antidepressants

Abstract

The present invention provides a composition for preventing, treating and / or alleviating diseases exhibiting depressive symptoms, which is highly safe and less likely to cause side effects. [Solution] According to the present invention, in order to solve the above problems, Compositions containing triterpenes The present invention also provides pharmaceutical compositions, foods and beverages, nutritional supplements, food additives, cosmetics, etc., containing the composition. By ingesting the composition, etc., of the present invention, it becomes possible to prevent, treat, and / or alleviate depression.

Description

[Technical Field]

[0001] The present invention relates to a composition for preventing, treating and / or alleviating depressive symptoms. [Background technology]

[0002] Of the approximately 6.14 million people in Japan suffering from mental illness, 1.69 million suffer from depression or bipolar disorder (Non-Patent Document 1). This is not only a social loss, but also a major medical economic problem. It is said that anyone can develop depression, and medical countermeasures are urgently needed, making the prevention and treatment of depression important issues.

[0003] The cause of depression is not clear, but the mechanism of action of antidepressants has been thought to involve a deficiency of monoamines such as serotonin and noradrenaline (monoamine hypothesis). However, this has not been able to fully explain the time lag of approximately six weeks required for recovery from depression, despite the fact that antidepressants increase monoamine concentrations in the synaptic cleft in a relatively short period of time. As such, the mechanism of action of antidepressants has not yet been fully elucidated. For this reason, recent studies have investigated the mechanisms of action of antidepressants, such as neurogenesis in the hippocampus, inhibition of interleukin-1 receptors, and GABA receptor activation. A It is believed that receptor agonists are involved in the antidepressant effect. (Non-patent Document 2)

[0004] Existing antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs), noradrenergic-specific serotonergic antidepressants (NaSSAs), tricyclic antidepressants, and tetracyclic antidepressants. However, these drugs are not immediately effective and require two to three weeks for therapeutic effects to be seen. Furthermore, side effects such as dry mouth, constipation, nasal congestion, difficulty urinating, palpitations, visual impairment, low blood pressure, fatigue, and general malaise may occur before the therapeutic effect is seen. These side effects can lead to poor adherence and worsen the condition, making long-term use difficult. Furthermore, these drugs are intended to treat depression after its onset, not prevent it. Furthermore, there are patients with treatment-resistant depression, and approximately 30% of patients are ineffective.

[0005] Many proposals have been made to prevent stress, including depression, by using drugs used to treat depression as prophylactic medications (Patent Documents 1 and 2). However, these drugs are expensive, and administering them to people living normal lives is not a realistic option in terms of side effects and cost, even though the incidence of depression is high. Therefore, there is a demand for substances that can be produced inexpensively, have stress prevention effects as well as other functions, and can be taken over a long period of time. In particular, there is a demand for substances that can be ingested as foods, as this would motivate continued use over a long period of time and facilitate prevention.

[0006] As a therapeutic agent for depression, various synthetic medicines as mentioned above have been developed, but antidepressants containing plant-derived components as active ingredients are known as therapeutic agents for depression. A representative herbal medicine is known to be St. John's wort. St. John's wort has traditionally been used as a medicinal plant, and in recent years it has been used to treat mild to moderate depression. In addition, various antidepressants containing plant components as active ingredients have been disclosed. For example, Japanese Patent Application Laid-Open Publication No. 2007-99660 discloses a preventive or therapeutic agent for depression containing quercetin 3-O-β-D-glucosyl-(1,2)-α-L-rhamnoside and quercetin 3-O-(6-p-coumaroyl)-β-D-glucosyl-(1,2)-α-L-rhamnoside extracted from ginkgo leaves as active ingredients; Japanese Patent Application Laid-Open Publication No. 2011-57585 discloses an antidepressant containing sterol glycoside extracted from germinated brown rice as an active ingredient; and Japanese Patent Application Laid-Open Publication No. 2014-193844 discloses an antidepressant containing L-ergothioneine extracted from mushrooms as an active ingredient.

[0007] Furthermore, JP 2012-102059 A discloses an antidepressant containing an active ingredient extracted from a plant of the Labiatae family, JP 2019-77662 A discloses an antidepressant containing glucosylceramide extracted from grains as an active ingredient, and JP 2022-53441 A discloses an agent for preventing or treating depression containing tomatidine and tomatine extracted from tomatoes as active ingredients. These antidepressants containing ingredients derived from natural products have the advantage of being mild and unlikely to cause side effects, but many of them are not necessarily fully effective. Therefore, there is a need for further exploration of ingredients derived from natural products that have effective antidepressant effects.

[0008] Previously, triterpenes such as ursolic acid, oleanolic acid, and betulinic acid, found in persimmon leaves and stems (Non-Patent Documents 3 and 4), thyme, rosemary, sage, and eucalyptus leaves (Non-Patent Document 5), and apple peel (Non-Patent Document 6), have been reported to have brain function-improving effects (Non-Patent Document 7), anti-anxiety effects (Non-Patent Document 8), blood glucose level-suppressing effects (Non-Patent Document 9), anti-cancer effects, anti-inflammatory effects, and antibacterial effects (Non-Patent Documents 10 and 11). Furthermore, Japanese Patent Publication No. 2004-10531 reports that barbinerbic acid, a triterpene found in persimmon leaves, has anti-allergic effects. Furthermore, Japanese Patent Publication No. 2020-33302 discloses a whitening agent and a topical skin preparation containing a persimmon leaf extract enriched in rotungic acid or its salt as an active ingredient. On the other hand, Japanese Patent Publication No. 2021-505692 discloses that persimmon leaf extract or a persimmon leaf flavonoid composition exhibits antidepressant effects in an unpredictable chronic mild stress model mouse. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Japanese Patent Application Laid-Open No. 2000-204040 [Patent Document 2] Special Publication No. 2008-538741 [Patent Document 3] Japanese Patent Application Laid-Open No. 2007-99660 [Patent Document 4] Japanese Patent Application Laid-Open No. 2011-57585 [Patent Document 5] Japanese Patent Application Laid-Open No. 2014-193844 [Patent Document 6] Japanese Patent Application Laid-Open No. 2012-102059 [Patent Document 7] Japanese Patent Application Publication No. 2019-77662 [Patent Document 8] Japanese Patent Publication No. 2022-53441 [Patent Document 9] Japanese Patent Application Laid-Open No. 2004-10531 [Patent Document 10] Japanese Patent Publication No. 2020-33302 [Patent Document 11] Special Publication No. 2021-505692 [Patent Document 12] Japanese Patent Application Publication No. 3-123781 [Patent Document 13] Japanese Patent Application Publication No. 8-333406 [Non-patent literature]

[0010] [Non-Patent Document 1] Ministry of Health, Labour and Welfare, "Overview of Patient Survey in 2020", [online], March 23, 2022, [Retrieved November 2, 2024], Internet<URL:https: / / www.mhlw.go.jp / toukei / saikin / hw / kanja / 20a / dl / 01.pdf> [Non-patent document 2] Shigenobu Kanba, Yoshiyuki Hashioka, Akira Moji. 2005. Pharmacological mechanisms of action of antidepressants: Recent findings. Proceedings of the 129th Symposium of the Japanese Medical Association, Depression. 24-31. [Non-patent document 3] Katsumi E,Oshima N,Kagawa N,Ohara H,Hada N.2021.Changes in the extracted amounts and seasonally variable constituents of Diospyros kaki at different growth stages.J Nat Med.75(1):105-115.

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[0011] The present invention aims to provide a composition that is highly safe and unlikely to cause problems such as side effects, and that has the effect of preventing, treating, or alleviating depression, as well as pharmaceuticals, foods and beverages, nutritional supplements, food additives, and cosmetics that contain the composition. [Means for solving the problem]

[0012] As a result of careful consideration to solve the above problems, On persimmon leaves It was discovered that the contained rotungic acid or barbinerbic acid has an antidepressant effect, leading to the completion of the present invention.

[0013] That is, the present invention is as follows. 1. A composition for preventing, treating and / or alleviating depressive symptoms, anxiety symptoms and / or obsessive-compulsive disorder, comprising as an active ingredient at least one selected from the group consisting of rotungic acid, barbinerbic acid, and their ester and alkoxy derivatives. (Excluding compositions containing persimmon leaf extract) . 2. A composition for preventing, treating and / or alleviating depression, anxiety and / or obsessive-compulsive disorder, comprising an alkali metal salt of rotungic acid or barbinerbic acid as an active ingredient. (Excluding compositions containing persimmon leaf extract). 3. 3. The composition according to any one of the above items 1 to 2, which is a pharmaceutical product. 4. 3. The composition according to any one of items 1 to 2 above, which is a food or drink, a nutritional supplement or a food additive. 5. 3. The composition according to any one of the above items 1 to 2, which is a cosmetic. [Effects of the Invention]

[0014] The present invention aims to provide a new, inexpensive antidepressant that has excellent antidepressant activity, is highly safe even when taken over a long period of time, and is less likely to cause side effects.

[0015] That is, the present invention Persimmon leaves The antidepressant effects of the active ingredients, rotungic acid and barbinerbic acid, are equivalent to or superior to those of conventional antidepressants. [Brief explanation of the drawings]

[0016] [Figure 1] FIG. 1 shows the chemical structures of rotungenic acid (RA) and barbinervic acid (BA). [Figure 2] FIG. 2 shows the results of a tail suspension test using mice (BALB / C mice). [Figure 3] FIG. 3 shows the results of a tail suspension test using mice (BALB / C mice) subjected to restraint stress. DETAILED DESCRIPTION OF THE INVENTION

[0017] Used in the present invention Persimmon leaves , obtained from persimmon (Diospyros kaki Thunberg) With leavesAs long as there is a suitable variety, the variety is not particularly limited, and persimmons from various varieties can be used. For example, so-called sweet-fruit varieties include Fuyu, Jiro, Ama Hyakunichi, Gosho, Hana Gosho, Ban Gosho, Tenjin Gosho, Fujiwara Gosho, Tokuda Gosho, Mikaya Gosho, Zenjimaru, Fujihachi, Mizushima, and Shogatsu, and so-called astringent varieties include Yokono, Hiratanenashi, Fuji, Saijo, Dojo Hachiya, Aizu Minashirazu, Koromo, Gionbo, Yotsumizo, Oyotsumizo, Atago, Hagakure, Kawabata, Takura, Sakushu Minashirazu, Nishimura, Fude, Tone Wase, and Koshu Hyakume, but are not limited to these. Persimmon leaves The best time to collect them is from summer to autumn, and more preferably from September to November. Persimmon leaves Although it may be used for extraction as it is, it is preferable to dry it before extraction. Examples of drying methods that can be used include natural drying by leaving it in a well-ventilated place, sun drying, drying by exposure to dried gas or heated gas, drying by exposure to high-temperature or high-pressure steam, drying by microwave irradiation, vacuum drying, and freeze drying. Of these, drying by exposure to dried gas or heated gas is preferred for hygienic reasons.

[0018] On persimmon leaves The extract is concentrated by adding an extraction solvent (water, organic solvent, or a mixture thereof) and soaking for a certain period of time, or by heating and extracting at the boiling point of the solvent. The extract is extracted using a lower alcohol (e.g., methanol, ethanol, n-propanol, isopropanol, n-butanol, etc.) or a water-containing alcohol. It is preferable that the ratio of water and lower alcohol is equal in mass, or that the lower alcohol content is higher.

[0019] Rotunic acid and barbinerbic acid contained in persimmon leaf extract It can be separated and purified from the extract by conventional methods such as solvent extraction, column chromatography, recrystallization, etc. For identification, various means such as nuclear magnetic resonance (NMR) and mass spectrometry (MS) are used (Non-Patent Document 4).

[0020] Rotuncular acid ( rotungenic acid ) and barbinerbic acid ( barbinervic acidThe chemical structure of ) is shown in Figure 1. Rotungic acid and barbinerbic acid are epimers of each other because they differ in the placement of the hydroxyl group at only one asymmetric carbon atom (position 3).

[0021] Triterpenes of the Present Invention The term refers to the free form, ester form, alkoxy form, and hydroxyl group of rotungic acid or barbinerbic acid. or alkali metal salts It refers to one or more selected from the following. The term "ester" refers to a substituent abbreviated as -COOR obtained by dehydration condensation of a carboxylic acid and an alcohol, and methyl ester (-COOCH3) and ethyl ester (-COOC2H5) are used. The term "alkoxy" refers to a group in which an alkyl group is bonded to an oxygen atom. n H 2n+1 O- is a monovalent group, abbreviated as RO-, and examples of such groups include methoxy (CHO-) and ethoxy (CHO-).

[0022] A method for synthesizing esters of rotungic acid or barbinerbic acid is disclosed in Japanese Patent Application Laid-Open No. 3-123781, and a method for synthesizing alkoxy, for example methoxy, of rotungic acid or barbinerbic acid is disclosed in Japanese Patent Application Laid-Open No. 8-333406.

[0023] The water solubility of rotungic acid or barbinerbic acid can be improved by converting it into a salt, thereby increasing its physiological availability. Examples of base substances for forming the salts of rotungic acid or barbinerbic acid used in the present invention include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide.

[0024] Depressive symptoms refer to depressed mood, sleep disorders, loss of interest and pleasure, appetite disorders, impaired thinking, concentration and decision-making ability, feelings of worthlessness and self-blame, fatigue and loss of energy, etc. In the present invention, the term "antidepressant" includes preventive, therapeutic and / or alleviating effects against depression, which is a disease characterized by persistent emotional disturbance as well as autonomic nervous system disorders and suppression of cognition and behavior.

[0025] Triterpenes dosage The dosage and frequency of administration vary depending on factors such as the dosage form, the subject's sex, body weight, age, duration of ingestion, and severity of symptoms, but typically, triterpenes are administered to adults at a dose of 0.1 mg to 10 g / kg / day, more preferably 10 mg to 1 g / kg / day. The dosage may be once or multiple times per day, or once every few days. For example, the dosage may be once or several times per day, such as 1 to 3 times, 1 to 2 times, or once per day. The duration of administration is not particularly limited, but continuous administration is preferred when used to prevent stress.

[0026] The present invention provides Contains triterpenes A composition having an antidepressant effect is provided, and the composition may be in the form of a medicine, a food or drink, a nutritional supplement, a food additive, or a cosmetic.

[0027] When the composition of the present invention is a pharmaceutical composition, its administration route may be oral or parenteral, such as intravenous, intraperitoneal, subcutaneous, or transdermal administration. Dosage forms include, for example, oral and parenteral preparations such as tablets, powders, granules, pills, suspensions, emulsions, infusions, decoctions, capsules, syrups, liquids, elixirs, extracts, tinctures, liquid extracts, injections, infusions, creams, and suppositories.

[0028] In the case of oral administration preparations such as tablets, powders or granules, sugars such as lactose, glucose, sucrose, mannitol or sorbitol, inorganic substances such as calcium carbonate, calcium sulfate or sodium bicarbonate, excipients such as crystalline cellulose or licorice powder, disintegrants such as starch, agar, gelatin powder, crystalline cellulose, calcium carbonate or sodium alginate, lubricants such as calcium stearate or talc, binders such as methylcellulose, ethyl cellulose, gelatin or starch paste, surfactants such as fatty acid esters, plasticizers such as glycerin, and further additives commonly used in foods and beverages such as sweeteners, colorants, preservatives, thickening stabilizers, antioxidants, color formers, bleaching agents, antifungal agents, gum bases, bittering agents, enzymes, glazing agents, acidulants, seasonings, emulsifiers, strengthening agents, manufacturing agents, flavors, spice extracts, etc. may be added to form the preparations.

[0029] Suitable for parenteral administration, for example, injections, can be prepared using a sterilized aqueous agent that is preferably isotonic with the recipient's blood, and a carrier such as a salt solution, a glucose solution, or a mixture of a salt solution and a glucose solution. These parenteral agents can also contain one or more auxiliary ingredients selected from the diluents, preservatives, flavors, excipients, disintegrants, lubricants, binders, surfactants, plasticizers, etc., exemplified for oral agents. Triterpene concentrationThe concentration of the drug is preferably 0.1 to 10 mg / mL. If the concentration is low, a large amount of injection is required, and if the concentration is high, crystals are more likely to precipitate.

[0030] The food or beverage of the present invention may be a health food, a nutrient-functional food, a food with functional claims, a food for specified health uses, etc. Examples of the form of the food or beverage include solid, semi-solid, or liquid foods, specifically, confectioneries (candy, gummies, chewing gum, jelly, etc.), frozen desserts (ice cream, sorbet, gelato, etc.), beverages (soft drinks, coffee drinks, fruit drinks, vegetable drinks, dairy drinks, lactic acid bacteria drinks, soy milk drinks, rice koji drinks, sports drinks, supplement drinks, powdered drinks, etc.), tea drinks (green tea, oolong tea drinks, black tea drinks, herbal tea drinks, persimmon leaf tea, etc.), processed fish products, processed meat products, noodles, fish sausages, side dishes, sauces, etc.

[0031] The nutritional supplement of the present invention may contain inorganic components such as iron and calcium, various vitamins, dietary fiber such as oligosaccharides and chitosan, proteins such as soybean extract, lipids such as lecithin, and sugars such as sucrose and lactose.

[0032] The food additive of the present invention may be mixed with a food-acceptable carrier, additive, etc., and may be in the form of a solid preparation such as a powder, granules, tablets, pills, capsules, or dry syrup, or a liquid preparation such as a liquid, drink, or syrup.

[0033] Cosmetics of the present invention include basic cosmetics such as lotions, emulsions, creams, ointments, gels, lotions, oils, packs, mists, and facial cosmetic sheets, as well as makeup cosmetics such as foundations and blushes. Well-known additives may be added as appropriate to the extent that they do not impair the effects of the present invention. Examples of such additives include oils and fats, waxes, mineral oils, fatty acids, alcohols, esters, metal soaps, surfactants, various vitamins, various amino acids, various additives derived from plant or animal sources, inorganic pigments, UV absorbers / screeners, whitening agents, tyrosinase activity inhibitors, cell activators, astringents, antioxidants, anti-inflammatory agents, antibacterial, germicidal, and disinfectant agents, moisturizers, fragrances, colorants, other hormones, sequestering agents, pH adjusters, chelating agents, antiseptic and antifungal agents, cooling agents, stabilizers, emulsifiers, foam boosters, thickeners, enzymes, and purified water (e.g., ion-exchanged water and ion-exchanged distilled water).

[0034] The compositions of the present invention can be used in pharmaceutical compositions, foods and beverages, nutritional supplements, food additives, cosmetics, and also as pet foods.

[0035] The present invention will be specifically explained below with reference to examples, but the present invention is not limited to these examples. [Example]

[0036] Example 1: Isolation of rotungic acid and barbinerbic acid from persimmon leaves 100 g of dried, chopped persimmon leaves were added to 1 L of 70% ethanol and extracted at room temperature for 3 weeks with occasional stirring. The mixture was filtered, and the filtrate was collected. This extraction procedure, which involved adding aqueous ethanol and collecting the filtrate, was repeated twice. The collected filtrate was evaporated to dryness, and the remaining filtrate extract was purified by column chromatography and recrystallization, isolating 360 mg of rotungic acid and 240 mg of barbinerbic acid. NMR spectroscopy and MS were used for identification (Non-Patent Document 4).

[0037] <Handling of animals> All procedures were approved by the Kawasaki Medical School Animal Care and Use Committee and conformed to the NIH (National Institutes of Health) Guide for the Care and Use of Laboratory Animals.

[0038] Example 2 : Administration of rotungic acid or barbinerbic acid to mice Ten-week-old male wild-type BALB / C mice (Jackson Laboratory Japan, Kanagawa Prefecture, Japan) were used. Mice were housed in cages of five per cage with free access to food and drink. The room temperature was maintained at 23–26°C, and the lights were on from 8:00 to 20:00.

[0039] Rotungic acid, barbinerbic acid, and the positive control substance (vortioxetine, Combi-Blocks, Inc., California, USA) were each dissolved in saline to a concentration of 30 mg / kg body weight and administered intraperitoneally 30 minutes before the tail suspension test. The vehicle control group received the same volume of saline intraperitoneally 30 minutes before the tail suspension test. The administration volume was 3 mL / kg body weight. There were five rats in each group.

[0040] Vortioxetine acts as a serotonin reuptake inhibitor, (5-hydroxytryptamine: 5-HT) receptor modulation (5-HT3 receptor, 5-HT7 receptor and 5-HT 1D Receptor antagonism, 5-HT 1B Partial receptor agonism, 5-HT 1A It is an antidepressant with serotonin receptor agonism and serotonin transporter inhibitory action, and regulates the release of not only serotonin but also noradrenaline, dopamine, acetylcholine, and histamine ( Non-patent document 12 ).

[0041] <Method for measuring antidepressant effects using the tail suspension test> The mice were hung upside down with their tails taped to a metal bar fixed 40 cm above the floor on a 60 cm high stand. The mice were initially very active, but gradually gave up moving. The antidepressant effect of the administered compound was evaluated using the reduction in the percentage (%) of immobility time during the 6 minutes after the start of tail suspension as an indicator. The mice were brought into the testing room one hour before the test to allow them to become accustomed to the testing environment.

[0042] Example 3 : Administration of rotunate or barbinerbic acid to depression model mice Currently, behavioral studies of depression in laboratory animals primarily focus on two aspects of depression: the efficacy of antidepressants and stress response. Depression models typically involve isolation, electric shock, forced immersion in water, and environmental or temperature changes to induce depression in animals. In this experiment, we used an animal model of restraint stress. Experimental animals were confined in a small, immobile space to induce symptoms equivalent to depression, and we examined whether the administration of test compounds had an antidepressant effect. Seven-week-old male wild-type BALB / C mice (Jackson Laboratory Japan, Kanagawa Prefecture, Japan) were used. Restraint stress was administered to mice by confining them in a stainless steel wire mesh mouse stress cage (Natsume Seisakusho, Tokyo, Japan) for 6 hours per day for three consecutive weeks.

[0043] The drug administration method and the tail suspension test method for measuring antidepressant effects in animal experiments using restraint stressed depression model mice were the same as those used in non-stressed mice. Example 2 was carried out in the same manner.

[0044] <Statistical processing> Representative values ​​for each group were expressed as the mean and standard error. One-way analysis of variance was performed between the vehicle control group, test substance group, and vortioxetine group. Significant differences compared to the vehicle control group were indicated as p<0.05 (*), p<0.01 (**), p<0.001 (***), and p<0.0001 (****). Statistical analysis was performed using the medical statistical analysis software GraphPad Prism (GraphPad Software, Boston, USA).

[0045] Figure 2 The figures show the results of a tail suspension test 30 minutes after a single intraperitoneal administration of rotungic acid, barbinerbic acid, or the positive control substance vortioxetine to mice. The vertical axis shows the percentage of immobility time (%), expressed as the mean value ± standard error of five mice per group. The * mark in the table indicates a significant difference compared to the percentage of immobility time (%) in the vehicle control group administered with saline. There was no significant difference between the percentage of immobility time (%) in the rotungic acid and barbinerbic acid groups and the vehicle control group administered with saline. On the other hand, the percentage of immobility time (%) was significantly reduced by administration of the positive control substance vortioxetine. When vortioxetine was administered at 30 mg / kg body weight to unstressed mice, it showed antidepressant effects. Hypomania induced by the antidepressant effects of vortioxetine has been reported ( Non-patent document 13 ), it is not clear whether this is the case with the experimental results.

[0046] Figure 3The results of the tail suspension test 30 minutes after a single intraperitoneal administration of rotun- gic acid, barbinerbic acid, or the positive control substance vortioxetine to mice subjected to restraint stress are shown. The vertical axis represents the percentage of immobility time (%), expressed as the mean ± standard error of five mice per group. An * in the table indicates a significant difference compared to the percentage of immobility time (%) in the vehicle control group administered saline. Compared to the vehicle control group, administration of rotun- gic acid, barbinerbic acid, or the positive control substance vortioxetine at 30 mg / kg body weight each significantly reduced all percentages of immobility time (%). In other words, rotun- gic acid or barbinerbic acid exhibits antidepressant effects when administered at 30 mg / kg body weight to mice subjected to restraint stress.

[0047] When rotogenic acid or barbinerbic acid was administered to non-stressed mice and mice subjected to restraint stress, no antidepressant effect was observed in the non-stressed mice, but an antidepressant effect was confirmed in the restraint stressed mice. Based on these results, rotogenic acid and barbinerbic acid are considered to be highly effective in the prevention, treatment, and / or alleviation of depression and can be used safely. [Industrial Applicability]

[0048] The present invention provides a composition that is highly safe and has the effect of preventing, treating, or alleviating depressive states, and can be widely used as a pharmaceutical, food or drink, dietary supplement, food additive, and cosmetic containing the composition. Ingestion of the product according to the present invention that has the effect of preventing, treating, and / or alleviating depressive states can lead to a reduction in the number of people suffering from depression, which is a social problem, and therefore has great industrial value. [Explanation of symbols]

[0049] saline solution BA Barbinerbic Acid RA rotunnic acid VORT vortioxetine

Claims

1. A composition for the prevention, treatment and / or alleviation of depressive symptoms, anxiety symptoms and / or obsessive-compulsive disorder (excluding compositions containing persimmon leaf extract), which contains as an active ingredient at least one selected from the group consisting of rotungic acid, barbinerbic acid, and their ester and alkoxy derivatives.

2. A composition for the prevention, treatment and / or alleviation of depressive symptoms, anxiety symptoms and / or obsessive-compulsive disorder (excluding compositions containing persimmon leaf extract), which contains at least one selected from alkali metal salts of rotungic acid or barbinerbic acid as an active ingredient.

3. A composition described in any one of claims 1 to 2, which is a pharmaceutical product.

4. A composition described in any one of claims 1 to 2, which is a food or beverage, a nutritional supplement, or a food additive.

5. A composition described in any one of claims 1 to 2, which is a cosmetic.

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