JP2015137249A - Agent for improving depression in winter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an agent for improving depression in winter.SOLUTION: An agent for improving depression in winter comprises L-serine as an active ingredient.

Description

  The present invention relates to an agent for improving winter depression.

Winter depression is a type of “seasonal emotional disorder” first announced in 1984 and is also called “winter depression”. So-called normal depression causes a loss of appetite, weight loss, and inability to sleep.
On the other hand, winter depression is depressed only from autumn to winter in the year. They continue to be addicted to carbohydrates such as rice and sweets, and continue to be sleepy and unbearable, and as with normal depression, they feel depressed, reduced concentration and motivation, and fatigue. Characteristic symptoms include overeating, oversleeping, weight gain, and craving for carbohydrates.
Patients are more common in women. Symptoms start around October, and in March, they naturally go to ease. If this continues for more than two years, the possibility of winter depression is diagnosed. Some patients with winter depression are light in summer, so they are overshopping and more social than usual.

The causes of winter depression are related to the duration of daylight and the length of daylight from sunrise to sunset. When the light stimulus felt by the eyes decreases, the amount of brain serotonin, a neurotransmitter, and melatonin, a pineal hormone, change. Serotonin, which stabilizes the mind, decreases and brain activity decreases, causing depression. On the other hand, it comes to want the carbohydrates necessary for the production of serotonin, and the appetite becomes strong mainly on carbohydrates. Melatonin that promotes sleep increases and sleep time is lengthened.
Winter depression is said to occur easily in areas with high latitudes and a lot of cloudy, rainy, and snowy days. It is recognized as a well-known disease in Scandinavia, and in Japan it is often found on the Sea of Japan side of Hokkaido, Tohoku and Hokuriku regions.
Various treatment methods have been proposed for winter depression. As a general treatment method for winter depression, “high illumination light therapy” that is exposed to bright light is considered effective. A special lighting fixture that emits light of 25,500 to 10,000 lux is used. If the light does not reach the retina of the eye, there is no effect, so place the instrument in front and irradiate it.
Patent Document 1 proposes an irradiation device for treating winter depression. Patent Document 2 describes a monoamine reuptake inhibitor for the indication of winter depression.

On the other hand, the present inventors have studied serine, which is a kind of amino acid, for many years.
Serine is a new amino acid obtained by hydrolysis of a silk surface protein (sericin) by Cramer in 1865 and is known to have sweetness. In 1902, Fischer and Skita separated from sericin hydrolyzate and further elucidated its structure by synthesis. It has been extracted from protein hydrolysates or synthesized from other amino acids in the past, but in recent years, it has been produced by industrial methods such as enzymatic methods and fermentation methods.

  Serine is a non-essential amino acid, interconverts with glycine in vivo, and is also involved in the synthesis of important biological components such as purine, creatine and porphine in the cell, and is important for proteins and various other biological functions. It is known to be a precursor of compounds. In recent years, serine has attracted attention as a neurotrophic factor. The present inventors have found that L-serine is useful as an anxiolytic agent and have applied for a patent (Patent Document 3).

JP 2008-245836 A Special table 2013-530144 gazette JP 2011-231116 A

  An object of the present invention is to provide an agent for improving winter depression.

The present invention has the following constitution (1) an agent for improving winter depression comprising L-serine as an active ingredient.
(2) An enhancer for improving winter depression caused by light irradiation containing L-serine as an active ingredient.

  The present invention provides an agent for improving winter depression. Moreover, the winter depression improving agent of this invention can enhance the improvement effect of winter depression by light irradiation.

The graph which shows the improvement effect by serine administration with respect to a winter depression model animal.

The present invention uses L-serine as an agent for improving winter depression.
L-serine related to the present invention can be produced by any of protein hydrolysis method, chemical synthesis method, enzyme method and fermentation method. Since L-serine is a structural component of tissue, it can be produced by extraction and purification from animals, plants, etc., although the yield is low. Furthermore, it can also be produced from components derived from animals, plants, etc., for example, from phosphoserine or phosvitin by chemical treatment, extraction and purification. The production method of L-serine related to the present invention is not particularly limited. Moreover, if it contains about 50% of L-serine, it can be set as the improvement agent of the winter depression of this invention.

In order to produce the winter depression ameliorating agent of the present invention, L-serine produced by the above method can be used, and it may be formulated in combination with a known non-toxic pharmaceutical carrier in accordance with a conventional method. The winter depression ameliorating agent according to the present invention can be administered in various dosage forms. For example, oral administration agents include solid agents such as tablets, granules, powders, capsules, soft capsules, solutions, suspensions, and the like. Examples include suspensions, liquids such as emulsions, freeze-dried preparations, etc. Parenteral preparations include injections, suppositories, sprays, transdermal absorption agents, and the like. It can be prepared by means.
Examples of the 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. Etc. If necessary, conventional additives such as stabilizers, lubricants, wetting agents, emulsifiers, binders and the like can be appropriately added. The winter depression ameliorating agent according to the present invention is appropriately selected and determined according to the patient's age, weight, symptom, degree of disease, administration schedule, formulation form, etc. The dose is about 0.1 mg / kg to 1000 mg / kg body weight per day, and may be administered in several divided doses a day.

In addition, L-serine according to the present invention is considered to be highly safe because it has abundant dietary experience, and can also be taken as a winter depression ameliorating agent or a functional food having a winter depression ameliorating action. The functional food characterized by containing L-serine related 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 L-serine, using conventional means, it is made into an edible form, for example, granular, granular, tablet, capsule, paste, etc. What was formed can be used. This functional food may be used as it is, or added to various foods (eg ham, sausage, kamaboko, chikuwa, bread, butter, milk powder, chocolate, etc.), water, alcoholic beverages, fruit juice It may be used by adding to drinks such as milk and soft drinks. The intake amount of L-serine of the present invention in the form of such food is appropriately selected and determined according to the age, weight, symptoms, intake schedule, formulation form, etc. of the subject, and for example, 0.1 mg / kg per day About 1000 mg / kg body weight.
The following examples and test examples further illustrate the present invention.

<Improvement test of winter depression model by L-serine administration>
1. Test animal model Experimental animals: C57BL / 6J mice (male, 6 weeks old, SLC Japan), 36 animals Reasons for animal selection: C57BL / 6J mice change depression-like behavior and serotonin content in the brain under day length conditions It can be used as a winter depression model.

2. Test method:
After purchasing the mice, they were acclimated for 3 weeks under group feeding conditions. Throughout the experiment period, the animals were allowed to eat and drink freely. The light conditions were 8 hours light period 16 hours dark period (light period was 5 lux, conditions that reproduced winter day length and sunshine).
The mice were divided into the following 4 groups (each group n = 8-10).
(1) Distilled water group (2) L-serine group (3) High illumination light irradiation + distilled water group (4) High illumination light irradiation + L-serine group The light illumination of 1000 lux starts in the high illumination light irradiation group Irradiation was performed every day for 1 hour after 1 hour.
Distilled water or L-serine (5 mmol / kg / 10 ml) was subcutaneously administered 15 minutes before the light irradiation start time.
On the 20th day from the start of light irradiation, a forced swimming test was performed. In a plastic container (height 27 cm, diameter 17 cm, water height 14.5 cm) filled with water at 25 ° C ± 1 ° C, the mouse was swam for 7 minutes and video-recorded. The time (the time when the person stopped swimming and showed a floating state) was measured.

3. Test results The results of the forced swimming test are shown in Table 1 and FIG. All results are shown as mean ± standard error. Dunnett's test was used for comparison with the control group, and the significance level was 5% (*), 1% (**), and 0.1% (***) in each two-sided test.

By making the light conditions 8 hours light period 16 hours dark period (the light period is 5 lux, conditions that reproduce the winter day length and sunshine), the mice have a remarkable depression-like behavior (long) in the forced swimming test It was found to be a symptom of winter depression. The symptoms of this winter depression could be improved by irradiating 1000 lux of light. Serine administration alone could only slightly improve the symptoms of winter depression, but using serine in combination with light irradiation significantly improved the symptoms of depression.
From the above test results, it became clear that L-serine improves winter depression symptoms and further enhances the improvement of winter depression symptoms by light irradiation.

Claims (2)

  An agent for improving winter depression comprising L-serine as an active ingredient. An agent for improving the improvement of winter depression by light irradiation comprising L-serine as an active ingredient.