JP2024065497A - Composition for improving stress-induced cognitive dysfunction and medicine, food, drink and feed containing the same - Google Patents

Abstract

The present invention provides a novel composition for improving cognitive function, which is used to prevent or improve stress-induced cognitive decline, and a medicine, food, drink, and feed containing the composition. The composition for improving cognitive function contains a processed product of Agaricus blazei fruiting body. [Selected Figure] Figure 4

Description

The present invention relates to a composition for improving stress-induced cognitive impairment, and to medicines, foods, beverages, and feeds that contain the composition.

Dementia is a condition in which cognitive function declines due to causes such as cerebrovascular disease and degenerative diseases such as Alzheimer's disease, and various research is being conducted on treatments to prevent and improve dementia.

In addition to the causes mentioned above, it is also known that mental stress can impair cognitive functions (memory, judgment, calculation, comprehension, learning, thinking, language, etc.).

Specifically, for example, it is known that loneliness stress increases the risk of developing dementia in the elderly (Non-Patent Document 1), and social isolation is a risk factor for dementia (Non-Patent Document 2).

Wilson et al., Arch. Gen. Psychiatry, 2007 Livingston et al., The Lancet Commissions, 2017

The mechanism behind the stress-related decline in cognitive function described above is not entirely clear, but it is thought to be a different pathology from senile dementia caused by organic brain damage associated with aging, as cognitive function can sometimes be restored by eliminating the stress factor.

Therefore, it is thought that it is necessary to consider preventive and improvement measures for stress-related cognitive decline (impairment) that are different from those for age-related dementia.

The present invention aims to provide a novel cognitive function improving composition for preventing or improving stress-induced cognitive decline, and a medicine, food, beverage, or feed containing the same.

In order to solve the above problems, the following cognitive function improving compositions, medicines, foods, beverages, and feeds are provided.
[1] A cognitive function improving composition for preventing or improving stress-induced cognitive decline,
A composition for improving cognitive function, comprising a processed Agaricus fruiting body.
[2] The composition for improving cognitive function according to [1], wherein the agaricus is King Agaricus 21 strain (accession number: FERM P-17695).
[3] The cognitive function improving composition according to [1] or [2], wherein the processed material is a dried processed material.
[4] A pharmaceutical composition for improving cognitive function comprising any one of the compositions [1] to [3].
[5] A food or drink comprising any one of the cognitive function improving compositions described in [1] to [3].
[6] A feed characterized by containing the cognitive function improving composition according to any one of [1] to [3].

The cognitive function improving composition of the present invention and the medicine, food, drink, and feed containing the same can prevent or improve stress-induced cognitive decline by administering or ingesting the composition.

This is a diagram showing an overview of the normal diet group (control group), the isolation + normal diet group, and the isolation + agaricus administration group. This is a graph showing changes in body weight in the normal diet group (control group), the isolation + normal diet group, and the isolation + agaricus administration group. This figure shows the change in distance traveled in the normal diet group (control group), the isolation + normal diet group, and the isolation + agaricus administration group. Statistical analysis was performed using 2-way ANOVA and Tukey's multiple comparisons test. This is a graph showing spatial cognitive function for the normal diet group (control group), the isolation + normal diet group, and the isolation + agaricus administration group. Statistical analysis was performed using 2-way ANOVA and Tukey's multiple comparisons test.

The present inventors discovered a new finding that agaricus (preferably Agaricus brasiliensis) fruiting bodies have an effect of improving stress-induced cognitive decline, leading to the completion of the present invention.

Hereinafter, one embodiment of the cognitive function improving composition of the present invention will be described. The cognitive function improving composition of the present invention is a composition for improving stress-induced cognitive decline (impairment) (composition for improving stress-induced cognitive impairment).

In the present invention, "stress-related cognitive decline" refers to decline in cognitive function (memory, judgment, calculation, understanding, learning, thinking, language, etc.) induced by mental stress due to, for example, loneliness, social isolation, neglect, etc.

The cognitive function improving composition of the present invention contains processed Agaricus fruiting bodies.

Examples of Agaricus fruiting bodies (fruiting bodies of Agaricus blazei Murill, Agaricus brasiliensis, Agaricus subrufescens, etc.) include wild fruiting bodies and cultivated fruiting bodies.

Among them, it is preferable that the agaricus is the King Agaricus 21 strain deposited at the National Institute of Technology and Evaluation with the accession number FERM P-17695 (deposit date: January 13, 2000, re-deposit date: July 1, 2016). When the cognitive function improving composition of the present invention contains a processed product of King Agaricus 21 (FERM P-17695), a superior cognitive function improving effect is achieved compared to other strains of agaricus.

The processed Agaricus fruiting body may be any of a variety of processed products obtained directly from the fruiting body or by physical, chemical or biological treatment.

Specific examples of physically and chemically treated products include products that have been dried by sun drying, air drying, freeze drying, etc., freeze-dried products, and products that have been pulverized using a blender, homogenizer, ball mill, etc. Examples of biological treatment methods include fermentation methods, etc. Among these, it is preferable that the fruiting bodies are in the form of dried products or freeze-dried products.

In addition, processed products of Agaricus fruiting bodies include extracts obtained from the fruiting bodies by various extraction methods, so long as they contain the active ingredients. Examples of extraction methods include various solvent extractions and supercritical fluid extraction. Extracts may be processed by various solid-liquid separation methods such as sedimentation, cake filtration, clarification filtration, centrifugal filtration, centrifugal sedimentation, compression separation, and filter press, various concentration methods, various drying methods, formulation methods such as granulation or powderization, various purification methods, etc.

Furthermore, processed Agaricus fruiting bodies may be added to a solvent such as water to form a liquid composition for improving cognitive function.

The method for producing the cognitive function improving composition of the present invention includes a step of blending a processed Agaricus fruiting body, and may also include various other steps that are conventionally known.

The cognitive function improving composition of the present invention can be in the form of a medicine, food or drink, or feed (or a feed additive), and can be administered or ingested by a mammal. That is, the medicine, food or drink, or feed of the present invention contains the cognitive function improving composition described above.

(Pharmaceuticals)
The pharmaceutical of the present invention is a pharmaceutical for preventing or improving stress-induced cognitive decline, and comprises the cognitive function improving composition of the present invention described above.

The pharmaceutical of the present invention may use the cognitive function improving composition of the present invention as an active ingredient as is, or may be formulated by adding pharma- ceutical acceptable ingredients.

The pharmaceutical of the present invention may be in a dosage form for oral use or a dosage form for parenteral use. Dosage forms for oral use include, for example, powders, granules, tablets, capsules, elixirs, microcapsules, etc. Dosage forms for parenteral use include, for example, injections, drips, ointments, inhalants, suppositories, etc.

The pharmaceutical of the present invention may contain a pharma- ceutically acceptable carrier. Examples of such carriers include known excipients, disintegrants, binders, lubricants, surfactants, buffers, solubilizers, stabilizers, isotonicity agents, suspending agents, emulsifiers, solvents, thickeners, mucolytic agents, wetting agents, and preservatives.

The pharmaceutical of the present invention may further contain additives. Examples of additives include lubricants such as magnesium stearate; sweeteners such as sucrose, lactose, saccharin, etc.; flavorings such as peppermint and saffron oil; stabilizers for benzyl alcohol and phenol; buffers such as phosphates and sodium acetate; solubilizers such as benzyl benzoate and benzyl alcohol; antioxidants; preservatives, etc.

The pharmaceutical of the present invention can be formulated by appropriately combining the above-mentioned carriers, additives, etc., and mixing them in a unit dosage form required for generally accepted pharmaceutical practice.

The dosage of the pharmaceutical of the present invention varies depending on the patient's weight and age, the patient's symptoms, the administration method, etc., but a person skilled in the art can appropriately select an appropriate dosage. The dosage when the cognitive function improving composition of the present invention is administered to a human varies depending on the symptoms, the patient's age, sex, weight, sensitivity difference, administration method, administration interval, type of active ingredient, and type of formulation, and is not particularly limited. For example, when administered or ingested orally, an amount selected from 0.1 mg/kg to 100 g/kg per day can be administered or ingested once or multiple times (e.g., 2 to 5 times, preferably 2 to 3 times).

The administration or ingestion period of the pharmaceutical of the present invention is not limited, but for example, the pharmaceutical of the present invention can be administered or ingested continuously for a period of one week or more, two weeks or more, one month or more, two months or more, six months or more, one year or more, or longer, in accordance with the above dosage and administration method.

(Food and beverages)
The food and drink (food and beverage) of the present invention is a food and drink for preventing or improving stress-induced cognitive decline, and includes the cognitive function improving composition of the present invention described above.

Examples of foods and beverages include health foods and beverages in the form of tablets, tablets, chewable tablets, tablets, powders, powders, capsules, granules, drinks, etc. (supplements, dietary supplements, dietary supplements, nutritionally adjusted foods, etc.), soft drinks, tea drinks, jelly drinks, sports drinks, coffee drinks, carbonated drinks, vegetable drinks, fruit juice drinks, fermented vegetable drinks, fermented fruit juice drinks, fermented milk drinks (yogurt, etc.), lactic acid bacteria drinks, milk drinks, powdered drinks, cocoa drinks, alcoholic drinks, confectionery, jellies, etc. In particular, foods and beverages are preferably in the form of health functional foods (foods for specified health uses, foods with nutrient functions, foods with functional claims) or health foods.

Furthermore, the "food and drink" of the present invention may contain ingredients that are commonly used in the field of food engineering. Specifically, for example, various oils and fats (e.g., vegetable oils such as soybean oil, corn oil, safflower oil, and olive oil, and animal oils and fats such as beef tallow and sardine oil), herbal medicines (e.g., royal jelly, ginseng, etc.), amino acids (e.g., glutamine, cysteine, leucine, arginine, etc.), polyhydric alcohols (e.g., ethylene glycol, polyethylene glycol, propylene glycol, glycerin, sugar alcohols such as sorbitol, erythritol, xylitol, maltitol, mannitol, etc.), natural polymers (e.g., gum arabic, agar, water-soluble corn fiber, gelatin, xanthan gum, etc.), and the like. Examples of such ingredients include gluten, casein, gluten or gluten hydrolysate, lecithin, starch, dextrin, etc.), vitamins (e.g. vitamin C, B vitamins, etc.), minerals (e.g. calcium, magnesium, zinc, iron, etc.), dietary fiber (e.g. mannan, pectin, hemicellulose, etc.), surfactants (e.g. glycerin fatty acid esters, sorbitan fatty acid esters, etc.), purified water, diluents, stabilizers, isotonicity agents, pH adjusters, buffers, wetting agents, solubilizers, suspending agents, colorants, flavorings, odorants, fragrances, antioxidants, sweeteners, taste-providing components, and acidulants.

The amount of food or beverage to be consumed varies depending on the patient's weight, age, symptoms, method of administration, etc., but a person skilled in the art can select an appropriate dosage. Specifically, the amount and period of intake may be the same as those of the medicine of the present invention.

(feed)
The cognitive function-improving composition of the present invention can be in the form of not only food and drink for humans, but also feed (or feed additive) for livestock, racehorses, pets (eg, dogs, cats, etc.), etc.

The dosage or intake of the medicine and food and beverage of the present invention can be adjusted appropriately taking into consideration the age and body weight of the subject, the route of administration, and the number of times of administration or intake.

The cognitive function improving composition, medicine, and food and drink of the present invention are not limited to the above embodiments. Since the cognitive function improving composition, medicine, food and drink, and feed of the present invention contain processed Agaricus fruiting bodies, they can achieve the conventionally known medicinal effects of strengthening and improving the liver, heart, gastrointestinal tract, stabilizing blood pressure and blood sugar levels, relieving lower back pain and stiff shoulders, improving hair loss and gray hair, preventing aging, improving immunity, anti-tumor effects, reducing the side effects of anti-cancer drugs, and healing wounds.

The cognitive function improving composition of the present invention will be described in detail below with reference to examples, but the cognitive function improving composition of the present invention is not limited to the following examples.

<1> Agaricus fruiting body The Agaricus brasiliensis KA21 strain cultivated outdoors in Brazil was used as the dried Agaricus fruiting body. This Agaricus was deposited at the National Institute of Technology and Evaluation (Accession No. FERM P-17695 King Agaricus 21).

<2> Administration of feed to mice Four-week-old mice were divided into a normal diet group (control group), an isolation + normal diet group, and an isolation + agaricus administration group (Figure 1).

Specifically, the normal diet group (control group) was fed a normal diet for 8 weeks without any stress such as isolation. In the isolation + normal diet group, mice were housed in groups and housed in isolation (social isolation) under stress and fed a normal diet for 8 weeks. In the isolation + agaricus group, mice were socially isolated and stressed and fed a normal diet as well as dried powder of agaricus fruiting bodies (King Agaricus 21) (5% by mass of the normal diet) for 8 weeks.

<3> Measurement of body weight and distance traveled Body weight and distance traveled were measured for the normal diet group (control group), the isolation + normal diet group, and the isolation + agaricus administration group. No significant difference was observed in body weight for the normal diet group (control group), the isolation + normal diet group, and the isolation + agaricus administration group (Figure 2). No significant difference was observed in distance traveled for the normal diet group (control group), the isolation + normal diet group, and the isolation + agaricus administration group (Figure 3).

<4> Evaluation of cognitive function To evaluate the spatial cognitive function of each group of mice, the Y-maze test was performed (Figure 4). The Y-maze test utilizes the tendency of mice to spontaneously enter different arms during exploratory behavior, and can be used to evaluate alternation responses as an index of spatial working memory (see, for example, Saito et al., Nat. Neurosci, 2014).

As a result, it was confirmed that cognitive function declined in the isolation + normal diet group due to the stress associated with isolation. In contrast, in the isolation + agaricus administration group, no decline in cognitive function due to the stress associated with isolation was confirmed. In other words, it was confirmed that administration of agaricus can prevent or improve stress-related decline in cognitive function.

Claims (6)

A cognitive function improving composition for preventing or improving stress-induced cognitive decline,
A composition for improving cognitive function, comprising a processed Agaricus fruiting body. The composition for improving cognitive function according to claim 1, characterized in that the agaricus is King Agaricus 21 strain (accession number: FERM P-17695). The composition for improving cognitive function according to claim 1, characterized in that the processed material is a dried processed material. A medicine comprising the cognitive function improving composition of claim 1. A food or drink comprising the cognitive function improving composition of claim 1. A feed comprising the cognitive function improving composition of claim 1.

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