JP2023054194A - Bofu-tsusho-san extract - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bofu-tsusho-san extract with an improved action of promoting the excretion of lipid into stool.

SOLUTION: When a bofu-tsusho-san extract contains 6-gingerol of 0.005-0.04 pts.wt. relative to 100 pts.wt. of the total amount of herbal medicine-derived components, the bofu-tsusho-san extract has an improved action of promoting the excretion of lipid into stool.

SELECTED DRAWING: None

COPYRIGHT: (C)2023,JPO&INPIT

Description

TECHNICAL FIELD The present invention relates to a bofutsushosan extract that is excellent in promoting the excretion of lipids into feces.

In recent years, with the westernization of food culture, the amount of lipid intake in Japanese people has increased, and excessive lipid intake causes weight gain and causes obesity and the like. Adverse effects of excessive intake of lipids can be improved to some extent by enhancing lipid decomposing ability and metabolic ability in the body, but there is a limit to improving lipid decomposing ability and metabolic ability by taking medication. In particular, 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, middle-aged and elderly people who have been obese for many years, etc., have a constitution in which lipid decomposition and metabolic capacity are essentially reduced. Therefore, it is considered difficult to improve lipid decomposition and metabolic capacity for people with such a constitution. Therefore, increasing the excretion of lipids by excreting lipids together with feces is useful for improving or avoiding health problems caused by excessive intake of lipids. For humans, it is thought to be effective in avoiding the adverse effects of lipid intake.

On the other hand, Bofutsushosan is known as a herbal medicine that is effective in reducing visceral fat and improving metabolic syndrome. In addition, 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 formulations of bofutsushosan extract have been developed from the viewpoint of improving the effect of reducing visceral fat and improving the taste (for example, Patent Documents 1 and 2).

However, there is no report that actually verifies that Bofutsushosan has an effect of promoting the excretion of ingested lipids into feces. In addition, it is thought that people with a constitution in which lipid decomposing ability and metabolic ability are essentially reduced cannot expect the effect of improving lipid decomposing ability and metabolic ability, and usually do not take Bofutsushosan. is the current situation.

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

JP 2009-242354 A JP 2009-242330 A

The inventor of the present invention conducted an intensive search for a component that promotes the excretion of ingested lipids into the feces. I found out that there is

On the other hand, in recent years, in response to the growing health consciousness, it is desired to further enhance functionality in the field of medicine. Accordingly, an object of the present invention is to provide a bofutsushosan extract having an enhanced effect of promoting excretion of lipids into feces.

As a result of intensive studies to solve the above-mentioned problems, the present inventors found that 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. In addition, it was found that the effect of promoting lipid excretion into the feces was improved. Furthermore, the present inventors found that the content of 6-gingerol satisfies the above range, and the crude drug preparation used for extracting the Bofutsushosan extract contains Glauber's salt in terms of sodium sulfate per 100 parts by weight of the crude drug preparation. It was found that the excretion-enhancing action of the bofutsushosan extract is further improved when the bofutsushosan extract contains 2 to 6 parts by weight. The present invention has been completed through further studies based on these findings.

That is, the present invention provides inventions in the following aspects.
Section 1. Bofutsushosan 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 crude drugs.
Section 2. Item 2. Bofutsushosan according to Item 1, wherein the crude drug preparation used for extracting the Bofutsushosan extract contains 2 to 6 parts by weight of Bosho in terms of anhydrous sodium sulfate per 100 parts by weight of the crude drug preparation. scattered extract.
Item 3. Item 3. An agent for promoting fecal lipid excretion, comprising the bofutsushosan extract according to item 1 or 2.
Section 4. Item 4. The fecal lipid excretion enhancer according to item 3, which is taken continuously for 6 days or more.
Item 5. Item 5. The agent for promoting fecal lipid excretion according to Item 3 or 4, 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.

The Bofutsushosan extract of the present invention has a high effect of promoting the excretion of ingested lipids into the feces, and is effective for people with a constitution in which lipid decomposition and metabolic capacity are essentially lowered. It becomes possible to effectively improve or avoid health problems caused by overdose.

The Bofutsushosan 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 herbal medicine-derived components. The Bofutsushosan extract of the present invention is described in detail below.

Bofutsushosan extract The crude drugs that make up Bofutsushosan are, according to the "Guidelines for General Use Kampo Prescriptions" (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Nichiyakuren Kampo Expert Committee, published by Yakugyo Jihosha). , Peony, Cnidium, Sanshishi, Forsythia, Mentha, Ginger, Limonium, Ephedra, Ephedra, Rhubarb, Rhubarb, Byakujutsu, Bellflower, Scutellaria root, Glycyrrhiza, Gypsum, and Casseki. Depending on the letter, among the above crude drugs, those that do not contain byakujutsu (for example, "Experience Kampo Prescription Quantity Collection", compiled by Keisetsu Otsuka and Michiaki Yakazu, published by Ido no Nihonsha) and those that do not contain scutellaria root (for example, " Zoku Kampo All That,” edited by Osaka Yomiuri Shimbun, published by Naniwa Publishing). The Bofu-tsusho-san extract used in the present invention may be obtained from any of these Bofu-tsu-sho-san extracts, as long as the content of 6-gingerol satisfies a predetermined range.

The Bofutsushosan 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 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 herbal medicine-derived ingredients. . In the Bofutsushosan extract of the present invention, since the 6-gingerol content is reduced to the range described above, it is possible to more effectively promote the excretion of lipids into feces. From the viewpoint of more effectively promoting the excretion of lipids into feces, 6-gingerol is preferably 0.007 to 0.03 parts by weight, more preferably 0.03 parts by weight, per 100 parts by weight of the total amount of herbal medicine-derived components. 007 to 0.025 parts by weight, particularly preferably 0.007 to 0.015 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 that does not contain additives such as excipients, the weight of the extract powder is the total amount of herbal medicine-derived ingredients, and additives such as excipients are mixed. In the case of the Bofutsushosan extract powder, the weight of the extract powder minus the weight of the additives contained therein is the total amount of the crude drug-derived components.

The content of 6-gingerol contained in ginger varies depending on the place of production and the number of growing years of ginger, and the extraction efficiency of 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 at the above ratio, the ratio of ginger in the crude drug preparation and the ginger to be extracted are determined according to the 6-gingerol content contained in ginger. (that is, the ginger used in herbal preparations) and the like may be appropriately set. Ginger is better to extract processed products sliced into slices with a thickness of about 1 to 3 mm than to extract slices that are about 1 to 8 mm square. The extraction amount can be reduced, and the bofutsushosan extract containing 6-gingerol in the above ratio can be preferably obtained. For example, 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 Aspect A described later, by adjusting the shape of ginger, 6-gingerol is within the content range. Bofutsushosan extract containing can be suitably obtained.

In addition, the amount of each crude drug that constitutes Bofutsushosan is based on the ``Guidelines for OTC Kampo Prescriptions'' (supervised by the Pharmaceutical Affairs Bureau of the Ministry of Health and Welfare, edited by the Kampo Specialist Committee of the Federation of Japanese Pharmacopoeia, published by Yakugyo Jihosha), ``17th According to the Revised Japanese Pharmacopoeia, etc., 1.2 parts by weight of Angelica keiskei, 1.2 parts by weight of peony, 1.2 parts by weight of neem, 1.2 parts by weight of Sanshishi, 1.2 parts by weight of forsythia, 1.2 parts by weight of mint parts, 0.3 to 1.2 parts by weight of ginger, 1.2 parts by weight of mussels, 1.2 parts by weight of foxtail or 1.2 parts by weight of horsetail, 1.2 parts by weight of ephedra, 1.5 parts by weight of rhubarb, yellow pepper (Converted to anhydrous sodium sulfate) 0.6 to 1.5 parts by weight, 2 parts by weight of bayakujutsu, 2 parts by weight of bellflower, 2 parts by weight of scutellaria root, 2 parts by weight of licorice, 2 to 3 parts by weight of gypsum, and 3 to 5 parts by weight of casseki Department. Also, in some letters, all 1.2 parts by weight are changed to 1.5 parts by weight (for example, "Keikai Kampo Prescription", co-authored by Kazuo Nishioka and Shintaro Takahashi, published by Naniwasha).

The amount of each crude drug in the crude drug preparation used for the production of Bofutsushosan extract is not particularly limited as long as the content of 6-gingerol satisfies the above range. Although the amount of each herbal medicine shown may be used, suitable examples include 1.2 parts by weight of angelica root, 1.2 parts by weight of peony, 1.2 parts by weight of nematode, 1.2 parts by weight of Japanese honeysuckle, and forsythia. 1.2 parts by weight, 1.2 parts by weight of peppermint, 1.2 parts by weight of mussels, 1.2 parts by weight of foxtail, 1.2 parts by weight of ephedra, 1.5 parts by weight of rhubarb, bosho (converted to anhydrous sodium sulfate) 0.6 to 1.5 parts by weight, 2 parts by weight of biakujutsu, 2 parts by weight of Bellflower, 2 parts by weight of Scutellaria root, 2 parts by weight of licorice, 2 to 3 parts by weight of gypsum (preferably 2 parts by weight), and 3 to 5 parts by weight of casseki parts (preferably 3 parts by weight), and ginger is 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 preferred is 0.3 parts by weight (hereinafter sometimes referred to as "Aspect A"). By adjusting the amount of ginger in the crude drug preparation used for the production of Bofutsushosan extract to the above range, the content of 6-gingerol is preferably satisfied within the above range, and lipids are added to the feces. Excretion can be promoted more effectively. In the present invention, the "preparation of herbal medicines 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 predetermined amounts of constituent herbal medicines.

In addition, as a suitable example of the above-described aspect A, the amount of red pepper is preferably 0.6 to 1 part by weight, more preferably 0.6 to 0.75 parts by weight, particularly preferably 0.6 to 0.75 parts by weight, in terms of anhydrous sodium sulfate 0.7 parts by weight. When the amount of red pepper satisfies such a range, it becomes possible to more effectively promote the excretion of lipids into feces. In the present invention, the conversion of sodium sulfate to anhydrous sodium sulfate refers to converting the hydrate to the weight of anhydrous sodium sulfate when sodium sulfate hydrate is used as the sodium sulfate. In addition, sodium sulfate hydrate (for example, decahydrate) and/or sodium sulfate anhydride is used as the salt.

A suitable example of the crude drug preparation used for the production of the bofutsushosan extract of the present invention is 1 to 5 parts by weight, preferably 1 to 4 parts by weight, of ginger per 100 parts by weight of the total amount of the crude drug preparation. , more preferably 1 to 3 parts by weight, particularly preferably 1 to 2 parts by weight. By obtaining the Bofutsushosan extract from the crude drug preparation with a low ginger ratio, the content of 6-gingerol is preferably satisfied within the above range, and lipid excretion into the feces is more effective. can be promoted to

In addition, as a preferred example of the crude drug preparation used in the production of the bofutsushosan extract used in the present invention, 2 to 6 bosho in terms of anhydrous sodium sulfate are added per 100 parts by weight of the total amount of the crude drug preparation. Part by weight, preferably 2 to 4 parts by weight, more preferably 2 to 3 parts by weight, particularly preferably 2 to 2.5 parts by weight. By including Bosho in the crude drug preparation in such a ratio, it becomes possible to more effectively promote the excretion of lipids into feces.

The Bofu-tsusho-san extract of the present invention can be obtained by extracting the crude drug preparation by a known method. As for the method of extracting the herbal medicine preparation, it may be carried out by the same method as the conventional Bofutsushosan extract extraction method. , and a method of extracting by stirring at about 80 to 100° C. for about 1 to 3 hours. After extraction, the extract is subjected to solid-liquid separation such as centrifugation or filtration to remove solids, and if necessary, subjected to concentration treatment or drying treatment to obtain the Bofutsushosan extract of the present invention.

In order to obtain the Bofu-tsusho-san extract of the present invention as an extract powder, the liquid extract from which solids have been removed is concentrated, if necessary, and then subjected to a drying treatment such as spray-drying, reduced-pressure concentration-drying, or freeze-drying. good. In addition, excipients such as dextrin may be added to the extract, if necessary, when subjected to drying treatment (especially drying treatment by spray drying). By adding excipients in this way, it is possible to shorten the drying time. The types and amounts of excipients to be added are the same as in the case of producing general Chinese herbal extract powder.

In order to obtain the Bofutsushosan extract of the present invention as a soft extract, the liquid extract from which the solid components have been removed may be concentrated by vacuum concentration or the like. In addition, an appropriate adsorbent (eg, silicic anhydride, starch, etc.) may be added to the soft extract to obtain an adsorbent powder.

The Bofu-tsusho-san extract of the present invention may be either powdered extract or soft extract.

Formulation The Bofu-tsusho-san extract of the present invention may be formulated as a single Bofu-tsu-sho-san extract, or may be formulated with additives and bases to obtain a desired formulation form. good. Such additives and bases are not particularly limited as long as they are pharmaceutically acceptable. Examples include excipients, binders, disintegrants, lubricants, tonicity 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, flavoring agents, fragrances, powders, Thickeners, pigments, chelating agents and the like are included. These additives may be used singly or in combination of two or more. The contents of these additives and bases are appropriately set according to the types of additives and bases used, the form of preparation, and the like.

In addition, the Bofutsushosan extract of the present invention may be formulated into a formulation in combination with other nutritional components and pharmacological components, if necessary. Such nutritional components and pharmacological components are not particularly limited as long as they are pharmaceutically acceptable. Antiemetics, antitussives, expectorants, antiphlogistic enzymes, sedatives, hypnotics, antihistamines, caffeines, cardiac diuretics, antibacterial agents, vasoconstrictors, vasodilators, local anesthetics, crude drug extracts, vitamins, menthol and the like. These nutritional ingredients and pharmacological ingredients may be used singly or in combination of two or more. In addition, the contents of these components are appropriately set according to the types of components used, formulation forms, and the like.

The formulation form of the Bofutsushosan extract of the present invention is not particularly limited as long as it can be administered orally. solid formulations (soft capsules, hard capsules); semi-solid formulations such as jelly; and liquid formulations such as solutions, suspensions and syrups. Among these formulation forms, solid formulations are preferred from the viewpoint of the stability of the ingredients, portability, and the like.

In order to prepare the Bofu-tsusho-san extract of the present invention in the above formulation form, the Bofu-tsu-sho-san extract and optionally added additives, bases, and pharmacological ingredients are used, and It can be formulated according to the usual formulation method.

Uses The Bofu-tsusho-san extract of the present invention, like the conventional Bofu-tsu-sho-san extract, is used for purposes such as reducing body weight and reducing visceral fat, but has the effect of promoting the excretion of ingested lipids into feces. and can be suitably used as an agent for promoting fecal lipid excretion. In addition, since the Bofutsushosan extract of the present invention has an excellent effect of promoting fecal excretion of cholesterol, it is suitable for use in promoting the fecal excretion of ingested cholesterol and blood cholesterol. used.

In addition, in people with a constitution in which lipid decomposing ability and metabolic ability are essentially reduced, the conventional Bofutsushosan extract cannot be expected to improve lipid decomposing ability and metabolic ability, resulting in weight loss and reduction of visceral fat. It was thought to be unrealizable, and there was no custom of taking the conventional Bofutsushosan extract. It is possible to suppress the adverse effects of lipid intake (weight gain, increase in visceral fat, etc.) even for people with a constitution in which lipid decomposition and metabolic capacity are essentially reduced. In view of such effects of the present invention, suitable subjects for application of the Bofutsushosan extract of the present invention include people with a constitution in which the ability to decompose and metabolize lipids is essentially reduced. Specifically, people with such a constitution include those who have a body fat percentage of 25% or more and a waist size of 85 cm or more for 5 years or more; , body fat percentage of 25% or more); lipolytic power measured in the following lipolytic power evaluation test is 5 mEq/g or less, preferably 3 mEq/g or less, more preferably 1 mEq/g or less, further preferably 0 0.5 mEq/g or less, particularly preferably 0.3 mEq/g or less, with adipose tissue.
<Lipolysis power evaluation test>
First, adipose tissue is collected from the subject's subcutaneous tissue. The resulting adipose tissue is washed with Krebs Ringer buffer (pH 7.4). The washed adipose tissue was weighed, and 0.2 g of washed adipose tissue was added to 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2% by weight of bovine serum albumin (BSA). Add and incubate for 2 hours at 37°C. After that, the supernatant is recovered, 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 determined as the lipolytic power.

It is known that adipose tissue is activated by noradrenaline stimulation, decomposes accumulated fat, and releases free fatty acids. In the lipolytic power evaluation test, the lipolytic power of adipose tissue is evaluated by measuring the release amount of this free fatty acid.

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

In addition, the bofutsushosan extract of the present invention promotes the excretion of lipids into stools by continuous ingestion. is preferably taken continuously for 6 days or more, preferably continuously taken for 12 days or more).

EXAMPLES The present invention will be specifically described below by way of examples, but the present invention is not limited to these examples.

Production and Analysis of Bofutsushosan Extract
1. Preparation of bofutsushosan extract powder Each crude drug shown in Table 1 was finely chopped or sliced, and predetermined amounts were mixed and finely chopped to obtain a crude drug formulation. 20 times the weight of water was added to the crude drug preparation, and extraction was performed with stirring at about 100° C. for 1 hour. Thereafter, the extract was collected by centrifugation, concentrated under reduced pressure, and dried using a spray dryer to obtain Bofutsushosan extract powder.

In Production Examples 1 and 2, the ginger was cut into 1 to 8 mm squares, and in Production Example 3, the ginger was sliced into 1 to 3 mm thick slices. Drying with a spray dryer was carried out by dropping the liquid extract onto an atomizer rotating at 10,000 rpm and supplying hot air at 150°C.

2. Measurement of 6-gingerol content in Bofutsushosan extract powder About 1 g of Bofutsushosan extract powder was precisely weighed, placed in a stoppered centrifuge tube, and mixed with methanol/water (volume ratio of methanol:water: 3:1). ) was added, shaken for 20 minutes, and then centrifuged to separate the extract. 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 of the extracts were combined, and a mixture of methanol and water (volume ratio of methanol:water of 3:1) was added to make exactly 100 mL to obtain a sample solution. Separately, about 5 mg of 6-gingerol for quantitative use was accurately weighed, dissolved in a mixed solution of methanol/water (volume ratio of methanol:water: 3:1) to make exactly 100 mL, and used as a standard solution. Exactly 10 μL each of the sample solution and the standard solution were taken and measured by liquid chromatography under the following test conditions.
(Test condition)
Detector : UV absorption photometer (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 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 about 19 minutes.

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

Table 2 shows the results. Bofutsushosan extract obtained from a herbal medicine preparation with a low ginger ratio of 1.11 parts by weight with respect to 100 parts by weight of the crude drug preparation has a remarkably low 6-gingerol content of 0.010% by weight. (Production Example 1). In addition, when the ginger to be extracted is sliced with a thickness of 1 to 3 mm, the content of 6-gingerol in the obtained Bofutsushosan extract is higher than when it is cut into 1 to 8 mm squares. The amount was reduced (Preparation Examples 2 and 3).

Test Example 1: Evaluation of lipid excretion promotion effect and body weight reduction effect Mice (C57BL/6J mice, 5 weeks old, male) were fed a high-fat diet (HFD32, CLEA Japan, Inc.) ad libitum for 4 weeks. and bred to produce obesity model mice. After measuring the weight of this obese model mouse, it was divided into a total of three groups: a control group (control example), test group 1, and test group 2 so that the average weight of each group was about 26 g (each group 6 to 11). In test group 1, obese model mice were fed with a feed containing 4% by weight of the bofutsushosan extract of Production Example 1 in the high-fat diet for 20 days. In test group 2, obese model mice were fed with a feed containing 4% by weight of the bofutsushosan extract of Production Example 2 in the high-fat diet for 20 days. The control group was fed a high-fat diet containing no bofutsushosan extract for 20 days. Feces were collected every 2 days during the study period. The collected feces were freeze-dried.

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

Furthermore, extracts (lipids) extracted from feces excreted between 12 and 14 days after the start of the test were redissolved in isopropanol and tested using Cholesterol E Test Wako (Wako Pure Chemical Industries, Ltd.). By operating according to the attached instruction manual, the weight of cholesterol was measured, the amount of cholesterol excreted in each group was calculated according to the following formula, and the amount of cholesterol excreted in each group was divided by the number of mice in each group. , the amount of cholesterol excreted per mouse was determined.

Taking the total lipid excretion per mouse in the control group as 100%, the relative values of the total lipid excretion per mouse in test groups 1 and 2 were calculated. Similarly, relative values of cholesterol excretion per mouse in Test Groups 1 and 2 were calculated, taking the cholesterol excretion per mouse in the control group as 100%.

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

Table 3 shows the results of total lipid excretion, Table 4 shows the results of cholesterol excretion, and Table 5 shows the rate of change in body weight.

No diarrhea was observed in any of the mice during the breeding period. In addition, the amount of feces per day for each mouse was 211.5 to 315.1 mg/day/mouse in terms of dry weight, and no significant difference was observed between the groups.

As can be seen from Table 3, in test groups 1 and 2, in which Bofutsushosan extract powder satisfying 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, After 6 days of feeding, an increase in total lipid excretion was observed compared to 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 increased by ingesting Bofutsushosan extract powder. In particular, after the 12th day of breeding, the amount of lipid excretion in test group 1 was greater than that in test group 2, and the amount of 6-gingerol per 100 parts by weight of the total amount of crude drug-derived components was 0.010 parts by weight. It was found that the use of a certain Bofutsushosan extract powder (Production Example 1) enhances the effect of promoting lipid excretion. Bofutsushosan extract powder (Bofutsushosan extract powder (total amount of crude drug-derived components ) Amount of 6-gingerol per 100 parts by weight: 0.012 parts by weight) was also subjected to the same test, and the effect of promoting lipid excretion was higher than when the Bofutsushosan extract powder of Production Example 2 was used. was found to increase.

Moreover, as is clear from Table 4, similar to the results of total lipid excretion, test groups 1 and 2 ingesting the Bofutsushosan extract powder of Production Examples 1 and 2 had higher cholesterol levels than the control group. increased excretion of Moreover, in Test Group 1, in which the bofutsushosan extract of Production Example 1 was ingested, cholesterol excretion increased more than in Test Group 2, in which the Bofutsushosan extract of Production Example 2 was ingested.

In addition, as shown in Table 5, the control group had increased body weight at the end of feeding compared to the start of feeding, whereas the test groups ingested the Bofutsushosan extract of Production Examples 1 and 2 In 1 and 2, the increase in body weight was suppressed. In particular, Test Group 1, in which the bofutsushosan extract of Production Example 1 was ingested, exhibited a higher body weight reduction effect than Test Group 2, in which the Bofutsushosan extract of Production Example 2 was ingested. Such suppression of body weight gain by the bofutsushosan extract is considered to be due to its effect of promoting the excretion of lipids into the feces.

Test Example 2: Evaluation of effect of reducing visceral fat and body weight
Preparation of young-onset obesity 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, and were subjected to early-onset obesity. A model mouse was produced.

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 prepare age-related obesity model mice. bottom.

In addition, epididymal fat was excised from each of three juvenile obesity model mice and three age-related obesity model mice prepared above, and lipolytic activity was measured. Specifically, first, the adipose tissue removed from around the epididymis was washed with Krebs Ringer buffer (pH 7.4). The washed adipose tissue was weighed, and 0.2 g of washed adipose tissue was added to 5 mL of Krebs Ringer buffer (pH 7.4) containing 1 μg/mL noradrenaline and 2% by weight of bovine serum albumin (BSA). and incubated for 2 hours at 37°C. After that, the supernatant was collected, and the amount of free fatty acids released in the supernatant by noradrenaline stimulation was measured with NEFA-C Test Wako (Wako Pure Chemical Industries, Ltd.), and the amount of free fatty acids released per 1 g of adipose tissue. (mEq/g) was determined as lipolytic power.

Bofutsushosan extract administration test After measuring the body weight of the young obese mouse model prepared above, control group A (control example), test group A1, and test group A1 were added so that the average weight of each group was about 26 g They were divided into group A2 (6-11 animals in each group). In addition, after measuring the weight of the age-related obesity model mice prepared above, they were divided into a control group B (control example) and a test group B so that the average weight of each group was about 42 g (6 mice in each group ).

In the test group A1, the above high-fat diet was fed with the Bofutsushosan extract powder of Production Example 1 in an amount of 2% by weight for 21 days. In the test group A2, the above high-fat diet was fed with the Bofutsushosan extract powder of Production Example 1 in an amount of 4% by weight for 21 days. In the test group B, the high-fat diet was fed with the Bofutsushosan extract powder of Production Example 1 in an amount of 2% by weight for 21 days. Control groups A and B were fed a high-fat diet containing no bofutsushosan extract for 21 days. On the final day of the test, the body weight of each mouse was measured, and the visceral fat was removed and the weight was measured.

Taking the average body weight of the control group A mice on the final day of the test as 100%, the relative values of the average body weights of the mice on the final day of the test in the test groups A1 and A2 were calculated. In addition, the relative value of the average body weight of the mice in the test group B on the final day of the test was calculated, taking the average body weight of the mice in the control group B on the final day of the test as 100%. Taking the average weight of visceral fat of mice on the final day of the test in the control group A as 100%, the relative value of the average weight of the mice in the test groups A1 and A2 on the final day of the test was calculated. Taking the average weight of visceral fat of mice on the final day of the test in control group B as 100%, the relative value of the visceral fat weight of mice in test group B on the final day of the test was calculated.

Results The results obtained are shown in Table 6. From these results, both the young obesity model mouse and the age-related obesity model mouse were found to reduce body weight and visceral fat with the Bofutsushosan extract powder. Feeding with the diet containing the tsushosan extract powder reduced the body weight and visceral fat more than the juvenile obese model mice fed with the diet containing 4% by weight of the bofu tsushosan extract powder.

The lipolytic capacity in the epididymal fat was 5.6 mEq/g on average in young obese model mice, whereas it was 0.28 mEq/g in age-related obese model mice. The lipolytic capacity decreased to 1/20 with age. It is an extremely unexpected result that bofutsushosan extract powder effectively reduced body weight and visceral fat even in an age-related obese mouse model with reduced lipolytic capacity. .

Test Example 3 Evaluation of Body Weight Reduction Effect by Age The body weight reduction effect of the bofutsushosan extract was evaluated for persons with a constitution essentially degraded in lipid decomposition and metabolic capacity. Specifically, the average weight of 9 men and women (each age group (20s, 30s, 40s to 50s)) who have a body fat percentage of 25% or more and a waist size of 85cm or more for 5 years or more. 5000 mg of Bofutsushosan extract powder of Production Example 1 was administered in 3 divided doses a day for 2 weeks, and changes in body weight compared to before the start of administration were measured.

Table 7 shows the results. By administering the bofutsushosan extract of Production Example 1 to people with a constitution in which lipid decomposition and metabolic capacity are essentially reduced, an average weight loss of about 1 kg was observed overall, and by age group. When analyzed, it was confirmed that the effect increases with age. In age-related obesity in people in their 40s and 50s, lipid decomposition and metabolic capacity are essentially reduced. As shown in Test Example 1, the Bofutsushosan extract of Example 1 has an excellent effect of promoting lipid excretion into feces, and this effect contributes to the body weight reduction effect on age-related obesity. presumably played.

Formulation Example Tablets (400 mg per tablet) containing bofutsushosan extract powder were prepared according to the formulations shown in Tables 8 to 13. As 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 the effect of promoting lipid excretion into feces.

Claims (3)

A fecal lipid excretion enhancer containing a bofutsushosan extract, wherein the bofutsushosan extract contains 0.005 to 0.015 wt. parts, and the crude drug preparation used for extracting the Bofutsushosan extract contains 2 to 3 parts by weight of Bosho in terms of anhydrous sodium sulfate per 100 parts by weight of the crude drug preparation. Moderate lipid excretion promoter. The fecal lipid excretion-promoting agent according to claim 1, which is taken continuously for 6 days or longer. 3. The fecal lipid excretion-promoting agent according to claim 1 or 2, 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.