JP2020068671A - α-GLUCOSIDASE INHIBITOR AND BLOOD GLUCOSE LEVEL ELEVATION INHIBITOR - Google Patents

Abstract

To provide a new composition having a superior blood glucose level elevation inhibitory capacity.SOLUTION: An α-glucosidase inhibitor and a blood glucose level elevation inhibitor of this invention include as active principle a Terminalia bellirica extract containing gallic acid or salt thereof.SELECTED DRAWING: None

Description

  TECHNICAL FIELD The present invention relates to an α-glucosidase inhibitor and an inhibitor of blood sugar level increase, which contain an extract of Terminaria berilica.

  It is known that obesity causes various diseases, and diabetes is one of the diseases caused by obesity. Improvement of diet is important for prevention of obesity and diabetes, and particularly for prevention of diabetes, it is effective to suppress absorption of sugar, that is, to suppress increase in blood glucose level after meal.

  Indigestible dextrin is known as one of the materials having an effect of suppressing an increase in blood glucose level (Patent Document 1). However, indigestible dextrins have the drawback that overdose causes loose stools.

JP, 2009-046448, A

  In view of the above problems, an object of the present invention is to provide a new composition having an excellent blood sugar level elevation suppressing effect.

  As a result of intensive studies, the present inventor has found that an extract of Terminaria berilica containing gallic acid has an excellent α-glucosidase inhibitory action and a blood glucose level increase inhibitory action, and arrived at the present invention.

  That is, the present invention relates to an α-glucosidase inhibitor and a blood sugar level increase inhibitor containing an extract of Terminaria berilica containing gallic acid.

  In the present invention, it is preferable that the extract of Terminaria berilica used as a blood glucose elevation inhibitor contains 11% by mass or more of gallic acid.

  According to the present invention, an extract of Terminaria berilica containing gallic acid has an excellent α-glucosidase inhibitory action and a blood glucose level increase inhibitory action, and can moderate sugar absorption.

It is a figure which shows the result of the sucrose tolerance test in the rat of the Terminaria beryllica extract.

  Hereinafter, the present invention will be described in detail. The present invention is not limited to the following description, and various modifications can be made within the scope of the claims that can be understood by those skilled in the art.

  Terminaria berilica is a broad-leaved tree of the genus Momotamana in the family Corsiformes. In the present invention, any part such as leaves, bark, roots, flowers, xylem, fruits, and seeds may be used, but it is preferable to use parts (pericarp or pulp part) excluding seeds of fruits or fruits. ..

  In the present invention, an extract of Terminaria berilica or a dry powder thereof (hereinafter also referred to as “extraction powder”) can be used, and from the viewpoint of stability during storage and easy handling, it is preferable to use the extraction powder. preferable. In the present invention, a commercially available product can be used as the extract of Terminaria berilica.

  Examples of the solvent used for extraction include water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, acetic acid, ethyl acetate, ether, hexane, or a mixed solvent thereof. It is preferable to use water from the viewpoint of the effect of suppressing an increase in blood sugar level and safety. The temperature of the extraction solvent can be appropriately set from room temperature to a boiling point or lower depending on the solvent used.

  The extraction time varies depending on the amount of the extraction solvent or the extraction temperature, but the lower limit value of the extraction time is preferably 10 minutes or longer, more preferably 30 minutes or longer, and particularly preferably 1 hour or longer. The upper limit of the extraction time is preferably 72 hours or less, more preferably 60 hours or less, and particularly preferably 48 hours or less.

The extract can be concentrated and / or dried and powdered if necessary. As a method for concentrating the extract, suitable concentration means such as vacuum concentration, reverse osmosis membrane (RO membrane) concentration, and freeze concentration can be adopted. As a method of dry-powdering the extract, a commonly used drying method may be used, and for example, a dry method such as spray-drying, freeze-drying or vacuum drying may be used. When it is dried and powdered, it can be dried together with an excipient such as dextrin.

  The terminalia beryllica extract used in the present invention contains gallic acid or a salt thereof. The content range of such gallic acid is 4% by mass or more, preferably 8% by mass or more, more preferably 11% by mass or more, particularly preferably 14% by mass or more in the Terminaria berilica extract. Is. Further, the content of gallic acid can be measured by an analysis method suitable for the situation of the measurement sample among the commonly known analysis methods of gallic acid. For example, it is possible to analyze by a liquid chromatography method, and at the time of measurement, an appropriate treatment may be performed as necessary, such as removing impurities in the sample in order to adapt to the separability of the device.

  The terminaria berilica extract used in the present invention is used as an α-glucosidase inhibitor and a blood sugar level elevation inhibitor. Carbohydrates that are ingested from food, such as starch, are ingested in the form of sugars that are disaccharides or higher. Therefore, in order to absorb sugar from the intestinal tract, it is necessary to decompose sugar into monosaccharide. Α-Glucosidase is involved in the decomposition of the carbohydrate during the absorption process, and the α-glucosidase inhibitory activity can suppress the absorption of sugar from the intestinal tract. Since the extract obtained from Terminaria berilica of the present invention has an excellent α-glucosidase inhibitory activity, it can suppress the absorption of sugar from the intestinal tract and promote the excretion of sugar out of the body. Further, by suppressing the absorption of sugar into the body, it has an effect of suppressing an increase in blood sugar level and moderateing the absorption of sugar after eating. From the above, the Terminaria beryllica extract used in the present invention is effective in preventing obesity and diabetes.

The Terminaria berilica extract has an α-glucosidase inhibitory action and a blood glucose level increase inhibiting action. There is no particular limitation on the intake amount and the compounding amount for obtaining these effects, but the intake amount per day for an adult is preferably 5 mg or more, more preferably 10 mg or more, and more preferably 15 mg or more as a lower limit value in terms of dry mass. Particularly preferred. The upper limit is preferably 10000 mg or less, more preferably 5000 mg or less, and particularly preferably 1000 mg or less. In addition, the compounding amount in the composition varies depending on the dosage form, but the lower limit is preferably 0.001 mass% or more in terms of dry mass, more preferably 0.005 mass% or more, and 0.01 mass%. % Or more is particularly preferable. The upper limit of the blending amount is preferably 90% by mass or less, more preferably 80% by mass or less, and particularly preferably 60% by mass or less.

When the Terminaria beryllica extract is made into a dosage form that can be orally administered, for example, royal jelly, propolis, vitamins (A, B ₁ , B ₂ , B ₆ , B ₁₂ , niacin, C , D, E, K, folic acid, pantothenic acid, biotin, derivatives thereof, etc.), minerals (iron, magnesium, calcium, zinc, etc.), selenium, chitin, chitosan, lecithin, polyphenols (flavonoids, derivatives thereof, etc.), Carotenoids (lycopene, astaxanthin, zeaxanthin, lutein, etc.), xanthine derivatives (caffeine, etc.), proteins or peptides (soy protein, collagen, elastin, silk, or decomposition products thereof), mucopolysaccharides (hyaluronic acid, chondroitin, dermatan) , Heparan, heparin, ketalan, this Derivatives, etc.), amino sugars (glucosamine, acetylglucosamine, galactosamine, acetylgalactosamine, neuraminic acid, acetylneuraminic acid, hexosamine, salts thereof, etc.), oligosaccharides (isomalto-oligosaccharides, cyclic oligosaccharides, etc.), dietary fiber, Phospholipids (phosphatidylcholine, phosphatidylserine, etc.), sphingolipids and their derivatives (sphingomyelin, ceramide, etc.), sulfur-containing compounds (allyin, sepaene, taurine, glutathione, methylsulfonylmethane, etc.), lignans (sesamin) Etc.), pearl powder, α-lipoic acid or a derivative thereof, coenzyme Q10, and animal and plant extracts containing these, root vegetables (ginger, etc.), excipients, lubricants, fluidizing agents, etc. You can

  Examples of the form of the composition of the present invention include tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, rounds, pastes, creams, and caplets. , Gel, chewable tablets, sticks and the like. Of these, tablet, capsule, powder, granule and liquid forms are preferable, and tablet, powder and granule forms are particularly preferable. Specifically, supplements, packaged beverages filled in PET bottles, cans, bottles, etc., instant beverages to be dissolved in water (hot water), milk, fruit juice, green juice, etc., and food additives. Can be illustrated. In particular, supplements and instant beverages are preferable in that they can be easily taken at meals and the taste can be enhanced.

  Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples, and the present invention can take various aspects as long as the problems of the present invention can be solved. ..

[Α-glucosidase inhibition test]
1. Sample Preparation An α-glucosidase inhibition test was performed using Terminaria beryllica extract powder (manufactured by Toyo Shinyaku Co., Ltd.). Specifically, an inhibition test was performed for maltase, sucrase, and isomaltase. To 100 mg of rat intestinal acetone powder (manufactured by SIGMA), 900 μL of 56 mM maleic acid buffer (pH = 6.0) was added, homogenized and centrifuged (3000 rpm, 10 minutes, 4 ° C.), and the supernatant was used as an enzyme solution. A diluted enzyme solution was used for the inhibition test, an 18-fold diluted enzyme solution was used for the maltase inhibition test, and a 2-fold diluted enzyme solution was used for the sucrase and isomaltase inhibition test. As a substrate, a 5 mM maltose, sucrose, or isomaltose solution dissolved in 56 mM maleic acid buffer (pH = 6.0) was used. The content of gallic acid contained in the Terminaria berilica extract powder used in this test was 14.7% by mass when analyzed by high performance liquid chromatography.

  The Terminaria berilica extract powder was dissolved in a 0.1% DMSO solution to a predetermined concentration, and then serially diluted 2-fold to prepare a test substance solution.

2. Activity measurement A test substance solution (15 μL) and an enzyme solution (15 μL) were added, and preincubation was performed at 37 ° C. for 5 minutes. After that, 90 μL of the substrate solution was added and incubated at 37 ° C. for 30 minutes. After the reaction, it was treated at 98 ° C. for 2 minutes to stop the enzymatic reaction. After stopping the reaction, absorbance at 550 nm was measured using Glucose Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) to measure the glucose concentration (measured value A).

The absorbance of the test solution obtained was measured by performing the same operation as in the procedure of the above-mentioned activity measurement except that a 0.1% DMSO solution was used in place of the test substance solution, which is referred to as measurement value B. ).

Instead of the enzyme solution, the same procedure as in the above activity measurement was performed except that an enzyme solution that had been heat-inactivated by treatment at 98 ° C. for 2 minutes was used, and the absorbance of the obtained test solution was measured (measurement The value is C.).

The same procedure as the above-described activity measurement, except that a 0.1% DMSO solution was used instead of the test substance solution, and an enzyme solution that had been heat-inactivated by treatment at 98 ° C. for 2 minutes was used instead of the enzyme solution. Then, the absorbance of the obtained test solution was measured (referred to as a measured value D).

  The α-glucosidase inhibition rate of the Terminaria beryllica extract powder was calculated by the following formula 1.

[Formula 1]

An inhibition curve was prepared from the α-glucosidase inhibition rate and the concentration of the test substance solution obtained from the above formula 1, and the final concentration (IC ₅₀ ) of the test substance showing a 50% inhibitory effect was calculated. The IC _{50 for} each enzyme was 61.1 μg / mL for maltase, 103.1 μg / mL for sucrase, and 335.1 μg / mL for isomaltase.

  From the above, it was suggested that the Terminaria berilica extract used in the present invention exhibits an excellent α-glucosidase inhibitory action.

[Sucrose tolerance test in rats]
A sucrose tolerance test in rats was performed using the Terminaria berilica extract powder (manufactured by Toyo Shinyaku Co., Ltd.). The content of gallic acid contained in the Terminaria berilica extract powder used in this test was 14.8 mass% when analyzed by high performance liquid chromatography.

Seven-week-old male SD rats (Japan SLC, Inc.) were fasted for 12 hours and divided into two groups, a test group and a control group, so that there was no difference in blood glucose level and body weight. To the rats in the test group, the Terminaria beryllica extract was prepared so as to be 1.0 g / 5 mL / kg body weight and orally administered into the stomach using a sonde. Distilled water was similarly administered to the rats in the control group. Then, 2.0 g / 5 mL / kg body weight sucrose solution was orally administered to the rats in each group. Blood was collected from the tail vein of each rat before and 30 and 60 minutes after the administration, and blood glucose concentration was measured using Glutest Ace R (Sanwa Chemical Laboratory Co., Ltd.). The results are shown in Figure 1.

From FIG. 1, the Terminaria beryllica extract suppressed the increase in blood glucose level 60 minutes after the administration of sucrose, as compared with the control group. From the above, it was shown that the Terminaria beryllica extract of the present invention has an excellent effect of suppressing an increase in blood glucose level.

(Production Example 1)
500 mL of beverage was prepared per unit in the following blending ratio (unit is mass%). When the beverage of Production Example 1 was ingested before meals, the effect of suppressing postprandial blood glucose increase was confirmed.

Terminaria berilica extract powder 0.01
(Contains 11% by mass of gallic acid)
Tea extract 0.1
Kuzuka extract 0.01
Guava leaf extract 0.01
L-carnitine tartrate 0.02
Fructose glucose 1.0
Trehalose 1.0
Vitamin B1 0.001
Remaining water

(Production Example 2)
Tablets of 200 mg per grain were prepared with the following blending amounts (unit is mg). When two tablets of Production Example 2 were ingested before meals, an effect of suppressing postprandial blood glucose elevation was confirmed.

Terminaria beryllica extract powder 30
(Contains 11% by mass of gallic acid)
Pine bark extract 30
Sodium ascorbate 50
Coenzyme Q10 5
L-carnitine tartrate 20
Sucrose ester 5.0
Silicon dioxide 2.5
Reduced maltose 57.5

  Used in the present invention, gallic acid-containing Terminaria beryllica extract has an excellent α-glucosidase inhibitory action and blood glucose level increase inhibitory action, the effect of moderate the absorption of sugar due to these actions Since it has, it is useful for prevention of obesity and diabetes.

Claims (3)

  An α-glucosidase inhibitor containing an extract of Terminaria berilica containing gallic acid or a salt thereof. A blood sugar level elevation inhibitor containing an extract of Terminaria berilica containing gallic acid or a salt thereof. The inhibitor of elevation of blood glucose level according to claim 2, which contains an extract of Terminaria berilica in which the content of gallic acid or a salt thereof is 11% by mass or more.