JP7258990B1 - Food composition for life extension - Google Patents

Abstract

A life-extending food composition, a life-extending agent, an anti-aging food composition, and an anti-aging agent are provided.
A life-extending food composition, a life-extending agent, an anti-aging food composition, and an anti-aging agent, characterized by containing a processed product of paramylon.
At this time, the processed product of paramylon has a median diameter of 5 times or more that of paramylon when the particle size is measured with an amorphous paramylon or a laser diffraction/scattering particle size distribution analyzer, and an optical electron microscope shows that the particles are adjacent to each other. It is preferable that the swollen paramylon is swollen by bonding with water at least four times as large as that of the paramylon.
[Selection drawing] Fig. 4

Description

TECHNICAL FIELD The present invention relates to a food composition for extending life, an agent for extending life, an anti-aging food composition and an anti-aging agent.

Healthy life expectancy is a health index advocated by WHO (World Health Organization), and indicates the period during which a person can live a healthy life while being physically and mentally independent. The difference between healthy life expectancy and average life expectancy, that is, the "unhealthy period" in which daily life is restricted, is said to be about 9 years for men and about 12 years for women in Japan.

From the viewpoint of improving QOL (Quality of life) in a super-aging society, technologies related to extension of healthy life expectancy and anti-aging are attracting attention. For the purpose of extending healthy life expectancy, extensive research has been conducted on cellular senescence and aging control mechanisms.

Patent Document 1 describes a senescent cell-removing agent containing a glutaminase inhibitor as an active ingredient, which is a drug for removing senescent cells in vivo. Patent Document 1 discloses that the glutaminase inhibitor should at least inhibit the activity of KGA (kidney-type glutaminase), and a nucleic acid such as siRNA or miRNA for knocking out the gene (GLS1) encoding KGA. It is also disclosed that it may be used as a glutaminase inhibitor.

WO2020/095971

Although the average life expectancy is increasing year by year, it is required to extend the healthy life expectancy and to extend the life span while suppressing aging. An object of the present invention is to provide a life-extending food composition, a life-extending agent, an anti-aging food composition and an anti-aging agent.

The problem is that the median diameter when the particle size is measured with a laser diffraction/scattering particle size distribution analyzer is at least five times that of paramylon, and the particles adhere to adjacent particles by an optical electron microscope. is observed, and contains a processed product of paramylon, which is a swollen paramylon that is swollen by binding water four times more than the paramylon, and suppresses the decline in motor function in middle-aged and elderly people. Life extension food compositions solve the problem .

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a life-extending food composition and a life-extending agent capable of remarkably extending life.
Moreover, according to the present invention, it is possible to provide an anti-aging food composition and an anti-aging agent capable of remarkably suppressing aging.

1 is a graph showing the effect of ingestion of paramylon on the lifespan of Drosophila melanogaster. 1 is a graph showing the effect of ingestion of paramylon on the motor function of Drosophila melanogaster. It is the graph which compared the lifetime extension effect of paramylon and the processed product of paramylon. 1 is a graph showing the effect of ingestion of a processed product of paramylon on the motor function of Drosophila melanogaster. It is a graph comparing the anti-aging effects of paramylon and a processed product of paramylon.

An embodiment of the present invention will be described below with reference to FIGS. 1 to 5. FIG. The present embodiment relates to a life-extending food composition, a life-extending agent, an anti-aging food composition and an anti-aging agent containing a processed product of paramylon.

<Life extension agent>
The agent for extending life according to the present embodiment contains a processed product of paramylon as an active ingredient and is used to extend the life. “Extending life expectancy” means extending intermediate life expectancy (the period until 50% of the population dies) and extending healthy life expectancy, which is the period during which people can become independent in mind and body and live in good health. It is a concept that includes

<Anti-aging agent>
The anti-aging agent according to this embodiment contains a processed product of paramylon as an active ingredient, and is used to suppress the progress of aging. Here, "anti-aging" is a concept that includes suppression of age-related decline in motor function.

<Euglena>
In the present embodiment, the term "euglena" includes taxonomically classified microorganisms classified into the genus Euglena, variants thereof, variants thereof, and closely related species of the family Euglenaceae. Here, the genus Euglena is a group of eukaryotic organisms belonging to Excoverta, Euglenozoa, Euglenomycetes, Euglenoides, and Euglenaceae.

Species included in the genus Euglena specifically include Euglena chadefaudii, Euglena deses, Euglena gracilis, Euglena granulata, Euglena mutabilis, Euglena proxima, Euglena spirogyra, and Euglena viridis. As Euglena, E. gracilis, particularly E. gracilis Z strain can be used, but in addition, Euglena gracilis Z strain mutant strain SM-ZK strain (chloroplast-deficient strain), variants of E. gracilis var. bacillaris, gene mutant strains such as chloroplast mutant strains of these species, and other Euglenoids such as Astasia longa.

Euglenoids are widely distributed in freshwater such as ponds and marshes, and may be used by separating from them, or any already isolated Euglenoids may be used. The genus Euglena includes all its variants. These mutant strains also include those obtained by genetic methods such as recombination, transduction, and transformation.

<Paramylon>
"Paramylon" is a porous polymer (β-1,3-glucan) in which about 700 glucoses are polymerized by β-1,3-bonds, and is a storage polysaccharide contained in the genus Euglena. is. Paramylon particles are flattened spheroidal particles and are formed by helically intertwined β-1,3-glucan chains.

Paramylon exists as granules in Euglena cells of all species and varieties, and the number, shape, and uniformity of the particles are characteristic depending on the species. Paramylon is composed only of glucose, and the average degree of polymerization of paramylon obtained from E. gracilis Z wild strain and chloroplast-deficient strain SM-ZK is about 700 in terms of glucose units. Paramylon is insoluble in water and hot water, but soluble in dilute alkali, strong acid, dimethyl sulfoxide, formaldehyde and formic acid. The average density of paramylon is 1.53 for E. gracilis Z and 1.63 for E. gracilis var. bacillaris SM-L1.

According to X-ray analysis using the powder pattern method, paramylon has a gentle helical structure in which three straight-chain β-1,3-glucans are twisted like a right-handed rope. Several of these glucan molecules aggregate to form paramylon granules. Paramylon granules have a very large crystal structure portion, accounting for about 90%, and are compounds with the highest crystal structure ratio among polysaccharides. The particle size distribution of paramylon (manufactured by Euglena Co., Ltd.) has a median diameter of 1.5 to 2.5 μm when measured with a laser diffraction/scattering particle size distribution analyzer.

Paramylon particles are isolated from cultured Euglena cells by any appropriate method and purified into fine particles, and are usually provided as powder. For example, paramylon particles can be (1) cultured Euglena cells in any appropriate medium, (2) separation of Euglena cells from the medium, (3) isolation of paramylon from the separated Euglena cells, ( 4) purification of the isolated paramylon, and optionally (5) cooling and subsequent lyophilization. Isolation of paramylon is performed, for example, using non-ionic or anionic detergents of the type that are largely biodegradable. Purification of paramylon occurs substantially simultaneously with isolation.

<Processed products of Paramylon>
Processed products of paramylon include water-soluble paramylon obtained by chemically or physically treating paramylon by various known methods, sulfated paramylon, and paramylon derivatives. Examples of processed products of paramylon include amorphous paramylon and emulsion paramylon.

(amorphous paramylon)
Amorphous paramylon is a substance obtained by amorphizing crystalline paramylon derived from Euglena. Amorphous paramylon has a relative crystallinity of 1 to 20% with respect to crystalline paramylon produced from Euglena by a known method. However, this relative crystallinity is obtained by the method described in JP-A-2011-184592.

That is, amorphous paramylon and paramylon were each pulverized with a pulverizer (ball mill MM400 manufactured by Retsh) for 5 minutes at a frequency of 20 times/second, and then analyzed using an X-ray diffractometer (H'PertPRO manufactured by Spectris). At a voltage of 45 KV and a tube current of 40 mA, scanning is performed in the range of 2θ from 5° to 30° to obtain diffraction peaks Pc and Pa near 2θ=20° of paramylon and amorphous paramylon. Using the values of Pc and Pa, the relative crystallinity of amorphous paramylon is calculated by the relative crystallinity of amorphous paramylon=Pa/Pc×100 (%).

Amorphous paramylon is prepared according to the method described in JP-A-2011-184592 by subjecting crystalline paramylon powder to alkali treatment, followed by neutralization with acid, followed by washing, water removal, and drying. Processed products of paramylon also include water-soluble paramylon obtained by chemically or physically treating paramylon by various known methods, sulfated paramylon, and paramylon derivatives.

(swelling paramylon, emulsion paramylon)
“Swollen paramylon” is a substance called emulsion paramylon because its processing method and physical properties are similar to emulsions, and is obtained by adding water to paramylon according to the method described in JP-A-2016-199650. It is processed paramylon that is swollen by bonding with water four times or more, obtained by performing a collision treatment in which the fluid is ejected from a fine nozzle at an ultrahigh pressure to collide with an object to be collided.

Swollen paramylon is a known physical property modifier that ejects a slurry obtained by adding a water-soluble solvent to a solid such as powder at an ultrahigh pressure from a fine-pore nozzle to collide with an object to be collided (for example, JP-A-2011-88108 It can be obtained by performing collision treatment one or more times at a nozzle pressure of 245 MPa at the time of jetting using a device described in Japanese Patent Application Laid-Open No. 6-47264.

The swollen paramylon has a median diameter of 5 times or more that of paramylon and 7 μm or more when the particle size is measured with a laser diffraction/scattering particle size distribution analyzer, and the particles are separated from adjacent particles by an optical electron microscope. Adhesion was observed, and it swelled by binding with water four times or more that of paramylon.

Slurry, which is a mixture of raw material paramylon and water, is a free-flowing fluid, but the swollen paramylon has a viscosity that increases as paramylon disperses in water molecules and sticks to hands when touched. It has excellent stickiness and elasticity, and has a paste-like feel. The processed paramylon obtained is called emulsion paramylon in this specification because of its processing method and physical properties, but it is unknown whether or not it is emulsified. is.

<Application>
The agent for extending life and the anti-aging agent according to the present embodiment are configured as a food composition such as a health food or a pharmaceutical composition, and are used, ingested, and administered prophylactically in order to extend life while suppressing aging. be done. Paramylon can be ingested as a food and has no side effects, so it can be used, ingested, and administered continuously.

(Food composition)
In the field of foods, the life-extending agent and anti-aging agent of the present embodiment can be obtained by adding an effective amount of processed paramylon to various foods as a food material that can effectively exhibit life-extending action and anti-aging action. It is possible to provide a food composition having the effect. That is, the present invention can provide food compositions labeled as anti-aging or the like in the field of foods. Examples of the food composition include general foods, foods for specified health uses, foods with nutrient function claims, foods with function claims, foods for hospital patients, supplements, and the like. It can also be used as a food additive.

Examples of the food composition include seasonings, processed meat products, processed agricultural products, beverages (lactic acid beverages, soft drinks, alcoholic beverages, carbonated beverages, milk beverages, fruit juice beverages, tea, coffee, nutritional drinks, etc.), powders Beverages (powdered juice, powdered soup, etc.), concentrated drinks, confectionery (candies, cookies, biscuits, gums, gummies, chewables, tablets, chocolate, etc.), breads, cereals and the like. In the case of food for specified health uses, food with nutrient function claims, food with function claims, etc., the shape may be capsule, troche, syrup, granule, powder, or the like.

Foods for Specified Health Uses are foods that contain functional health ingredients that affect physiological functions, etc., and can be labeled as suitable for specific health uses with the permission of the Director-General of the Consumer Affairs Agency. be. In the present invention, it is a food product that is marketed with an indication of specific anti-aging health uses.

A food with nutrient function claims is a food that is used to supplement nutritional ingredients (vitamins and minerals), and the functions of the nutritional ingredients are indicated. In order to be sold as a food with nutrient function claims, the amount of nutrients contained in the recommended daily intake must be within the specified upper and lower limits. also need to

Foods with function claims are foods labeled with functionalities based on scientific evidence under the responsibility of the business operator. Information on the grounds for safety and functionality was submitted to the Commissioner of the Consumer Affairs Agency before sales.

In the food composition according to the present embodiment, in addition to the processed product of paramylon, it is possible to freely select and add one or more components that can be used in ordinary food compositions. For example, all additives that can be commonly used in the food field, such as various seasonings, preservatives, emulsifiers, stabilizers, fragrances, coloring agents, preservatives, and pH adjusters, can be included.

(Pharmaceutical composition)
In the field of medicine, the life-extending agent and anti-aging agent of the present embodiment contain a processed product of paramylon in an amount that can effectively exhibit life-extending action and anti-aging action, together with pharmaceutically acceptable carriers and additives. By blending, a pharmaceutical composition having the action is provided. The pharmaceutical composition may be a drug or a quasi-drug.

The pharmaceutical composition is preferably applied internally (particularly orally), but may be applied externally. Therefore, the pharmaceutical composition is used in the form of an oral preparation, an injection such as an intravenous injection, a subcutaneous injection, an intradermal injection, an intramuscular injection and/or an intraperitoneal injection, a transmucosal application, a transdermal application, and the like. be able to. The dosage form of the pharmaceutical composition can be appropriately set depending on the application form. Semi-solid formulations such as ointments or gels are included.

The pharmaceutical composition according to this embodiment can contain one or more pharmaceutically acceptable additives by freely selecting them. For example, when the pharmaceutical composition according to this embodiment is applied to an oral formulation, for example, excipients, binders, disintegrants, surfactants, preservatives, coloring agents, flavoring agents, fragrances, stabilizers, preservatives All additives that can be commonly used in the field of pharmaceutical formulations, such as agents, antioxidants, etc., can be contained. In addition, a drug delivery system (DDS) can be used to prepare a sustained-release preparation or the like.

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

<Production Example 1: Paramylon>
Paramylon as a Euglena-derived substance was prepared by the following procedure.
Euglena gracilis powder (manufactured by Euglena Co., Ltd.) was added to distilled water and stirred at room temperature for 2 days. This was sonicated to destroy cell membranes, and crude paramylon particles were collected by centrifugation. The recovered paramylon particles were dispersed in a 1% sodium dodecylsulfate aqueous solution and treated at 95°C for 2 hours, and the paramylon particles recovered by centrifugation again were dispersed in a 0.1% sodium dodecylsulfate aqueous solution and treated at 50°C for 30 minutes. bottom. Lipids and proteins were removed by this operation, then washed with acetone and ether, and dried at 50° C. to obtain purified paramylon particles (paramylon powder).

<Production Example 2: Amorphous Paramylon>
Amorphous paramylon (paramylon treated with alkali) as a Euglena-derived substance was prepared by the following procedure.
5% (w/v) of the paramylon powder prepared in Production Example 1 was added to a 1N sodium hydroxide aqueous solution to dissolve it, stirred with a stirrer for 1 to 2 hours, and treated with an alkali. Thereafter, 1N hydrochloric acid was added dropwise to the 1N sodium hydroxide aqueous solution in which the paramylon powder was dissolved for neutralization. After centrifugation, the supernatant was discarded, and after repeating the steps of washing the precipitate with distilled water, the precipitated gel was collected, frozen, and freeze-dried with a freeze dryer to obtain amorphous paramylon.

<Production Example 3: Emulsion Paramylon>
Emulsion paramylon (swollen paramylon) was prepared by the following procedure using the paramylon prepared in Production Example 1.
Ion-exchanged water was added to crystalline paramylon powder (manufactured by Euglena Co., Ltd.) to obtain a paramylon slurry having a paramylon concentration of 10 wt %. The inside of the device circuit of a wet atomization device (Starburst 18KW medium-sized machine, manufactured by Sugino Machine Co., Ltd., oblique collision chamber) was replaced with ion-exchanged water. The nozzle of the device was pressurized to feed the paramylon slurry into the circuit, and the initial discharge liquid was discarded as dead volume in the circuit. After that, the jets of the paramylon slurry were ejected from a pair of nozzles facing each other at an angle, and the jets collided with each other by oblique collision. The processed slurry was collected from the outflow channel to make one pass. At this time, the treatment pressure was 245 MPa, the slurry treatment amount was 240 mL, and the nozzle diameter was 0.17 mm. This treatment was repeated three times for three passes to obtain an emulsion paramylon. The emulsion paramylon of Example 4 did not separate from the ion-exchanged water added during preparation of the slurry, but bound with water and swelled.

In the following tests, the effects of oral intake of paramylon and its processed products on life span were evaluated.

<Test 1: Effect of ingestion of paramylon on the life span of Drosophila melanogaster>
The survival rate was compared between Drosophila melanogaster fed with feed containing paramylon (Production Example 1) after emergence and Drosophila melanogaster fed with normal feed (control group). As a result, in the Drosophila melanogaster fed with the diet containing 1% or 3% paramylon, the intermediate lifespan was prolonged compared to the control group (5YE) (Fig. 1). Ingestion of paramylon extended the intermediate lifespan (time before 50% of the population died) in Drosophila melanogaster. Furthermore, when the paramylon content was adjusted to various concentrations (0.1 to 3%) and examined, it was found that, in particular, Drosophila melanogaster fed a diet containing 3% paramylon had an intermediate lifespan compared to the control group. It became 49 days, which is long by about two weeks, and the extension was remarkable, and a strong anti-aging effect was observed.

<Test 2: Effect of ingestion of paramylon on motor function of Drosophila melanogaster>
In the same manner as in Test 1, Drosophila was given a diet containing 0.1 to 3% paramylon (Production Example 1), and on days 7, 14, 21, 28, 35, and 42, exercise associated with aging Functional decline was assessed by the climbing assay. The climbing assay is a method of assessing age-related decline in motor function and symptoms of neurodegenerative diseases such as Alzheimer's disease. In the climbing assay, a fly was placed in a vial, the vial was tapped to place the fly at the bottom of the vial, and the fly was able to climb above the 3 cm line from the bottom of the vial within 10 seconds. was counted and the ratio was calculated.

In the control group, motor function decreased with age, but in the Drosophila melanogaster fed the diet containing paramylon, the decrease in motor function was suppressed. Paramylon was observed to significantly suppress the decline in motor function on the 28th and 35th days, which corresponds to the middle-aged stage of Drosophila. In particular, strong anti-aging effects were observed in Drosophila melanogaster fed with feed containing 3% paramylon (Fig. 2).

<Summary of test 1 and test 2>
In the Drosophila melanogaster that did not ingest paramylon-containing food, the survival rate was about 50% on the 35th day, and motor function decreased with age. On the other hand, in Drosophila melanogaster fed a diet containing 3% paramylon, not only did the intermediate lifespan extend by about two weeks, but also it was confirmed that age-related decline in motor function was suppressed. In other words, by ingesting food containing paramylon, more Drosophila lived longer, and more individuals were observed to maintain their motor functions, suggesting that ingestion of paramylon extended the healthy life span of Drosophila melanogaster. was suggested.

<Test 3: Effect of intake of processed products of paramylon on lifespan of Drosophila melanogaster>
In the same manner as in Test 1, Drosophila melanogaster was fed feed containing paramylon (manufacturing example 1), amorphous paramylon (manufacturing example 2), and emulsion paramylon (manufacturing example 3) after emergence, and normal feed was fed. The survival rate of Drosophila melanogaster (control group) was compared. In the emulsion paramylon group or the amorphous paramylon group, an extension of median life span was observed as compared with the control group. In addition, the average life spans of emulsion paramylon and amorphous paramylon were extended by 5.7 days and 6.9 days, respectively, compared to the control group (5YE) (Fig. 3).

<Test 4: Effects of ingestion of processed products of paramylon on motor functions of Drosophila melanogaster>
In the same manner as in Test 1, Drosophila were given feed containing 5% paramylon (Production Example 1), amorphous paramylon (Production Example 2), and emulsion paramylon (Production Example 3). On days 35, 42 and 49, age-related decline in motor function was assessed by climbing assay.

In the emulsion paramylon group, significant suppression of motor function decline was observed on the 14th, 21st, 28th and 35th days (Fig. 4). In the amorphous paramylon group, significant suppression of motor function decline was observed on the 28th, 35th, and 42nd days. In the paramylon group, significant suppression of motor function decline was observed on the 14th, 21st, and 28th days.

When the anti-aging effects were compared between the groups, the emulsion paramylon group and the amorphous paramylon group exhibited a more pronounced anti-aging effect than the paramylon group on day 35, which corresponds to the middle-aged stage of Drosophila (Fig. 5). ). Specifically, on the 35th day, the paramylon group increased by 3.809% compared to the control group, but the emulsion paramylon group increased by 19.92% (5.2 times that of the paramylon group), and amorphous The paramylon group had an increase of 17.74% (4.7 times that of the paramylon group).

On the 42nd day when aging further progressed, the amorphous paramylon group maintained motor function, and a higher anti-aging effect was observed than the emulsion paramylon group and the paramylon group.

<Summary of test 1 to test 4>
Based on the above results, oral intake of processed paramylon products such as amorphous paramylon and emulsion paramylon not only significantly extended life span compared to paramylon, but also significantly suppressed the decline in motor function due to aging. was confirmed. In other words, it was shown that processed products of paramylon can remarkably suppress deterioration of motor function and remarkably extend life span, that is, remarkably prolong healthy life expectancy.

Claims (1)

The median diameter when the particle size is measured with a laser diffraction/scattering particle size distribution analyzer is at least 5 times that of paramylon, and the particles are observed to adhere to adjacent particles by an optical electron microscope, Containing a processed product of paramylon, which is swollen paramylon that is swollen by binding water at least four times as much as the paramylon,
A food composition for extending lifespan characterized by suppressing deterioration of motor function in middle-aged and elderly people .

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