JPWO2005056031A1 - Lipase inhibitor - Google Patents

Abstract

Provided is a lipase inhibitor having high safety and excellent lipase inhibitory activity. A lipase inhibitor comprising, as an active ingredient, one or more plants selected from the group consisting of avocado, white-tailed cane, canister, jumbolan, peach peach, and lembu.

Description

  The present invention relates to a highly safe lipase inhibitor that effectively inhibits pancreatic lipase responsible for lipid digestion and absorption in vivo, and is effective in suppressing and preventing obesity and hyperlipidemia.

  Obesity associated with an increase in body fat and hyperlipidemia in which serum lipid levels are abnormally high are closely related to the development of various lifestyle-related diseases such as hypertension, arteriosclerosis and diabetes. Obesity is caused by constitutional factors, dietary factors, mental factors, central factors, metabolic factors, lack of exercise, etc., and as a result of the intake of calories exceeding the calories consumed, fat accumulates. The lipids in the diet are absorbed into the small intestine by breaking down triacylglycerol, which occupies most of the lipid, into monoacylglycerol and free fatty acids by lipase in pancreatic juice. Therefore, it is considered that by inhibiting this lipase action, absorption of diet-derived lipids can be suppressed, and obesity and hyperlipidemia can be suppressed.

From such a viewpoint, a search for a component having an excellent lipase inhibitory activity, that is, a naturally derived component having a lipid absorption inhibitory activity, has been energetically performed. To date, ginger, Tochu tea, white tea, green tea, black tea, oolong tea, phosphatidylcholine, soy protein, tannin, peonies, oren, peonies, buttonpi, gentian pepper, tea, kujin, bell pepper, pumpkin, shimeji, maitake, fujiki, It has been reported that dokkari, ryokyou, betel palm, yellow beetle, beetle, etc. have lipase inhibitory activity (Patent Documents 1 and 2). However, a sufficient effect has not been obtained yet.
JP 2002-179586 A JP 2002-275077 A

  Accordingly, an object of the present invention is to provide a lipase inhibitor having excellent lipase inhibitory activity and high safety. Another object of the present invention is to provide a lipid absorption inhibitor, an anti-obesity agent, and a hyperlipidemia improving agent.

  As a result of intensive studies on the lipase inhibitory action of many naturally derived plants, the present inventors have found that a specific plant or an extract thereof has excellent lipase inhibitory action and lipid absorption inhibitory action, and is highly safe. The present invention has been completed.

That is, the present invention relates to Avocado (Persea Americana Mill.), Flacotia inermis Roxb. The present invention provides a lipase inhibitor comprising as an active ingredient at least one plant selected from the group consisting of (Syzygium samarangense Merr & Perry) or an extract thereof.
The present invention also provides a lipid absorption inhibitor, an anti-obesity agent, and a hyperlipidemia-improving agent comprising these plants or extracts thereof as active ingredients.
Moreover, this invention provides use of these plants or its extract for manufacture of a lipid absorption inhibitor, an antiobesity agent, and a hyperlipidemia improving agent.
Furthermore, the present invention provides a method for inhibiting lipid absorption, a method for preventing obesity, and a method for improving hyperlipidemia, in which an effective amount of these plants or extracts thereof is administered.

  The fact that the specific plant or extract thereof used in the present invention has lipase inhibitory activity has never been known so far, and is a finding obtained for the first time by the present invention. These specific plants or extracts thereof have excellent lipase inhibitory activity and are extremely useful as lipase inhibitors, lipid absorption inhibitors, antiobesity agents, hyperlipidemia improving agents, and the like. Moreover, these specific plants or extracts thereof can be used as foods and drinks and cosmetics in order to suppress obesity and hyperlipidemia. Furthermore, since these specific plants or extracts thereof are naturally derived, it is possible to provide highly safe lipid absorption inhibitors, antiobesity agents, hyperlipidemia improving agents, and the like.

Plants used in the present invention include Avocado (Persea Americana Mill., Camphoraceae), White-footed Canco (Flacortia inermis Roxb., Musiaceae), Canister (Pouteria campechianae Baimni, Acatelana e. Family), yellow peach (Szygium jambos (Linn.) Alston, peach family) and renbu (Syzyum samarangense Merr & Perry, family peach family).
In addition to commercially available extracts of these plants, those obtained by performing an extraction operation from plants as described later may be used.

  The above-mentioned plant used in the present invention includes all parts such as leaves, stems, buds, flowers, woody parts, bark parts (barks), etc .; underground parts such as roots and tubers; seeds; fruits; Can be used. The plant or the extract thereof includes all of the pulverized product (raw or dried), the juice, the crude extract, and the purified product of the crude extract as they are. These may be used alone or in combination of two or more.

  Examples of extraction solvents for obtaining extracts from the above plants include lower alcohols such as methanol, ethanol, propanol, and butanol; esters such as ethyl acetate; ethylene glycol, butylene glycol, propylene glycol, 1,3-butylene alcohol, and glycerin. Examples thereof include polyhydric alcohols; ethers such as diethyl ether and petroleum ether; polar solvents such as acetone and acetic acid; hydrocarbon solvents such as benzene, hexane and xylene; physiological saline and water. As the extraction solvent, water or alcohol is preferable, and water is particularly preferable. These extraction solvents can be used singly or in combination of two or more.

As an extraction method, a general method can be used, for example, a method of immersing a dried product or a dried pulverized product in a solvent, a method of stirring under heating in a temperature range from room temperature to the boiling point of the solvent, and the like. Can do. The obtained extract may be used as it is after removing solids by filtration or centrifugation, if necessary, or may be used after concentration of the solvent or drying.
In the present invention, it is particularly preferable to use the solvent extract as a crude dried product of the plant extract after removing the solvent by means of reduced pressure drying, vacuum freeze drying or the like.

  For purification of the crude extract, a general method can be used, and examples thereof include adsorption / desorption using activated carbon, silica gel, polymer-based carrier, column chromatography, liquid-liquid extraction, fractional precipitation, and the like. be able to.

  The specific plant of the present invention or an extract thereof thus obtained has excellent lipase inhibitory activity as shown in the examples described later, and is a lipase inhibitor, lipid absorption inhibitor, antiobesity agent, and hyperlipidemia improving agent. It is effective as

  When the lipase inhibitor of the present invention is used as a medicine such as a lipid absorption inhibitor, an anti-obesity agent and a hyperlipidemia improving agent, either oral administration or parenteral administration can be used, and tablets, granules, Scattered, capsule, solution, suspension, emulsion, lyophilized preparation and the like. These preparations can be prepared by conventional means on the preparation. In order to prepare pharmaceutical formulations of such various dosage forms, other pharmaceutically acceptable carriers can be added as desired. For example, glucose, lactose, sucrose, starch, mannitol, dextrin, fatty acid glyceride, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid ester, amino acid, gelatin, albumin, water, physiological saline, etc. If necessary, conventional additives such as stabilizers, wetting agents, emulsifiers, binders, tonicity agents and the like can be appropriately added.

  The plant of this invention or its extract can also be mix | blended and used for food-drinks etc. Here, the food or drink is a health food useful for the treatment and prevention of obesity / hyperlipidemia by adding the above-mentioned plant or its extract as it is, or by adding various nutritional components or adding it to the food or drink. Or it is eaten as a food material. Examples of the form of the food and drink include granular forms, granular forms, tablets, capsules, pastes and the like obtained by adding conventional auxiliaries to active ingredients. In addition, processed meat products such as ham and sausage; processed fishery products such as kamaboko and chikuwa; foods such as bread, confectionery, butter, powdered milk and fermented dairy products, or beverages such as water, fruit juice, milk and soft drinks It can also be used.

  The effective dose of the plant of the present invention or an extract thereof is appropriately determined depending on the patient's age, body weight, symptoms, patient grade, administration route, administration schedule, formulation form, strength of inhibitory activity of the material, etc. For example, when the extract is administered orally, generally about 0.001 to 1000 mg / kg body weight in terms of dry weight per day is preferable. In the case of a hot water extract of Rembu (Syzygium samarangense Merr & Perry), about 5 to 300 mg / kg body weight in terms of dry weight per day is particularly preferable.

  Moreover, the plant of this invention or its extract can also be used as a lipase inhibitor containing cosmetic or cosmetic material. For example, the dried plant product of the present invention or an extract thereof can be added to wheat germ oil or olive oil to form a lipase inhibitor-containing composition, which can be used as a cosmetic material. Although the addition amount of the plant of this invention or its extract is not specifically limited, For example, it is 0.1-60 weight% or less in conversion of dry weight with respect to wheat germ oil or olive oil, Especially 0.5. -50% by weight is preferred.

When the above lipase inhibitor-containing composition is used as a cosmetic ingredient and is used as a cosmetic, various forms such as emulsion, cosmetic liquid, face cream, hand cream, lotion, essence, shampoo, rinse, etc. be able to. Such a cosmetic can be produced according to a conventional method. Moreover, the adjuvant generally used as a cosmetic ingredient can be used in any combination. The amount of the plant of the present invention or the extract thereof is preferably 0.01 to 20% by weight based on the total weight of the cosmetic in terms of dry weight.
Since the plant used in the present invention is naturally derived, its toxicity is low. For example, a hot water extract of Rembu (Syzygium samarangense Merr & Perry) is orally administered to rats over a long period of 1000 mg / kg every day for 100 days. Even after administration, no deaths were observed and no change in body weight was observed.

  Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited to these examples.

Example 1
(1) Extraction of plants Avocado (Persea Americana Mill.), Flacortia inermis Roxb. 200 mL of distilled water was added to 10 g of each of (Syzygium samarangense Merr & Perry, Myrtaceae), boiled at 100 ° C. for 30 minutes, and then freeze-dried to obtain each hot water extraction dried product.

(2) Lipase inhibitory activity test For measurement of lipase inhibitory activity, porcine pancreatic lipase (manufactured by Sigma) and "Lipase Kit S" manufactured by Dainippon Pharmaceutical Co., Ltd. were used. The measurement method was performed by partially modifying the manufacturer's instructions. That is, 150 μL of a sample solution containing an extract, 40 μL of an enzyme solution (porcine pancreatic lipase 0.05 mg / mL 125 mmol / L Tris-HCl (pH 7.5)), a coloring solution (0.1 mg / mL 5,5′-dithiobis ( 500 μL of a buffer solution containing 2-nitrobenzoic acid) was added and mixed, and then preheated at 30 ° C. for 5 minutes, and then the substrate solution (6.69 mg / mL dimercaprol tributyrate + 5.73 mg / mL sodium dodecyl sulfate) 50 μL After mixing, the mixture was reacted at 30 ° C. for 30 minutes in the dark. Thereafter, 1 mL of a reaction stop solution was added to stop the reaction. In the blank, a sample solution, an enzyme solution, and a coloring solution were added and heated at 30 ° C. for 5 minutes and at 30 ° C. for 30 minutes in the dark. After adding a reaction stop solution, a substrate solution was added. The absorbance of each sample was measured at a wavelength of 412 nm. The lipase inhibitory activity was calculated using the following formula.

(Equation 1)
Lipase inhibitory activity = 100- (AT-ABT) / (AC-ABC) × 100 (%)
AT: Absorbance of sample sample ABT: Blank absorbance of sample sample AC: Absorbance of blind sample ABC: Blank absorbance of blind sample

Comparative Example 1
Banaba, rosemary, guava, ruffa, rooibos, betel loin, allspice, hypericum, kawataketsume, salamander, gymnema, eucommia, elephant crotch, hawthorn, carrot, hypericum perforatum, lemongrass, cat's claw, jasmine, ginger, hop, sanshuyu, Similar tests were conducted for sun pens, carrots, wheat, savanna, pearl barley, beetle, apple, pumpkin, yacon, peonies, sendan, gymnema, and carrot.

The measurement results of the lipase inhibitory activity of each hot water extract are shown in Table 1.
All of the hot water extracts of the avocado, giant white cane, canister, jumbolan, peach peach and lembu of the present invention had high lipase inhibitory activity.

Example 2
(1) Extraction of plants In the same manner as in Example 1, from canister (Pouteria campechiana Baehni), Jamboran (Eugenia jambolana Lam.), Rembu (Syzygium samarangense Merr & Perg by dry water) Got.
(2) Lipid absorption inhibitory activity test ICR mice (male, 6-7 weeks old) fasted for 24 hours were forcibly administered with 200 μL of olive oil per mouse as a control group. On the other hand, in the test group, each hot water extract dried product was mixed with olive oil at a concentration of 100 mg / mL, and 200 μL was forcibly administered to each mouse. Blood samples were collected from the tail vein before forced administration and at 1, 2, 3, and 6 hours after administration, and serum was obtained by centrifugation. Triglyceride in serum was measured using “Triglyceride G Test Wako” of Wako Pure Chemical Industries. A graph with time on the horizontal axis and serum triglyceride concentration on the vertical axis was prepared, and the area under the curve was determined from the obtained curve, which was used as an index of lipid absorption inhibition activity. The lipid absorption inhibitory activity was expressed as a relative value of the area under the curve of each test group, where the area under the curve of the control group was 100.

Comparative Example 2
A similar test was conducted for banaba and green tea.

Table 2 shows the measurement results of the lipid absorption inhibitory activity of each hot water extract.
The extracts of canister, lembu and jumbolan of the present invention all had high lipid absorption inhibitory activity.

＊ 対照群の曲線下面積を１００とした。

* The area under the curve of the control group was 100.

Formulation Example 1
Various ingredients were mixed according to the following formulation, granulated, dried and sized, and then tableted to produce tablets.
(Prescription)
Jumbolan extract (Example 1) 40 mg
Microcrystalline cellulose 100
Lactose 80
Magnesium stearate 0.5
Methylcellulose 12

Formulation Example 2
According to the following formulation, each component was blended according to a conventional method and homogenized to obtain a soft drink. The obtained soft drink was filled in a brown bottle, sealed with an aluminum cap, and heat-treated. These had good appearance and flavor.
(Prescription)
Rembu extract (Example 1) 0.8g
Fragrance 0.8
Water 100
Reduced starch saccharified product 24
Fructose 18

Formulation Example 3
According to the following formulation, each component was blended according to a conventional method and homogenized to obtain a face cream.
(Prescription)
Isopropyl isostearate 8.0% by weight
Jojoba oil 6.0
Cetanol 8.0
Stearyl alcohol 2.0
Polyoxyethylene lauryl ether 1.5
Propylene glycol 6.0
Sorbitol 1.0
Paraben 0.4
Peach extract (Example 1) 0.5
Vitamin E 0.5
Fragrance 0.1
Water 66.0

Claims (10)

  A lipase inhibitor comprising, as an active ingredient, one or more plants selected from the group consisting of avocado, white-tailed cane, canister, jumbolan, peach peach, and lembu.   A lipid absorption inhibitor comprising, as an active ingredient, one or more plants selected from the group consisting of avocado, white-tailed cane, canister, jumbolan, peach peach, and lembu.   Use of one or more plants selected from the group consisting of avocado, white catfish, canister, jumbolan, peach peach and lembu or an extract thereof for the manufacture of a lipid absorption inhibitor.   A method for inhibiting lipid absorption, comprising administering an effective amount of one or more plants selected from the group consisting of avocados, canine milans, canisters, jumbolans, peach peaches, and lembes, or extracts thereof.   An antiobesity agent comprising as an active ingredient at least one plant selected from the group consisting of avocado, giant skeletal canistel, canister, jumbolan, peach peach and lembu.   Use of one or more kinds of plants selected from the group consisting of avocado, white-tailed cane, canister, jumbolan, peach peach and lembu or an extract thereof for the manufacture of an anti-obesity agent.   A method for preventing obesity, comprising administering an effective amount of at least one plant selected from the group consisting of avocado, giant cane, canister, jumbolan, peach peach and lembu, or an extract thereof.   A hyperlipidemia-improving agent comprising as an active ingredient at least one plant selected from the group consisting of avocado, white-tailed cane, canister, jumbolan, peach peach and lembu.   Use of one or more kinds of plants selected from the group consisting of avocado, giant skeletal dog, canister, jumbolan, peach peach and lembu or an extract thereof for the production of an agent for improving hyperlipidemia.   A method for improving hyperlipidemia, comprising administering an effective amount of one or more kinds of plants selected from the group consisting of avocados, canine milans, canisters, jumbo lans, peach peaches and lembes, or extracts thereof.