JP2003321351A - Lipase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a lipase inhibitor originating from a natural material which can be added in a food and drink, a cosmetic and a therapeutic agent for dermatosis as the lipase inhibitor having high safety, excellent heat resistance, taste and water-solubility. <P>SOLUTION: The lipase inhibitor contains a dihydrochalcone compound indicated in general formula (1) and the food and drink, the cosmetic and the therapeutic agent for dermatosis contain the lipase inhibitor. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a lipase inhibitor containing, as an active ingredient, a specific dihydrochalcone compound which can be used in foods, drinks, cosmetics or therapeutic agents for skin diseases.

[0002]

In the human body, lipase is a digestive enzyme secreted by the pancreas, and lipids taken orally are hydrolyzed into glycerin and free fatty acids by the action of lipase and absorbed and transferred into the body. Lipids have particularly high energy and tend to increase fat intake in Japanese in recent years, which is one of the causes of causing lifestyle-related diseases such as obesity, hyperlipidemia and diabetes. Also, the lipase produced by microorganisms decomposes the contained lipids into glycerin and free fatty acids when mixed in foods, cosmetics, etc., causing deterioration such as rancid odor and reducing its value as a product. . With lipase produced by microorganisms that are resident in human skin, lipids on the skin are decomposed into glycerin and free fatty acids, and some of these free fatty acids have an adverse effect on the skin, resulting in skin diseases such as acne. It is known that the above causes the free fatty acid to be further decomposed and causes the body odor. In order to solve such problems caused by lipase, lipase inhibitors that inhibit lipase have been developed.

As a lipase inhibitor, extracts of various crude drugs have hitherto been disclosed in JP-A-64-90131.
No. 602387, an extract of spices is disclosed in Japanese Patent Laid-Open No. 2001-2001.
It is disclosed in Japanese Patent No. 120237. However,
Many of the crude drugs and spices described in the official gazette are difficult to obtain and expensive. Further, lipase inhibitors derived from these extracts have taste qualities such as bitterness and astringency, and the addition amount may be limited when added to foods and drinks, and it is difficult to obtain sufficient effects. Bell pepper, pumpkin, shimeji, maitake,
Water extracts of hijiki, green tea, black tea, and oolong tea are disclosed as lipase inhibitors in JP-A-3-219872. Also, a lipid digestion absorption-suppressing food containing epicatechin gallate and / or epigallocatechin gallate contained in green tea is disclosed in JP-A-3-228664, and a lipase inhibitor containing various flavonoids is disclosed in Patent Document 2.
It is disclosed in JP-A-598873 and JP-A-9-143070. However, lipase inhibitors based on these water extracts such as tea and flavonoids have unique bitterness and astringency, and some have extremely low water solubility, and the addition amount is limited when added to foods and drinks. It may be difficult to obtain a sufficient effect. As described above, many lipase inhibitors have been developed so far, but they are sufficiently satisfactory in terms of safety, taste, and water solubility, which are important when added to foods and drinks, cosmetics, and skin disease therapeutic agents. What can be done is not yet developed.

[0004]

DISCLOSURE OF THE INVENTION The object of the present invention is to solve the above problems and to provide foods, cosmetics and skin diseases as lipase inhibitors which are highly safe and have excellent heat resistance, taste and water solubility. To provide a lipase inhibitor derived from a natural product that can be added to a therapeutic agent, and ingested as a food or drink,
It is to develop a substance capable of preventing obesity and hyperlipidemia by suppressing absorption of lipids in the body.
Another object is to develop a substance capable of preventing lipid deterioration in foods and drinks and cosmetics caused by lipase, and preventing body odor and skin diseases caused by lipase.

[0005]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies in order to solve the above problems and achieve the object, and as a result, have a lipase inhibitory action on specific dihydrochalcone compounds derived from natural products. Therefore, the present invention has been completed based on such findings.

That is, the present invention is based on the general formula (1)

[Chemical 2] (In the formula, R ₁ and R ₂ are each independently a hydrogen atom,
It represents a hydroxyl group or an alkoxy group, and R ₃ represents a hydrogen atom or a sugar residue. And a dihydrochalcone compound represented by the formula (1) as an active ingredient.

Further, the present invention relates to foods and drinks, cosmetics and therapeutic agents for skin diseases, which contain the above lipase inhibitor.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION R ₁ and R in the general formula (1)
₂ independently represents a hydrogen atom, a hydroxyl group or an alkoxy group. The alkyl part of the alkoxy group has 1 to 1 carbon atoms.
6 straight-chain or branched lower alkyl, such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, sec-butyl, tert-butyl,
n-pentyl, i-pentyl, 2-methylbutyl, se
Examples thereof include c-pentyl, 1,2-dimethylpropyl, neo-pentyl, 1-ethylpropyl, 1,1-dimethylpropyl and hexyl. Preferably, R ₁ and R ₂ each independently represent a hydrogen atom, a hydroxyl group, a methoxy group or an ethoxy group, and more preferably each independently represent a hydrogen atom, a hydroxyl group or a methoxy group.

R ₃ in the general formula (1) represents a hydrogen atom or a sugar residue. Examples of the sugar residue include glucoside, mannoside, galactoside, rhamnoside, fucoside, xyloside, arabinoside, rutinoside or neohesperidoside, and isomers thereof. R ₃ is preferably a hydrogen atom, glucoside, rutinoside or neohesperidoside, and particularly preferably a hydrogen atom.

Specific examples of the dihydrochalcone compound represented by the general formula (1) to be used as the active ingredient of the lipase inhibitor of the present invention include hesperetin dihydrochalcone, naringenin dihydrochalcone, eriodictyol dihydrochalcone, isosacranetin dihydro. Chalcone, hesperidin dihydrochalcone, eriocitrin dihydrochalcone, neohesperidin dihydrochalcone, naringin dihydrochalcone, neo eriocitrin dihydrochalcone, pohn syringe hydrochalcone, hesperetin dihydrochalcone glucoside or isosacranetin dihydrochalcone glucoside, preferably hesperetin Dihydrochalcone, naringenin dihydrochalcone,
Mention may be made of eriodictyol dihydrochalcone or isosakuranetin dihydrochalcone, particularly preferably hesperetin dihydrochalcone, eriodictythiol dihydrochalcone or isosakuranetin dihydrochalcone.
Table 1 shows each substituent in the general formula (1) of the above active ingredient.
Shown in.

[0011]

[Table 1]

The dihydrochalcone compound according to the present invention can be produced by reducing the flavanone glycoside mainly contained in citrus fruits. Furthermore, it can be produced by selectively hydrolyzing sugar chains.

As citrus fruits containing flavanone glycosides, there are unshiu mandarin orange, red sea bream, hassaku, natsuki mandarin orange, yokan, orange, bitter orange, lemon, grapefruit, yuzu, lime, navel, ponkan,
There are bergamot, sweety, buntan, and the like. These may be used alone in the extraction, or two or more kinds may be mixed and used.

When the flavanone glycoside is extracted from citrus fruits, the citrus fruits may be in the form of, for example, fruit juice, pulp, scallions, peels, squeezed lees, etc., which may be used alone or in appropriate combination. be able to.

For extraction from citrus fruits, water, heated water, alkaline water, organic solvents (eg, methanol, ethanol, acetone, etc.) or a mixture thereof can be used. The extraction temperature is 0 to 100 ° C., preferably 40 to 80
℃. The extract can be used as a crude flavanone glycoside as it is, but is purified if necessary before use.
For example, after concentration under reduced pressure, treatment with an ion exchange resin, membrane treatment, purification treatment such as chromatography is performed to collect active fractions, and further crystallization and lyophilization treatment are performed,
A purified powder of flavanone glycoside is obtained.

When an alkaline solution is added to the obtained crude flavanone glycoside or the purified product of flavanone glycoside and mixed in a hydrogen atmosphere in the presence of a catalyst, the flavanone glycoside is reduced to give dihydrochalcone glycoside. Converted to body. The crude dihydrochalcone glycoside having the lipase inhibitory activity thus obtained can be obtained as a purified product of the dihydrochalcone glycoside having the lipase inhibiting activity by the same purification treatment as that for flavanone glycosides.

The crude dihydrochalcone glycoside or the purified product of the dihydrochalcone glycoside obtained here is further bound to a sugar chain such as a mineral acid such as hydrochloric acid or sulfuric acid, or β-glucosidase, hesperidinase, narindinase or the like. By selectively hydrolyzing with an enzyme, it is converted into a crude dihydrochalcone compound having a lipase inhibitory action. The obtained crude dihydrochalcone compound having a lipase inhibitory effect can be obtained by a purification treatment similar to that of flavanone glycoside to obtain a purified product of the dihydrochalcone compound having a lipase inhibitory effect.

Further, as a method for obtaining a dihydrochalcone compound having a lipase inhibitory action, the obtained crude flavanone glycoside or the purified product of flavanone glycoside is a mineral acid such as hydrochloric acid or sulfuric acid, or β-glucosidase, hesperidinase, naringinase. After selectively hydrolyzing with an enzyme such as, an alkali solution is added and mixed in a hydrogen atmosphere in the presence of a catalyst to convert into a crude dihydrochalcone compound having a lipase inhibitory action. The obtained crude dihydrochalcone compound having a lipase inhibitory effect can be obtained by a purification treatment similar to that of flavanone glycoside to obtain a purified product of the dihydrochalcone compound having a lipase inhibitory effect.

Further, the dihydrochalcone compound having a lipase inhibitory action includes not only the above-mentioned method of extracting flavanone glycosides from citrus fruits and combining the reduction reaction and the hydrolysis reaction, but also the dihydrochalcone compound having a lipase inhibiting action. It is also possible to extract from plants. For example, the naringenin dihydrochalcone and the eriodictythiol dihydrochalcone are Kalm belonging to the Ericaceae family.
ia latifolia, isosakranetin dihydrochalcone belongs to the pearl nut family Iryanthera sagotiana, naringenin dihydrochalcone glucoside belongs to the Cypress family Symp
locos microcalyx, eriodictyol dihydrochalcone glucoside, belongs to the family Alantrifolia Balanophora to
Contained in biracola. Water, heated water, from these plants
Alkaline water, an organic solvent (for example, methanol, ethanol, acetone, etc.) or a suitable combination of them to extract a dihydrochalcone compound having a lipase inhibitory action, and if necessary, a hydrolysis reaction is combined and treated with an ion exchange resin, A purified product of a dihydrochalcone compound having a lipase inhibitory effect can be obtained by performing crystallization or freeze-drying treatment after purification treatment such as membrane treatment and chromatography.

The dihydrochalcone compound used in the present invention is a highly safe lipase inhibitor derived from a natural product, and also has high heat resistance, excellent water solubility, and no bitterness or astringency. Without adversely affecting the taste
It can be added to food and drink and can exert a desired lipase inhibitory action.

Therefore, it is expected that daily intake of the compound as a food or drink can suppress absorption of lipids into the body after intake of lipids and prevent obesity and hyperlipidemia. .

Further, when microorganisms are mixed in foods and drinks and cosmetics containing lipids, it is expected that the decomposition of lipids by lipase produced by the microorganisms can be suppressed and the deterioration of lipids such as rancid odor can be suppressed. It

Furthermore, on the skin, it is expected that the decomposition of sebum by lipase produced by skin-resident bacteria can be suppressed, and the body odor and skin diseases caused by the released fatty acids can be suppressed.

The lipase inhibitor of the present invention is, for example, oils and fats, margarine, butter, lard, seasonings, creams, dairy products, meats, seafood, eggs, cakes, chocolate, ice cream, coffee, cocoa, Black tea, milk tea, flavor tea, soft drink, carbonated drink,
It can be added to various foods and drinks such as lactic acid bacteria drinks, green tea, oolong tea, nutritional drinks, jams, yogurts, steamed buns, jellies, candies, tablets, confectionery, health foods and processed foods. The amount added at this time is not particularly limited as long as the effect expected by the compound can be effectively exhibited, but the total amount is 0.000.
1 to 10%, preferably 0.001 to 5%, more preferably 0.01 to 2% is suitable. Further, the lipase inhibitor of the present invention can be ingested in the form of tablets, capsules, granules, liquids and the like.

Further, the lipase inhibitor of the present invention includes, for example, moisturizing cosmetics, skin roughness preventing cosmetics, makeup cosmetics, dandruff preventing cosmetics, hair-growth cosmetics, itch preventing cosmetics, cleaning cosmetics, sunscreen preventing cosmetics, body odor preventing cosmetics, It can be added to cosmetics such as fragrance cosmetics and oral care products. The addition amount at this time is not particularly limited as long as the effect expected by the compound can be effectively exhibited, and is, for example, 0.0001 to 5% of the total amount, preferably 0.001. ~ 2
%, And more preferably about 0.01 to 1%. When the lipase inhibitor of the present invention is added to cosmetics, other active ingredients, pharmaceutically acceptable excipients, dyes, fragrances and the like can be appropriately combined and used. Further, the form of the product is also arbitrary, and for example, any of liquid form, powder form, cream form and the like is possible.

The lipase inhibitor of the present invention can be added to a therapeutic agent for skin diseases such as a therapeutic agent for acne and a therapeutic agent for dermatitis. The amount added at this time is not particularly limited as long as the effect expected by the compound can be effectively exhibited, and is, for example, 0.000% of the total amount.
1 to 5%, preferably 0.001 to 2%, more preferably 0.01 to 1% is suitable. When the lipase inhibitor of the present invention is added to the therapeutic agent for skin diseases, other active ingredients, pharmaceutically acceptable excipients, dyes, fragrances and the like can be appropriately combined and used. Further, the form of the product is also arbitrary, and for example, any of liquid form, powder form, cream form and the like is possible.

[0027]

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

Production Example 1: Preparation of Naringin dihydrochalcone 10 kg of grapefruit peel was crushed with a homogenizer, 100 L of warm water was added, and extraction treatment was carried out at 70 ° C for 1 hour. Next, the extract was concentrated with an evaporator, and the concentrate was refrigerated and stored at 4 ° C. to precipitate crystals. The crystals were separated by filtration and dried under reduced pressure to obtain about 50 g of crude crystals of naringin, which is one of flavanone glycosides. Then, 50 g of crude crystals of naringin were mixed with 1 L of 10% sodium hydroxide solution and 5
% Palladium carbon catalyst (5 g) was added, and the reduction reaction was carried out at room temperature and 1 MPa under hydrogen pressure for 1 hour. After the reduction reaction, the catalyst was removed from the reaction solution, hydrochloric acid was added to the reaction solution for neutralization, and the neutralized solution was refrigerated at 4 ° C. to precipitate crystals. The crystals were separated by filtration and dried under reduced pressure to obtain about 45 g of crude crystals of naringin dihydrochalcone.

Production Example 2: Preparation of Naringenin dihydrochalcone To 1 g of a 2M hydrochloric acid solution was added 45 g of the crude crystals of naringin dihydrochalcone obtained in Production Example 1 and a hydrolysis reaction was carried out at 80 ° C for 2 hours. After the hydrolysis reaction, sodium hydroxide was added to the reaction solution for neutralization, and the neutralized solution was refrigerated at 4 ° C. to precipitate crystals. The crystals were separated by filtration and dried under reduced pressure to obtain about 20 g of crystals of naringenin dihydrochalcone.

Production Example 3: Preparation of hesperetin dihydrochalcone glucoside To 50 g of commercially available hesperidin crystals, 1 L of 10% sodium hydroxide solution and 3 g of 5% palladium carbon catalyst were added, and reduction reaction was carried out at room temperature and 1 MPa of hydrogen pressure for 1 hour. I went. After the reduction reaction, the catalyst was removed from the reaction solution, hydrochloric acid was added to the reaction solution to neutralize, and the neutralized solution was packed with an adsorption resin column (1 L of Diaion HP20; manufactured by Mitsubishi Chemical Corporation). Shed to. After washing the column by pouring 3 L of water, elution was performed with 5 L of 25% ethanol. The eluate was concentrated by an evaporator and freeze-dried to obtain about 45 g of hesperidin dihydrochalcone powder. To 45 g of hesperidin dihydrochalcone, 1 L of 1M hydrochloric acid solution was added,
The hydrolysis reaction was carried out at 0 ° C. for 1 hour. After the hydrolysis reaction,
Sodium hydroxide was added to the reaction solution for neutralization, and the neutralized solution was passed through the adsorption resin column. After washing the column by pouring 3 L of water, it was eluted with 5 L of 30% ethanol. The eluate was concentrated with an evaporator, and the concentrate was refrigerated at 4 ° C. to precipitate crystals. The crystals were separated by filtration and dried under reduced pressure to obtain about 20 g of hesperetin dihydrochalcone glucoside crystals.

Example 1 Measurement of Porcine Pancreatic Lipase Inhibitory Activity With respect to the prepared compound, the inhibitory activity against lipase was measured by the following method using a commercially available pig pancreatic lipase (manufactured by Sigma). It was compared with the existing lipase inhibitor epigallocatechin gallate.

(Method for measuring lipase inhibitory activity) 4-methylumbelliferyl oleate (4-MeUm) as a substrate
bO) was used to measure the fluorescence of 4-methylumbelliferone (4-MeUmb) released by lipase, and the lipase inhibitory activity was evaluated. 0.1 mM 4-M
100 μl of eUmbO suspension solution, 40 μl of McIlvaine buffer (pH 7.4), 10 μl of dimethyl sulfoxide (DMSO) solution in which the sample was dissolved, 79 μg /
50 μl of ml porcine pancreatic lipase solution was added and reacted at 37 ° C. for 20 minutes. After stopping the enzymatic reaction by adding 1 ml of 0.1 M hydrochloric acid, 2 ml of 0.1 M sodium citrate
Added to bring pH to about 4.3. 4-Me has been released
Umb fluorescence (excitation wavelength 320 nm, fluorescence wavelength 450
nm) was quantified with a fluorimetric detector. Sample DM for control
DMSO was added instead of SO solution. Also, 4-M
In order to remove the influence of 4-MeUmb contained in the eUmbO solution, water was added to the blank instead of the lipase solution. Inhibition rate (%) = {(A−C) − (B−C)} / (A−
C) × 100 where A: free 4-MeUmb amount of control solution, B: free 4-MeUmb amount of sample solution, C: free 4-MeUmb amount of blank
The amount of MeUmb and the inhibitory activity were shown at the final concentration (IC ₅₀ ) ppm of each sample, which is a dihydrochalcone compound that inhibits the lipase activity of the control without addition of the sample by 50%. The results of the porcine pancreatic lipase inhibitory activity are shown in Table 2.

[0033]

[Table 2]

As is clear from Table 2, hesperetin dihydrochalcone, naringenin dihydrochalcone, eriodictyol dihydrochalcone and isosacranetin dihydrochalcone have superior porcine pancreatic lipase inhibitory activity to epigallocatechin gallate and lipids. Can be expected to have an effect of suppressing absorption in the body.

Example 2 Measurement of Microbial Lipase Inhibitory Activity 0.28 μg of porcine pancreatic lipase solution in Example 1
/ Ml Microorganism (Candida rugosa) -derived lipase was changed and measured in the same manner. The results of the lipase inhibitory activity from Candida rugosa are shown in Table 3.

[0036]

[Table 3]

As is clear from Table 3, hesperetin dihydrochalcone, naringenin dihydrochalcone, eriodictythiol dihydrochalcone, isosakuranetin dihydrochalcone, hesperidin dihydrochalcone, eriocitrin dihydrochalcone, neohesperidin dihydrochalcone, naringin dihydrochalcone, Neoeriocitrin dihydrochalcone, pohn syringe hydrochalcone, hesperetin dihydrochalcone glucoside, and isosacranetin dihydrochalcone glucoside have superior microbial-derived lipase inhibitory activity to epigallocatechin gallate and suppress lipid degradation and sebum degradation by microorganisms. A suppression effect can be expected.

Formulation Example 1 Production of Olive Oil 2 kg of hesperetin dihydrochalcone per 1 kg of olive oil
Was dissolved to produce olive oil.

Formulation Example 2: Production of Butter Cream 120 g of sugar, 100 g of lactose, 200 g of skim milk powder, 1 g of hesperetin dihydrochalcone, and 80 g of water were mixed, and the mixture was heated and dissolved at about 60 ° C. to prepare a mixed solution. Next, 500 g of margarine and 1 g of vanilla essence were mixed with the mixed solution to produce a vanilla-flavored butter cream.

Formulation Example 3: Production of milk tea 21 g of fresh cream (47% fat), 40 g of sugar, 1 g of emulsifier, 350 g of black tea extract, 586.5 g of water, 1.5 g of naringenin dihydrochalcone were mixed and homogenized.
After adjusting the pH to 6.8 using baking soda, heat sterilization was performed to produce milk tea.

Formulation Example 4: Production of tablets 10 g of hesperetin dihydrochalcone, 68 g of lactose, 14 g of crystalline cellulose, 4 of carboxymethylcellulose 4
g and 4 g of magnesium stearate were uniformly mixed, water was added and kneaded, and then granulated by an extrusion granulation base granulator, dried and sized to prepare granules. Then, tablets were produced with a single-shot tableting machine.

Formulation Example 5: Production of sardine surimi 250 g of sardine sardine was minced, and 10 g of ginger squeezed juice, 15 g of red miso, 5 g of flour, and 5 g of naringenin dihydrochalcone were uniformly mixed to prepare a sardine surimi.

Prescription example 6: Production of ingredients for gyoza 250 g ground pork, 300 g Chinese cabbage, 100 boiled bamboo shoots
g, 30 g of leeks, and 10 g of ginger were each chopped, soy sauce 15 g, sesame oil 5 g, and naringenin dihydrochalcone 10 g were uniformly mixed to prepare an ingredient for gyoza.

Formulation Example 7: Production of skin cream A skin cream containing the dihydrochalcone compound according to the present invention as an active ingredient was prepared according to the formulation shown in Table 4. That is, the components A and B were weighed, and the components were heated and dissolved to be uniform. The temperature of the melt was 80 ° C. Next, the B component is gradually added to the A component with stirring to emulsify, and then cooled with stirring to a temperature of 50 ° C.
The component C was added when the following was reached. After the C component was added, the temperature was further cooled to 30 ° C. to obtain a product.

[0045]

[Table 4]

[0046]

INDUSTRIAL APPLICABILITY Since the specific dihydrochalcone compound used as an active ingredient of the lipase inhibitor in the present invention is derived from a natural product, it is highly safe for human body and has heat resistance, taste and water solubility. Therefore, it is expected that daily intake as a food or drink can suppress lipid absorption in the body and prevent obesity and hyperlipidemia. Further, it is expected to suppress the deterioration of lipids in foods and drinks and cosmetics due to microbial lipase. Furthermore, body odor caused by lipase produced by skin indigenous bacteria,
It is expected to suppress skin diseases.

Front page continuation (51) Int.Cl. ⁷ identification code FI theme code (reference) A61K 7/48 A61K 31/7032 31/7032 A61P 17/00 A61P 17/00 43/00 111 43/00 111 C12N 9 / 99 C12N 9/99 A23L 2/00 FF term (reference) 4B017 LC03 LK06 LL09 4B018 LB08 MD08 ME14 4C083 AA122 AC012 AC022 AC102 AC122 AC211 AC212 AC442 AC482 AD391 AD392 BB51 CC02 DD31 EE10 EE13 4C086 MA16 MA01 MA34 MA08 MA52 MA63 NA14 ZA89 ZC20 4C206 AA02 CB19 EA01 KA01 MA01 MA04 MA36 MA48 MA54 MA55 MA72 MA83 NA14 ZA89 ZC20

Claims (6)

[Claims] 1. A compound represented by the general formula (1): (In the formula, R ₁ and R ₂ are each independently a hydrogen atom,
It represents a hydroxyl group or an alkoxy group, and R ₃ represents a hydrogen atom or a sugar residue. ) A lipase inhibitor comprising a dihydrochalcone compound represented by: 2. In the dihydrochalcone compound represented by the general formula (1), R ₁ and R ₂ are each independently a hydrogen atom, a hydroxyl group or a methoxy group, and R ₃ is a hydrogen atom, a glucoside, a rutinoside or The lipase inhibitor according to claim 1, which is neohesperidoside. 3. The dihydrochalcone compound represented by the general formula (1) is hesperetin dihydrochalcone, naringenin dihydrochalcone, eriodictyol dihydrochalcone, isosacranetin dihydrochalcone, hesperidin dihydrochalcone, eriocitrin dihydrochalcone, neo. The lipase inhibitor according to claim 1 or 2, which is hesperidin dihydrochalcone, naringin dihydrochalcone, neoeriocitrin dihydrochalcone, ponsyryne hydrochalcone, hesperetin dihydrochalcone glucoside or isosakuranetin dihydrochalcone glucoside. 4. A food or drink containing the lipase inhibitor according to claim 1. 5. A cosmetic containing the lipase inhibitor according to claim 1. 6. A therapeutic agent for skin diseases, which comprises the lipase inhibitor according to claim 1.