JP2007106725A - Composition for ameliorating mood disorder - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for ameliorating mood disorder by finding out a substance having mode disorder ameliorating activity and not increasing weight of uterine from a highly safety plant extract, and comprising the substance as an active ingredient. <P>SOLUTION: The composition for ameliorating mood disorder comprises an extract of Tillia platyphyllos as the active ingredient. The composition for ameliorating mood disorder comprises one or two or more kinds of flavonoids selected from a group comprising afzeline, quercetin-3-O-arabinopyranoside, kaempferol-3-O-rutinoside isolated from the extract of Tillia platyphyllos. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a composition for improving mood disorders, and more particularly, to a composition for improving mood disorders caused by depression, manic depression, climacteric disorder or a decrease in estrogen secretion.

  Stress such as physical / mental fatigue, life rhythm and human relations, and menopause cause anxiety and frustration, and present symptoms such as emotional disorders, sleep disorders, eating disorders, and communication problems with others. It is known to cause mood disorders. It is known that when women are menopause, the amount of estrogen, one of the female hormones, decreases, resulting in mood disorders.

  Examples of substances having the effect of preventing and treating mood disorders include tryptamine derivatives derived from cacao (see Patent Document 1), flavonoid compounds derived from Rafu hemp extract (see Patent Document 2), dihydropyridine (see Patent Document 3). In addition, muia plama extract (see Patent Document 4) and the like are known. In addition, a method of treating mood disorders due to menopause or a decrease in the amount of estrogen secretion by estrogen complementary therapy is known. However, estrogen complementation therapy can improve mood disorders due to decreased estrogen secretion, but supplementing estrogen increases the endometrium and increases uterine weight. There is a problem that contributes to cancer.

In addition, it is known that flavonoids are contained in linden flour (see non-patent document 1), liver function protecting action (see non-patent document 2), antioxidant action (see non-patent documents 3 and 4). ) Etc., but it was not known to have a mood disorder improving action.
JP 2003-137780 A JP 2002-201139 A Japanese Patent No. 2701402 JP 2000-119187 A Matsuda et al., Natural Organic Compound Discussion Meeting, 2000, Vol. 42, p. 469-474 Bioorganic & Medicinal Chemistry, 2002, Vol. 10, No. 3, p. 707-712 Phytotherapy Research, 2002, Vol. 16, No. 4, p. 364-367 International Journal of Food Sciences and Nutrition, 2001, Vol. 52, No. 6, p. 501-508

  An object of the present invention is to find a substance having a mood disorder improving action among plant extracts having high safety and not increasing the weight of the uterus, and to provide a composition for improving mood disorder using the substance as an active ingredient. And

  In order to solve the above-mentioned problems, the composition for improving mood disorders of the present invention is characterized by containing a linden flour extract as an active ingredient. The mood disorder improving composition of the present invention is selected from the group consisting of afzelin, quercetin-3-O-arabinopyranoside and kaempferol-3-O-rutinoside isolated from a lindenflower extract. It contains a seed or two or more flavonoids as an active ingredient.

  As used herein, “mood disorder” is a type of mental disorder, and symptoms of mood disorder include, for example, abnormal emotional expression of emotions such as emotions, depression, tragedy, guilt, Depressive mood such as despair; psychomotor cessation; anxiety; feelings of sleep, anorexia, loss of libido, constipation, dry mouth, headaches, etc. These symptoms are improved by improving mood disorders Can be improved.

  The mood disorder is preferably a mood disorder caused by at least one selected from the group consisting of depression, manic depression, menopause, and decreased estrogen secretion, and the composition is a pharmaceutical composition It is preferable that it is a food-drinks composition or a cosmetic composition.

  The composition for improving mood disorders of the present invention can improve mood disorders caused by depression, manic depression, climacteric disorder or a decrease in estrogen secretion without increasing uterine weight.

The present invention will be described below.
The composition for improving mood disorders of the present invention comprises an extract from linden flour, or afzelin, quercetin-3-O-arabinopyranoside and kaempferol-3-O-rutinoside isolated from the extract. One or more flavonoids selected from the group are contained as active ingredients.

  Here, in the present invention, the “extract” refers to an extract obtained from linden flour as an extraction raw material, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or a crude product thereof. Both purified products and purified products are included.

  The extraction raw material used in the present invention is linden flour. A linden flower is a flower with a small leaf of a linden (scientific name: Tilia plantyphillos, Tilia cordata, Tilia europaea, Tilia argentea) belonging to the family Lindenaceae. Linden flour as an extraction raw material may be any of collected flower parts and fresh leaf parts, and those dried or roasted, but dried flower parts and leaf parts, or roasted It is preferred to use roasted flower parts and leaves.

  An extract having a mood disorder-improving action can be obtained from linden flour by an extraction method generally used for plant extraction. For example, after the linden flour is dried, it is pulverized as it is or using a crusher, and is subjected to extraction with an extraction solvent, whereby an extract having a mood disorder improving action can be obtained. Drying may be performed in the sun or using a commonly used dryer. Moreover, after performing pretreatment, such as degreasing, with a nonpolar solvent such as hexane, it may be used as an extraction material. By performing pretreatment such as degreasing, extraction treatment with the polar solvent of the plant can be efficiently performed.

  As the extraction solvent, it is preferable to use a polar solvent, and examples thereof include water and hydrophilic organic solvents. These are used alone or in combination of two or more at room temperature or a temperature below the boiling point of the solvent. It is preferable.

  Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, and those subjected to various treatments. Examples of the treatment applied to water include purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, and the like. Therefore, the water that can be used as the extraction solvent in the present invention includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  Examples of hydrophilic organic solvents that can be used as extraction solvents include lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene. Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycol, propylene glycol and glycerin.

  When using the liquid mixture of 2 or more types of polar solvents as an extraction solvent, the mixing ratio can be adjusted suitably. For example, when using a liquid mixture of water and a lower aliphatic alcohol, it is preferable to mix 1 to 90 parts by weight of a lower aliphatic alcohol with respect to 10 parts by weight of water. When using a mixed solution, it is preferable to mix 1 to 40 parts by mass of a lower aliphatic ketone with 10 parts by mass of water, and when using a mixed solution of water and a polyhydric alcohol, water 10 It is preferable to mix 10 to 90 parts by mass of polyhydric alcohol with respect to parts by mass.

  The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be performed according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent 5 to 15 times (mass ratio) of the extraction raw material, the soluble components are extracted at room temperature or under reflux, and then filtered to remove the extraction residue. A liquid can be obtained.

  Since the extract thus obtained has an effect of improving mood disorders, it can be used as it is as an active ingredient of the composition of the present invention, but the concentrate of the extract or the extract is fractionated. -It is preferable to use flavonoids obtained by purification.

  Here, flavonoids refer to a group of substances in which two phenyl groups are bonded through three carbon atoms having a pyran ring or a similar structure, and are chalcone, dihydrochalcone, flavanoy, flavone, flavonol, flavonol, Includes flavanols, isoflavones, and anthocyans. Examples of the flavonoids contained in the linden flower extract include tiliroside, afzelin, kaempferol-3-O-arabinopyranoside, astragalin, kaempferol-3-O-lutinoside, kaempferol-3,7- Examples include O-dirhamnoside, isoquercitrin, quercitrin, quercetin-3-O-arabinopyranoside, naringenin-7-O-glucopyranoside, and among these, afzelin, quercetin-3-O-arabinopyra It is preferable to use one or more flavonoids selected from the group consisting of noside and kaempferol-3-O-rutinoside as the active ingredient of the composition for improving mood disorders.

  For fractionation / purification of flavonoids from the extract, known methods such as porous adsorption resin, ion exchange resin, silica gel, reverse phase silica gel, and gel filtration can be used alone or in combination.

Flavonoids can be chemically synthesized according to known methods, and chemically synthesized flavonoids can also be used as the active ingredient of the composition of the present invention.
Since flavonoids are substances contained in edible natural products with high safety, they are safe even if taken for a long time regardless of the type of production method.

  In the composition of the present invention, “mood disorder” to be improved is a kind of mental disorder, and symptoms of mood disorder include, for example, abnormal emotional expression of emotions; depression, tragedy, guilt Depressive mood such as feeling and despair; psychomotor control; anxiety; feelings of sleep disorder, loss of appetite, loss of libido, constipation, thirst, headache, etc. Symptoms can be improved.

  The mood disorder may be a mood disorder caused by any cause. Examples of mood disorders to be improved include mood disorders caused by depression or manic depression, mood disorders caused by menopause, mood disorders caused by decreased estrogen secretion, and the like.

  “Menopause” is a variety of physical and mental disorders that occur as a woman enters old age (especially before and after menopause when menstruation is irregular and menstruation ceases). Menopause is thought to be caused by disturbances in the secretion of ovarian hormones (estrogens) and modulation of the secretion of this hormone, and estrogen deficiency is caused by menstrual abnormalities; hot flashes and hot flashes due to changes in vascular reactivity; depression Psychological symptoms such as insomnia; physical and mental disorders such as genitourinary abnormalities, as well as osteoporosis, hyperlipidemia, arteriosclerosis and the like.

  The “decreased estrogen secretion amount” can occur, for example, in the menopause, but the cause of the decreased estrogen secretion amount is not limited thereto.

  Estrogen replacement therapy is generally used for mood disorders caused by climacteric disorders and mood disorders caused by decreased estrogen secretion. However, estrogen replacement therapy has a problem that uterine weight increases. In contrast, lindenflower extract or flavonoids isolated from the extract should improve mood disorders caused by menopause and mood disorders caused by decreased estrogen secretion without increasing uterine weight. Can do. Thus, the compositions of the present invention are useful as an alternative to estrogen replacement therapy.

  The form of the composition for improving mood disorders may be any form for internal use or external use as long as it can exert the effect of improving mood disorder. Specific examples thereof include a pharmaceutical composition, a food and drink composition, Examples include cosmetic compositions.

The composition of each composition can be suitably adjusted according to the form.
The pharmaceutical composition may comprise, for example, a lindenflower extract in an amount effective for ameliorating mood disorders or flavonoids isolated from the extract alone, or a pharmaceutically acceptable carrier and / or Or auxiliary agents (for example, binders, absorption promoters, lubricants, emulsifiers, surfactants, antioxidants, preservatives, colorants, flavors, sweeteners, extenders, diluents, dispersants, etc.) It may be formulated by doing. Examples of the dosage form of the pharmaceutical composition include granules, fine granules, tablets, capsules, pills, ointments, gels, pastes, creams, sprays, solutions, suspensions and the like. Examples of the route include oral administration, parenteral administration such as intravenous administration, intramuscular administration, subcutaneous administration, intraarticular administration, and vaginal administration.

  The food / beverage composition includes an amount of lindenflower extract effective for improving mood disorders or flavonoids isolated from the extract, such as sugars such as dextrin and starch; proteins such as gelatin, soybean protein, and corn protein. Amino acids such as alanine, glutamine and isoleucine; polysaccharides such as cellulose and gum arabic; and oils and fats such as soybean oil and medium chain fatty acid triglycerides.

  Moreover, food-drinks composition can also be manufactured by mix | blending flavonoids isolated from the quantity of the linden flower extract effective from the mood effective for improvement of mood disorders in arbitrary food-drinks. Here, “food and drink” are natural products and processed products containing one or more nutrients, and include all food and drink. Examples of foods and drinks that can be blended with the lindenflower extract or flavonoids isolated from the extract include confectionery such as chocolate, biscuits and candy; soft drinks such as juice, lactic acid drinks such as milk and yogurt, etc. Is mentioned.

  Cosmetic compositions can be used in lindenflower extract in an amount effective for improving mood disorders or flavonoids isolated from the extract, such as astringents, bactericides / antibacterial agents, whitening agents, UV absorbers, moisturizers, Manufactured by blending cell activators, anti-inflammatory / antiallergic agents, antioxidant / active oxygen scavengers, fats, waxes, hydrocarbons, fatty acids, alcohols, esters, surfactants, fragrances, etc. be able to.

  The cosmetic composition can also be produced by blending an arbitrary amount of a lindenflower extract or flavonoids isolated from the extract in an amount effective for improving mood disorders. Cosmetics that can contain lindenflower extract or flavonoids isolated from the extract are not particularly limited, and specific examples thereof include ointments, creams, emulsions, lotions, packs, bath preparations, lip balms, lipsticks, etc. Skin cosmetics.

  The dose and frequency of administration of the composition of the present invention can be appropriately changed according to age, sex, individual differences, medical conditions, administration routes, etc. The dose of the composition of the present invention is an active ingredient. In terms of the amount of lindenflower extract or flavonoids isolated from the extract, it is usually 0.1 to 500 mg / kg body weight per day, preferably 0.5 to 200 mg / kg body weight, Can be administered once to several times.

  Hereinafter, although a manufacture example and a test example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to each following example at all.

[Production Example 1] Production of Linden Flour Extract Dry linden flour was pulverized, 10 L of 50 mass% ethanol was added to 1 kg of the pulverized product, heated and extracted at 80 ° C for 2 hours, and filtered while hot. The extraction residue was subjected to the same extraction treatment, and the resulting extracts were combined and concentrated under reduced pressure at 50 ° C. Then, it dried under reduced pressure at 40 degreeC overnight and obtained 248g of linden flour extracts.

[Production Example 2] Preparation of Linden Flower Extract Fraction The Linden Flower Extract (solid content 211 g) obtained in Production Example 1 is a porous adsorption resin (trade name: Diaion HP-20, manufactured by Mitsubishi Chemical Corporation). And eluted with water, 60% by mass methanol and methanol in this order. The solvent was distilled off from each of the water fraction, the 60 mass% methanol fraction, and the methanol fraction under reduced pressure to obtain 128 g of the water fraction, 61 g of the 60 mass% methanol fraction, and 13 g of the methanol fraction.

[Production Example 3] Isolation of flavonoids The solid fraction of the methanol fraction (11 g) obtained in Production Example 2 was sequentially treated by silica gel column chromatography, gel filtration column chromatography, and recycle preparative HPLC for fractionation. Tiliroside (91 mg), afzelin (15 mg), kaempferol-3-O-arabinopyranoside (43 mg), astragalin (195 mg), kaempferol-3-O-rutinoside (21 mg), kaempferol-3 , 7-O-dirhamnoside (37 mg), isoquercitrin (80 mg), quercitrin (153 mg), quercetin-3-O-arabinopyranoside (145 mg) and naringenin-7-O-glucopyranoside (34 mg) Got a kind.

  These flavonoids were identified by NMR analysis. NMR spectral data obtained by NMR analysis are literature values (Tyriloside Astragalin: “Chemical and Pharmaceutical. Bulletin.”, 1978, Vol. 26, p. 3594-3596, Afzelin: “Phytochemistry”, 1980, No. 1 19, p.2643, naringenin-7-O-glucoside: “Phytochemistry”, 1978, 17, p. 1064, quercetin-3-O-arabinopyranoside kaempferol-3-O-arabi Nopyranoside quercitrin kaempferol-3-O-lutinoside isoquercitrin: “Tetrahedron”, 1978, Vol. 34, p.1389-1397, kaempferol-3,7-O-ziramnoside: “ Table 1 shows the results compared with “Turkish Journal of Chemistry”, 2000, Vol. 24, p.191-197).

[Test Example 1] Forced swimming test for mice The linden flower extract obtained in Production Example 1 was subjected to a forced swimming test as follows. In the forced swimming test, an aqueous suspension of Lindenflower extract was administered at a rate of 75 mg / kg / day, 150 mg / kg / day, 300 mg / kg / day, 450 mg / kg / day for 2 weeks. The method was performed according to the method (Porsolt et al., Nature, 266: 730-732, 1977) and the method of Yoshimura et al. (Yoshimura / Yamakawa, Brain Science, 22: 49-54, 2000).

  As a test animal, a menopausal model animal obtained by removing bilateral ovaries of an ICR female mouse (9 weeks old, weight 30 to 34 g) was used. All mice were housed in groups of 10 per gauge, and the floor covering was changed once a week. After removing both ovaries under anesthesia, the awake mouse was returned to its original home gauge. During the test period, food and water were freely ingested, and the animals were reared for a certain period of time at a room temperature of 23 ± 1 ° C. and a 12 hour light / dark cycle.

As an experimental group, a normal group, a sham operation group, and an operation group were set.
“Surgery group” means that under pentobarbital anesthesia, about 5 mm incision is made in the dorsal abdomen of the mouse, the ovary and the fat tissue around the ovary are temporarily exposed outside the body, and ligation is made between the ovary and the end of the uterus. Then, the ovaries were excised, and then the uterus and surrounding tissues were returned to the body, and the abdominal wall and skin were sutured.
The “sham surgery group” is a group of animals that are sutured without excision of the ovaries after laparotomy in the same manner as the surgery group.
The “normal group” is a group of animals not subjected to anesthesia and surgical invasion.

  Each sample was orally administered to the mice in the surgical group once a day for 2 weeks from the day when the ovaries were removed to the end of the forced swimming test. The normal group and sham operation group were orally administered with water alone for 2 weeks. In addition, a group in which only water was orally administered to the operation group was used as a control group for comparing the effects of the test substance.

In the forced swimming test, water at 25 ° C. was poured into a transparent polycarbonate graduated cylinder (inner diameter: 10 cm, height: 25 cm), and the water surface was adjusted to a position 10 cm from the bottom. Each experimental animal (mouse) was gently placed in a graduated cylinder and allowed to swim for 6 minutes. The video system was used for recording, and then the event recorder was operated to measure the time of floating in the immobile state from the second to sixth minutes.
The results are shown in Table 2.

  As shown in Table 2, in the group to which the aqueous suspension of linden flower extract was administered, the immobility time prolonged by ovariectomy was significantly shortened. From this, it was confirmed that the linden flower extract has an action to improve mood disorders caused by depression and the like, and the action was confirmed to be dose-dependent.

[Test Example 2] Measurement of mouse uterine weight The uterine weight of the lindenflower extract obtained in Production Example 1 was measured as follows.

After the observation of immobility time was completed in Test Example 1, the mouse was administered with an excessive amount of pentobarbital (100 mg / kg or more) to cause respiratory arrest, sacrificed, opened, and the uterus was removed. The excised uterus was spread on a filter paper to remove the adhering scholar membrane and blood vessels, and immediately wet weight was weighed with an analytical balance.
The results are shown in Table 3.

  As shown in Table 3, no increase in uterine weight was observed in the group to which the lindenflower extract was administered.

[Test Example 3] Forced swimming test About the lindenflower extract obtained in Production Example 1, each fraction of the lindenflower extract obtained in Production Example 2, and the flavonoids obtained in Production Example 3, the following Thus, a forced swimming test was conducted.

Aqueous suspension prepared by suspending the lindenflower extract obtained in Production Example 1, each fraction of the lindenflower extract obtained in Production Example 2, and the flavonoids obtained in Production Example 3 in water Each solution was orally administered for 2 weeks, and mice were subjected to forced swimming test in the same manner as in Test Example 1.
The results are shown in Table 4.

  As shown in Table 4, the immobility time was significantly shortened in the group administered with lindenflower extract, 60% by mass methanol fraction, methanol fraction, afzelin, kaempferol-3-O-rutinoside and aviculaline. From this, the linden flower extract, 60% by mass methanol fraction, methanol fraction, aphzelin, kaempferol-3-O-rutinoside and quercetin-3-O-arabinopyranoside are caused by depression and the like. It was confirmed to have an effect of improving mood disorders, and the effect was confirmed to be dose-dependent.

[Test Example 4] Measurement of uterine weight After observing immobility time in Test Example 3, mice were given an excessive amount of pentobarbital (100 mg / kg or more) to cause respiratory arrest, sacrificed, and opened. The uterus was removed. The excised uterus was spread on a filter paper to remove the adhering scholar membrane and blood vessels, and immediately wet weight was weighed with an analytical balance.
The results are shown in Table 5.

  As shown in Table 5, Lindenflower extract, 60% by mass methanol fraction, methanol fraction, various flavonoids (tililloside, afzelin, kaempferol-3-O-arabinopyranoside, quercetin-3-O- In the group administered arabinopyranoside, astragalin, naringenin-7-O-glucopyranoside, quercitrin, kaempferol-3,7, O-dirhamnoside, kaempferol-3-O-lutinoside or isoquercitrin) There was no increase in uterine weight.

The composition of the present invention is useful for improving mood disorders caused by depression or manic depression, mood disorders caused by climacteric disorders, and mood disorders caused by decreased estrogen secretion.

Claims (4)

  A composition for improving mood disorders, comprising a linden flower extract as an active ingredient.   Contains one or more flavonoids selected from the group consisting of afzelin, quercetin-3-O-arabinopyranoside and kaempferol-3-O-rutinoside isolated from lindenflower extract as an active ingredient A composition for improving mood disorders.   The mood disorder according to claim 1 or 2, wherein the mood disorder is a mood disorder caused by at least one selected from the group consisting of depression, manic depression, menopause, and decreased estrogen secretion. Disability improving composition. The composition for improving mood disorders according to any one of claims 1 to 3, wherein the composition is a pharmaceutical composition, a food / beverage product composition, or a cosmetic composition.