JP2008056628A - Sleep inducer and stress insomnia ameliorating agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sleep inducer and a stress insomnia ameliorating agent. <P>SOLUTION: The sleep inducer comprises glutathione. The stress insomnia ameliorating agent comprises the glutathione. Furthermore, in the sleep inducer or stress insomnia ameliorating agent, the glutathione is produced by any method of a protein hydrolysis method, a chemical synthesis method, an enzyme method, a fermentation method or extraction or purification from a natural raw material. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a sleep inducer and a stress insomnia ameliorating agent.

Sleep is an important physiological function of animals that have developed brains, and is an indispensable behavior for survival. If you don't sleep well, your brain's ability to process information will be adversely affected. Therefore, higher animals with a developed cerebrum have a greater role for sleep. Only when there is good quality sleep, the brain can demonstrate high-level information processing ability.
In recent years, there has been a greater interest in sleep than ever before. There are two main reasons. For one thing, advances in brain science have gradually recognized the importance of sleep. Another is that modern society has become a mode of action that chronically sacrifices sleep, causing various adverse effects.

Serious sleep disorders are increasing worldwide. Measures for sleep disorders such as insomnia will continue to increase in specific gravity.
Insomnia is a state in which the amount of sleep time required to maintain a person's health is insufficient in terms of quantity or quality, which hinders social life and is also worried consciously. Depending on how long the insomnia continues, it is called “transient insomnia” for a few days, “short-term insomnia” for 1-3 weeks, and “long-term insomnia” for more than a month. The causes of insomnia vary, but often they are associated with some kind of stress, and the longer this stress is, the more likely the symptoms of insomnia become. For insomnia, administration of sleeping pills, tranquilizers, stress relievers, etc. is used as a general treatment.
However, the effect of improving insomnia is greatly affected by the psychological state of the subject and the surrounding environment, and is limited by the side effects and drug dependence as well as the characteristics of the action point of the drug used. There are also many. Therefore, development of new medicines and functional foods is required to improve the drawbacks of these sleeping pills, tranquilizers, and stress relievers.

  In the previous test, the present inventors found an anxiolytic effect on a compound having a serine unit such as serine and phosphatidylserine, glycine, phosphatidic acid, etc., and filed a patent application (see Patent Document 1). Moreover, as an extension of the test, it was discovered that administration of L-serine or the like markedly exerted a sleep-inducing effect under stress load conditions, and the effect was found (Japanese Patent Application No. 2006-206140).

Japanese Patent Laid-Open No. 2005-247841

  The present invention provides a new sleep inducer and stress insomnia improving agent.

  As a result of intensive studies to develop a drug, a food, a food for specified health use, a nutritional functional food, or a health food that supports insomnia such as a sleep inducer and a stress insomnia improving agent, Was found to have an effect of improving sleep induction or stress insomnia. That is, the present invention is based on the following means.

(1) A sleep inducer comprising glutathione.
(2) A stress insomnia ameliorating agent characterized by containing glutathione.
(3) Glutathione is produced by a protein hydrolysis method, chemical synthesis method, enzyme method, fermentation method, or extraction / purification method from natural raw materials (1) to ( 2) The sleep inducer or stress insomnia ameliorating agent described in the above.
(4) The sleep inducer or stress insomnia improving agent according to any one of (1) to (3), wherein the glutathione content is 5% by mass or more.
(5) A sleep-inducing or stress-induced insomnia-improving pharmaceutical comprising the sleep-inducing agent or stress-related insomnia improving agent described in any one of (1) to (4).
(6) A sleep-inducing or stress-induced insomnia-improving food comprising the sleep-inducing agent or stress-induced insomnia-improving agent described in any one of (1) to (4), and for specific health use Food, functional nutritional food, or health food.
(7) A feed containing the sleep inducer or stress insomnia improving agent described in any one of (1) to (4).

1. It was confirmed that glutathione has an effect of improving sleep induction and stress insomnia.
2. According to the present invention, it is possible to provide a safe sleep inducer and a stress insomnia improving agent that cause no side effects.
3. A food for sleep induction or for improving stress insomnia, a food for specified health use, a nutritional functional food, or a health food can be provided.
4). Livestock and pets can be targeted in addition to humans.

It was confirmed that the compound effective for the sleep induction and stress insomnia improvement effect according to the present invention is glutathione.
Glutathione is a tripeptide corresponding to γ-L-glutamyl-L-cysteinyl-glycine and is represented by the following general formula 1.
Glutathione is naturally found in animals, yeast and most other living cells, and plays an extremely important role in the respiration of living tissues. It is also a growth factor for certain microorganisms. -Including SH, which is easily reversibly oxidized to an oxidized form, and thus plays an important role in redox in vivo. A flavin enzyme that reduces oxidized glutathione [GS-SG] to give glutathione [GSH] is called glutathione reductase.

(General formula 1)

  Glutathione according to the present invention can be produced by any of protein hydrolysis, chemical synthesis, enzymatic method and fermentation method. In addition, since glutathione is a structural component of tissue, it can be produced by extraction and purification from natural raw materials such as animals and plants although the yield is low. Furthermore, it can be produced, extracted and purified by chemical treatment from components derived from animals and plants. The production method of glutathione according to the present invention is not particularly limited.

  An example of the structure of glutathione is shown in FIG.

  In order to produce the sleep inducer and the stress insomnia improving agent according to the present invention, those containing glutathione produced by the above method as an active ingredient or those containing commercially available glutathione as an active ingredient can be used as raw materials. According to a conventional method, it may be formulated in combination with a known non-toxic pharmaceutical carrier.

  The sleep inducer and stress insomnia improving agent according to the present invention can be administered in various dosage forms. For example, oral administration agents include solids such as tablets, granules, powders, capsules, and soft capsules. Liquids such as pills, solutions, suspensions and emulsions, lyophilized preparations and the like, and parenteral administration agents include suppositories, sprays, transdermal absorption agents, etc. in addition to injections. These preparations can be prepared by conventional means on preparations. Examples of the non-toxic pharmaceutical carrier include glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, albumin, water And physiological saline. If necessary, conventional additives such as stabilizers, lubricants, wetting agents, emulsifiers, binders and the like can be appropriately added.

In the sleep inducer and stress insomnia ameliorating agent according to the present invention, the dose of glutathione is appropriately selected and determined according to the patient's age, weight, symptom, degree of disease, administration schedule, formulation form, etc. For example, the dose is about 0.1 to 10,000 mg / kg body weight per day, and the dose may be divided into 1 to several times a day.
In addition, glutathione according to the present invention is a biologically produced or constituent component, and is considered to be highly safe because it is a component that is universally contained in foods, but it is considered to be highly safe. Sleep induction, stress insomnia For the purpose of improvement, it can be ingested as a functional food for improving sleep induction and stress insomnia.

  The sleep induction and stress insomnia improving functional food characterized by containing glutathione according to the present invention can be positioned as a food for specified health use, a nutritional functional food, or a health food. As a functional food, for example, after adding an appropriate auxiliary agent to these compounds, using a conventional means, a form suitable for food, for example, granular, granular, tablet, capsule, soft capsule, paste What was formed in the shape etc. can be used. This sleep-inducing and stress-induced insomnia-improving functional food may be used for food as it is, or used by adding it to various foods (eg ham, sausage, kamaboko, chikuwa, bread, butter, powdered milk, confectionery, etc.) Or added to drinks such as water, alcoholic beverages, fruit juice, milk, soft drinks, etc. The intake amount of glutathione of the present invention in the form of such food is appropriately selected and determined according to age, weight, symptom, degree of disease, form of food, etc. For example, 0.1 to 10,000 mg / kg per day About weight

The sum of the content of each of these compounds in the above-mentioned glutathione-containing sleep inducer, drug for the purpose of improving stress insomnia, food for specified health use, nutritional functional food, or health food is the composition It is desirable to be 5% by mass or more in the total amount. It is further desirable that the total content of these compounds is 20% by mass or more based on the total amount of the composition.
Furthermore, by giving an anxiolytic agent containing glutathione as feed to livestock and pets, the emotion of the livestock can be stabilized and growth can be promoted. In particular, it is effective for young pets and livestock that are bred away from their parents soon after birth.

In verifying the sleep induction and stress insomnia ameliorating function of a composition containing glutathione as an active ingredient, the present inventor first administered reduced glutathione (GSH) directly into the cerebral ventricles of newborn chickens, and then chicken chicks. Observed behavior.
EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[Test condition 1]
Test condition 1 applies to Example 1.
Test animals: Egg breed male chicks (Julia, 5 or 6 days old) were used in the test. Prior to sample administration, the test animals were grouped according to their body weight, and 6-7 birds were grouped together.
Rearing conditions: Under the conditions of 30 ± 1 ° C., commercially available feed (Toyohashi Feed Co., Ltd., AX) and water were freely fed.
Test sample: The following reagents were prepared by dissolving in 0.85% physiological saline containing 0.1% Evans blue (added with 5% DMSO when necessary).

Reagents used in the examples:
Reduced glutathione (may be indicated as “GSH”) (Wako Pure Chemical Industries, 98%),

Test method: 10 μl of the reagent was administered to the chick ventricle using a microsyringe. In the Control group, 10 μl of ventricle was administered with 0.85% physiological saline containing 0.1% Evans blue.
Behavioral observation: Five minutes after administration, each chick was transferred from the group cage to a separate cage for behavioral observation. Immediately following ventricular administration, a 10-minute behavior under isolated stress conditions was recorded with a video camera from three angles.

  Results analysis: Observed the emotional behavior of chicks from recorded videos, and the effect of reduced glutathione on (1) cry, (2) sleep state time, and (3) locomotor activity under chick isolation stress. Shown in the graph.

In Example 1, the following administration concentrations of GSH were divided into two types, a low concentration and a high concentration, and used as test samples. The call (number of times), sleep state time (seconds), and amount of spontaneous exercise (number of times) under chick isolation stress were measured. Numerical data of the measurement results are shown in Tables 1 to 5, and graphs are shown in FIGS. Specifically, the call (number of times) at a low concentration is shown in Table 1 and FIG. 1, the call (number of times) at a high concentration is shown in Tables 2 and 2, and the sleep behavior (number of seconds) at a low concentration is shown in Tables 3 and 3. Table 4 and FIG. 4 show sleep behavior (seconds) at a high concentration, and Table 5 and FIG. 5 show spontaneous momentum (number of times) at a low concentration.
Low concentration experiment (1) Control group (7 animals),
(2) GSH 0.05 μmol administration group (7 animals),
(3) GSH 0.2 μmol administration group (6 animals),
High concentration experiment (4) Control group (7 animals),
(5) GSH 0.5 μmol administration group (7 animals),
(6) GSH 1 μmol administration group (7 animals),
(7) GSH 2 μmol administration group (6 animals).

  As shown in Table 1 and FIG. 1, when the control group was taken as 100%, the number of calls decreased to about 34% with glutathione 0.05 μmol and about 40% with 0.20 μmol. The glutathione-administered group showed a tendency to reduce stress.

  As shown in Table 2 and FIG. 2, when the control group is 100%, the number of calls decreases to about 24% with 0.50μmol glutathione, about 14% with 1.00μmol, and about 3% with 2.00μmol. did. The glutathione administration group showed a significant stress relieving effect.

  As shown in Table 3 and FIG. 3, when the control group was 1, the sleep state time increased by about 6.7 times with 0.05 μmol glutathione and about 5 times with 0.20 μmol administration. The glutathione administration group showed a tendency of sleep induction effect and stress insomnia improvement effect.

  As shown in Table 4 and FIG. 4, the sleep state time increased in a dose-dependent manner in the glutathione administration group, although it was 0 in the control group. The glutathione administration group showed a tendency of sleep-inducing effect and stress-induced insomnia improvement effect.

  As shown in Table 5 and FIG. 5, when the control group was taken as 100%, the locomotor activity decreased to about 26% with glutathione 0.05 μmol administration and to about 32% with 0.20 μmol administration. The glutathione-administered group showed a tendency to reduce stress.

  In particular, as shown in Table 2 and FIG. 2, the glutathione 0.5 μmol, 1 μmol, and 2 μmol administration groups showed clear sleep-inducing effects and stress-induced insomnia improvement effects compared to the control group. Moreover, also in Table 1, Table 3-Table 5, FIG.1 and FIG.3-FIG.5, the stress relieving effect by glutathione administration was shown. Moreover, concentration dependency was not necessarily observed in the low concentration test, but concentration dependency was observed in all of the high concentration tests.

The figure which shows the call (number of times) under the chick isolation stress of the administration group according to reduced glutathione (GSH) density | concentration in Example 1. FIG. (Low concentration experiment) The figure which shows the call (number of times) under the chick isolation stress of the administration group according to reduced glutathione (GSH) density | concentration in Example 1. FIG. (High concentration experiment) The figure which shows the sleep action (second) under the chick isolation stress of the administration group according to the reduced glutathione (GSH) density | concentration in Example 1. FIG. (Low concentration experiment) The figure which shows the sleep action (second) under the chick isolation stress of the administration group according to the reduced glutathione (GSH) density | concentration in Example 1. FIG. (High concentration experiment) The figure which shows the amount of spontaneous exercises (number of times) under the chick isolation stress of the administration group according to reduced glutathione (GSH) concentration in Example 1. (Low concentration experiment) The figure which shows a glutathione (Glutathione) structure.

Claims (7)

  A sleep inducer comprising glutathione.   An agent for improving stress insomnia characterized by containing glutathione.   Glutathione is produced by a protein hydrolysis method, chemical synthesis method, enzyme method, fermentation method, or extraction / purification method from a natural raw material. Inducing agent or stress insomnia improving agent.   The sleep inducer or stress insomnia improving agent according to any one of claims 1 to 3, wherein the glutathione content is 5% by mass or more.   A sleep-inducing or stress-induced insomnia-improving pharmaceutical comprising the sleep-inducing agent or stress-induced insomnia-improving agent according to any one of claims 1 to 4.   A sleep-inducing or stress-induced insomnia-improving food, a specified health food, or a nutritional functional food, comprising the sleep-inducing agent or stress-induced insomnia-improving agent according to any one of claims 1 to 4. Or health food.   The feed containing the sleep inducer or stress insomnia improving agent described in any one of Claims 1-4.