JP7523889B2 - Pharmaceutical composition for improving activity level - Google Patents

Description

The present invention relates to a pharmaceutical composition that can improve physical and/or mental activity. The present invention also relates to a pharmaceutical composition that can improve fatigue.

In order to live a healthy daily life with improved quality of life, it is important to prevent a decrease in activity and the accumulation of fatigue. It is known that a decrease in activity and fatigue can be caused by a wide range of factors, including insomnia, decreased physical strength, decreased metabolic capacity, stress such as excessive tension, and decreased blood flow. In recent years, against the backdrop of an aging and stressful society, there has been a trend for an increasing number of people to experience a decrease in activity and accumulation of fatigue.

Various oral preparations effective for improving activity or fatigue have been proposed. For example, Patent Document 1 discloses that oleuropein contained in olive leaf extract is effective in suppressing a decrease in activity. Patent Document 2 discloses that isoleucine and threonine can suppress a decrease in activity. Patent Document 3 discloses that arachidonic acid and/or a compound containing arachidonic acid as a constituent fatty acid can suppress a decrease in activity.

On the other hand, Poria cocos is a herbal medicine made by drying the sclerotium of Polyporaceae fungus and removing the outer skin, and has traditionally been used in herbal medicines and herbal medicines. However, there have been no reports that Poria cocos has the effect of improving activity levels or fatigue.

JP 2016-132657 A International Publication No. 2015/133627 JP 2007-8861 A

The object of the present invention is to provide a pharmaceutical composition that can improve activity levels. Another object of the present invention is to provide a pharmaceutical composition that can improve fatigue.

The inventors conducted extensive research to solve the above problems and found that Poria cocos and/or an extract thereof have the effect of improving activity and fatigue, and that a pharmaceutical composition containing Poria cocos and/or an extract thereof can be used to improve activity and recover from fatigue. The present invention was completed based on this knowledge and through further research.

That is, the present invention provides the following aspects.
Item 1. A pharmaceutical composition for improving activity, comprising Poria cocos and/or an extract thereof.
Item 2. The pharmaceutical composition for improving activity according to Item 1, comprising a Chinese medicine containing Poria cocos or an extract thereof.
Item 3. The pharmaceutical composition for improving activity according to Item 2, wherein the Chinese medicine is at least one selected from the group consisting of Kamikihito, Tokishakuyakusan, and Sanzaoninto.
Item 4. The pharmaceutical composition for improving physical activity according to any one of Items 1 to 3, which is used to improve physical activity.
Item 5. A pharmaceutical composition for improving fatigue, comprising Poria cocos and/or an extract thereof.
Item 6. The pharmaceutical composition for improving fatigue according to Item 5, comprising a Chinese medicine containing Poria cocos or an extract thereof.
Item 7. The pharmaceutical composition for improving fatigue according to Item 6, wherein the Chinese medicine is at least one selected from the group consisting of Kamikihito, Tokishakuyakusan, and Sanzaoninto.
Item 8. The pharmaceutical composition for improving fatigue according to any one of Items 5 to 7, which is used to improve fatigue caused by stress.

The present invention makes it possible to suppress a decrease in activity level and restore a decreased activity level, and therefore has the effects of increasing the frequency or duration of exercise, increasing the frequency or duration of going out, increasing the frequency or duration of work or housework, improving concentration, restoring physical strength during or after illness, suppressing or restoring a decrease in physical strength when healthy, suppressing or promoting recovery from fatigue, preventing or improving a frail constitution, and maintaining the physical functions of the elderly, thereby contributing to improving QOL. Furthermore, the present invention can also effectively improve fatigue.

FIG. 1 shows the results of measuring the activity of mice in each group in Test Example 1. FIG. 1 shows the results of measuring the activity of mice in each group in Test Example 2. FIG. 13 is a diagram showing the results of measuring the activity of mice in each group in Test Example 3. FIG. 13 is a diagram showing the results of measuring the activity of mice in each group in Test Example 4.

1. Pharmaceutical composition for improving activity The pharmaceutical composition of the present invention is used for improving activity and is characterized by containing Poria cocos and/or an extract thereof. The pharmaceutical composition of the present invention will be described in detail below.

[Poria cocos and/or its extract]
Poria cocoon is a herbal medicine made by drying the sclerotium of Polyporaceae fungus and removing the outer skin. Poria cocoon is preferably in the form of crushed or chopped material.

Poria extract can be obtained by extracting Poria using known methods. The method for producing Poria extract may be the same as the method for producing general herbal extracts, for example, by adding about 10 to 20 times the amount of water to the Poria and stirring at about 80 to 100°C for about 1 to 3 hours to extract. After extraction, the solids are removed by solid-liquid separation such as centrifugation and filtration, and the extract is obtained by concentration or drying as necessary.

To obtain Poria cocos extract in the form of extract powder, the extract liquid from which the solids have been removed may be concentrated as necessary, and then subjected to a drying process such as spray drying, vacuum concentration drying, or freeze drying. When subjected to a drying process (especially drying by spray drying), excipients such as dextrin may be added to the extract liquid as necessary. The types and amounts of excipients added are the same as those used when producing general herbal extract powders.

To obtain a soft extract of Poria cocos, the extract from which the solids have been removed may be concentrated by vacuum concentration or the like. A suitable adsorbent (e.g., silicic anhydride, starch, etc.) may also be added to the soft extract to produce an adsorbed powder.

The Poria extract may be in the form of either a soft extract or an extract powder.

In the pharmaceutical composition of the present invention, Poria cocos or its extract may be used alone or in combination.

In addition, since the pharmaceutical composition of the present invention only needs to contain Poria cocos and/or an extract thereof as an ingredient, it is also possible to use a Chinese herbal medicine containing Poria cocos and/or an extract thereof.

Specific examples of Chinese herbal medicines that contain Poria include Kamikihito, Tokishakuyakusan, and Sanzaoninto.

Kamikihi-to is a Chinese herbal medicine prescription consisting of Poria cocos, ginseng, Bupleurum Root, Zhuo jujube kernel, Longan flesh, Atractylodes orbiculatus (or Atractylodes Root), Astragalus Root, Angelica Root, Gardenia Fruit, Polygala Root, Ginger, Licorice Root, Wood Fragrance, Jujube, and Peony Peel (the peony peel is optional). According to the "Guidelines for Prescribing Traditional Chinese Herbal Medicine" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Japanese Pharmaceutical Federation's Traditional Chinese Medicine Expert Committee, published by Yakugyo Jihosha), the amounts of each herbal medicine that make up Kamikishuto are as follows: 3 parts by mass of Bouleng, 3 parts by mass of ginseng, 2.5 to 3 parts by mass of Chaihu, 3 parts by mass of Sour Jujube, 3 parts by mass of Longan Seed, 3 parts by mass of White Persimmon 2 to 3 parts by mass, 2 parts by mass of Toki, 2 to 2.5 parts by mass of Japanese radish, 1 to 2 parts by mass of Toshi, 1 to 1.5 parts by mass of ginger, 1 part by mass of licorice, 1 part by mass of wood incense, 1 to 2 parts by mass of jujube, and 2 parts by mass of peony bark (peony bark can be omitted).

Toki-shakuyakusan is a Kampo prescription consisting of Poria cocos, Angelica acutiloba, Szechuan ginger, White Atractylodes or Atractylodes rhizome, Zelkova serrata, and Peony root. According to the "Guide to General Kampo Prescriptions" (supervised by the Ministry of Health, Labor and Welfare's Pharmaceutical Affairs Bureau, edited by the Japan Pharmaceutical Manufacturers Association Kampo Specialist Committee, published by Yakugyo Times), the amounts of each herb that makes up Toki-shakuyakusan are 4-5 parts by weight of Poria cocos, 3-3.9 parts by weight of Angelica acutiloba, 3 parts by weight of Szechuan ginger, 4-5 parts by weight of White Atractylodes rhizome (Zelkova serrata), 4-12 parts by weight of Zelkova serrata, and 4-16 parts by weight of Peony root.

Sanzaoninto is a Chinese herbal medicine prescription consisting of Poria cocos, Jujube seed, Szechuan ginger, Anemone rhizome, and Licorice root. According to the "Guide to General Chinese Herbal Medicine Prescriptions" (supervised by the Ministry of Health and Welfare's Pharmaceutical Affairs Bureau, edited by the Japan Pharmaceutical Manufacturers Association Kampo Specialist Committee, published by Yakugyo Jihosha), the amounts of each herb that makes up Sanzaoninto are 2-5 parts by weight of Poria cocos, 10-18 parts by weight of Jujube seed, 2-3 parts by weight of Szechuan ginger, 2-3 parts by weight of Anemone rhizome, and 1 part by weight of Licorice root.

The herbal medicine extract can be obtained by extracting the herbal medicine (herbal medicine preparation) by a known method. The method for extracting the herbal medicine extract may be the same as the conventional method for extracting herbal medicine extract, for example, a method in which about 10 to 20 times the amount of water is added to the herbal medicine and the mixture is stirred at about 80 to 100°C for about 1 to 3 hours to extract. After extraction, the solids are removed by solid-liquid separation such as centrifugation and filtration, and the herbal medicine extract is obtained by subjecting the mixture to concentration or drying treatment as necessary.

To obtain the herbal extract as an extract powder, the extract liquid from which the solids have been removed may be concentrated as necessary, and then subjected to a drying process such as spray drying, vacuum concentration drying, or freeze drying. In addition, when subjected to a drying process (particularly drying by spray drying), an excipient such as dextrin may be added to the extract liquid as necessary. By adding an excipient in this way, it is possible to obtain an extract powder with reduced hygroscopicity. The type and amount of excipient added are the same as when producing a general herbal extract powder.

To obtain the herbal extract as a soft extract, the extract liquid from which the solids have been removed may be concentrated by vacuum concentration or the like. A suitable adsorbent (e.g., silicic anhydride, starch, etc.) may also be added to the soft extract to obtain an adsorbed powder.

The herbal extract may be either a powdered extract or a soft extract.

In the pharmaceutical composition of the present invention, either one of the above-mentioned herbal extracts or the extracts thereof may be used alone or in combination.

The pharmaceutical composition of the present invention may use one or more of Poria cocos itself, an extract of Poria cocos, a Chinese medicine containing Poria cocos, or a Chinese medicine extract containing Poria cocos, either singly or in combination.

In the pharmaceutical composition of the present invention, the content of Poria cocoon and/or its extract may be appropriately set depending on the daily dose, dosage form, etc., and may be, for example, 0.01 to 20 g, preferably 0.1 to 15 g, and more preferably 2 to 10 g, of Poria cocoon in terms of herbal medicine per 1 g of the pharmaceutical composition of the present invention. In the present invention, the "herbal medicine equivalent amount of Poria cocoon" refers to the weight (dry weight) of Poria cocoon required to obtain the amount of ingredient. In the case of Poria cocoon itself or a Chinese medicine containing Poria cocoon, the weight of the Poria cocoon to be mixed, or the weight of the Poria cocoon contained in the Chinese medicine to be mixed, is the herbal medicine equivalent amount. In addition, in the case of Poria extract or a herbal extract containing Poria, the dry weight of Poria needed to obtain the amount of Poria extract to be mixed, or the dry weight of Poria needed to obtain the amount of herbal extract to be mixed, is the raw herbal drug equivalent amount.

More specifically, when Kawei Kihi Tang or an extract thereof is used, the content of Kawei Kihi Tang or an extract thereof in the pharmaceutical composition of the present invention is, for example, 1.9 to 5.7 g, preferably 2.6 to 5.0 g, and more preferably 3.6 to 3.9 g, in terms of the amount of Kawei Kihi Tang in raw herbal medicine per 1 g of the pharmaceutical composition of the present invention.

When using Tokishakuyakusan or an extract thereof, the content of Tokishakuyakusan or an extract thereof in the pharmaceutical composition of the present invention is, for example, 2.3 to 7.2 g, preferably 3.3 to 6.3 g, and more preferably 4.5 to 5.1 g, in terms of the amount of Tokishakuyakusan in raw herbal medicine per 1 g of the pharmaceutical composition of the present invention.

When Sanzaoninto or an extract thereof is used, the content of Sanzaoninto or an extract thereof in the pharmaceutical composition of the present invention is, for example, 3.6 to 14.2 g, preferably 4.8 to 9.2 g, and more preferably 6.7 to 7.4 g, in terms of the amount of Sanzaoninto in raw herbal medicine per 1 g of the pharmaceutical composition of the present invention.

In the present invention, in the case of Kamikihito itself, the "equivalent amount of Kamikihito in raw herbal medicine form" is the weight of Kamikihito added, and in the case of Kamikihito extract, the equivalent amount of raw herbal medicine form is the dry weight of the total amount of herbal medicine preparations required to obtain the amount of Kamikihito extract added. The same applies to the "equivalent amount of raw herbal medicine form of Toki-shakuyakusan" and the "equivalent amount of raw herbal medicine form of Sanzaonin-to."

[Other ingredients]
The pharmaceutical composition of the present invention may contain other pharmacological ingredients, if necessary, in addition to the above-mentioned ingredients. The type of such pharmacological ingredients is not particularly limited, and examples thereof include anti-inflammatory analgesics, intestinal motility improving agents, antacids, gastric mucosa protecting agents, digestive agents, antispasmodics, mucosa repair agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzymes, sedatives, hypnotics, antihistamines, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, proton pump inhibitors, caffeines, menthols, polyphenols, etc. These pharmacological ingredients may be used alone or in combination of two or more kinds. The content of these pharmacological ingredients may be appropriately set according to the type of pharmacological ingredients used and the dosage form of the pharmaceutical composition.

The pharmaceutical composition of the present invention may contain pharma- ceutically acceptable bases and additives, etc., as necessary, in order to prepare the pharmaceutical composition into a desired dosage form. Examples of such bases and additives include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV protection agents, preservatives, flavorings, fragrances, powders, thickeners, dyes, chelating agents, etc. These bases and additives may be used alone or in combination of two or more. The content of these bases and additives may be appropriately set according to the type of additive used and the dosage form of the pharmaceutical composition.

[Dosage form]
The dosage form of the pharmaceutical composition of the present invention is not particularly limited, and may be any of a solid preparation, a semi-solid preparation, or a liquid preparation.

Specific examples of solid preparations include tablets, pills, capsules (soft capsules, hard capsules), powders, and granules (including dry syrups).Specific examples of semi-solid preparations include jellies.Specific examples of liquid preparations include solutions, suspensions, and syrups.

Among these dosage forms, solid formulations are preferred from the standpoint of the stability of the ingredients and portability.

[Dosage and Administration]
The pharmaceutical composition of the present invention is used for improving the amount of activity. In the present invention, the "amount of activity" includes both physical activity and mental activity.

"Physical activity" refers to various physical movements that consume energy through skeletal muscles, and includes all activities such as work, exercise, housework, and hobbies. "Amount of physical activity" is an index that indicates the degree of energy consumed by physical activity. "Improvement of physical activity" includes suppressing a decrease in the amount of physical activity and restoring a decreased amount of physical activity. A decrease in physical activity is caused not only by physical factors such as physical fatigue and aging, but also by mental factors such as stress, unstable mental state, and loss of motivation, as well as external factors such as climate change and a drop in temperature. However, the decrease in physical activity that is the target of improvement by the pharmaceutical composition of the present invention may be caused by any of physical factors, mental factors, or external factors.

"Mental activity" refers to non-physical actions such as thinking, will, and memory. "Amount of mental activity" is related to concentration, decisiveness, perseverance, and the like, and is an index of mental activity activity. "Improving the amount of mental activity" includes suppressing a decrease in the amount of mental activity and restoring a decreased amount of mental activity. A decrease in mental activity can be caused not only by mental factors such as stress, an unstable mental state, and a decrease in motivation, but also by physical factors such as physical fatigue and aging, and external factors such as climate change and a decrease in temperature. However, the decrease in mental activity that is the target of improvement by the pharmaceutical composition of the present invention may be caused by any of mental factors, physical factors, and external factors.

The use of the pharmaceutical composition of the present invention for improving activity level is preferably to suppress or recover a decrease in activity level caused by mental factors, more preferably to suppress or recover a decrease in physical activity level caused by mental factors, and particularly preferably to suppress or recover a decrease in physical activity level caused by stress.

In addition, improving the amount of activity brings about effects such as increasing the frequency or duration of exercise such as sports, increasing the frequency or duration of going outside, increasing the frequency or duration of work or housework, improving concentration, recovering physical strength during or after illness, suppressing or recovering from a decline in physical strength when healthy, suppressing or promoting recovery from fatigue, preventing or improving a frail constitution, and maintaining physical function in the elderly, and therefore the pharmaceutical composition of the present invention can also be used for the purpose of imparting these effects.

The pharmaceutical composition of the present invention is administered orally. The dosage of the pharmaceutical composition of the present invention is appropriately determined depending on the age, sex, constitution, etc. of the recipient, but may be, for example, 30 to 550 mg, preferably 50 to 550 mg, and more preferably 300 to 550 mg, of Poria cocos per day in terms of the amount of the original herbal drug.

More specifically, when using Kawei Kihi Tang or an extract thereof, the dosage of the pharmaceutical composition of the present invention is, for example, 14.5 to 34.5 g, preferably 16 to 32 g, per day in terms of the amount of Kawei Kihi Tang in raw herbal medicine.

When using Toki-shakuyakusan or an extract thereof, the dosage of the pharmaceutical composition of the present invention is, for example, 9 to 27 g, preferably 11 to 22 g, per day in terms of the amount of Toki-shakuyakusan raw herb.

When Sanzaoninto or an extract thereof is used, the dosage of the pharmaceutical composition of the present invention is, for example, 11 to 27 g, preferably 13.5 to 25 g, per day in terms of the amount of Sanzaoninto raw herbal medicine.

The pharmaceutical composition of the present invention may be administered in the above-mentioned dose 1 to 3 times a day, preferably 2 or 3 times a day. There are no particular limitations on the timing of administration, and the composition may be administered before, after, or between meals, but it is preferable to administer the composition before meals (30 minutes before a meal) or between meals (2 hours after a meal).

2. Pharmaceutical composition for improving fatigue The pharmaceutical composition of the present invention is used for improving fatigue and is characterized by containing Poria cocos and/or an extract thereof. The pharmaceutical composition for improving fatigue of the present invention will be described in detail below.

The Poria cocos and/or its extract used in the pharmaceutical composition of the present invention is the same as that described above in "1. Pharmaceutical composition for improving activity level."

In addition, in the pharmaceutical composition of the present invention, as in the case of "1. Pharmaceutical composition for improving activity level" above, a Chinese herbal medicine containing Poria and/or an extract thereof can be used as Poria and/or an extract thereof. The Chinese herbal medicine containing Poria and/or an extract thereof is the same as in the case of "1. Pharmaceutical composition for improving activity level" above.

The content of Poria cocos and/or its extract, the content of Chinese medicine containing Poria cocos and/or its extract, other ingredients, dosage form, etc. in the pharmaceutical composition of the present invention are the same as those in "1. Pharmaceutical composition for improving activity level" above.

The pharmaceutical composition of the present invention is used for improving fatigue. In the present invention, "fatigue" includes both physical fatigue caused by exercise, etc., and mental fatigue caused by mental factors such as stress, an unstable mental state, and loss of motivation. Furthermore, "improving fatigue" includes suppressing the onset of fatigue and promoting recovery from fatigue.

The fatigue to be improved by the pharmaceutical composition of the present invention is preferably fatigue caused by psychological factors, and more preferably fatigue caused by stress.

The dosage of the pharmaceutical composition of the present invention is the same as that of "1. Pharmaceutical composition for improving activity level" above.

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

Test Example 1: Verification of the effect of Poria cocos in improving activity and fatigue Six-week-old C57BL/6 male mice (Japan SLC Co., Ltd.) were kept for one week for acclimation and then divided into four groups (three mice per group): normal group, stressed/control group, stressed/Poria cocos group, and stressed/vitamin group.

The normal group was not subjected to stress (sleep stress as described below) or drug administration and was kept in a normal breeding environment (12 hours light and 12 hours dark).

The stressed/control group, stressed/Polycoris group, and stressed/vitamin group were raised in an environment with a 4 hour light period and a 20 hour dark period on the first day of the study (the day of grouping) to stress the mice. No drugs were administered to the stressed/control group. In the stressed/Polycoris group, Polycoris powder was orally administered to the mice once a day at 1000 mg/kg from the first day to the seventh day of the study. In the stressed/vitamin group, vitamins were orally administered to the mice once a day at 455 mg/kg from the first day to the seventh day of the study. The vitamins used contained 109.16 mg of fursultiamine hydrochloride, 12 mg of vitamin B2, 20 mg of vitamin B6, 60 μg of vitamin B12, and 15 mg of calcium pantothenate per 445 mg.

On the seventh day after the start of the test (after all procedures had been completed), an open field test was conducted on the mice of each group, and the activity level of each mouse in a 30 cm square box was measured using video analysis software, measuring the distance traveled per minute. The average activity level of each group was calculated, and the activity level (average value) of the normal group was set as 100%, and the relative activity level (average value) of each group was calculated.

The results are shown in Figure 1. As a result, jet lag stress significantly reduced the activity of the mice (stressed/control group). Furthermore, administration of vitamin supplements was unable to fully suppress the decrease in activity caused by jet lag stress (stressed/vitamin group). In contrast, administration of Poria cocoon powder effectively suppressed the decrease in activity caused by jet lag stress (stressed/Poria cocoon group). These results confirmed that Poria cocoon has the effect of suppressing the decrease in activity caused by stress and suppressing fatigue caused by stress.

Test Example 2: Verification of the effect of Kamikihito extract in improving activity and fatigue Six-week-old C57BL/6 male mice (Oriental Yeast Co., Ltd.) were kept for one week to acclimate them, and then divided into four groups (three mice per group): a normal group, a stressed/control group, a stressed/Kamikihito extract group, and a stressed/vitamin group.

The normal group was not subjected to stress from encountering different animals and was not administered drugs, and was kept in a normal breeding environment. The stressed/control group was not administered drugs. The stressed/Kamikihito extract group was orally administered Kamikihito extract powder at 2000 mg/kg (approximately 1.4 g/kg of Poria cocos raw herb equivalent, approximately 7.6 g/kg of Kamikihito raw herb equivalent) once a day from the first day of the test (the day of grouping) to the 12th day. The stressed/vitamin group was orally administered vitamins (same composition as used in Test Example 1) at 82.7 mg/kg from the first day of the test to the 12th day. In the stressed/control group, stressed/Kaweikihito extract group, and stressed/vitamin group, the mice were placed in a cage for aggressor mice (ICR male mice, retired, Oriental Yeast Co., Ltd.) for 10 minutes between the first and tenth days of the study, and then moved to an adjacent cage once a day to expose them to stress from encountering a different animal. Note that the exposure to stress from encountering a different animal was applied after administration of the drug on that day.

On the 12th day after the start of the test, an open field test was conducted on the mice of each group, and the activity of each mouse in a 30 cm square box (distance traveled per minute) was measured using video analysis software. The average activity of each group was calculated, and the activity of the normal group (average) was set as 100%, and the relative activity of each group (average) was calculated.

The results are shown in Figure 2. As a result, the activity of the mice was significantly reduced by the stress of encountering a different species of animal (stressed/control group). Furthermore, administration of vitamin supplements further exacerbated the decrease in activity caused by the stress of encountering a different species of animal (stressed/vitamin supplement group). In contrast, administration of Kamikihito extract effectively suppressed the decrease in activity caused by the stress of encountering a different species of animal (stressed/Kamikihito extract group). These results confirmed that Kampo extracts containing Poria cocos have the effect of suppressing the decrease in activity caused by stress and suppressing fatigue caused by stress.

Test Example 3: Verification of the effects of Toki-shakuyakusan extract in improving activity and fatigue Six-week-old male ddy mice (Japan SLC Co., Ltd.) were kept for one week to acclimate them, and then divided into four groups (three mice per group): a normal group, a stressed/control group, a stressed/Toki-shakuyakusan extract group, and a stressed/vitamin group.

The normal group was not administered betamethasone, was not subjected to low temperature stress, and was not administered drugs, and was kept in a normal breeding environment. The stressed/control group was not administered drugs. The stressed/Toki-shakuyakusan extract group was orally administered 1000 mg/kg Toki-shakuyakusan extract powder once a day from the first day of the test (the day of grouping) to the seventh day of the test (870 mg/kg in terms of the original herbal medicine of Poria, approximately 4.7 g/kg in terms of the original herbal medicine of Toki-shakuyakusan). The stressed/vitamin group was orally administered 63.9 mg/kg vitamins (same composition as used in Test Example 1) once a day from the first day of the test to the seventh day of the test. In the stressed/control group, stressed/Toki-shakuyakusan extract group, and stressed/vitamin group, betamethasone was administered once a day at 1.6 mg/kg via intramuscular injection into the hind legs from the first day to the seventh day of the study, and during that period, the animals were exposed to a 10°C environment for one hour every day to administer betamethasone and to impose cold stress. Note that betamethasone administration and cold stress were administered after drug administration on that day.

On the seventh day after the start of the test (after all procedures had been completed), an open field test was conducted on the mice of each group, and the activity level of each mouse (distance traveled per minute) in a 30 cm square box was measured using video analysis software. The average activity level of each group was calculated, and the activity level (average value) of the normal group was set as 100%, and the relative activity level (average value) of each group was calculated.

The results are shown in Figure 3. As a result, the mice's activity level was significantly reduced by the administration of betamethasone and the application of low-temperature stress (stressed/control group). Furthermore, the administration of vitamin supplements was unable to fully suppress the decrease in activity level caused by the administration of betamethasone and the application of low-temperature stress (stressed/vitamin supplement group). In contrast, when Toki-shakuyakusan extract was administered, the decrease in activity level caused by the administration of betamethasone and the application of low-temperature stress was effectively suppressed (stressed/Toki-shakuyakusan extract group). From these results, as in Test Example 2, it was confirmed that the extract of a Kampo medicine containing Poria cocos has the effect of suppressing the decrease in activity level caused by stress and suppressing fatigue caused by stress.

Test Example 4: Verification of the effect of Sansoninto extract in improving activity and fatigue Six-week-old C57BL/6 male mice (Japan SLC Co., Ltd.) were kept for one week to acclimate them, and then divided into four groups (three mice per group): a normal group, a stressed/control group, a stressed/Sansoninto extract group, and a stressed/vitamin group.

In the stress/Sanzoninto extract group, Sanzoninto extract powder was orally administered to mice once a day at 1000 mg/kg (equivalent to approximately 1300 mg/kg of Poria cocos raw herb, or approximately 7.1 g/kg of Sanzoninto raw herb). Except for this, the same procedures as in Test Example 1 were carried out to determine the average activity level in each group, and the relative activity level (average value) of each group was calculated, assuming the activity level (average value) of the normal group to be 100%.

The results are shown in Figure 4. As a result, the activity of the mice was significantly reduced by the jet lag stress (stressed/control group). Furthermore, the administration of vitamin supplements was not able to fully suppress the decrease in activity caused by jet lag stress (stressed/vitamin supplement group). In contrast, when Sansoninto extract was administered, the decrease in activity caused by jet lag stress was effectively suppressed (stressed/Toki-shakuyakusan extract group). These results, as in Test Examples 2 and 3, confirm that Kampo extracts containing Poria cocos have the effect of suppressing the decrease in activity caused by stress and suppressing fatigue caused by stress.

Claims (6)

A pharmaceutical composition for improving physical activity, comprising Poria cocos and/or an aqueous extract thereof, and used for suppressing or recovering a decrease in physical activity caused by stress, (provided that [i] one containing an ethanol extract of Poria cocos, [ii] one containing eight or more kinds of herbal medicines selected from the group consisting of Ginseng, Astragalus Root, Acanthopanax Root, Licorice Root, Chinese Rhizome, Dioscorea Root, Rehmannia Root, Dong Qui, Lycium Root, Cistanche, Jasminum Root, Eucommia Root, Zingiber officinale, Bupleurum Root, Cornus Cherry, and Gossypium Root, and containing Poria cocos, [iii] one or more kinds selected from the group consisting of glucuronolactone, licorice, and Lycium Root, and one or more kinds selected from the group consisting of Crathorn, Gossypium Root Tincture, and Rehmannia Root , [ iv] one containing Juzentaihoto , [v] [v-1] a mixture of Messeria japonica, Reishi mushroom, Mistletoe, Byadeniko, Poria columbine, Kaliphia rhizome, Bornum, Gokapi, Cnidium rhizome, Dongqi, Rehmannia rhizome and Licorice; [v-2] a mixture of the mixture of [v-1] not containing Messeria japonica and Reishi mushroom; [v-3] a mixture of the mixture of [v-1] not containing Messeria rhizome; [v-4] a mixture of the mixture of [v-1] not containing Byadeniko; and [v-5] a mixture of the mixture of [v-1] not containing Kaliphia rhizome, Bornum, and Gokapi; [vi] a mixture containing Keishibukuryoganryoka Yokuinin; and [vii] a mixture containing a Kampo medicine or an extract thereof selected from Kihito, Hachimijiogan, Goshajinkigan, Juhogan, and Jinkigan ). The pharmaceutical composition for improving activity level according to claim 1, which contains a Chinese herbal medicine containing Poria cocos or a water extract thereof. The pharmaceutical composition for improving activity level according to claim 2, wherein the herbal medicine is at least one selected from the group consisting of Kamikihito, Tokishakuyakusan, and Sanzaoninto. A pharmaceutical composition for improving fatigue, which contains Poria cocos and/or a water extract thereof and is used to improve fatigue caused by stress (provided that [i] one containing an ethanol extract of Poria cocos, [ii] one containing eight or more kinds of herbal medicines selected from the group consisting of Ginseng, Astragalus Root, Acanthopanax Root, Licorice Root, Chinese Rhizome, Dioscorea Rhizome, Rehmannia Root, Dong Qui, Lycium Root, Cistanche, Jasminum Root, Eucommia Root, Zingiber officinale, Bupleurum Root, Cornus Cherry, and Gossypium Root, and which contains Poria cocos, [iii] one or more kinds selected from the group consisting of glucuronolactone, licorice, and Lycium Root, and one or more kinds selected from the group consisting of Crathorn, Gossypium Root Tincture, and Rehmannia Root , [ iv] one containing Juzentaihoto , [v] [v-1] a mixture of Messeria japonica, Reishi mushroom, Mistletoe, Byadeniko, Poria columbine, Kaliphia rhizome, Bornum, Gokapi, Cnidium rhizome, Dongqi, Rehmannia rhizome and Licorice; [v-2] a mixture of the mixture of [v-1] not containing Messeria japonica and Reishi mushroom; [v-3] a mixture of the mixture of [v-1] not containing Messeria rhizome; [v-4] a mixture of the mixture of [v-1] not containing Byadeniko; and [v-5] a mixture of the mixture of [v-1] not containing Kaliphia rhizome, Bornum, and Gokapi; [vi] a mixture containing Keishibukuryoganryoka Yokuinin; and [vii] a mixture containing a Kampo medicine or an extract thereof selected from Kihito, Hachimijiogan, Goshajinkigan, Juhogan, and Jinkigan ). The pharmaceutical composition for improving fatigue according to claim 4, which contains a Chinese herbal medicine containing Poria cocos or a water extract thereof. 6. The pharmaceutical composition for improving fatigue according to claim 5, wherein the herbal medicine is at least one selected from the group consisting of Kamikihi-to, Toki-shakuyakusan, and Sanzaonin-to.