JP7602854B2 - Bofutsushosan Extract - Google Patents

Description

The present invention relates to a bofutsushosan extract that has an excellent effect of promoting the excretion of lipids into the stool.

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 is a cause of obesity. The adverse effects of excessive lipid intake can be improved to some extent by increasing the body's lipid decomposition and metabolic ability, but there is a limit to how much lipid decomposition and metabolic ability can be improved by taking medication. In particular, people who have had a body fat percentage of 25% or more and a waist size of 85 cm or more for more than five years, and middle-aged and elderly people who have been obese for many years, have a constitution in which lipid decomposition and metabolic ability are essentially reduced, and it is considered difficult to improve lipid decomposition and metabolic ability in such people. Therefore, excreting lipids with stool to increase the amount of lipid excretion is useful for improving or avoiding health disorders caused by excessive lipid intake, and is considered to be effective in avoiding the adverse effects of lipid intake, especially for people with a constitution in which lipid decomposition and metabolic ability are essentially reduced.

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

However, there have been no reports that have actually verified that Bofutsushosan has the effect of promoting the excretion of ingested lipids in the feces. Also, it is thought that people with constitutions that have an inherently reduced lipid breakdown and metabolic ability cannot expect to see any benefits from improved lipid breakdown and metabolic ability, and so at present, they do not usually take Bofutsushosan.

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

JP 2009-242354 A JP 2009-242330 A

The inventors conducted an intensive search for components that promote the excretion of ingested lipids into the feces and discovered that Bofutsushosan extract has an excellent effect of promoting the excretion of ingested lipids into the feces.

On the other hand, in recent years, with the rise in health consciousness, there is a demand in the pharmaceutical field for improved functionality. Therefore, the object of the present invention is to provide a bofu-tsushosan extract with an enhanced effect of promoting the excretion of lipids into the stool.

The inventors conducted extensive research to solve the above problems and found that when bofutsushosan extract contains 0.005 to 0.04 parts by weight of 6-gingerol per 100 parts by weight of the total amount of herbal medicine-derived ingredients, the effect of promoting the excretion of lipids into stool is improved. Furthermore, the inventors found that when the content of 6-gingerol is within the above range and the herbal medicine preparation used to extract the bofutsushosan extract contains 2 to 6 parts by weight of Glauber's salt, calculated as sodium sulfate, per 100 parts by weight of the herbal medicine preparation, the excretion promoting effect of the bofutsushosan extract is further improved. The present invention was completed based on these findings and through further research.

That is, the present invention provides the following aspects.
Item 1. A bofu-tsushosan extract 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.
Item 2. The Bofu-tsushosan extract according to Item 1, wherein the herbal preparation used for extracting the Bofu-tsushosan extract contains 2 to 6 parts by weight of Bofu-tsushosan in terms of anhydrous sodium sulfate per 100 parts by weight of the herbal preparation.
Item 3. A fecal lipid excretion promoter comprising the bofutsushosan extract according to item 1 or 2.
Item 4. The fecal lipid excretion promoter according to Item 3, which is administered continuously for 6 days or more.
Item 5. The fecal lipid excretion promoter according to Item 3 or 4, 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.

The Bofutsushosan extract of the present invention has a strong effect of promoting the excretion of ingested lipids in the feces, and can effectively improve or avoid health problems caused by excessive lipid intake, even in people with constitutions that are essentially impaired in lipid decomposition and metabolic ability.

The bofu-tsushosan extract of the present invention is characterized by 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. The bofu-tsushosan extract of the present invention is described in detail below.

According to the "Guide to General Kampo Prescriptions " (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Kampo Specialist Committee of the Japan Pharmaceutical Manufacturers Association, and published by Yakugyo Jihosha), the herbal medicines that make up Bofutsushosan are Angelica, Peony Root, Cnidium Root, Sanshishi, Forsythia, Mint, Ginger, Cabbage, Saxifraga, Ephedra, Rhubarb, Bougainvillea, Byakujutsu, Platycodon, Scutellaria Root, Licorice, Scutellaria Root, and Catharanthus Radix. Some letters do not include Byakujutsu 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, "Continued Kampo Arekore," edited by Osaka Yomiuri Shimbun, published by Naniwasha). The bofu-tsushosan extract used in the present invention may be obtained from any of these bofu-tsushosan extracts, so long as the 6-gingerol content falls within the specified range.

The bofu-tsushosan extract of the present invention 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. 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 bofu-tsushosan extract of the present invention, the content of 6-gingerol is reduced to the above-mentioned range, making it possible to more effectively promote the excretion of lipids into the feces. From the viewpoint of more effectively promoting the excretion of lipids into the feces, the extract contains 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. Here, the ingredients derived from herbal medicines are ingredients extracted from the herbal medicines that make up 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 ingredients derived from herbal medicines, and in the case of Bofutsushosan extract powder that contains additives such as excipients, the weight of the extract powder minus the weight of the additives contained is the total amount of ingredients derived from herbal medicines.

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

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), "17th Revised Japanese Pharmacopoeia", etc., the amounts of each crude drug that makes up Bofu-tsushosan are 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, 0.3 to 1.2 parts by weight of Zingiber Root, 1.2 parts by weight of Japanese Crown Root, 1.2 parts by weight of Bohu Root or 1.2 parts by weight of Glycyrrhiza Root, 1.2 parts by weight of Ephedra Root, 1.5 parts by weight of Rhubarb, 0.6 to 1.5 parts by weight of Atractylodes Rhizome (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 Root, and 3 to 5 parts by weight of Polygala Root. Also, in some letters, all of the 1.2 parts by weight listed above are changed to 1.5 parts by weight (for example, "Meikai Kampo Prescriptions," co-authored by Nishioka Kazuo and Takahashi Shintaro, published by Naniwasha).

The amount of each herb in the herbal preparation used to manufacture Bofu-tsushosan extract is not particularly limited, so long as the content of 6-gingerol is within the above range, and each herb may be used in the amount shown in the letter exemplified above. 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 Japanese Pear, 1.2 parts by weight of Bohu, 1.2 parts by weight of Ephedra Root, 1.2 parts by weight of Rhubarb, 1. 5 parts by weight, Boshou (calculated as anhydrous sodium sulfate) 0.6-1.5 parts by weight, Atractylodes Root 2 parts by weight, Platycodon Root 2 parts by weight, Scutellaria Root 2 parts by weight, Licorice Root 2 parts by weight, Gypsum Root 2-3 parts by weight (preferably 2 parts by weight), and Ginseng Root 3-5 parts by weight (preferably 3 parts by weight) and Zingiber officinale 0.3-1.5 parts by weight, preferably 0.3-1.2 parts by weight, more preferably 0.3-0.4 parts by weight, and particularly preferably 0.3 parts by weight (hereinafter sometimes referred to as "Mode A"). By adjusting the amount of Zingiber officinale in the herbal preparation used for producing the Bofu-tsushosan extract within the above range, the content of 6-gingerol can be suitably satisfied within the above range, and the excretion of lipids in the feces can be more effectively promoted. In the present invention, the "herbal medicine preparation used in the production of Bofutsushosan extract" refers to the raw material preparation used for extraction in the production of Bofutsushosan extract, i.e., a preparation containing a predetermined amount of the herbal medicines that make up Bofutsushosan.

In addition, as a suitable example of the above-mentioned aspect A, the amount of the lipid is preferably 0.6 to 1 part by weight, more preferably 0.6 to 0.75 parts by weight, and particularly preferably 0.7 parts by weight, calculated as sodium sulfate anhydride. By ensuring that the amount of the lipid falls within such a range, it becomes possible to more effectively promote the excretion of lipids in the feces. In this invention, the amount of the lipid in anhydrous sodium sulfate refers to converting the hydrate to an anhydrous weight when sodium sulfate hydrate is used as the lipid. As the lipid, sodium sulfate hydrate (e.g., decahydrate) and/or sodium sulfate anhydride are used.

A suitable example of a herbal preparation to be used in the production of the bofutsushosan extract of the present invention is one containing 1 to 5 parts by weight, preferably 1 to 4 parts by weight, more preferably 1 to 3 parts by weight, and particularly preferably 1 to 2 parts by weight of ginger per 100 parts by weight of the total amount of the herbal preparation. By obtaining bofutsushosan extract from a herbal preparation with such a low ratio of ginger, it is possible to suitably satisfy the 6-gingerol content within the above range and more effectively promote the excretion of lipids in the stool.

A suitable example of a herbal preparation used in the manufacture of the Bofu-tsushosan extract used in the present invention is one that contains 2 to 6 parts by weight, preferably 2 to 4 parts by weight, more preferably 2 to 3 parts by weight, and particularly preferably 2 to 2.5 parts by weight of Boshou, calculated as anhydrous sodium sulfate, per 100 parts by weight of the total amount of the herbal preparation. By containing Boshou in such a ratio in the herbal preparation, it becomes possible to more effectively promote the excretion of lipids in the stool.

The bofutsushosan extract of the present invention can be obtained by extracting the herbal preparation by a known method. The method for extracting the herbal preparation may be the same as the conventional method for extracting bofutsushosan extract, for example, by 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. After extraction, the solid matter is removed by solid-liquid separation such as centrifugation or filtration, and if necessary, by subjecting it to concentration or drying treatment, the bofutsushosan extract of the present invention can be obtained.

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

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

The bofutsushosan extract of the present invention may be either an extract powder or a soft extract.

Preparation The Bofutsushosan extract of the present invention may be prepared by preparing the Bofutsushosan extract alone, or may be prepared with additives and bases to prepare a desired preparation form. Such additives and bases are not particularly limited as long as they are pharmacologic acceptable, and examples thereof include excipients, binders, disintegrants, lubricants, isotonicity agents, plasticizers, dispersants, emulsifiers, solubilizers, wetting agents, stabilizers, suspending agents, adhesives, coating agents, glossing agents, water, oils and fats, waxes, hydrocarbons, fatty acids, higher alcohols, esters, water-soluble polymers, surfactants, 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 content of these additives and bases is appropriately set according to the type of additives and bases used, the preparation form, etc.

The Bofutsushosan extract of the present invention may be formulated in combination with other nutritional components or pharmacological components as necessary. 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 depending on the type of components used, the formulation form, etc.

The formulation form of the Bofutsushosan extract of the present invention is not particularly limited, so long as it can be administered orally. Examples of the formulation form include solid formulations such as powders, fine granules, granules (including dry syrup), tablets, pills, and capsules (soft capsules and hard capsules); semi-solid formulations such as jellies; and liquid formulations such as solutions, suspensions, and syrups. Among these formulation forms, solid formulations are preferred from the viewpoints of the stability and portability of the contained ingredients.

To prepare the bofutsushosan extract of the present invention in the above-mentioned formulation form, the bofutsushosan extract, and additives, bases, and pharmacological ingredients added as necessary may be formulated according to the usual formulation methods used in the pharmaceutical field.

Uses The Bofutsushosan extract of the present invention is used for weight loss, visceral fat reduction, etc., just like the conventional Bofutsushosan extract, but it has excellent effect of promoting the excretion of ingested lipids into feces, so it can be suitably used as a lipid excretion promoter in feces.In addition, the Bofutsushosan extract of the present invention has excellent effect of promoting the excretion of cholesterol into feces, so it can be suitably used for promoting the excretion of ingested cholesterol or cholesterol in blood into feces.

In addition, for people with a constitution that is essentially reduced in lipid decomposition and metabolism, the conventional Bofutsushosan extract is not expected to improve lipid decomposition and metabolism, and is not expected to achieve weight loss or visceral fat reduction, and so there has been no custom of taking the conventional Bofutsushosan extract. However, the Bofutsushosan extract of the present invention can promote the excretion of lipids in feces, thereby making it possible to suppress the adverse effects (weight gain, visceral fat increase, etc.) caused by lipid intake, even for people with a constitution that is essentially reduced in lipid decomposition and metabolism. Considering the effects of the present invention, the Bofutsushosan extract of the present invention is preferably applicable to people with a constitution that is essentially reduced in lipid decomposition and metabolism. Specific examples of people with such a constitution include people 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; middle-aged or older people (45 years or older) who are obese (for example, a body fat percentage of 25% or more); and people with adipose tissue whose lipolytic power, as measured in the lipolytic power evaluation test described below, is 5 mEq/g or less, preferably 3 mEq/g or less, more preferably 1 mEq/g or less, even more preferably 0.5 mEq/g or less, and particularly preferably 0.3 mEq/g or less.
<Lipid decomposition ability evaluation test>
First, adipose tissue is collected from the subcutaneous tissue of a subject. The obtained adipose tissue is washed with Krebs Ringer buffer (pH 7.4). The weight of the washed adipose tissue is measured, and 0.2 g of the washed adipose tissue is added to 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2 wt% bovine serum albumin (BSA), and incubated at 37° C. for 2 hours. The supernatant is then collected, and the amount of free fatty acid released into the supernatant by noradrenaline stimulation is measured, and the amount of free fatty acid released per 1 g of adipose tissue (mEq/g) is calculated as the lipolysis power.

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

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

In addition, the effect of the bofutsushosan extract of the present invention in promoting the excretion of lipids into the stool is achieved by continuous administration, so it is preferable to take the bofutsushosan extract of the present invention continuously (specifically, for 6 days or more, preferably for 12 days or more).

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

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

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

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

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

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

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

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

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

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

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

The results of total lipid excretion are shown in Table 3, the results of cholesterol excretion are shown in Table 4, and the rate of change in body weight is shown in Table 5.

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

As can be seen from Table 3, in test groups 1 and 2 that were administered bofutsushosan extract powder containing 0.005-0.04 parts by weight of 6-gingerol per 100 parts by weight of total herbal medicine-derived ingredients, an increase in total lipid excretion was observed compared to the control group from the 6th day of rearing. Since there was no significant difference in the amount of dry feces between the groups, it was clear 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 clear that the use of bofutsushosan extract powder (production example 1), which contains 0.010 parts by weight of 6-gingerol per 100 parts by weight of total herbal medicine-derived ingredients, enhances the lipid excretion-promoting effect. In addition, a similar test was also carried out on Bofutsushosan extract powder (6-gingerol content: 0.012 parts by weight per 100 parts by weight of Bofutsushosan extract powder (total amount of ingredients derived from herbs)) produced under the same conditions as in Production Example 1, except that the amount of ginger in the herbal preparation was 0.4 parts by weight. It was found that the lipid excretion-promoting effect was greater than when the Bofutsushosan extract powder in Production Example 2 was used.

As is clear from Table 4, similar to the results for total lipid excretion, cholesterol excretion was increased in test groups 1 and 2, which were administered the bofutsushosan extract powders of Production Examples 1 and 2, compared to the control group. Also, cholesterol excretion was increased in test group 1, which was administered the bofutsushosan extract of Production Example 1, compared to test group 2, which was administered the bofutsushosan extract of Production Example 2.

Furthermore, as shown in Table 5, the control group had increased in body weight at the end of feeding compared to the start of feeding, whereas weight gain was suppressed in test groups 1 and 2 which had received the bofutsushosan extracts of Production Examples 1 and 2. In particular, test group 1 which had received the bofutsushosan extract of Production Example 1 had a greater effect on reducing body weight than test group 2 which had received the bofutsushosan extract of Production Example 2. This suppression of weight gain by the bofutsushosan extract is thought to be due in part to its effect of promoting the excretion of lipids into the feces.

Test Example 2: Evaluation of the effect of reducing visceral fat and body weight
Preparation of Juvenile Obese Model Mice Young mice (C57BL/6J mice, 5 weeks old, male) were fed a high fat diet (HFD32, CLEA Japan, Inc.) ad libitum for 4 weeks to prepare juvenile obese model mice.

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

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

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

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

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

The results are shown in Table 6. 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, and in particular, the aged obese mouse model fed with a feed containing 2% by weight of the bofutsushosan extract powder reduced body weight and visceral fat more than the juvenile obese mouse model fed with a feed containing 4% by weight of the bofutsushosan extract powder.

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

Test Example 3: Evaluation of weight reduction effect by age group The weight reduction effect of the Bofutsushosan extract was evaluated for people with a constitution that essentially reduces lipid decomposition and metabolic ability. Specifically, 9 men and women (selected so that the difference in average weight between each age group (20s, 30s, 40s to 50s) who have had a body fat rate of 25% or more and a waist size of 85 cm or more for 5 years or more) were given 5000 mg of the Bofutsushosan extract powder of Production Example 1 three times a day for 2 weeks, and the change in weight compared to before the start of administration was measured.

The results are shown in Table 7. When subjects with a constitution that is inherently impaired in lipid decomposition and metabolic ability were administered the bofutsushosan extract of Production Example 1, an average weight loss of approximately 1 kg was observed overall, and analysis by generation confirmed that the effect increased with age. In age-related obesity in people in their 40s and 50s, lipid decomposition and metabolic ability are essentially impaired, and it was previously thought that bofutsushosan extract would be ineffective, but as shown in Test Example 1 above, the bofutsushosan extract of Production Example 1 has an excellent effect of promoting lipid excretion in the stool, and it is believed that this effect is one of the factors that contributed to the weight loss effect in age-related obesity.

Tablets containing bofutsushosan extract powder (400 mg per tablet) were prepared according to the formulations shown in Formulation Examples Tables 8 to 13. The extract powder produced according to the above Preparation Examples 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.

Claims (3)

A fecal lipid excretion promoter containing a bofutsushosan extract, wherein the bofutsushosan extract contains extracted 6-gingerol in an amount of 0.007 to 0.015 parts by weight per 100 parts by weight of a total amount of components derived from herbal medicines, and a herbal medicine preparation used for extracting the bofutsushosan extract contains 2 to 3 parts by weight of ginger, calculated as anhydrous sodium sulfate, per 100 parts by weight of the herbal medicine preparation. The agent for promoting lipid excretion in feces according to claim 1, which is taken continuously for 6 days or more. 3. The fecal lipid excretion promoter according to claim 1 or 2, 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.