JP2024092065A - Lipid excretion promoter - Google Patents

Abstract

[Problem] The object of the present invention is to provide a fecal lipid excretion promoter that promotes the excretion of ingested lipids into the feces. [Solution] Bofu-tsushosan extract has the effect of promoting the excretion of ingested lipids into the feces, making it possible to improve or avoid health problems caused by excessive lipid intake, even for people with a constitution that is essentially impaired in lipid decomposition and metabolic ability. [Selected Figure] None

Description

The present invention relates to a fecal lipid excretion promoter that promotes the excretion of ingested lipids into feces.

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 or older 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 problems 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 benefit 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 object of the present invention is to provide a fecal lipid excretion promoter that promotes the excretion of ingested lipids into the feces.

The inventors conducted extensive research to solve the above problems and discovered that Bofutsushosan extract has the effect of promoting the excretion of ingested lipids in the feces, making it possible to improve or avoid health problems caused by excessive lipid intake, even in people with constitutions that are essentially impaired in lipid decomposition and metabolism. The present invention was completed based on this knowledge and through further research.

That is, the present invention provides the following aspects.
Item 1. A fecal lipid excretion promoter containing bofutsushosan extract.
Item 2. The agent for promoting lipid excretion in feces according to Item 1, which is used for promoting the excretion of cholesterol in feces.
Item 3. The fecal lipid excretion promoter according to Item 1 or 2, wherein the herbal preparation used for extracting the Bofu-tsusho-san extract contains 1 to 5 parts by weight of Zingiber officinale per 100 parts by weight of the herbal preparation.
Item 4. The fecal lipid excretion promoter according to any one of Items 1 to 3, which is taken continuously for 6 days or more.
Item 5. The fecal lipid excretion promoter according to any one of Items 1 to 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 present invention can promote the excretion of ingested lipids in feces, making it possible to improve or avoid health problems caused by excessive lipid intake, even for people with a constitution that is inherently impaired in lipid decomposition and metabolic ability.

The fecal lipid excretion promoter of the present invention is characterized by containing Bofu-tsushosan extract. The fecal lipid excretion promoter 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, Scutellaria, Ephedra, Rhubarb, Byakujutsu, Platycodon, Scutellaria Root, Licorice, Scutellaria Root, and Catseki. Some letters do not contain Byakujutsu (for example, "Experience Kampo Prescription Quantities Collection," supervised by Otsuka Keisetsu and Yakazu Domyo, published by Ido no Nihonsha), and some do not contain Scutellaria Root (for example, "Continuation of Kampo Arekore," compiled by Osaka Yomiuri Shimbun, published by Naniwasha). The Bofutsushosan extract used in the present invention may be obtained from any of these Bofutsushosan.

According to the "Guide to General Kampo Prescriptions" (supervised by the Ministry of Health, Labor and Welfare's Pharmaceutical Affairs Bureau, edited by the Kampo Specialist Committee of the Japan Pharmaceutical Manufacturers Association, and published by Yakugyo Jihosha) and the "17th Revised Japanese Pharmacopoeia," the amounts of each herb that makes up Bofutsushosan are as follows: 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, 1.2 parts by weight of Mentha Root, 0.3 to 0.4 parts by weight of Ginger Root. 1.2 parts by weight, 1.2 parts by weight of Chinese holly, 1.2 parts by weight of Bougainvillea or 1.2 parts by weight of Glehnia gracilis, 1.2 parts by weight of Ephedra, 1.5 parts by weight of Rhubarb, 0.6 to 1.5 parts by weight of Bougainvillea (calculated as anhydrous sodium sulfate), 2 parts by weight of Atractylodes Root, 2 parts by weight of Platycodon Root, 2 parts by weight of Scutellaria Root, 2 parts by weight of Licorice Root, 2 to 3 parts by weight of Gypsum, and 3 to 5 parts by weight of Kasseki. Some letters also state that all of the 1.2 parts by weight in the above amounts are 1.5 parts by weight (for example, "Meikai Kampo Prescriptions," co-authored by Nishioka Kazuo and Takahashi Shintaro, published by Naniwasha).

There are no particular limitations on the amount of each herb in the herb preparation used to manufacture the Bofu-tsushosan extract, and the amount of each herb shown in the letter exemplified above may be used, but suitable examples include 1.2 parts by weight of Angelica acutiloba, 1.2 parts by weight of Peony Root, 1.2 parts by weight of Cnidium Root, 1.2 parts by weight of Sanshi Fruit, 1.2 parts by weight of Forsythia Fruit, 1.2 parts by weight of Mentha Root, 1.2 parts by weight of Japanese Scutellaria Root, 1.2 parts by weight of Japanese Scutellaria Root, 1.2 parts by weight of Bofu-tsushosan Root, 1.2 parts by weight of Ephedra Root, 1.5 parts by weight of Rhubarb (sodium sulfate), and The composition may be one in which the amount of Zingiber officinale in the herbal preparation used for the preparation of the Bofu-tsushosan extract is 0.6-1.5 parts by weight (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, 2-3 parts by weight (preferably 2 parts by weight) of Glycyrrhiza Root, and 3-5 parts by weight (preferably 3 parts by weight) of Ginger Root, and 0.3-1.5 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, this may be referred to as "Mode A"). By adjusting the amount of Ginger Root in the herbal preparation used for the preparation of the Bofu-tsushosan extract within the above range, it is possible to more effectively promote the excretion of lipids in the feces. In addition, in the above-mentioned Mode A, the amount of Boshou in the herbal preparation may be 0.6-1 part by weight, more preferably 0.6-0.75 parts by weight, and particularly preferably 0.7 parts by weight, in terms of anhydrous sodium sulfate. By satisfying this range of the amount of bofutsushosan, it becomes possible to more effectively promote the excretion of lipids into the feces. In the present invention, the "herb preparation used for 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 herbs that constitute Bofutsushosan. In addition, the term "sodium sulfate anhydrous equivalent of bofutsushosan" refers to the conversion of the hydrate to an anhydrous weight when sodium sulfate hydrate is used as bofutsushosan. In addition, sodium sulfate hydrate (e.g., decahydrate) and/or sodium sulfate anhydrous are used as bofutsushosan.

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 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 bofu-tsushosan extract from a herbal preparation with such a low ratio of ginger, it is possible to 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.

A suitable example of the bofutsushosan extract used in the present invention is one in which 6-gingerol is 0.005 to 0.04 parts by weight per 100 parts by weight of the total amount of ingredients derived from herbal medicines. 6-Gingerol is a component contained in ginger, and conventional bofutsushosan extracts usually contain 0.05 parts by weight or more of 6-gingerol per 100 parts by weight of the total amount of ingredients derived from herbal medicines. In the present invention, by using a bofutsushosan extract with a reduced content of 6-gingerol, it is possible to more effectively promote the excretion of lipids into the stool. From the viewpoint of more effectively promoting the excretion of lipids into the stool, 6-gingerol is 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 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 in ginger. The amount of 6-gingerol extracted can be reduced by subjecting ginger to extraction in a processed product sliced into slices about 1 to 3 mm thick rather than cutting into thin pieces about 1 to 8 mm square. This makes it possible to preferably obtain a bofu-tsushosan extract containing 6-gingerol in the above ratio. For example, by setting the ratio of ginger per 100 parts by weight of the total amount of the herbal preparation within the range shown in the above-mentioned embodiment A and adjusting the shape of the ginger, it is possible to suitably obtain a bofu-tsushosan extract containing 6-gingerol within the above-mentioned content range.

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

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

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

The bofutsushosan extract used in the present invention may be either an extract powder or a soft extract, and either the extract powder or the soft extract may be appropriately selected depending on the form of the fecal lipid excretion promoter of the present invention.

Other components The fecal lipid excretion promoter of the present invention may be composed of Bofutsushosan extract alone, or may contain additives and bases according to the formulation. Such additives and bases are not particularly limited as long as they are pharmacologic acceptable, and 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 formulation form of the fecal lipid excretion promoter, etc.

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

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

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

Uses The fecal lipid excretion promoter of the present invention is used to promote the excretion of ingested lipids into feces. In this way, it is possible to promote the excretion of lipids into feces, and thus improve or avoid health disorders (weight gain, visceral fat gain, etc.) caused by excessive lipid intake. In addition, since the fecal lipid excretion promoter of the present invention has an excellent effect of promoting the excretion of cholesterol into feces, it is preferably used to promote 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 metabolic ability, conventional obesity improving agents cannot be expected to improve lipid decomposition and metabolic ability, and so people have not been in the habit of taking conventional obesity improving agents.However, the fecal lipid excretion promoter of the present invention can promote lipid excretion into feces, thereby making it possible to suppress the adverse effects of lipid intake even for people with a constitution that is essentially reduced in lipid decomposition and metabolic ability.In view of the effects of the present invention, the fecal lipid excretion promoter of the present invention can be suitably applied to people with a constitution that is essentially reduced in lipid decomposition and metabolic ability. 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 fecal lipid excretion promoter of the present invention is used by oral administration. The dosage of the fecal lipid excretion promoter of the present invention is appropriately set according to the age, sex, constitution, etc. of the subject of administration, but for example, the total amount of the herbal medicine-derived components of the Bofu-tsushosan extract per person per day is about 1 to 10 g, preferably about 1.5 to 8 g, more preferably about 1.5 to 6 g, and may be taken 1 to 3 times, preferably 2 or 3 times, per day. The timing of administration is not particularly limited, and may be either before meals, after meals, or between meals, but it is preferable to take it before meals (30 minutes before meals) or between meals (2 hours after meals).

In addition, since the effect of promoting the excretion of lipids into the stool by the fecal lipid excretion promoter of the present invention is achieved by continuous administration, it is preferable to continuously administer the fecal lipid excretion promoter of the present invention (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, centrifuged, and the extract was separated. 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 condition)
Detector : ultraviolet spectrophotometer (measurement wavelength: 205 nm)
Column : A stainless steel tube having an inner diameter of 4.6 mm and a length of 15 cm packed with 5 μm octadecylsilylated silica gel for liquid chromatography (COSMOSIL 5C18 MS-II (5 μm, 4.6×150 mm) (Nacalai Tesque, Inc.)).
Column temperature : constant temperature around 40°C
Mobile phase : Water/acetonitrile/phosphoric acid mixture (volume ratio of water:acetonitrile:phosphoric acid 3800:2200:1)
Flow rate : adjusted so that the retention time of 6-gingerol was approximately 19 minutes.

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

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

Test Example 1: Evaluation of the Effect of 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.

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

As can be seen from Table 3, in test groups 1 and 2 that received bofutsushosan extract powder, an increase in total lipid excretion was observed compared to the control group from the 6th day of rearing. Since there was no significant difference in the amount of dried feces between the groups, it was clear that the lipid concentration in the feces increased by feeding bofutsushosan extract powder. In particular, from the 12th day of rearing onwards, the lipid excretion amount in test group 1 was greater than that in test group 2, making it clear that the use of bofutsushosan extract powder (production example 1) obtained from a herbal preparation containing a small amount of ginger enhances the lipid excretion promoting effect. In addition, a similar test was also carried out on Bofutsushosan extract powder (6-gingerol content: 0.012 parts by weight per 100 parts by weight of Bofutsushosan extract powder (total amount of 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 that ingested bofutsushosan extract powder compared to the control group. Also, cholesterol excretion was increased in test group 1 that ingested bofutsushosan extract powder of Production Example 1 compared to test group 2 that ingested bofutsushosan extract of Production Example 2.

Furthermore, as shown in Table 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 were fed bofutsushosan extract. In particular, test group 1 which was fed bofutsushosan extract of Production Example 1 showed a greater weight reduction effect than test group 2 which was fed bofutsushosan extract of Production Example 2. Such suppression of weight gain by bofutsushosan extract is thought to be partly due to its effect of promoting the excretion of lipids into the feces.

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

In addition, aged mice (C57BL/6J mice, 40-60 weeks old, male) were fed a high-fat diet (HFD32, CLEA Japan, Inc.) ad libitum for one week to create age-related obesity model mice.

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, first, the adipose tissue extracted from around the epididymis was 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 aged 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 Bofutsushosan extract powder effectively reduced body weight and visceral fat even in the aged obese mouse model, where lipolytic capacity has decreased.

Reference Test Example 2: Evaluation of weight reduction effect by age group The weight reduction effect of 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 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 people with a constitution that is inherently impaired in lipid decomposition and metabolic ability were administered Bofutsushosan extract, an average weight loss of approximately 1 kg was observed overall, and when analyzed by generation, it was confirmed that the effect increases 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, Bofutsushosan extract has the 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 (400 mg per tablet) containing bofutsushosan extract powder 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 (5)

A stool lipid excretion promoter that contains a water extract of Bofutsushosan and is used by people in their 40s and 50s to promote the excretion of cholesterol in the stool. The agent for promoting lipid excretion in feces according to claim 1, which is used to promote the excretion of ingested lipids into feces. The fecal lipid excretion promoter according to claim 1 or 2, wherein the herbal preparation used in extracting the water extract of Bofutsushosan contains 1 to 5 parts by weight of Zingiber officinale per 100 parts by weight of the herbal preparation. The agent for promoting lipid excretion in feces according to any one of claims 1 to 3, which is taken continuously for 6 days or more. The fecal lipid excretion promoter according to any one of claims 1 to 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.