JP6018817B2 - Fat accumulation inhibitor - Google Patents

Description

  The present invention relates to a fat accumulation inhibitor containing an acidic mucopolysaccharide produced by marine bacteria as an active ingredient.

  In modern lifestyles, there are many occasions of overeating, and furthermore, fat metabolism in the living body is not performed well due to various factors such as stress, disorder of hormone balance, and aging, resulting in abnormal accumulation of fat. Increased body fat and hypertrophy cause obesity and contribute to various lifestyle-related diseases such as diabetes, hypertension, arteriosclerosis, and ischemic heart disease. In addition, with the recent increase in interest in health and beauty, the number of people who want to make their bodies healthy and slim, regardless of age or gender, is increasing. High interest.

  Looking at obesity at the cellular level, the accumulation of body fat is due to the uptake of fat into the fat cells. In other words, it is expected that obesity can be prevented if this decrease in adipocytes can be controlled.

  Conventionally, many anti-obesity agents for eliminating obesity have an effect of suppressing fat accumulation by decomposing accumulated fat. However, anti-obesity agents that show an effect of suppressing fat accumulation by suppressing an increase in the number of fat cells have not been well known.

  Anti-obesity agents that show an effect of suppressing fat accumulation by suppressing an increase in the number of fat cells include peptides (Patent Document 1), mushrooms and plant extracts (Patent Document 2), activated whey (Patent Document 3), It has been proposed that polysaccharide derivatives (Patent Document 4) and the like have a preadipocyte differentiation inhibitory action.

Japanese Unexamined Patent Publication No. 6-293396 JP 2004-75640 A JP 2002-37738 A Japanese Patent No. 4944412 Japanese Patent Application No. 2012-57185

  However, the above-mentioned conventional anti-obesity agents are not effective enough, and there is a possibility that a safety problem may occur when blended to a high concentration where the effect is recognized. Therefore, there has been a demand for a natural and safe fat accumulation inhibitor that exhibits a sufficient fat accumulation inhibitory effect by suppressing an increase in the number of fat cells as a component used in an anti-obesity agent.

  Therefore, the present invention provides a fat accumulation inhibitor that has a fat accumulation inhibitory action from among highly safe natural products produced by marine microorganisms, which have been delayed until now, and uses it as an active ingredient. The purpose is to do.

  In order to solve the above-mentioned problems, the present inventors have conducted extensive research on what has a preadipocyte differentiation inhibitory action among safe polysaccharides produced by marine microorganisms rich in unused resources, Acidic mucopolysaccharides produced by marine bacteria have the effect of inhibiting the accumulation of preadipocytes to suppress fat accumulation, and by using it as an active ingredient, they are effective in inhibiting fat accumulation and preventing or improving obesity. The present inventors have found that a fat accumulation inhibitor can be obtained and have completed the present invention.

  That is, the present invention relates to a fat accumulation inhibitor characterized by containing an acidic mucopolysaccharide produced by marine bacteria or a physiologically acceptable salt or derivative thereof as an active ingredient.

  The fat accumulation inhibitor of the present invention contains the present acidic mucopolysaccharide represented by the following formula (1) or a physiologically acceptable salt or derivative thereof (hereinafter referred to as “the present acidic mucopolysaccharide”) as an active ingredient. It is characterized by doing.

（上記の構造式において、GlcNAcpはピラノース型Ｎ-アセチルグルコサミン残基を、GlcUApはピラノース型グルクロン酸残基を、Gluはグルタミン酸を、ＤはＤ型を、ＬはＬ型を、ｎは分子量が５万より大きいことを示す繰り返しの数をそれぞれ表す。）

(In the above structural formula, GlcNAcp is a pyranose type N-acetylglucosamine residue, GlcUAp is a pyranose type glucuronic acid residue, Glu is glutamic acid, D is D type, L is L type, and n is molecular weight. Each represents the number of repetitions indicating greater than 50,000 .)

  The fat accumulation inhibitor containing the present acidic mucopolysaccharide produced by marine bacteria as an active ingredient suppresses differentiation of preadipocytes into adipocytes without showing cytotoxicity to the preadipocytes.

  Since the fat accumulation inhibitor of the present invention contains the present acidic mucopolysaccharide produced by marine bacteria, it is highly safe and can exhibit an excellent fat accumulation inhibitory action. As an obesity agent, it has utility not found in conventional polysaccharides.

FIG. 1 is a graph showing the effect of inhibiting differentiation of preadipocytes.

  The present invention will be described below with reference to embodiments, but the present invention is not limited to the following embodiments.

  The acidic mucopolysaccharide has a melanin production inhibitory effect on mouse melanoma cells, and its derivative is known to have an antiviral effect. However, there have been reports that it has been used as a fat accumulation inhibitor. Is not known at all.

  In the present invention, the fat accumulation inhibitor is a composition effective for inhibiting fat accumulation and preventing or improving obesity by inhibiting differentiation of preadipocytes. The fat accumulation-suppressing agent of the present invention is a skin external preparation composition or an oral composition, and is used as a cosmetic or quasi-drug lotion, milky lotion, cream, pack, soap and other medicinal cosmetics, and as a pharmaceutical product. It includes oral preparations such as lotions, emulsions, creams, ointments and the like, as well as cosmetic foods and drinks.

The skin external preparation composition for fat accumulation suppression according to the present invention comprises the present acidic mucopolysaccharide as an active ingredient and various components generally used in skin external preparations, such as oils, surfactants, ultraviolet absorbers, alcohols. , Moisturizers, preservatives, bactericides, colorants, fragrances, thickeners, buffering agents, and the like are prepared by appropriately blending the dosage forms within a range not impairing the effects of the present invention.
The oral composition for fat accumulation suppression according to the present invention comprises the present acidic mucopolysaccharide as an active ingredient and various components commonly used in oral compositions, such as excipients, preservatives, It is prepared by blending a coloring agent, a fragrance, and the like as appropriate in accordance with the dosage form as long as the effects of the present invention are not impaired.

  In blending the acidic mucopolysaccharide with the skin external preparation composition for inhibiting fat accumulation according to the present invention, it is preferable to consider the fat accumulation inhibiting action of these compounds and the keratin permeability of the skin. May be added as an active ingredient at least 0.001% by weight or more, preferably about 0.01 to 20.0% by weight. It is not always necessary to isolate and use the active ingredient, and a crude product containing the compound of the present invention can be used as long as the effects of the present invention are not impaired.

The dosage form of the skin external preparation composition for fat accumulation suppression according to the present invention is arbitrary, and may be a solubilizing system such as lotion, an emulsifying system such as emulsion or cream, or an ointment or dispersion. it can.
Moreover, the dosage form of the oral preparation for fat accumulation suppression of this invention is arbitrary, For example, dosage forms, such as a tablet, a capsule, a liquid agent, a syrup agent, a powder agent, a jelly agent, can be taken.
In this way, the desired fat accumulation suppression effect, for example, an external skin preparation, an improvement effect on the local fat accumulation such as face, upper arm and thigh, and an oral preparation, an accumulation improvement effect on the fat accumulation of body fat in the whole body is obtained. An inhibitor is provided.

  The fat accumulation inhibitor of the present invention can significantly suppress the differentiation of preadipocytes into adipocytes, compared to the case where such a fat accumulation inhibitor is not added.

  The fat accumulation inhibitor of the present invention effectively suppresses preadipocyte differentiation, and has both stability and high safety for living bodies. Therefore, it can be effectively used in the pharmaceutical field, food field and cosmetic field where anti-obesity effect is expected. It is particularly effective for the prevention or treatment of diseases caused by lifestyle-related diseases including obesity, diabetes, hypertension, arteriosclerosis, ischemic heart disease, and hyperuricemia. It can also be used for sleep apnea syndrome, lipodystrophy, Graves' ophthalmopathy and the like. Furthermore, it can also be used for the prevention or treatment of various diseases related to differentiation-inducing action of preadipocytes such as skin wrinkles and sagging and complications derived from diabetes.

(Active ingredient)
The fat accumulation inhibitor containing the present acidic mucopolysaccharide as an active ingredient has a PPARγ agonist activation inhibitory action. As the acidic mucopolysaccharide used in the present invention, those prepared by various methods can be used as long as they are purified to such an extent that they can be used as pharmaceuticals. Various methods are known as methods for preparing the present mucopolysaccharide. For example, it can be obtained by collecting and purifying polysaccharides produced by culturing marine microorganisms as sucrose as a carbon source, peptone as a nitrogen source, and seawater containing yeast extract in a medium solidified with agar.

The microorganism used for production of the present acidic mucopolysaccharide can be used without particular limitation as long as it can produce the present acidic mucopolysaccharide . Preferably, marine microorganisms, more preferably marine microorganisms capable of producing the present acidic mucopolysaccharide are used. Specific examples include bacteria belonging to the genus Covetia, and more specifically, strains belonging to the genus Cobecia and deposited with a deposit number of FERM P-21297 or mutants thereof. This strain is a marine bacterium isolated from seawater by the present inventors in the Seto Inland Sea, and its taxonomic characteristics are described in Patent Document 5.

  As a basic medium for culturing microorganisms that produce this acidic mucopolysaccharide, microorganisms capable of producing polysaccharides can grow, and at least a carbon source, a nitrogen source, various inorganic salts, and trace elements are contained. What contains an appropriate amount is used. More preferably, as the basic medium, one capable of growing microorganisms belonging to the genus Cobetia is used. Examples of the carbon source include sugars such as glucose, fructose, galactose, and sucrose, and molasses and molasses. One or two or more carbon sources can be used alone or in combination. Nitrogen sources include compounds such as nitrates and ammonium salts, and natural products such as peptone, yeast extract and amino acids. One or two or more nitrogen sources can be used alone or in combination. Examples of the inorganic salt include phosphate, magnesium salt, potassium salt and the like. One or two or more inorganic salts can be used alone or in combination. In the case of a solid medium, agar is used.

  Culture conditions such as the medium to be used, the pH of the medium, the additive to the medium, and the culture temperature can be set according to the conditions normally used for culturing microorganisms.

  The culture conditions in the present invention are not limited as long as the pH during culture is a range in which microorganisms can grow and produce polysaccharides, but a pH in the range of 6 to 7.5 is usually preferable. The culture temperature is not limited as long as microorganisms grow and produce polysaccharides, but a range of 25 ° C. to 30 ° C. is good for producing polysaccharides. The culture period varies depending on the pH and temperature of the culture, but usually 2 to 5 days is appropriate.

  By culturing microorganisms using the above-described medium and microorganisms using a conventional method, the present acidic mucopolysaccharide, which is an active ingredient of the present invention, is efficiently produced.

  The acidic mucopolysaccharide used in the present invention has a constituent sugar molar ratio of N-acetyl-D-glucosamine: D-glucuronic acid: L-glutamic acid of 2: 1: 1 (molar concentration ratio) and gel filtration chromatography. It is preferable that the average molecular weight measured by lithography is 100 to 1,500,000 with pullulan as a standard. Cellulose acetate membrane electrophoresis or high performance liquid chromatography can be used for the analysis of the constituent components. For analysis of this component, a polysaccharide was hydrolyzed with 2M trifluoroacetic acid (TFA) or 4N-HCl at 100 ° C. for 12 hours, and TFA or HCl was removed with a rotary evaporator as a sample. Analyzes sugars, uronic acids, organic acids, amino acids and amino sugars. In addition to this, an enzymatic method can be used for analysis of constituent organic acids.

  The molecular weight of the present acidic mucopolysaccharide can be measured by gel filtration chromatography. Specifically, high-performance liquid chromatography (manufactured by Shimadzu Corporation) using Asahipak GFA-7M (manufactured by Showa Denko) as a column, 0.1M-NaCl as a mobile phase, and pullulan (Shodex STANDARD with a known molecular weight). KIT P-82 (manufactured by Showa Denko KK) can be measured using a molecular weight retention time standard curve prepared as a standard sample.

(Method for producing active ingredient)
Next, a method for producing the present acidic mucopolysaccharide, which is an active ingredient of the fat accumulation inhibitor of the present invention, will be described with reference to preferred embodiments. In addition, the production method of this acidic mucopolysaccharide is not limited to the following production method.
The method for producing the present acidic mucopolysaccharide as one preferred embodiment includes (a) a step of culturing a microorganism in a medium to produce a polysaccharide, and (b) a step of extracting and recovering the produced present acidic mucopolysaccharide. And have.

Subsequently, the above-described embodiment will be described in detail for each step.
It is desirable to use a medium suitable for the production of the present acidic mucopolysaccharide, which is an active ingredient of the above-described fat accumulation inhibitor of the present invention. In this case, sucrose is used as the carbon source, peptone is used as the nitrogen source, and yeast extract is used. More desirable.
(A) Step of culturing microorganisms in medium to produce polysaccharides The microorganisms are cultured using the medium prepared as described above to produce the desired polysaccharides, and the present acidic mucopolysaccharides are obtained. Therefore, it is preferable to use a bacterium belonging to the genus Cobetia as a microorganism. More preferably, it is desirable to use a strain belonging to the genus Cobetia and deposited with a deposit number of FERM P-21297 or a mutant thereof. The acidic mucopolysaccharide can be efficiently produced by using the strain or a mutant thereof as a microorganism.
And it becomes possible to obtain this acidic mucopolysaccharide of high purity by a high yield by passing through the extraction and collection | recovery process demonstrated below.

(B) Step of extracting and recovering the produced predetermined polysaccharide As a method for extracting the acidic mucopolysaccharide from the culture solution obtained by the above production method, a method known in the art should be used. Can do. For example, after sterilizing the culture solution as it is or at a high temperature, the microbial cells are removed by centrifugation, and after adding or concentrating this, add 2-3 times the amount of ethanol, isopropanol, or acetone, This causes precipitation. After this precipitate is dissolved again in water or 1-15% sodium chloride solution, precipitation with alcohol or the like is repeated 2-3 times, dialyzed with water, and using a spray dryer or freeze dryer, etc. The acidic mucopolysaccharide is obtained by drying. In addition, electrodialysis and ultrafiltration can be used. For further purification, various types of chromatography such as ion exchange and gel filtration, precipitation with quaternary ammonium salts, salting out, and the like can be used.

  Thus, the acidic mucopolysaccharide will be produced and recovered. The acidic mucopolysaccharide obtained by the present invention can be used for various applications without any particular limitation, but is preferably used as the above-described fat accumulation inhibitor.

（上記の構造式において、GlcNAcpはピラノース型Ｎ-アセチルグルコサミン残基を、GlcUApはピラノース型グルクロン酸残基を、Gluはグルタミン酸を、ＤはＤ型を、ＬはＬ型を、ｎは分子量が５万より大きいことを示す繰り返しの数をそれぞれ表す。） Here, the present acidic mucopolysaccharide has the following structural units.

(In the above structural formula, GlcNAcp is a pyranose type N-acetylglucosamine residue, GlcUAp is a pyranose type glucuronic acid residue, Glu is glutamic acid, D is D type, L is L type, and n is molecular weight. Each represents the number of repetitions indicating greater than 50,000 .)

In the present invention, at least 0.001% by weight or more, preferably 0.01 to 20% by weight of the present acidic mucopolysaccharide is added to the fat accumulation inhibitor as an active ingredient.
The fat accumulation inhibitor containing this acidic mucopolysaccharide as an active ingredient can be made into a suitable form such as cream, emulsion, lotion, etc. by using a commonly used skin external preparation base material. . Furthermore, this fat accumulation inhibitor should contain arbitrary additives such as ultraviolet absorbers, ultraviolet scattering agents, melanin synthesis inhibitors such as arbutin, other medicinal ingredients, thickeners, plasticizers, colorants, and fragrances. Can do. The acidic mucopolysaccharide, which is an active ingredient of the fat accumulation inhibitor of the present invention, is neither toxic nor irritating to the skin and has no side effects.

  The acidic mucopolysaccharide has a fat accumulation-inhibiting action and is excellent in safety, so it is suitable for blending into health foods and drinks, functional foods and drinks, etc. It is.

  When the present acidic mucopolysaccharides are blended in cosmetic foods and drinks, the amount of active ingredients in them can be appropriately changed in consideration of the purpose of use, symptoms, sex, etc. In consideration of the correct intake, it is preferable that the intake of the present acidic mucopolysaccharide per day for an adult is about 1 to 1000 mg.

  The cosmetic food / beverage product of the present invention may be a blend of the present acidic mucopolysaccharides in any food / beverage product that does not impede its activity, or a nutritional supplement food / drink comprising the present acidic mucopolysaccharides as the main component. It may be a product.

  The fat accumulation inhibitor, the skin external preparation and the cosmetic food and drink of the present invention described above are preferably applied to humans. However, as long as each effect is exerted, it is applied to animals other than humans. It can also be applied to.

  EXAMPLES Next, although an Example is given and this invention is demonstrated in more detail, this invention is not restrict | limited at all to these Examples. Unless otherwise specified, percentages (%) are based on weight.

Example 1
A medium prepared with seawater having a composition of 0.5% peptone, 0.1% yeast extract and 3% sucrose was sterilized in an autoclave at a temperature of 121 ° C. for 15 minutes, and the strain (FERM P-21297) From the slant culture, one platinum loop is inoculated into the above-mentioned sterilized medium (10 ml) in a test tube, and statically cultured at a temperature of 25 ° C. for 24 hours, and then this preculture solution is placed in a 500 ml Erlenmeyer flask. The medium was inoculated into 100 ml (121 ° C., sterilized for 15 minutes) and subjected to stationary culture at 25 ° C. for 3 days. After culturing, the culture broth is centrifuged, filtered through GF-75 filter paper (manufactured by Advantec) using a filter aid (Radiolite # 500), and the hollow fiber having a molecular weight of 50,000 cut from the culture filtrate from which the cells are removed. The polymer fraction obtained by a membrane filtration apparatus equipped with a UF membrane module (manufactured by Spectrum) was concentrated, desalted and recovered within 5 to 6 hours, treated with activated carbon, and powdered by freeze drying. The membrane filtration apparatus used was SYLS-SB04 manufactured by Toyobo Engineering.
The polysaccharide fraction obtained in this manner was confirmed by homogeneity using cellulose acetate membrane electrophoresis, and by using DEAE-cellulose ion exchange column chromatographic analysis, chemical analysis, and nuclear magnetic resonance analysis, The mucopolysaccharide was confirmed.

(Example 2)
Until the preculture, the same treatment as in Example 1 was performed, and then this preculture was inoculated into a 500 ml Erlenmeyer flask to 100 ml of sterilized medium (121 ° C, 15 minutes) prepared from seawater having the above composition, and 25 ° C. The shaking culture was performed at the temperature of 3 days. Next, after centrifuging the culture solution, it was filtered through GF-75 filter paper (manufactured by Advantec) using a filter aid (Radiolite # 500), and the hollow fiber UF membrane having a molecular weight of 50,000 cut from the culture filtrate from which the cells were removed. The polymer fraction obtained by a membrane filtration apparatus equipped with a module (manufactured by Spectrum) was concentrated, desalted and recovered within 5 to 6 hours, treated with activated carbon, and pulverized by freeze drying. The membrane filtration apparatus used was SYLS-SB04 manufactured by Toyobo Engineering. The polysaccharide fraction obtained in this manner was confirmed by homogeneity using cellulose acetate membrane electrophoresis, and by using DEAE-cellulose ion exchange column chromatographic analysis, chemical analysis, and nuclear magnetic resonance analysis, The mucopolysaccharide was confirmed.

Example 3
Until the pre-culture, the same treatment as in Example 1 was performed, and 250 ml of agar plate medium obtained by adding 1.5% of agar to the medium described in Example 2 was spread on a flat plate (18 × 26 cm) and smeared with the pre-culture solution. The culture was performed at a temperature of 25 ° C. for 4 days. The sticky matter generated on the surface of the agar plate is scraped off, suspended in 1% phenol solution, centrifuged, and filtered through GF-75 filter paper using a filter aid (Radiolite # 500) to remove the cells. Fraction precipitated by adding ethanol to the supernatant was collected, dissolved in water, ethanol added again to collect the precipitated fraction, dissolved in water, and dialyzed. Subsequently, it was treated with activated carbon, and a polysaccharide fraction was obtained by freeze-drying. In addition, as a practical purification level, a polymer fraction obtained from a membrane filtrate equipped with a hollow fiber UF membrane module (Spectrum) having a molecular weight of 50,000 cut from the culture filtrate is obtained within 5 to 6 hours. Concentrated, desalted and recovered, treated with activated carbon, and powdered by lyophilization. The membrane filtration apparatus used was SYLS-SB04 manufactured by Toyobo Engineering. The polysaccharide fraction obtained in this manner was confirmed by homogeneity using cellulose acetate membrane electrophoresis, and by using DEAE-cellulose ion exchange column chromatographic analysis, chemical analysis, and nuclear magnetic resonance analysis, The mucopolysaccharide was confirmed.

Example 4
(Fat accumulation inhibitor)
The in vitro differentiation inhibitory activity of human subcutaneous preadipocytes into adipocytes was examined. Measurement of the fat accumulation inhibitory action of human subcutaneous fat cells was performed by the following method according to the protocol of Zen-Bio, Inc. (USA). Using this acidic mucopolysaccharide obtained in Example 1, the effect of inhibiting fat accumulation in human subcutaneous adipocytes was examined, and the inhibition rate in the sample addition system was determined as compared with the case of no sample addition. The adipocyte fat accumulation-inhibiting action is based on the concentration of triglyceride accumulated in adipocytes as an index. The effect of the addition of the PPARγ agonist and the absence of this sample (control) and the PPARγ agonist and TNF-α (tumor necrosis factor-α) It compared with the inhibitory effect (P) by simultaneous addition. The lower the fat accumulation amount, the lower the differentiation of preadipocytes.
The results are shown in FIG. 1 (mean value ± SE).

  As is clear from FIG. 1, differentiation induction was observed in the control in which the PPARγ agonist was added and the acidic mucopolysaccharide was not added. On the other hand, it was confirmed that the addition of the acidic mucopolysaccharide suppresses differentiation induction in a concentration-dependent manner and has an action of suppressing fat accumulation in human subcutaneous fat cells. Moreover, compared with the inhibitory effect (P) by simultaneous addition of PPARγ agonist and TNF-α known as a preadipocyte differentiation inhibitory substance via PPARγ agonist, the acidic mucopolysaccharide was added at 1000 μg / ml. When added, the suppression value was about 1/2. At the same concentration, there was no change in cell morphology associated with cytotoxicity.

  The fat accumulation inhibitor according to the present invention is used in various dosage forms. As an example, a serum, a cream, a milky lotion, a soap, an emulsified foundation using the acidic mucopolysaccharide obtained in Example 1 and Formulation examples of bath preparations will be described below as Formulation Examples 1 to 6, and formulation examples of cosmetic foods and beverages as Formulation Examples 7 and 8.

Formulation Example 1 (Cosmetic liquid)
A cosmetic solution was prepared in the usual manner using the following components.

Formulation Example 2 (Cream)
The following component A and component B were heated and dissolved to prepare A solution and B solution, respectively. The B solution was added to the A solution to emulsify, and cooled with stirring to prepare a cream.

Formulation Example 3 (Emulsion)
The following component A and component B were heated and dissolved to prepare A solution and B solution, respectively. The B solution was added to the A solution to emulsify, and cooled with stirring to prepare an emulsion.

Formulation example 4 (soap)
The soap was manufactured by mixing the following components according to a conventional method for manufacturing soap.

Formulation Example 5 (Emulsification Foundation)
The following component A is sufficiently mixed and pulverized into powder part A, component B is liquid B, and component C is liquid C. After the liquid C is heated and stirred, A is added and homomixed, and the liquid B which has been heated and mixed is added and homomixed. While stirring, the mixture was cooled to room temperature to prepare an emulsified foundation.

Formulation Example 6 (Bath Agent)
A bath preparation was prepared by a conventional method using the following components.

Formulation Example 7 (tablet)
The following component A was sifted and mixed, and then component B was added and mixed. Thereafter, tableting was performed by a conventional method to obtain a tablet having a total amount of 600 mg.

Formulation example 8 (soft drink)
A soft drink was prepared by the conventional method using the following components.

The above-mentioned FERM P-21297 strain used in the present example is the center of Japan National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center 1-5-1, Higashi 1-chome, Tsukuba, Ibaraki, Japan 305-8586 Japan And deposited under the accession number FERM P-21297 on May 16, 2007.

Claims (3)

A fat accumulation inhibitor comprising as an active ingredient an acidic mucopolysaccharide having a structure represented by the following formula (1) or a physiologically acceptable salt thereof .

(In the above structural formula, GlcNAcp is a pyranose type N-acetylglucosamine residue, GlcUAp is a pyranose type glucuronic acid residue, Glu is glutamic acid, D is D type, L is L type, and n is molecular weight. Each represents the number of repetitions indicating greater than 50,000 .)   The fat accumulation inhibitor according to claim 1, which is an external preparation for skin. The fat accumulation inhibitor according to claim 1, which is a beauty food or drink.

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