JPH11180869A - Blood lipid improving agent, cyclic amp phosphodiesterase inhibitor, drink and food, and skin preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a blood lipid improving agent effective for treating hyperlipemia, an inhibitor which inhibits cyclic AMP phosphodiesterase activity to reduce body fat, drinks and foods effective for improving blood lipid and reducing body fat, and the like by including bergenin as an active component. SOLUTION: Bergenin of the formula obtained, for example, by extracting bergenin containing pars of a plant raw material with water, methanol, ethanol, propanol, 1,3-butylene glycol or the like, and purifying the extract is compounded as an active component. Suitable daily intake in terms of bergenin is 10-3,000 mg, preferably 50-1,000 mg, for an adult.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a blood lipid improving agent effective for preventing and treating hyperlipidemia, a cyclic AMP phosphodiesterase inhibitor which inhibits the action of cyclic AMP phosphodiesterase to reduce body fat, The present invention relates to a food and drink which is effective for improving blood lipids and reducing body fat, and an external preparation for skin.

[0002] In this specification, the action of lowering the total cholesterol level in blood is generically called "improvement of blood lipid".

[0003]

2. Description of the Related Art In recent years, as eating habits have become westernized, more and more Japanese people are suffering from circulatory diseases such as hyperlipidemia and obesity due to excessive accumulation of body fat.

Hyperlipidemia is a disease in which one or more components among serum lipids, ie, cholesterol, triglycerides, phospholipids, free fatty acids, etc., abnormally increase, causing various disorders. Cholesterol and hypertriglyceridemia.

[0005] Conventionally, as a drug for lowering the blood cholesterol concentration, a drug comprising many synthetic chemical substances such as pravastatin has been developed and used for treatment. However, they are superior in efficacy but have side effects and cannot be used unless prescribed by a physician, and are not suitable for healthy individuals to regularly use for the purpose of preventing hyperlipidemia and obesity. there were.

In order to eliminate the excessive accumulation of body fat, which often accompanies hyperlipidemia, the action of the cyclic AMP phosphodiesterase, an enzyme that degrades cyclic AMP involved in promoting fat metabolism, is required. It is effective to suppress. That is, when the action of cyclic AMP phosphodiesterase is suppressed, the concentration of intracellular cyclic AMP increases, fat metabolism becomes active, and obesity is eliminated.

[0007] As substances having a cyclic AMP phosphodiesterase inhibitory activity, extracts of soybean arbor, chile, and the like are conventionally known, but the effect is not remarkable.

[0008]

An object of the present invention is to provide a novel means for improving blood lipids and preventing and eliminating obesity.

Another object of the present invention is to find a substance having both a blood lipid improving action and a cyclic AMP phosphodiesterase inhibitory action from natural components having high safety and to improve blood lipids and prevent obesity. It is to provide a new means for solving the problem.

[0010] Still another object of the present invention is to provide a highly safe natural substance to improve blood lipids and improve cyclic A activity.
An object of the present invention is to provide a novel food or drink having an MP phosphodiesterase inhibitory action.

Still another object of the present invention is to provide a skin external preparation which has an effect of eliminating an excessive accumulation of subcutaneous fat by adding a natural substance having a cyclic AMP phosphodiesterase inhibitory action.

[0012]

The present invention is based on the novel finding that bergenin has both a blood lipid improving action and a cyclic AMP phosphodiesterase inhibitory action, and is a blood lipid improving agent comprising bergenin; It is intended to provide a cyclic AMP phosphodiesterase inhibitor.

[0013] The present invention also provides a food and drink and an external preparation for skin, which are characterized by being added with bergenin to thereby impart a blood lipid improving effect and a cyclic AMP phosphodiesterase inhibitory effect.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION Bergenin is a compound having the structural formula shown in Chemical formula 1 and belongs to the genus Himalaya (Berg).
genia) plants such as Bergenia classifolia (Nagaba Yukinoshita), Bergenia perprusens,
In addition to Bergenia syriata, Bergenia cordifolia, Bergenia strati, Bergenia ligrata, etc., Akame-giwa, Koenboku, Tosumi-mizuki, and some legumes (Caesalpinia digyna, Ardisi)
a hortorum, Astilbe macroflora, etc.) and can be easily extracted from these plants.

[0015]

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In order to obtain bergenin from a bergenin-containing plant, the bergenin-containing site of the starting plant (depending on the plant) is prepared using water, methanol, ethanol, propanol, 1,3-butylene glycol, or a mixture thereof. May be extracted. If the obtained extract is adsorbed on a porous adsorption resin such as Diaion HP-20 and then purified by a method of fractionation in a process of elution or any other purification method, white crystals of bergenin can be easily obtained. .

Although bergenin can be synthesized, it can be said that those extracted from plants are preferable in consideration of safety when added to foods and drinks.

Bergenin is sparingly soluble in water, chloroform, ether and the like, but is well soluble in methanol and ethanol.

When taken orally, bergenin reduces the total cholesterol in the blood, which has been increased by a high-fat diet or the like, by the action of improving blood lipids.

When applied to the skin in the form of an external preparation for skin, bergenin promotes the burning of fat accumulated in fat cells in the subcutaneous tissue by a cyclic AMP phosphodiesterase inhibitory action, and exerts a slimming action.

In order to use bergenin as a blood lipid improving agent / cyclic AMP phosphodiesterase inhibitor, bergenin is provided as powder or as a solution or emulsion using ethanol or the like as a solvent; The mixture may be mixed with an agent and the like, and further granulated to form a granule or tablet; a powdery formulation mixed with any auxiliaries such as dextrin; and the like, depending on the intended use.

The blood lipid improving agent / cyclic AMP phosphodiesterase inhibitor containing bergenin as an active ingredient may be taken as it is, but it may be added to any food or drink to be taken through daily eating and drinking. It may be. In each case, the preferred dosage is about 10 to 3000 mg, particularly preferably about 50 to 1000 mg, of bergenin per adult day.

Bergenin, when administered orally with an aqueous extract of bark wrinkles containing it, has no toxic symptoms even at a dose of 7.17 g / kg, confirming that the toxicity is extremely low. In addition, it is odorless with only weak bitterness. Therefore, even if a small amount is added to food or drink, there is no problem in safety, and the original flavor of the food or drink to be added is not impaired.

When the blood lipid improver / cyclic AMP phosphodiesterase inhibitor according to the present invention is added to foods and drinks, there is no limitation on the foods and drinks to be added. For example, Japanese confectionery, Western confectionery, ice confectionery, spread, paste, pickles, bottles It can be widely added to canned food, processed meat, processed fish, processed marine products, processed milk and eggs, processed vegetables, processed fruits, processed cereals, various seasonings, and various beverages. It can also be added to pet foods and drinks such as so-called dog food to maintain the health of pet animals.

When a blood lipid improving agent / cyclic AMP phosphodiesterase inhibitor containing bergenin as an active ingredient is added to an external preparation for skin, it is selected according to the dosage form of the external preparation for skin and the type of other components. The appropriate dosage form of the bergenin preparation may be added at any stage of the preparation of the external preparation for skin and mixed uniformly. The preferred concentration of bergenin in the skin external preparation is about 0.01 to 10% by weight. Examples of suitable skin external preparations for transdermal absorption of bergenin include ointments, creams, emulsions, lotions, packs, bath preparations and the like.

[0026]

The present invention will be described below in further detail with reference to examples. In each example, “parts” means parts by weight,
Bergenin used in the examples is purified bergenin prepared in the production examples.

Production Example 700 kg of dried root of Bergenia classifolia
Was extracted with 50% ethanol, and the resulting extract 15
0 g was adsorbed on a column of porous adsorption resin, Diaion HP20 (manufactured by Mitsubishi Chemical Corporation), and the column was sequentially eluted with water, 30% methanol, 60% methanol, and methanol. Bergenin was confirmed in the 30% methanol eluted part, and this was concentrated under reduced pressure, dried, and recrystallized using a methanol-water mixture as a solvent to obtain 12 g of purified bergenin. The elemental analysis value of this product was the same as the theoretical value, and the result of structural analysis by ¹³ C-NMR was in good agreement with the literature value [Phytochem, 29, (1), 267-270 (1990)].

Example 1 Female Wistar rats (10 weeks of age) were tested for the effects of bergenin on improving blood lipids and inhibiting weight gain. That is, the rats were divided into a bergenin administration group and a bergenin non-administration group (7 rats per group),
100 mg of bergenin per kg was suspended in a 5% aqueous solution of gum arabic and forcibly administered orally once a day for 6 consecutive days. The control group received only the same amount of a 5% gum arabic aqueous solution. Each group was fasted for 17 hours before the start of the administration test.

Two hours after the end of the administration on the 6th day, blood was collected from the orbit of the mouse under restraint from anesthesia, and the total cholesterol concentration of the serum was measured using a drychem analyzer.
As a result, the control group was 93.4 ± 5.2 mg / dl, while the test group was 79.3 ± 3.7 mg / dl, and the measured value of the test group was significantly lower (risk Rate 0.05%).

The body weight was measured immediately before the start of the administration and after the end of the administration, and the change in body weight during the administration period was compared. The results are shown in Table 1. The test group showed a significantly greater weight loss than the control group (risk rate 0.05).
%).

[0031]

Table 1 Body weight before administration (g) Body weight after administration (g) Weight loss rate (%) Control group 136.6 ± 3.2 134.4 ± 2.9 1.6 Test group 134.0 ± 2.4 129.0 ± 2.5 3.7

Example 2 50 mM Tris-HCl buffer containing 5 mg of MgCl ₂ (pH 7.
5) is added to a mixture of 0.2 ml of BSA solution, 0.1 ml of BSA solution and 0.1 ml of cyclic AMP phosphodiesterase solution in 0.05 ml of ethanol solution of bergenin, and pre-incubated at 37 ° C. for 5 minutes. Next, 0.05 ml of a cyclic AMP solution is added thereto and reacted at 37 ° C. for 30 minutes. The reaction is stopped by boiling on a boiling water bath for 3 minutes, cooled, centrifuged at 4 ° C., and the reaction product (5′-AMP) in the supernatant is quantified by high performance liquid chromatography. The same enzyme reaction and analysis of the reaction product were performed without adding the bergenin solution, and the cyclic AMP phosphodiesterase inhibition rate by bergenin was determined from the ratio of the amount of the reaction product when the bergenin was added to the amount of the reaction product when the bergenin was not added. .

The above measurement was carried out by changing the concentration of bergenin in the bergenin solution to be added to the reaction solution, and the concentration of bergenin which inhibits the enzyme activity by 50% was determined by interpolation. The 50% inhibitory concentration was 293.6 ppm.

Example 3 The following raw materials were mixed by a conventional method for producing candy, and were further boiled down to form a candy having a blood lipid improving effect and a cyclic AMP phosphodiesterase inhibitory effect ("part" was Parts by weight; the same applies to the following examples).

Sucrose 70 parts starch syrup 30 citric acid 1 fragrance 0.1 bergenin 0.01

Example 4 The following raw materials were treated by a conventional method for producing chewing gum to produce a chewing gum having a blood lipid improving action and a cyclic AMP phosphodiesterase inhibitory action.

Chewing gum base 70 parts sucrose 54 starch syrup 20 softener 4 fragrance (mint oil) 1 bergenin 1

Example 5 The following ingredients were treated in the usual manner for chocolate production,
A chocolate having a blood lipid improving action and a cyclic AMP phosphodiesterase inhibitory action was produced.

Chocolate 45 parts sucrose 15 cocoa butter 20 whole milk powder 25 bergenin 0.1

Example 6 The following raw materials were mixed, and 40 parts of water was added to 100 parts of the obtained mixture, and the mixture was heated and shaped into a pellet while being heated with an extruder to improve blood lipid improving action and cyclic AMP. Dog food having a phosphodiesterase inhibitory action was produced.

Wheat flour 45 parts Corn flour 15 Soy flour 15 Meat meal 20 Sucrose 5 Tallow 5 Salt 1 Calcium phosphate 2 Calcium sorbate 0.5 Fragrance 0.5 Propylene glycol 7 Bergenin 0.1

Example 7 A lotion having the following composition was produced by a conventional method. Bergenin 0.1% by weight glycerin 4 1,3-butylene glycol 4 ethanol 7 polyoxyethylene oleyl alcohol 0.5 methyl paraben 0.5 citric acid 0.01 sodium citrate 0.1 fragrance 0.05 remaining purified water

Example 8 A cream having the following composition was produced by a conventional method. Bergenin 0.1% by weight setosteryl alcohol 3.5 squalane 40 beeswax 3 reduced lanolyl 5 ethyl paraben 0.3 polyoxyethylene 2 stearic acid monoglyceride 2 1,3-butylene glycol 5 glycerin 5 fragrance 0.03 balance purified water

[0044]

As described above, the blood lipid improver / cyclic AMP phosphodiesterase inhibitor of the present invention containing bergenin as an active ingredient is extremely excellent in its action, high in safety, stable, and presents. Since there is no problem in taste, it is suitable for preventing hyperlipidemia and obesity by adding it to ordinary foods and drinks or so-called health foods and taking it on a daily basis. Further, even when applied to the skin, it is well absorbed without causing skin damage and contributes to the reduction of subcutaneous fat, so that it is a skin external preparation having a slimming action to reduce excess subcutaneous fat.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁶ Identification code FI A23K 1/16 302 A23K 1/16 302B 1/18 1/18 A A23L 1/30 A23L 1/30 Z A61K 7/00 A61K 7 / 00 DKW 7/48 ADN 7/48 ADN // A61K 35/78 35/78 C C07D 493/04 106 C07D 493/04 106A

Claims (5)

[Claims] 1. A blood lipid improving agent comprising bergenin as an active ingredient. 2. A cyclic AMP phosphodiesterase inhibitor comprising bergenin as an active ingredient. 3. A blood lipid improving agent and cyclic AMP, wherein the active ingredient is bergenin.
Those that are phosphodiesterase inhibitors. 4. A food or drink comprising bergenin. 5. An external preparation for skin, comprising bergenin.