Agents for improving age-related obesity and lipolysis

Abstract

To provide an obesity improver that exhibits excellent improvement effect on age-related obesity.SOLUTION: A bofu-tsusho-san extract has an action of promoting the excretion of ingested lipid into stool, and exhibits excellent improvement effect on even age-related obesity with substantial decrease of lipolytic capacity and metabolism capacity.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an agent for improving age-related obesity, which can effectively improve age-related obesity. The present invention also relates to an agent for improving lipolytic ability, which can improve a decreased lipolytic ability. [Background technology]

[0002] In recent years, as food culture has become 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 lipid decomposition and metabolic ability in the body, 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 (especially those 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 impaired in lipid decomposition and metabolic ability, and it is thought that conventional obesity improvement agents cannot be expected to be effective.

[0003] 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). In addition, various formulations of Bofutsushosan extract have been developed from the viewpoints of improving the effect of reducing visceral fat and improving taste (e.g., Patent Documents 1 and 2).

[0004] However, as mentioned above, it is believed that conventional obesity treatments are not effective for obesity seen in middle-aged and older people, especially 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 Bofu-tsushosan.

[0005] In addition, adipocytes break down fat accumulated in the cells into free fatty acids in response to noradrenaline stimulation. This is called the lipolytic response. The free fatty acids generated by the lipolytic response are released into the blood, transported to the liver, skeletal muscles, and brown fat, and are metabolized and burned and consumed. It is known that the ability of adipocytes to respond to noradrenaline stimulation decreases when the function of adipocytes declines, and this symptom 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.

[0006] To date, lipolysis promoters such as soybean extract (Patent Document 3) and Pu-erh tea extract (Patent Document 4) have been found to enhance fat decomposition. However, it has been difficult for these lipolysis promoters to be effective against fat that has already lost its lipolysis ability in response to noradrenaline stimulation.

[0007] On the other hand, Bofutsushosan is a herbal medicine composed of 18 kinds of herbal medicines, and is known as an effective herbal medicine for reducing visceral fat and improving metabolic syndrome. The herbal medicine Ephedra, which is a component of Bofutsushosan, contains ephedrine and increases the release of noradrenaline from sympathetic nerve endings. In addition, the herbal medicines licorice, sclerotium, and forsythia have phosphodiesterase inhibitory effects 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 response ability (lipolysis ability) to noradrenaline stimulation has already decreased. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] Chinese Medicine, Vol. 37, No. 1, 2013, pp. 38-40 [Patent documents]

[0009] [Patent Document 1] JP 2009-242354 A [Patent Document 2] JP 2009-242330 A [Patent Document 3] Japanese Patent Application Publication No. 11-228430 [Patent Document 4] JP 2002-275078 A Summary of the Invention [Problem to be solved by the invention]

[0010] The object of the present invention is to provide an obesity improving agent that has an excellent improving effect on age-related obesity. Also, 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). [Means for solving the problem]

[0011] In age-related obesity, lipid decomposition and metabolic ability are often essentially decreased, and conventional obesity improving agents that enhance lipid decomposition and metabolic ability cannot be expected to be effective, but if there is an effect of promoting the excretion of ingested lipid into feces, it is considered to be effective in improving obesity. From this point of view, the present inventors have conducted intensive research to solve the above-mentioned problem, and have found that Bofutsushosan extract has the effect of promoting the excretion of ingested lipid into feces, and has an excellent obesity improving effect even for 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 ability. The present invention was completed based on such knowledge and further research.

[0012] That is, the present invention provides the following aspects. Item 1. An agent for improving age-related obesity containing 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. <Fat decomposition ability evaluation test> 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% by weight bovine serum albumin (BSA), and incubated at 37°C for 2 hours. The supernatant is then collected, and the amount of free fatty acids released into the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acids released per 1 g of adipose tissue (mEq / g) is calculated as the lipolytic power. Item 4. The agent for improving age-related obesity according to any one of Items 1 to 3, wherein the bofutsushosan 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. Item 5. A fat-decomposing agent containing Bofutsushosan extract. Item 6. The lipolysis ability improving agent according to Item 5, which is applied to people who have 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. <Fat decomposition ability evaluation test> 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% by weight bovine serum albumin (BSA), and incubated at 37°C for 2 hours. The supernatant is then collected, and the amount of free fatty acids released into the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acids released per 1 g of adipose tissue (mEq / g) is calculated as the lipolytic 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 ingredients derived from herbal medicines. Effect of the Invention

[0013] The age-related obesity improving agent of the present invention can also improve obesity in age-related obesity in which the decomposition and metabolic ability of lipids have essentially decreased. For example, middle-aged or older people who have been in a state of having a body fat percentage of 25% or more and a waist size of 85 cm or more for more than 5 years cannot expect 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 lipolysis ability improving agent of the present invention can improve the decreased lipolysis ability. For example, middle-aged or older people who have been in a state of having a body fat percentage of 25% or more and a waist size of 85 cm or more for more than 5 years often have already decreased lipolysis ability in response to noradrenaline stimulation due to aging, but the lipolysis ability improving agent of the present invention can be expected to rejuvenate lipolysis ability. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] The agent for improving age-related obesity and the agent for improving lipolysis ability of the present invention are characterized by containing Bofu-tsushosan extract. The agent for improving age-related obesity and the agent for improving lipolysis ability of the present invention will be described in detail below.

[0015] Bofutsushosan Extract 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 Root, Peony Root, Cnidium Root, Sanshishi, Forsythia Root, Mint, Ginger Root, Cabbage Root, Saxifraga Root, Ephedra Root, Rhubarb, Bougainvillea Root, Byakujutsu Root, Platycodon Root, Scutellaria Root, Licorice Root, Scutellaria Root, and Catharanthus Radix. Some letters do not include Byakujutsu Root among the above herbal medicines (for example, "Experience Kampo Prescription Quantities Collection," supervised by Otsuka Keisetsu and Yakazu Domyo, published by Ido no Nihonsha), and some do not include 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.

[0016] According to the "Guide to General Kampo Prescriptions" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health, Labor and Welfare, edited by the Kampo Specialist Committee of the Japan Pharmaceutical Manufacturers Association, and published by Yakugyo Jihosha), "17th Revised Japanese Pharmacopoeia," etc., the amounts of each herb that makes up Bofutsushosan are 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 Chinese Chickweed, 1.2 parts by weight of Forsythia, 1.2 parts by weight of Mentha Root, 0.3 to 1.5 parts by weight of Ginger, 0.2 to 1.5 parts by weight of Citrus Fruit ... 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 Glycyrrhiza Root. 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, "Clear Chinese Medicine Prescriptions," co-authored by Nishioka Kazuo and Takahashi Shintaro, published by Naniwasha).

[0017] The amount of each herb in the herb preparation used to manufacture the Bofutsushosan extract is not particularly limited, and may be the amount shown in the above-mentioned example. Suitable examples include 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 Chinese Cabbage, 1.2 parts by weight of Bofufu, 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). Also, Ginger Root 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 Safflower 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), The amount of Zingiber officinale in the herbal preparation used for the production of the Bofu-tsushosan extract is adjusted to the range of the above-mentioned A1 or A2, and the hardness and disintegration ability of the tablet can be improved by adjusting the amount of Zingiber officinale in the herbal preparation used for the production of the Bofu-tsushosan extract to the range of the above-mentioned A1 or A2, and the hardness and disintegration ability of the tablet can be improved by adjusting the amount of Zingiber officinale in the herbal preparation used for the production of the Bofu-tsushosan extract to the range of the above-mentioned A2, depending on the dosage and the preparation form.

[0018] In addition, in the above-mentioned aspect A1, the amount of sucrose, in terms of sodium sulfate anhydride, is preferably 0.6 to 1 part by weight, more preferably 0.6 to 0.75 parts by weight, particularly preferably 0.7 parts by weight, and in the above-mentioned aspect A2, the amount of sucrose, in terms of sodium sulfate anhydride, is preferably 1 to 1.5 parts by weight, more preferably 1.3 to 1.5 parts by weight, particularly preferably 1.5 parts by weight. Although it depends on the dosage and the formulation form, by satisfying such a range of the amount of sucrose, it is possible to more effectively improve age-related obesity and / or lipolysis ability. In addition, in the above-mentioned aspect A2, by satisfying the amount of sucrose, in terms of sodium sulfate anhydride, preferably 1 to 1.5 parts by weight, more preferably 1.3 to 1.5 parts by weight, particularly preferably 1.5 parts by weight, when formed into a tablet, the hardness and disintegration of the tablet can be improved.

[0019] In the present invention, the term "herbal 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 herbal medicines 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.

[0020] A suitable example of the herbal preparation used in the production of the Bofu-tsushosan extract used in the present invention is one containing 1-5 parts by weight, preferably 1-4 parts by weight, more preferably 1-3 parts by weight, and particularly preferably 1-2 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 lipolysis ability. Another suitable example of the herbal preparation used in the production of the Bofu-tsushosan extract used in the present invention is one containing 2-5 parts by weight, preferably 3-5 parts by weight, more preferably 4-5 parts by weight, and particularly preferably 4-4.5 parts by weight of ginger per 100 parts by weight of the total amount of the herbal preparation. Depending on the dosage and formulation form, etc., by obtaining Bofutsushosan extract from a herbal medicine preparation with such a low ratio of ginger, it is possible to more effectively improve age-related obesity and / or fat decomposition ability, and when formed into tablets, it is possible to improve the hardness and disintegration properties of the tablets.

[0021] In addition, a suitable example of the herbal preparation used in the production of the Bofu-tsushosan extract used in the present invention is one in which Boshou is contained in an amount of 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, calculated as anhydrous sodium sulfate 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 Boshou in the herbal preparation in such a ratio, it becomes possible to more effectively improve age-related obesity and / or lipolysis ability. Another suitable example of the herbal preparation used in the production of the Bofu-tsushosan extract used in the present invention is one in which Boshou is contained in an amount of 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, calculated as anhydrous sodium sulfate per 100 parts by weight of the total amount of the herbal preparation. Although it depends on the dosage and formulation form, by including Boshou in the herbal medicine preparation in such a ratio, it becomes possible to more effectively improve age-related obesity and / or fat decomposition ability, and when molded into tablets, it becomes possible to improve the hardness and disintegration property of the tablets.

[0022] In addition, 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 of the composition 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 a tablet, from the viewpoint of improving the hardness and disintegration of the tablet, preferably 0.02 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 herbal medicine, 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. Here, the ingredients derived from the herbal medicine are ingredients extracted from the herbal medicines 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 herbal medicine, 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 herbal medicine.

[0023] The 6-gingerol content in ginger varies depending on the place of origin and the number of years of growth of ginger, and the extraction efficiency of 6-gingerol from ginger also varies depending on the extraction conditions. Therefore, in order to obtain a bofutsushosan 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 in ginger. The amount of 6-gingerol extracted can be reduced by subjecting ginger to a processed product sliced ​​to a thickness of about 1 to 3 mm rather than to a product cut into thin strips of about 1 to 8 mm square and subjecting it to extraction, and a bofutsushosan extract containing 6-gingerol in the above ratio can be suitably obtained. 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 then 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.

[0024] 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 the bofutsushosan extract, for example, adding about 10 to 20 times the amount of water to the herbal preparation, and stirring at about 80 to 100°C for about 1 to 3 hours to extract. After extraction, the solid content is removed by solid-liquid separation such as centrifugation and filtration, and if necessary, the bofutsushosan extract is obtained by subjecting it to concentration treatment or drying treatment.

[0025] To obtain Bofutsushosan extract as an extract powder, the extract 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 (particularly a drying process by spray drying), an excipient such as dextrin may be added to the extract as necessary. By adding an excipient in this way, it is possible to shorten the drying time. The type and amount of excipient added are the same as those used in the production of general herbal extract powders.

[0026] To obtain Bofu-tsushosan extract as a soft extract, the extract from which the solid components have been removed may be concentrated by vacuum concentration, etc. Alternatively, a suitable adsorbent (e.g., silicic anhydride, starch, etc.) may be added to the soft extract to obtain an adsorbed powder.

[0027] The Bofutsushosan extract used in the present invention may be either extract powder or soft extract, and depending on the form of the agent for improving age-related obesity or the agent for improving lipolysis ability of the present invention, extract powder or soft extract may be appropriately selected. In addition, when it is molded into a tablet, it is preferable to use extract powder from the viewpoint of obtaining a tablet excellent in hardness and disintegration property.

[0028] Other Ingredients 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.

[0029] 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 examples include carmellose calcium, light anhydrous silicic acid, magnesium stearate, and synthetic aluminum silicate. The content of these additives and bases is appropriately set depending on the type of additive and base used.

[0030] When formed into a tablet, it is preferable to contain at least starch as an additive and base from the viewpoint of obtaining a tablet excellent in hardness and disintegration. Examples of starch include potato starch, corn starch, etc., and preferably potato starch. The content of starch 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 of the tablet when formed into a tablet.

[0031] 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 disintegrability, 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.

[0032] In addition, the age-related obesity improving agent and lipolysis ability improving agent of the present invention may contain other nutritional components or 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 enzymes, 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 according to the type of components used, the formulation form of the age-related obesity improving agent or lipolysis ability improving agent, etc.

[0033] Formulation The formulation of the age-related obesity improving agent and lipolysis ability improving agent 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.

[0034] 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 rectangular. 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.

[0035] When the age-related obesity improving agent and lipolysis ability improving agent of the present invention are formed into tablets, the tablets may be plain tablets (plain tablets) or coated tablets with a coating 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 or gastrosoluble polymer base. Preferably, the hardness of the plain tablets is 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.

[0036] 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 is, 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.

[0037] Purpose The age-related obesity improving agent of the present invention is used for preventing or improving age-related obesity. Age-related obesity is obesity in which lipid decomposition and metabolic ability are reduced 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).

[0038] 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 feces. By thus also having the effect of promoting the excretion of lipids into feces, it becomes possible to effectively improve or avoid health disorders (weight gain, visceral fat gain, etc.) caused by excessive lipid intake in age-related obesity.

[0039] 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 capacity, as measured in the lipolytic capacity 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. <Fat 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 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg / mL noradrenaline and 2% by weight bovine serum albumin (BSA) is added to 0.2 g of the washed adipose tissue, and incubated at 37°C for 2 hours. The supernatant is then collected, and the amount of free fatty acids released into the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acids released per 1 g of adipose tissue (mEq / g) is calculated as the lipolysis power.

[0040] It is known that adipose tissue is activated by noradrenaline stimulation, and the accumulated fat is broken down to release free fatty acids. In the lipolysis ability evaluation test, the decomposition ability of adipose tissue is evaluated by measuring the amount of this free fatty acid released.

[0041] The lipolysis ability improving agent of the present invention is used for preventing the decline of lipolysis ability or improving the declined lipolysis ability. The state of decline of lipolysis ability is a state of decline of the response ability of fat cells to noradrenaline stimulation, and often causes a decline in fat burning and consumption. Therefore, examples of people with decline of lipolysis ability include middle-aged or older people (45 years or older) and / or obese people (e.g., body fat percentage is 25% or more), particularly middle-aged or older people (45 years or older) and obese people (e.g., body fat percentage is 25% or more).

[0042] In addition, in people with reduced lipolysis ability, the response ability to noradrenaline stimulation itself is reduced, so conventional lipolysis promoters cannot be expected to improve lipolysis ability, and people have not been accustomed to taking conventional lipolysis promoters, but the lipolysis ability improving agent of the present invention can enhance the response ability to noradrenaline stimulation itself, so it is possible to effectively improve lipolysis ability or effectively avoid the decline of lipolysis ability.In view of the effects of the present invention, the suitable subjects for the lipolysis ability improving agent of the present invention include people with a constitution that reduces lipolysis ability due to aging, and people who are obese due to the decline in fat burning and consumption caused by the decline in lipolysis ability. Specific examples of people with such a constitution include those who are middle-aged or older (45 years or older) and 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 those who have adipose tissue with a lipolytic power of 5mEq / g or less, preferably 3mEq / g or less, more preferably 1mEq / g or less, even more preferably 0.5mEq / g or less, and particularly preferably 0.3mEq / g or less, as measured in the above-mentioned lipolytic power evaluation test.

[0043] Dosage / Usage The age-related obesity improving agent and lipolysis ability improving agent of the present invention are used by oral administration. 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 day for one human 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 either before meals, after meals, or between meals, but it is preferable to take it before meals (30 minutes before meals) or between meals (2 hours after meals).

[0044] Furthermore, since the effect of promoting excretion of lipids into the stool by the age-related obesity improving agent of the present invention is achieved by continuous administration, it is preferable to take the fecal age-related obesity improving agent of the present invention continuously (specifically, for 6 days or more, preferably for 12 days or more).

[0045] Furthermore, since the improvement in response ability to norepinephrine stimulation by the lipolysis ability improving agent of the present invention is achieved by continuous administration, it is preferable to take the lipolysis ability improving agent of the present invention continuously (specifically, for continuous administration for 6 days or more, preferably for continuous administration for 12 days or more). EXAMPLES

[0046] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0047] Production and analysis of Bofutsushosan extract 1. Manufacturing of Bofutsushosan extract powder Each herb shown in Table 1 was chopped or sliced, mixed in the specified amounts, and chopped to obtain a herb preparation. Water was added to the herb preparation in an amount 20 times by weight, 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.

[0048] In Production Examples 1 and 2, ginger was used that was cut into 1-8 mm cubes, while ginger was used in slices having a thickness of 1-3 mm in Production Example 3. Drying with a spray dryer was performed by dropping the extract into an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

[0049] [Table 1]

[0050] 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 tube 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 of each of the sample solution and standard solution were accurately taken and measured by liquid chromatography under the following test conditions. (Test conditions) Detector :Ultraviolet absorption photometer (measurement wavelength: 205nm) column : A stainless steel tube with 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℃ mobile phase : Water / acetonitrile / phosphoric acid mixture (volume ratio of water:acetonitrile:phosphoric acid 3800:2200:1) flow rate The retention time of 6-gingerol was adjusted to be approximately 19 minutes.

[0051] 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.

number

[0052] The results are shown in Table 2. In the bofutsushosan extract obtained from a herbal preparation in which the ratio of ginger was as low as 1.11 parts by weight per 100 parts by weight of the herbal preparation, the 6-gingerol content was as low as 0.010% by weight (Production Example 1). In addition, when the ginger used for extraction was sliced ​​into slices with a thickness of 1 to 3 mm, the 6-gingerol content in the obtained bofutsushosan extract was reduced compared to when it was cut into thin strips of 1 to 8 mm cubes (Production Examples 2 and 3).

[0053] [Table 2]

[0054] Test Example 1: Evaluation of the effect of reducing visceral fat and body weight Generation of juvenile obese mouse models 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 create a juvenile obese mouse model.

[0055] In addition, age-related obesity model mice were generated 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.

[0056] In addition, epididymal fat was removed from three young obese model mice and three aged obese model mice prepared above, and lipolytic power was measured. Specifically, the adipose tissue removed from the epididymis was first washed with Krebs Ringer buffer (pH 7.4). The weight of the adipose tissue after washing was measured, and 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg / mL noradrenaline and 2 wt% 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 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.

[0057] Administration test of Bofutsushosan extract After measuring the body weight of the young obese model mice prepared above, they were divided into a control group A (control example), a test group A1, and a test group A2 (6 to 11 mice per group) so that the average body weight of each group was about 26 g. In addition, after measuring the body weight of the aging obese model mice prepared above, they were divided into a control group B (control example) and a test group B (6 mice per group) so that the average body weight of each group was about 42 g.

[0058] Test group A1 was fed a feed in which the bofutsushosan extract powder of Production Example 1 was mixed with the high-fat diet at 2% by weight for 21 days. Test group A2 was fed a feed in which the bofutsushosan extract powder of Production Example 1 was mixed with the high-fat diet at 4% by weight for 21 days. Test group B was fed a feed in which the bofutsushosan extract powder of Production Example 1 was mixed with the high-fat diet at 2% by weight 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 the weight was measured.

[0059] The average weight of the mice on the final day of the test in the control group A was taken as 100%, and the relative values ​​of the average weight of the mice on the final day of the test in the test groups A1 and A2 were calculated. The average weight of the mice on the final day of the test in the control group B was taken as 100%, and the relative values ​​of the average weight of the mice on the final day of the test in the test group B were calculated. The average weight of the visceral fat of the mice on the final day of the test in the control group A was taken as 100%, and the relative values ​​of the average weight of the mice on the final day of the test in the test groups A1 and A2 were calculated. The average weight of the visceral fat of the mice on the final day of the test in the control group B was taken as 100%, and the relative values ​​of the visceral fat weight of the mice on the final day of the test in the test group B were calculated.

[0060] result 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 bofutsushosan extract powder reduced body weight and visceral fat more than the juvenile obese mouse model fed a diet containing 4% by weight of bofutsushosan extract powder.

[0061] The lipolytic capacity of the epididymal fat was 5.6mEq / g on average in the young obese model mice, while it was 0.28mEq / g in the aged obese model mice, and the lipolytic capacity decreased to one-twentieth of that in the old obese model mice with aging. It was an unexpected result that Bofutsushosan extract powder effectively reduced body weight and visceral fat even in the old obese mouse model with reduced lipolytic capacity.

[0062] [Table 3]

[0063] Test Example 2: Evaluation of weight loss effects by age group The weight-reducing effect of Bofutsushosan extract on people with a constitution that is essentially impaired in lipid decomposition and metabolism was evaluated. Specifically, 9 men and women (selected so that the difference in average weight between each age group (20s, 30s, 40s to 50s) who had a body fat rate of 25% or more and a waist size of 85 cm or more for 5 years or more) were administered 5,000 mg of Bofutsushosan extract powder of Preparation Example 1 three times a day for 2 weeks, and the change in weight compared to before the start of administration was measured.

[0064] The results are shown in Table 4. For people with a constitution in which lipid decomposition and metabolic ability are essentially decreased, a weight loss of about 1 kg was observed on average for the entire group when Bofutsushosan extract was administered. When the effect of Bofutsushosan extract was analyzed by generation, the effect increased with age, and the improvement effect on age-related obesity in people in their 40s and 50s was particularly excellent. In people in their 40s and 50s, the lipid decomposition and metabolic ability are essentially decreased in the case of age-related obesity, so it was previously thought that Bofutsushosan extract would not be effective. However, as shown in Reference Test Example 1 described later, Bofutsushosan extract has an effect of promoting lipid excretion in the stool, and it is believed that this effect is one of the factors that contributed to the excellent weight reduction effect on age-related obesity.

[0065] [Table 4]

[0066] 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 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), test group 1, and test group 2 (6 to 11 mice per group), so that the average weight of each group was about 26 g. In test group 1, the obese model mice were fed a feed in which the high-fat diet was mixed with 4% by weight of the bofutsushosan extract of Production Example 1 for 20 days. In test group 2, the obese model mice were fed a feed in which the high-fat diet was mixed with 4% by weight of the bofutsushosan extract of Production Example 2 for 20 days. In the control group, the high-fat diet not containing the bofutsushosan extract was fed for 20 days. Feces were collected every two days during the test period. The collected feces were freeze-dried.

[0067] 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.

number

[0068] Furthermore, the extracts (lipids) extracted from the feces excreted between 12 and 14 days after the start of the test were 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 included with the kit. The amount of cholesterol excreted in each group was calculated using the following calculation formula, and the amount of cholesterol excreted per mouse was calculated by dividing the amount of cholesterol excreted in each group by the number of mice in each group.

number

[0069] 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 the 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 the test groups 1 and 2 were calculated.

[0070] In addition, 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 (%).

[0071] The results of total lipid excretion are shown in Table 5, the results of cholesterol excretion in Table 6, and the rate of change in body weight in Table 7.

[0072] [Table 5]

[0073] [Table 6]

[0074] [Table 7]

[0075] No diarrhea was observed in any of the mice during the breeding period. The daily fecal mass of each mouse was 211.5-315.1 mg / day / mouse in dry weight, with no significant difference between groups.

[0076] As can be seen from Table 5, in test groups 1 and 2 that were administered Bofutsushosan extract powder, an increase in the 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 revealed that the lipid concentration in the feces was increased by administering 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 revealed that the use of Bofutsushosan extract powder (Production Example 1) obtained from a herbal medicine preparation containing a small amount of ginger enhances the lipid excretion promoting effect. In addition, a similar test was conducted 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 of Production Example 2 was used.

[0077] 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 had been administered Bofutsushosan extract powder compared to the control group. Also, cholesterol excretion was increased in test group 1 that had been administered Bofutsushosan extract powder of Production Example 1 compared to test group 2 that had been administered Bofutsushosan extract of Production Example 2.

[0078] Furthermore, as shown in Table 7, the control group had an increase in body weight at the end of feeding compared to the start of feeding, whereas the body weight increase was suppressed in test groups 1 and 2 which had been administered the bofutsushosan extract. In particular, test group 1 which had been administered the bofutsushosan extract of Production Example 1 had a greater effect on reducing body weight than test group 2 which had been administered the bofutsushosan extract of Production Example 2. Such suppression of body weight increase by the bofutsushosan extract is thought to be partly due to its effect of promoting the excretion of lipids into feces.

[0079] Test Example 3: Evaluation of lipolysis improvement effect Two types 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 (Bofutsushosan extract administered 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 diet containing 2% by weight of the Bofutsushosan extract powder of Production Example 2 mixed into the high-fat diet for 4 weeks.

[0080] After feeding, the epididymal fat was removed from each group of mice, and the response ability (lipolytic ability) to noradrenaline stimulation was evaluated. Specifically, first, the adipose tissue removed from around the epididymis was washed with Krebs Ringer buffer (pH 7.4). The weight of the adipose tissue after washing was measured, and 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg / mL noradrenaline and 2 wt% bovine serum albumin (BSA) was added to 0.2 g of the washed adipose tissue, and incubated at 37 ° C for 2 hours. Thereafter, the supernatant was 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 was calculated as the lipolytic ability. Table 8 shows the lipolytic rate in each group when the lipolytic ability in the control group of young mice is set to 100%, and the change rate of the lipolytic rate due to the administration of Bofu-tsusho-san.

[0081] result As shown in Table 8, when comparing the control groups of young and aged mice, the fat decomposition capacity of the aged mice was significantly reduced to 53.1% of that of the young mice. On the other hand, the fat decomposition capacity 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 the young mice and 1.386 times for the aged mice, and the degree of improvement in fat decomposition capacity was higher in the aged mice. This shows that Bofutsushosan has the effect of increasing fat decomposition capacity in response to nordrenaline stimulation, and furthermore, it shows a more excellent effect on aged mice than on young mice.

[0082] [Table 8]

[0083] Reference Test Example 2: Manufacture 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. In addition, 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.

[0084] Usually, when tablets contain Kampo extract powder, the amount of active ingredient (Kampo extract powder) taken per day is larger than that of general drugs, so the tablets are large and the number of tablets taken at one time is large, which is a drawback for consumers. In order to overcome such drawbacks, it is effective to increase the content of Kampo extract powder in the tablet, but when the content of Kampo extract powder in the tablet is increased, the content of excipients is relatively decreased, resulting in a problem of reduced tablet hardness. In such a 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 extract powder can be increased (the content of excipients can be relatively reduced), and the tablets can be made smaller and the number of tablets taken at one time can be reduced.

[0085] [Table 9]

[0086] [Table 10]

[0087] [Table 11]

[0088] [Table 12]

[0089] [Table 13]

[0090] [Table 14]

[0091] Reference Test Example 3: Manufacture of tablets containing Bofutsushosan extract powder 2 According to the formulation shown in Table 15, the Bofutoujisan 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 compressing with a pressure of 5 kN or 7 kN.

[0092] [Table 15]

[0093] The tablets produced were evaluated for disintegration 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 molded 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 greatly shortened. Furthermore, although test tablet 3 was molded at a lower impact pressure (5 kN) than the impact pressure (7 kN) used to mold test tablet 2, it achieved the same hardness and better disintegration as test tablet 1 molded at a higher impact pressure (7 kN). Therefore, when test tablet 3 is manufactured, the load on the tablet press is small, and the life of the tablet press can be extended.

[0094]

Table 16

[0095]

Table 17

Claims

1. An age-related obesity improving agent containing Bofu-tsushosan extract 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.

2. 2. The agent for improving age-related obesity 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. 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.

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