JP5282202B2 - Anti-stress agent or sleep-improving agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an anti-stress agent or a sleep-improving agent which is highly safe and exhibits a strong anti-stress effect or sleep improving effect. <P>SOLUTION: The anti-stress agent or sleep-improving agent includes an extract from a mixture of clove, nutmeg, cinnamon, and Hedychium spicatum as an effective ingredient. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

  The present invention relates to an anti-stress agent or sleep-improving agent comprising an extract of a mixture of clove, bean paste, meat katsura and yamana as an active ingredient.

  In modern societies that are sophisticated, complex, and active 24 hours a day, people are exposed to various types of physical, chemical, psychological and social stress. Especially for modern people living in complex human relationships, there are many psychological factors that constitute stress.

  Various studies have been conducted on psychological stress and the various symptoms caused by it.For example, when psychological stress is detected in the cerebrum, the release of noradrenaline is enhanced in a wide range of brain regions, which is triggered. It has been reported that it causes money and causes mental symptoms such as anxiety and tension (Non-patent Document 1). Moreover, as a mechanism of these, corticotropin-releasing factor (CRF) is released from the hypothalamus, and in response, secretion of adrenocorticotropic hormone (ACTH) increases from the pituitary gland. It has been reported that a biological defense mechanism works by secreting (Non-patent Document 2).

  On the other hand, since the hypothalamus is also the center of the autonomic nerve, the sympathetic nerve is stimulated and noradrenaline is secreted. Sympathetic nerves are also distributed in the adrenal medulla, and adrenaline is released into the blood by stimulation, and physical effects such as increased heart rate, increased blood pressure, and flushing of the face appear due to the action of these catecholamines. This is considered (Non-patent Document 3).

  When stress is strong or lasts for a long time, it affects various organs throughout the body, resulting in symptoms such as peptic ulcer, ischemic heart disease, cerebrovascular disorder, hypertension, and antilipidemia. May cause.

  Currently, drugs used for the purpose of stress reduction and disease prevention are mainly benzodiazepine anxiolytics and sleeping pills. Although these are relatively safe drugs, they are addictive and have side effects, so it is not preferable to take them frequently against temporary stress in daily life. In addition, if the use is interrupted after continuous use, a recoil phenomenon may occur, and the symptoms may be worsened, which is not an ideal antistress agent.

Thus, in consideration of not only the increase in stress load in modern society and mental health given by stress, but also the serious influence on the living body, development of a truly effective and safe anti-stress agent has been desired. In particular, from a preventive standpoint, development of an anti-stress material that can be used for food and luxury goods has been desired (Patent Documents 1 and 2).
On the other hand, there is no report that an extract of a mixture consisting of 4 types of clove, bean paste, meat katsura and yamana used in the present invention reduces stress or improves sleep.

Japanese Patent Laid-Open No. 6-100442 JP 2006-327970 A Tanaka Masatoshi, Metabolism, Vol. 26, p122-131, 1989 Brandenberger, G. et al: Biol. Physiol. Vol. 10, p239-252, 1980 Dimsdale, JE., Moss, J: J. Am. Med. Assoc.Vol.243, p340-342, 1980

  An object of the present invention is to provide an anti-stress agent or sleep-improving agent that has high safety and can exhibit a high anti-stress effect or sleep-improving effect.

  As a result of intensive studies to solve the above-mentioned problems, the inventors of the present invention have prolonged the dormancy time caused by the isolation and breeding of a mouse by using an extract of a mixture of clove, bean paste, meat katsura and yamana. Based on this finding, it has been found that it has a remarkable improvement effect on shortening sleep time, a remarkable suppression effect on aggression, and a remarkable anti-stress effect with an anxiety state caused by the elevated plus maze as an index. Research progressed and the present invention was completed.

That is, the present invention
[1] An anti-stress agent or sleep-improving agent characterized by containing an extract of a mixture of clove, bean paste, meat katsura and yamana as an active ingredient,
[2] The antistress agent or sleep-improving agent according to [1], wherein the extract is a supercritical extract,
[3] The above-mentioned [1], wherein the weight ratio of clove, bean candy, meat katsura and yamana in the mixture is 1: 0.01-100: 0.01-100: 0.01-100. Or the anti-stress agent or sleep-improving agent according to [2],
[4] An anti-stress agent comprising an extract of a mixture of clove, bean paste, meat katsura and yamana as an active ingredient,
[5] An anti-stress or sleep improving food and drink additive comprising the anti-stress agent or sleep improving agent according to any one of [1] to [3], and [6] described in [4] above. Anti-stress food and beverage additives comprising the anti-stress agent of
About.

  The anti-stress agent of the present invention can significantly prevent and / or reduce stress. Moreover, the sleep improving agent of the present invention can remarkably improve sleep. Furthermore, the anti-stress agent or sleep-improving agent of the present invention has a feature that it is very toxic.

  The present invention relates to an anti-stress agent or sleep-improving agent comprising an extract of a mixture of clove, bean paste, meat katsura and yamana as an active ingredient.

The anti-stress agent or sleep-improving agent of the present invention contains an extract of a mixture of clove, bean paste, meat katsura and yamana as an active ingredient.
The clove used in the present invention (also referred to as clove, clove) is a herbal medicine obtained by drying the buds of Eugenia caryophyllata Thunberg. Meat bean meal (Nikuzuku) used in the present invention is a herbal medicine using seeds of Myristica fragrans. Meat cinnamon (also referred to as Nikkei or Keihi) used in the present invention is a herbal medicine obtained by drying the bark of Cinnamomum cassia Blume. The sana used in the present invention is a herbal medicine dried by cutting the rhizomes of the ginger family Sanna (Hedychium spicatum).
Examples of the form of the extract of the mixture of Japanese alphabet, bean candy, meat katsura and yamana used in the present invention include solids, aqueous solutions and slurries.

  Extraction means for producing an extract of a mixture of Japanese characters, bean paste, meat katsura and yamana used in the present invention is not particularly limited, and hot water extraction, cold water extraction, supercritical extraction, solvent extraction, etc. may be used. Although it is possible, it is preferable to use the extract of the mixture of the sword, the bean paste, the meat katsura and the Yamana used in the present invention after supercritical extraction, filtration, cooling and drying. The weight ratio of the clove, bean paste, meat katsura and yamana in the mixture used for extraction is not particularly limited, but is usually about 1: 0.01 to 100: 0.01 to 100: 0.01 to 100, preferably 1. : 0.02-50: 0.02-50: about 0.02-50, more preferably about 1: 0.1-10: 0.1-10: 0.1-10.

  The anti-stress agent or sleep-improving agent of the present invention may be composed only of an extract of the mixture of the above-mentioned letter, meat bean paste, meat katsura and yamana, and other additions acceptable to foods or pharmaceuticals to the extract. A thing can also be added. Additives are not particularly limited as long as they are acceptable for food or pharmaceuticals. For example, excipients (lactose, sucrose, starch syrup, dextrin, corn starch, crystalline cellulose, etc.), lubricants (magnesium stearate, sucrose) Fatty acid esters, glycerin fatty acid esters, etc.), disintegrating agents (carboxymethyl cellulose calcium, anhydrous calcium hydrogen phosphate, calcium carbonate, etc.), binders (starch glue solution, hydroxypropyl cellulose solution, gum arabic solution, etc.), solubilizing agents (Arabic Rubber, polysorbate 80, etc.), sweeteners (sugar, fructose / glucose liquid sugar, honey, aspartame, etc.), colorants (β-carotene, food tar pigment, riboflavin, etc.), preservatives (sorbic acid, methyl paraoxybenzoate, Sodium sulfite, etc.), thickener (alginate sodium , Sodium carboxymethylcellulose, sodium polyacrylate, etc.), antioxidants (BHT, BHA, ascorbic acid, tocopherol, etc.), flavors (mint, strawberry flavor, etc.), acidulants (citric acid, lactic acid, DL-malic acid, etc.) ), Seasonings (DL-alanine, sodium 5'-inosinate, sodium L-glutamate, etc.), emulsifiers (glycerin fatty acid ester, sucrose fatty acid ester, etc.), pH adjusters (citric acid, trisodium citrate, etc.), Vitamins (vitamin C, vitamin E, etc.), minerals (calcium, iron, magnesium, zinc, potassium, etc.), amino acids and the like can be used.

  The method for producing the anti-stress agent or sleep-improving agent of the present invention is not particularly limited, and is a method for producing a mixture of extract of a mixture of clove, bean curd, meat katsura and yamana and other additives if necessary, solvent General methods such as a method of dissolving a mixture of clove, meat bean paste, meat katsura and Yamana and other additives as necessary to make a mixed solution, a method of freeze-drying the mixed solution, a method of spray drying, etc. Food additive and pharmaceutical manufacturing methods apply.

  The anti-stress agent or sleep-improving agent of the present invention may be solid (eg, tablet, granule, powder, capsule, etc.), sol, gel, and liquid, such as capsule, tablet, It can be made into preparations such as powders, granules and drinks. Moreover, it is good also as an easily soluble preparation added to a drink or mineral water at the time of use. In the case of a drink, if desired, it can be given a taste of a favorite beverage by mixing other medicinal ingredients, vitamins, minerals, hormones, nutritional ingredients, flavoring agents and the like. The medicinal ingredients, vitamins, minerals, hormones, nutritional ingredients or flavoring agents are not particularly limited as long as they do not inhibit the anti-stress action and sleep-improving effect of the clove, meat bean paste, meat katsura and yamana of the present invention.

  The anti-stress agent or sleep-improving agent of the present invention can be used as a pharmaceutical preparation or as a food or drink additive.

  When the anti-stress agent or sleep-improving agent of the present invention is used as a pharmaceutical preparation, it is preferably used by oral administration, and the dose of a mixture of dichroic, meat bean paste, meat katsura and yamana (also referred to as herbal mixed extract) is used. Since it varies depending on the sex, age, health condition, etc. of the person who ingests it, it cannot be generally stated, but a sufficient effect can be obtained if 8 mg / kg or more is administered as an herbal mixed extract. Therefore, in order for the anti-stress agent or sleep-improving agent of the present invention to fully exert its effect, the herb mixed extract is usually taken at about 0.1 to 10 g, preferably about 0.1 to 5 g per dose. It is preferable.

When the antistress agent or sleep improving agent of the present invention is used as a food or drink additive, the applied food or drink includes soft drinks, drops, candy, chewing gum, chocolate, gummy, yogurt, ice cream, pudding, jelly confectionery, Cookies, margarines, shortenings, mayonnaise, dressings and the like.
When the anti-stress agent or sleep-improving agent of the present invention is used as a food or drink additive, the compounding amount of the anti-stress agent or sleep-improving agent in the food or drink varies depending on the type of food or drink, but usually as an active ingredient About 0.01 to 10% by weight, preferably about 0.1 to 3% by weight.

  The anti-stress agent of the present invention can be taken when a stress load is expected or when it is stressed to prevent or reduce stress, and can be prevented or reduced by regular use. The sleep improving agent of the present invention can be taken about 1 hour before going to bed to about 30 minutes before bedtime to improve sleep.

  The present invention will be described below with reference to examples, but the present invention is not limited to these examples.

[Production example]
The antistress agent or sleep improving agent of the present invention was prepared under the following conditions.
Weighed 10 kg each of the conforming raw material raw material test products described in the Chinese Pharmacopoeia (Choji, Meat Beans, Meat Katsura and Yamana) and mixed. The mixed product was pulverized, and fine powder was obtained and mixed again with a 15-20 mesh sieve. The remixed powder was filled into an extraction kettle and supercritically extracted with carbon dioxide at 50 ° C., 25-30 MP for 4 hours (carbon dioxide flow rate: space velocity (SV) = 4 (1 / h)). After extraction, an oily extract was separated to obtain a crude herbal mixed extract. The crude herb mixed extract was filled in a heating and stirring kettle, stirred at 60 ° C. for 1 hour, then cooled to room temperature over 10 to 12 hours, and filtered through a 120 mesh filter to obtain about 4 kg of the herb mixed extract. This herb mixed extract was subjected to heavy metal test, arsenic test and microbial limit test described in the 8th edition of the Food Additives Standard, heavy metal 20ppm or less, arsenic 2ppm or less, bacteria count 1000cfu / g, fungus count 100cfu / g or less And did not recognize E. coli. Moreover, when the component of this herb mixed extract was analyzed, 18-19% of eugenol was contained.

[Example 1]
A drink was prepared according to the following formulation.

[Example 2]
With the following formulation, the herbal mixed extract produced in Production Example 1 was coated with gelatin and glycerin to produce a soft capsule.

[Test Example 1]
Improving effect on stress-induced prolongation and shortening of sleep time by isolation breeding Test animals were 5 weeks old ddY male mice (Japan SLC, body weight 20-30 g) after 1 week pre-breeding Used in the experiment. Breeding is room temperature 23 ± 2 ° C, humidity 30-80%, ventilation rate 12 times / hour (all fresh air system), lighting time (12 hours / day, 6:30 am on, 6:30 pm off) ) In the breeding room set up in isolation, one for each cage in a polycarbonate cage (manufactured by Claire Japan, 180W × 250D × 140Hmm), and one for a group of individuals in a polycarbonate cage (manufactured by Claire Japan, 265W × 450D) 5 x 160 Hmm) were raised for 4 weeks. The feed was solid feed CRF-1 (produced by Oriental Yeast Co., Ltd.), and drinking water was freely taken.
Each test solution was prepared by suspending 30 mg, 100 mg, and 300 mg of the herbal mixed extract produced in Production Example in 3 ml of olive oil adjusted to 50% concentration with distilled water. In addition, 100 mg and 300 mg of γ-aminobutyric acid (hereinafter referred to as GABA) were used as comparative agents and dissolved in 3 ml of distilled water to obtain test solutions.
After 4 weeks of isolation and rearing, the test solution as a group of 10 animals so that the herbal mixed extract dosage is 100, 300, 1000 mg / kg, and the GABA dosage is 300, 1000 mg / kg. The mice were orally administered to mice, and pentobarbital sodium 40 mg / kg was intraperitoneally administered 1 hour after administration. The herb mixed extract and GABA non-administration group was used as a control, the group-bred mice were used as a group-bred control group, and the isolated-bred mice were used as an isolated-bred control group. The time from when the pentobarbital sodium was administered until the specular reflex disappeared (hereinafter referred to as “sleep time”) and the time from the disappearance of the direct reflex (hereinafter referred to as “sleep time”) were measured. Experimental results are shown as mean ± standard error, and Bonferroni / Dunn type multiple comparison test was used for the significance test. The results are shown in FIG.

  As shown in FIG. 1, in the isolated breeding control group, the dormancy time was extended by the isolated breeding, and the sleeping time was shortened. However, in the herbal mixed extract administration group, both of them were remarkably improved by administration of 1000 mg / kg (significant difference of 0.1% or less), and the lead time and sleep time of the mice in the 1000 mg / kg administration group were the same as those in the group-bred control group. It was about. On the other hand, in the GABA administration group, no improvement was observed in the sleep time and sleep time.

[Test Example 2]
Inhibitory effect on stress-induced aggression by isolated breeding Test animals were 5-week-old ddY male mice (Japan SLC Co., Ltd., body weight 20-30 g) used for experiments after 1 week of preliminary breeding. Breeding is room temperature 23 ± 2 ° C, humidity 30-80%, ventilation rate 12 times / hour (all fresh air system), lighting time (12 hours / day, 6:30 am on, 6:30 pm off) ) In the breeding room set up in isolation, one for each cage in a polycarbonate cage (manufactured by Claire Japan, 180W × 250D × 140Hmm), and one for a group of individuals in a polycarbonate cage (manufactured by Claire Japan, 265W × 450D) 5 x 160 Hmm) were raised for 4 weeks. The feed was solid feed CRF-1 (produced by Oriental Yeast Co., Ltd.), and drinking water was freely taken.
After 4 weeks of isolation, the test solution prepared in the same manner as in Test Example 1 as 10 animals per group was adjusted so that the herbal mixed extract dosage was 100, 300, 1000 mg / kg, and the GABA dosage was Mice were orally administered at 300 and 1000 mg / kg, and two mice were placed in the observation cage 1 hour after administration, and the time from the start of the battle until the start of the struggle, and the struggle during the 20-minute observation period The number of times and struggle time were measured. The herb mixed extract and GABA non-administration group was used as a control, the group-bred mice were used as a group-bred control group, and the isolated-bred mice were used as an isolated-bred control group. Experimental results are shown as mean ± standard error, and Bonferroni / Dunn type multiple comparison test was used for the significance test. The results are shown in Table 3.

表中、＃＃＃は、群飼育対照に対してｐ＜０．００１であることを意味し、＊は隔離飼育対照に対してｐ＜０．０５であることを意味し、＊＊＊は隔離飼育対照に対してｐ＜０．００１であることを意味する。
表３に示すように、隔離飼育対照群では、隔離飼育により闘争開始までの時間は短縮、闘争回数は増加、および闘争時間は延長した。しかし、ハーブ混合エキス投与群では用量依存的にいずれも著しく改善し（３００ｍｇ／ｋｇ投与群で有意差５％以下、１０００ｍｇ／ｋｇ投与群で有意差０．１％以下）、ハーブ混合エキス１０００ｍｇ／ｋｇ投与群のマウスは、群飼育対照群のマウスと同じく闘争を起こさなかった。一方、ＧＡＢＡ投与群では、闘争開始までの時間、闘争回数および闘争時間のいずれにも改善は見られなかった。

In the table, ## means p <0.001 with respect to group control, * means p <0.05 with respect to isolated control, *** means It means p <0.001 relative to the quarantine control.
As shown in Table 3, in the isolated breeding control group, the time until the start of the struggle was shortened, the number of struggles increased, and the struggle time was prolonged by the breeding. However, in the herbal mixed extract administration group, all dose-dependently improved (significant difference 5% or less in the 300 mg / kg administration group, significant difference 0.1% or less in the 1000 mg / kg administration group). The mice in the kg administration group did not struggle as the mice in the group-bred control group. On the other hand, in the GABA administration group, there was no improvement in any of the time until the start of the struggle, the number of struggles, and the struggle time.

[Test Example 3]
Effect on Anxiety Using Elevated Cross Maze Test animals were 5-week-old ddY male mice (Japan SLC Co., Ltd., body weight 20-30 g) used for experiments after 1 week of preliminary breeding. Breeding is room temperature 23 ± 2 ° C, humidity 30-80%, ventilation rate 12 times / hour (all fresh air system), lighting time (12 hours / day, 6:30 am on, 6:30 pm off) ) And was raised in polycarbonate cages (manufactured by CLEA Japan, 265W × 450D × 160Hmm). The feed was solid feed CRF-1 (produced by Oriental Yeast Co., Ltd.), and drinking water was freely taken.
The elevated cross maze is a cross of two black vinyl chloride plates, 40 cm high, 65 cm long and 5 cm wide, that are 40 cm above the floor. A wall with a height of 30 cm is attached except for the central intersection. Accordingly, the maze is composed of two open arms without walls, two closed arms with walls, and a central intersection.
Test solution prepared in the same manner as in Test Example 1 as 10 animals per group so that the herbal mixed extract dosage is 100, 300, 1000 mg / kg, and the GABA dosage is 300, 1000 mg / kg. 1 hour after administration, place the mouse at one crossed arm at the center of the elevated plus maze, let it freely explore the maze for 5 minutes, observe its behavior, The number of intrusions into the open arm and the closed arm and the accumulated stay time on the open arm were measured, and the ratio of the number of intrusions into the open arm and the accumulated stay time ratio on the open arm were calculated therefrom. The herbal mixed extract and GABA non-administered group was used as a control. Experimental results are shown as mean ± standard error, and Bonferroni / Dunn type multiple comparison test was used for the significance test. The results are shown in FIG.

  As shown in FIG. 2, the herbal mixture extract administration group increased the open arm intrusion frequency ratio and the open arm cumulative residence time ratio in a dose-dependent manner, and the 1000 mg / kg administration significantly improved both (significant difference of 1% or less) ). On the other hand, in the GABA administration group, neither the open arm intrusion frequency ratio nor the open arm cumulative residence time ratio was improved.

[Test Example 4]
Improving effect on sleep time shortening Test animals used were 5-week-old ddY male mice (Japan SLC Co., Ltd., body weight 24-28 g) after 1 week of preliminary breeding. Breeding is room temperature 23 ± 2 ° C, humidity 30-80%, ventilation rate 12 times / hour (all fresh air system), lighting time (12 hours / day, 6:30 am on, 6:30 pm off) ) In the breeding room set up. The feed was solid feed CRF-1 (produced by Oriental Yeast Co., Ltd.), and drinking water was freely taken.
In the same manner as in Test Example 1, a test solution of the herbal mixed extract was prepared. As a group of 10 animals, the test solution was orally administered to mice so that the herbal mixed extract dosage was 100, 300, 1000 mg / kg. One hour after administration, pentobarbital sodium 40 mg / kg was intraperitoneally administered. The time (sleeping time) until recovery from the disappearance of the reflex was measured. The herb mixture extract non-administration group was used as a control. Experimental results are shown as mean ± standard error, and Bonferroni / Dunn type multiple comparison test was used for the significance test. The results are shown in FIG.

  As shown in FIG. 3, in the herb mixed extract administration group, the sleep time was remarkably improved by administration of 300 mg / kg or more.

  From the above Test Examples 1 to 4, the anti-stress agent or sleep-improving agent of the present invention improves prolongation of sleep time and shortening of sleep time caused by isolating and breeding mice, and suppresses the expression of aggressiveness. Furthermore, it was confirmed that the state of anxiety caused by the elevated plus maze was reduced.

[Test Example 5]
Anti-stress effect in humans Healthy individuals (13 males, ages 32 to 59 years old) are paneled, and while continuing their daily lives, first, a week before taking herbal mixed extract soft capsules, test for stress using GHQ questionnaire After measuring blood pressure and heart rate and measuring salivary IgA, cortisol and chromogranin A, 2 capsules of the herbal mixed extract soft capsule prepared in Example 2 (amount of herbal mixed extract: 500 mg in total) were taken for 3 days. The same examination / measurement was performed one hour after taking the day. Saliva was collected with “Salivet” (manufactured by SARESTDT), collected by centrifugation, and stored frozen until measurement. For the measurement of IgA, a fully automatic EIA measurement device (POSEIDON II, manufactured by Aloka) was used. For the measurement of cortisol, a gamma counter (ARC-950, manufactured by Aloka) was used. For the measurement of chromogranin A, “YK070 human chromogranin A was used. "EIA kit" (manufactured by Yauchihara Laboratory) was used.
The experimental results were displayed in proportions with the measured values before taking each being 100. The results are shown in FIG. 4, FIG. 5 and FIG.
From the results of FIG. 4, FIG. 5 and FIG. 6, by taking the herb mixed extract, the stress state was reduced, the blood pressure was slightly decreased, the salivary cortisol and chromogranin A decreased and the IgA increased. Improvement was observed.

  According to the present invention, it is possible to provide an anti-stress agent or sleep improving agent that has high safety and can exhibit a high anti-stress effect or sleep improving effect.

FIG. 1 shows changes in the sleeping time and sleeping time of the herbal mixed extract or GABA administration group produced in Production Example. (A) shows the sleeping time (unit: minute), and (B) shows the sleeping time (unit: minute). FIG. 2 shows the anti-stress effect when the herbal mixed extract produced in the production example or GABA is administered in the elevated plus maze test. (A) shows the open arm intrusion frequency ratio (%), and (B) shows the open arm accumulated stay time ratio (%). FIG. 3 shows the effect of improving sleep time shortening in the herb mixed extract administration group. The vertical axis represents sleep time (unit: minutes). FIG. 4 shows the effect on the GHQ test score of herbal mixed extract taken for 3 days. The vertical axis shows the rate of change when the score before taking is taken as 100. The mean ± standard error of the GHQ test score before taking was 7 ± 3. FIG. 5 shows the effect on the systolic blood pressure and diastolic blood pressure of the herbal mixed extract taken for 3 days. The vertical axis shows the rate of change when the blood pressure and heart rate before taking are taken as 100. The mean ± standard error of systolic blood pressure, diastolic blood pressure and heart rate before taking were 128 ± 5 mmHg, 81 ± 3 mmHg and 78 ± 3 beats / min, respectively. FIG. 6 shows the influence on salivary IgA, cortisol and chromogranin A taken for 3 days. The vertical axis shows the rate of change when each parameter measurement before taking is 100. The mean ± standard error of IgA, cortisol and chromogranin A before administration were 404 ± 64 μg / mL, 0.39 ± 0.04 μg / dL and 2.66 ± 0.56 pmol / mg protein, respectively.

Claims (5)

An antihypertensive agent comprising, as an active ingredient, an extract of a mixture of clove, bean paste, meat katsura and yamana. Extract Ri supercritical extract der, after supercritical extraction, filtration, and cooling, blood pressure lowering agent according to claim 1, wherein the dried extract der Rukoto. The blood pressure-lowering agent according to claim 1 or 2, wherein the extract contains eugenol, and the content of eugenol is 18 to 19%. The blood pressure-lowering agent according to any one of claims 1 to 3, wherein the extract has a heavy metal content of 20 ppm or less, arsenic 2 ppm or less, a bacterial count of 1000 cfu / g or less, and a fungal count of 100 cfu / g or less. Clove in the mixture, Nikumame寇, the weight ratio of cassia and Yamana is 1: 0.01: 0.01: any of the preceding claims, characterized in that 0.01 to 100 blood pressure-lowering agents of crab described.

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