JP2022105650A - Age-related obesity improver and lipolysis improver - Google Patents

Abstract

PROBLEM TO BE SOLVED: 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

COPYRIGHT: (C)2022,JPO&INPIT

Description

The present invention relates to an age-related obesity improving agent capable of effectively improving age-related obesity. The present invention also relates to a lipolytic power improving agent capable of improving the reduced lipolytic power.

In recent years, with the westernization of food culture, the amount of lipid intake of Japanese people has increased, and excessively ingested lipid causes weight gain and causes obesity. To improve obesity, it is effective to increase the resolution and metabolic capacity of lipids in the body. There is a limit to improving resolution and metabolic capacity. In particular, obesity seen in middle-aged and elderly people (especially 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 5 years or more) is essentially the resolution and metabolic capacity of lipids. It is considered that the conventional obesity-improving agent cannot be expected to be effective.

On the other hand, Bofutsushosan is known as an effective Chinese herbal medicine for reducing visceral fat and improving metabolic syndrome. Regarding the mechanism of action of Bofutsushosan, activation of heat production in brown adipocytes via the sympathetic nervous system, promotion of fat decomposition in white adipocytes, etc. have been clarified (see Non-Patent Document 1). ). In addition, various pharmaceutical formulations have been developed for Bofutsushosan extract from the viewpoint of improving the effect of reducing visceral fat and improving the taste (for example, Patent Documents 1 and 2).

However, as mentioned above, for obesity seen in middle-aged and older people, especially in middle-aged and older people who have a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more. It is thought that conventional obesity-improving agents cannot be expected to be effective, and such middle-aged and older people are often unwilling to restrict their diet and are not taking Bofutsushosan. Met.

In addition, adipocytes decompose the fat accumulated in the cells into free fatty acids by stimulation with noradrenaline. This is called a lipolytic response. Free fatty acids produced by the lipolysis response are released into the blood, transported to the liver, skeletal muscle, and brown fat, metabolized, and burned and consumed. It is known that when the function of adipocytes declines, the ability to respond to noradrenaline stimuli decreases, and this symptom is known to progress particularly with aging. Furthermore, such a decrease in the ability to respond to noradrenaline stimulation leads to a decrease in fat burning and consumption, and is considered to be one of the causes of weight gain with aging.

So far, lipolysis promoters such as soybean extract (Patent Document 3) and Pu'er tea extract (Patent Document 4) have been found for the purpose of enhancing fat decomposition. However, it has been difficult for these lipolytic promoters to exert their effects on fats whose lipolytic ability in response to noradrenaline stimulation has already decreased.

On the other hand, Bofutsushosan is a herbal medicine composed of 18 kinds of crude drugs, and is known as an effective herbal medicine for reducing visceral fat and improving metabolic syndrome. Ephedra, a constituent crude drug, contains ephedrine and increases noradrenaline release from sympathetic nerve endings. In addition, the constituent crude drugs licorice, schizonepeta, and forsythia have a phosphodiesterase inhibitory effect, and have a function of sustaining the effect of noradrenaline released by ephedrine. In other words, the mechanism of action of Bofutsushosan works on the release of noradrenaline. Due to this mechanism of action, it was common knowledge that Bofutsushosan had little effect on adipocytes whose ability to respond to noradrenaline stimulation (lipolytic ability) itself had already declined. ..

Chinese medicine, Vol. 37, No. 1, 2013, pp. 38-40

Japanese Unexamined Patent Publication No. 2009-242354 Japanese Unexamined Patent Publication No. 2009-242330 Japanese Unexamined Patent Publication No. 11-228430 Japanese Unexamined Patent Publication No. 2002-275078

An object of the present invention is to provide an obesity ameliorating agent having an excellent ameliorating effect on age-related obesity. Another object of the present invention is to provide a lipolytic power improving agent capable of improving a reduced response ability to noradrenaline stimulation (hereinafter, also referred to as a reduced lipolytic power).

In age-related obesity, the resolution and metabolic capacity of lipids are often inherently reduced, and conventional obesity-improving agents that enhance the resolution and metabolic capacity of lipids cannot be expected to be effective, but ingested lipids in the stool. If it has the effect of promoting excretion into obesity, it is considered to be effective in improving obesity. From this point of view, the inventor of the present invention has made a diligent study to solve the above-mentioned problems. It has been found that it has an excellent obesity-improving effect even for age-related obesity, in which the resolution and metabolic capacity are essentially reduced. Furthermore, the present inventors have found that Bofutsushosan has an unexpected effect of improving the reduced lipolytic power. The present invention has been completed by further studies based on such findings.

That is, the present invention provides the inventions of the following aspects.
Item 1. An age-related obesity improving agent containing Bofutsushosan extract.
Item 2. Item 2. The age-related obesity improving agent according to Item 1, which is applied to a person having a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more.
Item 3. Item 2. The age-related obesity improving agent according to Item 1 or 2, which is applied to a person having adipose tissue having a lipolytic power measured in the following lipolytic power evaluation test of 5 mEq / g or less.
<Lipolysis ability evaluation test>
Adipose tissue collected subcutaneously is washed with Krebs Ringer's buffer (pH 7.4). Weigh the adipose tissue after washing, and add 1 μg / mL of noradrenaline and 2 wt% bovine serum albumin (BSA) to 5 mL of Krebs Ringer buffer (pH 7.4) in 0.2 g of the washed adipose tissue. In addition, incubate at 37 ° C. for 2 hours. Then, the supernatant is collected, the amount of free fatty acid released into the supernatant by stimulation with noradrenaline is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq / g) is determined as the lipolytic power. Item 4. Item 3. The age-related obesity improving agent 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 crude drug-derived component. Item 5. A lipolytic power improving agent containing Bofutsushosan extract.
Item 6. Item 5. The adipose-decomposing ability improving agent according to Item 5, which is applied to a person who has a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more.
Item 7. Item 5. The lipolytic power improving agent according to Item 5 or 6, which is applied to a person having adipose tissue having a lipolytic power measured in the following lipolytic power evaluation test of 5 mEq / g or less.
<Lipolysis ability evaluation test>
Adipose tissue collected subcutaneously is washed with Krebs Ringer's buffer (pH 7.4). Weigh the adipose tissue after washing, and add 1 μg / mL of noradrenaline and 2 wt% bovine serum albumin (BSA) to 5 mL of Krebs Ringer buffer (pH 7.4) in 0.2 g of the washed adipose tissue. In addition, incubate at 37 ° C. for 2 hours. Then, the supernatant is collected, the amount of free fatty acid released into the supernatant by stimulation with noradrenaline is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq / g) is determined as the lipolytic power. Item 8. Item 5. The lipolytic power improving agent according to any one of Items 5 to 7, wherein the bofutsushosan extract contains 0.005 to 0.04 parts by weight of 6-gingerol per 100 parts by weight of the crude drug-derived component.

According to the age-related obesity ameliorating agent of the present invention, it is possible to exert an obesity-improving effect even on age-related obesity in which the resolution and metabolic capacity of lipids are substantially reduced. For example, middle-aged and older 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 cannot expect an improvement effect with conventional obesity improving agents and are not willing to restrict their diet. In many cases, the age-related obesity ameliorating agent of the present invention can bring the gospel of obesity amelioration to such middle-aged and older people. Further, according to the lipolytic power improving agent of the present invention, the reduced lipolytic power can be improved. For example, middle-aged and older people who have a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more have already reduced their lipolytic ability to respond to noradrenaline stimulation due to aging. However, the lipolytic power improving agent of the present invention can be expected to rejuvenate the lipolytic power.

The age-related obesity improving agent and the lipolytic power improving agent of the present invention are characterized by containing bofutsushosan extract. Hereinafter, the age-related obesity improving agent and the lipolytic power improving agent of the present invention will be described in detail.

Bofutsushosan Extract The crude drugs that make up Bofutsushosan are according to the "Guide for General Chinese Medicine Prescription" (supervised by the Ministry of Health and Welfare, Pharmaceutical Affairs Bureau, edited by the Japan-Yakuren Chinese Medicine Expert Committee, published by Yakuhin Jihosha). , Shakyaku, Senkyu, Sanshishi, Forsythia, Hakka, Shokyo, Schizonepeta, Siler, Maou, Daiou, Bosho, Byakujutsu, Kikyo, Ogon, Kanzo, Sekou, and Kaseki. Some letters do not include the herbal medicines (for example, "Experienced Chinese Medicine Prescription Amount Collection", Keisetsu Otsuka / Domei Yakazu, published by the Japanese company of Ido), and those that do not contain Ogon (for example, "" There is a series of Chinese herbal medicines, edited by Osaka Yomiuri Shimbun, published by Naniwasha). The bofutsushosan extract used in the present invention may be obtained from any of these bofutsushosan.

In addition, the amount of each crude drug that makes up Bofutsushosan is "Guide for General Chinese Medicine Prescription" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Japan-Yakuren Chinese Medicine Expert Committee, published by Yakuhin Jihosha), "17th. According to the revised Japanese Pharmacy Law, 1.2 parts by weight of Touki, 1.2 parts by weight of Shakuyaku, 1.2 parts by weight of Senkyu, 1.2 parts by weight of Sanshishi, 1.2 parts by weight of Renkyo, 1.2 parts by weight of Hacka. Parts, Shokyo 0.3-1.2 parts by weight, Keigai 1.2 parts by weight, Bowfu 1.2 parts by weight or Hamaboufu 1.2 parts by weight, Maou 1.2 parts by weight, Sodium 1.5 parts by weight, Bowsho (Sodium sulfate anhydrous equivalent amount) 0.6 to 1.5 parts by weight, 2 parts by weight of Byakujutsu, 2 parts by weight of Kikyo, 2 parts by weight of Ogon, 2 parts by weight of Kanzo, 2 to 3 parts by weight of Sekko, and 3 to 5 parts of Kaseki It is a part by weight. In addition, depending on the letter, 1.2 parts by weight of the above amount may be 1.5 parts by weight (for example, "Meikyou Kampo Prescription", co-authored by Kazuo Nishioka and Shintaro Takahashi, published by Naniwasha).

The amount of each biopharmaceutical in the biopharmaceutical formulation used for producing the windbreak tsuseisan extract is not particularly limited, and may be used in the amount of each biopharmaceutical shown in the above-exemplified letter, but is preferable. As an example, 1.2 parts by weight of Touki, 1.2 parts by weight of Shakuyaku, 1.2 parts by weight of Senkyu, 1.2 parts by weight of Sanshishi, 1.2 parts by weight of Renkyo, 1.2 parts by weight of Hacka, 1.2 parts by weight of Keigai. By weight, 1.2 parts by weight of Bowfu, 1.2 parts by weight of Maou, 1.5 parts by weight of Daiou, 0.6 to 1.5 parts by weight of Bowsho (sodium sulfate anhydride equivalent), 2 parts by weight of Byakujutsu, 2 parts by weight of Kikyo 2 parts by weight of Ogon, 2 parts by weight of Kanzo, 2 to 3 parts by weight of Sekko (preferably 2 parts by weight), and 3 to 5 parts by weight of Casseki (preferably 3 parts by weight), and 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 preferably 0.3 parts by weight (hereinafter, "Aspect A1"). (May be written as), or 1.2 parts by weight of Touki, 1.2 parts by weight of Shakuyaku, 1.2 parts by weight of Senkyu, 1.2 parts by weight of Sanshishi, 1.2 parts by weight of Renkyo, 1.2 parts by weight of Hacker. Weight parts, Keigai 1.2 parts by weight, Bowfu 1.2 parts by weight, Maou 1.2 parts by weight, Daiou 1.5 parts by weight, Bowsho (sodium sulfate anhydride equivalent amount) 0.6 to 1.5 parts by weight, 2 parts by weight of Byakujutsu, 2 parts by weight of Kyoko, 2 parts by weight of Ogon, 2 parts by weight of Kanzo, 2 to 3 parts by weight of Sekko (preferably 2 parts by weight), and 3 to 5 parts by weight of Kaseki (preferably 3 parts by weight). In addition, the amount of the show is 0.6 to 1.5 parts by weight, preferably 0.8 to 1.4 parts by weight, more preferably 1 to 1.3 parts by weight, and particularly preferably 1.2 parts by weight (. Hereinafter, it may be referred to as “aspect A2”). Although it depends on the dose and the form of the preparation, by adjusting the amount of ginger in the crude drug formulation used for producing the bofutsushosan extract to the range in the above-mentioned A1 or A2, age-related obesity and / Alternatively, the lipolytic power can be improved more effectively, and by adjusting to the range in the aspect A2, the hardness and disintegration property of the tablet can be improved when it is formed as a tablet.

Further, in the above aspect A1, the amount of sodium sulfate is preferably 0.6 to 1 part by weight, more preferably 0.6 to 0.75 part by weight, and particularly preferably 0.7 weight by weight in terms of sodium sulfate anhydride. In the above aspect A2, the amount of sodium sulfate is preferably 1 to 1.5 parts by weight, more preferably 1.3 to 1.5 parts by weight, and particularly preferably 1 in terms of sodium sulfate anhydride. .5 parts by weight can be mentioned. Although it depends on the dose and the form of the pharmaceutical product, when the amount of the bow show satisfies such a range, it becomes possible to more effectively improve the age-related obesity and / or the lipolytic ability. Further, in the above-mentioned aspect A2, the amount of the bow show is preferably 1 to 1.5 parts by weight, more preferably 1.3 to 1.5 parts by weight, and particularly preferably 1.3 to 1.5 parts by weight in terms of sodium sulfate anhydride. By satisfying 1.5 parts by weight, the hardness and disintegration property of the tablet can be improved when it is molded as a tablet.

In the present invention, the "herbal preparation used for the production of bofutsushosan extract" refers to the raw material preparation used for extraction in the production of bofutsushosan extract, that is, bofutsushosan. It is a formulation containing a predetermined amount of a constituent crude drug. Further, the sodium sulfate anhydride conversion of bow show means that when a sodium sulfate hydrate is used as the bow show, the hydrate is converted into an anhydride weight. As the bow show, sodium sulfate hydrate (for example, 10 hydrate) and / or sodium sulfate anhydride is used, and from the viewpoint of improving the hardness and disintegration property of the tablet when it is molded as a tablet. , Sodium sulfate anhydrate is preferably used.

As a suitable example of the crude drug formulation used for producing the bofutsushosan extract used in the present invention, 1 to 5 parts by weight, preferably 1 to 5 parts by weight of ginger per 100 parts by weight of the crude drug formulation. Examples thereof include 4 parts by weight, more preferably 1 to 3 parts by weight, and particularly preferably 1 to 2 parts by weight. Although it depends on the dose and the form of the preparation, by obtaining the bofutsushosan extract from the crude drug preparation having such a low ratio of ginger, the age-related obesity and / or the lipolytic power is more effectively improved. Will be possible. As another suitable example of the crude drug formulation used in the production of the bofutsushosan extract used in the present invention, ginger is preferably 2 to 5 parts by weight, preferably 2 to 5 parts by weight, per 100 parts by weight of the total amount of the crude drug formulation. Examples thereof include those containing 3 to 5 parts by weight, more preferably 4 to 5 parts by weight, and particularly preferably 4 to 4.5 parts by weight. Although it depends on the dose and the form of the preparation, by obtaining the bofutsushosan extract from the crude drug preparation having such a low ratio of ginger, the age-related obesity and / or the lipolytic power is more effectively improved. This makes it possible to improve the hardness and disintegration of tablets when they are molded as tablets.

Further, as a suitable example of the crude drug formulation used for producing the bofutsushosan extract used in the present invention, the amount of sodium sulfate anhydrous is 2 to 6 per 100 parts by weight of the crude drug formulation. Examples thereof include those contained in 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. Although it depends on the dose and the form of the formulation, the inclusion of the bow in the crude drug formulation at such a ratio makes it possible to more effectively improve the age-related obesity and / or the lipolytic ability. As another suitable example of the crude drug formulation used in the production of the bofutsushosan extract used in the present invention, the amount of sodium sulfate anhydrous is 3 to 6 per 100 parts by weight of the crude drug formulation. Examples thereof include those contained in 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. Although it depends on the dose and the form of the preparation, the inclusion of the bow in the crude drug preparation at such a ratio makes it possible to more effectively improve the age-related obesity and / or the lipolytic power. When molded as a tablet, it is possible to improve the hardness and disintegration of the tablet.

In addition, a suitable example of the bofutsushosan 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 crude drug-derived components. .. 6-gingerol is a component contained in ginger, and the conventional bofutsushosan extract usually contains 0.05 parts by weight or more of 6-gingerol per 100 parts by weight of the total amount of crude drug-derived components. .. In the present invention, by using the bofutsushosan extract having a reduced content of 6-gingerol, it becomes possible to more effectively improve age-related obesity and / or lipolytic ability. Although it depends on the dose and the form of the preparation, 6-gingerol is preferably 0. 007 to 0.03 parts by weight, more preferably 0.007 to 0.025 parts by weight, particularly preferably 0.007 to 0.015 parts by weight, or per 100 parts by weight of the total amount of the raw medicine-derived component. 6-Gingerol is preferably 0.02 to 0.04 parts by weight, more preferably 0.025 to 0.04 parts by weight, still more preferably 0.03 to 0.04 parts by weight, and particularly preferably 0.035 to 0.035 parts by weight. Those contained in 0.04 parts by weight can be mentioned. Further, in the case of being molded as a tablet, from the viewpoint of improving the hardness and disintegration of the tablet, the amount of 6-gingerol is preferably 0.02 to 0.04 part by weight per 100 parts by weight of the total amount of the ingredients derived from the raw medicine. It is preferable to use 0.025 to 0.04 parts by weight, more preferably 0.03 to 0.04 parts by weight, and particularly preferably 0.035 to 0.04 parts by weight. Here, the crude drug-derived component is a component extracted from the crude drug constituting Bofutsushosan. That is, in the case of bofutsushosan extract powder containing no additives such as excipients, the weight of the extract powder is the total amount of crude drug-derived components, and additives such as excipients are added. In the case of Bofutsushosan extract powder, the total amount of crude drug-derived components is the weight obtained by subtracting the weight of the additive contained from the weight of the extract powder.

The content of 6-gingerol contained in ginger varies depending on the place of origin of ginger, the number of years of growth, etc., and the efficiency of extracting 6-gingerol from ginger also varies depending on the extraction conditions and the like. Therefore, in order to obtain a bofutsushosan extract containing 6-gingerol in the above ratio, the ratio of ginger in the crude drug formulation and the ginger used for extraction are determined according to the content of 6-gingerol contained in ginger. The shape and the like (that is, ginger used in the crude drug formulation) may be appropriately set. For gingerol, it is better to use the processed product sliced to a thickness of about 1 to 3 mm for extraction than to use it for extraction by cutting it into small pieces with a square of about 1 to 8 mm. The amount of extraction can be reduced, and a bofutsushosan extract containing 6-gingerol in the above ratio can be preferably obtained. For example, 6-gingerol is within the range of the content by adjusting the shape of the ginger after setting the ratio of ginger per 100 parts by weight of the total amount of the crude drug formulation to the range shown in the above-mentioned aspect A1. The bofutsushosan extract contained in the above can be preferably obtained.

The bofutsushosan extract used in the present invention can be obtained by extracting the crude drug formulation by a known method. The method for extracting the crude drug formulation may be the same as the conventional extraction method for bofutsushosan extract. For example, about 10 to 20 times the amount of water is added to the crude drug formulation. , A method of extracting by stirring at about 80 to 100 ° C. for about 1 to 3 hours can be mentioned. After extraction, the solid content is removed by subjecting it to solid-liquid separation such as centrifugation or filtration, and if necessary, it is subjected to a concentration treatment or a drying treatment to obtain a bofutsushosan extract.

In order to obtain the bofutsushosan extract as an extract powder, the extract from which the solid content has been removed may be concentrated as necessary and then subjected to drying treatment such as spray drying, vacuum concentration drying, freeze drying and the like. Further, when subjected to a drying treatment (particularly, a drying treatment by spray drying), an excipient such as dextrin may be added to the extract, if necessary. By adding the excipient in this way, it becomes possible to shorten the drying time. The type and amount of the excipient to be added are the same as in the case of producing a general Chinese herbal extract powder.

Further, in order to obtain the bofutsushosan extract as a soft extract, the extract from which the form has been removed may be concentrated by vacuum concentration or the like. Further, an appropriate adsorbent (for example, silicic acid anhydride, starch, etc.) may 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 depending on the form of the age-related obesity improving agent or the lipolytic power improving agent of the present invention, the extract powder or the extract powder or the soft extract may be used. The soft extract may be appropriately selected. Further, in the case of molding as a tablet, the extract powder is preferable from the viewpoint of obtaining a tablet having excellent hardness and disintegration property.

Other Ingredients The age-related obesity improving agent and the lipolytic power improving agent of the present invention may be composed of bofutsushosan extract alone, or may contain additives and bases according to the pharmaceutical form. good. Such additives and bases are not particularly limited as long as they are pharmaceutically acceptable, but for example, excipients, binders, disintegrants, lubricants, tonicity agents, plasticizers, etc. Dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, pressure-sensitive agents, coating agents, brighteners, water, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols , Esters, water-soluble polymers, surfactants, metal soaps, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, UV inhibitors, preservatives, emulsifiers, fragrances, powders, Examples include thickeners, pigments, chelating agents and the like. These additives may be used alone or in combination of two or more. The content of these additives and bases is appropriately set according to the type of additives and bases to be used, the form of the aging obesity improving agent or the lipolytic power improving agent, and the like.

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 phosphate. Calcium hydrogen hydrogen, carmellose, sodium croscarmellose, sodium starch glycolate, crospopidone, preferably carmellose calcium, light anhydrous silicic acid, magnesium stearate, and synthetic aluminum silicate. The contents of these additives and bases are appropriately set according to the types of additives and bases used.

When molded as a tablet, it is preferable to contain at least starch as an additive and a base from the viewpoint of obtaining a tablet having excellent hardness and disintegration property. Examples of the starch include potato starch, corn starch and the like, 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. Be done. The inclusion of starch in such proportions makes it possible to improve the hardness and disintegration of tablets when molded as tablets.

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, and the amount of magnesium stearate is, for example. 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. Can be mentioned. When molded as a tablet, the content of carmellose calcium is preferably 1 to 7% by weight, more preferably 1 to 1.5% by weight, and further, from the viewpoint of obtaining a tablet having excellent hardness and disintegration property. The content is preferably 1 to 1.2% by weight, and the content of the light anhydrous silicic acid is preferably 4 to 15% by weight, more preferably 4 to 5% by weight, and further preferably 4 to 4.3. ..

Further, the age-related obesity improving agent and the lipolytic power improving agent of the present invention may contain other nutritional components and pharmacological components, if necessary, in addition to the bofutsushosan extract. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable, but for example, antispasmodics, stomachic agents, digestive agents, intestinal regulators, antispasmodics, mucosal repair agents, anti-inflammatory agents, and astringents. Agents, antiemetics, antitussives, sputum, anti-inflammatory enzyme agents, sedative hypnotics, antihistamines, caffeines, cardiotonic diuretics, antibacterial agents, vasoconstrictors, vasoconstrictors, local anesthetics, crude drug extracts, vitamins, menthol Kind and the like. These nutritional components and pharmacological components may be used alone or in combination of two or more. Further, the content of these components is appropriately set according to the type of the component to be used, the formulation form of the age-related obesity improving agent or the lipolytic power improving agent, and the like.

Formulation form The formulation form of the age-related obesity-improving agent and the lipolytic ability improving agent of the present invention is not particularly limited as long as it can be orally administered, and is, for example, a powder, a fine granule, or a granule (dry syrup). ), Tablets, pills, capsules (soft capsules, hard capsules) and other solid formulations; semi-solid formulations such as jelly; liquid formulations such as liquids, suspending agents and syrups. .. Among these pharmaceutical forms, a solid pharmaceutical form is preferable from the viewpoint of stability and portability of the contained components.

When the age-related obesity improving agent and the lipolytic power improving agent of the present invention are molded as tablets, the shape and size of the tablets are not particularly limited. Examples of the tablet shape include a round shape, an elliptical shape, a triangular shape, and a square shape. In the case of a round lock, the diameter is 6 to 12 mm, preferably 8 to 10 mm. The thickness of the tablet may be 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 the lipolytic power improving agent of the present invention are molded as tablets, the tablets may be uncoated tablets (bare tablets), stabilize the drug, and taste, taste, etc. It may be a coated tablet having a coating on the surface for the purpose of. Examples of the coated tablet include a sugar-coated tablet and a film coating agent (gastric-dissolved tablet, enteric-coated tablet) coated with a film containing a water-soluble, enteric-soluble or gastric-soluble polymer base. The hardness of the uncoated tablet is preferably 40 N or more, preferably 50 N or more, more preferably 70 N or more, still more preferably 80 N or more, still more preferably 100 N or more, and particularly preferably 130 N or more.

Production method In order to prepare the age-related obesity improving agent and the lipolytic power improving agent of the present invention in the above-mentioned pharmaceutical form, bofutsushosan extract and additives, bases and pharmacological components added as necessary are required. It may be formulated according to the usual formulation method adopted in the pharmaceutical field. When formulated as tablets, preferably, the method for producing the age-related obesity improving agent and the lipolytic power improving agent of the present invention is bofutsushosan extract, or if necessary, additives, base materials, and other nutrients. It comprises a granulation step of granulating a bofutsushosan extract mixture mixed with an ingredient and / or other pharmacological components, and a tableting step of tableting the granulated product. Examples of the tableting pressure in the tableting step include 4 to 20 kN, preferably 4 to 15 kN in the case of producing a tablet of 200 to 490 mg / tablet. From the viewpoint of reducing the load on the locking device and extending the life of the locking device, the locking pressure may be set to a lower value of 4 to 12 kN.

Uses The age-related obesity improving agent of the present invention is used for the prevention or amelioration of age-related obesity. Age-related obesity is obesity in which the resolution and metabolic capacity of lipids are reduced due to aging. As a person with age-related obesity, for example, obesity (for example, body fat percentage) in middle-aged or older (45 years or older) 25% or more).

The age-related obesity improving agent of the present invention also has an action of promoting excretion of ingested lipids such as cholesterol into feces. In this way, by also having the effect of promoting the excretion of lipids into the stool, it effectively improves or avoids health disorders (weight gain, visceral fat increase, etc.) due to excessive intake of lipids in age-related obesity. Will be possible.

In addition, among people with age-related obesity, those with a constitution in which the resolution and metabolic capacity of lipids are essentially reduced cannot be expected to improve the resolution and metabolic capacity of lipids with conventional obesity improving agents. Although there was no habit of taking obesity-improving agents, according to the age-related obesity-improving agent of the present invention, the resolution and metabolism of such lipids are achieved by having the effect of promoting the excretion of lipids into the stool. Even for age-related obesity whose ability is essentially reduced, it becomes possible to effectively improve or avoid health disorders (weight gain, visceral fat gain, etc.) due to excessive intake of lipids. In view of such effects of the present invention, suitable application targets of the age-related obesity improving agent of the present invention include age-related obesity having a constitution in which the resolution and metabolic capacity of lipids are substantially reduced. Specific examples of age-related obesity with such a constitution include those who are middle-aged or older (45 years or older), have a body fat percentage of 25% or more, and have a waist size of 85 cm or more for 5 years or more. The fat-decomposing power measured in the following fat-decomposing power evaluation test is 5 mEq / g or less, preferably 3 mEq / g or less, more preferably 1 mEq / g or less, still more preferably 0.5 mEq / g or less, and particularly preferably 0. Examples thereof include persons having adipose tissue having an adipose tissue of 3 mEq / g or less.
<Lipolysis ability evaluation test>
First, adipose tissue is collected from the subcutaneous part of the subject. The resulting adipose tissue is washed with Krebs Ringer's buffer (pH 7.4). Weigh the adipose tissue after washing, and add 1 μg / mL of noradrenaline and 2 wt% bovine serum albumin (BSA) to 5 mL of Krebs Ringer buffer (pH 7.4) in 0.2 g of the washed adipose tissue. In addition, incubate at 37 ° C. for 2 hours. Then, the supernatant is collected, the amount of free fatty acid released into the supernatant by stimulation with noradrenaline is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq / g) is determined as the lipolytic power.

It is known that adipose tissue is activated by stimulation with noradrenaline, the accumulated fat is decomposed, and free fatty acid is released. In the lipolytic power evaluation test, the decomposing power of adipose tissue is evaluated by measuring the amount of this free fatty acid released.

The lipolytic power improving agent of the present invention is used for preventing a decrease in lipolytic power or improving the reduced lipolytic power. A state in which lipolytic ability is reduced is a state in which the ability of adipocytes to respond to noradrenaline stimulation is reduced, which often causes a decrease in fat burning and consumption. Therefore, examples of people with reduced adipose decomposition ability include those who are middle-aged or older (45 years or older) and / or obese (for example, body fat percentage of 25% or more), and in particular, those who are middle-aged or older. Examples include people (45 years and older) and obese (eg, body fat percentage of 25% or higher).

In addition, in people with reduced lipolysis ability, the ability to respond to noradrenaline stimulation itself is also reduced, so conventional lipolysis promoters cannot be expected to improve lipolysis ability, and conventional lipolysis promoters can be used. Although I had no habit of taking it, according to the lipolytic power improving agent of the present invention, the ability to respond to noradrenaline stimulation itself can be enhanced, so that the lipolytic power is effectively improved or the lipolytic power is effectively reduced. It becomes possible to avoid it. In view of such effects of the present invention, suitable application targets of the lipolytic power improving agent of the present invention are a person having a constitution in which the lipolytic power is reduced due to aging, and a fat caused by the decrease in the lipolytic power. Some people are obese due to burning or reduced consumption. Specifically, as a person with such a constitution, a person who is middle-aged or older (45 years old or older) and has a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more; The lipolytic force measured in the lipolytic force evaluation test is 5 mEq / g or less, preferably 3 mEq / g or less, more preferably 1 mEq / g or less, still more preferably 0.5 mEq / g or less, and particularly preferably 0.3 mEq / g. Examples thereof include people having adipose tissue of g or less.

Dosage and Usage The age-related obesity-improving agent and lipolytic ability-improving agent of the present invention are used by oral administration. The doses of the age-related obesity-improving agent and the lipolytic ability-improving agent of the present invention are appropriately set according to the age, sex, constitution, etc. of the administration subject. The total amount of crude drug-derived components of Bofutsushosan extract is about 1 to 10 g, preferably about 1.5 to 8 g, more preferably about 1.5 to 6 g, 1 to 3 times a day, preferably 2 Alternatively, it may be taken 3 times. The timing of administration is not particularly limited and may be before meals, after meals, or between meals, but it is preferably before meals (30 minutes before meals) or between meals (2 hours after meals).

Further, since the effect of the aging-related obesity improving agent of the present invention on promoting the excretion of lipids into the stool is achieved by continuous administration, the stool-related obesity improving agent of the present invention is continuously taken ( Specifically, continuous administration for 6 days or longer, preferably continuous administration for 12 days or longer) is preferable.

Furthermore, since the improvement of the ability to respond to noradrenaline stimulation by the lipolytic power improving agent of the present invention is achieved by continuous administration, the lipolytic power improving agent of the present invention is continuously taken (specifically, 6). It is preferable to take the drug continuously for 12 days or longer, preferably for 12 days or longer.

Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.

Manufacture and analysis of Bofutsushosan extract
1. 1. Production of Bofutsushosan Extract Powder Each crude drug shown in Table 1 was shredded or sliced, mixed in a predetermined amount, and shredded to obtain a crude drug formulation. To the crude drug formulation, 20 times the amount of water by weight was added, and extraction was performed with stirring at about 100 ° C. for 1 hour. Then, the extract was collected by centrifugation, concentrated under reduced pressure, and then dried using a spray dryer to obtain Bofutsushosan extract powder.

In Production Examples 1 and 2, ginger was sliced into 1 to 8 mm squares, and in Production Example 3, ginger was sliced to a thickness of 1 to 3 mm. Further, the drying with a spray dryer was performed by dropping the extract onto an atomizer having a rotation speed of 10000 rpm and supplying hot air at 150 ° C.

2. 2. Measurement of 6-gingerol content in Bofutsushosan extract powder Weigh accurately about 1 g of Bofutsushosan extract powder, put it in a co-plugged centrifugal settling tube, and mix methanol / water (methanol: water volume ratio 3: 1). ) 30 mL was added, and the mixture was shaken for 20 minutes, then centrifuged, and the extract was separated. 30 mL of a 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 a sample solution. Separately, about 5 mg of 6-gingerol for quantification 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 a standard solution. Accurately 10 μL each of the sample solution and the standard solution were taken and measured by liquid chromatography under the following test conditions.
(Test conditions)
Detector : Ultraviolet absorptiometer (measurement wavelength: 205 nm)
Column : A stainless steel tube with an inner diameter of 4.6 mm and a length of 15 cm filled with 5 μm of octadecylsilylated silica gel for liquid chromatography (COSMOSIL 5C18 MS-II (5 μm, 4.6)).
× 150 mm) (Nacalai Tesque Co., Ltd.)).
Column temperature : Constant temperature around 40 ° C
Mobile phase : Water / acetonitrile / phosphoric acid mixed solution (water: acetonitrile: phosphoric acid volume ratio 3800: 2200: 1)
Flow rate : The retention time of 6-gingerol was adjusted to about 19 minutes.

The amount of 6-gingerol in the sample solution was calculated according to the following formula, and the content of 6-gingerol in the extract powder of each bofutsushosan was determined.

The results are shown in Table 2. The ratio of ginger to 100 parts by weight of the crude drug formulation was as low as 1.11 parts by weight. In the bofutsushosan extract obtained from the crude drug formulation, the content of 6-gingerol was as low as 0.010% by weight. (Production Example 1). In addition, when the ginger to be extracted is sliced to a thickness of 1 to 3 mm, the content of 6-gingerol in the obtained bofutsushosan extract is higher than that in the case of slicing into 1 to 8 mm squares. The amount was reduced (Productions 2 and 3).

Test Example 1: Evaluation of visceral fat and weight reduction effect
Preparation of juvenile obesity model mice Young mice (C57BL / 6J mice, 5 weeks old, male) were bred by free feeding a high-fat diet (HFD32, Nippon Claire Co., Ltd.) for 4 weeks. A model mouse was produced.

In addition, an aging mouse (C57BL / 6J mouse, 40-60 weeks old, male) was bred by free feeding a high-fat diet (HFD32, Nippon Claire Co., Ltd.) for one week to prepare an aging obesity model mouse. did.

In addition, peritesticular fat was removed from each of the three juvenile obesity model mice and the age-related obesity model mice prepared above, and the lipolytic ability was measured. Specifically, first, the adipose tissue removed from the periphery of the epididymis was washed with Krebs Ringer's buffer (pH 7.4). Weigh the adipose tissue after washing, and add 1 μg / mL noradrenaline and 2 wt% bovine serum albumin (BSA) to 5 mL of Krebs Ringer buffer (pH 7.4) in 0.2 g of the washed adipose tissue. In addition, it was incubated at 37 ° C. for 2 hours. After that, the supernatant was collected, and the amount of free fatty acid released into the supernatant by stimulation with noradrenaline was measured by NEFA-C Testwaco (Wako Pure Chemical Industries, Ltd.), and the amount of free fatty acid released per 1 g of adipose tissue. (MEq / g) was determined as the lipolytic power.

Administration test of bofutsushosan extract After measuring the body weight of the juvenile obesity model mice prepared above, control group A (control example), test group A1 and test so that the average body weight of each group is about 26 g. Divided into groups A2 (6-11 animals in each group). In addition, after measuring the body weight of the age-related obesity model mice prepared above, they were divided into control group B (control example) and test group B so that the average body weight of each group was about 42 g (6 animals in each group). ).

In the test group A1, a feed prepared by blending the high-fat diet with the bofutsushosan extract powder of Production Example 1 in an amount of 2% by weight was fed for 21 days. In the test group A2, a feed prepared by blending the high-fat diet with the bofutsushosan extract powder of Production Example 1 in an amount of 4% by weight was fed for 21 days. In the test group B, a feed containing the bofutsushosan extract powder of Production Example 1 in an amount of 2% by weight was fed to the high-fat diet for 21 days. In control groups A and B, a high-fat diet containing no bofutsushosan extract was fed for 21 days. On the final day of the test, each mouse was weighed, and the visceral fat was removed and weighed.

The relative value of the average body weight of the mice on the final day of the test in the test groups A1 and A2 was calculated, assuming that the average body weight of the mice on the final day of the test in the control group A was 100%. In addition, the relative value of the average body weight of the mice on the final day of the test in the test group B was calculated, assuming that the average body weight of the mice on the final day of the test in the control group B was 100%. The relative value of the average body weight of the mice on the last day of the test of the test groups A1 and A2 was calculated, assuming that the average weight of the visceral fat of the mice on the last day of the test of the control group A was 100%. The relative value of the visceral fat weight of the mice on the final day of the test of the test group B was calculated, assuming that the average weight of the visceral fat of the mice on the final day of the test of the control group B was 100%.

Results The results obtained are shown in Table 3. From this result, both the juvenile obesity model mouse and the age-related obesity model mouse were found to have reduced body weight and visceral fat by bofutsushosan extract powder, but in the age-related obesity model mouse, 2% by weight was observed. Feeding a feed containing Bofutsushosan extract powder resulted in a higher decrease in body weight and visceral fat than in juvenile obesity model mice fed a feed containing 4% by weight of Bofutsushosan extract powder.

The average value of lipolytic activity in the fat around the accessory testicle was 5.6 mEq / g in the juvenile obesity model mouse, whereas it was 0.28 mEq / g in the age-related obesity model mouse. With age, the lipolytic ability decreased to 1/20. It is an extremely unexpected result that bofutsushosan extract powder effectively reduced body weight and visceral fat even in the age-related obese mouse model in which the lipolytic ability was reduced. ..

Test Example 2: Evaluation of body weight reduction effect by age group The body weight reduction effect of Bofutsushosan extract was evaluated for people with a constitution in which the resolution and metabolic capacity of lipids were essentially reduced. Specifically, the average weight of 9 men and women (20s, 30s, 40s to 50s) 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. (Selected so that the difference was within 5 kg), 5000 mg of Bofutsushosan extract powder of Production Example 1 was administered 3 times a day for 2 weeks, and the change in body weight was measured before the start of administration.

The results are shown in Table 4. By taking Bofutsushosan extract to people with a constitution in which the resolution and metabolic capacity of lipids were essentially reduced, an average weight loss of about 1 kg was observed. When the effect of Bofutsushosan extract was analyzed by generation, the effect increased with aging, and the improvement effect on age-related obesity in people in their 40s and 50s was particularly excellent. In age-related obesity in people in their 40s and 50s, the resolution and metabolic capacity of lipids are essentially reduced, so it was conventionally thought that Bofutsushosan extract would not be effective. Bofutsushosan extract has a lipid excretion promoting action in the stool as shown in Reference Test Example 1 described later, and this action is one of the causes of excellent weight loss against age-related obesity. It is probable that the effect was achieved.

Reference test example 1: Evaluation of the effect of promoting excretion of lipids into feces and the effect of reducing body weight Freely ingest a high-fat diet (HFD32, Nippon Claire Co., Ltd.) in mice (C57BL / 6J mice, 5 weeks old, male) for 4 weeks. The mice were fed and bred to produce obesity model mice. After measuring the body weight of this obesity model mouse, the mice were divided into a total of three groups (control group 1), test group 1 and test group 2 so that the average body weight of each group was about 26 g (6 to 6 in each group). 11 animals). In the test group 1, obese model mice were fed with a feed containing the high-fat diet and the bofutsushosan extract of Production Example 1 in an amount of 4% by weight for 20 days. In the test group 2, obese model mice were fed with a feed containing the high-fat diet and the bofutsushosan extract of Production Example 2 in an amount of 4% by weight for 20 days. In the control group, a high-fat diet containing no bofutsushosan extract was fed for 20 days. Feces were collected every two days during the test period. The collected feces were freeze-dried.

Lipids were extracted from lyophilized stool with a low polar solvent, and the total amount of lipids in the stool was measured by the gravimetric method. Specifically, after crushing the lyophilized feces, 100 mg is weighed and extracted twice with 500 μL of a chloroform / ethanol solution (chloroform: ethanol (volume ratio) = 2: 1), and this extract is extracted at 30 ° C. After vacuum drying, the weight of the extract (lipid) was measured. The total lipid excretion of each group was calculated according to the following formula, and the total lipid excretion of each group was calculated by dividing the total lipid excretion of each group by the number of mice in each group.

Furthermore, the extract (lipid) extracted from the feces excreted between the 12th and 14th days from the start of the test was redissolved in isopropanol and used as a kit using cholesterol E test Wako (Wako Pure Chemical Industries, Ltd.). By operating according to the attached instruction manual, the weight of cholesterol is measured, the amount of cholesterol excreted in each group is calculated according to the following formula, and the amount of cholesterol excreted in each group is divided by the number of mice in each group. , Cholesterol excretion per mouse was determined.

The relative value of the total lipid excretion per mouse in the test groups 1 and 2 was calculated with the total lipid excretion amount per mouse in the control group as 100%. Similarly, the relative value of the cholesterol excretion amount per mouse in the test groups 1 and 2 was calculated with the cholesterol excretion amount per mouse in the control group as 100%.

In addition, the body weights of the obese model mice in each group at the start of breeding (day 0) and the final day of breeding (day 20) were measured. The body weight at the start of breeding of each group was set as 100%, and the ratio of the body weight on the last day of breeding was calculated as the body weight change rate (%).

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

No diarrhea was observed in all mice during the breeding period. The daily fecal volume of each mouse was 211.5 to 315.1 mg / day / animal by dry weight, and no significant difference was observed between the groups.

As can be seen from Table 5, in the test groups 1 and 2 ingested with Bofutsushosan extract powder, an increase in total lipid excretion was observed after the 6th day of breeding as compared with the control group. Since there was no significant difference in the amount of dry feces between the groups, it was clarified that the lipid concentration in the feces was increased by ingesting Bofutsushosan extract powder. In particular, after the 12th day of breeding, the amount of lipid excreted in the test group 1 was higher than that in the test group 2, and the bofutsushosan extract powder (manufactured) obtained from the crude drug formulation having a small amount of ginger. It was clarified that the use of Example 1) enhances the effect of promoting the excretion of lipids. Bofutsushosan extract powder (total amount of crude drug-derived ingredients) produced under the same conditions as in Production Example 1 except that the amount of ginger in the crude drug formulation was 0.4 parts by weight. ) 6-gingerol amount per 100 parts by weight: 0.012 parts by weight) was also subjected to the same test. Was found to increase.

In addition, as is clear from Table 6, the excretion amount of cholesterol was increased in the test groups 1 and 2 ingested with the bofutsushosan extract powder as compared with the control group, as in the result of the excretion amount of total lipid. Was there. In addition, the amount of cholesterol excreted in the test group 1 ingested with the bofutsushosan extract powder of Production Example 1 was higher than that in the test group 2 ingested with the bofutsushosan extract of Production Example 2.

In addition, as shown in Table 7, in the control group, the body weight increased at the end of the breeding as compared with the start of the breeding, whereas in the test groups 1 and 2 ingested the bofutsushosan extract, the body weight was increased. The increase was suppressed. In particular, in the test group 1 ingested with the bofutsushosan extract of Production Example 1, a higher weight reduction effect was observed than in the test group 2 ingested with the bofutsushosan extract of Production Example 2. It is considered that the suppression of body weight gain by such bofutsushosan extract is partly due to the action of promoting the excretion of lipids into feces.

Test Example 3: Evaluation of lipolytic ability improving effect Two types of male C57BL / 6J mice with different ages (young: 9 weeks, aging: 43-63)
Week age) was divided into a control group and a test group (Bofutsushosan extract administration group) (5-8 animals in each group, 4 groups in total). The control group was fed with a high-fat diet (HFD32, Japan Claire) for 4 weeks, and the test group was fed with a feed containing Bofutsushosan extract powder of Production Example 2 so as to be 2% by weight in the high-fat diet. Feeded for 4 weeks.

After feeding, the epididymal fat was removed from each group of mice, and the ability to respond to noradrenaline stimulation (lipolytic ability) was evaluated. Specifically, first, the adipose tissue removed from the periphery of the epididymis was washed with Krebs Ringer's buffer (pH 7.4). Weigh the adipose tissue after washing, and add 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg / mL noradrenaline and 2 wt% bovine serum albumin (BSA) to 0.2 g of the adipose tissue after washing. In addition, it was incubated at 37 ° C. for 2 hours. After that, the supernatant was collected, and the amount of free fatty acid released into the supernatant by stimulation with noradrenaline was measured by NEFA-C Testwaco (Wako Pure Chemical Industries, Ltd.), and the amount of free fatty acid released per 1 g of adipose tissue. Was calculated as the lipolytic power. Table 8 shows the fat decomposition rate in each group when the fat decomposition power in the control group of young mice was set to 100%, and the change rate of the fat decomposition rate by the administration of Bofutsushosan.

Results As shown in Table 8, when the control groups of young and aged mice were compared, the lipolytic ability of the aged mice was significantly reduced to 53.1% of that of the young mice. On the other hand, the lipolytic ability of the test group was higher than that of the respective control groups in both young and aged mice. The rate of change was 1.196 times in young mice and 1.386 times in aged mice, and the degree of improvement in lipolytic ability was higher in aged mice. From this, it was clarified that Bofutsushosan has an effect of enhancing the lipolytic power against Nordrenaline stimulation, and further shows a superior effect on aged mice rather than young mice.

Reference test example 2: Production 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. As the bofutsushosan extract powder, the extract powder produced according to Production Example 1 or 2 was used. All of the obtained tablets were expected to have an effect of promoting lipid excretion in feces. Further, when the hardness and disintegration time of the obtained tablets were measured, the bofutsushosan extract powder of Production Example 2 was compared with the case where the bofutsushosan extract powder of Production Example 1 was used. When the extract powder was used, the hardness was higher and it had the property of being easily disintegrated.

Normally, when tablets contain Chinese herbal extract powder, the amount of active ingredient (Chinese herbal extract powder) taken daily is larger than that of general drugs, so the tablets become larger and the number of tablets taken at one time is larger. It has the disadvantage that it is difficult for consumers to take because it increases in number. In order to overcome such a drawback, it is effective to increase the content of the Chinese herbal extract powder in the tablet, but if the content of the Chinese herbal extract powder in the tablet is increased, the content of the excipient is relatively high. There is a problem that the amount is reduced, and as a result, the hardness of the tablet is reduced. In such a situation, the bofutsushosan extract powder of Production Example 2 can be used as a tablet having a high hardness, so that the content of the extract powder can be increased (relatively containing excipients). It was found that the amount can be reduced), the tablets can be made smaller, and the number of tablets taken at one time can be reduced.

Reference test example 3: Production of tablets containing bofutsushosan extract powder 2
According to the formulation shown in Table 15, the bofutsushosan extract powder obtained in Production Example 1 or Production Example 2 and other components are mixed, granulated, and then tableted with a pressing force of 5 kN or 7 kN to obtain tablets ( Weight 200 mg, diameter 8 mm) was prepared.

The manufactured tablets were evaluated for disintegration according to the disintegration test method described in the Japanese Pharmacopoeia (17th revision). The disintegration time was the average value of 6 tablets. The hardness was measured at a breaking operation speed of 0.5 mm / min using a load cell type tablet hardness meter. The results are shown in Tables 16 and 17.
Although the test tablet 2 was molded with the same pressing force (7 kN) as the test tablet 1, a tablet having a thinner thickness was obtained. Further, the test tablet 2 has a higher hardness than the test tablet 1 and is superior in physical stability. Further, although the test tablet 2 has a higher hardness than the test tablet 1, the disintegration time is greatly shortened. Further, the test tablet 3 is the same as the test tablet 1 formed with a higher pressing pressure (7 kN) even though the test tablet 2 is formed with a lower pressing pressure (5 kN) than the molded pressure (7 kN). A degree of hardness and better disintegration have been achieved. Therefore, when the test lock 3 is manufactured, the load on the locking device is small, and the life of the locking device can be extended.

Claims (4)

A lipolytic power improving agent containing Bofutsushosan extract. The adipose-decomposing ability improving agent according to claim 1, which is applied to a person having a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more. The lipolytic power improving agent according to claim 1 or 2, which is applied to a person having adipose tissue having a lipolytic power measured in the following lipolytic power evaluation test of 5 mEq / g or less.
<Lipolysis ability evaluation test>
Adipose tissue collected subcutaneously is washed with Krebs Ringer's buffer (pH 7.4). Weigh the adipose tissue after washing, and add 1 μg / mL of noradrenaline and 2 wt% bovine serum albumin (BSA) to 5 mL of Krebs Ringer buffer (pH 7.4) in 0.2 g of the washed adipose tissue. In addition, incubate at 37 ° C. for 2 hours. Then, the supernatant is collected, the amount of free fatty acid released into the supernatant by stimulation with noradrenaline is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq / g) is determined as the lipolytic power. The lipolytic power improving agent according to any one of claims 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 crude drug-derived component.