JP2022132561A - Composition for preventing deterioration in sustained attention with aging - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition useful for improving cognitive functions other than memory and learning, and a method for producing the composition.

SOLUTION: A composition for improving the speed of cognitive functions in the brain contains L-ergothioneine as an active ingredient.

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention relates to compositions for use in improving cognitive function.

With the advent of an aging society, attention has been focused on brain health. It is said that the improvement of eating habits is effective for maintaining brain health. Various studies have been conducted on compositions (such as food compositions) for maintaining brain health.

Patent Literature 1 describes a food or drink for improving brain function containing, as an active ingredient, a cinnamic acid derivative called 3-(4-hydroxy-3-methoxyphenyl)propionic acid.

In addition, Non-Patent Document 1 describes that ergothioneine has the potential as a brain food. Specifically, it was found that ergothioneine has a neurogenic effect, that the neurogenic effect promotes the metabolism of nerve cells and may exert an effect on memory and learning. It is described that when an object search test was conducted, oral intake of ergothioneine was suggested to improve memory and learning ability.

Japanese Patent No. 6236185

Masao Kato et al., "Ergothioneine as a transporter-mediated brain food", FOOD STYLE 21, 2017, Vol.21, No.2, p.21-24

By the way, the cognitive functions in the brain have not been fully elucidated. Under such circumstances, in neurocognitive disorders (NCD: Neurocognitive Disorders) classified by DSM-5 (Diagnostic and Statistical Manual of Mental Disorders V), cognitive function areas that are impaired in NCD (neurocognitive disorder) patients are It is classified into six areas: "complex attention", "executive function", "learning and memory", "language", "perception-motor", and "social cognition". Conventionally, the effect of ergothioneine has been suggested to improve memory and learning ability among these six areas. However, the effects of other classifications have not been elucidated. The DSM is a classification manual for mental illnesses and mental disorders created by the American Psychiatric Association, and is officially called the "Diagnostic and Statistical Manual of Mental Disorders."

An object of the present invention is to provide a composition useful for improving cognitive functions other than memory and learning, and a method for producing the composition.

The inventors of the present application have made intensive studies to solve the above problems, and found that L-ergothioneine has the effect of improving cognitive function speed and the effect of improving verbal memory with aging. It was found that it has the effect of improving sustained attention with aging, and that it has the effect of improving simple attention with age. These findings led to the completion of the present invention.

The present invention is a composition for improving the speed of cognitive function containing L-ergothioneine as an active ingredient, or a composition for improving the speed of cognitive function containing an extract of Pleurotus lucidum as an active ingredient. L-ergothioneine may be contained in the extract of Pleurotus cornucopia. Also, the intake of L-ergothioneine can be 1 mg to 30 mg per adult per day. In addition, the present invention can improve information processing speed in the brain as cognitive function speed. In addition to cognitive function speed, it can be used to improve age-related verbal memory, age-related sustained attention, or age-related simple attention.

In addition, regarding the present invention, the composition can be a food composition, in which case the food composition is a health food, a functional food, a dietary supplement, a supplement, a food for specified health use, a food for sick people / disease It can be a combination food for the elderly or a food for the elderly. Also, the composition can be a pharmaceutical composition. The composition can also be a composition consisting of the Pleurotus cornucopia extract, a freeze-dried composition, or a spray-dried composition.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a composition useful for improving cognitive functions other than memory and learning, and a method for producing the composition.

4 is a graph showing test results of comprehensive memory in the Cognitrax test. 4 is a graph showing test results of verbal memory ability in the Cognitrax test. 4 is a graph showing test results of visual memory in the Cognitrax test. 2 is a graph showing test results of cognitive function speed in the Cognitrax test. 4 is a graph showing test results of reaction speed in a Cognitrax test. 10 is a graph showing test results of comprehensive attentiveness in the Cognitrax test. 2 is a graph showing test results of cognitive flexibility in the Cognitrax test. 7 is a graph showing inspection results of processing speed in Cognitrax inspection. 4 is a graph showing test results of executive functions in the Cognitrax test. 10 is a graph showing test results of working memory in the Cognitrax test. FIG. 10 is a graph showing test results of sustained attention in the Cognitrax test. FIG. 10 is a graph showing test results of simple attention in the Cognitrax test. 4 is a graph showing the results of a motion speed test in a Cognitrax test.

Hereinafter, embodiments of the present invention will be described in detail. The following embodiments are examples of the present invention, and are not intended to limit the scope of the present invention, its applications, or its uses.

[Composition for improving cognitive function speed]
The present embodiment is a composition for improving cognitive function speed in the human brain (hereinafter sometimes referred to as "this improving composition") containing L-ergothioneine as an active ingredient. The composition for improvement (food composition or pharmaceutical composition for improving cognitive function speed) is, for example, orally ingested to be used in a method for improving cognitive function speed of a patient who needs improvement in cognitive function speed. be able to. Note that the cognitive function speed represents the speed at which the brain and body understand and react to information and objects (information processing speed in the brain, etc.), and correlates with the amount of physical activity as well as the amount of exercise.

The composition for improvement and the method for improving cognitive function speed are useful for improving cognitive function speed in elderly people and people with mild dementia (MCI). In addition, it is useful for improving cognitive speed in middle-aged, young and adolescents. It is also useful for improving cognitive function speed in animals other than humans (eg, mammals such as dogs, cats, and monkeys).

In addition, the composition for improvement and the method for improving cognitive function speed are also useful for improving age-related verbal memory and for improving age-related attention (sustained attention, simple attention). be. Therefore, it is possible to improve verbal memory and attention in the elderly and middle-aged people. The improving composition can also be a composition, freeze-dried composition, or spray-dried composition consisting of a Pleurotus cornucopia extract (such as Pleurotus cornucopia concentrate).

Here, L-ergothioneine is a kind of amino acid having a chemical structure of the following formula (1) in a crystalline state.

L-ergothioneine is known to form a tautomer with a thiol structure in solution, and is stable against heat and acid. In addition, L-ergothioneine, like ascorbic acid, is an antioxidant substance and cannot be synthesized in vivo and must be taken from the outside. L-ergothioneine to be contained in the composition for improvement can be an extract from mushrooms containing L-ergothioneine or sake lees from the viewpoint of digestibility, safety, taste, etc. in food applications and pharmaceutical applications. preferable. However, commercially available L-ergothioneine obtained by chemical synthesis may also be used.

Mushrooms from which L-ergothioneine is extracted include Pleurotus cornucopiae var. citrinopileatus, Flammulina velutipes belonging to the genus Flammulina, and Leucopaxillus belonging to the genus Leucopaxillus. giganteus), etc., Phellinus linteus belonging to the genus Phellinus, etc., Tricholoma sp. belonging to the genus Tricholoma, etc., Coprinus comatus belonging to the genus Coprinus, etc. Hericium erinaceum, etc. belonging to the genus Hericiaceae, Lyophyllum shimeji, etc. belonging to the genus Lyophyllum, Lyophyllum decastes, etc., Rozites caperata, etc. belonging to the genus Rozites, Pleurotus pulmonarius, Pleurotus ostreatus, Pleurotus eryngii, etc. belonging to the genus Pleurotus, Mycoleptodonoides belonging to the genus Mycoleptodonoides aitchisonii), Agrocybe cylindracea belonging to the genus Agrocybe, and Grifola gargal belonging to the genus Grifola. In particular, from the viewpoint of low side effects and safety when the extract is used for a long period of time, Tamogitake, Enokitake, Enokitake, Coprinus comatus, Yamabushitake, Honshimeji, Nameko, Oyster mushroom, King oyster mushroom, and Bunaharitake are preferable. Among these, Tamogitake is also easy to collect domestically.

In addition, when the composition for improvement is made into a food composition (including beverages), in addition to L-ergothioneine, other ingredients commonly used for food and drink (nutritional ingredients such as vitamins and minerals, food materials, or food additives, etc.). Other ingredients include ethanol and water as solvents, sweeteners, flavors, seasonings, coloring agents, preservatives, bulking agents, thickeners, thickening stabilizers, antioxidants, bittering agents, acidulants, emulsifiers, Strengthening agents, manufacturing agents, excipients, disintegrants, binders, lubricants, coating agents, plasticizers and the like can be used.

In addition, the food composition for improving the cognitive function speed of the present embodiment can be a solid, semi-solid or liquid food, such as confectionery (cookies, jelly, etc.), bread, processed fish products, and livestock meat. Processed products, noodles, soups, sauces, side dishes, etc. can be provided as beverages (milk drinks, lactic acid bacteria drinks, soft drinks, vegetable drinks, powdered drinks, sports drinks, nutritional drinks, etc.). In addition, the food composition for improving the cognitive function speed of the present embodiment is a health food, a functional food, a dietary supplement, a supplement, a food for specified health use, a food for the sick, a combination food for the sick, or a food composition for the elderly. It can be provided as a food or the like. In addition, the improving composition can be provided as a drug or quasi-drug. That is, it can be provided as a cognitive function speed improving agent.

In addition, the composition for improvement can be in a form (dosage form) such as solid, liquid, powder, granule, paste, mousse, gel, jelly, or tablet. In addition, the improvement composition can be wrapped in a bag, container, capsule, or the like. In the case of a solid or tablet form, each one may contain the amount of L-ergothioneine to be taken, which will be described later. In addition, in the case of liquid, powder, granule, paste, mousse, gel, or jelly, the intake amount of L-ergothioneine, which will be described later, can be included in one package.

In addition, the composition for improvement can be used so that the intake of L-ergothioneine (intake per adult per day) is 1 mg to 30 mg, more preferably 3 mg to 25 mg. , 5 mg to 25 mg. When the L-ergothioneine is in a solidified or packaged form, it can be made to contain 1 mg to 30 mg per adult per day in total in the number of packages to be ingested per day. The intake amount of L-ergothioneine can be indicated on the package or the like as a recommended intake amount per day. In addition, the number of intakes per day to achieve the daily intake may be once or multiple times.

[Method for producing composition for improving cognitive function speed]
A method for producing the composition for improvement (hereinafter sometimes referred to as "the present production method") will be described.

In this production method, Pleurotus cornucopia is used as a raw material for L-ergothioneine. The Pleurotus cornucopia used in the present production method may be naturally grown or artificially cultivated. In addition, raw Tamogitake mushrooms may be used, or harvested Tamogitake mushrooms processed may be used. As processed Tamogitake mushrooms, dried ones or powdered ones after drying can be used. As a raw material for L-ergothioneine, mushrooms other than Tamogitake may be used.

In this production method, an extract production step is performed to produce an aqueous solvent extract of Pleurotus cornucopia (for example, Pleurotus cornucopia extract). The aqueous solvent extract of Tamogitake is a liquid (Tamogitake concentrate), semi-solid, or solid substance containing components extracted from Tamogitake with an aqueous solvent, or 1 or 2 selected from these substances It is a mixture of the above substances.

In the extract production step, for example, an aqueous solvent extract of Pleurotus cornucopia can be produced according to a standard method. For example, an aqueous solvent extract of Pleurotus cornucopia can be produced by adding Pleurotus cornucopiae to an aqueous solvent, heating the mixture while pulverizing and stirring, and then separating the liquid component by solid-liquid separation by filtration or the like to recover the liquid component.

In addition, in the extract manufacturing process, ultrafiltration, ultrasonic treatment, or the like may be further performed after the liquid component is recovered. In this case, such an ultrafiltrate (filtrate and filtrate) or ultrasonically treated product becomes the aqueous solvent extract of Pleurotus cornucopia finally obtained in this step.

In addition, after subjecting the broth obtained by boiling Tamogitake to an ion exchange resin, the eluate of the cationic compound is obtained from the ion exchange resin, the eluate is concentrated, and the concentrated liquid is subjected to high-performance liquid chromatography. Separation and purification of L-ergothioneine may be carried out by passing through a graph. In this case, the Pleurotus cornucopia extract obtained by separation and purification becomes the aqueous solvent extract of Pleurotus cornucopia finally obtained in this step.

Here, a solvent mainly composed of a polar solvent can be used as the aqueous solvent used in the extract production step. As the aqueous solvent, one kind of polar solvent may be used, or a mixture of two or more kinds of polar solvents may be used. Polar solvents applicable to this production method include water, methanol, ethanol, acetic acid, formic acid, 1-butanol, 1-propanol, 2-propanol and the like. A preferred polar solvent is water.

In addition, the aqueous solvent may be used as it is without adding the solute to the polar solvent, or may be used after preliminarily mixing or dissolving the solute in the polar solvent. Examples of the aqueous solvent in which the solute is mixed or dissolved include an aqueous citric acid solution in which citric acid is mixed or dissolved in water, an aqueous sodium bicarbonate solution in which sodium bicarbonate is mixed or dissolved in water, and a common salt in which salt is mixed or dissolved in acetic acid. An acetic acid solution or the like can be used. Moreover, the properties of the aqueous solvent may be acidic, neutral or basic. The temperature of the water-based solvent is not particularly limited as long as its function is not impaired, and may be any of low temperature, room temperature, or high temperature, and hot water can be used as a suitable water-based solvent. The temperature of the hot water in the extract manufacturing process can be set at 90° C., for example.

Regarding this production method, when the composition for improvement is a freeze-dried composition or a spray-dried composition, after the extract production step, from the aqueous solvent extract of Pleurotus cornucopia, dried L-ergothioneine A drying step is performed to produce (eg powder). A freeze-drying method or a spray-drying method can be used for the drying step. When the freeze-drying method is used, for example, hot water is used as the aqueous solvent used in the extract production process, and the hot water extract of Pleurotus cornucopiae (aqueous solvent extract of Pleurotus cornucopiae) is freeze-dried to obtain a dried product of L-ergothioneine. can be manufactured. In addition, when the present composition for improvement is a composition composed of Pleurotus cornucopia extract, the drying step is not performed. A beverage comprising an aqueous solvent extract of Pleurotus cornucopia, a beverage prepared by diluting an aqueous solvent extract of Pleurotus cornucopiae, etc., is the improving composition.

Specifically, regarding the drying process, a case of producing a dried product of L-ergothioneine from the extract of Pleurotus lucidum using a freeze-drying method will be described. In this case, the drying process includes a preparation process of dissolving dextrin in the cornucopia extract to create a material liquid, a preliminary freezing process of freezing the material liquid obtained in the preparation process, and a material after the preliminary process under low temperature and low pressure conditions. and a freeze-drying step of freeze-drying the liquid.

In the preparation process, first, Tamogitake extract is put into the tank. Then, the extract in the tank is heated at a predetermined temperature for a predetermined time while being stirred. Tamogitake extract is sterilized by heating. Next, a predetermined amount of dextrin is gradually added to the tank while water is added appropriately. When it is confirmed that the dextrin has completely dissolved after the completion of the addition, the preparation process is completed. As a result, a material liquid in which the dextrin is dissolved in the extract of Pleurotus cornucopia is obtained.

In addition, for example, the stirring time (predetermined time described above) of the extract of Pleurotus cornucopia can be set to 30 minutes, and the heating temperature (predetermined temperature described above) can be set to 90°C. Also, the input amount D (kg) of dextrin can be obtained by the following formula 1. In Formula 1, E represents the weight (kg) of the mushroom extract, Bx represents the Brix value (%) of the mushroom extract, and α represents a coefficient (eg, 0.4).
Formula 1: D=E×Bx×α

For example, when 10 kg of Pleurotus lucidum extract with a Brix of 20% is put into the tank, the amount of dextrin put into the tank is 0.8 kg. For example, an extract having a Brix of 20 to 25% can be used, and a high-molecular cluster dextrin (registered trademark) having a ring structure in the molecule can be used as the dextrin.

Next, in the pre-freezing step, the liquid material obtained in the mixing step is subdivided into transparent bags (eg, transparent bags with zippers) by, for example, 1 kg each, and the transparent bags are frozen in a freezer. The transparent bag is placed in a freezer while being placed on a metal tray made of aluminum or the like. The temperature inside the freezer is set to -30° C., for example. Also, the freezing time is, for example, 18 hours to 42 hours. The material liquid is thereby frozen.

Next, in the freeze-drying step, the upper surface of the transparent bag containing the material liquid frozen in the preliminary freezing step is cut off with a cutter or the like. Then, the cut transparent bag is placed in a low-temperature, low-pressure space (for example, inside a freeze dryer). Inside the freeze dryer, the shelf temperature is set to a low temperature range (-25°C to -30°C) at the start. In the freeze dryer, pressure reduction is started from the start time, and the shelf temperature is maintained in this low temperature range until the internal pressure reaches the switching threshold value (for example, 133 Pa). Then, when the internal pressure reaches the switching threshold, the shelf temperature is set to 25° C. and heating is started. When the heating is started, the pressure inside the chamber is further reduced and the internal pressure is set to an extremely low pressure range (for example, 20 Pa to 40 Pa), and the frozen material liquid is removed by evaporating water, and freeze-drying proceeds. go. The freeze-drying time is, for example, 40 to 50 hours. As a result, a low-moisture solid is obtained from the frozen liquid material.

After the freeze-drying step, the solid matter obtained by the freeze-drying step is crushed, and the crushed solid matter is passed through a sieve. For the sieve, for example, a 30-mesh (nominal mesh size of 600 μm) is used. As a result, a powdery composition for improvement is obtained.

In the extract manufacturing process or drying process, pulverization, purification, concentration, drying, sterilization, etc. may be performed according to the required purity and shape. Examples of the crushing method include crushing with a roll crusher, cutting with a food processor, grinding with a ball mill crusher, and pulverizing with a hammer crusher. be able to. As a purification method, for example, a filtration method, a distillation method, a recrystallization method, a reprecipitation method, a method using various types of chromatography, and the like can be used. As a concentration method, for example, a boiling concentration method, a vacuum concentration (reduced pressure concentration) method using an evaporator or the like, a freeze concentration method, a membrane concentration method using a reverse osmosis membrane, or the like can be used. As a sterilization method, for example, a method using an autoclave, a high frequency method, a filter filtration method, or the like can be used.

Hereinafter, as an example of the present invention, a clinical test on cognitive function using an ergothioneine-containing food derived from Pleurotus lucidum will be described for healthy subjects or subjects with mild cognitive impairment (MCI). It should be noted that the present invention is not limited to the present embodiment as long as it does not exceed the scope of the present invention. In addition, unless otherwise specified, the units and measurement methods described in the examples are based on JIS standards.

-Test method-
As the method of the clinical trial, a placebo-controlled randomized parallel group double-blind comparative study was adopted using two test food intake groups, an ergothioneine intake group (test food group) and a placebo intake group (control group). . Hereinafter, the ergothioneine intake group is referred to as "ergo group", and the placebo intake group is referred to as "placebo group".

-Subject allocation-
When selecting subjects, a screening survey was conducted on 70 subjects, and 52 subjects who met all of the eligibility criteria (1) to (11) and did not meet all of the exclusion criteria (A) to (D) were selected as subjects. incorporated into.

<Eligibility Criteria>
(1) Persons with MMSE results of 23 points or more by screening test (2) Age: 20 to 80 years old (3) Gender: Any (4) No smoking habit (5) Large amount of ergothioneine Those who do not have a habit of eating foods containing ergothioneine (meals containing large amounts of ergothioneine: mushrooms, liver, grains, beans)
(6) Those who do not regularly use supplements or health foods (7) Those who do not suffer from lifestyle-related diseases (high blood pressure, diabetes, etc.), rheumatism, liver disorders, renal disorders, or other chronic diseases (8) Malignant tumors, heart failure (9) Subjects with no history of allergy to ergothioneine-rich mushrooms or pharmaceuticals (10) Subjects who do not go to the hospital or take medication for treatment (11) Clinical trials A person who fully understands the content of and has obtained written consent

The eligibility criteria (1), MMSE (Mini Mental State Examination), is a test that evaluates the degree of progression of dementia with a total score of 30 points, and dementia is suspected with a score of 20 or less It is In this test, those with an MMSE score of 23 to 27 were judged to have MCI, and those with an MMSE score of 28 to 30 were judged to be healthy.

<Exclusion Criteria>
(A) Pregnant or breastfeeding women, or those intending to become pregnant during the study period (B) Participants in other clinical trials or clinical trials, and other clinical trials within 3 months , or those who have participated in clinical trials (C), who are unable to follow the instructions of the attending physician and medical institution staff, (D), or those who are judged to have some kind of problem by the person in charge of the study.

Then, the 52 subjects were randomly assigned to the ergo group of 26 subjects and the placebo group of 26 subjects by the permuted block method so that the MMSE score would not be biased as subject background. The average MMSE score was 27.2 in the ergo group and 27.1 in the placebo group, which were similar.

In terms of subject backgrounds other than the MMSE score, there were 11 males and 15 females in the ergo group, and 7 males and 19 females in the placebo group. Regarding data on subject background, no significant difference was observed between the groups in data on height, weight, BMI, systolic blood pressure, diastolic blood pressure, pulse rate, and body temperature.

－Inspection schedule, contents of inspection－
Each subject visited a medical institution (testing institution) according to the schedule shown in Table 1, and underwent examinations, diagnoses, and tests described in the examination items. For this schedule, the 0th week of intake (0w: first test date) is the starting date, the 4th week of intake (4w: within 28 days ± 3 days from the first test date), and the 8th week of intake (8w: first test date). Within 56 days ± 6 days from the date of examination) and at 12 weeks of intake (12w: within 84 days ± 6 days from the date of the first examination).

On each examination day, each subject took breakfast after waking up, and then underwent medical interview, physical measurement, blood pressure measurement, and blood test. A blood test measured the blood concentration of ergothioneine. Cognitrax tests for cognitive function were then administered to each subject according to the "Cognitrax test administration guide". In order to accurately measure cognitive function, each subject refrained from overeating and drinking the day before each test day.

Here, the Cognitrax test is a cognitive function test service designed for Japan by Health Solution Co., Ltd. based on the cognitive function test technology developed by CNS Vital Signs in the United States. The Cognitrax test consisted of a verbal memory test, a visual memory test, a finger tapping test, a coding test (SDC test), a Stroop test, a sustained processing test, and a four-part sustained processing test. Each of 13 items (cognitive-related test items): cognitive function speed, reaction speed, overall attention, cognitive flexibility, processing speed, executive function, working memory, sustained attention, simple attention, and motor speed The inspection results are digitized.

－Test food, method of intake of test food－
Regarding the test food, for the ergo group, it was a food containing 5 mg of ergothioneine obtained from Pleurotus cornucopia extract (per 4 tablets), and for the placebo group, it was a food containing 0 mg of ergothioneine (per 4 tablets). . The test foods in each group were stored in aluminum pouches and stored at room temperature. The test food was blinded and handed over to the subject based on the identification number assigned to the food. All persons involved in the study (subjects, interventionists, evaluators, etc.) were blinded, and the randomization table was not opened until the subjects for analysis were fixed.

Each subject was to take 2 tablets at breakfast and 2 tablets at dinner with water from the day after the first examination (that is, the daily intake of ergothioneine in the ergo group was 5 mg). No particular dietary content was specified, and instructions were given to refrain from eating large amounts of mushrooms during the intake period. If they forgot to take it after breakfast, they were instructed to take it as soon as possible. As a general rule, we decided to treat cases with a food intake rate of 80% or more as subjects for analysis.

The test foods of the ergo group were produced using the freeze-drying method. Specifically, the test food of the ergo group consists of a preparation process of dissolving dextrin in the Tamogi mushroom extract to create a material liquid, a preliminary freezing process of freezing the material liquid obtained in the preparation process, and a preliminary freezing process under low temperature and low pressure conditions. A freeze-drying step of freeze-drying the material liquid after the step was performed in order to use the material obtained.

－Analysis method, analysis object－
As a statistical method, Student's t-test was used for comparison between groups. A paired t-test was performed for intragroup comparisons by comparison with pre-ingestion values. The significance level was 5% on both sides. Measured values and variations in each data were used for analysis data. StatMate V (Atoms Co., Ltd.) was used as statistical analysis software.

In addition, among the 52 subjects, there were 2 subjects who contracted influenza and could not be tested during the predetermined test period, and 2 subjects who had a food intake rate of 80% or more but could not eat food for 2 weeks. 1 person, 1 person whose food intake rate was less than 80% was excluded from the analysis, and statistical analysis was performed in the target population Per Protocol Set (PPS) cases that conformed to the study protocol (hereinafter, "PPS case analysis" ) was performed. In addition, in order to confirm the effect of improving cognitive function decline due to aging, statistical analysis was conducted in a specific age group targeting healthy subjects aged 40 and over and MCI subjects aged 30 and over with an MMSE score of 27 points or less (hereinafter referred to as , called “stratified analysis”). Those in their 20s with an MMSE score of 27 or less were excluded from the stratified analysis because it is difficult to determine age-related cognitive decline.

Regarding the number of subjects for PPS case analysis, the ergo group was 25 (1 excluded) and the placebo group was 23 (3 excluded). There were 5 males and 18 females. In addition, regarding healthy subjects or subjects with MCI, there were 14 healthy subjects and 11 subjects with MCI in the ergo group, and 9 healthy subjects and 14 subjects with MCI in the placebo group. In addition, the number of subjects in the stratified analysis was 20 in the ergo group and 19 in the placebo group. Regarding gender, there were 8 males and 12 females in the ergo group, and 3 males and 16 females in the placebo group. there were. Regarding healthy subjects or subjects with MCI, there were 10 healthy subjects and 10 subjects with MCI in the ergo group, and 5 healthy subjects and 14 subjects with MCI in the placebo group.

- result of blood test -
Table 2 shows changes in the mean ergothioneine blood concentration of the subjects for each of the ergo group and the placebo group. According to Table 2, it was confirmed that the ergothioneine blood concentration increased due to intake of the test food in the ergo group. On the other hand, in the placebo group, an increase in ergothioneine blood concentration due to ingestion of the test food could not be confirmed.

-Analysis results of Cognitrax inspection-
1 to 13, for 13 items in the Cognitrax test, the solid line indicates the results of PPS case analysis, the wavy line indicates the results of stratified analysis, the thick line indicates the ergo group, and the thin line indicates the placebo group. In other words, the thick solid line is the ergo group result in the PPS case analysis, the thin solid line is the placebo group result in the PPS case analysis, the thick wavy line is the ergo group result in the stratified analysis, and the thin wavy line is indicates 'Results of placebo group in stratified analysis'. In the legend of each figure, the results of PPS case analysis are indicated as "PPS", and the results of stratified analysis are indicated as "stratified".

In each figure, the vertical axis represents the average value of the subjects for analysis with respect to the amount of change in the score of the corresponding test item (the amount of change based on 0 weeks of intake). The horizontal axis represents the test timing (0 weeks of intake: 0 w, 4 weeks of intake: 4 w, 8 weeks of intake: 8 w, 12 weeks of intake: 12 w). Regarding the score of each test item, the lower the score of "reaction speed" and "general attention" (that is, the larger the amount of decrease), the better. In other words, the one with the larger amount of increase) represents a better state.

In addition, Table 3 shows the result (p value) of the significant difference test of the ergo group among the results of the PPS case analysis. Table 4 shows the detailed analysis results of test items for which a significant difference or a significant tendency between groups was confirmed among the results of the significance test shown in Table 3.

According to the significant difference test results in the PPS case analysis, a significant difference (p<0.05) between the groups was confirmed at 8 weeks for "cognitive function speed." In addition, "verbal memory" at 12 weeks, "cognitive function speed" at 12 weeks, "working memory" at 12 weeks, "sustained attention" at 4 weeks, "simple attention" at 4 weeks A significant tendency (p<0.1) between the groups was confirmed at 8 weeks and 8 weeks, and at 8 weeks and 12 weeks for "exercise speed". In any item, there was no significant difference between the groups at 0 weeks of intake. According to these results, L-ergothioneine was found to be effective in improving the speed of cognitive function regardless of whether the subject was healthy or mildly demented.

Table 5 shows the results (p value) of the significant difference test for the ergo group among the results of stratified example analysis. Further, Table 6 shows detailed analysis results of test items for which a significant difference or a significant tendency between groups was confirmed among the results of the significance test shown in Table 5.

According to the results of a significant difference test in stratified analysis, a significant difference (p<0.05) was confirmed between the groups at 12 weeks for "verbal memory" and at 8 weeks for "simple attention". In addition, there was a significant tendency (p<0.1) between the groups at 8 weeks for "cognitive function speed", at 4 weeks for "sustained attention", and at 4 weeks and 12 weeks for "simple attention". could be confirmed. In addition, although not shown in Table 6, a significant difference (p<0.05) between the groups was confirmed in the measured values of "sustained attention" at 4 weeks. In any item, there was no significant difference between the groups at 0 weeks of intake. These results show that L-ergothioneine is effective in improving age-related verbal memory, age-related sustained attention, and age-related simple attention.

From the above, L-ergothioneine is effective in improving cognitive function speed, improving verbal memory, and improving attention (sustained attention, simple attention (especially each attention associated with aging)). rice field. The above-mentioned composition containing L-ergothioneine as an active ingredient is a composition for improving cognitive function speed, a composition for improving verbal memory, attention (sustained attention, simple attention (especially aging) It can be used as a composition for improving attention)).

INDUSTRIAL APPLICABILITY The present invention is applicable to compositions used for improving cognitive function in the brain.

Claims (8)

A composition containing L-ergothioneine as an active ingredient for improving age-related persistent attention deficits. 2. The composition according to claim 1, wherein the L-ergothioneine is contained in an extract of Pleurotus cornucopia. The composition according to claim 1 , wherein the L-ergothioneine intake is 1 mg to 30 mg per adult per day. A composition for ameliorating age-related persistent attention deficit, comprising an extract of Pleurotus cornucopia as an active ingredient. 5. A composition according to any one of claims 1 to 4 , wherein said composition is a food composition. 6. The composition according to claim 5 , wherein the food composition is a health food, a functional food, a dietary supplement, a supplement, a food for specified health uses, a food for the sick, a combination food for the sick, or a food for the elderly. thing. 5. The composition of any one of claims 1-4 , wherein said composition is a pharmaceutical composition. 5. The composition according to any one of claims 1 to 4 , wherein the composition is a composition, a freeze-dried composition, or a spray-dried composition consisting of an extract of Pleurotus cornucopia.

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