WO2010010949A1 - Lipase inhibitor - Google Patents

Abstract

Disclosed is a lipase inhibitor which has an excellent lipase-inhibiting activity, is highly safe, can be ingested orally, and has the potential to prevent/ameliorate postprandial hyperlipemia, lipid metabolism disorder, obesity, glucose metabolism disorder such as insulin resistance, a dermal disease induced by a bacterial or fungal lipase, and a body odor. The lipase inhibitor comprises at least one plant selected from the group consisting of Aralia cordata, Abelmoschus esculentus, a skin of a tuber of Colocasia esculenta, Sinapis albam, Fagopyrum esculentum, Lactuca sativa, a seed of Myristica fragrans, Daucus carota, Allium grayi, Lagenaria siceraria, Patasites japonicus, Persicaria hydropiper, Ocimum basilicum, Parasenecio delphiniifolius and Dioscorea japonica, or an extract from at least one plant selected from the group consisting of the above-mentioned plants.

Description

Lipase inhibitor

The present invention relates to a lipase inhibitor containing a specific plant or an extract thereof as an active ingredient.

In Japan, an increase in obesity has become a problem due to an increase in high-fat diet intake due to westernization of diet, overeating due to stress, lack of exercise, and the like. Among obesity, visceral fat-type obesity in which fat accumulates in the abdominal cavity results in an increase in the free fatty acid concentration in the portal vein and abnormal secretion of adipocytokines from adipocytes, a decrease in insulin action in the liver and a marked increase in adiponectin The decrease causes insulin resistance and hyperinsulinemia, and induces abnormal glucose metabolism (abnormal glucose tolerance) and abnormal lipid metabolism. In such obesity, diabetes, and dyslipidemia (hyperlipidemia / low HDL cholesterolemia), it is known that the risk of developing arteriosclerotic diseases such as myocardial infarction and cerebrovascular disorder is increased. It has been.

In recent years, abnormal rise in blood lipid concentration after meals and long-lasting state of increased blood lipid concentration have attracted attention as new risk factors for arteriosclerotic diseases. An increase in blood lipid concentration after a meal induces an increase in the amount of neutral fat in blood lipoproteins and increases in remnant lipoproteins and remnant-like particles (RLP). RLP is a risk factor involved in the development of atherosclerosis, and promotes impaired vascular endothelial function and macrophage foaming. In particular, it has been pointed out that in patients with diabetes or dyslipidemia, an increase in blood lipid concentration after meal becomes more prominent and the risk of developing arteriosclerosis is increased. That is, it can be said that suppressing the increase in blood lipid concentration observed after meal rather than the normal blood lipid concentration is an important therapeutic strategy in suppressing the risk of developing arteriosclerosis (Non-patent Document 1). ).

From the above, in order to prevent and ameliorate postprandial hyperlipidemia and dyslipidemia caused by intake of a high fat diet, it is useful to suppress the absorption of diet-derived fat in the body. The fat in the ingested food is hydrolyzed by the lipase secreted from the pancreas into the intestinal tract, where the ester bond of triacylglycerol, which is the main component of fat, is hydrolyzed into monoacylglycerol and free fatty acids. Is absorbed into the body. Therefore, if the degradation of fat in food can be suppressed by inhibiting the action of this lipase, absorption of fat into the body can be suppressed, and postprandial hyperlipidemia caused by high fat diet intake And prevention or improvement of dyslipidemia. Furthermore, improvement of glucose metabolism abnormalities such as obesity caused by high fat diet intake, insulin resistance and increase in blood insulin concentration can be expected.

In addition, lipases produced by resident human skin bacteria such as Propionibacterium acnes decompose fat in sebum into glycerin and free fatty acids. Among these free fatty acids, there are substances that adversely affect the skin, which may cause acne vulgaris, seborrheic dermatitis, etc., and free fatty acids may be further decomposed to cause body odor It has been known. Inhibiting the action of lipase is also useful for preventing and improving skin diseases such as acne vulgaris and body odor.

In view of the above, a lipase inhibitor that can be used easily such as oral ingestion, and can be used safely and continuously for a long period of time is desired, and a search for a substance having lipase inhibitory activity in natural products such as plants is conducted. I have been. As a lipase inhibitor derived from natural products known so far, an active ingredient is at least one solvent extract selected from mate leaves, amla fruits, cassis fruits, mugwort leaves, melissa leaves, and propolis. (Patent Document 1), Madr lilac (Glirichidia sepium (Jacq.) Walp), Nanban akazuki (Adenanthera pavonina), Kumikakan (Citrus hystrix), Ginkgoboku (Michelia alba), Buwasuwan (Gustavia gracillima), Chiermai (P) And an extract of a plant belonging to the genus Hipphophae (Patent Document 2), or an extract of a plant belonging to the genus Hipphophae (Patent Document 2) selected from Thunbergia laurifolia Patent Document 3), containing chestnut skin extract (Patent Document 4), Kidney chicken extract, Octopus plant extract, Maun Ten blueberry fruits, evergreen blueberry fruits, bilberry fruits, and one or more selected from bittern (Patent Document 5), Saponalia officinalis and ukogi (Acanthopanax sieboldianus) extract (Patent Document 6), an extract containing kale (Brassicaracoleracea var. Acephala) (Patent Document 7), Eucommia ulmoides tea ground product or an extract thereof (Patent Document 6) 8), those containing extracts such as Arjun and Akarakara (Patent Document 9), those containing an extract of Eugenia uniflora (Non-Patent Document 2), gallotannins separated from tea or Tellima grandiflora and There are ellagitannins (patent document 10), epigallocatechin dimer (patent document 11), etc., derived from oolong tea Compounds oolong theanine-3'-O-gallate (Patent Document 12) and is also known, such as myricitrin (Patent Document 13). In addition, although the nutmeg extract is also disclosed by patent document 9, in the said patent document, the outstanding lipase inhibitory action which the nutmeg seed extract used in this invention has is not shown. Moreover, although the taro (Colocasia esculenta) extract is also disclosed by patent document 13, in the said patent document, the outstanding lipase inhibitory action which the taro tuber peel extract used in this invention has is not shown.

However, many of the lipase inhibitors that have been presented in the past cannot actually exert an effective lipase inhibitory effect when they are actually formulated and used by oral ingestion, or the lipase inhibitory activity is not practical. Based on experimental results under no ingestion conditions, few were fully satisfactory.

JP 2008-50301 A JP 2007-246429 A JP 2007-161645 A JP 2007-145802 A JP 2007-145753 A JP 2006-348054 A JP 2006-62985 A JP 2005-289951 A Japanese Patent Laying-Open No. 2005-8572 JP 2006-56850 A JP 2006-16367 A JP 2006-1909 A International Publication No. 2007/119837 Pamphlet

J. Atheroscler. Thromb. 11 322-329 (2004) J. Ethnopharmacol. 68 307-314 (1999)

Therefore, in the present invention, it has an excellent lipase inhibitory action, is highly safe and can be taken orally, and in particular prevents or improves postprandial hyperlipidemia and dyslipidemia caused by high fat diet intake Furthermore, it is an object of the present invention to provide a lipase inhibitor that is effective in preventing and improving obesity and is also expected to prevent and improve glucose metabolism abnormalities such as insulin resistance and an increase in blood insulin concentration. In addition, by inhibiting lipases produced by human skin resident bacteria such as Propionibacterium acnes, skin diseases and body odors caused by bacterial or fungal lipases such as acne vulgaris and seborrheic dermatitis An object of the present invention is to provide a lipase inhibitor capable of preventing and improving the above.

In order to solve the above-mentioned problems, the present inventors have sought edible plant extracts and components containing lipase inhibitory activity and conducted intensive studies. As a result, specific plants or extracts thereof are excellent. It has been found that the lipase has a lipase inhibitory activity, and the present invention has been completed.

That is, the present invention relates to the following [1] to [13].
[1] Udo (Aralia cordata), okra (Abelmoschus esculentus), taro (Colocasia esculenta) tuber bark, white pepper (Sinapis alba), buckwheat (Fagopyrum esculentum), chisha (Lactuca sativa), sea urchin (Myristica fragrans) Carrots (Daucus carota), Nobil (Allium grayi), Gourd (Lagenaria siceraria), Japanese cypress (Patasites japonicus), Purple sardine (Persicaria hydropiper), Japanese cypress (Ocimum basilicum), Japanese mosquito (Parasenecio delphiniifolius), Damacore (Dioscore) A lipase inhibitor containing one or more of a plant selected from the above or an extract thereof.
[2] The lipase inhibitor according to [1] above, wherein the plant extract is prepared by extraction with water, an organic solvent, or a mixed solvent thereof.
[3] The organic solvent is one or more selected from the group consisting of lower alcohol, 1,3-butanediol, glycerin, ethers, ethyl acetate, acetone, chloroform, dichloromethane, acetonitrile and hexane, The lipase inhibitor according to [2].
[4] Fat absorption inhibitor, agent for preventing or improving postprandial hyperlipidemia, agent for preventing or improving dyslipidemia, anti-obesity agent, agent for improving insulin resistance, agent for improving or reducing blood insulin concentration, bacterial property Or any one of the above-mentioned [1] to [3] used as one or more selected from the group consisting of a preventive or ameliorating agent for skin diseases caused by fungal lipase and a prophylactic or improving agent for body odor The lipase inhibitor described in 1.
[5] Fat absorption inhibitor, postprandial hyperlipidemia preventive or ameliorating agent, dyslipidemia preventive or ameliorating agent, anti-obesity agent, insulin resistance improving agent, blood insulin concentration improving or decreasing agent, bacterial Or any one of [1] to [3] above for producing one or more selected from the group consisting of a prophylactic or improving agent for skin diseases caused by fungal lipase and a prophylactic or improving agent for body odor Use of the lipase inhibitor according to claim 1.
[6] A method for suppressing fat absorption, comprising administering an effective amount of the lipase inhibitor according to any one of [1] to [3] to an administration subject.
[7] A method for preventing or improving postprandial hyperlipidemia, comprising administering an effective amount of the lipase inhibitor according to any one of [1] to [3] to an administration subject.
[8] A method for preventing or improving dyslipidemia, comprising administering an effective amount of the lipase inhibitor according to any one of [1] to [3] to an administration subject.
[9] A method for preventing or ameliorating obesity, comprising administering an effective amount of the lipase inhibitor according to any one of [1] to [3] to an administration subject.
[10] A method for preventing or improving abnormal sugar metabolism, comprising administering an effective amount of the lipase inhibitor according to any one of [1] to [3] to an administration subject.
[11] A method for preventing or ameliorating a skin disease caused by a bacterial or fungal lipase, comprising administering an effective amount of the lipase inhibitor according to any one of [1] to [3] to an administration subject.
[12] A method for preventing or improving body odor, comprising administering an effective amount of the lipase inhibitor according to any one of [1] to [3] to an administration subject.
[13] The lipase inhibitor according to any one of [1] to [3], and the lipase inhibitor as a fat absorption inhibitor, a preventive or ameliorating agent for postprandial hyperlipidemia, a prevention or improvement of dyslipidemia Selected from agents, anti-obesity agents, insulin resistance improving agents, blood insulin concentration improving or decreasing agents, preventing or improving skin diseases caused by bacterial or fungal lipases, and preventing or improving body odor Or a commercial package containing documents stating that it can or should be used as two or more.

According to the present invention, a novel lipase inhibitor can be provided. The lipase inhibitor has an excellent lipase inhibitory action, is excellent in safety and can be taken orally, and is a fat absorption inhibitor, a postprandial hyperlipidemia, a preventive or ameliorating agent for dyslipidemia, anti-obesity It is useful as an agent, an insulin resistance improving agent, and a blood insulin concentration improving or reducing agent. It can also be used externally, and as a lipase inhibitor in the skin, it is also useful for the prevention and improvement of skin diseases and body odor caused by bacterial or fungal lipases such as acne vulgaris and seborrheic dermatitis.

In measurement of the blood triglyceride concentration increase inhibitory effect, it is a figure which shows the area under the time curve of the blood triglyceride density | concentration of the lipase inhibitor of an Example and a control ingestion group.

In the present invention, Udo (Aralia cordata), Okra (Abelmoschus esculentus), taro (Colocasia esculenta) tuber skin, Sinapis alba, buckwheat (Fagopyrum esculentum), chisha (Lactuca sativa), ク fragrant (Myrist) Seeds, carrots (Daucus carota), nobil (Allium grayi), gourd (Lagenaria siceraria), Japanese cypress (Patasites japonicus), purple sardine (Persicaria メ hydropiper), Japanese cypress (Ocimum basilicum), Japanese moth (ios) One kind or two or more kinds of plants selected from the group or an extract thereof are used.

For the purposes of the present invention, all parts such as inflorescences, leaves, stems, buds, woody parts, bark parts (bark) of the above plants, underground parts such as roots, rhizomes, seeds, fruits, mugagos, etc. are used. be able to. Further, a resin or a leachate may be used, or whole plant may be used, but it is preferable to use a site containing a large amount of a component having lipase inhibitory activity. However, the tuber bark is used for taro, and the seed is used for nutmeg.

The Udo (Aralia cordata) used in the present invention is a perennial plant belonging to the genus Araliaceae (Araliaceae), and the alias is referred to as independent. For the purpose of the present invention, mainly leaves, stems, buds and buds are preferably used.

The okra (Abelmoschus esculentus) used in the present invention is an annual plant of the genus Malvaceae, Abelmoschus, and there is another name for American noodles and okarenkon. For the purpose of the present invention, mainly fruits and seeds are preferably used.

The taro (Colocasia （esculenta) used in the present invention is a plant belonging to the genus Araceae (Colocasia), and the varieties of the genus include shrimp potato, celebes, hoopoe, potato, ishikawase, dodare, etc. It is included in the taro of the present invention. For the purposes of the present invention, the bark of the underground part of the stem (tuber) is used.

<Sinapis alba> used in the present invention is a perennial of the family Brassicaceae (Cruciferae), and the alias is also referred to as chrysanthemum. For the purposes of the present invention, buds are mainly preferably used.

The buckwheat (Fagopyrum esculentum) used in the present invention is an annual plant of the family Polygonaceae (Fagopyrum). For the purposes of the present invention, buds are mainly preferably used.

The chisha (Lactuca sativa) used in the present invention is an annual or biennial plant of the genus Lactuca (Compositae), and another name is lettuce. For the purposes of the present invention, mainly leaves are preferably used.

The nutmeg (Myristica fragrans) used in the present invention is an evergreen tree belonging to the genus Myristicaceae (Myristica), and the alias is called nutmeg. Seeds are used for the purposes of the present invention.

The carrot (Daucus carota) used in the present invention is an annual or biennial plant of the genus Umbelliferae carrot (Daucus). For the purposes of the present invention, mainly leaves are preferably used.

The nobil (Allium grayi) used in the present invention is a perennial plant belonging to the genus Liliaceae (Allium). For the purposes of the present invention, mainly bulbs or roots are preferably used.

The gourd (Lagenaria siceraria var. Gourda) used in the present invention is a plant belonging to the genus Cucurbitaceae and Lagenaria. For the purposes of the present invention, mainly leaves are preferably used.

The cypress (Patasites japonicus) used in the present invention is a perennial of the Compositae genus (Patasites). For the purposes of the present invention, mainly leaves, stems and flower stems (Fukinotou) are preferably used.

The Murasakide (Persicaria hydropiper) used in the present invention is an annual plant of the family Polygonaceae (Persicaria), and is also referred to as Yanagita or Benitade. In addition to inflorescences, leaves, and stems, whole plants are preferably used for the purposes of the present invention.

«Ocimum basilicum used in the present invention is an annual plant of the genus Labiatae (Ocimum), and is also referred to as basil or basil. For the purposes of the present invention, mainly leaves and seeds are preferably used.

The Japanese maple (Parasenecio delphiniifolius) used in the present invention is a plant belonging to the genus Compositae (Parasenecio), and is also referred to as Sidke, Sitgi, Sidoki or Momijisou. For the purposes of the present invention, inflorescences, leaves and stems are preferably used.

The Dioscorea japonica used in the present invention is a vine perennial plant belonging to the genus Dioscoreaceae and Dioscorea Rhizoma, and is a base plant of the herb medicine “Dioscoreae Rhizoma”, also called as yam and jinenjo The For the purposes of the present invention, rooted roots and mugagos that have been developed mainly as cocoons are preferably used.

In the present invention, the above-mentioned plant shredded product, dried product, pulverized product, pressed product or extract is used. The cut pieces may be of a size that can be taken orally or can be blended into an external preparation for skin, and a cut piece having a size of about 0.1 to 10 mm is usually used. However, the cut pieces may be dipped in water, warm water, hot water, hydrous alcohol, or the like, or may be blended in a skin external preparation. The dried product may be in a solid state, for example, preferably having a moisture content of 1% or less. The dried product is preferably in a powdered or granular state, or compressed into tablets, encapsulated, or suspended in an aqueous carrier, or incorporated into an external preparation for skin. The pulverized product may be in a solid or semi-solid state, in a powder or granule state, or tableted, encapsulated, or suspended in an aqueous carrier, or incorporated into an external preparation for skin. Is preferred. The pressed product may be in a solid or semi-solid state, in a powder or granule state, or tableted, encapsulated, or suspended in an aqueous carrier, or incorporated into an external preparation for skin. Is preferred.

Next, the extract will be described. Depending on the plant, the extraction method may be slightly different, but it is generally prepared by the following procedure. That is, the plant may be subjected to extraction as it is, but considering the extraction efficiency, it is preferable to perform the extraction after processing such as shredding, drying, and pulverization. Extraction is performed by immersing in an extraction solvent. In order to increase the extraction efficiency, stirring may be performed, or homogenization may be performed in an extraction solvent. The extraction temperature can be performed at room temperature or under heating, and is suitably from about 1 ° C. to the boiling point of the extraction solvent, usually 1 ° C. to 100 ° C., preferably 20 ° C. to 90 ° C. . The extraction time varies depending on the plant to be extracted, the type of extraction solvent, and the extraction temperature, but it is appropriate that the extraction time be about 4 hours to 14 days.

Examples of the extraction solvent include water, lower alcohols such as methanol, ethanol, propanol, and isopropanol, polyhydric alcohols such as 1,3-butanediol, propanediol, dipropanediol, and glycerin, diethyl ether, dipropyl ether, and the like. Ethers, esters such as ethyl acetate and butyl acetate, ketones such as acetone and ethyl methyl ketone, and organic solvents such as chloroform, dichloromethane, acetonitrile and hexane can be used, and one or more of these can be selected. And use. Further, physiological saline, phosphate buffer, phosphate buffered physiological saline, or the like may be used.

Among the above extraction solvents, water, an organic solvent, or a mixed solvent thereof can be preferably used in the present invention. As the organic solvent, lower alcohol, 1,3-butanediol, glycerin, ethers, ethyl acetate, acetone, chloroform, dichloromethane, acetonitrile and hexane can be preferably used, and one or more of these are selected and used. Further, as the lower alcohol, methanol and ethanol are particularly preferable, and as the ether, diethyl ether is particularly preferable.

Although the extract of the above-mentioned plant by the above-mentioned solvent can be used as it is as the lipase inhibitor according to the present invention, the concentrated and dried solid is not dissolved again in water or an organic solvent, or the lipase-inhibiting action is not impaired. It may be used after performing purification treatment such as decolorization, deodorization, and desalting within a range, or fractionation treatment by column chromatography using an ion exchange resin or the like. For storage, it can be freeze-dried after purification and dissolved in a solvent before use. In the present invention, the extract of the above-mentioned plant or the above-mentioned processed product of the above-mentioned plant is contained as it is or in an aqueous carrier such as water or lower alcohol, a base such as an emulsion, gel or cream, or powdered or granulated. A lipase inhibitor. It can also be encapsulated in vesicles such as liposomes or microcapsules.

Further, the lipase inhibitor according to the present invention includes cellulose and derivatives thereof such as crystalline cellulose and hydroxypropylcellulose, starch and derivatives thereof such as wheat starch, corn starch, sodium carboxymethyl starch, dextrin, gum arabic, sodium alginate and the like. Natural polymer compounds, sugars such as glucose, maltose, sorbitol, maltitol, mannitol and their derivatives, excipients such as inorganic salts such as sodium chloride, calcium carbonate, magnesium silicate, guar gum, synthetic aluminum silicate, stearic acid , High molecular weight polyvinylpyrrolidone, binders such as lactose, lubricants such as talc, magnesium stearate, polyethylene glycol 6000, adipic acid, calcium stearate, sucrose, etc. Agent, surfactant such as sucrose fatty acid ester, soybean lecithin, polyoxyethylene hydrogenated castor oil, polyoxyethylene monostearate ester, thickener such as sodium carboxymethylcellulose, carboxyvinyl polymer, xanthan gum, gelatin, ethyl acrylate・ Methyl methacrylate copolymer dispersion, caramel, carnauba wax, shellac, sucrose, pullulan and other coating agents, citric acid, sodium citrate, acetic acid, sodium acetate, sodium hydroxide and other pH adjusters, ascorbic acid, tocopherol acetate, natural Antioxidants such as vitamin E and propyl gallate, aspartame, licorice extract, flavoring agents such as saccharin, sodium benzoate, sodium edetate, sorbic acid, sodium sorbate, paraoxy Preservatives such as methyl benzoate and butyl paraoxybenzoate, bengara, yellow iron oxide, black iron oxide, carmine, edible blue No. 1, edible yellow No. 4, edible yellow No. 4 aluminum lake, edible red No. 2, copper chlorophyllin Additives such as colorants such as sodium can be included.

The lipase inhibitor according to the present invention is excellent in safety when taken orally, and therefore can be applied by a simple method of oral administration or by a method such as external use. In the present invention, one or more selected from the above plants or extracts thereof may be administered as they are, or may be administered together with various additives. Furthermore, it is formulated using various carriers or bases, additives, etc., and includes tablets, pills, capsules, ampoules, syrups, suspensions, emulsions, elixirs, drops, including sugar-coated tablets and film coating agents. , Lozenges, chewables, powders, granules and the like. In addition, the lipase inhibitor according to the present invention is added to foods and drinks such as liquid, semi-solid, solid or powder, health functional foods such as food for specified health use, nutritional functional foods, nutritional supplements, etc. And can be added to veterinary drugs such as mice, rats, hamsters, rabbits, cats, dogs, cows, sheep, monkeys, and animal feeds. Further, it can be added to external preparations as a lipase inhibitor in the skin and provided as external medicines, cosmetics and the like.

In addition, when the food or drink is a health functional food such as a food for specified health use, a nutritional functional food or the like, or a nutritional supplement, the food containing a single dose of the lipase inhibitor according to the present invention is A beverage in which a single dose of a lipase inhibitor according to the present invention is suspended or dissolved in a form that is packaged or filled in a bag or a box in the form of a single-feeding amount per serving. It can be provided in a form filled in a bottle or the like in the form of a drink per meal.

In the lipase inhibitor according to the present invention, the content of one or more selected from the above-mentioned plants or extracts thereof is different depending on the extraction conditions, addition form, dosage form, dosage form, etc. of the plant, but usually dried The weight is 0.05 to 100% by weight, preferably 0.5 to 90% by weight.

The lipase inhibitor according to the present invention has an excellent lipase inhibitory action and effectively inhibits fat hydrolysis and absorption. Therefore, the lipase inhibitor according to the present invention includes a fat absorption inhibitor, a postprandial hyperlipidemia, a prophylactic or ameliorating agent for dyslipidemia, an anti-obesity agent, an insulin resistance ameliorating agent, a blood insulin concentration improving or decreasing agent. Therefore, it can be used for producing the fat absorption inhibitor and the like. In addition, the lipase inhibitor according to the present invention inhibits lipases produced by human skin resident bacteria such as acne bacteria, thereby preventing bacterial or fungal lipases such as acne vulgaris and seborrheic dermatitis. It can be used for the prevention and improvement of the resulting skin diseases and body odors, and thus can be used to produce preventive or ameliorating agents for the skin diseases and the like.

Furthermore, the present invention provides a method for suppressing fat absorption, comprising administering an effective amount of the above lipase inhibitor to an administration subject such as a person or animal who needs to suppress fat absorption.

Further, the present invention is to administer an effective amount of the above lipase inhibitor to an administration subject such as postprandial hyperlipidemia or dyslipidemia, or a patient or animal exhibiting the above symptoms. The prevention or improvement method of those containing is provided. Here, “postprandial hyperlipidemia” means that the fasting lipid level is normal, but the postprandial lipid level is abnormally high, or the lipid level remains high even after the postprandial time State. In addition, “dyslipidemia” refers to hyperlipidemia in which one or both of cholesterol and triglyceride constituting serum lipids are increased, and low HDL cholesterol blood in which high-density lipoprotein (HDL) cholesterol levels are decreased. Refers to illness.

Furthermore, the present invention provides a method for preventing or ameliorating obesity, comprising administering an effective amount of the above lipase inhibitor to a subject who is likely to be obese or an obese patient. “Obesity” generally refers to a state in which the body weight is higher than in a normal state or a state in which body fat is excessively accumulated. According to the standards of the Japanese Society of Obesity, the body mass index (BMI) is 25 or more. This is the case.

Furthermore, the present invention provides prevention of abnormal glucose metabolism, comprising administering an effective amount of the above lipase inhibitor to a subject to be administered, improving insulin resistance of the subject to be administered, or improving or lowering blood insulin concentration. Or provide an improvement method. “Abnormal glucose metabolism” refers to an abnormality in glucose metabolism (abnormal glucose tolerance). The lipase inhibitor of the present invention has normal glucose metabolism in a state where the blood glucose lowering ability of secreted insulin is reduced, and as a result, insulin production is increased and blood insulin concentration is increased. It is effective in preventing or improving the state of being lost.

Furthermore, the present invention provides a method for preventing or ameliorating a skin disease caused by a bacterial lipase or a fungal lipase, which comprises administering an effective amount of the above lipase inhibitor to the skin of the administration subject. Skin diseases caused by bacterial lipase include acne vulgaris involving lipase produced by Propionibacterium acnes. Acne vulgaris is commonly referred to as “acne” and refers to a skin rash (comedo) caused by a clogged hair follicle. When the hair follicle is inflamed, it becomes a red papule. Skin diseases caused by fungal lipase include seborrheic dermatitis involving lipase produced by Malassezia fungus (Malassezia sp.), Dandruff involving lipase produced by dandruff (Malassezia furfur), etc. It is done.

Furthermore, the present invention provides a method for preventing or improving body odor such as odor, which comprises administering an effective amount of the above lipase inhibitor to a subject of administration.

When using the lipase inhibitor according to the present invention as the fat absorption inhibitor or the like, or when providing a method for suppressing fat absorption, a method for preventing or improving hyperlipidemia, a method for preventing or improving body odor, The dose of one or more selected from plants or extracts thereof varies depending on the condition of the administration subject (patient etc.), disease state, age, preparation method of the extract, dosage form, administration form, administration route, etc. The dry weight is about 0.01 to 20 g / day for human adults, preferably about 0.05 to 10 g / day, more preferably about 0.1 to 3 g / day. This can be administered once, but can be divided into 2 to 5 doses as needed.

Further, in the present invention, the lipase inhibitor according to the present invention, and the lipase inhibitor as a fat absorption inhibitor, a postprandial hyperlipidemia preventive or ameliorating agent, a lipid metabolism abnormality preventive or ameliorating agent, an antiobesity agent As one or more selected from an agent for improving insulin resistance, an agent for improving or reducing blood insulin concentration, an agent for preventing or improving skin diseases caused by bacterial or fungal lipase, and an agent for preventing or improving body odor Commercial packages can be provided that contain documents that can be used or should be used.

Further, the present invention will be described in detail by examples.

40 mL of methanol was added to 1 g of the lyophilized powder of the plant shown in Table 1 and allowed to stand overnight at room temperature, followed by filtration to collect the filtrate. The filtrate was then evaporated to dryness to obtain the lipase inhibitors of Examples 1 to 15.

The lipase inhibitory activity of the lipase inhibitors of Examples 1 to 15 was measured. The measurement of lipase inhibitory activity was carried out using porcine pancreatic lipase (manufactured by Sigma) and 4-methylumbelliferyl oleate (4-MUO) (manufactured by Sigma) as a substrate. It carried out on condition of this. Specifically, 10 mg of the lipase inhibitor of each example was dissolved in dimethyl sulfoxide (DMSO), 5 μL of the solution and an enzyme solution (0.25 mg / mL porcine pancreatic lipase phosphate buffered saline (PBS) solution) After mixing with 45 μL for 5 minutes, 50 μL of substrate solution (100 mM 4-MUO PBS solution) was added and reacted at 37 ° C. for 30 minutes. Immediately after the decomposition of 4-MUO at an excitation wavelength of 355 nm and a fluorescence wavelength of 460 nm Fluorescence intensity was measured. In addition, 5 μL of DMSO was used as a control, and a blank measured by adding only PBS without adding enzyme at each of the addition of the lipase inhibitor and the control was added as a blank. The lipase inhibitory activity was calculated by the following formula. The results are summarized in Table 1.
Lipase inhibitory activity (%) = {1− (EM _s −EM _sb ) / (EM _c −EM _cb )} × 100
EM _s : fluorescence intensity of the 4-MUO degradation product when the lipase inhibitor of the example was added EM _sb : fluorescence intensity of the blank when the lipase inhibitor of the example was added EM _c : fluorescence of the 4-MUO degradation product when the control was added Intensity EM _cb : fluorescence intensity of blank at the time of control addition

As is clear from Table 1, all of the lipase inhibitors of the examples of the present invention showed strong lipase inhibitory activity, and an inhibition rate of 70% or more was recognized in the lipase inhibitors of all the examples. In particular, in the lipase inhibitors of Example 2, Example 3, Example 5, Example 7, Example 9, and Example 15, an inhibitory activity of 90% or more was observed.

Subsequently, about the lipase inhibitor of the said Example 2 and Example 7 of this invention, the blood neutral fat concentration raise inhibitory effect was measured. The measurement was performed by suspending the lipase inhibitor of each Example in a 0.5% by weight aqueous sodium carboxymethylcellulose solution as a sample, and using a 0.5% by weight aqueous sodium carboxymethylcellulose solution as a control for 5 weeks in each group. Aged C57BL / 6J male mice were used. That is, each sample and control was orally administered to the mice at a rate of 1 g / kg body weight, and 15 minutes later, extra virgin olive oil (manufactured by J-Oil Mills) was orally administered 4.5 g / kg body weight. . Blood was collected from the fundus vein every 90 minutes, FUJI DRI-CHEM 7000 (manufactured by Fuji Photo Film Co., Ltd.) to measure the blood neutral fat concentration using, the time from the change graph of area under the curve AUC 0-6 _(mg / dL · hr) was calculated. The measurement results are shown in FIG. 1 as the mean value ± standard error of each group.

As is clear from FIG. 1, AUC _0-6 increased to about 6400 (mg / dL · hr) in the control intake group, but 3500 (mg / dL · hr) in the lipase inhibitor intake group of Example 2. ), About 4200 (mg / dL · hr) in the lipase inhibitor intake group of Example 7, and in the lipase inhibitor intake group of the Example of the present invention, blood neutral fat after lipid intake It was shown that the increase in concentration was remarkably suppressed. The suppression of the increase in blood triglyceride concentration was significant at p <0.01 between the lipase inhibitor intake group of Example 2 and the lipase inhibitor intake group of Example 7 and the control intake group, respectively. Differences were noted.

According to the present invention, it has excellent lipase inhibitory action and safety, resulting from abnormal glucose metabolism such as postprandial hyperlipidemia, dyslipidemia, obesity, insulin resistance, and bacterial or fungal lipase It is possible to provide an orally ingestible lipase inhibitor that is expected to prevent and improve skin diseases and body odor.

Although several specific embodiments of the present invention have been described in detail, those skilled in the art will recognize that various modifications may be made to the specific embodiments shown without departing from the teachings and advantages of the invention. It is possible to make changes. Accordingly, all such modifications and changes are intended to be included within the spirit and scope of the invention as claimed in the following claims.

This application is based on Japanese Patent Application No. 2008-191208 filed in Japan, the contents of which are incorporated in full herein.

Claims (13)

Udo (Aralia cordata), okra (Abelmoschus esculentus), taro (Colocasia esculenta) tuber bark, white pepper (Sinapis alba), buckwheat (Fagopyrum esculentum), chisha (Lactuca sativa), Nikuzuku (Myristica fragrans) carota), nobil (Allium grayi), gourd (Lagenaria siceraria), Japanese cypress (Patasites japonicus), purple sardine (Persicaria hydropiper), Japanese cypress (Ocimum basilicum), maple mosquito (Parasenecio delphiniifolius), Dioscorea (D) A lipase inhibitor containing one or more of plants or extracts thereof. The lipase inhibitor according to claim 1, wherein the plant extract is prepared by extraction with water, an organic solvent, or a mixed solvent thereof. The organic solvent is one or more selected from the group consisting of lower alcohol, 1,3-butanediol, glycerin, ethers, ethyl acetate, acetone, chloroform, dichloromethane, acetonitrile, and hexane. The lipase inhibitor described. Fat absorption inhibitor, postprandial hyperlipidemia prevention or improvement agent, lipid metabolism disorder prevention or improvement agent, anti-obesity agent, insulin resistance improvement agent, blood insulin concentration improvement or reduction agent, bacterial or fungal The lipase inhibition according to any one of claims 1 to 3, which is used as one or more selected from a preventive or ameliorating agent for skin diseases caused by lipase and a prophylactic or improving agent for body odor. Agent. Fat absorption inhibitor, postprandial hyperlipidemia prevention or improvement agent, lipid metabolism disorder prevention or improvement agent, anti-obesity agent, insulin resistance improvement agent, blood insulin concentration improvement or reduction agent, bacterial or fungal The method according to any one of claims 1 to 3, for producing one or more selected from the group consisting of a preventive or ameliorating agent for skin diseases caused by lipase and a prophylactic or improving agent for body odor. Use of lipase inhibitors. A method for suppressing fat absorption, comprising administering an effective amount of the lipase inhibitor according to any one of claims 1 to 3 to an administration subject. A method for preventing or improving postprandial hyperlipidemia, comprising administering an effective amount of the lipase inhibitor according to any one of claims 1 to 3 to an administration subject. A method for preventing or improving dyslipidemia, comprising administering an effective amount of the lipase inhibitor according to any one of claims 1 to 3 to an administration subject. A method for preventing or ameliorating obesity, comprising administering an effective amount of the lipase inhibitor according to any one of claims 1 to 3 to an administration subject. A method for preventing or improving glucose metabolism abnormality, comprising administering an effective amount of the lipase inhibitor according to any one of claims 1 to 3 to an administration subject. A method for preventing or ameliorating a skin disease caused by a bacterial or fungal lipase, comprising administering an effective amount of the lipase inhibitor according to any one of claims 1 to 3 to an administration subject. A method for preventing or improving body odor, comprising administering an effective amount of the lipase inhibitor according to any one of claims 1 to 3 to an administration subject. The lipase inhibitor according to any one of claims 1 to 3, and the lipase inhibitor as a fat absorption inhibitor, an agent for preventing or improving postprandial hyperlipidemia, an agent for preventing or improving dyslipidemia One selected from anti-obesity agents, insulin resistance improving agents, blood insulin concentration improving or decreasing agents, preventing or improving skin diseases caused by bacterial or fungal lipase, and preventing or improving body odor A commercial package containing documents stating that it can or should be used as two or more.

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