JP2018184361A - Composition for autonomic nerve control - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel composition for autonomic nerve control that can effectively control the autonomic nerve and can be daily ingested.SOLUTION: This invention relates to a composition for autonomic nerve control containing diketopiperazine or a salt thereof as an active ingredient.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an autonomic nervous composition.

  In modern society, stress is a big problem. The living body keeps the homeostasis (homeostasis) constant against various external changes including stress, and the autonomic nervous system, endocrine system, immune system, etc. interact to balance each other. Among these, the most important system in the living body can be said to be the autonomic nervous system.

  The autonomic nervous system unconsciously adjusts the organ activity to correspond to the external environment and internal environment, regardless of conscious control. This autonomic nervous system is composed of a sympathetic nervous system in which activity increases in a tension state and a parasympathetic nervous system in which activity increases in a relaxed state such as when relaxed.

  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. . If it continues to be exposed to excessive stress at this time, the balance of the autonomic nerve is broken, and it is said that autonomic dysfunction such as insomnia such as insomnia is caused. On the other hand, activation of the sympathetic nerve can be expected to have an effect of clearing the head, reducing drowsiness, and maintaining concentration. Therefore, it is desired to provide a method for adjusting the autonomic nerve safely and simply.

  In recent years, techniques using aroma such as aromatherapy have been widely used. Aromatherapy is a method for improving these symptoms by aspirating or applying aroma components contained in essential oils or the like in order to relieve or soothe sympathetic nerve tension. This is because the aroma component absorbed through the nose or lung acts on the autonomic nerve through the hypothalamus of the cerebrum.

  Moreover, the exchange nerve activation fragrance | flavor composition using fragrance | flavor compositions, such as grapefruit oil, fenne oil, and pepper oil, is proposed (patent documents 1 and 2). In addition, for the purpose of continuing activation of sympathetic nerves, a sympathetic nerve activated cotton fabric in which a composition for sympathetic nerve activation is contained in a cotton fabric has been proposed (Patent Document 3).

  However, the method using a fragrance or a fragrance composition has a great influence on taste, and its use for food and drink is limited. Moreover, the component used for aromatherapy is not necessarily a food-use component that can be taken orally.

  Furthermore, heat-generating sympathetic nerve activators using plant extracts (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 heat-producing sympathetic nerves, and the effect obtained is limited to the slimming effect.

  On the other hand, Patent Document 6 relates to a psychological condition-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 with ethanol. Have been described.

JP 2002-193824 A JP 2002-265977 A JP 2004-250804 A JP 2004-51486 A JP 2004-115440 A JP 2010-209022 A

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

  An object of the present invention is to provide a novel composition for regulating autonomic nerves that can effectively regulate autonomic nerves and can be taken daily.

  As a result of intensive 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 has been completed.

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

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

FIG. 1 shows the skin sympathetic nerve when cyclo-prolyl-phenylalanine [Cyclo (L-Pro-L-Phe)] was intragastrically administered with a 3 ppm (w / v) aqueous solution at a dose of 1 ml / 300 g body weight. It is a graph which shows a time-dependent change of activity (cutaneous arterial symmetrical activity, CASNA). The vertical axis indicates the percentage when the value before starting stimulation (0 minute value) is 100%. The horizontal axis represents the elapsed time (minutes) after sample administration. The white triangle is a graph when cyclo-prolyl-phenylalanine is administered, and the black diamond is a graph when water is used as a control. FIG. 2 shows the skin sympathetic nerve when cyclo-prolyl-proline [Cyclo (L-Pro-L-Pro)] was administered to the stomach intragastrically at a dose of 1 ml / 300 g body weight with a 3 ppm (w / v) aqueous solution. It is a graph which shows a time-dependent change of activity (cutaneous arterial symmetrical activity, CASNA). The vertical axis indicates the percentage when the value before starting stimulation (0 minute value) is 100%. The horizontal axis represents the elapsed time (minutes) after sample administration. A black circle is a graph when cyclo-prolyl-proline is administered, and a black diamond is a graph when water is used as a control.

  The autonomic nervous composition according to the present invention (hereinafter also referred to as the composition of the present invention) contains diketopiperazines or salts thereof as active ingredients.

  In the present invention, “autonomic nerve modulation” means to improve the autonomy of the autonomic nervous system, and suppresses sympathetic nerve activity (sympathetic nerve suppression) in a subject whose sympathetic nerve 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. In addition, this phenomenon can be evaluated by calculating | requiring the activity level of a sympathetic nerve by the method mentioned later in an Example.

  Examples of sympathetic nerves include sympathetic nerves that control the adrenal gland, cutaneous artery, brown adipose tissue, white adipose tissue, liver, spleen, pancreas, or kidney.

  The salt of diketopiperazines refers to any pharmacologically acceptable salt of diketopiperazines (including inorganic salts and organic salts), such as sodium, potassium, calcium, and diketopiperazines, Magnesium, ammonium, hydrochloride, sulfate, nitrate, phosphate and organic acid salts (eg acetate, citrate, maleate, malate, oxalate, lactate, succinate, fumarate) Acid salts, propionates, formates, benzoates, picrates, benzenesulfonates, etc.), but are not limited thereto. Salts of diketopiperazines can be prepared by methods known in the art.

  The diketopiperazines are preferably cyclic dipeptides. A cyclic dipeptide is a compound in which two amino acid molecules are cyclized by dehydration condensation. 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 [Cyclo (Pro-Trp)], cyclo-prolyl-valine [Cyclo (Pro-Val)], 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)] and the like. Among these, cyclo-prolyl-phenylalanine and cyclo-prolyl-proline are preferable from the viewpoint of the autonomic nervous control effect. These may be used alone or in combination of two or more.

  In particular, when the autonomic nerve modulation is sympathetic nerve activation, the cyclic dipeptide is preferably cyclo-prolyl-phenylalanine. In addition, when the autonomic regulation is sympathetic inhibition, 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 structure of the cyclic dipeptide is the same, any of the description order thereof may be first. For example, Cyclo (Pro-Phe) and Cyclo (Phe-Pro) are the same cyclic dipeptide. Is expressed. 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 methods known in the art. For example, it may be produced by a chemical synthesis method, an enzymatic method or a microbial fermentation method, as described in JP 2003-252896 A, Journal of Peptide Science, 10, 737-737, 2004, JP 2014-125427 A. It can be prepared according to the method.

  As the diketopiperazines or salts thereof, commercially available synthetic reagents may be used, but those extracted from natural products are preferred from the viewpoint of safety. As a method for obtaining diketopiperazines or salts thereof from natural products, specifically, for example, a method for obtaining diketopiperazines or salts thereof as roasting ingredients by roasting food or drink raw materials, and food and drinks Examples thereof include a method of obtaining diketopiperazines or salts thereof by subjecting the raw material to heat treatment, aging treatment, enzyme treatment, or the like.

  As the food / beverage material, a food / beverage material containing a large amount of protein is preferable, and examples thereof include plant materials, milk materials, poultry, seafood, shellfish, and eggs. Among these, a plant raw material and a milk raw material are preferable from the viewpoint of productivity.

  The plant raw material is not particularly limited as long as it is a plant-derived material that is generally used in the production of food and drink, and examples thereof include grains, beans, teas, and herbs. preferable.

  Examples of grains include barley (for example, Nijo barley, Rojo barley, and bare barley), wheat, hato barley, fried rice, raw brown rice, germinated brown rice, ancient rice (for example, black rice, red rice, and green rice), Examples include buckwheat, white rice, corn, sweet potato, black sesame and white sesame. Examples of the beans include coffee beans, cacao beans, black soybeans, broad beans, chickpeas, kidney beans, and red beans. Examples of teas include green tea leaves, oolong tea leaves, and black tea leaves. Examples of herbs include chicory root and dandelion root.

  Examples of milk ingredients include skim milk, processed milk, cream, concentrated milk, skim milk powder called powdered milk, whole milk powder, prepared milk powder, prepared skim milk powder, sweetened condensed milk, sugar-free condensed milk, fermented milk, butter, butter oil, Cheese, ice cream and whey powder.

  Examples of animal poultry include, for example, cattle, pigs, horses, sheep and goats, which are livestock meat, meat other than livestock meat, such as boar and deer, poultry, chicken, turkey, quail, ducks and duck And meat of birds other than poultry meat that is wild bird meat (for example, duck, pheasant, sparrow, thrush, etc.).

  Examples of the seafood or shellfish include seafood and shellfish eaten in general eating habits. Examples of eggs include chicken eggs and quail eggs. The said food-drinks raw material can be used individually or in combination of 2 or more types.

  In the present invention, the roasting component includes components produced by roasting the food and drink raw materials, for example, bitterness components, sweetness components, richness components, aroma components, and coloring components. A roasting component can be obtained by processing the said food-drinks raw material in order of a roasting process and an extraction process, for example. The roasting step is a step of roasting the food / beverage raw material and generating a roasting component in the food / beverage raw material. As the roasting method, a roasting method and a roasting machine known in the art can be used.

  Examples of roasting methods include direct fire, hot air, far-infrared rays, and microwaves, if classified according to the heating method. Examples of the roasting machine include a continuous flow 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 raw material for food and drink. Specifically, for example, if the food or drink raw material is six-row barley, diketopiperazines can be obtained as roasting components 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 with an L-value meter.

  An extraction process is a process of extracting a roasting component by performing an extraction process to said roasted food-drinks raw material. 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 simply.

  The water has only to be water quality that can be used for food processing. For example, distilled water, demineralized water, alkaline ionized water, deep sea water, ion-exchanged water, deoxygenated water, and water-soluble organic compounds (for example, alcohols) ) Or water containing inorganic salts, preferably pure water.

  According to a preferred embodiment, the extraction step is performed by adding an extraction solvent having a mass of 100 to 1000%, more preferably 200 to 500%, based on the mass of the roasted food and beverage raw material, It is good to hold in the state 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 the extraction solvent. The extraction process may be left standing or stirred. In the extraction step, extraction conditions can be set according to the form of the apparatus used in the extraction step, the type and amount of extraction solvent, and the like.

  In order for diketopiperazines or salts thereof to act effectively, the content of the active ingredient diketopiperazines or salts thereof (when including a plurality of types) is preferably It is 0.0000001 mass% or more, More preferably, it is 0.0000001-0.0001 mass%.

  The usage form of the composition of the present invention is not particularly limited, and for example, to be blended in a food / beverage composition, an additive used for blending in the food / beverage composition, a pharmaceutical composition, or the pharmaceutical composition thereof. And additives used in the above. The form of the composition of the present invention is not particularly limited, and may be any of granular, granular, paste, gel, liquid, semi-liquid, and solid.

  The composition of the present invention may be used not only for humans but also for pets (for example, dogs, cats, reptiles, birds and fishes), livestock (including poultry), or farmed fish. Moreover, you may make the composition of this invention contain the other component which adjusts an autonomic nerve other than the said active ingredient.

  The food and beverage composition in the present invention includes so-called health foods, functional foods, dietary supplements, and supplements, and health functional foods such as foods with a disease risk reduction label (for example, foods for specific insurance, nutritional functions) Foods and functional label foods, etc.), foods for the sick and food additives.

  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 candy; Candy, gums, gummy, frozen confectionery and iced confectionery; including edible oils, dressings, mayonnaise and margarine Products; Carbohydrate-containing foods such as rice, rice cakes, noodles, breads and pasta; Livestock processed foods such as ham and sausages; Fish processed foods such as kamaboko, dried fish and salted fish; Vegetable processed foods such as pickles; Curry; Retort products such as ankake and Chinese soup; Instant foods such as instant soup and instant miso soup; Food for microwave ovens; Eggs Using workpieces, and seafood or meat processed products; seasonings; and the like. Furthermore, health foods and drinks prepared in the form of powder, granules, tablets, capsules, liquid, paste or jelly are also included. Manufacture of the food-drinks composition in this invention can be implemented with a manufacturing technique well-known in the said technical field.

  Non-alcoholic beverages include, for example, mineral water, near water, sports drinks, tea beverages, milk beverages, soft drinks, coffee beverages, fruit juice beverages, vegetable juice beverages, fruit juices and vegetable juice beverages, carbonated beverages and alcohol Beer-taste beverages that do not contain, but are not limited to. It may be a beer beverage having an alcohol content of less than 1%, such as non-alcohol beer. Mineral water includes both foaming and non-foaming mineral water.

  The tea beverage refers to a beverage made of tea leaves (tea leaves) which are evergreen trees of the camellia family or extracted from leaves or grains of plants other than tea trees, and any of fermented tea, semi-fermented tea and non-fermented tea Are also included. Examples of the tea beverage include Japanese tea (for example, green tea and barley tea), black tea, herbal tea (for example, jasmine tea), Chinese tea (for example, Chinese green tea and oolong tea), hoji tea, and the like.

  The milk beverage refers to beverages made mainly from raw milk, milk, etc. or foods made from these raw materials. In addition to those made from milk itself, for example, nutrient-enriched milk, flavored milk, and sugar decomposition What uses processed milk, such as milk, as a raw material is also included.

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

  When used as a food / beverage composition, the intake amount of diketopiperazines or salts thereof as active ingredients is usually preferably 10 to 1000 μg, more preferably 100 to 500 μg, still more preferably 200 to 100 per day per adult. 300 μg (when multiple types are included, the total is converted).

  Moreover, when using as a food-drinks composition, it is the form which contains 10-1000 micrograms of diketopiperazines or its salt (it is the total conversion, when multiple types are included) in the container divided | segmented into 1 serving or 1 serving. It is preferable that it is a form containing 100 to 500 μg, more preferably a form containing 200 to 300 μg.

  Although diketopiperazines or their salts have an autonomic nervous control effect even after a single ingestion, if the autonomic nerve balance can be adjusted appropriately by continuous ingestion as a food and drink composition, stress etc. It is also possible to reduce the vulnerability to environmental factors, i.e., to be resistant to stress.

  The pharmaceutical composition contains diketopiperazines or salts thereof as an active ingredient, and can be produced by mixing a carrier, an excipient, a binder or a diluent. It can be administered orally or parenterally, and when administered orally, it may be in any form such as granules, powders, tablets, pills, capsules or syrups. Examples of parenteral dosage forms include, but are not limited to, external preparations such as injections, infusions, and nasal preparations.

  When used as a pharmaceutical composition, the dosage varies depending on the dosage form, patient age, body weight, nature or severity of symptoms 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 day per adult, more preferably 100 to 500 μg, and even more preferably 200 to 300 μg (when multiple types are included, the total conversion). In the case of parenteral administration, for example, intravenous administration, the dose of diketopiperazines or a salt thereof is preferably 10 to 1000 μg per day per adult, more preferably 100 to 500 μg, still more preferably 200 to 300 μg. Yes (when multiple types are included, the total is converted). Regarding these doses, an optimal form may be selected as appropriate according to various conditions.

Example 1: Activation effect of skin sympathetic nerve activity by diketopiperazines The experiment was carried out in a constant temperature animal room at 24 ° C. for 1 week or more under a light / dark cycle every 12 hours (lighted from 8 o'clock to 20 o'clock). Wistar male rats (about 9 weeks old) weighing about 300 g were used. On the day of the experiment, the rats were fasted for 3 hours and then anesthetized with urethane, a cannula for intragastric administration was inserted, the distal branch of the dermal sympathetic nerve of the right thigh was lifted with a silver electrode, and the electrical activity of the nerve was measured.

  When these measured values settled (around 13:00), 3 ppm aqueous solution of Cyclo (L-Pro-L-Phe) was intragastrically administered at a dose of 1 ml / 300 g body weight using a cannula. Changes in cutaneous arterial sympathetic nerve activity were measured electrophysiologically over 90 minutes. The Cyclo (L-Pro-L-Phe) 3 ppm aqueous solution used here was water so that the concentration of Cyclo (L-Pro-L-Phe) (manufactured by Peptide Research Institute) was 3 ppm (w / v). Diluted. As a control experiment, water was administered intragastrically at a dose of 1 ml / 300 g body weight, and the resulting change in cutaneous arterial sympathetic nerve activity was measured electrophysiologically over 90 minutes.

  A tube was inserted into the trachea from the start of surgery to the end of measurement to secure the airway, and the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C. with a heat retaining device.

  The obtained data of cutaneous arterial sympathetic nerve activity was analyzed by the average value of the firing frequency (pulse / 5s) per 5 seconds every 5 minutes, and the percentage before the start of stimulation (0 minute value) was taken as a percentage. Expressed in In addition, while calculating the average value +/- standard error from data, the test of the statistical significance difference as a group was performed by analysis of variation (ANOVA) with repeated measurements. The results are shown in FIG.

  As shown in FIG. 1, statistical analysis of CASNA values between 5 minutes and 90 minutes after the start of intragastric administration in the Cyclo (L-Pro-L-Phe) administration group and the water administration group The CASNA value in the Cyclo (L-Pro-L-Phe) administration group was found to be significantly higher (p <0.01, One way ANOVA) than the CASNA value in the water administration group. 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 For experiments, body weight kept for more than 1 week in a constant temperature animal room at 24 ° C under a light / dark cycle every 12 hours (lights on from 8 o'clock to 20 o'clock) About 300 g of Wistar male rats (about 9 weeks old) were used. On the day of the experiment, the rats were fasted for 3 hours and then anesthetized with urethane, a cannula for intragastric administration was inserted, the distal branch of the dermal sympathetic nerve of the right thigh was lifted with a silver electrode, and the electrical activity of the nerve was measured.

  When these measured values settled (around 13:00), Cyclo (L-Pro-L-Pro) 3 ppm aqueous solution was administered intragastrically at a dose of 1 ml / 300 g body weight using a cannula, Changes in cutaneous arterial sympathetic nerve activity were measured electrophysiologically over 90 minutes. The Cyclo (L-Pro-L-Pro) 3 ppm aqueous solution used here is water so that the concentration of Cyclo (L-Pro-L-Pro) (manufactured by Peptide Research Institute) is 3 ppm (w / v). Diluted. As a control experiment, water was administered intragastrically at a dose of 1 ml / 300 g body weight, and the resulting change in cutaneous arterial sympathetic nerve activity was measured electrophysiologically over 90 minutes.

  A tube was inserted into the trachea from the start of surgery to the end of measurement to secure the airway, and the body temperature (rat rectal temperature) was maintained at 35.0 ± 0.5 ° C. with a heat retaining device.

  The obtained data of cutaneous arterial sympathetic nerve activity was analyzed by the average value of the firing frequency (pulse / 5s) per 5 seconds every 5 minutes, and the percentage before the start of stimulation (0 minute value) was taken as a percentage. Expressed in In addition, while calculating the average value +/- standard error from data, the test of the statistical significance difference as a group was performed by analysis of variation (ANOVA) with repeated measurements. The results are shown in FIG.

  As shown in FIG. 2, statistical analysis of CASNA values between 5 minutes and 90 minutes after the start of intragastric administration in the Cyclo (L-Pro-L-Pro) administration group and the water administration group The CASNA value in the Cyclo (L-Pro-L-Pro) administration group was found to be significantly lower (p <0.01, One way ANOVA) than the CASNA value in the water administration group. From this result, it was found that Cyclo (L-Pro-L-Pro) has an effect of suppressing skin sympathetic nerves.

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

Claims (7)

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

Images