JPH09143070A - Lipase inhibitor and blood triglyceride lowering agent - Google Patents

Abstract

(57) [Abstract] [PROBLEMS] To provide a lipase inhibitor which is highly safe, can prevent deterioration of foods caused by lipase, and is useful for the prevention and treatment of adult diseases such as obesity and hyperlipidemia. (EN) It is intended to provide a blood triglyceride lowering agent which is highly safe, exhibits an excellent blood triglyceride lowering action, and is useful for the prevention and treatment of hypertriglyceridemia. SOLUTION: A lipase inhibitor containing at least one selected from the group consisting of flavonoids and glycosides thereof as an active ingredient; a blood triglyceride lowering agent containing hesperidin as an active ingredient.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a lipase inhibitor, and more particularly to a lipase inhibitor having high safety and capable of preventing deterioration of foods caused by lipase. Further, it relates to a lipase inhibitor useful for preventing adult diseases such as obesity and hyperlipidemia. The present invention also relates to a blood triglyceride lowering agent, and more particularly to a blood triglyceride lowering agent which is highly safe and useful for treating and preventing hypertriglyceridemia.

[0002]

2. Description of the Related Art Fat contained in foods is hydrolyzed by lipase contained in food materials and lipases derived from microorganisms mixed in foods and decomposed into glycerol and free fatty acids. This free fatty acid causes deterioration and malodor, and it is an important subject to suppress the generation of free fatty acid from the viewpoint of maintaining the quality of foods. In recent years, various adult diseases due to overnutrition and the like have been increasing. Among such adult diseases, inhibitors for digestive enzymes such as lipase inhibitors have been attracting attention for the purpose of preventing or treating hyperlipidemia such as diabetes and hypertriglyceridemia, obesity and the like. Further, a method has been considered in which an inhibitor for an enzyme is previously added to food.

Until now, phosphatidylcholine (K. Tanig
uti et al., Bull. Facul. Agric. Meiji Univ. 73, 9-
26 (1986)), soy protein (K. Satouchi et al., Agric. B
iol.Chem. 38, 97-101 (1974); K. Satouchi
Et al., Agric. Biol. Chem. 40, 889-897 (1976).
)), Tannin (S. Ahimura et al., Solar Eclipse, Volume 41, 561-5
64 (1994)), solvent-extracted extracts of crude drugs such as peony, oren, psyllium, button pie, ginger ginger, tea, and ginseng (JP-A-64-90131), peppers,
Water extract of pumpkin, shimeji mushroom, maitake mushroom, hijiki, green tea, black tea and oolong tea (JP-A-3-219872) Extracts of dokkatu, ryokkyo, areca, yobaihi, sunpens, ketsumeishi (JP-A-5-255100) , Etc. are known to have lipase inhibitory activity, but they are still insufficient in terms of properties and effects of the substance itself. In addition, it was recently disclosed that free flavonoids containing no sugar, such as quercetin, also exhibit a lipase inhibitory action (JP-A-7-61927). Deterioration such as spoilage and malodor due to fat in food is known to be caused by free fatty acids which are decomposed by lipase derived from microorganisms, but the inhibitory activity against the lipase derived from microorganisms of the above flavonoids is examined. Was not done.

[0004]

The object of the present invention is to show excellent lipase inhibitory activity, high safety, and useful for prevention and treatment of diabetes, hyperlipidemia, obesity, etc. It is to provide a lipase inhibitor which has an excellent inhibitory activity against the lipase and is useful for preventing the deterioration of foods. Another object of the present invention is to provide a blood triglyceride lowering agent which exhibits a highly safe and excellent blood triglyceride lowering action. Further, an object of the present invention is to provide a food additive containing the lipase inhibitor or the blood triglyceride lowering agent, and further to provide a food containing the lipase inhibitor, the blood triglyceride lowering agent or the food additive. It is to be.

[0005]

[Means for Solving the Problems] In order to find a novel lipase inhibitor that is highly safe and simultaneously inhibits lipases derived from mammals and microorganisms, the inventors of the present invention considered sugars while considering solubility. The various flavonoids were intensively studied centering on the flavonoids contained therein. as a result,
The present inventors have found that certain flavonoids and their glycosides have excellent lipase inhibitory activity, and completed the present invention. Furthermore, it was found that hesperidin, which is one of the above-mentioned flavonoid glycosides, has an excellent blood triglyceride lowering action. Therefore, the present invention
The present invention relates to a lipase inhibitor containing as an active ingredient at least one selected from the group consisting of flavonoids represented by the following general formula (I) or the following general formula (II) and glycosides thereof.

[0006]

Embedded image

[Wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are each independently a hydrogen atom or —OR (R is a hydrogen atom,
Methyl group, -C (O) - (CH 2) a ₂ -CH ₃ or the residue of a sugar. ). However, both R ² and R ⁴ are -O
When H, at least one of R ¹ , R ³ and R ⁵ is —O.
R '(where R' is a methyl group, -C (O) - (CH 2) 2 -
CH ₃ or a sugar residue. ). ]

[0008]

Embedded image

[In the formula, R ⁶ , R ⁷ and R ⁸ each independently represent a hydrogen atom or —OR (R is a hydrogen atom, a methyl group or a sugar residue). ] The present invention also relates to a food additive containing the above lipase inhibitor. The present invention further relates to a food containing the above lipase inhibitor or food additive. The present invention also relates to a blood triglyceride lowering agent containing hesperidin as an active ingredient. The blood triglyceride lowering agent can also be added to foods, and therefore the present invention provides a food additive containing the blood triglyceride lowering agent, and further a food containing the blood triglyceride lowering agent or food additive. Regarding

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Examples of the sugar constituting the glycoside of the flavonoids represented by the general formula (I) or (II) include glucose and rutinose (L-rhamnose-D-
Glucose), apiosyl-glucose and the like. Specific examples of the flavonoids represented by the general formula (I) and their glycosides, which are the active ingredients of the lipase inhibitor of the present invention, include kaempferol 7,4′-dimethoxy-
8-butyryl ester, luteolin-7-glucoside,
Luteolin-4'-glucoside, luteolin-3 ', 7-diglucoside, isoquercitrin, apigenin-7-glucoside, kaempferol-3-rutinoside, apiin and the like can be mentioned. The specific structure of the above active ingredient in the general formula (I) is as follows.

[0011]

[Table 1] ──────────────────────────────────── R ¹ R ² R ³ R ⁴ R ⁵ Kaempferol 7,4'-dimethoxy -OH -OCH_Three -H -OCH_Three -O-C (O)--8-butyryl ester (CH_Two)_TwoCH_Three Luteolin-7-Glucoside -H -O-Glc -OH -OH H Apigenin-7-Glucoside -H -O-Glc -H -OH H Luteolin-3 ', 7-Diglucoside -H -O-Glc -O-Glc -OH H Isoquercitrin -O-Glc -OH -OH -OH H Kaempferol-3-Lutinoside -O- (β-D-Glc)--OH -H -OH H (α-L-Rha) Luteolin -4'-Glucoside -H -OH -OH -O-Glc H Apiin -H -apiosyl-Glc -H -OH H ─────────────────────── ──────────────

Specific examples of the flavonoids represented by the above general formula (II) and their glycosides, which are the active ingredients of the lipase inhibitor of the present invention, include hesperidin, naringenin, naringenin-7-glucoside and hesperetin. Can be mentioned. The specific structures in these general formulas (II) are as shown below.

[0013]

[Table 2] ────────────────────────────────── R ⁶ R ⁷ R ⁸ Hesperidin -O- (β -D-Glc)-(α-L-Rha) -0H -OCH ₃ Naringenin -OH -H -OH Naringenin-7-Glucoside -O-Glc -H -OH Hesperetin -OH -OH -OCH ₃ ──── ──────────────────────────────

The compounds represented by the general formulas (I) and (II) can be obtained mainly from natural products such as plants, and are often extracted, separated and purified as a mixture of several kinds. In the present invention, since it is characterized by lipase inhibitory activity, it can be used at any stage, in the state of an extracted extract of a natural product, in the state of being subjected to purification treatment, or in the state of being separated into a single substance. Luteolin-7-glucoside, for example, is found in the whole plant of Reededa luteola L., honeysuckle flowers, digitalis leaves, clara leaves, etc. Isoquercitrin is a glycoside of quercetin and is found in dokudami, cotton and mulberry. Apigenin-7-glucoside is contained in the white flowers of cosmos. Kaempferol-3-
Rutinoside is found in stems and leaves of bindweed, and in the leaves of the grass. Apiin is a glycogen of avigenin, which is contained in leaves and seeds of parsley and above-ground parts of Peas.

Hesperidin is a flavone glycoside obtained from the peels of mandarin oranges, lemons, oranges and the like and the skin of crude drugs, and is contained in the methanol extract of mandarin oranges in an amount of about 4%. In the present invention, it is possible to use such an extract as it is or to purify hesperidin into a single substance. Furthermore, when hesperidin itself as a single substance is treated with an acid, an alkali, an enzyme, or the like, the sugar of hesperidin can be cleaved into hesperetin, and hesperetin also exhibits a lipase inhibitory effect. Hesperidin is already available in the Natural Products Handbook (19
It has been used as a bittering agent since it was recorded in Food and Science Co., Ltd., p. 152, 1981). Hesperetin is contained as hesperidin in the peels of lemons, mandarins, oranges, and the like. Those with developed mesocarps contain naringin, and those with thin mesocarps often contain hesperidin.Natsumi mandarin is considered to be a species between both lines, but naringin and hesperidin Contains. Hesperidin is a glycoside of hesperetin and has an anti-capillary permeation action. Naringenin, which is a glycoside naringin, is contained in the peels of oranges, Wenzhou mandarin oranges, summer mandarin oranges, pomelo and the like, and has no bitterness. Some of the active ingredients of the lipase inhibitor or the blood triglyceride lowering agent of the present invention are commercially available, and such commercially available products may be used in the present invention. Each of the above active ingredients used in the present invention has extremely low toxicity.

[0016]

Test Example 1 Various flavonoids, which are the active ingredients of the present invention, and their glycosides were tested for lipase inhibitory activity. The method and the result will be described. The lipase inhibitory activity was 0.1% in McIlvaine buffer (0.1 M; pH 7.4) containing 0.1 mM 4-methylumbelliferyl oleate.
Using ml as a substrate, 10 μl of each flavonoid solution, an appropriate amount of porcine pancreatic lipase (manufactured by Sigma) and McIlvaine buffer were used to bring the total amount to 0.2 ml, followed by enzymatic reaction at 37 ° C. for 20 minutes. As a control, a flavonoid solution was tested in the same manner without addition. After the reaction, 0.1 N HCl 1.0 ml was added to the reaction solution to stop the enzymatic reaction, and then the reaction solution was adjusted to pH 4.3 with sodium citrate solution, and 4-methylumbelliferone produced from the substrate by lipase Was quantified at an excitation wavelength of 320 nm and a fluorescence wavelength of 450 nm. The inhibition rate (%) of each sample was calculated by [(fluorescence intensity of control −
The fluorescence intensity of each sample) / the fluorescence intensity of the control] × 100. The same procedure was performed by changing the lipase derived from porcine pancreas to a lipase derived from Pseudomonas (manufactured by Sigma). As a result, the addition of flavonoids at 100 μg / ml showed an inhibitory effect as shown in Table 3 below.

[0017]

[Table 3] ─────────────────────────────────── Material name Porcine pancreas-derived Pseudomonas-derived lipase inhibition rate (%) Lipase inhibition rate (%) ─────────────────────────────────── Kaempferol-7,4 '-Dimethoxy 100 94 -8-butyryl ester luteolin-7-glucoside 75 40 luteolin-4'-glucoside 88 72 luteolin-3', 7-diglucoside 77 67 isoquercitrin 95 60 apigenin-7-glucoside 32 44 kaempferol -3-Lutinoside 34 41 Apiin 86 45 Hesperidin 96 34 Naringenin 96 59 Naringenin-7-Glucoside 83 40 Hesperetin 78 42 42 ────────────────────────── ──────────

Regarding quercetin and apigenin, which are conventionally known to inhibit lipase derived from pig pancreas,
The same test as above was performed. The results are shown below.

[0019]

[Table 4] ────────────────────────── Porcine pancreatic origin Pseudomonas derived lipase inhibition rate (%) Lipase inhibition rate (%) ─── ─────────────────────── Quercetin 92 0 Apigenin 95 0 ───────────────────── From the above results, it was found that quercetin and apigenin do not show inhibitory activity against lipase derived from microorganisms.

[0020]

Test Example 2 Hesperidin was tested for its blood triglyceride lowering action. The method and the result will be described. Fifteen 5-week-old SD rats (purchased from SLC) were divided into five groups, and each group was preliminarily fed with a solid feed for 1 week in a metabolic gauge made of stainless steel, and then the experimental feed was administered for 4 weeks.
Hesperidin (made by Nacalai Tesque) in the experimental feed was
Addition was made such that the group was 0%, the group II was 5%, and the group III was 10%. Food and water were available ad libitum. After completion of the feed administration test, the animals were fasted overnight, and blood was collected from the heart under ether anesthesia,
Blood triglyceride was measured with a vision kit (manufactured by Dynabot). The results are shown in Table 5 below.

[0021]

[Table 5] ────────────────────────────── Group Hesperidin in blood Feed triglyceride level Addition amount (%) (mg) / dl) ────────────────────────────── I 0 89.7 II 5 69.7 III 10 10 64.1 ── ────────────────────────────

[0022]

[Test Example 3] The rat of Test Example 2 was replaced with a CDF mouse (purchased from SLC), and the same test was conducted. The results are shown in Table 6 below.

[Table 6] ────────────────────────────── Group Hesperidin in blood Feed triglyceride level Addition amount (%) (mg) / dl) ────────────────────────────── I 0 73.2 II 5 69.4 III 10 10 59.7 ── ──────────────────────────── As is clear from the results shown in Tables 5 and 6, hesperidin is significantly triglyceride in blood. The value was lowered.

Production Examples The active ingredients of the lipase inhibitor or blood triglyceride lowering agent of the present invention are commercially available and can be easily obtained. For example, an example of extraction of hesperidin from mandarin orange peel (cuticle) is shown below. Chen skin (made by Uchida Kampo Co., Ltd.) 10
0 g of the mixture was refluxed and extracted with 500 ml of methanol for 2 hours while boiling. The extract was obtained by filtration and the methanol was concentrated to dryness under reduced pressure. 30 g of a methanol extract was obtained. Hesperidin can be purified from the methanol extract by an appropriate means such as column chromatography. As an example, hesperidin can be separated and purified to a single substance by high performance liquid chromatography. When LiChrosorb PR18 (4 × 250 nm) was used as the column and 20% acetonitrile aqueous solution was used as the mobile phase, the measurement was performed using 285 nm as an index.
It was possible to obtain mg of hesperidin. Here, the skin peel methanol extract and hesperidin were tested for lipase inhibitory activity at various concentrations. The test method is the same as in Test Example 1. The results are shown in Tables 7 and 8.

[0024]

[Table 7] Hesperidin lipase inhibitory activity ───────────────────────────── Addition amount Porcine pancreatic origin Pseudomonas origin (μg / ml) Lipase inhibition rate (%) Lipase inhibition rate (%) ───────────────────────────── 100 96 34 50 50 86 23 23 25 17 8 13 100 ───────────────────────────── 50% inhibition was 32 μg / ml against porcine pancreatic lipase
, Pseudomonas lipase 132 μg /
It was ml.

[0025]

[Table 8] Lipase inhibitory activity of Chen skin methanol extract ───────────────────────────── Addition amount Porcine pancreatic origin Pseudomonas origin (μg / ml) Lipase inhibition rate (%) Lipase inhibition rate (%) ───────────────────────────── 625 87 86 312.5 65 68 ───────────────────────────── 50% inhibition is 250 μg / m 2 against porcine pancreatic lipase
l, 228 μg against Pseudomonas lipase /
It was ml.

The active ingredient of the lipase inhibitor of the present invention includes flavonoids represented by the above formula (I) and their glycosides, and flavonoids represented by the above formula (II) and their glycosides. It may be one kind selected from the above or two or more kinds. The lipase inhibitor of the present invention may contain additives in addition to the flavonoids and their glycosides which are the active ingredients thereof. In addition, the active ingredient can be formulated into an arbitrary form with a suitable auxiliary agent to give a lipase inhibitor which can be orally or parenterally administered.
Furthermore, the lipase inhibitor of the present invention may contain other active ingredients. The blood triglyceride lowering agent of the present invention may contain additives in addition to hesperidin which is its active ingredient. In addition, hesperidin can be formulated into an arbitrary form with an appropriate auxiliary agent to obtain a blood triglyceride lowering agent that can be orally or parenterally administered. Furthermore, the blood triglyceride lowering agent of the present invention may contain other active ingredients.

The administration method, dose and formulation method of the lipase inhibitor and blood triglyceride lowering agent of the present invention are shown below. The lipase inhibitor and blood triglyceride lowering agent of the present invention can be used both orally and parenterally, and when orally administered, they are used as soft / hard capsules or tablets, granules, fine granules and powders. Is administered. When administered parenterally, it can be administered in the form of suppositories such as injections, drops, and solid or suspended viscous liquids so that continuous mucosal absorption can be maintained. External administration methods such as internal, subcutaneous, intramuscular and intravenous injections, topical application, spraying, suppositories, and intravesical injections can also be used. The dose may vary depending on the method of administration and the malignancy of the disease, the age of the patient, the medical condition and general condition, the degree of progression of the disease, etc., but in adults, it is usually 0.5-5,000 mg as an active ingredient per day. , For dwarfs, usually 0.5-300
0 mg is suitable. The ratio of the active ingredient in the lipase inhibitor or the blood triglyceride lowering agent of the present invention is
Although it may vary depending on the dosage form, generally, about 0.3 to 15.0% by weight is suitable when administered orally or mucosally, and about 0.01 to 10% by weight when parenterally administered.
Is appropriate. Further, in formulating the lipase inhibitor or blood triglyceride lowering agent of the present invention, according to a conventional method, an aqueous solution, an oily preparation or the like, which can be a subcutaneous or intravenous injection preparation, a capsule, a tablet, It can be formulated into a dosage form such as a fine granule and used for oral administration.

Further, in order to impart stability and acid resistance to long-term storage to the active ingredient and to completely maintain the medicinal effect, it is excellent if a pharmaceutically acceptable film is further formed into a formulation. It can be used as a stable lipase inhibitor or a blood triglyceride lowering agent. Surfactants used in the formulation of the lipase inhibitor or blood triglyceride lowering agent of the present invention, excipients, lubricants, adjuvants and pharmaceutically acceptable film-forming substances, and the like,
It is as follows. In order to improve disintegration and dissolution of the lipase inhibitor or the blood triglyceride lowering agent of the present invention, a surfactant such as alcohol, ester,
One or more of polyethylene glycol derivatives, sorbitan fatty acid esters, sulfated fatty alcohols and the like can be added. In addition, as an excipient, for example, sucrose, lactose, starch, crystalline cellulose, mannitol, light anhydrous silicic acid, magnesium aluminate, magnesium metasilicate aluminate, synthetic aluminum silicate, calcium carbonate, sodium hydrogen carbonate, calcium hydrogen phosphate , Carboxymethylcellulose calcium and the like can be added alone or in combination of two or more.

As the lubricant, for example, magnesium stearate, talc, hydrogenated oil or the like can be added alone or in combination of two or more, and as a flavoring agent and a flavoring agent, salt,
Saccharin, sugar, mannitol, orange oil, licorice extract, citric acid, glucose, menthol, eucalyptus oil,
Sweetening agents such as malic acid, flavors, coloring agents, preservatives and the like may be contained. Suspending agents, as adjuvants such as wetting agents, for example, coconut oil, olive oil, sesame oil, peanut oil,
It can contain calcium lactate, safflower oil, soybean phospholipids, and the like. As the film-forming substance, cellulose acetate phthalate (CAP) is used as a carbohydrate derivative such as cellulose or saccharide, and methyl acrylate / methacrylic acid is used as a polyvinyl derivative such as an acrylic acid copolymer or a dibasic acid monoester. Examples thereof include copolymers and methyl methacrylate / methacrylic acid copolymers. Also,
In coating the above-mentioned film-forming substance, the properties of the film-forming agent can be improved by adding various additives for preventing adhesion of the agents during the coating operation, in addition to a commonly used coating agent such as a plasticizer. Or make the coating operation easier.

The lipase inhibitor or blood triglyceride lowering agent of the present invention can also be incorporated into foods and health foods, and can be used as a component of food additives. When blended in food, it should be used as an active ingredient in food.
001 to 15% by weight is suitable, and 0.01 to 10% by weight
It is preferable to add the composition in an amount of wt%, but depending on the type of food, the amount may be smaller or larger than the above range. For example, when it is blended with supplementary foods such as tablet confections and biscuits, it can be blended in an amount of 15% by weight or more. Depending on the food, the lipase inhibitor of the present invention or the blood triglyceride lowering agent can be appropriately added during the production process. The lipase inhibitor of the present invention, the type of food to be mixed with blood triglyceride lowering agent or food additive is not particularly limited, for example, bread, noodles, biscuits, hot cakes, tablet confectionery such as flour and starch. The food, dressing, drink etc. which it contains can be mentioned.

[0031]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the invention is limited thereto. Example 1 (tablet and tablets) 108 g of egg shell calcium, 2 g of ferric pyrophosphate, 40 g of ascorbic acid, 40 g of microcrystalline cellulose, 285 g of reduced maltose, 0.5 g of hesperidin were mixed by a conventional method and then tableted. , Tablet confectionery and tablets were produced. Example 2 (biscuits) 120 g wheat flour, 0.12 g hesperidin, 35 g sugar,
Using 20 g of shortening, 1.5 g of whole egg powder, 1 g of salt, 0.6 g of sodium hydrogen carbonate, 0.75 g of ammonium carbonate, and 20 g of water, a dough was prepared by a conventional method, molded and roasted to produce a biscuit. .

Example 3 (bread) Using 3 kg of wheat flour, 30 g of hesperidin, 60 g of yeast, 3 g of yeast food, 150 g of sugar, 60 g of salt, 150 g of shortening, 60 g of skim milk powder, and 2070 g of water, a dough was prepared by a conventional method and molded. , Baked to make bread. Example 4 (noodle) 1% by weight of hesperidin, 34, based on semi-strong wheat flour
A mixture of 1% by weight of water, 1% by weight of salt, and 1% by weight of kneaded kneading mixture for 12 minutes, and then rolling and molding with a noodle machine several times to prepare Chinese noodles raw noodle strips and raw noodle strings. Got

[0033]

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a lipase inhibitor which is highly safe and has a high lipase inhibitory activity against lipase derived not only from the pancreas but also from microorganisms. Further, it is possible to provide a blood triglyceride lowering agent which is highly safe and exhibits an excellent blood triglyceride lowering action. These lipase inhibitors and blood triglyceride lowering agents can be easily added to and mixed with foods, and particularly lipase inhibitors can prevent deterioration of foods due to lipase. It can also reduce the calories of food. Furthermore, it is also useful for the prevention and treatment of adult diseases such as obesity due to excessive intake of lipids and hyperlipidemia such as hypertriglyceridemia, which reflect recent dietary habits.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display location C07H 17/07 C07H 17/07 C12N 9/99 C12N 9/99

Claims (7)

[Claims] 1. The following general formula (I) or the following general formula (I
From flavonoids shown in I) and their glycosides
At least one selected from the group consisting of
A lipase inhibitor having. Embedded image[Where R¹, R^Two, R^Three, R^FourAnd R^FiveAre independent
And a hydrogen atom or -OR (R is a hydrogen atom, a methyl group,
-C (O)-(CH_Two)_Two-CH_ThreeOr a sugar residue
You. ). Where R^TwoAnd R^FourWhen both are -OH
Is R¹, R^ThreeAnd R^FiveAt least one of -OR '
(R 'is a methyl group, -C (O)-(CH_Two)_Two-CH _ThreeMa
Or is a sugar residue. ). [Chemical formula 2][Where R⁶, R⁷And R⁸Are each independently a hydrogen atom or
Or -OR (R is a hydrogen atom, a methyl group or a sugar residue.
is there. ). ] 2. The flavonoids represented by the general formula (I) and their glycosides are kaempferol 7,4′-dimethoxy-8-butyryl ester, luteolin-7-glucoside, luteolin-4′-glucoside and luteolin. −3 ', 7
-Diglucoside, isoquercitrin, apigenin-7
-Glucoside, kaempferol-3-rutinoside and apiin, and the flavonoids represented by the general formula (II) and their glycosides are hesperidin, naringenin, naringenin-7-glucoside and hesperetin. Inhibitor. 3. A food additive containing the lipase inhibitor according to claim 1. 4. A food containing the lipase inhibitor according to claim 1 or 2, or the food additive according to claim 3. 5. A blood triglyceride lowering agent containing hesperidin as an active ingredient. 6. A food additive containing the blood triglyceride lowering agent according to claim 5. 7. A food containing the blood triglyceride lowering agent according to claim 5 or the food additive according to claim 6.