JP7602857B2 - Agents for improving age-related obesity and lipolysis - Google Patents

Description

The present invention relates to an agent for improving age-related obesity that can effectively improve age-related obesity. The present invention also relates to an agent for improving lipolysis ability that can improve reduced lipolysis ability.

In recent years, as food culture becomes more Westernized, the amount of lipid intake by Japanese people has increased, and excessive lipid intake leads to weight gain and obesity. In order to improve obesity, it is effective to increase the body's lipid decomposition and metabolic ability, but conventional obesity improvement agents have limitations in improving lipid decomposition and metabolic ability in people with chronically decreased lipid decomposition and metabolic ability. In particular, obesity seen in middle-aged and elderly people (particularly obesity in middle-aged and elderly people who have a body fat percentage of 25% or more and a waist size of 85 cm or more for more than 5 years) is essentially due to decreased lipid decomposition and metabolic ability, and it is thought that conventional obesity improvement agents cannot be expected to be effective.

On the other hand, Bofutsushosan is known as a herbal medicine that is effective in reducing visceral fat and improving metabolic syndrome. The mechanism of action of Bofutsushosan has also been revealed to be activation of heat production in brown fat cells via the sympathetic nervous system and promotion of fat decomposition in white fat cells (see Non-Patent Document 1). Various formulations of Bofutsushosan extract have been developed from the perspective of improving the effect of reducing visceral fat and improving taste (for example, Patent Documents 1 and 2).

However, as mentioned above, it is believed that conventional obesity treatments are not effective for obesity seen in middle-aged and older people, particularly those who have had a body fat percentage of 25% or more and a waist size of 85 cm or more for more than five years. As a result, many of these middle-aged and older people do not even have the motivation to restrict their diet, and so do not take Bofutsushosan.

In addition, in response to stimulation by noradrenaline, fat cells break down fat stored within the cells into free fatty acids. This is called the lipolytic response. The free fatty acids produced by the lipolytic response are released into the blood and transported to the liver, skeletal muscles, and brown fat, where they are metabolized and burned and consumed. It is known that the ability of fat cells to respond to noradrenaline stimulation decreases when the function of the cells declines, and this condition is known to progress particularly with age. Furthermore, this decrease in the ability to respond to noradrenaline stimulation also leads to a decrease in the burning and consumption of fat, and is therefore thought to be one of the causes of weight gain with age.

To date, lipolysis promoters such as soybean extract (Patent Document 3) and Pu-erh tea extract (Patent Document 4) have been discovered with the aim of enhancing fat breakdown. However, it has been difficult for these lipolysis promoters to be effective against fat that has already lost its ability to break down fat in response to noradrenaline stimulation.

On the other hand, Bofutsushosan is a herbal medicine made up of 18 kinds of herbal medicines, and is known to be effective in reducing visceral fat and improving metabolic syndrome. The herbal medicine Ephedra, which is one of the constituent herbs, contains ephedrine, which increases the release of noradrenaline from sympathetic nerve endings. In addition, the herbal medicines licorice, stinging root, and forsythia fruit, which are also constituent herbs, have a phosphodiesterase inhibitory effect and work to prolong the effect of noradrenaline released by ephedrine. In other words, the mechanism of action of Bofutsushosan is to act on the release of noradrenaline. Due to this mechanism of action, it was technically common knowledge that Bofutsushosan has almost no effect on fat cells whose ability to respond to noradrenaline stimulation (lipolysis ability) itself has already decreased.

Kampo Medicine, Vol. 37, No. 1, 2013, pp. 38-40

JP 2009-242354 A JP 2009-242330 A Japanese Patent Application Publication No. 11-228430 JP 2002-275078 A

The object of the present invention is to provide an obesity improving agent that has an excellent improving effect on age-related obesity. In addition, the object of the present invention is to provide a lipolytic ability improving agent that can improve the decreased response ability to noradrenaline stimulation (hereinafter also referred to as decreased lipolytic ability).

In age-related obesity, lipid decomposition and metabolic ability are often essentially decreased, and conventional obesity improvement agents that increase lipid decomposition and metabolic ability cannot be expected to be effective. However, if there is an effect of promoting the excretion of ingested lipids into the feces, it is thought that it will be effective in improving obesity. From this perspective, the present inventors have conducted extensive research to solve the above problem and have found that Bofutsushosan extract has the effect of promoting the excretion of ingested lipids into the feces, and has an excellent obesity improvement effect even in age-related obesity, in which lipid decomposition and metabolic ability are essentially decreased. Furthermore, the present inventors have unexpectedly found that Bofutsushosan has the effect of improving decreased lipolysis. The present invention was completed based on such findings and through further research.

That is, the present invention provides the following aspects.
Item 1. An agent for improving age-related obesity, comprising Bofutsushosan extract.
Item 2. The agent for improving age-related obesity according to Item 1, which is applied to a person who has had a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more.
Item 3. The agent for improving age-related obesity according to Item 1 or 2, which is applied to a person having adipose tissue with a lipolytic power of 5 mEq/g or less as measured in the following lipolytic power evaluation test.
<Lipid decomposition ability evaluation test>
The adipose tissue collected from the subcutaneous tissue is washed with Krebs Ringer buffer (pH 7.4). The weight of the washed adipose tissue is measured, and 0.2 g of the washed adipose tissue is added to 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2 wt% bovine serum albumin (BSA), and incubated at 37° C. for 2 hours. The supernatant is then collected, and the amount of free fatty acid released in the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq/g) is calculated as the lipolysis power.
Item 4. The agent for improving age-related obesity according to any one of Items 1 to 3, wherein the bofu-tsushosan extract contains 0.005 to 0.04 parts by weight of 6-gingerol per 100 parts by weight of the total amount of the components derived from herbal medicines.
Item 5. A fat decomposition ability improving agent containing Bofutsushosan extract.
Item 6. The lipolysis ability improving agent according to Item 5, which is applied to a person who has had a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more.
Item 7. The lipolytic power improving agent according to item 5 or 6, which is applied to a person having adipose tissue with a lipolytic power of 5 mEq/g or less as measured in the following lipolytic power evaluation test.
<Lipid decomposition ability evaluation test>
The adipose tissue collected from the subcutaneous tissue is washed with Krebs Ringer buffer (pH 7.4). The weight of the washed adipose tissue is measured, and 0.2 g of the washed adipose tissue is added to 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2 wt% bovine serum albumin (BSA), and incubated at 37° C. for 2 hours. The supernatant is then collected, and the amount of free fatty acid released in the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq/g) is calculated as the lipolysis power.
Item 8. The lipolysis ability improving agent according to any one of Items 5 to 7, wherein the bofu-tsushosan extract contains 0.005 to 0.04 parts by weight of 6-gingerol per 100 parts by weight of the total amount of the components derived from herbal medicines.

The age-related obesity improving agent of the present invention can also improve obesity in age-related obesity in which the decomposition ability and metabolic ability of lipids have essentially decreased. For example, middle-aged or older people who have had a body fat percentage of 25% or more and a waist size of 85 cm or more for more than five years cannot expect any improvement effects from conventional obesity improving agents, and often have no motivation to restrict their diet, but the age-related obesity improving agent of the present invention can bring the good news of obesity improvement to such middle-aged or older people. Furthermore, the lipolytic ability improving agent of the present invention can improve the decreased lipolytic ability. For example, middle-aged or older people who have had a body fat percentage of 25% or more and a waist size of 85 cm or more for more than five years often have already decreased lipolytic ability in response to noradrenaline stimulation due to aging, but the lipolytic ability improving agent of the present invention can be expected to rejuvenate the lipolytic ability.

The agent for improving age-related obesity and the agent for improving lipolysis ability of the present invention are characterized by containing Bofutsushosan extract. The agent for improving age-related obesity and the agent for improving lipolysis ability of the present invention are described in detail below.

According to the "Guide to General Kampo Prescriptions " (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Kampo Specialist Committee of the Japan Pharmaceutical Manufacturers Association, and published by Yakugyo Jihosha), the herbal medicines that make up Bofutsushosan are Angelica, Peony Root, Cnidium Root, Sanshishi, Forsythia, Mint, Ginger, Cabbage, Scutellaria, Ephedra, Rhizome, Boswellia, Byakujutsu, Platycodon, Scutellaria Root, Licorice, Scutellaria Root, and Scutellaria Root. Some letters do not contain Byakujutsu (for example, "Experience Kampo Prescription Quantities Collection," supervised by Otsuka Keisetsu and Yakazu Domyo, published by Ido no Nihonsha), and some do not contain Scutellaria Root (for example, "Continuation of Kampo Arekore," edited by Osaka Yomiuri Shimbun, published by Naniwasha). The Bofutsushosan extract used in the present invention may be obtained from any of these Bofutsushosan.

According to the "Guide to General Kampo Prescriptions" (supervised by the Ministry of Health, Labor and Welfare's Pharmaceutical Affairs Bureau, edited by the Kampo Specialist Committee of the Japan Pharmaceutical Manufacturers Association, and published by Yakugyo Jihosha) and the "17th Revised Japanese Pharmacopoeia," the amounts of each herb that makes up Bofutsushosan are as follows: Angelica acutiloba 1.2 parts by weight, Peony root 1.2 parts by weight, Cnidium rhizome 1.2 parts by weight, Gardenia fruit 1.2 parts by weight, Forsythia serrata 1.2 parts by weight, Mentha arvensis 1.2 parts by weight, and Ginger 0.3 to 1.2 parts by weight. 1.2 parts by weight, 1.2 parts by weight of Chinese holly, 1.2 parts by weight of Bougainvillea or 1.2 parts by weight of Glehnia gracilis, 1.2 parts by weight of Ephedra, 1.5 parts by weight of Rhubarb, 0.6 to 1.5 parts by weight of Bougainvillea (calculated as anhydrous sodium sulfate), 2 parts by weight of Atractylodes Root, 2 parts by weight of Platycodon Root, 2 parts by weight of Scutellaria Root, 2 parts by weight of Licorice Root, 2 to 3 parts by weight of Gypsum, and 3 to 5 parts by weight of Kasseki. Some letters also state that all of the 1.2 parts by weight in the above amounts are 1.5 parts by weight (for example, "Meikai Kampo Prescriptions," co-authored by Nishioka Kazuo and Takahashi Shintaro, published by Naniwasha).

There are no particular limitations on the amount of each herb in the herb preparation used to manufacture Bofutsushosan extract, and the amounts of each herb shown in the letter exemplified above may be used, but suitable examples include 1.2 parts by weight of Angelica acutiloba, 1.2 parts by weight of Peony Root, 1.2 parts by weight of Cnidium Root, 1.2 parts by weight of Sanshi Fruit, 1.2 parts by weight of Forsythia Fruit, 1.2 parts by weight of Mentha Root, 1.2 parts by weight of Japanese Scutellaria, 1.2 parts by weight of Japanese Scutellaria, 1.2 parts by weight of Bofufu Root, 1.2 parts by weight of Ephedra Root, Rhubarb 1.5 parts by weight, Bougainvillea (calculated as anhydrous sodium sulfate) 0.6 to 1.5 parts by weight, Atractylodes Root 2 parts by weight, Platycodon 2 parts by weight, Scutellaria Root 2 parts by weight, Licorice Root 2 parts by weight, Gypsum 2 to 3 parts by weight (preferably 2 parts by weight), and Ginseng 3 to 5 parts by weight (preferably 3 parts by weight), and Zingiber officinale 0.3 to 1.5 parts by weight, preferably 0.3 to 1.2 parts by weight, more preferably 0.3 to 0.4 parts by weight, particularly or preferably 0.3 parts by weight (hereinafter, sometimes referred to as "Aspect A1"), or 1.2 parts by weight of Angelica Root, 1.2 parts by weight of Peony Root, 1.2 parts by weight of Cnidium Root, 1.2 parts by weight of Sanshi Fruit, 1.2 parts by weight of Forsythia Fruit, 1.2 parts by weight of Mentha Root, 1.2 parts by weight of Crown Root, 1.2 parts by weight of Scutellaria Root, 1.2 parts by weight of Ephedra Root, 1.2 parts by weight of Rhubarb, 0.6 to 1.5 parts by weight of Bougainvillea (calculated as anhydrous sodium sulfate), Examples of such a composition include 2 parts by weight of Atractylodes Root, 2 parts by weight of Platycodon Root, 2 parts by weight of Scutellaria Root, 2 parts by weight of Licorice Root, 2-3 parts by weight (preferably 2 parts by weight) of Glycyrrhiza Root, and 3-5 parts by weight (preferably 3 parts by weight) of Ginger Root, and 0.6-1.5 parts by weight, preferably 0.8-1.4 parts by weight, more preferably 1-1.3 parts by weight, and particularly preferably 1.2 parts by weight (hereinafter, sometimes referred to as "Aspect A2"). Depending on the dosage and formulation, etc., age-related obesity and/or lipolytic ability can be more effectively improved by adjusting the amount of Ginger Root in the herbal preparation used for the production of Bofu-tsushosan extract to the range of Aspect A1 or A2, and the hardness and disintegration property of the tablet can be improved when the tablet is formed by adjusting the amount of Ginger Root to the range of Aspect A2.

In the above-mentioned embodiment A1, the amount of sucrose is preferably 0.6 to 1 part by weight, more preferably 0.6 to 0.75 parts by weight, and particularly preferably 0.7 parts by weight, calculated as anhydrous sodium sulfate. In the above-mentioned embodiment A2, the amount of sucrose is preferably 1 to 1.5 parts by weight, more preferably 1.3 to 1.5 parts by weight, and particularly preferably 1.5 parts by weight, calculated as anhydrous sodium sulfate. Depending on the dosage and formulation, etc., by making the amount of sucrose satisfy such a range, it becomes possible to more effectively improve age-related obesity and/or lipolysis. In the above-mentioned embodiment A2, the amount of sucrose is preferably 1 to 1.5 parts by weight, more preferably 1.3 to 1.5 parts by weight, and particularly preferably 1.5 parts by weight, calculated as anhydrous sodium sulfate, and when formed into a tablet, the hardness and disintegration property of the tablet can be improved.

In the present invention, the term "herb preparation used in the production of Bofutsushosan extract" refers to a raw material preparation used for extraction in the production of Bofutsushosan extract, i.e., a preparation containing a predetermined amount of herbs that constitute Bofutsushosan. In addition, the term "sodium sulfate anhydrous equivalent of Bofutsushosan" refers to the conversion of the hydrate to the anhydrous weight when sodium sulfate hydrate is used as Bofutsushosan. As Bofutsushosan, sodium sulfate hydrate (e.g., decahydrate) and/or sodium sulfate anhydrous is used, and sodium sulfate anhydrous is preferably used from the viewpoint of improving the hardness and disintegrability of the tablet when it is formed into a tablet.

A suitable example of a herbal preparation used in the manufacture of the bofu-tsushosan extract used in the present invention is one containing 1 to 5 parts by weight, preferably 1 to 4 parts by weight, more preferably 1 to 3 parts by weight, and particularly preferably 1 to 2 parts by weight of ginger per 100 parts by weight of the total amount of the herbal preparation. Although it depends on the dosage and the formulation form, by obtaining the bofu-tsushosan extract from a herbal preparation with such a low ratio of ginger, it is possible to more effectively improve age-related obesity and/or fat decomposition ability. Another suitable example of a herbal preparation used in the manufacture of the bofu-tsushosan extract used in the present invention is one containing 2 to 5 parts by weight, preferably 3 to 5 parts by weight, more preferably 4 to 5 parts by weight, and particularly preferably 4 to 4.5 parts by weight of ginger per 100 parts by weight of the total amount of the herbal preparation. Although it depends on the dosage and formulation, obtaining bofutsushosan extract from a herbal preparation with such a low ratio of ginger makes it possible to more effectively improve age-related obesity and/or fat decomposition, and when formed into tablets, it makes it possible to improve the hardness and disintegration properties of the tablets.

A suitable example of a herbal preparation used in the manufacture of the Bofu-tsushosan extract used in the present invention is one containing 2 to 6 parts by weight, preferably 2 to 4 parts by weight, more preferably 2 to 3 parts by weight, and particularly preferably 2 to 2.5 parts by weight of Bofu-tsushosan per 100 parts by weight of the total amount of the herbal preparation. Although it depends on the dosage and the formulation form, by containing Bofu-tsushosan in such a ratio, it becomes possible to more effectively improve age-related obesity and/or lipolysis. Another suitable example of a herbal preparation used in the manufacture of the Bofu-tsushosan extract used in the present invention is one containing 3 to 6 parts by weight, preferably 4 to 6 parts by weight, more preferably 5 to 6 parts by weight, and particularly preferably 5 to 5.5 parts by weight of Bofu-tsushosan per 100 parts by weight of the total amount of the herbal preparation. Although it depends on the dosage and formulation, the inclusion of this ratio in the herbal medicine preparation makes it possible to more effectively improve age-related obesity and/or fat decomposition, and when formed into tablets, it makes it possible to improve the hardness and disintegration properties of the tablets.

A suitable example of the bofu-tsushosan extract used in the present invention is one containing 0.005 to 0.04 parts by weight of 6-gingerol per 100 parts by weight of the total amount of ingredients derived from herbal medicines. 6-Gingerol is an ingredient contained in ginger, and conventional bofu-tsushosan extracts usually contain 0.05 parts by weight or more of 6-gingerol per 100 parts by weight of the total amount of ingredients derived from herbal medicines. In the present invention, by using a bofu-tsushosan extract with a reduced content of 6-gingerol, it becomes possible to more effectively improve age-related obesity and/or lipolysis ability. Although it depends on the dosage and formulation form, from the viewpoint of more effectively improving age-related obesity and/or lipolysis ability, examples include those containing preferably 0.007 to 0.03 parts by weight, more preferably 0.007 to 0.025 parts by weight, and particularly preferably 0.007 to 0.015 parts by weight of 6-gingerol per 100 parts by weight of the total amount of ingredients derived from herbal medicines, or those containing preferably 0.02 to 0.04 parts by weight, more preferably 0.025 to 0.04 parts by weight, even more preferably 0.03 to 0.04 parts by weight, and particularly preferably 0.035 to 0.04 parts by weight of 6-gingerol per 100 parts by weight of the total amount of ingredients derived from herbal medicines. In addition, when formed into tablets, from the viewpoint of improving the hardness and disintegration of the tablets, preferably 0.02 to 0.04 parts by weight, more preferably 0.025 to 0.04 parts by weight, even more preferably 0.03 to 0.04 parts by weight, and particularly preferably 0.035 to 0.04 parts by weight of 6-gingerol is contained per 100 parts by weight of the total amount of the ingredients derived from the herbs. Here, the ingredients derived from the herbs are the ingredients extracted from the herbs that constitute Bofutsushosan. That is, in the case of Bofutsushosan extract powder that does not contain additives such as excipients, the weight of the extract powder is the total amount of the ingredients derived from the herbs, and in the case of Bofutsushosan extract powder that contains additives such as excipients, the weight obtained by subtracting the weight of the additives contained therein from the weight of the extract powder is the total amount of the ingredients derived from the herbs.

The 6-gingerol content in ginger varies depending on the place of origin and number of years of growth of ginger, and the extraction efficiency of 6-gingerol from ginger also varies depending on the extraction conditions. Therefore, to obtain a bofu-tsushosan extract containing 6-gingerol in the above ratio, the ratio of ginger in the herbal preparation and the shape of ginger used for extraction (i.e., ginger used in the herbal preparation) can be appropriately set according to the 6-gingerol content contained in ginger. The amount of 6-gingerol extracted can be reduced by subjecting ginger to extraction in a processed product sliced into slices about 1 to 3 mm thick rather than cutting into thin pieces about 1 to 8 mm square. This makes it possible to preferably obtain a bofu-tsushosan extract containing 6-gingerol in the above ratio. For example, by setting the ratio of ginger per 100 parts by weight of the total amount of the herbal preparation within the range shown in the above-mentioned embodiment A1 and adjusting the shape of the ginger, it is possible to suitably obtain a bofu-tsushosan extract containing 6-gingerol within the above-mentioned content range.

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

To obtain Bofutsushosan 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. Adding an excipient in this way makes it possible to shorten the drying time. The type and amount of excipient added are the same as when producing general herbal extract powders.

To obtain Bofutsushosan extract as a soft extract, the extract from which the solid components 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 bofutsushosan extract used in the present invention may be either an extract powder or a soft extract, and either extract powder or soft extract may be appropriately selected depending on the form of the agent for improving age-related obesity or the agent for improving lipolysis ability of the present invention. In addition, when formed into tablets, it is preferable to use an extract powder from the viewpoint of obtaining tablets with excellent hardness and disintegration properties.

Other components The age-related obesity improving agent and lipolysis improving agent of the present invention may be composed of Bofutsushosan extract alone, or may contain additives and bases according to the formulation. Such additives and bases are not particularly limited as long as they are pharmacologic acceptable, and may include, for example, 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, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, flavorings, fragrances, powders, thickeners, dyes, chelating agents, etc. These additives may be used alone or in combination of two or more. The contents of these additives and bases are appropriately set depending on the types of additives and bases used, the formulation form of the agent for improving age-related obesity or the agent for improving lipolysis ability, etc.

Examples of additives and bases include starch, carmellose calcium, light anhydrous silicic acid, magnesium stearate, synthetic aluminum silicate, magnesium aluminometasilicate, calcium silicate, magnesium silicate, synthetic hydrotalcite, anhydrous calcium hydrogen phosphate, carmellose, croscarmellose sodium, sodium starch glycolate, and crospovidone, and preferred are carmellose calcium, light anhydrous silicic acid, magnesium stearate, and synthetic aluminum silicate. The content of these additives and bases is appropriately set according to the type of additive and base used.

When formed into tablets, it is preferable to contain at least starch as an additive and base, from the viewpoint of obtaining tablets with excellent hardness and disintegration properties. Examples of starch include potato starch, corn starch, etc., and preferably potato starch. The starch content is 0.5 to 3% by weight, preferably 1 to 2.5% by weight, more preferably 1.5 to 2.5% by weight, and particularly preferably 1.5 to 2% by weight. By containing starch in such a ratio, it is possible to improve the hardness and disintegration properties of the tablet when formed into a tablet.

The content of carmellose calcium is, for example, 0.5 to 10% by weight, the content of light anhydrous silicic acid is, for example, 3 to 25% by weight, the amount of magnesium stearate is, for example, 0.2 to 1% by weight, preferably 0.5 to 0.7% by weight, and the content of synthetic aluminum silicate is, for example, 0.5 to 10% by weight, preferably 1 to 10% by weight. When formed into tablets, from the viewpoint of obtaining tablets excellent in hardness and disintegration property, the content of carmellose calcium is, for example, 1 to 7% by weight, more preferably 1 to 1.5% by weight, and even more preferably 1 to 1.2% by weight, and the content of light anhydrous silicic acid is, for example, 4 to 15% by weight, more preferably 4 to 5% by weight, and even more preferably 4 to 4.3% by weight.

In addition, the age-related obesity improving agent and lipolysis ability improving agent of the present invention may contain other nutritional components and pharmacological components as necessary, in addition to the Bofutsushosan extract. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include antacids, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, astringents, antiemetics, antitussives, expectorants, anti-inflammatory enzyme agents, sedatives, hypnotics, antihistamines, caffeine, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, herbal extracts, vitamins, and menthols. These nutritional components and pharmacological components may be used alone or in combination of two or more. The content of these components is appropriately set depending on the type of component used, the formulation form of the age-related obesity improving agent or lipolysis ability improving agent, etc.

The formulation of the agent for improving age-related obesity and the agent for improving lipolysis ability of the present invention is not particularly limited as long as it can be administered orally, and examples of the formulation include solid formulations such as powders, fine granules, granules (including dry syrup), tablets, pills, capsules (soft capsules, hard capsules), etc.; semi-solid formulations such as jellies; and liquid formulations such as liquids, suspensions, syrups, etc. Among these formulations, solid formulations are preferred from the viewpoints of the stability and portability of the contained ingredients.

When the age-related obesity improving agent and lipolysis ability improving agent of the present invention are formed into tablets, the shape and size of the tablets are not particularly limited. Examples of tablet shapes include round, oval, triangular, and square. In the case of round tablets, the diameter is 6 to 12 mm, preferably 8 to 10 mm. The thickness of the tablet is 3 to 8 mm, preferably 4 to 7 mm. The weight per tablet is 200 to 800 mg, preferably 300 to 600 mg.

When the age-related obesity improving agent and lipolysis improving agent of the present invention are formed into tablets, the tablets may be plain tablets (bare tablets) or coated tablets in which a coating has been applied to the surface for the purpose of stabilizing the drug and masking the taste and odor. Examples of coated tablets include sugar-coated tablets and film-coated tablets (gastrosoluble tablets, enteric-coated tablets) coated with a film containing a water-soluble, enteric-soluble or gastrosoluble polymer base. The hardness of the plain tablets is preferably 40N or more, preferably 50N or more, more preferably 70N or more, even more preferably 80N or more, even more preferably 100N or more, and particularly preferably 130N or more.

Manufacturing method In order to prepare the age-related obesity improving agent and lipolysis ability improving agent of the present invention in the above-mentioned formulation form, the agent may be formulated according to a conventional formulation method adopted in the pharmaceutical field using the bofutsushosan extract and additives, base materials, and pharmacological ingredients added as necessary. When the agent is formulated as a tablet, the manufacturing method of the age-related obesity improving agent and lipolysis ability improving agent of the present invention preferably includes a granulation step of granulating the bofutsushosan extract or a bofutsushosan extract mixture mixed with additives, base materials, other nutritional ingredients, and/or other pharmacological ingredients as necessary, and a tableting step of tableting the granulated product. The tableting pressure in the tableting step may be, for example, 4 to 20 kN, preferably 4 to 15 kN, when producing tablets of 200 to 490 mg/tablet. From the viewpoint of reducing the load on the tableting device and extending the life of the tableting device, the tableting pressure may be lower, 4 to 12 kN.

The age-related obesity improving agent of the present invention is used for preventing or improving age-related obesity. Age-related obesity is obesity caused by a decrease in lipid decomposition and metabolic ability due to aging, and examples of people with age-related obesity include middle-aged or older people (45 years or older) who are obese (for example, have a body fat percentage of 25% or more).

The age-related obesity improving agent of the present invention also has the effect of promoting the excretion of ingested lipids such as cholesterol into the stool. In this way, by also having the effect of promoting the excretion of lipids into the stool, it becomes possible to effectively improve or avoid health problems (weight gain, visceral fat gain, etc.) caused by excessive lipid intake in age-related obesity.

Furthermore, among people with age-related obesity, those with a constitution that is essentially reduced in lipid decomposition and metabolic ability cannot expect improvement in lipid decomposition and metabolic ability with conventional obesity improving agents, and therefore have not been in the habit of taking conventional obesity improving agents. However, the age-related obesity improving agent of the present invention also has the effect of promoting the excretion of lipids into feces, so that it is possible to effectively improve or avoid health disorders (weight gain, visceral fat gain, etc.) caused by excessive lipid intake even for age-related obesity with essentially reduced lipid decomposition and metabolic ability. In view of such effects of the present invention, suitable subjects for the age-related obesity improving agent of the present invention include age-related obesity with a constitution that is essentially reduced in lipid decomposition and metabolic ability. Specific examples of age-related obesity with this constitution include middle-aged or older people (45 years or older) who have had a body fat percentage of 25% or more and a waist size of 85 cm or more for more than 5 years; and people with adipose tissue whose lipolytic power, as measured in the lipolytic power evaluation test described below, is 5 mEq/g or less, preferably 3 mEq/g or less, more preferably 1 mEq/g or less, even more preferably 0.5 mEq/g or less, and particularly preferably 0.3 mEq/g or less.
<Lipid decomposition ability evaluation test>
First, adipose tissue is collected from the subcutaneous tissue of a subject. The obtained adipose tissue is washed with Krebs Ringer buffer (pH 7.4). The weight of the washed adipose tissue is measured, and 0.2 g of the washed adipose tissue is added to 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2 wt% bovine serum albumin (BSA), and incubated at 37° C. for 2 hours. The supernatant is then collected, and the amount of free fatty acid released into the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq/g) is calculated as the lipolysis power.

It is known that adipose tissue is activated by noradrenaline stimulation, causing the breakdown of accumulated fat and the release of free fatty acids. In the lipolysis power evaluation test, the decomposition power of adipose tissue is evaluated by measuring the amount of free fatty acids released.

The lipolytic ability improving agent of the present invention is used to prevent a decrease in lipolytic ability or to improve a decreased lipolytic ability. A state in which lipolytic ability is decreased is a state in which the ability of fat cells to respond to noradrenaline stimulation is decreased, and often leads to a decrease in fat burning and consumption. Therefore, examples of people with decreased lipolytic ability include middle-aged or older people (45 years or older) and/or obese people (e.g., body fat percentage of 25% or more), and particularly middle-aged or older people (45 years or older) and obese people (e.g., body fat percentage of 25% or more).

In addition, in people with reduced lipolysis, the response ability to noradrenaline stimulation itself is reduced, so conventional lipolysis promoters cannot be expected to improve lipolysis, and there has been no habit of taking conventional lipolysis promoters. However, the lipolysis improver of the present invention can increase the response ability to noradrenaline stimulation itself, making it possible to effectively improve lipolysis or effectively avoid a decline in lipolysis. In view of the effects of the present invention, suitable subjects for the lipolysis improver of the present invention include people with a constitution in which lipolysis has declined due to aging, and people who are obese due to a decline in fat burning and consumption caused by a decline in lipolysis. Specific examples of people with this constitution include middle-aged or older people (over 45 years old) who have had a body fat percentage of 25% or more and a waist size of 85 cm or more for more than 5 years; and people with adipose tissue whose lipolysis capacity as measured in the above-mentioned lipolysis capacity evaluation test is 5 mEq/g or less, preferably 3 mEq/g or less, more preferably 1 mEq/g or less, even more preferably 0.5 mEq/g or less, and particularly preferably 0.3 mEq/g or less.

Dosage and Usage The age-related obesity improving agent and lipolysis ability improving agent of the present invention are administered orally. The dosage of the age-related obesity improving agent and lipolysis ability improving agent of the present invention is appropriately set according to the age, sex, constitution, etc. of the subject of administration, but for example, the total amount of the herbal medicine-derived components of the Bofu-tsushosan extract per person per day is about 1 to 10 g, preferably about 1.5 to 8 g, more preferably about 1.5 to 6 g, and may be taken 1 to 3 times, preferably 2 or 3 times, per day. The timing of administration is not particularly limited, and may be before, after, or between meals, but is preferably before (30 minutes before a meal) or between meals (2 hours after a meal).

In addition, the effect of promoting the excretion of lipids into the feces by the age-related obesity improving agent of the present invention is achieved by continuous administration, so it is preferable to continuously take the age-related obesity improving agent of the present invention (specifically, continuous administration for 6 days or more, preferably continuous administration for 12 days or more).

Furthermore, since the improvement in responsiveness to noradrenaline stimulation by the lipolysis ability improving agent of the present invention is achieved by continuous administration, it is preferable to continuously take the lipolysis ability improving agent of the present invention (specifically, continuous administration for 6 days or more, preferably continuous administration for 12 days or more).

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

Production and analysis of Bofutsushosan extract
1. Production of Bofutsushosan Extract Powder Each herb shown in Table 1 was finely chopped or sliced, mixed in a given amount, and finely chopped to obtain a herb preparation. Twenty times the weight of water was added to the herb preparation, and extraction was performed while stirring at about 100°C for 1 hour. The extract was then collected by centrifugation, concentrated under reduced pressure, and dried using a spray dryer to obtain Bofutsushosan extract powder.

In Production Examples 1 and 2, ginger was used that had been cut into 1-8 mm cubes, while in Production Example 3, ginger was used that had been sliced into 1-3 mm slices. Drying using a spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

2. Measurement of 6-gingerol content in Bofutsushosan extract powder Approximately 1 g of Bofutsushosan extract powder was precisely weighed and placed in a stoppered centrifuge tube, 30 mL of methanol/water mixture (methanol:water volume ratio 3:1) was added, and the mixture was shaken for 20 minutes, then centrifuged to separate the extract. 30 mL of methanol/water mixture (methanol:water volume ratio 3:1) was added to the residue, and this operation was repeated twice. All the extracts were combined, and a methanol/water mixture (methanol:water volume ratio 3:1) was added to make exactly 100 mL, which was used as the sample solution. Separately, approximately 5 mg of 6-gingerol for quantitative analysis was precisely weighed and dissolved in a methanol/water mixture (methanol:water volume ratio 3:1) to make exactly 100 mL, which was used as the standard solution. 10 μL each of the sample solution and standard solution were precisely taken and measured by liquid chromatography under the following test conditions.
(Test conditions)
Detector : ultraviolet spectrophotometer (measurement wavelength: 205 nm)
Column : A stainless steel tube having an inner diameter of 4.6 mm and a length of 15 cm packed with 5 μm octadecylsilylated silica gel for liquid chromatography (COSMOSIL 5C18 MS-II (5 μm, 4.6×150 mm) (Nacalai Tesque, Inc.)).
Column temperature : constant temperature around 40°C
Mobile phase : Water/acetonitrile/phosphoric acid mixture (volume ratio of water:acetonitrile:phosphoric acid 3800:2200:1)
Flow rate : adjusted so that the retention time of 6-gingerol was approximately 19 minutes.

The amount of 6-gingerol in the sample solution was calculated according to the formula below, and the 6-gingerol content in each Bofu-tsusho-san extract powder was determined.

The results are shown in Table 2. In the bofutsushosan extract obtained from a herbal preparation with a low ratio of ginger (1.11 parts by weight) per 100 parts by weight of the herbal preparation, the 6-gingerol content was low (0.010% by weight) (Production Example 1). In addition, when the ginger used for extraction was sliced into 1-3 mm thick slices, the 6-gingerol content in the obtained bofutsushosan extract was reduced compared to when it was cut into 1-8 mm cubes (Production Examples 2 and 3).

Test Example 1: Evaluation of the effect of reducing visceral fat and body weight
Preparation of Juvenile Obese Model Mice Young mice (C57BL/6J mice, 5 weeks old, male) were fed a high fat diet (HFD32, CLEA Japan, Inc.) ad libitum for 4 weeks to prepare juvenile obese model mice.

Age-related obesity model mice were also created by feeding aged mice (C57BL/6J mice, 40-60 weeks old, male) ad libitum with a high-fat diet (HFD32, CLEA Japan, Inc.) for one week.

In addition, epididymal fat was extracted from three each of the young obese model mice and aged obese model mice prepared above, and lipolytic power was measured. Specifically, the adipose tissue extracted from around the epididymis was first washed with Krebs Ringer buffer (pH 7.4). The weight of the adipose tissue after washing was measured, and 0.2 g of the washed adipose tissue was added to 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2 wt% bovine serum albumin (BSA), and incubated at 37°C for 2 hours. The supernatant was then collected, and the amount of free fatty acid released into the supernatant by noradrenaline stimulation was measured using NEFA-C Test Wako (Wako Pure Chemical Industries, Ltd.), and the amount of free fatty acid released per 1 g of adipose tissue (mEq/g) was calculated as lipolytic power.

Administration test of Bofutsushosan extract After measuring the body weight of the young obese model mice prepared above, they were divided into control group A (control example), test group A1, and test group A2 (6-11 mice per group) so that the average body weight of each group was about 26g. In addition, after measuring the body weight of the aged obese model mice prepared above, they were divided into control group B (control example) and test group B (6 mice per group) so that the average body weight of each group was about 42g.

Test group A1 was fed a feed in which the high-fat diet was mixed with 2% by weight of the bofutsushosan extract powder of Production Example 1 for 21 days. Test group A2 was fed a feed in which the high-fat diet was mixed with 4% by weight of the bofutsushosan extract powder of Production Example 1 for 21 days. Test group B was fed a feed in which the high-fat diet was mixed with 2% by weight of the bofutsushosan extract powder of Production Example 1 for 21 days. Control groups A and B were fed a high-fat diet without bofutsushosan extract for 21 days. On the final day of the test, the body weight of each mouse was measured, and visceral fat was removed and weighed.

The average weight of the mice in control group A on the final day of the test was set as 100%, and the relative values of the average weight of the mice in test groups A1 and A2 on the final day of the test were calculated. The average weight of the mice in control group B on the final day of the test was set as 100%, and the relative values of the average weight of the mice in test group B on the final day of the test were calculated. The average weight of the visceral fat of the mice in control group A on the final day of the test was set as 100%, and the relative values of the average weight of the mice in test groups A1 and A2 on the final day of the test were calculated. The average weight of the visceral fat of the mice in control group B on the final day of the test was set as 100%, and the relative values of the visceral fat weight of the mice in test group B on the final day of the test were calculated.

The results are shown in Table 3. From the results, it was confirmed that the bofutsushosan extract powder reduced body weight and visceral fat in both the juvenile obese mouse model and the aged obese mouse model, but in the aged obese mouse model, feeding a diet containing 2% by weight of the bofutsushosan extract powder reduced body weight and visceral fat more than the juvenile obese mouse model fed a diet containing 4% by weight of the bofutsushosan extract powder.

The lipolytic capacity of the epididymal fat was 5.6 mEq/g on average in the young obese model mice, whereas it was 0.28 mEq/g in the age-related obese model mice, meaning that lipolytic capacity decreased to one-twentieth of that with age. This is an extremely unexpected result, as it shows that even in an age-related obese mouse model with a decreased lipolytic capacity, effective reductions in body weight and visceral fat were observed with Bofutsushosan extract powder.

Test Example 2: Evaluation of weight reduction effect by age group The weight reduction effect of the Bofutsushosan extract was evaluated for people with a constitution that essentially reduces lipid decomposition and metabolic ability. Specifically, 9 men and women (selected so that the difference in average weight between each age group (20s, 30s, 40s to 50s) who have had a body fat rate of 25% or more and a waist size of 85 cm or more for 5 years or more) were given 5000 mg of the Bofutsushosan extract powder of Production Example 1 three times a day for 2 weeks, and the change in weight compared to before the start of administration was measured.

The results are shown in Table 4. When subjects with constitutions that are inherently impaired in lipid decomposition and metabolic capacity were administered Bofutsushosan extract, an average weight loss of approximately 1 kg was observed for the entire group. When the effects of Bofutsushosan extract were analyzed by generation, the effect increased with age, and it was particularly effective in improving age-related obesity in people in their 40s and 50s. Since the lipid decomposition and metabolic capacity of people in their 40s and 50s is essentially impaired in age-related obesity, it was previously thought that Bofutsushosan extract would be ineffective. However, as shown in Reference Test Example 1 described below, Bofutsushosan extract promotes lipid excretion in the stool, and it is believed that this effect is one of the factors that contributed to the excellent weight loss effect on age-related obesity.

Reference Test Example 1: Evaluation of the Effect of Promoting the Excretion of Lipids into Feces and the Effect of Reducing Body Weight Mice (C57BL/6J mice, 5 weeks old, male) were fed with a high-fat diet (HFD32, CLEA Japan, Inc.) ad libitum for 4 weeks to prepare obese model mice. After measuring the weight of the obese model mice, they were divided into a total of three groups, a control group (control example), a test group 1, and a test group 2, so that the average weight of each group was about 26 g (6 to 11 mice per group). In the test group 1, the obese model mice were fed a feed in which the high-fat diet was mixed with the bofutsushosan extract of Production Example 1 at 4% by weight for 20 days. In the test group 2, the obese model mice were fed a feed in which the high-fat diet was mixed with the bofutsushosan extract of Production Example 2 at 4% by weight for 20 days. In the control group, the high-fat diet without the bofutsushosan extract was fed for 20 days. Feces were collected every two days during the test period. The collected feces was freeze-dried.

Lipids were extracted from the freeze-dried feces with a low polarity solvent, and the total lipid content in the feces was measured by gravimetric analysis. Specifically, after crushing the freeze-dried feces, 100 mg was weighed out and extracted twice with 500 μL of a chloroform/ethanol solution (chloroform:ethanol (volume ratio) = 2:1), and the extract was vacuum dried at 30°C, after which the weight of the extract (lipid) was measured. The total lipid excretion amount of each group was calculated according to the following calculation formula, and the total lipid excretion amount of each group was divided by the number of mice in each group to calculate the total lipid excretion amount per mouse.

Furthermore, the extract (lipids) extracted from the feces excreted between 12 and 14 days after the start of the test was redissolved in isopropanol and the weight of cholesterol was measured using a Cholesterol E Test Wako (Wako Pure Chemical Industries, Ltd.) according to the instructions attached to the kit. The cholesterol excretion amount of each group was calculated according to the following calculation formula, and the cholesterol excretion amount per mouse was calculated by dividing the cholesterol excretion amount of each group by the number of mice in each group.

The total lipid excretion amount per mouse in the control group was set to 100%, and the relative values of the total lipid excretion amount per mouse in test groups 1 and 2 were calculated. Similarly, the cholesterol excretion amount per mouse in the control group was set to 100%, and the relative values of the cholesterol excretion amount per mouse in test groups 1 and 2 were calculated.

The weight of the obese model mice in each group was measured at the start of breeding (day 0) and on the final day of breeding (day 20). The weight at the start of breeding for each group was set as 100%, and the percentage of the weight on the final day of breeding was calculated as the weight change rate (%).

The results of total lipid excretion are shown in Table 5, the results of cholesterol excretion in Table 6, and the rate of weight change in Table 7.

During the breeding period, no diarrhea was observed in any of the mice. Furthermore, the daily fecal mass of each mouse was 211.5-315.1 mg/mouse/day in dry weight, with no significant difference observed between groups.

As can be seen from Table 5, in test groups 1 and 2 that received bofutsushosan extract powder, an increase in total lipid excretion was observed compared to the control group from the 6th day of rearing. Since there was no significant difference in the amount of dried feces between the groups, it was clear that the lipid concentration in the feces increased by feeding bofutsushosan extract powder. In particular, from the 12th day of rearing onwards, the lipid excretion amount in test group 1 was greater than that in test group 2, and it was clear that the use of bofutsushosan extract powder (production example 1) obtained from a herbal preparation containing a small amount of ginger enhances the lipid excretion promoting effect. In addition, a similar test was also carried out on Bofutsushosan extract powder (6-gingerol content: 0.012 parts by weight per 100 parts by weight of Bofutsushosan extract powder (total amount of herbal ingredients)) produced under the same conditions as in Production Example 1, except that the amount of ginger in the herbal preparation was 0.4 parts by weight. It was found that the lipid excretion-promoting effect was greater than when the Bofutsushosan extract powder in Production Example 2 was used.

As is clear from Table 6, similar to the results for total lipid excretion, cholesterol excretion was increased in test groups 1 and 2 that ingested bofutsushosan extract powder compared to the control group. Also, cholesterol excretion was increased in test group 1 that ingested bofutsushosan extract powder of Production Example 1 compared to test group 2 that ingested bofutsushosan extract of Production Example 2.

Furthermore, as shown in Table 7, the control group had increased in body weight at the end of feeding compared to the start of feeding, whereas weight gain was suppressed in test groups 1 and 2 which were fed bofutsushosan extract. In particular, test group 1 which was fed bofutsushosan extract of Production Example 1 showed a greater weight reduction effect than test group 2 which was fed bofutsushosan extract of Production Example 2. Such suppression of weight gain by bofutsushosan extract is thought to be partly due to its effect of promoting the excretion of lipids into the feces.

Test Example 3: Evaluation of lipolysis ability improvement effect Two kinds of male C57BL/6J mice of different ages (young: 9 weeks old, aged: 43-63 weeks old) were divided into a control group and a test group (Bofu-tsushosan extract administration group) (5-8 mice per group, total of 4 groups). The control group was fed a high-fat diet (HFD32, Nippon Clea) for 4 weeks, and the test group was fed a feed in which the Bofu-tsushosan extract powder of Production Example 2 was mixed into the high-fat diet at 2% by weight for 4 weeks.

After feeding, the epididymal fat was removed from each group of mice, and the response to noradrenaline stimulation (lipolytic ability) was evaluated. Specifically, the adipose tissue removed from around the epididymis was first washed with Krebs Ringer buffer (pH 7.4). The weight of the washed adipose tissue was measured, and 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2% by weight bovine serum albumin (BSA) was added to 0.2 g of the washed adipose tissue, and incubated at 37°C for 2 hours. The supernatant was then collected, and the amount of free fatty acids released into the supernatant by noradrenaline stimulation was measured using a NEFA-C Test Wako (Wako Pure Chemical Industries, Ltd.), and the amount of free fatty acids released per 1 g of adipose tissue was calculated as lipolytic ability. Table 8 shows the lipolysis rate in each group, assuming the lipolysis ability of the control group of young mice to be 100%, and the rate of change in lipolysis rate due to administration of Bofu-tsushosan.

As shown in Table 8, when comparing the control groups of young and aged mice, the fat decomposition ability of the aged mice was greatly reduced to 53.1% of that of the young mice. Meanwhile, the fat decomposition ability of the test group was higher than that of the control groups of both young and aged mice. The rate of change was 1.196 times for young mice and 1.386 times for aged mice, and the degree of improvement in fat decomposition ability was higher in aged mice. From this, it was revealed that Bofutsushosan has the effect of enhancing fat decomposition ability in response to nordrenaline stimulation, and furthermore, it shows a superior effect on aged mice than on young mice.

Reference Test Example 2: Preparation of tablets containing Bofutsushosan extract powder 1
Tablets (400 mg per tablet) containing bofutsushosan extract powder were prepared according to the formulations shown in Tables 9 to 14. The extract powder produced according to Production Example 1 or 2 was used as the bofutsushosan extract powder. All of the obtained tablets were expected to have the effect of promoting lipid excretion into feces. Furthermore, when the hardness and disintegration time of the obtained tablets were measured, the tablets using the bofutsushosan extract powder of Production Example 2 had higher hardness and were more easily disintegrated than the tablets using the bofutsushosan extract powder of Production Example 1.

Usually, when tablets contain herbal extract powder, the amount of active ingredient (herbal extract powder) taken per day is greater than in general drugs, so the tablets are large and the number of tablets taken at one time is greater, which is a drawback for consumers, as they are difficult to take. In order to overcome this drawback, it is effective to increase the content of the herbal extract powder in the tablet, but when the content of the herbal extract powder in the tablet is increased, the content of the excipients is relatively reduced, resulting in a problem of reduced tablet hardness. In this situation, it was found that the bofutsushosan extract powder of Production Example 2 can be used to make tablets with high hardness, so the content of the extract powder can be increased (the content of the excipients can be relatively reduced), making it possible to reduce the size of the tablets and the number of tablets taken at one time.

Reference Test Example 3: Preparation of tablets containing Bofutsushosan extract powder 2
According to the formulation shown in Table 15, the Bofu-tsushosan extract powder obtained in Production Example 1 or Production Example 2 and other ingredients were mixed and granulated, and then tablets (weight 200 mg, diameter 8 mm) were produced by tableting with a pressure of 5 kN or 7 kN.

The disintegration properties of the tablets produced were evaluated according to the disintegration test method described in the Japanese Pharmacopoeia (17th edition). The disintegration time was the average value of six tablets. The hardness was measured using a load cell type tablet hardness tester at a breaking speed of 0.5 mm/min. The results are shown in Tables 16 and 17. Although test tablet 2 was formed at the same impact pressure (7 kN) as test tablet 1, a thinner tablet was obtained. Furthermore, test tablet 2 had a higher hardness than test tablet 1 and was more excellent in physical stability. Furthermore, although test tablet 2 had a higher hardness than test tablet 1, the disintegration time was significantly shortened. Furthermore, although test tablet 3 was formed at a lower impact pressure (5 kN) than test tablet 2 (7 kN), it achieved the same hardness and better disintegration properties as test tablet 1, which was formed at a higher impact pressure (7 kN). Therefore, when test tablet 3 is produced, the load on the tablet press is small, and the life of the tablet press can be extended.

Claims (3)

An agent for improving age-related obesity, which contains bofu-tsushosan extract and is intended for use in people having adipose tissue with a lipolytic power of 1 mEq/g or less as measured in the lipolytic power evaluation test described below.
<Lipid decomposition ability evaluation test>
The adipose tissue collected from the subcutaneous tissue is washed with Krebs Ringer buffer (pH 7.4). The weight of the washed adipose tissue is measured, and 0.2 g of the washed adipose tissue is added to 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2 wt% bovine serum albumin (BSA), and incubated at 37° C. for 2 hours. The supernatant is then collected, and the amount of free fatty acid released in the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq/g) is calculated as the lipolysis power. The age-related obesity improving agent according to claim 1, which is applied to a person who has had a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more. 3. The agent for improving age-related obesity according to claim 1, wherein the Bofu-tsusho-san extract contains 0.005 to 0.04 parts by weight of 6-gingerol per 100 parts by weight of the total amount of ingredients derived from herbal medicines.