JP2022099458A - Glucagon-like peptide-1 secretion promoting composition - Google Patents

Abstract

To provide an oral composition having sufficient actions of promoting glucagon-like peptide-1 secretion and inhibiting appetite.SOLUTION: A glucagon-like peptide-1 secretion promoting composition contains Terminalia bellirica. An appetite inhibitory composition contains Terminalia bellirica.SELECTED DRAWING: None

Description

The present invention relates to a glucagon-like peptide-1 secretagogue-promoting composition containing Terminaria verylica and an appetite-suppressing composition containing Terminaria verylica.

In recent years, an increasing number of people are worried about metabolic syndrome due to changes in the environment in various aspects. Since metabolic syndrome increases the risk of various diseases, its improvement is a social issue.

Glucagon-like peptide-1, which is a hormone secreted from L cells scattered in the gastrointestinal tract, has been confirmed to have actions such as stimulation of the satiety center and suppression of peristaltic movement of the gastrointestinal tract by stimulation of food. In addition, glucagon-like peptide-1 has been attracting attention for its obesity-suppressing effect, and is expected to have an effect on metabolic syndrome. However, since glucagon-like peptide-1 has very low stability in the body, it is necessary to optimize the administration method and route of administration, and to search for a functional analog having high stability in the body.

Therefore, studies have been conducted on substances that promote the secretion of glucagon-like peptide-1 in the gastrointestinal tract, instead of directly administering glucagon-like peptide-1. For example, Patent Document 1 discloses that hydroxybutyl-β-cyclodextrin has a glucagon-like peptide-1 secretagogue action.

Japanese Unexamined Patent Publication No. 2016-098173

An object of the present invention is to provide a novel composition having an excellent glucagon-like peptide-1 secretagogue action.

The applicant has conducted extensive studies on various substances in order to solve the above-mentioned problems, and surprisingly, Terminaria verylica has an excellent glucagon-like peptide-1 secretagogue-promoting effect and appetite-suppressing effect. I found that there is. The present invention is a completed invention based on such findings.

The outline of the present invention is as follows.
<1> A glucagon-like peptide-1 secretagogue-promoting composition comprising Terminaria verylica.
<2> The composition for promoting glucagon-like peptide-1 secretion according to <1>, wherein the glucagon-like peptide-1 is an active glucagon-like peptide-1.
<3> An appetite-suppressing composition comprising Terminaria verylica.
<4> The composition according to any one of <1> to <3>, which contains gallic acid derived from Terminaria verylica or a salt thereof.

According to the present invention, by containing Terminaria verylica, it is possible to provide a composition having an excellent glucagon-like peptide-1 secretagogue action. Further, according to the present invention, since it has a glucagon-like peptide-1 secretagogue by containing Terminaria verylica, it is possible to provide a composition having an excellent appetite-suppressing effect.

Hereinafter, the present invention will be described in detail.

[1. Terminaria Beririka]
Terminaria belliricca is a broad-leaved tree of the genus Tropical almond in the family Combretaceae. In the present invention, any of leaves, stems and fruits can be used, but it is preferable to use fruits, and from the viewpoint of glucagon-like peptide-1 secretion promoting action and appetite suppressing action, a portion of the fruit excluding seeds. (Pericarp and flesh) are more preferably used.

As the Terminaria berylica of the present invention, processed products such as pulverized products, squeezed juices and extracts can be used. Examples of the crushed product include powder, granules and the like. The squeezed juice and the extract may be liquid, but can also be used as a paste or a dry powder. In the case of a paste or a dry powder, it may be produced using only the squeezed juice or the extract itself obtained from Terminaria verylica, or it may be processed together with an excipient. The extract can be obtained by extracting with a suitable solvent, and examples of the solvent that can be used include water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, and propylene glycol. Examples thereof include glycerin, acetic acid, ethyl acetate, diethyl ether, hexane, or a mixed solvent thereof. In the present invention, it is preferable to use water, methanol, ethanol, or a mixed solvent thereof from the viewpoint of effectively exerting a glucagon-like peptide-1 secretagogue action. The temperature at the time of extraction can be appropriately adjusted from room temperature to a temperature below the boiling point of the extraction solvent. In the present invention, a commercially available product can be used.

The content of Terminaria verylica in the oral composition of the present invention is not particularly limited as long as it has a glucagon-like peptide-1 secretion-promoting action and an appetite-suppressing action, but is, for example, 0.005% by mass in the composition. It is preferably 80% by mass or more, more preferably 0.01% by mass or more and 50% by mass or less, and particularly preferably 0.05% by mass or more and 30% by mass or less.

In the present invention, it is preferable to contain gallic acid derived from Terminaria berylica or a salt thereof. The content of gallic acid or a salt thereof in the oral composition of the present invention is preferably 0.0001% by mass or more, more preferably 0.0005% by mass or more, and particularly preferably 0.001% by mass in the composition. That is all. The upper limit of the content of gallic acid or a salt thereof is not particularly limited, but is preferably 30% by mass or less, more preferably 20% by mass or less, and particularly preferably 10% by mass or less in the composition.

The content of gallic acid or a salt thereof in the oral composition of the present invention can be measured by an analytical method suitable for the situation of the measurement sample among the generally known analytical methods for gallic acid or a salt thereof. For example, it can be analyzed by a liquid chromatography method. At the time of measurement, in order to match the separability of the device, impurities in the sample may be removed, and other treatments may be performed as necessary.

[2. Oral composition]
The oral composition of the present invention is characterized by containing Terminaria verylica.

The form of the oral composition of the present invention is not particularly limited and may be any form. For example, forms suitable for oral use, specifically powder, granules, granules, tablets, liquids, beverages, gels, pastes, capsules such as hard capsules and soft capsules, caplets, chewables. Various forms such as shapes are listed, and various excipients, binders, lubricants, stabilizers, diluents, bulking agents, thickeners, gelling agents, emulsifiers, and colorants are used according to the form to be used. , Fragrances, sweeteners, additives and the like can be blended. From the viewpoint of stability and ease of ingestion at the same time as meals, the oral composition of the present invention is preferably in the form of powder, granules, granules, tablets, chewables or capsules, and more preferably in the form of tablets or powders. preferable.

The oral composition of the present invention may contain only Terminaria verylica or may contain other components. Other ingredients are not limited as long as they are usually used as foods, for example, nutritional ingredients such as vitamins and minerals, plant-derived ingredients, animal-derived ingredients, functional sugars, polypeptides, vitamins, lactic acid bacteria, and bifidus. Bacteria such as fungi and butyric acid bacteria can be mentioned, and water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B12, B13, B15, from the viewpoint of glucagon-like peptide-1 secretion promoting action and appetite suppressing action. Vitamins such as B17, biotin, choline, folic acid, inositol, PABA, vitamin C, vitamin P), oil-soluble vitamins (vitamins A, D, E, K); minerals such as magnesium, phosphorus, zinc, iron; taurine , Sulfur-containing compounds contained in garlic, etc .; flavanoids or flavonoids such as hesperidin, kelcetin; proteins such as collagen; peptides; amino acids; animal fats and oils; vegetable fats and oils; crushed products or extracts of animals and plants. Can be done.

The daily intake of the oral composition of the present invention is not particularly limited and may be appropriately set according to the mode of use, the content of use by the user, etc., but for example, 0.01 to 0.01 based on the body weight of the user. It is 160 g / 60 kg, preferably 0.05 to 80 g / 60 kg, and more preferably 0.1 to 40 g / 60 kg from the viewpoint of promoting glucagon-like peptide-1 secretion and suppressing appetite. Similarly, the amount of the oral composition of the present invention used at one time is not particularly limited, and is, for example, 0.005 to 160 g / 60 kg, preferably 0.01 to 80 g / 60 kg, based on the body weight of the user. It is more preferably 0.02 to 40 g / 60 kg from the viewpoint of promoting glucagon-like peptide-1 secretion and suppressing appetite. When the ingestion form is a beverage, it is the amount of solid content (the amount excluding water) in the beverage.

The oral composition of the present invention may be, for example, a pharmaceutical product (including a non-medicinal product), a food product for specified health use, a food product with a nutritional function, a food product with a functional claim, or the like, a functional food product whose efficacy has been approved by a predetermined organization. It can be used as a so-called health food, general food, food additive, feed and the like. The oral composition of the present invention may be ingested before, between, after, or at the same time as a meal, but from the viewpoint of the glucagon-like peptide-1 secretion promoting effect and the appetite suppressing effect, it is taken before, after, or at the same time as a meal. It is preferable, and it is more preferable to take it at the same time as a meal.

The oral composition of the present invention can be used as a composition for promoting glucagon-like peptide-1 secretion. Glucagon-like peptide-1, also called GLP-1, is a type of hormone in the body and is known to be secreted from the small intestine. As will be described in detail in Examples, the oral composition of the present invention is particularly excellent in promoting the secretion of active glucagon-like peptide-1. The composition for promoting glucagon-like peptide-1 secretion in the present invention contains Terminaria verylica and can be distinguished from other products as a product in that it is used for promoting the secretion of glucagon-like peptide-1. If there is, the present invention is not particularly limited, and for example, the present invention indicates that any of the main body, packaging, instruction manual, and advertisement of the product according to the present invention has a function of promoting glucagon-like peptide-1 secretion. Is included in the range of. In addition, the composition for promoting glucagon-like peptide-1 secretion of the present invention is not limited to the one in which Terminaria verylica is displayed as an active ingredient for promoting glucagon-like peptide-1 secretion on the packaging of a product or the like. It may not be specified.

Specifically, the composition for promoting the secretion of Glucagon-like peptide-1 of the present invention is effective from predetermined institutions such as pharmaceuticals (including non-pharmaceutical products), foods for specified health use, foods with nutritional function, and foods with functional claims. Examples thereof include so-called health foods such as functional foods that have been approved for labeling, and examples of so-called health foods that have been labeled as "promoting the secretion of glucagon-like peptide-1".

In addition, the oral composition of the present invention can be used as an appetite-suppressing composition. Glucagon-like peptide-1 is known to have an appetite-suppressing effect, such as a feeling of fullness during meals by suppressing gastric motility and a difficulty in getting hungry between meals. The composition for suppressing appetite is not particularly limited as long as it contains Terminaria verylica and can be distinguished from other products as a product in that it is used for suppressing appetite. For example, the present invention. The scope of the present invention includes an indication that any of the main body, packaging, instruction manual, and advertised product of the product according to the above has an appetite-suppressing function. The appetite-suppressing composition of the present invention is not limited to the one in which Terminaria verylica is displayed as an active ingredient for appetite-suppressing on the packaging of the product, and may be one in which the active ingredient is not specified. ..

Specifically, as the appetite-suppressing composition of the present invention, labeling of efficacy has been approved by predetermined institutions such as pharmaceuticals (including non-pharmaceutical products), foods for specified health use, foods with nutritional function, foods with functional claims, etc. So-called health foods such as functional foods are mentioned. In so-called health foods, "suppress appetite", "prevent overeating", "for those who are worried about overeating", and "excessive dietary intake". Examples of those displaying "suppress", "for those who want to feel full", "difficult to get hungry", "for those who want to reduce snacks", "suppress stomach movement", etc. can be exemplified.

The packaging form of the oral composition of the present invention is not particularly limited and may be appropriately selected depending on the dosage form and the like. For example, a blister pack such as PTP; strip packaging; heat seal; aluminum pouch; plastic or synthetic resin is used. Film packaging; glass containers such as vials; plastic containers such as ampoules.

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. ..

Glucagon-like peptide-1 secretion promoting effect by ingestion of composition containing Terminaria verylica (1) Test substance Example 1: Reduced palatinose, powdered cellulose, calcium stearate and fine silicon dioxide to Terminaria verylica extract (manufactured by Toyo Shinyaku Co., Ltd.) The mixed and tableted tablets were used. The tablet was 250 mg per tablet, and 4 tablets containing 20.8 mg of gallic acid (derived from Terminaria berylica) were used.
Comparative Example 1: The Terminaria verylica extract of Example 1 was changed to a caramel color, and the one colored in the same manner as in Example 1 was used.

(2) Glucagon-like peptide-1 (GLP-1) secretion promotion test A placebo-controlled randomized double-blind crossover study was conducted in healthy adult men and women using the test substance of Example 1 or Comparative Example 1. .. Seven subjects (20 to 65 years old, 4 males, 3 females) were divided into 2 groups, and either Example 1 or Comparative Example 1 was ingested once each and twice with meals. did. That is, four grains of each of the test substances of Example 1 or Comparative Example 1 were ingested with water or lukewarm water for the first time, and 300 g of rice was ingested as a load food within 10 minutes. In the second ingestion, four test substances opposite to those in the first test (eg, ingesting Example 1 in the first ingestion, ingesting Comparative Example 1 in the second ingestion) are ingested with water or lukewarm water, and at the same time. As a load food, 300 g of rice was ingested within 10 minutes. The second test was carried out with a rest period of 2 weeks or more so as not to be affected by the first test.

Blood was collected before, 30 minutes, 60 minutes, 90 minutes, 120 minutes, and 180 minutes after ingestion of the test food and the loaded food, and active GLP-1 was measured. A Glucagon-Like Peptide-1 (Active) ELISA KIT (manufactured by Millipore) was used for the measurement of active GLP-1. Based on the pre-ingestion, the difference in GLP-1 after 30 minutes, 60 minutes, 90 minutes, 120 minutes, and 180 minutes after ingestion was calculated. In addition, the area under the blood concentration curve (iAUC) was calculated by the trapezoidal method based on the obtained results.

The iAUC of the active GLP-1 at the time of ingestion of Comparative Example 1 was 288 pmol · min / L, and the iAUC of the active GLP-1 at the time of ingestion of Example 1 was 369 pmol · min / L. It showed a significantly high value.

From the above, it can be seen that ingestion of an oral composition containing Terminaria verylica with a meal exhibits an excellent glucagon-like peptide-1 secretagogue effect. From this, it can be seen that the oral composition containing Terminaria verylica has an excellent appetite-suppressing effect.

Example 2
A tablet (250 mg) consisting of the following components was produced. By ingesting the obtained tablets three times a day, two tablets at a time, an excellent glucagon-like peptide-1 secretion-promoting action and appetite-suppressing action can be obtained.

Example 3
A liquid beverage consisting of the following ingredients was produced. By ingesting 100 ml of the obtained liquid beverage three times a day, an excellent glucagon-like peptide-1 secretion-promoting action and appetite-suppressing action can be obtained.

Example 4
A granule composed of the following components was produced. By dissolving 3 g of the obtained granules in 100 ml of water three times a day and ingesting them, an excellent glucagon-like peptide-1 secretion-promoting action and appetite-suppressing action can be obtained.

Example 5
Granules consisting of the following components were produced, and 200 mg was encapsulated in capsules. By ingesting the obtained capsules three times a day, two capsules at a time, an excellent glucagon-like peptide-1 secretion-promoting action and appetite-suppressing action can be obtained.

The oral composition of the present invention has excellent glucagon-like peptide-1 secretion-promoting action and appetite-suppressing action, and is therefore highly industrially useful.

Claims (2)

A glucagon-like peptide-1 secretagogue composition comprising Terminaria verylica. An appetite-suppressing composition comprising Terminaria verylica.