JP2007246471A - Blood neutral fat increase inhibitor and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a blood neutral fat increase inhibitor originated from a safe food raw material, to provide a method for producing the same, and to provide a composition. <P>SOLUTION: This blood neutral fat increase inhibitor contains, as an active ingredient, the extract of dry Perilla frutescens with an aqueous ethanol solution having concentration of 90 to 99.9 vol.%, and the composition for preventing and/or improving hyperlipemia, especially neutral hyperlipemia, contains the same. The composition is safe and is effective for preventing and/or improving, treating hyperlipemia, especially neutral hyperlipemia. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a blood neutral fat elevation inhibitor and a method for producing the same.

  In recent years, cardiovascular disorders such as hyperlipidemia are increasing due to a rapid increase in total caloric intake and fat intake and a longer life due to advances in medical technology. In addition, these phenomena are remarkable even in a young group in which the increase in fat intake is particularly remarkable. The increase in cardiovascular disorders and the younger age are one of the social problems.

  Hyperlipidemia is said to be a disease caused by excessive intake of animal foods, lack of exercise and stress. It is known that as hyperlipidemia progresses, neutral fat and cholesterol are deposited on the blood vessel wall, leading to diseases such as arteriosclerosis, hypertension, myocardial infarction, and cerebrovascular disorder.

  In general, a state in which the blood neutral fat level is 150 mg / dl or higher or the cholesterol level is 220 mg / dl or higher is called hyperlipidemia. Hyperlipidemia is classified into three types: hypercholesterolemia with high blood cholesterol level, hypertriglyceridemia with high blood triglyceride level, and complex hyperlipidemia with high levels of both. Can be divided. The average triglyceride value for Japanese is said to be 140 mg / dl. The number of people with high triglycerides of 150 mg / dl or more is one in three for men and one in four for women, and the number of affected individuals is very high. Therefore, in order to prevent diseases such as arteriosclerosis induced from hyperlipidemia, it is very important to reduce the blood triglyceride level.

  Lipids ingested by meals are broken down into fatty acids and monoglycerides by pancreatic lipase secreted from the pancreas and absorbed from the small intestine. Therefore, it is known that a composition that inhibits pancreatic lipase can inhibit lipid absorption from the digestive tract.

  In addition, blood neutral fat has been proposed as a risk of metabolic syndrome, and it is considered that reducing its value can contribute to prevention or improvement of metabolic syndrome. Peroxisome proliferator-activated receptor (hereinafter referred to as PPAR) ligand is expected to improve obesity and insulin resistance and prevent metabolic syndrome related to hyperlipidemia and diabetes. PPAR is a ligand-dependent transcription factor belonging to the nuclear receptor family responsible for gene regulation of lipid and sugar metabolism. In mammals, the presence of three subtypes of PPARα, PPARδ (PPARβ, NUC-1, FAAR) and PPARγ is known (Non-patent Document 1). Among the three subtypes, in particular, the ligand of PPARα is known to have a blood lipid lowering action by mainly activating liver PPARα and enhancing lipid metabolism ( Non-patent document 2).

  Conventionally, orlistat, which is a lipase inhibitor, fibrates, EPA preparations, nicotinic acid preparations, etc., which are lipase inhibitors, have been used as drugs to improve the pathology of blood lipid balance such as hypertriglyceridemia. Yes. However, the fibrate agent has side effects such as abdominal pain, rash, and liver damage, the EPA preparation has side effects such as bleeding and stomach discomfort, and the nicotinic acid preparation has side effects such as systemic flushing and an increase in blood glucose level. Therefore, it is desired to develop a blood triglyceride rise inhibitor that is excellent in action to reduce blood triglyceride level and improve the balance of blood lipid level, and is safe and can be administered for a long time. It was.

Perilla is a plant belonging to the genus Perilla frutescens, and there are varieties such as red perilla, blue perilla, chillimen dizo, chirimenka diso, and is widely used as a raw material for condiments, tempura, perilla rolls and confectionery. In addition, it has been known to have various effects such as antiseptic, antibacterial, detoxification, healthy stomach, antipyretic, sedation, cough, sweating, diuresis, intestinal action, etc. It is used as one of the main ingredients of traditional Chinese medicines such as Kososan (Non-patent Document 3). It is also known that perilla extracts have α-glucosidase inhibitory activity (Patent Document 1) and perilla hot water extract has anti-allergic action (Patent Document 2). Yes. Further, it has been reported that isoflavones or analogs thereof have a PPAR-dependent gene transcription activation action, and perilla is an example of a plant containing isoflavones or analogs thereof (Patent Document 3).
JP 2000-102383 A Japanese Patent No. 3071669 JP 2002-80362 A Journal of Medicinal Chemistry, 2000, 43, 527-550 Diabetes, 2001, 50, 411-417. Monthly Food Chemical, 2000, Vol. 7, pp. 37-42

  In view of the above, the present invention has an effect of improving the disintegration of blood lipid balance, in particular, an effect of suppressing an increase in blood neutral fat, and a high safety of food-derived blood neutral fat. It is an object of the present invention to provide an inhibitor, a method for producing the same, and a composition containing the blood neutral fat elevation inhibitor.

  As a result of intensive studies in view of the above circumstances, the present inventors have extracted a perilla extract with an aqueous ethanol solution having a concentration of 90 to 99.5% by volume. I found out that I could get it.

That is, the present invention provides the following.
[1] A blood neutral fat elevation inhibitor comprising, as an active ingredient, an extract of an aqueous ethanol solution having a concentration of 90 to 99.9% by volume of dried perilla frutescens.
[2] The perilla is at least one selected from the group consisting of Perilla frutescens Britton var. Acuta Kudo, Perilla frutescens Britton var. Crispa Decaisne forma crispa Makino and Perilla frutescens Britton var. Crispa Decaisne forma crispi-discolor Makino [1] The blood neutral fat elevation inhibitor according to [1].
[3] The blood neutral fat elevation inhibitor according to [1] or [2], wherein the dried perilla product is a dried product having a water content of less than 25%.
[4] A lipid absorption inhibitor comprising the blood neutral fat elevation inhibitor according to any one of [1] to [3].
[5] A lipase inhibitor comprising the blood neutral fat elevation inhibitor according to any one of [1] to [3].
[6] A peroxisome proliferator-responsive receptor α ligand agent comprising the blood neutral fat elevation inhibitor according to any one of [1] to [3].
[7] A composition for preventing or improving hyperlipidemia, comprising the blood neutral fat elevation inhibitor according to any one of [1] to [3].
[8] A composition for preventing or improving metabolic syndrome, comprising the blood neutral fat elevation inhibitor according to any one of [1] to [3].
[9] The composition according to [7] or [8], which is used for medicine or veterinary medicine.
[10] The composition according to [7] or [8], which is for eating and drinking.
[11] The composition according to [7] or [8], which is for quasi drugs.
[12] A method for producing a blood neutral fat elevation inhibitor, comprising extracting dried perilla frutescens with an aqueous ethanol solution having a concentration of 90 to 99.9% by volume.
[13] The perilla is at least one selected from the group consisting of Perilla frutescens Britton var. Acuta Kudo, Perilla frutescens Britton var. Crispa Decaisne forma crispa Makino and Perilla frutescens Britton var. Crispa Decaisne forma crispi-discolor Makino [12] The method for producing a blood neutral fat elevation inhibitor according to [12].
[14] The method for producing a blood neutral fat elevation inhibitor according to [12] or [13], wherein the dried perilla product is a dried product having a water content of less than 25%.

  According to the present invention, a food-derived blood neutral fat elevation inhibitor is obtained. The blood neutral fat elevation inhibitor obtained in the present invention is useful in preventing, alleviating and treating hyperlipidemia, particularly hypertriglyceremia.

  Hereinafter, embodiments of the present invention will be described in detail.

  The blood neutral fat elevation inhibitor of the present invention is a composition having an action of inhibiting blood neutral fat elevation, comprising an extract of an aqueous ethanol solution having a concentration of 90 to 99.9% by volume of dried perilla as an active ingredient It is.

  The blood neutral fat elevation inhibitory action is an action that improves the balance of blood lipid balance, particularly an action that inhibits blood neutral fat rise. The blood triglyceride increase inhibitor of the present invention can prevent, alleviate, or improve hyperlipidemia, particularly hypertriglyceremia, by suppressing the increase in blood triglyceride. Among them, the blood triglyceride elevation inhibitor of the present invention is useful for preventing hyperlipidemia, particularly hypertriglyceremia. In the present invention, prevention of hyperlipidemia refers to the state of hyperlipidemia or borderline condition defined by the Japanese Society for Arteriosclerosis in the Guidelines for the Treatment of Arteriosclerotic Diseases (issued in September 2002). Refers to preventing or delaying. Further, the improvement of hyperlipidemia refers to the approach to the state defined as the normal range in the above guidelines from the above-described hyperlipidemia state or boundary state.

  The perilla used in the present invention is not particularly limited as long as it is a plant belonging to the genus Perilla frutescens. Specifically, red perilla (Perilla frutescens Britton var. Acuta Kudo), blue perilla (Perilla frutescens Britton var. Acuta Kudo forma viridis Makino), chile miso (Perilla frutescens Britton var. Crispa Decaisne forma crispa Makino) Britton var. Crispa Decaisne forma crispi-discolor Makino), etc. -discolor Makino is more preferred. The above perilla can be used alone or in combination of two or more. Moreover, the plant part used for obtaining the perilla extract is not particularly limited, but perilla leaves are preferred in the present invention. As the form of the above-mentioned perilla, any one of a pulverized product, a cut product or a powder obtained by a prototype, a blender or the like may be used. The perilla in the present invention is used in the form of a dried product, and the dried perilla product preferably has a water content of 25% or less, more preferably a water content of 15% or less, and further preferably a water content of 8% or less. . Dry perilla products with a high water content may be spoiled during storage of raw materials, and moisture in perilla dry matter may be transferred to the solvent during extraction, resulting in a decrease in the concentration of the extract solvent and sufficient neutrality in the blood. There is a possibility that the fat elevation inhibitory action cannot be obtained.

  The blood neutral fat elevation inhibitor of the present invention comprises, as an active ingredient, an extract obtained by extracting the dried perilla product with an aqueous ethanol solution having a concentration of 90 to 99.9% by volume. The extract can be obtained, for example, by immersing the dried perilla product in an extraction solvent, stirring or standing under normal pressure, and performing stationary separation, filtration, centrifugation, or the like. The extraction solvent used in the present invention needs to be an ethanol aqueous solution having a concentration of 90 to 99.5% by volume. In an ethanol aqueous solution of less than 90% by volume, a sufficient blood neutral fat elevation suppressing action cannot be obtained. The extraction temperature is generally -20 to 100 ° C, usually 1 to 90 ° C, preferably 1 to 70 ° C. The extraction time is usually 0.1 hours to 1 month, preferably 0.5 hours to 7 days. Further, the amount of the extraction solvent is preferably 1 to 50 times, more preferably 3 to 20 times the amount of 1 part by weight of dried perilla. If the amount is less than 1-fold, the dried perilla is not sufficiently immersed in the solvent and the extract recovery rate is low. On the other hand, when the amount is 50 times or more, a container such as an extraction tank used for extraction becomes large, and the energy required for solvent removal tends to be extremely large and the production cost tends to increase.

  In the present invention, the form of the perilla extract may be in the form of an extract or may be obtained by removing the solvent. Further, it may be in a form dissolved and suspended in another appropriate solvent. In addition, operations such as deodorization and purification can be added to these perilla extracts as long as they do not lose their activity as blood neutral fat elevation inhibitors. Furthermore, the perilla extract can be used in the present invention as an extract, as a crude extract or as a semi-purified extract, as long as it does not contain impurities that are inappropriate for foods and beverages and pharmaceuticals.

  The perilla extract obtained by the above production method not only has an action of suppressing an increase in blood neutral fat, but also has a lipid absorption inhibitory action, a lipase inhibitory activity, and a PPARα ligand activity. The blood neutral fat elevation inhibitor of the invention can also be used as a lipid absorption inhibitor, a lipase inhibitor, or a PPARα ligand agent.

  The lipid absorption inhibitor as used in the field of this invention is a composition which can suppress absorption of the fat contained in a meal. The lipid absorption inhibitor of the present invention can suppress an increase in blood neutral fat level after a meal. That is, the lipid absorption inhibitor of the present invention can prevent, ameliorate, or alleviate a state where the balance of blood lipids such as hypertriglyceridemia is lost.

  The lipase inhibitor referred to in the present invention is a composition that suppresses the activity of lipase, particularly pancreatic lipase. The lipase inhibitor of the present invention can suppress the absorption of fat in the meal in order to suppress the decomposition of fat in the meal. That is, the lipase inhibitor of the present invention can prevent, ameliorate, or treat a state in which the balance of blood lipids such as hypertriglyceridemia is lost.

  Here, the lipase activity is, for example, the fluorescence intensity of 4-methylumbelliferone (4-MU) produced using 4-methylumbelliferone oleate (4-MUO) as the substrate and porcine pancreatic lipase as the enzyme. Can be measured. In these assays, the activity of the sample is generally compared to the solvent control, and a sample showing a lipase activity lower than that of the solvent control is evaluated as “with lipase inhibitory activity”.

  The PPARα ligand agent referred to in the present invention is a composition having the ability to bind to the PPARα ligand binding region, that is, PPARα ligand activity. The PPARα ligand agent of the present invention regulates lipid and sugar metabolism in tissues such as liver via PPARα, thereby preventing / improving metabolic syndrome related to obesity, insulin resistance, hyperlipidemia, diabetes, etc. Can be relaxed. That is, the PPARα ligand agent of the present invention can control the expression of various genes related to metabolic syndrome related to obesity, insulin resistance, hyperlipidemia, diabetes and the like. Examples of the various genes include acyl CoA oxidase, medium chain acyl CoA dehydrogenase, carnitine palmitoyltransferase, long chain acyl CoA synthase, fatty acid binding protein, lipoprotein lipase, apolipoprotein, and uncoupling protein. It is not limited to.

  Here, the PPAR ligand activity is, for example, a reporter assay (Cell, 1995, 83, 803-812) for evaluating the binding of a PPAR ligand binding region to a fusion protein of GAL4 by expression of luciferase, PPAR ligand binding It can be measured by a competition binding assay (Cell, 1995, 83, 813-819) using a protein containing a region. In these assays, the activity of the sample is generally compared to the solvent control, and a sample showing significantly higher activity than the solvent control is evaluated as “with PPAR ligand activity”.

  The blood triglyceride elevation inhibitor of the present invention is a pharmaceutical or veterinary drug for the prevention and / or treatment of hyperlipidemia, particularly hypertriglyceremia, and a composition containing the same. It can be used as a composition for eating and drinking. Furthermore, since the blood neutral fat elevation inhibitor of the present invention has a blood neutral fat reducing action, it can also be used as a composition for preventing and / or improving metabolic syndrome. Moreover, those forms are not limited, for example, foods and drinks such as health foods (special health foods, foods with nutritional functions), health foods, dietary supplements, etc., or OTC drugs or other quasi-drugs that are readily available It can be used as goods and veterinary drugs.

  The content of the perilla extract in the composition of the present invention is not particularly limited, but is preferably 0.001 to 99.999% by weight, more preferably 0, based on the weight of the composition, as the extracted solid content weight. 0.01 to 99.9% by weight.

  The blood neutral fat elevation inhibitor of the present invention and the composition containing the same can be directly ingested as they are, or a capsule, an additive such as a known carrier or auxiliary agent, It can be ingested in a form that is easy to take such as tablets and granules. For the purpose of enhancing nutrition, various vitamins such as vitamins A, C, D, and E can be added and used in combination. The content of the blood neutral fat elevation inhibitor of the present invention in these molding agents is preferably 0.1 to 100% by weight, more preferably 10 to 90% by weight. Furthermore, mixed with food and drink ingredients, confectionery such as chewing gum, chocolate, candy, jelly, biscuits and crackers; frozen confectionery such as ice cream and ice confectionery; beverages such as tea, soft drinks, energy drinks and beauty drinks; udon Noodles such as Chinese noodles, spaghetti and instant noodles; kneaded products such as rice cakes, bamboo rings and hampen; seasonings such as dressings, mayonnaise and sauces; fats and oils such as margarine, butter and salad oil; bread, ham, soup, retort food It can be used for all foods and drinks such as frozen foods. When ingesting these edible compositions, the intake is converted to the amount of perilla extract, which is an active ingredient, per adult day, preferably 0.01 to 1000 mg / kg body weight, more preferably 1 to 300 mg. / Kg body weight.

  When used as a pharmaceutical, the dosage form is not particularly limited, and examples thereof include capsules, tablets, granules, injections, suppositories, and patches. In formulation, other pharmaceutically acceptable formulation materials such as excipients, disintegrants, lubricants, binders, antioxidants, colorants, anti-aggregation agents, absorption enhancers, solubilizers An agent, a stabilizer and the like can be added as appropriate. The dosage of these preparations is preferably 0.01 to 1000 mg / kg body weight, more preferably 0.1 to 100 mg / kg body weight per adult day, in terms of the amount of perilla extract as an active ingredient. Administer once or several times.

  When used as a quasi-drug, other additives are added as necessary, for example, ointments, liniments, aerosols, creams, soaps, facial cleansers, whole body cleansers, lotions, lotions, baths It can be used for agents and the like, and can be used locally.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated further more concretely, this invention is not limited to these Examples.

<Preparation of perilla extract>
Example 1
1000 g of Chilemen Katajiso (purchased from Shinwa Bussan Co., Ltd.) was immersed in 5 L of a 99.5% by volume ethanol aqueous solution, extracted with stirring at 45 ° C. for 6 hours under normal pressure, and then an extract was obtained by filtration. The solvent was removed from the extract by concentration under reduced pressure to obtain 65.6 g of a semi-solid perilla extract.

(Comparative Example 1)
1000 g of Chilemen Katajiso (purchased from Shinwa Bussan Co., Ltd.) was immersed in 5 L of 70% by volume ethanol aqueous solution, extracted with stirring at 45 ° C. for 6 hours under normal pressure, and then an extract was obtained by filtration. The extract was concentrated under reduced pressure and the solvent was removed by lyophilization to obtain 93.0 g of a powdery perilla 70% ethanol extract.

<Confirmation of blood triglyceride increase suppression effect>
(Example 2)
KK-Ay mice (female, 6 weeks old) are divided into 4 groups (6 animals each), and high-fat and high-sugar diet (Oriental Yeast Co., Ltd., Table 1) is used as a basic feed, and no feed (control group) ), Feed supplemented with 0.125%, 0.25%, 0.5% of the perilla extract obtained in Example 1 (0.125% added group, 0.25% added group, 0.5% respectively) The addition group) was given for 4 weeks with free intake.

After completion of sample administration, whole blood was collected under ether anesthesia to obtain plasma. Thereafter, plasma neutral fat was measured. The results are shown in Table 2.

As apparent from Table 2, intake of perilla extract significantly suppressed an increase in blood triglyceride level.

(Comparative Example 2)
KK-Ay mice (female, 6 weeks old) are divided into 2 groups (6 animals each), and high-fat and high-sugar diet (Oriental Yeast Co., Ltd., Table 1) is used as a basic feed and no feed (control group) ), A feed (1.0% perilla 70% ethanol extract added group) supplemented with 1.0% perilla 70% ethanol extract obtained in Comparative Example 1 was given for 4 weeks.

  After completion of sample administration, whole blood was collected under ether anesthesia to obtain plasma. Thereafter, plasma neutral fat was measured. The results are shown in Table 3.

As apparent from Table 3, intake of perilla 70% ethanol extract did not suppress an increase in blood neutral fat level.

<Confirmation of lipid absorption inhibitory activity>
(Example 3)
Wister rats (male, 7 weeks old) were divided into 3 groups (6 animals in each group), the perilla extract obtained in Example 1 was 1000 mg / Kg, and 5 mg / kg of orlistat, a commercially available lipase inhibitor, was used as a positive control. The suspension was suspended in a 0.2% Tween 80 solution so as to give Kg, and the suspension was orally administered to rats. As a control, only 0.2% Tween 80 was administered. Thereafter, 2 mL of a lipid emulsion in which corn oil and a 0.2% Tween 80 solution were mixed at a ratio of 1: 1 was orally administered.

  Blood was collected from the carotid artery before administration and 1, 2, 4 and 6 hours after administration to obtain plasma. Thereafter, neutral fat in plasma was measured. The results are shown in Table 4.

As is clear from Table 4, the absorption of neutral fat was suppressed by administration of perilla extract, thereby suppressing an increase in blood neutral fat level.

<Confirmation of lipase inhibitory activity>
Example 4
21 μl Mcllvain buffer (adjusted to pH 7.4 with 0.1 M disodium hydrogen phosphate, 0.1 M citric acid), 4 μl test substance, and 50 μl pig in black 96-well plate for fluorescence measurement Mcllvain buffer in which pancreatic lipase (Sigma) was dissolved was added, and further 25 μl of Mcllvain buffer in which 0.1 mM 4-MUO (Sigma) was suspended was added and reacted at 37 ° C. for 30 minutes. The reaction was stopped by adding 50 μl of 0.1N hydrochloric acid, and 100 μl of 1M sodium citrate was added to adjust the pH to around 4.3, and fluorescence with an excitation wavelength of 340 nm and a fluorescence wavelength of 450 nm was expressed by Wallac 1420 ARVOsx (Perkin Elmer). DMSO was used as a control, and the 4-MU amount (reaction value) produced by lipase in the reaction solution to which the control and test substances were added was obtained by subtracting the fluorescence intensity in the absence of lipase from the fluorescence intensity in the presence of lipase. Asked. The inhibitory activity was determined from the following formula.
Inhibitory activity (%) = {1− (response value of test substance / response value of control)} × 100
The lipase inhibitory activity of the perilla extract obtained in Example 1 is shown in Table 5.

As is apparent from Table 5, the perilla extract obtained in Example 1 exhibited lipase inhibitory activity. IC50 was 16.3 μg / mL.

<Confirmation of PPARα ligand activity>
(Example 5)
Hep-G2 cells (cultured cells derived from human liver cancer) were implanted in a 96-well culture plate at 2 × 10 ⁴ cells / well and cultured at 37 ° C. under 5% CO ₂ for 24 hours. DMEM containing 10% FBS (fetal bovine serum), 10 ml / L penicillin / streptomycin solution (5000 IU / ml, 5000 μg / ml, Invitrogen, respectively), 37 mg / L ascorbic acid (Wako Pure Chemical Industries, Ltd.) (Dulbecco's Modified Eagle Medium: Invitrogen) was used. The cells were washed with OPTI-MEM (Invitrogen) and then transfected with pM-PPARα and 4xUASg-luc using Lipofectamine Plus (Invtrogen). PM-PPARα is a chimeric protein in which a yeast-derived transcription factor GAL4 gene (amino acid sequence 1-147) and a human PPARα ligand binding site gene (amino acid sequence 167-468) are linked to a mammalian expression plasmid pM (Clontech). 4xUASg-luc is a reporter plasmid in which GAL4 response element (UASg) is incorporated four times upstream of the luciferase gene (Cell, 1995, 83, 803-812, etc.) Can be created by the method described). About 24 hours after transfection, the medium was replaced with a medium containing a test substance (n = 4) and cultured for 24 hours. DMSO was used as a solvent control, and 1/1000 amount was added to the medium. After washing the cells with phosphate buffered saline (PBS +) containing Ca and Mg, Looklite (PerkinElmer) was added, and luciferase was emitted using a top-count microplate scintillation / luminescence counter (PerkinElmer). The strength was measured. The ratio of the sample emission intensity to the control emission intensity was defined as the sample PPARα ligand activity.

  Table 6 shows the PPARα ligand activity of the perilla extract obtained in Example 1.

As a positive control, fenofibrate, a known PPARα ligand agent, was used. As apparent from Table 7, the perilla extract obtained in Example 1 showed significant PPARα ligand activity.

<Adjustment of capsule>
(Example 6)
A gelatin capsule (size: 40 parts by weight of the perilla extract prepared in Example 1, 30 parts by weight of carboxymethylcellulose sodium, 20 parts by weight of crystalline cellulose, and 10 parts by weight of vitamin C was mixed and ground. No. 02, Capsugel Japan Co., Ltd.) and a capsule for food and drink containing 40% by weight of the extract was prepared.

  According to the present invention, blood neutral fat elevation that can be used for foods and drinks such as health foods and health function foods (food for specified health use, nutritional function foods), pharmaceuticals, quasi drugs, cosmetics, and the like An inhibitory agent and a method for producing the same can be obtained.

  The blood triglyceride elevation inhibitor of the present invention has an excellent blood triglyceride elevation-suppressing action, and is effective for the prevention and / or improvement / treatment of hyperlipidemia, especially hypertriglyceremia. is there.

Claims (14)

  A blood neutral fat elevation inhibitor comprising as an active ingredient an extract of an aqueous ethanol solution having a concentration of 90 to 99.9% by volume of dried perilla frutescens.   Perilla frutescens Britton var. Acuta Kudo, Perilla frutescens Britton var. Crispa Decaisne forma crispa Makino and Perilla frutescens Britton var. Crispa Decaisne forma crispi-discolor Makino The blood neutral fat elevation inhibitor according to claim 1.   3. The blood neutral fat elevation inhibitor according to claim 1 or 2, wherein the dried perilla product is a dried product having a water content of less than 25%.   A lipid absorption inhibitor comprising the blood neutral fat elevation inhibitor according to any one of claims 1 to 3.   A lipase inhibitor comprising the blood neutral fat elevation inhibitor according to any one of claims 1 to 3.   A peroxisome proliferator-responsive receptor α-ligand agent comprising the blood neutral fat elevation inhibitor according to any one of claims 1 to 3.   The composition for prevention or improvement of hyperlipidemia containing the blood neutral fat rise inhibitor of any one of Claims 1-3.   The composition for prevention or improvement of the metabolic syndrome containing the blood neutral fat rise inhibitor of any one of Claims 1-3.   The composition according to claim 7 or 8, which is used for pharmaceuticals or veterinary drugs.   The composition according to claim 7 or 8, which is for food and drink.   The composition according to claim 7 or 8, which is used for quasi drugs.   A method for producing a blood neutral fat elevation inhibitor, wherein a dried perilla frutescens product is extracted with an aqueous ethanol solution having a concentration of 90 to 99.9% by volume.   Perilla frutescens Britton var. Acuta Kudo, Perilla frutescens Britton var. Crispa Decaisne forma crispa Makino and Perilla frutescens Britton var. Crispa Decaisne forma crispi-discolor Makino The manufacturing method of the blood neutral fat rise inhibitor of Claim 12.   14. The method for producing a blood neutral fat elevation inhibitor according to claim 12 or 13, wherein the dried perilla product is a dried product having a water content of less than 25%.