Cognitive function improving composition

Abstract

The present invention provides a composition for a cognitive function improver, which does not require expensive culture facilities for its active ingredient (lactic acid bacteria of the genus Tetragenococcus), does not require much labor or cost during production, is a safe food material, and can further improve cognitive function. [Solution] A cognitive function improving composition containing at least one selected from the group consisting of Tetragenococcus lactic acid bacteria cells that improve cognitive function and cultures of these bacteria. The Tetragenococcus lactic acid bacteria is preferably Tetragenococcus halophilus.

Description

[Technical Field]

[0001] The present invention relates to a composition for improving cognitive function. More specifically, the present invention relates to a composition for improving cognitive function that can improve cognitive function, does not require expensive culture equipment, is less time-consuming and costly to produce, and contains a safe food material (lactic acid bacteria) as an active ingredient. [Background technology]

[0002] Human cognitive functions consist of abilities such as memory, thinking, orientation, comprehension, calculation, learning, language, and judgment. However, accidents or illnesses can cause cognitive disorders such as memory impairment, attention disorders, disorientation, akinetic behavior, aphasia, agnosia, and executive dysfunction.

[0003] In addition to accidents and illnesses, it is known that physiological cognitive decline can occur due to brain aging and even stress (this decline in cognitive function can occur in anyone, regardless of gender), and when symptoms become apparent, they can cause memory disorders such as forgetfulness, decline in language ability such as being unable to speak or making mistakes, decreased attention and concentration, and decreased learning ability.Depending on the severity, these symptoms can interfere with daily life.

[0004] Here, doctors prescribe anti-dementia drugs to patients suffering from diseases related to cognitive impairment (dementia patients), but these drugs are not prescribed for the purpose of preventing or improving the decline in physiological cognitive function, that is, the decline in cognitive function in healthy individuals.

[0005] On the other hand, as described above, the decline in physiological cognitive function may interfere with daily life, and even if a person does not fall into the category of a dementia patient, it is necessary to suppress or improve the decline in cognitive function, and there is a demand for the development of an improving agent (an improving agent composition) for this purpose. Therefore, for example, a cognitive function improving agent to be administered to a person who has not developed dementia, such as a healthy person, has been reported (see Patent Document 1). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Patent No. 7189393 Summary of the Invention [Problem to be solved by the invention]

[0007] However, the cognitive function improving agent described in Patent Document 1 has the problem that the strain serving as its active ingredient requires cultivation equipment in which anaerobic gases such as carbon dioxide are aerated while the strain is cultivated, which increases the time and cost required for production.

[0008] Therefore, there is a need for the development of a composition for improving cognitive function that can improve cognitive function, does not require expensive culture equipment, is less time-consuming and costly to manufacture, and contains a safe food material (lactic acid bacteria) as an active ingredient.

[0009] The present invention has discovered that Tetragenococcus lactic acid bacteria can improve cognitive function, and that Tetragenococcus lactic acid bacteria do not require expensive culture equipment, are less time-consuming and costly to produce, and are also a safe food ingredient. [Means for solving the problem]

[0010] According to the present invention, the following composition for a cognitive function improver is provided.

[0011] [1] A composition for improving cognitive function, comprising at least one selected from the group consisting of Tetragenococcus lactic acid bacteria cells that improve cognitive function and cultures of the cells.

[0012] [2] The composition for improving cognitive function according to [1], wherein the Tetragenococcus lactic acid bacteria is Tetragenococcus halophilus.

[0013] [3] The composition for improving cognitive function according to [1], wherein the Tetragenococcus lactic acid bacteria is Tetragenococcus lactic acid bacteria having accession number NITE BP-02318.

[0014] [4] The composition for cognitive function improvement according to any one of [1] to [3] above, which improves one or more items selected from the group consisting of verbal memory, overall memory, cognitive function speed, and cognitive flexibility in the Cognitrax Cognitive Function Test. [Effects of the Invention]

[0015] The composition for improving cognitive function of the present invention does not require expensive cultivation equipment for its active ingredient (Tetragenococcus lactic acid bacteria), is less time-consuming and costly to produce, is a safe food ingredient, and further has the effect of improving cognitive function. DETAILED DESCRIPTION OF THE INVENTION

[0016] The following describes embodiments of the present invention, but the present invention is not limited to the following embodiments. In other words, it should be understood that modifications and improvements to the following embodiments, based on the ordinary knowledge of a person skilled in the art, as long as they do not deviate from the spirit of the present invention, also fall within the scope of the present invention.

[0017] (1) Composition for cognitive function improvement: The cognitive function improver composition of the present invention contains at least one selected from the group consisting of Tetragenococcus lactic acid bacteria cells that improve cognitive function and cultures of the cells.

[0018] This cognitive function improver composition does not require expensive culture facilities for its active ingredient (Tetragenococcus lactic acid bacteria), is a safe food material, and is less time-consuming and costly to produce, while also improving cognitive function. This cognitive function improver composition particularly improves one or more items selected from the group consisting of verbal memory, overall memory, cognitive speed, and cognitive flexibility in the Cognitrax cognitive function test.

[0019] Here, when ordinary lactic acid bacteria (lactic acid bacteria that do not have salt tolerance, etc.) are commercially produced, concentration and purification of the bacterial cells and treatment of the culture medium (for example, sterilization using an autoclave or similar) are required. Furthermore, during cultivation, an environment must be maintained that prevents contamination by contaminating bacteria such as miscellaneous bacteria, which increases the effort and cost of production. On the other hand, the Tetragenococcus lactic acid bacteria, which are active ingredients in the composition for improving cognitive function of the present invention, are salt-tolerant, and therefore can be cultivated in a high-salt environment where contaminating bacteria have difficulty growing, making it easy to cultivate them under conditions that suppress the growth of contaminating bacteria.

[0020] (1-1) Tetragenococcus lactic acid bacteria cells and cultures of the cells: Tetragenococcus lactic acid bacteria are salt-tolerant lactic acid bacteria. "Having salt tolerance" means that they have the property of being able to be cultured in a medium with a high salt concentration (specifically, a salt concentration of 11 w / v% or more).

[0021] As described above, the Tetragenococcus lactic acid bacteria are salt-tolerant lactic acid bacteria, making them easy to cultivate. Furthermore, cultivation is even easier when the growth rate is 30 times or more when cultured in a medium with a salt concentration of 12 w / v%. The "growth rate" refers to the value calculated by the formula: "number of bacteria after 20 hours of culture (cfu / ml) / initial number of bacteria (cfu / ml)."

[0022] The Tetragenococcus lactic acid bacteria can be, for example, those isolated during the brewing process of miso (particularly rice miso). Specific examples of salt-tolerant lactic acid bacteria isolated during the brewing process of rice miso include the trade name "Zoka Lactic Acid Bacteria LTK-1" (manufactured by Ichibiki Co., Ltd.).

[0023] Furthermore, lactic acid bacteria "isolated during the miso brewing process" refers to salt-tolerant lactic acid bacteria that are established in the "kura," "muro," and "oke" (wood vats) used in the miso brewing process. Furthermore, it refers to lactic acid bacteria that can grow from the preparation of miso to the maturation process. These lactic acid bacteria "isolated during the miso brewing process" can also be called salt-tolerant lactic acid bacteria contained in miso (i.e., miso lactic acid bacteria), or, in other words, salt-tolerant lactic acid bacteria derived from miso (i.e., salt-tolerant lactic acid bacteria originating from miso). In the present invention, lactic acid bacteria "isolated during the miso brewing process" are not limited to those isolated during the miso brewing process, but also include those isolated and preserved during the miso brewing process and subsequently cultured.

[0024] As mentioned above, the Tetragenococcus lactic acid bacteria are not particularly limited as long as they improve cognitive function, but Tetragenococcus halophilus is a good example. In particular, the Tetragenococcus lactic acid bacteria under accession number NITE BP-02318 can be mentioned. The Tetragenococcus lactic acid bacteria under accession number NITE BP-02318 is known under the trade name "Zoka Lactic Acid Bacteria LTK-1" (manufactured by Ichibiki Co., Ltd.).

[0025] The Tetragenococcus lactic acid bacteria with accession number NITE BP-02318 was deposited at the National Patent Microorganisms Depositary (NPMD) of the National Institute of Technology and Evaluation on August 3, 2016 (domestic deposit date), and was transferred to international deposit under the Budapest Treaty on September 6, 2017.

[0026] The Tetragenococcus lactic acid bacteria may be killed or live.

[0027] There is no particular limit to the intake concentration (effective concentration when ingested) of Tetragenococcus lactic acid bacteria, but it can be 1.25 mg / day or more, with the upper limit being approximately 1,250 mg / day. In other words, similar to regular lactic acid bacteria, approximately 5 billion (equivalent to approximately 1.25 mg) to 5 trillion (equivalent to approximately 1.25 g) of bacteria can be ingested per day. For example, it can be taken orally before or after meals as a medicine or supplement.

[0028] (1-2) Cultivation method of Tetragenococcus lactic acid bacteria: There are no particular limitations on the culture conditions for Tetragenococcus lactic acid bacteria, but they can be cultured, for example, in a medium with a salt concentration of 11 to 18 w / v%, preferably 11 to 16 w / v%, and particularly preferably 12 to 14 w / v%. Note that "w / v%" means (mass (g) / volume (100 mL))%.

[0029] Cultivation under these conditions makes it difficult for other bacteria (contaminants such as miscellaneous bacteria) to grow, while Tetragenococcus lactic acid bacteria can be cultivated, allowing for easy and efficient cultivation of Tetragenococcus lactic acid bacteria as a primary agent. Furthermore, culturing at a salt concentration within the above range prevents the proliferation of non-halotolerant contaminants while allowing the proliferation rate to be faster than that of salt-tolerant bacteria (halotolerant contaminants), such as halotolerant Staphylococcus bacteria. In other words, even with respect to halotolerant contaminants, the culture can be terminated and the product can be harvested before the proliferation of the contaminants. Cultivation in a medium with a salt concentration of less than 11 w / v% tends to facilitate the proliferation of contaminants, making it difficult to ensure a sufficient yield. Furthermore, culturing in a medium with a salt concentration of more than 18 w / v% makes it more difficult for contaminants to grow, but the required cultivation period to obtain the required yield is prolonged, potentially resulting in the proliferation of halotolerant contaminants.

[0030] As described above, when cultured in a medium with the above-mentioned salt concentration, Tetragenococcus lactic acid bacteria can be cultured efficiently and in large quantities even in a simple open culture device (which can be sterilized and kept warm) without using special equipment such as a closed sterile culture device or an anaerobic culture device that cultures while aerating anaerobic gases such as carbon dioxide. This culture may be used in a composition for improving cognitive function.

[0031] The culture temperature is preferably 20 to 40° C., more preferably 28 to 37° C. The culture time is about 24 to 120 hours, and the culture may be stirred during culture. The pH of the medium is preferably 5 to 9, more preferably 6 to 7.

[0032] The medium used may contain a nitrogen source and a carbon source.

[0033] The nitrogen source is not particularly limited and examples thereof include soy sauce, miso, meat extract, peptone, gluten, casein, yeast extract, amino acids, etc. The carbon source is also not particularly limited and examples thereof include glucose, koji digestion liquid, rice saccharification liquid, sucrose, starch, powdered sugar, glycerin, etc. Furthermore, in addition to the nitrogen source and carbon source, the culture medium may contain inorganic substances such as inorganic salts such as sodium acetate, magnesium, manganese, and iron, and may also contain vitamins.

[0034] Lactic acid bacteria of the genus Tetragenococcus can be prepared by sterilization or other treatments after cultivation. Specifically, after cultivation is completed, medium components including salt are removed by centrifugation or other means, followed by washing and purification. If necessary, heat sterilization is performed, and then the bacteria are dried and concentrated by freeze-drying, vacuum drying, hot air drying or other means. In this way, lactic acid bacteria of the genus Tetragenococcus can be prepared after cultivation.

[0035] The heat sterilization is not particularly limited, but specifically, autoclave sterilization (121°C, 20 minutes) or a similar sterilization method is preferred.

[0036] (1-3) Other ingredients: The composition for improving cognitive function of the present invention may be composed solely of Tetragenococcus lactic acid bacteria (or a composition containing a culture of the lactic acid bacteria, etc.) that have the ability to improve cognitive function, but may also contain other components in addition to the Tetragenococcus lactic acid bacteria.

[0037] As other ingredients, ingredients that are appropriately blended depending on the application, such as pharmaceuticals, quasi-drugs, foods and beverages, can be used.

[0038] In the case of pharmaceuticals and quasi-drugs, other ingredients may include, for example, excipients, coating agents, binders, bulking agents, disintegrants, surfactants, lubricants, diluents, dispersants, buffers, osmotic pressure adjusters, pH adjusters, emulsifiers, preservatives, stabilizers, antioxidants, colorants, UV absorbers, moisturizers, thickeners, activity enhancers, anti-inflammatory agents, disinfectants, flavoring agents, odor enhancers, etc. Active ingredients or pharmacological ingredients other than Tetragenococcus lactic acid bacteria may also be contained, provided that the object of the present invention is not impaired.

[0039] In the case of foods and beverages, other ingredients can include, for example, sweeteners, acidulants, carbon dioxide gas, inorganic salts, flavorings, fruit juice, vitamins, antioxidants, esters, colorants, emulsifiers, preservatives, seasonings, vegetable extracts, nectar extracts, quality stabilizers, bitterness suppressors, etc. In the case of foods and beverages, active ingredients and pharmacological ingredients other than Tetragenococcus lactic acid bacteria may also be contained, as long as they do not impair the object of the present invention.

[0040] The cognitive function improver composition of the present invention can be ingested in any form (oral or parenteral). For example, when ingested orally, it can be in a solid form such as a tablet, coated tablet, granule, powder, or capsule, or in a liquid form such as an elixir or syrup.

[0041] (2) Method for producing a composition for cognitive function improvement: The cognitive function improver composition of the present invention can be produced, for example, by a method including a lactic acid bacteria preparation step and a raw material preparation step. This method allows for the simple production of a cognitive function improver composition. This method has the advantage that Tetragenococcus lactic acid bacteria are salt-tolerant and therefore can be easily cultured.

[0042] The lactic acid bacteria preparation step is a step of preparing the above-mentioned Tetragenococcus lactic acid bacteria. The Tetragenococcus lactic acid bacteria may be prepared by obtaining a seed culture and culturing the seed culture by the above-mentioned method, or by purchasing a commercially available lactic acid bacteria (for example, the trade name "Zoka Lactic Acid Bacteria LTK-1" (manufactured by Ichibiki Co., Ltd.)).

[0043] The raw material preparation step is a step of preparing a raw material for a composition for cognitive function improver by mixing the Tetragenococcus lactic acid bacteria prepared in the lactic acid bacteria preparation step with other components as needed.

[0044] In the case of a solid form such as a tablet, a step for forming the solid form (a forming step) may be adopted after the raw material preparation step.

[0045] (3) Intake period of the composition for cognitive function improvement: The cognitive function improver composition of the present invention is preferably taken for one week or more, more preferably for two weeks or more.

[0046] (4) Cognitive function improvers: The cognitive function improver composition of the present invention may be used as is, or may be formulated with other ingredients as appropriate, similar to conventionally known cognitive function improvers. This cognitive function improver is easy to produce because its active ingredient, Tetragenococcus lactic acid bacteria, is easy to culture, does not require expensive production equipment, and does not require complicated manufacturing processes; it is an inexpensive, stable, and safe food material (lactic acid bacteria). Furthermore, this cognitive function improver can improve cognitive function by ingesting it for a certain period of time.

[0047] This cognitive function improver can be appropriately produced by the same method as that used for conventionally known cognitive function improvers. [Example]

[0048] The present invention will be specifically described below based on examples, but the present invention is not limited to these examples.

[0049] Example 1 (1) Test food: Two types of test foods were prepared: a test food and a control food. These test foods and control foods are shown in Table 1 below.

[0050] [Table 1]

[0051] Table 2 shows the shape and form of each test food (test food, control food).

[0052] [Table 2]

[0053] Furthermore, the ingredients of each test food are shown in Table 3 below. The single dose is 2 tablets / day (600 mg), and in Table 3, the ingredients of the test food show the amount of ingredients per 2 tablets. In Table 3, Zouka Lactic Acid Bacteria LTK-1 (manufactured by Ichibiki Co., Ltd.) was used at 125 mg / tablet.

[0054] [Table 3]

[0055] (2) Dosage and Administration: The packaging of each test food was opened along the cut edge, and two tablets were orally taken with water per day. The intake times (timing) were aimed to be as consistent as possible.

[0056] (3) Intake period: The intake period was 4 weeks.

[0057] (4) Efficacy evaluation items: Cognitive function tests were conducted both at the start of intake of the test food or control food (day 0) and four weeks after the start of intake (week 4) to evaluate the effectiveness of taking the test food. Cognitrax cognitive function tests were used for cognitive function tests.

[0058] The Cognitrax cognitive function test is based on the cognitive function testing technology developed by CNS Vital Signs, Inc. in the United States, and is an online cognitive function testing service designed for Japan by Health Solutions Co., Ltd. In this invention, the cognitive function test evaluated using "Cognitrax Basic" provided by Health Solutions Co., Ltd. was used as the index.

[0059] "Cognitrax Basic" is a test that evaluates 11 cognitive function domains (Table 5) based on the results of seven tests (test items) shown in Table 4: "Verbal Memory Test," "Visual Memory Test," "Finger Tapping Test," "Encoding (SDC) Test," "Stroop Test," "Attention Shift Test," and "Sustained Processing Test." The "Contents" in Table 4 provide an overview of each test item. The "Brief Meaning" and "Examples" in Table 5 are based on the explanations in "Cognitrax Basic."

[0060] [Table 4]

[0061] [Table 5]

[0062] (5) Clinical study design: The clinical research design was a stratified randomized, double-blind, parallel-group comparative study.

[0063] (6) Inclusion criteria for subjects: Subjects were recruited based on the criteria that they met all of the following criteria A to G at the time of consenting to this clinical study. There were 44 subjects. A: Healthy Japanese people aged between 55 and 80 at the time of consent B: Those who are not receiving any medication, therapy, or treatment, regardless of whether it is seasonal, chronic, or sudden. C: Participants in this clinical study have fully understood the contents of the study and have voluntarily given written consent. D: Those with a body temperature of 35.5℃ to 37.0℃ E: Those who can avoid overeating and drinking, and eat three meals a day during the clinical study period. F: Subjects who can use appropriate contraception during the clinical study period G: Able to understand and comply with the management requirements during this clinical study.

[0064] Please note that those who fall into any of the following categories a to i were not eligible. a: People with diseases of the digestive tract, liver, kidney, heart, or circulatory system that affect the absorption, distribution, metabolism, or excretion of the test food b: Those who have had major surgery in the gastrointestinal tract, such as gastrectomy, gastrointestinal suture, or intestinal resection (excluding polypectomy and appendectomy) c: People with a history of cerebrovascular disease d: People with food allergies or other specific physical conditions related to the test food e: People suspected of alcohol or drug dependence f: Those who have participated in other clinical trials or clinical research within the past 84 days from the date of consent acquisition g: Those who have donated 400 mL of blood within the past 84 days, 200 mL of blood within the past 28 days, or blood components (plasma and platelet components) within the past 14 days from the date of consent acquisition h: Breastfeeding or pregnant i: People working night shifts

[0065] The test results for the Cognitrax cognitive function test are shown in Table 6 below.

[0066] [Table 6]

[0067] In Table 6, the actual measured values ​​are shown as "average values ​​± standard deviations." * p<0.05, ** p<0.01 indicates a significant difference compared to the start of intake. # p<0.05, ## p<0.01 indicates a significant difference compared to the control food group.

[0068] As can be seen from the test results in Table 6, the cognitive function improver composition of Example 1 improves human cognitive function. More specifically, in the cognitive function domains of verbal memory and overall memory, the actual measured values ​​were significantly higher (improved) 4 weeks after the start of intake (4 weeks after intake) and between the control food group and the test food group. Furthermore, in the cognitive function domains of cognitive function speed and cognitive flexibility, the actual measured values ​​were significantly higher (improved) 4 weeks after the start of intake (4 weeks after intake).

[0069] In addition to the above cognitive function areas, improvements were also observed in some areas in the control food group around four weeks after intake. However, if there was a significant difference in both the control food group and the test food group, this was likely a placebo effect, and therefore it was determined that there was no effect (no improvement was recognized).

[0070] Furthermore, Tetragenococcus lactic acid bacteria, which are the active ingredient of the composition for cognitive function improvement, do not require expensive culture equipment, are less time-consuming and costly to produce, and are also a safe food material. [Industrial Applicability]

[0071] The composition for cognitive function improver of the present invention can be used as an agent for improving cognitive function. [Accession number]

[0072] Accession number: NITE BP-02318

Claims

1. A composition for improving cognitive function, comprising at least one selected from the group consisting of Tetragenococcus lactic acid bacteria cells that improve cognitive function and cultures of said bacteria cells.

2. The composition for improving cognitive function according to claim 1, wherein the Tetragenococcus lactic acid bacterium is Tetragenococcus halophilus.

3. The composition for improving cognitive function according to claim 1, wherein the Tetragenococcus lactic acid bacterium is a Tetragenococcus lactic acid bacterium having accession number NITE BP-02318.

4. The composition for improving cognitive function according to any one of claims 1 to 3, which improves one or more items selected from the group consisting of verbal memory, overall memory, cognitive function speed, and cognitive flexibility in the Cognitrax Cognitive Function Test.

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