JP2012012358A - Brain function improving agent and food and drink for improving brain function - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a drug or food and drink for improving brain function.SOLUTION: The invention relates to a brain function improving agent including a milk casein-derived peptide as an active ingredient, and the food and drink for improving the brain function including the milk casein-derived peptide.

Description

  The present invention relates to a brain function improving agent and a food and drink for improving brain function.

  In recent years, with the aging of the population, learning disorders and memory disorders based on dementia that frequently occur in the elderly have become problems. In young and middle-aged people, for example, stress is caused, and brain function disorders such as depression, emotional instability, and insomnia are observed. Therefore, the development of methods for preventing and treating brain dysfunction is strongly desired.

  So far, many drugs for improving brain function have been developed, but the problem of side effects remains as a problem to be solved. Moreover, as a highly safe composition for improving brain function, food-derived components such as docosahexaenoic acid (Patent Document 1, Patent Document 2), eicosapentaenoic acid (Patent Document 2), phosphatidylserine (Patent Document 2), A composition comprising arachidonic acid (patent document 3), astaxanthin (patent document 4), theanine (patent document 5), lecithin (patent document 6), or γ-aminobutyric acid (GABA) (patent document 7) as an active ingredient Is disclosed.

  In addition, the three major nutrients in food, carbohydrates as an energy source, proteins as a source of neurotransmitters, and lipids, which are the main components of neuronal cell membranes, all play an important role in brain activity. Is responsible. For example, many of the neurotransmitters that play a major role in brain activity are biosynthesized from various amino acids, and the concentration of neurotransmitters reflects the amount of protein ingested and the amino acid composition in the food. (Non-patent document 1, Non-patent document 2). Moreover, it has been reported that the activity of the prefrontal cortex becomes active in the subject under calculation by ingesting soy peptide (Non-patent Document 3). From these findings, brain function is expected to be affected in various ways depending on the protein taken.

  Evaluation of brain function can be performed by measuring the brain physiologically or by measuring work efficiency. Here, as a method of physiologically measuring the brain, measurement of an electroencephalogram, measurement by functional nuclear magnetic resonance imaging (fMRI), or near-infrared spectroscopy (NIRS) )) And the like.

The measurement of brain function by NIRS is based on the absorption of near-infrared rays irradiated to the brain by blood hemoglobin. Here, it is known that when brain activity is locally improved, an increase in oxyhemoglobin concentration is observed at that site. That is, it can be determined that the higher the oxyhemoglobin concentration, the higher the brain activity level at that site. By using NIRS, the concentration of oxyhemoglobin (HbO ₂ ) or deoxyhemoglobin can be measured separately, and thus the degree of brain activity and its change can be measured. Furthermore, NIRS has many advantages over other approaches, such as a simple measuring device, a non-invasive technique, and the subject is not physically limited. Therefore, according to NIRS, changes in local brain activity can be measured in real time with the subject receiving little stress. Previously, since the optical path length of the irradiated near-infrared was unknown, only a relative change in hemoglobin concentration could be measured. However, in recent years, by introducing a time-resolved measurement method using an ultrashort pulse light source into NIRS, it has become possible to measure the absolute value of the hemoglobin concentration based on the light diffusion equation. Therefore, at present, the hemoglobin concentration can be compared for the same subject at different times and conditions.

JP-A-01-279827 JP 07-017855 JP 2003-048831 A JP2007-126455A JP 08-073350 JP 08-133984 A JP2007-230870

Metabolism 2008; 35: p837-842 Journal of Nutrition (J Nutr) 1987; 117: p42-47 Soy Protein Research 2003; 6: p147-152

  The subject of this invention is providing the pharmaceutical or food-drinks for improving a brain function.

  Proteins are broken down into their constituent components, peptides and amino acids, and absorbed. Short-chain or small-molecular-weight peptides are preferentially absorbed from the small intestinal epithelium. That is, these peptides have the advantage of being excellent in terms of availability.

  Here, casein occupying 80% of milk protein is a protein having an amino acid score of 100, which is excellent in nutrition, and contains abundant branched chain amino acids having various physiological activities.

  The present inventors focused on the fact that the fatigue after exercise was reduced by ingesting a milk casein-derived peptide obtained by hydrolyzing milk casein, and the milk casein-derived peptide was subjected to mental stress. I guessed it could affect the activity.

  The present inventors have found that by ingesting a milk casein-derived peptide, the oxyhemoglobin concentration in the prefrontal cortex is increased and the working efficiency is improved, and the present invention has been completed.

  That is, the present invention is as follows.

  1st invention is a brain function improving agent which contains a milk casein origin peptide as an active ingredient. In a preferred embodiment of the first invention, the improvement in brain function is an improvement in work efficiency. Moreover, in the preferable aspect of 1st invention, the average molecular weight of a milk casein origin peptide is 200-500 Dalton. In a preferred embodiment of the first invention, the brain function improving agent further contains one or more compounds selected from the group consisting of docosahexaenoic acid, arachidonic acid, and phosphatidylserine.

  2nd invention is the food-drinks for brain function improvement which contain a milk casein origin peptide as an active ingredient. In a preferred embodiment of the second invention, the improvement in brain function is an improvement in work efficiency. Moreover, in the preferable aspect of 2nd invention, the average molecular weight of a milk casein origin peptide is 200-500 Dalton. In a preferred embodiment of the second invention, the brain function improving food or drink further contains one or more compounds selected from the group consisting of docosahexaenoic acid, arachidonic acid, and phosphatidylserine.

  The brain function such as work efficiency can be improved by the brain function improving agent or the food or drink for improving brain function of the present invention. Therefore, the brain function reduction can be effectively prevented or treated by the brain function improving agent or the food or drink for brain function improvement of the present invention.

FIG. 1 is a diagram showing a schedule of a brain function measurement test. In the figure, P is a psychological questionnaire, H is an oxyhemoglobin concentration measurement in the left and right prefrontal cortex, and W is a work efficiency test. FIG. 2 (A) is a graph showing the oxyhemoglobin concentration in the left prefrontal cortex before and after mental stress when each beverage is ingested, and FIG. 2 (B) shows the oxyhemoglobin concentration in the right prefrontal cortex. It is a graph to show. Data are shown as mean ± standard error. “*” Indicates that there is a significant difference at a risk rate of 5% (paired t-test). FIG. 3 is a graph showing the number of erased characters before and after mental stress when each beverage is ingested. Data are shown as mean ± standard error. “*” And “#” indicate that there is a significant difference at a risk rate of 5% (Wilcoxon signed rank test).

  Next, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the following preferred embodiments, and can be freely changed within the scope of the present invention.

  The present invention relates to a brain function improving agent containing a milk casein-derived peptide as an active ingredient (hereinafter also referred to as a pharmaceutical of the present invention), and a food and drink for improving brain function containing a milk casein-derived peptide as an active ingredient (hereinafter referred to as the present invention). Also referred to as food or drink of the invention.

  In the present invention, the improvement of the brain function includes, for example, an improvement in work efficiency. Therefore, for example, the brain function can be evaluated by measuring work efficiency.

  In the present invention, the method for measuring the work efficiency is not particularly limited. For example, the work efficiency can be measured by a character erasure test. The character erasure test is, for example, a test in which an operation for erasing a specific number from a table in which numbers are randomly entered is performed for 2 minutes. The greater the number of erased characters in the character erase test, the higher the work efficiency.

  Alternatively, the brain function may be indirectly evaluated by measuring the oxyhemoglobin concentration in the prefrontal cortex. The oxyhemoglobin concentration in the prefrontal cortex can be measured by, for example, near infrared spectroscopy (NIRS). The measurement of the oxyhemoglobin concentration by NIRS may be measured as a relative value or an absolute value, but is preferably measured as an absolute value using a time-resolved method. It can be determined that the higher the oxyhemoglobin concentration, the higher the brain activity level at that site.

  The milk casein-derived peptide contained in the medicament and food and drink of the present invention is not particularly limited as long as it contains a peptide obtained by hydrolyzing milk casein. The milk casein may be a mixture of milk proteins or may be obtained by separating and purifying casein therefrom. As the milk casein, separated and purified casein can be suitably used. The hydrolysis may be acid hydrolysis or enzymatic hydrolysis. The hydrolysis is preferably enzymatic hydrolysis. For example, various proteases can be suitably used. After hydrolysis, the hydrolyzate may be further separated and purified. Separation and purification can be performed using, for example, an ultrafiltration membrane. By separation and purification, for example, impurities can be removed, or the molecular weight of the hydrolyzate can be unified within an arbitrary range. In the present invention, the average molecular weight of the milk casein-derived peptide is preferably 200 to 500 daltons. As the milk casein-derived peptide, for example, CU2500A commercially available from Morinaga Milk Industry Co., Ltd. can be preferably used. CU2500A is a product in which about 25% of the peptide bonds in milk casein are hydrolyzed.

  The medicament of the present invention is not particularly limited as long as it contains a milk casein-derived peptide as an active ingredient. As the medicament of the present invention, a milk casein-derived peptide may be used as it is, or a physiologically acceptable liquid or solid preparation carrier may be blended and formulated for use.

  The pharmaceutical dosage form of the present invention is not particularly limited, and specific examples include tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, and syrups. In addition, additives such as excipients, binders, disintegrants, lubricants, stabilizers, flavoring agents, diluents, or surfactants that are commonly used as pharmaceutical carriers should be used for formulation. Can do.

  The medicament of the present invention further comprises any component having an effect of improving brain function, such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), phosphatidylserine (PS), arachidonic acid, astaxanthin, theanine, lecithin, or γ -You may contain aminobutyric acid (GABA) etc. The medicament of the present invention can preferably contain one or more compounds selected from, for example, DHA, arachidonic acid, and PS.

  The content of the milk casein-derived peptide in the medicament of the present invention can be appropriately set depending on the dosage form, usage, patient age, sex, degree of brain function, and other conditions. The content of the milk casein-derived peptide in the medicament of the present invention is, for example, preferably in the range of 0.01 to 1 g / g, and more preferably in the range of 0.1 to 1 g / g.

  The medicament of the present invention is preferably administered orally. By administering the medicament of the present invention, brain functions such as work efficiency are improved. Therefore, the medicament of the present invention is useful for improving or preventing various symptoms caused by a decrease in brain function. Moreover, as long as the brain function improvement effect of this invention is not impaired, you may use together the pharmaceutical of this invention containing a milk casein origin peptide, and another pharmaceutical, for example, another brain function improvement agent etc.

  The food and drink of the present invention is not particularly limited as long as it contains a milk casein-derived peptide as an active ingredient. Examples of the food and drink include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit juice drinks, and lactic acid bacteria drinks (these drinks) Ice cream, sherbet, shaved ice, etc .; confectionery such as candy, chewing gum, candy, gum, chocolate, tablet confectionery, snack confectionery, biscuits, jelly, jam, cream, and baked confectionery Dairy products such as processed milk, milk beverage, fermented milk, drink yogurt, and butter; bread; enteral nutritional food, liquid food, milk for childcare, sports drink, and other functional foods. Moreover, the food / beverage products of this invention may be provided as a supplement. As a supplement, a tablet-like supplement can be illustrated, for example. Moreover, you may use a milk casein origin peptide as a supplement as it is. When the food / beverage product of the present invention is a supplement, the milk casein-derived peptide can be ingested without worrying about the amount of meals or calorie intake per day in consideration of other foods.

  The food or drink of the present invention can be produced by adding a milk casein-derived peptide to the raw material of the food or drink, and can be produced in the same manner as a normal food or drink, except that a milk casein-derived peptide is added. it can. The addition of the milk casein-derived peptide may be performed at any stage of the production process of the food or drink. As a raw material for food or beverage, a raw material used for a normal beverage or food can be used.

  The food / beverage product of the present invention further comprises any brain function activating component such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), phosphatidylserine (PS), arachidonic acid, astaxanthin, theanine, lecithin, and γ- One or more compounds selected from aminobutyric acid (GABA) and the like may be contained. The medicament of the present invention can preferably contain one or more compounds selected from, for example, DHA, arachidonic acid, and PS.

  Content of the milk casein origin peptide in the food / beverage products of this invention can be suitably set with the aspect etc. of food / beverage products. The content of the milk casein-derived peptide in the food or drink of the present invention is preferably in the range of 0.001 to 0.1 g / g, for example, and in the range of 0.01 to 0.1 g / g. Is more preferable.

  The food and drink of the present invention can be taken orally. By ingesting the food or drink of the present invention, brain functions such as work efficiency are improved. Therefore, the food / beverage products of this invention are useful for the improvement or prevention of the various symptoms resulting from the fall of a brain function, and can be used for the various uses using a brain function improvement effect. For example, the food / beverage products of this invention can be used for uses, such as food / beverage products suitable for those who are worried about a memory fall, and food / beverage products useful for improvement of learning efficiency.

  The food / beverage products of the present invention can be sold as food / beverage products for which the use for improving brain function is displayed, for example, “food / beverage products containing milk casein-derived peptide displayed for brain function improvement” and the like. . That is, it is possible to display “for improving brain function” or the like on the food or drink of the present invention. In addition to this, it goes without saying that any wording that expresses the effect of improving brain function or any word that expresses an effect that is secondarily generated by improving brain function can be used. Examples of such words include words such as “work efficiency improves” or “helps improve learning ability”.

  The “display” means all acts for informing the consumer of the use, and if it is a display that can recall and analogize the use, the purpose of the display, the content of the display, the display Regardless of the object and medium to be processed, all fall under the “display” of the present invention. However, it is preferable to display in such an expression that the consumer can directly recognize the application. Specifically, the act of describing the above-mentioned use in the product or product packaging relating to the food or drink of the present invention, the product or product packaging describing the above-mentioned use is transferred, and displayed for delivery, transfer or delivery And importing, displaying advertisements on products, price lists or transaction documents for display or distribution, or describing the above uses in information containing these, electromagnetic (Internet, etc.) methods In particular, it is preferable to display on advertising materials at sales sites such as packaging, containers, catalogs, pamphlets, POPs, and other documents.

  In addition, the display is preferably a display permitted by the government or the like (for example, a display which is approved based on various systems determined by the government and is performed in a mode based on such approval). For example, indications such as health foods, functional foods, enteral nutrition foods, special purpose foods, functional nutrition foods, quasi-drugs, and other indications approved by the Ministry of Health, Labor and Welfare, such as specific Examples of health foods and labels approved by similar systems. Examples of the latter include a display as a food for specified health use, a display as a food for specified specific health use, a display that affects the structure and function of the body, a display for reducing disease risk, and the like. In more detail, the indication as food for specified health (especially the indication of the use of insurance) stipulated in the Enforcement Regulations of the Health Promotion Act (Ministry of Health, Labor and Welfare Ordinance No. 86 of April 30, 2003), and Similar displays can be exemplified.

  The administration target of the medicine and food and drink of the present invention is not particularly limited, and is preferably used from children to the elderly. That is, the medicine and food and drink of the present invention can be used, for example, for improving the learning ability of children. Moreover, the pharmaceutical and food / beverage products of this invention can be used for the prevention of brain activation and a brain function fall of an adult or elderly person.

  The intake of the medicament and food and drink of the present invention can be appropriately set according to the content of milk casein-derived peptide, usage, age, sex, degree of symptoms, and other conditions. The intake of the medicament and food or drink of the present invention is preferably 0.01 g / kg body weight / day to 1.0 g / kg body weight / day in terms of the dose of the milk casein-derived peptide, 0.1 g / kg More preferably, the weight is kg body weight / day to 0.5 g / kg body weight / day. The medicine and food and drink of the present invention can be taken once a day or divided into a plurality of times. In addition, it may be taken once every several days or weeks. The intake at each intake may be constant or may be different in terms of the dose of the milk casein-derived peptide. Moreover, ingestion may be continued through the period from a child to elderly people, and it may be ingested only in a part of period. In addition, continuation and interruption of intake may be repeated for an arbitrary period.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, the scope of the present invention is not limited to a following example.

〔Example〕
In this example, the milk casein-derived peptide was measured by measuring changes in the prefrontal oxyhemoglobin concentration before and after mental stress loading, and changes in work efficiency, with and without the intake of milk casein-derived peptide. The effect on the brain function was evaluated.

<Materials and methods>
The test was conducted according to the schedule shown in FIG. That is, P: psychological questionnaire (5 minutes), H: oxyhemoglobin concentration measurement (2 minutes), and W: work efficiency test (2 minutes) were sequentially performed. Thereafter, a drink was ingested, and after a 45-minute break, a 15-minute Kraepelin test was performed for mental stress. Thereafter, P, H, and W were further performed in the same manner as before drinking. The schedule shown in FIG.

  The subjects were 16 healthy male university students. The age of the subjects was 20-23, and the average value ± standard deviation was 21.4 ± 0.9. The subject was fasted for 4 hours before the test.

  The subject ingested either a beverage (peptide beverage) containing a milk casein-derived peptide or water as a beverage. Hereinafter, each of the peptide beverage and water is also referred to as each beverage. The group that ingested the peptide beverage was the test group, and the group that ingested water was the control group. CU2500A (Morinaga Milk Industry Co., Ltd., average molecular weight 337) was used as the milk casein-derived peptide. The intake of milk casein-derived peptide was 0.2 g / kg body weight, and the intake of peptide beverage was 4 g / kg body weight. Similarly, the water intake was 4 g / kg body weight.

  The test was conducted by a cross test. That is, 16 subjects are divided into 8 groups, A group and B group, and in group A, a set of tests (peptide test) for ingesting peptide beverages is performed first, and then water is reingested afterwards. A set of tests (control tests) were conducted. In the group B, the reverse order was adopted.

  In order to evaluate changes in brain function, changes in oxyhemoglobin concentrations in the left and right prefrontal cortex before and after mental stress loading, and changes in work efficiency were measured.

  NIRS (TRS-10, manufactured by Hamamatsu Photonics Co., Ltd.) was used for measuring the oxyhemoglobin concentration. The measurement was performed in a measurement room adjusted to 24 ° C., relative humidity 50%, and illuminance 50 lux, and the subject took measurements with his eyes open while sitting. A pair of optical probes was fixed to the left and right prefrontal cortex of the subject. The pair of optical probes is composed of two optical probes for near-infrared irradiation and light reception. In the left and right optical probe pairs, the distance between the light transmitting probe and the light receiving probe was 40 mm. In the left and right optical probe pairs, the center positions of the light transmitting probe and the light receiving probe are made to coincide with Fp1: the left frontal pole part and Fp2: the right frontal pole part in the electrode arrangement of the international method 10-20 when measuring an electroencephalogram. It was.

  For the measurement of work efficiency, a character erasure test for erasing specific numbers from a table in which numbers were randomly entered was used. The work efficiency was evaluated by the total number of erased characters in 2 minutes.

<Result>
FIG. 2 (A) shows the oxyhemoglobin concentration in the left prefrontal cortex before and after each beverage intake and mental stress, and FIG. 2 (B) shows the oxyhemoglobin concentration in the right prefrontal cortex. Comparison between the two groups regarding the oxyhemoglobin concentration was performed by statistical analysis using a paired t-test, and P <0.05 was considered significant. In the test group, a significant increase in oxyhemoglobin concentration was observed from 66.0 ± 2.5 μM to 69.0 ± 2.7 μM in the left prefrontal cortex. Similarly, in the right prefrontal cortex, a significant increase in oxyhemoglobin concentration was observed from 66.9 ± 2.6 μM to 68.9 ± 2.7 μM. On the other hand, in the control group, no significant difference was observed before and after drinking. The oxyhemoglobin concentration is an index of the activity level of the prefrontal cortex, and the increase in the oxyhemoglobin concentration supports the improvement of the activity level of the prefrontal cortex. Therefore, it was shown that brain function is improved by ingestion of milk casein-derived peptide.

  FIG. 3 shows the number of erased characters in the character erase test before and after each beverage intake and mental stress load. Comparison between the two groups regarding the number of erased characters was performed by statistical analysis using a Wilcoxon signed-rank test, and P <0.05 was considered significant. In the test group, the number of erased characters increased significantly from 1122 ± 91 characters to 1250 ± 103 characters by ingestion of the peptide beverage, and an improvement in work efficiency was observed. On the other hand, in the control group, it was 1130 ± 78 characters after ingestion compared to 1107 ± 82 characters before ingestion, and no significant difference was observed before and after water intake. Furthermore, it was found that the work efficiency of the test group after ingesting the peptide drink was significantly higher than that of the control group after ingesting water. Therefore, the measurement results of work efficiency also showed that the brain function was improved by ingestion of the milk casein-derived peptide.

  In this example, the change in the oxyhemoglobin concentration in the left and right prefrontal cortex before and after each beverage intake was the same in group A and group B of the cross test. Moreover, the change of the work efficiency before and after each drink intake was the same in the A group and B group of the cross test. Therefore, in the crossover test of this example, it was determined that the result would not be affected by any of the peptide test and the control test.

  From the above, by ingesting a milk casein-derived peptide, an increase in the prefrontal oxyhemoglobin concentration and an improvement in work efficiency were observed before and after mental stress. Therefore, it was clarified that the brain function was improved by ingestion of the milk casein-derived peptide.

  The brain function improving agent and food / beverage product for improving brain function of the present invention containing a milk casein-derived peptide can be used for improving brain function. Therefore, the brain function improving agent and the food and drink for improving brain function of the present invention are useful for preventing or treating the decrease in brain function.

Claims (8)

  A brain function improving agent comprising a milk casein-derived peptide as an active ingredient.   The brain function improving agent according to claim 1, wherein the brain function improvement is an improvement in work efficiency.   The brain function improving agent according to claim 1 or 2, wherein the milk casein-derived peptide has an average molecular weight of 200 to 500 daltons.   The brain function improving agent according to any one of claims 1 to 3, further comprising one or more compounds selected from the group consisting of docosahexaenoic acid, arachidonic acid, and phosphatidylserine.   Food / beverage for brain function improvement containing the milk casein origin peptide.   The food / beverage product for brain function improvement of Claim 5 whose brain function improvement is an improvement of work efficiency.   The food / beverage product for brain function improvement of Claim 5 or 6 whose average molecular weight of a milk casein origin peptide is 200-500 Dalton.   Furthermore, the food-drinks for brain function improvement of any one of Claims 5-7 containing 1 or more compounds selected from the group which consists of docosahexaenoic acid, arachidonic acid, and phosphatidylserine.

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