JP2022048337A - Composition for autonomic nerve regulation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel composition for autonomic nerve regulation that can effectively regulate autonomic nerves and can be ingested on a daily basis.

SOLUTION: Provided is a composition for autonomic nerve regulation comprising diketopiperazines or salts thereof as an active ingredient.

SELECTED DRAWING: Figure 1

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention relates to a composition for autonomic nervous regulation.

Stress has become a major problem in modern society. In order to keep the homeostasis of the living body constant against various external changes including stress, the autonomic nervous system, the endocrine system, the immune system, etc. interact with each other to maintain a balance. Among these,
It can be said that the most important system in the living body is the autonomic nervous system.

The autonomic nervous system unconsciously regulates the activity of organs in response to the external and internal environment, regardless of conscious control. This autonomic nervous system is composed of a sympathetic nervous system whose activity increases in a tense state and a parasympathetic nervous system whose activity increases in a relaxed state such as during relaxation.

The two types of autonomic nervous system respond to changes in the external environment such as temperature and mental stress and changes in the internal environment such as nutritional status, and each of them works antagonistically to make the body respond to these changes. .. It is said that if the patient continues to be exposed to excessive stress at this time, the balance of the autonomic nerves is disturbed, causing autonomic nervous system imbalance represented by poor physical condition such as insomnia. On the other hand, activation of the sympathetic nerve can be expected to have the effects of clearing the head, reducing drowsiness, and maintaining concentration. Therefore, it is desired to provide a safe and convenient method for regulating the autonomic nerve.

In recent years, methods using scents such as aromatherapy have been widely used. Aromatherapy is a method for improving these symptoms by sucking or applying an aroma component contained in an essential oil or the like in order to relieve or calm the tension of the sympathetic nerve. This is because the aroma component absorbed through the nose or lungs acts on the autonomic nerves via the hypothalamus of the cerebrum.

Further, exchange nerve activating fragrance compositions using fragrance compositions such as grapefruit oil, fennen oil, and pepper oil have been proposed (Patent Documents 1 and 2). Further, for the purpose of continuing the activation of the sympathetic nerve, a sympathetic nerve activating cloth cotton containing a sympathetic nerve activating composition in the cloth has been proposed (Patent Document 3).

However, the method using a fragrance or a flavor composition has a large effect on the taste, and its use in food and drink is limited. In addition, the ingredients used for aromatherapy are not always ingredients for food use that can be taken orally.

In addition, a heat-producing sympathetic nerve activator using a plant extract (see Patent Documents 4 and 5) and activation of brown adipocyte sympathetic nerves by flavangenol (see Non-Patent Document 1) have been proposed. However, these are limited to the sympathetic nerves of the heat-producing system, and the obtained effect is limited to the slimming effect.

On the other hand, Patent Document 6 relates to a psychological state improving agent containing iso-alpha acid or reduced iso-alpha acid as an active ingredient, and this document describes the effect of ingesting iso-alpha acid together with ethanol. Are listed.

JP-A-2002-193824 Japanese Unexamined Patent Publication No. 2002-265977 Japanese Unexamined Patent Publication No. 2004-250804 Japanese Unexamined Patent Publication No. 2004-51486 Japanese Unexamined Patent Publication No. 2004-115440 Japanese Unexamined Patent Publication No. 2010-209022

Biosci Biotechnol Biochem. 2009 Nov; 73 (11): 2374-8

An object of the present invention is to provide a novel composition for autonomic nerve regulation that can effectively regulate autonomic nerves and can be ingested on a daily basis.

As a result of diligent studies to solve the above problems, the present inventors have found that administration of diketopiperazines can activate or suppress the activity of skin sympathetic nerves, and based on this finding. The present invention was completed.

That is, the present invention is as follows.
[1] A composition for autonomic nervous regulation containing diketopiperazines or a salt thereof as an active ingredient.
[2] The composition for autonomic nervous regulation according to [1], wherein diketopiperazines or a salt thereof is a roasting component.
[3] The composition for autonomic nervous regulation according to [1] or [2], wherein the diketopiperazines are cyclic dipeptides.
[4] The composition for autonomic nervous regulation according to [3], wherein the cyclic dipeptide contains at least proline as a constituent unit.
[5] The composition for autonomic nervous regulation according to [4], wherein the cyclic dipeptide is cyclo-prolyl-phenylalanine or cyclo-prolyl-proline.
[6] The composition for autonomic nervous regulation according to [5], wherein the autonomic nervous regulation is sympathetic nerve activation and the cyclic dipeptide is cyclo-prolyl-phenylalanine.
[7] The composition for autonomic nerve regulation according to [5], wherein the autonomic nerve regulation is sympathetic nerve suppression and the cyclic dipeptide is cyclo-prolyl-proline.
[8] The composition for autonomic nerve regulation according to any one of [1] to [7], which is a food and drink composition.
[9] The composition for autonomic nerve regulation according to any one of [1] to [7], which is a pharmaceutical composition.
[10] An autonomic nerve regulating agent containing diketopiperazines or a salt thereof as an active ingredient.

The composition for autonomic nerve regulation of the present invention has an excellent autonomic nerve regulation action, and can effectively function as a means for safely and easily regulating the balance of autonomic nerves.

FIG. 1 shows the skin sympathetic nerve when a 3 ppm (w / v) aqueous solution of cyclo-prolyl-phenylalanine [Cyclo (L-Pro-L-Phe)] was intragastrically administered to a rat at a dose of 1 ml / 300 g body weight. It is a graph which shows the time-dependent change of activity (cutaneous artificial nervous activity, CASNA). The vertical axis shows the percentage when the value before the start of stimulation (0 minute value) is set to 100%. The horizontal axis shows the elapsed time (minutes) after administration of the sample. The white triangle is a graph when cyclo-prolyl-phenylalanine is administered, and the black rhombus is a graph when water is used as a control. FIG. 2 shows the skin sympathetic nerve when a 3 ppm (w / v) aqueous solution of cyclo-prolyl-proline [Cyclo (L-Pro-L-Pro)] was intragastrically administered to a rat at a dose of 1 ml / 300 g body weight. It is a graph which shows the time-dependent change of activity (cutaneous artificial nervous activity, CASNA). The vertical axis shows the percentage when the value before the start of stimulation (0 minute value) is set to 100%. The horizontal axis shows the elapsed time (minutes) after administration of the sample. Black circles are graphs when cyclo-prolyl-proline is administered, and black diamonds are graphs when water is used as a control.

The composition for autonomic nervous regulation according to the present invention (hereinafter, also referred to as the composition of the present invention) contains diketopiperazines or a salt thereof as an active ingredient.

In the present invention, "autonomic nervous regulation" means to improve the disorder of the autonomic nervous system, and suppresses sympathetic nerve activity (sympathetic nerve suppression) or suppresses sympathetic nerve activity in a subject whose sympathetic nervous activity is higher than usual. It is defined by observing a phenomenon that activates sympathetic nerve activity (sympathetic nerve activation) in a subject whose sympathetic nerve activity is lower than usual. The phenomenon can be evaluated by determining the activity of the sympathetic nerve by the method described later in the examples.

Examples of the sympathetic nerve include adrenal gland, cutaneous artery, brown adipose tissue, white adipose tissue, liver, spleen, pancreas, sympathetic nerve that controls the kidney, and the like.

The salt of diketopiperazines refers to any pharmacologically acceptable salt of diketopiperazines (including inorganic and organic salts), for example, sodium salt, potassium salt, calcium salt, etc. of diketopiperazines. Magnesium salts, ammonium salts, hydrochlorides, sulfates, nitrates, phosphates and organic acid salts (eg acetates, citrates, maleates, malate, oxalates, lactates, succinates, fumals) Examples thereof include, but are not limited to, acid salts, propionates, nitates, benzoates, picrates, benzenesulfonates, etc.). Salts of diketopiperazines can be prepared by methods known in the art.

The diketopiperazines are preferably cyclic dipeptides. What is a cyclic dipeptide?
It is a compound obtained by dehydration condensation and cyclization of two amino acid molecules. The cyclic dipeptide preferably contains at least one amino acid selected from proline, phenylalanine, leucine, tyrosine, tryptophan, valine, isoleucine, histidine, alanine, glycine and methionine as a constituent unit, and more preferably contains at least proline as a constituent unit. preferable.

Examples of the cyclic dipeptide include cyclo-prolyl-phenylalanine [Cyclo].
(Pro-Phe)], cyclo-prolyl-leucine [Cyclo (Pro-Leu)]
, Cyclo-Prolyl-Proline [Cyclo (Pro-Pro)], Cyclo-Prolyl-
Tyrosine [Cyclo (Pro-Tyr)] and cyclo-prolyl-tryptophan [C
iclo (Pro-Trp)], cyclo-prolyl-valine [Cyclo (Pro-Va)
l)], cyclo-prolyl-isoleucine [Cyclo (Pro-Ile), cyclo-prolyl-histidine [Cyclo (Pro-His)], cyclo-prolyl-alanine [
Cyclo (Pro-Ala)], cyclo-prolyl-glycine [Cyclo (Pro-)
Gly)] and cyclo-prolyl-methionine [Cyclo (Pro-Met)]. Among these, cyclo-prolyl-phenylalanine and cyclo-prolyl-proline are preferable from the viewpoint of the autonomic nervous regulation effect. These may be used alone or in combination of two or more.

In particular, if the autonomic regulation is sympathetic activation, the cyclic dipeptide is preferably cyclo-prolyl-phenylalanine. Further, when the autonomic nerve regulation is sympathetic nerve suppression, the cyclic dipeptide is preferably cyclo-prolyl-proline. These may be used alone or in combination.

In the present specification, as long as the amino acid composition of the cyclic dipeptide is the same, the order of description thereof may be any first, for example, Cyclo (Pro-Phe) and Cyclo.
o (Phe-Pro) represents the same cyclic dipeptide. The cyclic dipeptide may be a cis form or a trans form.

The diketopiperazines or salts thereof used in the present invention can be prepared according to a method known in the art. For example, it may be produced by a chemical synthesis method, an enzymatic method or a microbial fermentation method, and JP-A-2003-252896, Journal of Peptide Science, 10, 737-737,
It can be prepared according to the method described in 2004, Japanese Patent Application Laid-Open No. 2014-125427.

As the diketopiperazines or salts thereof, commercially available synthetic reagents may be used, but from the viewpoint of safety, those extracted from natural products are preferable. Specific examples of the method for obtaining diketopiperazines or salts thereof from natural products include, for example, a method for obtaining diketopiperazines or salts thereof as a roasting component by roasting food and drink raw materials, and foods and drinks. Examples thereof include a method of obtaining diketopiperazines or a salt thereof by heat-treating, aging, or enzymatically treating the raw material.

As the food and drink raw material, a food and drink raw material containing a large amount of protein is preferable, and examples thereof include plant raw materials, dairy raw materials, animal and poultry meats, fish and shellfish, shellfish and eggs. Among these, plant raw materials and dairy raw materials are preferable from the viewpoint of productivity.

The plant raw material may be any plant-derived material generally used for producing foods and drinks, and is not particularly limited. Examples thereof include grains, beans, teas and herbs, and beans are used from the viewpoint of productivity. preferable.

Examples of grains include barley (eg, Nijo barley, 6-row barley, bare barley, etc.), wheat, barley, roasted rice, raw brown rice, germinated brown rice, ancient rice (eg, black rice, red rice, green rice, etc.), etc. Examples include buckwheat, white rice, corn, sweet potato, black sesame and white sesame. As beans, for example
Examples include coffee beans, cocoa beans, black soybeans, broad beans, chick beans, green beans and red beans. Examples of teas include green tea leaves, oolong tea leaves and black tea leaves. Examples of herbs include chicory roots and dandelion roots.

Milk raw materials include, for example, milk, processed milk, cream, concentrated milk, defatted milk powder called milk powder, whole milk powder, prepared milk powder, prepared defatted milk powder, sweetened milk, sugar-free milk, fermented milk, butter, butter oil, etc. Examples include cheese, ice cream and whey powder.

Examples of animal and poultry meat include cattle, pigs, horses, sheep and goats, which are livestock meat, meat other than livestock meat (for example, wild boar and deer, etc.), poultry chicken, turkey, quail, duck, and duck. Meat of birds other than poultry meat which is wild poultry meat (for example, duck, pheasant, sardine, tsugumi, etc.) and the like can be mentioned.

Examples of fish and shellfish include fish and shellfish and shellfish that are eaten in a general diet. Examples of eggs include chicken eggs and quail eggs. The food and drink ingredients can be used alone or in combination of two or more.

In the present invention, the roasting component includes components produced by roasting the above-mentioned food and drink raw materials, for example, a bitterness component, a sweetness component, a rich taste component, an aroma component, and a coloring component. The roasting component can be obtained, for example, by treating the food and drink raw materials in the order of the roasting step and the extraction step. The roasting step is a step of roasting food and drink raw materials to generate roasting components in the food and drink raw materials. As the roasting method, a roasting method and a roasting machine known in the art can be used.

Examples of the roasting method include open flame, hot air, far infrared rays, and microwaves, if classified according to the heating method. Examples of the roasting machine include a continuous flow type roasting machine and a rotary drum type roasting machine.

In the roasting step, the type of roasted component obtained can be adjusted by adjusting the roasting degree (L value) of the food and drink raw material. Specifically, for example, when the raw material for food and drink is six-row barley, diketopiperazines can be obtained as a roasting component by setting the L value to 17 to 40. Here, the L value is a numerical value representing brightness by a colorimetric method in which black is 0 and white is 100, and can be measured by an L value meter.

The extraction step is a step of extracting the roasted components by subjecting the above-mentioned roasted food and drink raw materials to an extraction process. As the extraction method, an extraction method known in the art can be used. When the roasting component is a water-soluble component such as diketopiperazines, examples of the extraction method include immersion extraction and drip extraction. When the roasting component is a water-soluble component, the extraction solvent used in the extraction step is not particularly limited as long as it is a solvent suitable for extraction, but is preferably an aqueous solvent, and water can be used most conveniently.

The water may be of any water quality that can be used for food treatment, for example, distilled water, desalted water, alkaline ionized water, deep ocean water, ion-exchanged water, deoxidized water and water-soluble organic compounds (eg, alcohols). ) Or water containing inorganic salts, but pure water is preferably used.

According to a preferred embodiment, the extraction step is preferably 10 relative to the mass of roasted food and drink ingredients.
It is preferable to add an extraction solvent having a mass of 0 to 1000%, more preferably 200 to 500%, and keep the roasted food and drink raw materials immersed in the extraction solvent. The immersion state is preferably maintained for 1 to 60 minutes, more preferably 5 to 50 minutes from the start of charging the extraction solvent. The extraction step may be allowed to stand or may be stirred. In the extraction step, extraction conditions can be set according to the form of the apparatus used in the extraction step, the type of the extraction solvent, the amount of addition, and the like.

In order for the diketopiperazines or salts thereof to act effectively, the content of the active ingredient diketopiperazines or salts thereof (in the case of containing a plurality of types, the total conversion thereof) is preferable. 0.000000001% by mass or more, more preferably 0.00000
It is 01 to 0.0001 mass%.

The form of use of the composition of the present invention is not particularly limited, and for example, a food or drink composition, an additive used for blending in the food or drink composition, a pharmaceutical composition, or a pharmaceutical composition thereof. Examples thereof include additives used in the above. The composition of the present invention is not particularly limited in its form, and may be in the form of granules, granules, pastes, gels, liquids, semi-liquids, or solids.

The composition of the present invention may be used not only for humans but also for pet animals (for example, dogs, cats, reptiles, birds and fish, etc.), livestock (including poultry), farmed fish and the like. In addition to the above active ingredients, the composition of the present invention may further contain other components that regulate the autonomic nerves.

The food and drink composition in the present invention includes so-called health foods, functional foods, nutritional supplements, and supplements, and has health functional foods such as foods with a disease risk reduction label (for example, foods for specified insurance, nutritional functions). (Sex foods and foods with functional claims, etc.), foods for the sick and food additives are also included.

Specific examples of the food and beverage composition include liquid foods such as drinks, soups, non-alcoholic beverages, alcoholic beverages, jelly-like beverages and functional beverages; semi-solid foods such as jelly and yogurt; miso and fermented beverages, etc. Fermented foods; Western confectionery such as cookies and cakes, Japanese confectionery such as buns and sheep, various confectionery such as candy, gums, gummy, chilled confectionery and ice confectionery; Products; Rice, rice cakes, noodles,
Carbohydrate-containing foods such as bread and pasta; Processed livestock foods such as ham and sausage; Processed marine foods such as kamaboko, dried fish and salted foods; Processed vegetable foods such as pickles; Retort products such as curry, ankake and Chinese soup; Instant Instant foods such as soups and instant miso soups; Convenience foods; Processed eggs and processed seafood or livestock meats; Seasonings;
And so on. Further, healthy foods and drinks prepared in the form of powder, granules, tablets, capsules, liquid, paste or jelly can be mentioned. The food and drink composition in the present invention can be produced by a production technique known in the art.

Non-alcoholic beverages include, for example, mineral water, near water, sports drinks, tea beverages, dairy beverages, refreshing beverages, coffee beverages, fruit juice-containing beverages, vegetable juice-containing beverages, fruit juice and vegetable juice beverages, carbonated beverages and alcohol. Examples include, but are not limited to, beer-taste beverages that do not contain. A beer beverage having an alcohol content of less than 1%, such as non-alcoholic beer, may be used. Mineral water includes both effervescent and non-effervescent mineral water.

The tea beverage refers to a beverage extracted from the leaves (tea leaves) of a tea plant, which is an evergreen tree of the family Tea plant, or the leaves or grains of plants other than the tea plant, and is either fermented tea, semi-fermented tea or non-fermented tea. Is included. Examples of tea beverages include Japanese tea (eg, green tea and barley tea, etc.), black tea, herbal tea (eg, jasmine tea, etc.), Chinese tea (eg, Chinese green tea, Karyu tea, etc.), and the like.
Hojicha and the like can be mentioned.

The milk beverage refers to a beverage whose main raw material is raw milk, milk, or a food produced from these, and in addition to those made from milk itself, for example, nutrient-enriched milk, flavor-added milk, and sweetened decomposition. Those made from processed milk such as milk are also included.

Examples of fruits used in the beverage containing fruit juice or the beverage containing fruit juice or vegetable juice include apples, oranges, grapes, bananas, pears, peaches, mangoes, acai and blueberries. Examples of the vegetables used in the beverage containing vegetable juice or the beverage containing fruit juice or vegetable juice include tomatoes, carrots, celery, pumpkins and cucumbers.

When used as a food and drink composition, the intake of diketopiperazines or salts thereof, which are active ingredients, is usually preferably 10 to 1000 μg per adult per day, more preferably 100.
It is up to 500 μg, and even more preferably 200 to 300 μg (when a plurality of types are included, the total conversion).

In addition, when used as a food and drink composition, diketopiperazines or salts thereof (in the case of containing a plurality of types, the total conversion thereof) is 10 to 1 in a container subdivided into one serving or one serving.
The form containing 000 μg is preferable, the form containing 100 to 500 μg is more preferable, and the form containing 200 to 300 μg is more preferable.

Diketopiperazines or their salts have an autonomic nervous regulation effect even when taken once, but if the balance of the autonomic nerves can be adjusted appropriately by continuously taking them as a food and drink composition, stress etc. It is also possible to reduce the vulnerability to environmental factors, that is, to make it resistant to stress.

The pharmaceutical composition contains diketopiperazines or salts thereof as an active ingredient, and is a carrier, an excipient, etc.
It can be produced by mixing a binder, a diluent and the like. It can be administered orally or parenterally, and in the case of oral administration, it may be in any form such as granules, powders, tablets, pills, capsules or syrups. In addition, as an administration form for parenteral use,
Examples thereof include, but are not limited to, external preparations such as injections, infusions and nasal administration preparations.

When used as a pharmaceutical composition, the dose thereof varies depending on the dosage form, age, body weight of the patient, nature or severity of the symptom to be treated, etc., but in the case of oral administration, diketopiperazines or salts thereof. The dose is usually preferably 10 to 1000 μg per adult per day, more preferably 100 to 500 μg, still more preferably 200 to 300 μg (when a plurality of types are included, the total conversion thereof). In the case of parenteral administration, for example, intravenous administration, the dose of diketopiperazines or salts thereof is preferably 10 to 1000 μg, more preferably 100 to 500 μg, still more preferably 200 to 300 μg per adult per day. be(
If multiple types are included, the total conversion). With regard to these doses, the optimum form may be appropriately selected depending on various conditions.

Example 1: Activation effect of skin sympathetic nerve activity by diketopiperazines In the experiment, the animals were bred in a warm-blooded animal room at 24 ° C. for 1 week or more under a light-dark cycle (lights up from 8:00 to 20:00) every 12 hours. A Wistar male rat (about 9 weeks old) weighing about 300 g was used.
On the day of the experiment, after fasting for 3 hours, urethane anesthesia was performed, a cannula for intragastric administration was inserted, and the distal branch of the cutaneous arterial sympathetic nerve of the right thigh was lifted by a silver electrode, and the electrical activity of the nerve was measured.

Cyclo (L-) using a cannula when these measured values settled down (around 13:00)
A 3 ppm aqueous solution of Pro-L-Phe) was intragastrically administered at a dose of 1 ml / 300 g body weight, and the changes in these cutaneous arterial sympathetic nerve activities generated at that time were electrophysiologically measured over 90 minutes. The Cyclo (L-Pro-L-Phe) 3 ppm aqueous solution used here is Cy.
Clo (L-Pro-L-Phe) (manufactured by Peptide Institute) was diluted with water to a concentration of 3 ppm (w / v). As a control experiment, water was intragastrically administered at a dose of 1 ml / 300 g body weight, and the change in cutaneous arterial sympathetic nerve activity generated at that time was electrophysiologically measured for 90 minutes.

From the start of surgery to the end of measurement, a tube was inserted into the trachea to secure the airway, and a heat insulating device was used to keep the body temperature (rat rectal temperature) at 35.0 ± 0.5 ° C.

The obtained cutaneous artery sympathetic nerve activity data shows the firing frequency per 5 seconds every 5 minutes (pul).
It was analyzed by the average value of se / 5s) and expressed as a percentage with the value (0 minute value) before the start of stimulation as 100%. In addition, the mean value ± standard error is calculated from the data, and the test of statistically significant difference as a group is analyzed by variance (ANOVA) with rep.
It was performed by eated causes. The results are shown in FIG.

As shown in FIG. 1, the CASNA value between 5 minutes and 90 minutes after the start of gastric administration is Cyc.
Comparing the two groups, the lo (L-Pro-L-Phe) -administered group and the water-administered group, by statistical examination, the CASNA value of the Cyclo (L-Pro-L-Phe) -administered group is the CASNA value of the water-administered group.
It was revealed that the value was significantly higher than the NA value (p <0.01, One way ANOVA). From this result, it was found that Cyclo (L-Pro-L-Phe) has an effect of exciting the skin sympathetic nerve.

Example 2: Suppressive effect of skin sympathetic nerve activity by diketopiperazines In the experiment, the body weight was bred in a constant temperature animal room at 24 ° C. under a light-dark cycle (lights from 8:00 to 20:00) every 12 hours for 1 week or more. About 300 g of Wistar male rats (about 9 weeks old) were used.
On the day of the experiment, after fasting for 3 hours, urethane anesthesia was performed, a cannula for intragastric administration was inserted, and the distal branch of the cutaneous arterial sympathetic nerve of the right thigh was lifted by a silver electrode, and the electrical activity of the nerve was measured.

Cyclo (L-) using a cannula when these measured values settled down (around 13:00)
A 3 ppm aqueous solution of Pro-L-Pro) was intragastrically administered at a dose of 1 ml / 300 g body weight, and the changes in these cutaneous arterial sympathetic nerve activities generated at that time were electrophysiologically measured over 90 minutes. The Cyclo (L-Pro-L-Pro) 3 ppm aqueous solution used here is Cy.
Clo (L-Pro-L-Pro) (manufactured by Peptide Institute) was diluted with water to a concentration of 3 ppm (w / v). As a control experiment, water was intragastrically administered at a dose of 1 ml / 300 g body weight, and the change in cutaneous arterial sympathetic nerve activity generated at that time was electrophysiologically measured for 90 minutes.

From the start of surgery to the end of measurement, a tube was inserted into the trachea to secure the airway, and a heat insulating device was used to keep the body temperature (rat rectal temperature) at 35.0 ± 0.5 ° C.

The obtained cutaneous artery sympathetic nerve activity data shows the firing frequency per 5 seconds every 5 minutes (pul).
It was analyzed by the average value of se / 5s) and expressed as a percentage with the value (0 minute value) before the start of stimulation as 100%. In addition, the mean value ± standard error is calculated from the data, and the test of statistically significant difference as a group is analyzed by variance (ANOVA) with rep.
It was performed by eated causes. The results are shown in FIG.

As shown in FIG. 2, the CASNA value between 5 minutes and 90 minutes after the start of gastric administration is Cyc.
Comparing the two groups, the lo (L-Pro-L-Pro) -administered group and the water-administered group, by statistical examination, the CASNA value of the Cyclo (L-Pro-L-Pro) -administered group is the CASNA value of the water-administered group.
It was revealed that the NA value was significantly lower (p <0.01, One way ANOVA). From this result, it was found that Cyclo (L-Pro-L-Pro) has an effect of suppressing the skin sympathetic nerve.

The autonomic nerve regulating action composition of the present invention is expected to be used as a safe and convenient means for maintaining a normal balance of autonomic nerves.

Claims (7)

A composition for autonomic nervous regulation containing diketopiperazines or a salt thereof as an active ingredient. The composition for autonomic nervous regulation according to claim 1, wherein diketopiperazines or a salt thereof is a roasting component. The composition for autonomic nervous regulation according to claim 1 or 2, wherein the diketopiperazines are cyclic dipeptides. The composition for autonomic nervous regulation according to claim 3, wherein the cyclic dipeptide contains at least proline as a constituent unit. The composition for autonomic nervous regulation according to claim 4, wherein the cyclic dipeptide is cyclo-prolyl-phenylalanine or cyclo-prolyl-proline. The composition for autonomic nervous regulation according to claim 5, wherein the autonomic nervous regulation is sympathetic nerve activation and the cyclic dipeptide is cyclo-prolyl-phenylalanine. The composition for autonomic nerve regulation according to claim 5, wherein the autonomic nerve regulation is sympathetic nerve suppression and the cyclic dipeptide is cyclo-prolyl-proline.

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