-Ala are known to have various physiological effects. Patent Document 1 discloses a composition containing a tripeptide consisting of Leu-Arg-Ala, for improving sugar metabolism, suppressing blood glucose level rise, and for antidiabetic purposes. Patent Document 2 discloses a composition containing a tripeptide consisting of Leu-Arg-Ala for lowering blood pressure. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2020-14 A [Patent Document 2] JP 2019-99526 A Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a composition for improving brain function that has an excellent effect of improving brain function. [Means for solving the problem]

[0005] The present inventors conducted research to solve the above problems and discovered that a tripeptide consisting of Leu-Arg-Ala exhibits an excellent effect of improving brain function. This invention is based on this discovery.

[0006] In order to achieve the above object, a composition for improving brain function according to one embodiment of the present invention is characterized by containing a tripeptide consisting of Leu-Arg-Ala. In the composition for improving brain function, the improvement of brain function may be improvement of cognitive function.

[0007] The composition for improving brain function may be an oral composition. A food composition or pharmaceutical composition in another embodiment of the present invention is characterized by comprising the above-mentioned composition for improving brain function. Effect of the Invention

[0008] According to the present invention, an excellent effect of improving brain function can be exhibited. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Hereinafter, one embodiment of the composition for improving brain function (hereinafter also referred to as the composition) of the present invention will be described. The composition included in this embodiment contains a specific tripeptide (Leu-Arg-Ala). In addition, in this specification, the tripeptide consisting of the amino acid sequence Leu-Arg-Ala may be referred to as "LRA peptide".

[0010] LRA peptides can be prepared by chemical synthesis using, for example, known peptide synthesis methods. Examples of peptide synthesis methods include the azide method, acid chloride method, acid anhydride method, mixed acid anhydride method, DDC method, active ester method, carboimidazole method, and oxidation-reduction method. These peptide synthesis methods can be performed by either solid-phase synthesis or liquid-phase synthesis.

[0011] In the above-mentioned peptide synthesis method, it is preferable to protect the amino group, carboxy group, and / or side chain functional group (e.g., the guanidino group of arginine (Arg)) with a protecting group. The protecting group is not particularly limited and any known protecting group can be used, for example, benzyloxycarbonyl group (Cbz), tert-butoxycarbonyl group (Boc), fluorenylmethoxycarbonyl group (Fmoc), benzyl group (Bz), p-toluenesulfonyl group (p-Ts), etc.

[0012] Furthermore, after synthesizing the LRA peptide by the above-mentioned peptide synthesis method, the peptide can be purified by a known method, if necessary, and then used as the LRA peptide. Alternatively, the LRA peptide may be obtained by hydrolyzing a protein with a protease or the like, followed by purification or crude purification.

[0013] A composition containing an LRA peptide exerts an excellent effect of improving brain function, particularly when taken orally. The composition of this embodiment is applied to improve brain dysfunction, particularly cognitive disorders such as memory disorder, attention disorder, executive dysfunction, and social behavior disorder. Specifically, it is used for treating, improving, and preventing dementia that develops cognitive disorders.

[0014] Specific examples of dementia include Alzheimer's disease, vascular dementia, Lewy body dementia, frontotemporal dementia, alcoholic dementia, etc. Improvement of dementia includes not only improvement of the core symptoms of dementia such as memory disorder, attention disorder, executive dysfunction, and social behavior disorder, but also improvement of peripheral symptoms such as delusions, depression, wandering, insomnia, hallucinations, and decreased motivation.

[0015] The application form of the composition is not particularly limited, and may be, for example, a food composition or a pharmaceutical composition. The LRA peptide may be used as a raw material for a food composition or pharmaceutical composition as is, or may be made into a product by appropriately mixing with a carrier, additive, etc. that is pharmacologically or food hygienically acceptable.

[0016] When used as a food composition, in addition to the LRA peptide as described above, other ingredients may be included as necessary. The other ingredients are not particularly limited and may be appropriately selected depending on the purpose, and examples thereof include bases, carriers, and additives that are acceptable from the standpoint of food hygiene, as well as other ingredients and materials that can be used as foods.

[0017] When used as a food composition, the intake form is oral intake. In this case, the form of the composition of this embodiment is not particularly limited, and can be used as general food, health functional food, or special purpose food. For example, specific health food, nutritional functional food, functional food, food for sick people, food for people with swallowing difficulties, dietary supplements, nutritional supplements, hospital food, nursing food, processed food, beverages, etc. can be mentioned. These can be prepared by ordinary methods. When the use is indicated in the food composition, indications stipulated by various laws, enforcement regulations, guidelines, etc. can be mentioned. The indication of use includes indication on packages such as packaging and containers, as well as indication on advertising media such as pamphlets.

[0018] The contents of the display of the use of the composition of this embodiment include, in addition to the display of improvement or prevention of brain function, the display of improvement or prevention of the above-mentioned core symptoms and peripheral symptoms. Also included are displays suggesting these improvements or preventions. For example, displays of maintaining, supporting, or improving memory, attention, judgment, and spatial recognition, which are part of cognitive function, can be exemplified. More specifically, expressions such as maintaining or supporting the ability to remember and recall information about things seen and heard, such as words, numbers, figures, colors, position information, and faces, helping to remember information or improving accuracy, maintaining or supporting short-term memory (the ability to retain information in a short time and process it at the same time), maintaining attention (speed and accuracy of clerical work), and maintaining the efficiency of calculation work can be exemplified.

[0019] In addition, the dosage form of the food composition may be, for example, a hard capsule, a soft capsule, a supplement, a chewable tablet, a beverage, a powdered beverage, a granule, a film, etc., or, when used as a food or drink, for example, a beverage such as a tea-based beverage, a sports beverage, a beauty beverage, a fruit juice beverage, a carbonated beverage, an alcoholic beverage, a soft drink, a jelly beverage, a concentrated type beverage diluted with water, hot water, carbonated water, etc., a powder or granule dissolved or suspended in water or hot water, etc., a dry solid such as a tablet, a tablet confectionery, a jelly, a snack, a baked confectionery, a fried confectionery, a cake, a chocolate, a gum, a candy, a gummy, etc., a soup, a noodle, a rice, a cereal, etc. Among these, in normal life, a supplement type, a chewable tablet, a one-shot drink type, etc. are preferable, and when taken for the purpose of enhancing the effect of exercise, a beverage such as a sports drink is also preferable. In particular, when the product is intended as a health functional food, dietary supplement, or nutritional supplement, it is preferable that the product be in the form of, for example, a powder, granules, paste, capsule, tablet or pill (including chewable tablets), beverage (drink powder, drink, etc.), jelly, etc., in order to facilitate continuous intake.

[0020] When the composition is used as a food additive composition or a food ingredient composition, the form is not particularly limited, and examples thereof include liquid, powder, flake, granule, and paste. More specifically, examples thereof include seasonings (sweeteners, salt substitute compositions, soy sauce, vinegar, miso, sauces, ketchup, dressings, spices, herbs, flakes (furikake, rice cooking additives, etc.), barbecue sauce, roux paste (curry roux paste, etc.)), and food premixes.

[0021] When the composition is used as a food composition, the amount of LRA peptide in the food composition is not particularly limited as long as the above-mentioned effect of the LRA peptide is exerted, and can be set appropriately.

[0022] In addition, when the composition of the present invention is used as a food composition, the intake amount, intake interval, intake subject, etc. are not particularly limited and can be set appropriately. For example, the intake amount can be set appropriately depending on the age, sex, weight, health condition, and other conditions of the intake subject. For example, the intake interval, when the above-mentioned amount is taken, may be once or multiple times a day (preferably 2 to 3 times), or once or multiple times every few days to weeks. In addition, the intake subject may be a human being, or a domestic animal such as a pet or livestock, for example, a dog, a cat, a cow, a horse, a sheep, a llama, a rat, a mouse, etc.

[0023] In particular, when the subject of administration is a human, the amount of LRA peptide administered (ingested) is, for example, preferably about 10 to 5000 μg, more preferably about 100 to 4000 μg per day for an adult (60 kg). The administration (ingestion) period is not particularly limited, but may be, for example, 3 days to 12 weeks, or longer.

[0024] There are no particular limitations on the human subject to intake, but it is preferable for the human subject to intake to be a human who has a desire or need for improvement or prevention of brain function. When the subject of intake is a domestic animal, the form, intake amount, intake interval, etc. can be appropriately determined with reference to the case when the subject of intake is a human.

[0025] Pharmaceutical compositions include pharmaceuticals and quasi-drugs. When the composition of the present embodiment is used as a pharmaceutical composition, the administration method is not particularly limited, and it is possible to adopt oral administration (oral ingestion), enteral administration, intravascular administration (particularly intravenous injection), etc. When applied as a pharmaceutical composition, in addition to the LRA peptide as described above, other components may be included as necessary. The other components are not particularly limited and can be appropriately selected depending on the purpose, and examples thereof include pharma- ceutically acceptable bases, carriers, and / or additives (e.g., solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, etc.). The blending amount of the other components can be appropriately set depending on the purpose.

[0026] The dosage form of the pharmaceutical composition is not particularly limited, and examples thereof include tablets such as orally disintegrating tablets, chewable tablets, effervescent tablets, dispersible tablets, and dissolving tablets; troches; powders; suspensions; emulsions; elixirs; lemonades; syrups; lotions; granules; capsules such as hard capsules and soft capsules; creams; ointments; suppositories; poultices, tapes, microneedles, transdermal / mucosal administration agents such as iontophoresis and electroporation; aerosols, etc. These forms can be prepared by a conventional method by combining the LRA peptide with the other components described above as necessary.

[0027] The amount of the LRA peptide in the pharmaceutical composition is not particularly limited as long as the amount is an amount that exerts the above-mentioned effects of the LRA peptide, and can be set appropriately. When used as a pharmaceutical composition, the dosage, administration interval, administration subject, etc. are not particularly limited and can be set appropriately. For example, the dosage can be set appropriately depending on the age, sex, weight, health condition, and other conditions of the administration subject. For example, the administration interval may be once or multiple times a day (preferably 2 to 3 times), or once or multiple times every few days to weeks. In addition, the administration subject may be a human being, or a domestic animal such as a pet or livestock, for example, a dog, a cat, a cow, a horse, a sheep, a llama, a rat, a mouse, etc.

[0028] In particular, when the subject of administration is a human, the amount of LRA peptide administered (ingested) is, for example, preferably about 10 to 5000 μg, more preferably about 100 to 4000 μg per day for an adult (60 kg). The administration (ingestion) period is not particularly limited, but may be, for example, 3 days to 12 weeks, or longer.

[0029] When the subject of administration is a domestic animal, the administration form, dosage form, dosage amount, administration interval, etc. can be appropriately determined with reference to the case where the subject of administration is a human. The effects of the composition for improving brain function of this embodiment will be described.

[0030] (1) In this embodiment, the composition contains an LRA peptide. Therefore, it can exert an excellent effect of improving brain function. In particular, it exerts an excellent effect on improving cognitive function. Furthermore, in the case of cognitive function decline caused by lifestyle habits such as a high-fat diet, short-term intake can contribute to recovery of cognitive function.

[0031] The above embodiment may be modified as follows. The composition of the above embodiment may be administered to patients for the purpose of improving symptoms related to brain function, or may be ingested by healthy individuals for the purpose of preventing the worsening of symptoms, delaying the decline of symptoms, and preventing the decline of brain function.

[0032] In the compositions of the above embodiments, the amount of LRA peptide contained in the food composition or pharmaceutical composition is not particularly limited as long as the effects of the present invention are obtained, and the amount can be, for example, 0.1 to 100% by mass, preferably 1 to 90% by mass, of the solid content.

[0033] In addition, in this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present invention includes any combination of the constituent elements described in this specification.

[0034] Furthermore, the various characteristics (properties, structures, functions, etc.) described in each embodiment of the present invention above may be combined in any way to specify the subject matter included in the present invention. In other words, the present invention includes all subject matter consisting of all combinations of the combinable characteristics described in this specification. EXAMPLES

[0035] The above-mentioned embodiment will be described in more detail below with reference to test examples, but the present invention is not limited thereto. (Synthesis of LRA peptides) Production Example 1: Synthesis of tripeptide by Fmoc method A tripeptide consisting of Leu-Arg-Ala was synthesized by solid phase synthesis using the Fmoc method. The resulting LRA peptide was purified by HPLC and sequenced using a protein sequencer, confirming that it was a tripeptide consisting of Leu-Arg-Ala.

[0036] Production Example 2: Synthesis of tripeptides by the Boc method We requested the synthesis of a tripeptide consisting of Leu-Arg-Ala by the Boc method from Peptide Institute, Inc. The delivered LRA peptide was confirmed to be a tripeptide consisting of Leu-Arg-Ala by RP-HPLC, mass spectrometry and amino acid analysis.

[0037] (Measurement of cognitive function) The test method was based on the mouse object recognition test method (Marianne. Leger et al., Nature Protocols 8 (12), 2531-2537, 2013).

[0038] The mice used in the study were 11-week-old male ddY mice. They were fed a high-fat diet for one week to acclimate them, and then divided into two groups. Both groups were kept on a high-fat diet for one week (free food and water intake). One group (the LRA peptide group) was orally administered 1 mg / kg of LRA peptide prepared in saline using a Teflon tube, and the other control group was orally administered the same amount of saline on the 5th, 6th, and 7th days of the week.

[0039] The high-fat diet used was HFD-60 (manufactured by Oriental Bio Co., Ltd.) consisting of the ingredients shown in Table 1.

[0040] [Table 1] On the sixth day of rearing, one mouse from each group was placed in a box of a given size and allowed to acclimate to the environment for five minutes (acclimatization 1). 24 hours later, the mouse was placed in a box with two substances, one on each side, and allowed to move around until the total exploration time for both substances reached 20 seconds, after which it was removed from the box and returned to its cage (acclimatization 2). At this time, both substances in the box were the same, either building blocks or flasks. Another hour later, the mouse was placed in a box in which one of the two substances had been replaced with a substance of a different shape, and allowed to move around until the total exploration time for both substances reached 20 seconds, and the percentage (%) of the time spent exploring the new substance that had been replaced was calculated.

[0041] In addition, the test was conducted in a completely random manner, so that the novel substance was placed on the right side or the left side. The test box was placed in an area separated by a partition, and the tester observed the behavior of the mouse from outside the partition through a video camera installed above the box, so that the mouse could not see it. All of the tests were conducted in a facility set at 23°C with a 12-hour light and 12-hour dark cycle.

[0042] The average value ± standard deviation was calculated for each test group. The results for each group are shown in Table 2. There was no significant difference in body weight between the groups during the test period. * indicates vs. Control: p<0.05 (Tukey's multiple test).

[0043] [Table 2] As shown in Table 2, the group of subjects to whom the LRA peptide was added on a high-fat diet showed a significantly increased proportion of time spent exploring the novel substance compared to the control group.

Claims

1. A composition for improving brain function, comprising a tripeptide consisting of Leu-Arg-Ala, wherein the improvement of brain function is improvement of cognitive function.

2. The composition for improving brain function according to claim 1, which is an oral composition.

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

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