Agent for inhibiting body fat accumulation and agent for inhibiting body weight gain

Abstract

To provide an agent for inhibiting body fat accumulation capable of exhibiting an effect of inhibiting body fat accumulation in a relatively small amount, which is derived from natural products, is highly safe, and can be stably supplied.SOLUTION: An agent for inhibiting body fat accumulation comprises 3.38 mg or more of oenothein B, represented by the following formula (I), as an effective amount per day.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an agent for suppressing body fat accumulation and an agent for suppressing body weight. [Background technology]

[0002] Excessive energy not consumed in daily life due to the Westernization of food culture, overeating, and excessive calorie intake from unbalanced diets accumulates in the body as fat. Examples of fat that accumulates in the body include visceral fat that accumulates around internal organs such as the stomach and intestines, liver fat that accumulates in the liver, and subcutaneous fat that accumulates in the subcutaneous tissue. Obesity is a condition in which fat accumulates in the body in this way.

[0003] Obesity causes health problems such as dyslipidemia, diabetes, hypertension, fatty liver, and vascular disease. In order to reduce the risk of such health problems, it is important to prevent obesity. Therefore, one method of preventing obesity is to prevent excess fat from accumulating in the body.

[0004] For example, Patent Document 1 describes a visceral fat reducing agent containing a grain culture of Cordyceps mycelium. However, the visceral fat reducing agent described in Patent Document 1 requires complicated steps for production, such as preparation of a medium, ingestion of Cordyceps, and cultivation. Furthermore, the culture may have variations in the content of active ingredients depending on the cultivation conditions, etc., and the visceral fat reducing agent may not be stably supplied. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2020-80708 A DISCLOSURE OF THEINVENTION [Problem to be solved by the invention]

[0006] The object of the present invention is to provide a body fat accumulation inhibitor that is derived from a natural product, is highly safe, can be supplied stably, and exerts a body fat accumulation inhibitory effect in a relatively small amount. Another object of the present invention is to provide a body weight inhibitor that is derived from a natural product, is highly safe, can be supplied stably, and exerts a body weight inhibitory effect in a relatively small amount. [Means for solving the problem]

[0007] As a result of intensive research into solving the above problems, the present inventors have found a solution comprising the following configuration, and have completed the present invention. (1) A body fat accumulation inhibitor containing oenothein B represented by the following formula (I) in an effective amount per day of 3.38 mg or more: [ka] G in formula (I) represents a structure of the following formula (II). [ka] (2) A body fat accumulation inhibitor according to (1) above, which contains an extract of a Eucalyptus plant containing oenothein B. (3) The body fat accumulation inhibitor according to (1) above, wherein the body fat is visceral fat. (4) The agent for suppressing body fat accumulation according to (1) above, wherein the body fat is liver fat. (5) The body fat accumulation inhibitor according to (1) or (2) above, which is in a unit package form per day. (6) A weight control agent containing oenothein B represented by the following formula (I) in an effective amount per day of 3.38 mg or more. [ka] G in formula (I) represents a structure of the following formula (II). [ka] (7) The body weight suppressant according to (6) above, which contains an extract of a Eucalyptus plant containing oenothein B. (8) The body weight suppressant according to (6) or (7) above, which is in a unit package form per day. Effect of the Invention

[0008] The body fat accumulation inhibitor according to the present invention is derived from a natural product, is highly safe, can be supplied stably, and exerts a body fat accumulation inhibitory effect in a relatively small amount.Furthermore, the body weight inhibitor according to the present invention is derived from a natural product, is highly safe, can be supplied stably, and exerts a body weight inhibitory effect in a relatively small amount. [Brief description of the drawings]

[0009] [Figure 1] Graphs showing the test results from Example 1, where (A) is a graph showing the amount of change in visceral fat area (VFA), (B) is a graph showing the amount of change in body weight, and (C) is a graph showing the amount of change in body mass index (BMI). [Diagram 2] 1 is a graph showing the test results obtained in Example 2, in which (A) is a graph showing the amount of change in VFA, and (B) is a graph showing the amount of change in liver fat level (CAP). [Diagram 3] 1 is a graph showing the results of a test on the amount of change in VFA carried out in Example 3. [Figure 4] 1 is a graph showing the results of a test performed in Comparative Example 1, in which (A) is a graph showing the amount of change in body weight, and (B) is a graph showing the amount of change in VFA. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The body fat accumulation inhibitor of the present invention contains oenothein B. Hereinafter, the body fat accumulation inhibitor according to one embodiment of the present disclosure will be described.

[0011] Oenothein B contained in the body fat accumulation inhibitor according to one embodiment is also called oenothein B, and is a compound belonging to hydrolyzable tannins and a type of polyphenol. Oenothein B is represented by the following formula (I). G in formula (I) represents the structure of the following formula (II).

[0012] [ka]

[0013] [ka]

[0014] The oenothein B contained in the body fat accumulation inhibitor according to one embodiment may be derived from a natural product or may be obtained by chemical synthesis. Naturally derived oenothein B is contained in, for example, angiosperms, dicotyledonous plants (Engler system) that contain hydrolyzable tannins.

[0015] The method of obtaining oenothein B from a plant containing hydrolyzable tannins is not limited, and may be, for example, extraction. In the extraction process, various parts of the plant containing hydrolyzable tannins (whole plant, flowers, calyx, seeds, fruits, leaves, branches, bark, root bark, rhizomes, roots, etc.) may be used as they are or may be dried. If necessary, they may be cut, crushed, or powdered.

[0016] Examples of plants containing hydrolyzable tannins include plants belonging to the Myrtaceae, Rosaceae, Casuarinae, Fagaceae, Theaceae, Onagraceae, Lythraceae, Trachyspermaceae, Pomegranate, Melastomataceae, Combretaceae, and Barringtoniaceae. These plants contain a lot of hydrolyzable tannins. Therefore, by using these plants as raw materials, hydrolyzable tannins can be efficiently obtained. Among these, plants belonging to the Myrtaceae family are preferred. Furthermore, among the Myrtaceae family, many plants of the genus Eucalyptus, Myrtaceae, Pimenta, and Melaleuca are used in foods, spices, and fragrances. Therefore, using plants belonging to these families as raw materials is preferred from the viewpoints of food experience and safety. In particular, eucalyptus is preferred because it contains a lot of oenothein B.

[0017] The extraction method is not limited, and examples thereof include room temperature homogenized extraction, reflux extraction, and supercritical fluid extraction. Extraction using a solvent is performed under conditions that allow hydrolyzable tannins to be dissolved. For example, extraction may be performed for about 10 minutes to 1 week under normal pressure to pressure conditions and temperature conditions from room temperature to the boiling point of the solvent according to the solvent used. In the case of relatively mild extraction conditions such as room temperature and normal pressure, it is preferable to immerse a plant containing hydrolyzable tannins in the extraction solvent for a relatively long time (for example, about 1 week). On the other hand, in the case of relatively severe extraction conditions such as high temperature conditions or pressure conditions, it is preferable to complete the extraction work in a relatively short time (for example, 10 minutes to 3 hours).

[0018] Examples of the solvent used for extraction include solvents that are commonly used according to the plant species and processing steps. Specific examples of such solvents include water; alcohols (e.g., lower alcohols such as methanol and ethanol, polyhydric alcohols such as ethylene glycol, propylene glycol, 1,3-butylene glycol, and glycerin); ketones having relatively high polarity such as acetone; and organic solvents such as esters such as ethyl acetate. The extraction solvent may be used alone or in combination of two or more kinds. Considering that the body fat accumulation inhibitor according to one embodiment is ingested into the body, water, ethanol, and aqueous ethanol are preferred among these.

[0019] The form of use after extraction is not particularly limited, and the extract containing oenothein B may be used as it is, or may be processed by drying or spray drying after concentration. It may be purified as necessary. In the case of purification, it is necessary to go through a complicated process to isolate oenothein B, which is also disadvantageous in terms of cost. Therefore, instead of refining to isolate oenothein B, purification may be performed to remove only the extract components that are relatively easy to remove and to increase the concentration of oenothein B contained in the extract. Such purification can be performed, for example, using an adsorption resin such as Diaion HP20 (manufactured by Mitsubishi Chemical Corporation). An extract containing oenothein B in the extract components, for example, preferably 0.5% by mass or more, more preferably 1% by mass or more, may be used. The amount of an extract with an increased concentration of oenothein B can be reduced compared to an unpurified extract.

[0020] In one embodiment of the body fat accumulation inhibitor, in order to exert the body fat accumulation inhibitory effect, it is necessary to contain 3.38 mg or more of onotein B as an effective amount per day. When using an extract, it is sufficient to use it so that 3.38 mg or more of onotein B is contained as an effective amount per day. If the daily intake of onotein B is less than 3.38 mg, the effect of inhibiting the accumulation of body fat is not fully exerted. On the other hand, the daily intake of onotein B may be 8.12 mg or less. Although there is no problem with safety even if it is taken in an amount exceeding 8.12 mg, for example, when it is mixed with food and drink and taken, it may affect the flavor depending on the food and drink.

[0021] The body fat accumulation inhibitor according to one embodiment efficiently inhibits the accumulation of visceral fat and liver fat, among other types of body fat. Visceral fat is fat that accumulates mainly around organs such as the intestine and stomach. Liver fat is fat that accumulates in the liver (hepatocytes). Accumulation of visceral fat and liver fat leads to health disorders such as dyslipidemia, diabetes, hypertension, fatty liver, and vascular disease. In particular, it is known that liver fat, when severe, can cause nonalcoholic steatohepatitis (NASH), which progresses from liver cirrhosis to liver cancer.

[0022] The form of the body fat accumulation inhibitor according to one embodiment is not limited, and may be any form that allows the effective daily intake of 3.38 mg or more of oenothein B. The mixture may be in the form of a solid, semi-solid (e.g., paste, etc.), liquid, or the like.

[0023] Examples of pharma- ceutically acceptable carriers include excipients, binders, disintegrants, lubricants, preservatives, stabilizers, buffers, suspending agents, surfactants, etc. Specific examples include solid carriers (e.g., starch, dextrin, sugars, lactose, mannitol, modified starch, gelatin, cellulose, carboxymethylcellulose, hydroxypropylmethylcellulose, casein, organic acids, inorganic salts, etc.), liquid carriers (e.g., distilled water, physiological saline, aqueous glucose solution, fructose glucose liquid sugar, high fructose liquid sugar, ethanol, propylene glycol, polyethylene glycol, glycerin, etc.), and oily carriers (e.g., various animal and vegetable oils, white petrolatum, paraffin, wax, etc.).

[0024] The dosage form of the body fat accumulation inhibitor according to one embodiment may be, for example, an orally administered agent such as a tablet, capsule, pill, granule, powder, emulsion, suspension, or syrup. In addition to such an orally administered agent, it is considered that onotein B can be blended into various processed foods and beverages such as prepared foods, retort foods, canned foods, breads, confectioneries (cookies, chocolates, candies, gummies, rice crackers, etc.), dairy products (yogurt, milk-based drinks, etc.), beverages (tea-based drinks, soft drinks, etc.), soups, and the like, so that onotein B can be ingested at 3.38 mg or more per day. The body fat accumulation inhibitor according to one embodiment may be, for example, in a unit package form per day. When the body fat accumulation inhibitor according to one embodiment is in a unit package form per day, an effective amount of onotein B per day can be easily ingested by simply ingesting one packet per day.

[0025] The body fat accumulation inhibitor according to one embodiment, which contains 3.38 mg or more of oenothein B as an effective amount per day, exerts a body fat accumulation inhibitory effect. Specifically, by continuously taking the body fat accumulation inhibitor according to one embodiment for 4 weeks or more, the accumulation of body fat, particularly visceral fat and liver fat, can be significantly suppressed compared to the case where the inhibitor is not taken.

[0026] In this way, the body fat accumulation inhibitor according to one embodiment exerts an effect of suppressing the accumulation of body fat such as visceral fat and liver fat. As a result, an effect of suppressing body weight is also exerted. Therefore, the body fat accumulation inhibitor according to one embodiment also functions as a body weight suppressing agent. EXAMPLES

[0027] EXAMPLES The present invention will be specifically described below with reference to examples and comparative examples, but the present invention is not limited to these examples.

[0028] <Preparation Example 1> Oenothein B was prepared by the following procedure: Eucalyptus leaves were extracted with aqueous ethanol, filtered and concentrated, and then dextrin was added as an excipient. The extract was spray-dried to obtain a powdered extract containing oenothein B as the main component.

[0029] <Test food 1> Test Food 1 was prepared using a capsule coated with gelatin and colored brown with caramel coloring, and was composed of the powdered extract obtained in Preparation Example 1, gelatin, cellulose, dextrin, starch, calcium stearate, caramel coloring, vegetable lecithin, and talc.

[0030] <Placebo food 1> Placebo food 1 was prepared in the same manner as test food 1, except that the powdered extract obtained in Preparation Example 1 was not used.

[0031] The components of test food 1 and placebo food 1 were analyzed using high performance liquid chromatography, and the amount of onotein B contained in one day's supply (3 tablets) of test food 1 was 3.38 mg. On the other hand, the amount of onotein B contained in one day's supply (3 tablets) of placebo food 1 was 0 mg. Test food 1 and placebo food 1 were indistinguishable in appearance and flavor.

[0032] Example 1 Age 20 to 65 and BMI 23 kg / m 2 More than 30kg / m 2 A randomized, placebo-controlled, double-blind, parallel study was conducted with healthy male and female subjects of less than 18 years of age. An identification number was assigned to the person in charge of allocation by the test food distributor. The person in charge of allocation generated random numbers using a computer and created an allocation list using a completely randomized design with defined variables as factors.

[0033] The subjects were randomly assigned to either the test food group or the placebo group based on stratified random allocation that took into account VFA, BMI, age, sex, etc. The allocation list was only disclosed to the person who shipped the test food. The allocation list was kept locked by the person in charge of allocation until the day of key release. Those involved in the study were not informed of the group allocation and were not involved in the allocation process.

[0034] Subjects took a daily dose (3 capsules) of test food 1 or placebo food 1 with water or lukewarm water every day after 2:00 pm or immediately before dinner for 12 weeks. Subjects with a capsule intake rate of 80% or more were selected for data analysis. Height was measured only at the first examination. The first examination was used as the baseline, and weight and umbilical cross-section tomography (CT) were measured every 4 weeks. The statistical significance level was set at 5% using a two-sided test.

[0035] Data were expressed as mean ± SD for subject characteristics, and mean ± SEM for evaluation items. Data for each time point and change from baseline were compared between groups by time using a linear mixed model with baseline values ​​as covariates, time, group, and time-group interactions, baseline value-time interactions, and study participant as factors for each time point.

[0036] Of the 198 subjects, 189 were accepted for data analysis. The test food group (94 subjects) consisted of 45 men and 49 women, with an average age of 46.5 ± 10.7 years, height of 164.4 ± 8.5 cm, weight of 69.6 ± 8.9 (kg), and VFA of 99.6 ± 38.9 (cm 2 The placebo group (95 subjects) consisted of 45 men and 50 women, with an average age of 48±10 years, height of 164.6±8.9cm, weight of 69.6±9.2kg, and VFA of 99.3±36.5cm. 2 ) was.

[0037] Comparisons between the groups showed that the test food group had significantly lower VFAs after 8 and 12 weeks (Figure 1A), and significantly lower weight (Figure 1B) and BMI (Figure 1C) after 12 weeks compared to the placebo food group. These results demonstrated that the test food intake had a suppressive effect on VFAs, weight, and BMI. No adverse events attributable to the test food were confirmed.

[0038] Example 2 Age 20 to 60 and BMI 23 kg / m 2 More than 30kg / m 2 A randomized, placebo-controlled, double-blind, parallel study was conducted with healthy male subjects of less than 18 years of age. The randomization manager was assigned an identification number by the test food distributor. The randomization manager used a computer to generate random numbers and created an allocation list using a completely randomized design with defined variables as factors.

[0039] The subjects were randomly assigned to either the test food group or the placebo group based on stratified random allocation that took into account VFA, liver fat level (CAP), BMI, age, etc. The allocation list was only disclosed to the person who shipped the test food. The allocation list was kept locked by the person in charge of allocation until the day of key release. Those involved in the study were not informed of the group allocation and were not involved in the allocation process.

[0040] The subjects took one day's worth (3 capsules) of test food 1 or placebo food 1 with a beverage containing 18g of sucrose every day after 3pm or at dinner for 12 weeks. Subjects with a capsule intake rate of 85% or more were included in the data analysis. Height was measured only at the first examination. The first examination was used as the baseline, and umbilical VFA was measured using the dual impedance method with Omron's Dual Scan HDS-2000, and CAP (Controlled Attenuation Parameter) was measured using the ultrasound elastography method with Integral's Fibroscan 530 Compact every 6 weeks. The statistical significance level was set at 5% using a two-sided test.

[0041] Data are presented as mean ± standard deviation for subject background and mean ± standard error for evaluation items, and comparisons within groups were performed using Dunnett's multiple test. Thirty-eight of the 40 subjects were accepted for data analysis. The average age of the test food group (18 subjects) was 47 ± 10 years, the height was 172.5 ± 4.1 cm, and the VFA was 95.1 ± 17.0 (cm 2 ), and CAP was 292±48 (dB / m). On the other hand, the average age of the placebo food group (20 people) was 46±9 years, the average height was 170.9±6.0 cm, and the VFA was 94.6±14.1 (cm 2 ), and the CAP was 276±46 (dB / m).

[0042] When comparing the groups, the placebo group showed a significant increase in VFA (p<0.01) and CAP (p<0.05) after 12 weeks, whereas no significant change was observed in the test food group, demonstrating that the test food had an inhibitory effect on the increase in VFA and CAP (Figure 2). No adverse events attributable to the test food were confirmed.

[0043] <Test food 2> Test Food 2 was prepared in the same manner as Test Food 1, except that the powdered extract obtained in Preparation Example 1 was used so that one daily dose (6 tablets) contained 8.12 mg of onotein B. The content of onotein B was measured using high performance liquid chromatography.

[0044] <Placebo food 2> Placebo food 2 was prepared in the same manner as test food 2, except that the powdered extract obtained in Preparation Example 1 was not used. As a result of analyzing the ingredients using high performance liquid chromatography, the amount of onotein B contained in one day's dose (6 tablets) of placebo food 1 was 0 mg. Test food 2 and placebo food 2 were indistinguishable in appearance and flavor.

[0045] Example 3 A randomized, placebo-controlled, double-blind, crossover study was conducted on healthy male subjects aged 20 years or older. An identification number was assigned to the person responsible for allocation by the distributor of the test food. The person responsible for allocation used a computer to generate random numbers and created an allocation table using a completely randomized design with defined variables as factors.

[0046] The subjects were randomly assigned to either the test food group or the placebo group based on a stratified random allocation that took into account VFA, BMI, age, etc. The allocation list was only disclosed to the person who shipped the test food. The allocation list was kept locked by the person in charge of allocation until the day of key release. Those involved in the study were not informed of the group allocation and were not involved in the allocation process.

[0047] The subjects took three capsules of either test food 2 or placebo food 2 with water or lukewarm water at 3:00 pm and 9:00 pm every day for four weeks, for a total of six capsules (one day's worth). Immediately after taking the three capsules, they consumed food or beverages containing 20g of sugar in sucrose equivalent (a total of 40g per day in sucrose equivalent). Those with a capsule intake rate of 85% or more were selected for data analysis. Height was measured only at the time of the test before the start of intake. The visceral fat area of ​​the umbilicus was measured using the dual scan method before and after the intake. After a four-week rest period, the subjects were given test food 2 and placebo food 2, and the intake test was conducted again for four weeks. The statistical significance level was set at 5% using a two-sided test.

[0048] Data are presented as mean ± standard deviation for subject background and mean ± standard error for evaluation items, and comparisons between and within groups were performed using Student's t-test. All six subjects were included in the analysis. The average age was 47 ± 12 years, and the height was 170.7 ± 6.7 cm. The VFA at the start of test food intake was 88.5 ± 11.1 (cm 2 ), and VFA at the start of placebo intake was 78.2 ± 10.8 (cm 2 ) was.

[0049] Between-group comparisons showed that VFAs were significantly lower in the test food group than in the placebo group after 4 weeks (Figure 3). Intra-group comparisons showed that VFAs increased significantly in the placebo group (p<0.005), whereas a significant decrease was observed in the test food group (p<0.05), demonstrating the VFA-suppressing effect of test food intake. No adverse events attributable to the test food were confirmed.

[0050] <Test food 3> Test Food 3 was prepared in the same manner as Test Food 1, except that the powdered extract obtained in Preparation Example 1 was used so that one daily dose (6 tablets) contained 1.12 mg of onotein B. The content of onotein B was measured using high performance liquid chromatography.

[0051] <Placebo food 3> Placebo food 3 was prepared in the same manner as test food 3, except that the powdered extract obtained in Preparation Example 1 was not used. Analysis of the ingredients using high performance liquid chromatography revealed that the amount of onotein B contained in one day's dose (6 tablets) of placebo food 1 was 0 mg. Test food 3 and placebo food 3 were indistinguishable in appearance and flavor.

[0052] Comparative Example 1 Age 20 years or older and BMI 23 kg / m 2 More than 30kg / m 2 A randomized, placebo-controlled, double-blind, parallel study was conducted with healthy male and female subjects of less than 18 years of age. An identification number was assigned to the person in charge of allocation by the test food distributor. The person in charge of allocation generated random numbers using a computer and created an allocation list using a completely randomized design with defined variables as factors.

[0053] The subjects were randomly assigned to either the test food group or the placebo group based on stratified random allocation that took into account VFA, BMI, age, sex, etc. The allocation list was only disclosed to the person who shipped the test food. The allocation list was kept locked by the person in charge of allocation until the day of key release. Those involved in the study were not informed of the group allocation and were not involved in the allocation process.

[0054] Subjects took one day's worth (6 capsules) of test food 3 or placebo food 3 with water or lukewarm water every day after 2:00 p.m. or immediately before dinner for 12 weeks. Subjects with a capsule intake rate of 80% or more were included in the data analysis. Height was measured only at the first examination. The first examination was used as the baseline, and visceral fat area at the umbilicus was measured every 6 weeks using the dual scan method. The statistical significance level was set at 5% using a two-sided test.

[0055] Data is presented as mean ± standard deviation for subject background and mean ± standard error for evaluation items. Intergroup comparisons were performed using Student's t-test, and intragroup comparisons were performed using Dunnett's multiple test. Intragroup comparisons were performed. All 20 subjects were included in the analysis. The test food group (10 subjects) consisted of 4 men and 6 women, with an average age of 51.5 ± 9.5 years, height of 162.4 ± 9.9 cm, weight of 69.2 ± 9.1 (kg), and VFA of 78.4 ± 22.5 (cm 2 The placebo group (10 participants) consisted of 4 men and 6 women, with an average age of 51.1±7.8 years, height of 161.3±5.8 cm, weight of 68.3±6.1 kg, and VFA of 75.2±21.4 cm. 2 ) was.

[0056] No significant changes in body weight or VFA were observed in either between-group or within-group comparisons, and no effect of test food intake was observed (Figure 4). No adverse events attributable to the test food were confirmed.

Claims

1. A body fat accumulation inhibitor containing oenothein B represented by the following formula (I) in an effective amount per day of 3.38 mg to 8.12 mg: 【Chemistry 1】 G in formula (I) represents a structure of formula (II) below. 【Chemistry 2】

2. 2. The body fat accumulation inhibitor according to claim 1, comprising an extract of a plant of the genus Eucalyptus containing oenothein B.

3. 3. The body fat accumulation inhibitor according to claim 1, wherein the body fat is visceral fat.

4. 3. The body fat accumulation inhibitor according to claim 1, wherein the body fat is liver fat.

5. 3. The body fat accumulation inhibitor according to claim 1, which is in a unit package form for one day.

6. A weight-controlling agent containing oenothein B represented by the following formula (I) in an effective amount per day of 3.38 mg to 8.12 mg: 【Transformation 3】 G in formula (I) represents a structure of formula (II) below. 【Chemistry 4】

7. The body weight suppressant according to claim 6, comprising an extract of a Eucalyptus plant containing oenothein B.

8. The body weight suppressing agent according to claim 6 or 7, which is in a unit package form per day.

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