CN111557957A - Composition for oral administration comprising processed myrobalan and use of processed myrobalan - Google Patents

Abstract

The present invention provides an oral composition which contains (A) a processed myrobalan product and (B) a lubricant and/or (C) an excipient, wherein the total amount of (B) and/or (C) is 7 mass% or more relative to the total amount of (A), (B) and (C). The present invention also provides use of a processed myrobalan product for producing a body fat accumulation inhibitor, a body fat reducing agent, a lipid absorption inhibitor, an α -glucosidase inhibitor, a blood glucose level increase inhibitor, a visceral fat reducing agent, a weight reducing agent, or an anti-obesity agent.

Description

Composition for oral administration comprising processed myrobalan and use of processed myrobalan

Technical Field

The present invention relates to a composition for oral administration comprising a processed product of myrobalan (Terminalia).

The present invention also relates to the use of a processed myrobalan product for producing a body fat accumulation inhibitor, a body fat reducing agent, a lipid absorption inhibitor, an α -glucosidase inhibitor, a blood glucose level increase inhibitor, a visceral fat reducing agent, a weight reducing agent, or an anti-obesity agent.

Background

In recent years, attention has been paid to prevention of adult diseases, measures against diabetes, reduction of blood glucose level, elimination of obesity, and the like, and various health foods have been developed. In health foods, development of a functional material having the above-mentioned effects is required. Suppression of postprandial increase in blood glucose level is effective for prevention of diabetes, which is one of symptoms easily caused by obesity, for example. Indigestible dextrin is known to have an effect of inhibiting an increase in blood glucose level in addition to an effect of regulating the intestinal tract and improving hypercholesterolemia (patent document 1).

In particular, the accumulation of visceral fat leads to a significant increase in the risk of cardiovascular attacks due to the accumulation of risk factors such as hyperglycemia, hypertension values, lipid abnormalities, and the like. The stage of cardiovascular disease and risk factor accumulation, broadly referred to as metabolic syndrome, is in need of improvement. It has been reported that visceral fat accumulation is associated with the onset of not only cardiovascular diseases but also diseases such as hyperuricemia, fatty liver disease, menstrual disorder, and the like. Therefore, there is an increasing demand for agents that can be safely ingested and that can reduce visceral fat.

In addition, recently, the demand for health foods that provide various effects with one kind of commercial product has been rapidly increasing (non-patent document 1).

On the other hand, myrobalan (Terminalia) is a plant of the family quisqualaceae, the fruit of which has been used as a medicine in india, the fruit of which is mainly used for antidiarrheal, and the mature fruit of which has been used as an antidiarrheal.

In recent years, myrobalan has been found to have an effect of preventing vascular fibrosis, and has been found to be useful as a prophylactic or therapeutic agent for vascular fibrosis (for example, see patent document 2).

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open publication No. 2009-046448;

patent document 2: japanese patent laid-open publication No. 2004-75584.

Non-patent document

Non-patent document 1: korea beverage company news issue "New proposal! A specific health food in two statement of health W (duplicate) ' sixteen teas taken daily with food W (2) ' 4 month 15 day (Tuesday) New products on the market ' homepage (URL: https:// www.asahiinryo.co.jp/company/news release/2014/pick _0205-2. html).

Disclosure of Invention

Problems to be solved by the invention

However, the processed myrobalan has a high hygroscopicity, and has a problem of stability during storage after preparation into a preparation, and has a characteristic bitter taste, and a solution method thereof has been required to be studied.

In addition, there is a problem that the effects and functions of myrobalan are not sufficiently studied and are not effectively utilized.

Technical scheme for solving problems

The present inventors have conducted intensive studies in view of the above-mentioned problems, and as a result, have found that an oral composition having high storage stability and reduced bitterness can be produced by containing a processed myrobalan product and a lubricant and/or an excipient and adjusting the amount of the lubricant and/or the excipient, and have completed the present invention.

In addition, the present inventors have also conducted intensive studies on the effects or functions of myrobalan. As a result, they have found that myrobalan has excellent body fat accumulation-inhibiting activity, body fat-reducing activity, lipid absorption-inhibiting activity, α -glucosidase-inhibiting activity, blood glucose level-increasing-inhibiting activity, visceral fat-reducing activity, body weight-reducing activity and anti-obesity activity, and have completed the present invention.

The outline of the present invention is as follows.

< 1 > an oral composition which comprises (A) a processed product of myrobalan, and (B) a lubricant and/or (C) an excipient, wherein the total amount of (B) and/or (C) is 7% by mass or more relative to the total amount of (A), (B) and (C).

< 2 > an oral composition comprising (A) a processed product of myrobalan and (B) a lubricant and/or (C) an excipient, wherein the total amount of (B) and/or (C) is 7% by mass or more based on the total amount of (A), (B) and (C) (except the case of containing both sucrose fatty acid ester and reduced maltose).

The oral composition of < 3 > such as < 1 > or < 2 >, wherein the content of the processed myrobalan (A) is 10% by mass or more relative to the total amount of (A), (B) and (C).

The composition for oral administration of < 4 > such as < 1 > -3 >, wherein the lubricant (B) is at least one selected from stearic acid or a salt thereof, a fatty acid ester, and a hydrogenated rapeseed oil.

< 5 > the composition for oral administration according to any one of < 1 > - < 4 >, wherein the excipient (C) is at least one member selected from the group consisting of starch or a derivative thereof, cellulose or a derivative thereof, a sugar alcohol and a disaccharide.

The composition for oral administration described in any of < 6 > to < 1 > -5 > further comprising (D) a plasticizer.

The composition for oral administration of < 7 > such as < 1 > -6 > wherein the total amount of the lubricant (B) and the plasticizer (D) is 1 mass% or more based on the total amount of the components (A), (B), (C) and (D).

< 8 > the composition for oral administration according to any one of < 1 > -7 >, wherein the gallic acid or salt thereof is contained in the composition in an amount of 0.1 mass% or more.

The composition for oral administration of < 9 > as defined in any one of < 1 > - < 8 > which is a tablet.

< 10 > use of a processed product of myrobalan for producing a body fat accumulation retardant or a body fat reducing agent.

Use of < 11 > myrobalan processed product for the manufacture of a lipid absorption blocker.

Use of < 12 > myrobalan processed product for the manufacture of a carbohydrate absorption retardant.

< 13 > use of a Terminalia bellirica extract (Terminalia bellirica extract) comprising gallic acid or a salt thereof for the manufacture of an alpha-glucosidase inhibitor.

< 14 > use of a Terminalia bellirica extract containing gallic acid or a salt thereof for producing a blood glucose level increase retardant.

< 15 > or < 14 > wherein the content of gallic acid or a salt thereof in the Terminalia bellirica extract is 11% by mass or more.

Use of < 16 > a myrobalan processed product for the manufacture of a visceral fat reducing agent.

Use of < 17 > myrobalan processed product for the manufacture of a weight reducing agent.

Less than 18 is more than the application of the myrobalan processed product in the preparation of anti-obesity agents.

The use of a processed product of Terminalia chebula as described in any one of < 19 > to < 16 > wherein the medicament is produced such that the daily intake of gallic acid or a salt thereof by an adult is 20mg or more.

Drawings

FIG. 1: photographs of comparative example 1 and example 3 after the storage stability test are shown.

FIG. 2: is a graph showing the results of a sucrose tolerance test in rats with an extract of Terminalia bellirica.

Detailed Description

The present invention will be explained below. The present invention is not limited to the following embodiments.

I. Processed product of myrobalan

In the present invention, the processed product of myrobalan refers to a processed product obtained by processing an arbitrary portion of myrobalan by a general processing method such as extraction, pulverization, and drying. The myrobalan extract is particularly preferable as the myrobalan processed product from the viewpoint of the remarkable effect of the present invention. The myrobalan extract of the present invention is an extract obtained by extracting any part of myrobalan with a solvent, and is a concept including not only an extract but also a powder obtained by drying the extract. The aqueous extract of myrobalan is particularly preferable from the viewpoint of the remarkable effect of the present invention.

Terminalia chebula is a broad-leaved forest of the family Combretaceae, genus Terminalia (Terminalia). Examples of myrobalan include: terminalia bellirica (belerica), Terminalia catappa, Chrysanthemum indicum, Terminalia cordifolia, Canarium schneider, Terminalia convolvulus, Terminalia arvensis, Terminalia muelleri, Terminalia arvensis, Terminalia chebula, etc. The myrobalan is particularly preferably Terminalia bellirica (Terminalia bellirica) from the viewpoint of the remarkable effect of the present invention.

The processed product of fructus Chebulae can be obtained from leaf, bark, root, flower, xylem, fruit, seed, etc. Any part of myrobalan may be used. From the viewpoint of exerting effects of blocking body fat accumulation, reducing body fat, blocking lipid absorption, inhibiting α -glucosidase, blocking blood glucose level increase, reducing visceral fat, reducing body weight, and preventing obesity, it is preferable to use a site other than seeds, and most preferable to use a site other than seeds of fruits (pericarp or pulp site).

The processed product of fructus Chebulae can be processed into powder, paste, juice, extract, etc. From the viewpoint of the remarkable effect of the present invention, a myrobalan extract is particularly preferable. Examples of the pulverized product include powder and granules. The squeezed juice or extract may be in the form of liquid, paste, or dried extract. In the present invention, commercially available products can be used.

The method for obtaining a pulverized product as one form of the processed product of the present invention is not particularly limited, and examples thereof include the following methods: the dried product obtained by drying in the sun, half-sun, shade, heat drying, room-temperature drying, freeze drying, or the like is powdered using a ball mill, a hammer mill, or the like.

In addition, a paste or a squeezed juice which is one form of the processed product of the present invention can be obtained by, for example, pulverizing a myrobalan fruit without drying with a substance gelatinizer or the like, and further filtering or centrifuging the paste to obtain a squeezed juice. Alternatively, the myrobalan fruit may be squeezed to obtain a squeezed juice.

The extract as one form of the processed product of the present invention may be extracted from, for example, a fruit of myrobalan by directly adding water or an organic solvent, or may be extracted from a ground product or a dried product obtained by drying once. In particular, it is preferable to pulverize the fruit to form a paste, or to dry and pulverize the fruit to extract the fruit.

Examples of the solvent used for the extraction include water, an organic solvent, or a mixed solution of water and an organic solvent, and examples of the organic solvent include methanol, ethanol, n-propanol, isopropanol, n-butanol, acetone, hexane, cyclohexane, 1, 3-butanediol, ethylene glycol, propylene glycol, methyl ethyl ketone, glycerol, methyl acetate, ethyl acetate, diethyl ether, methylene chloride, edible oils and fats, 1,1,1, 2-tetrafluoroethane, 1,1, 2-trichloroethylene, or a mixed solvent thereof. Preferably, water, a polar organic solvent, or a mixture thereof is preferred in terms of effectively exerting the effect of inhibiting the increase in blood glucose level and the effect of inhibiting the increase in neutral fat. The polar organic solvent is preferably ethanol, n-butanol, methanol, acetone, propylene glycol, or ethyl acetate, and preferably ethanol. From the above aspect, the most preferable extraction solvent is water. The temperature during extraction may be suitably adjusted from room temperature to a temperature equal to or lower than the boiling point of the extraction solvent. The obtained extract can be used as it is, but if necessary, a person skilled in the art can concentrate the extract by a method generally employed to obtain a liquid, paste or powder extract.

Next, a method for effectively utilizing the processed myrobalan will be specifically described. The matters described below in connection with the composition for oral administration described in "II" can be applied to the drug for each use described in "III" below. In addition, the matters described below in connection with the drugs for each use described in the section "III" can be applied to the composition for oral administration of "II".

Composition for oral administration

The composition for oral administration of the present invention (hereinafter, may be simply referred to as "composition") is preferably bellirica (bellerica) or myrobalan among the above-exemplified varieties as the processed product of myrobalan (a), and particularly preferably bellirica which exhibits various effects such as an effect of retarding an increase in blood glucose level, an effect of retarding an increase in neutral fat, and an effect of reducing neutral fat. From the above reasons, the fruit of myrobalan is preferably used. The content of the processed myrobalan in the composition for oral administration of the present invention is not particularly limited, but is preferably 5% by mass or more and 95% by mass or less, and more preferably 10% by mass or more and 90% by mass or less.

The lubricant (B) in the composition for oral administration of the present invention is used for alleviating the friction between the die and the tablet of a tablet press machine and preventing the problem of the tablet such as sticking when the powder for tablet is compressed. The lubricant that can be used in the present invention is not particularly limited as long as it is a component that can achieve the above object, and examples thereof include stearic acid, stearic acid or a salt thereof, fatty acid esters such as sodium stearyl fumarate, polyethylene glycol, sucrose fatty acid esters, vegetable fats and oils, hydrogenated oils, talc, and the like. The salt of stearic acid is preferably a metal salt, more preferably an alkaline earth metal salt, and particularly preferably calcium stearate, magnesium stearate, or the like. These lubricants may be used alone or in combination of two or more. Commercially available lubricants can be used. From the viewpoint of improving the storage stability of the obtained composition for oral administration and improving bitterness, stearic acid or a salt thereof, a fatty acid ester, and rapeseed hydrogenated oil are preferable, and calcium stearate, a sucrose fatty acid ester, and rapeseed hydrogenated oil are more preferable.

The content of the lubricant in the composition for oral administration of the present invention is preferably 0.1% by mass or more, and more preferably 0.5% by mass or more.

Excipients are added to improve handling or shaping of the composition and to facilitate administration. The excipient that can be used in the composition for oral administration of the present invention is not particularly limited, and examples thereof include starch such as starch, pregelatinized starch, partially pregelatinized starch, and starch decomposition products, and derivatives thereof; sugar alcohols such as dextrin, reduced palatinose, and reduced maltose; disaccharides such as lactose and maltose; cellulose or its derivatives such as beer yeast, crystalline cellulose, low-substitution hydroxypropyl cellulose, and hydroxypropyl methyl cellulose; refined white sugar, light anhydrous silicic acid, calcium silicate, titanium oxide, precipitated calcium carbonate, etc. These excipients may be used alone or in combination of two or more. Commercially available excipients can be used. In the present invention, from the viewpoints of improving the productivity, improving the storage stability of the composition, and improving bitterness, saccharides such as starch or a derivative thereof, cellulose or a derivative thereof, sugar alcohols, and disaccharides are preferable, and pregelatinized starch, crystalline cellulose, hydroxypropyl cellulose, dextrin, reduced palatinose, reduced maltose, lactose, and maltose are more preferable.

In the present invention, the content of the lubricant (B) and/or the excipient (C) may be 7 mass% or more, preferably 10 mass% or more, based on the total amount of the processed myrobalan (a), the lubricant (B), and the excipient (C). Further, it is preferably 95% by mass or less, and more preferably 90% by mass or less. By setting the mixing ratio as described above, the obtained composition for oral administration has high stability during storage and can suppress bitterness. (B) The content of the lubricant and/or (C) excipient is an amount when the composition for oral administration contains only one of (B) and (C), and in the case of containing both, their total amount.

In the present invention, in order to sufficiently exhibit the effects of the processed myrobalan product, the content of the processed myrobalan product (a) is preferably 5 mass% or more, more preferably 10 mass% or more, based on the total amount of the processed myrobalan product (a), the lubricant (B), and the excipient (C). The content is preferably 93% by mass or less, and more preferably 90% by mass or less.

In the present invention, (D) a plasticizer is preferably used in addition to (a) the processed myrobalan product, (B) the lubricant, and (C) the excipient. The plasticizer is used for improving the fluidity of mixed powder and particles. The plasticizer usable in the present invention is not particularly limited, and examples thereof include silica, aluminum silicate, magnesium aluminum silicate, calcium phosphate, magnesium carbonate, and magnesium oxide. These plasticizers may be used alone or in combination of two or more. As the plasticizer, a commercially available one can be used. In the present invention, from the viewpoints of improving the productivity, improving the storage stability of the composition, and improving bitterness, silica, aluminum silicate, magnesium aluminum silicate, and calcium phosphate are preferable, and silica and calcium phosphate are more preferable.

In the present invention, when the plasticizer (D) is contained, it is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and particularly preferably 0.5% by mass or more in the composition. The amount of the plasticizer (D) is preferably 0.01 mass% or more, more preferably 0.1 mass% or more, and particularly preferably 0.5 mass% or more, based on the total amount of the processed myrobalan product (a), the lubricant (B), the excipient (C), and the plasticizer (D).

In the present invention, from the viewpoint of improving storage stability and bitterness, the total amount of the lubricant (B) and the plasticizer (D) is preferably 0.5% by mass or more, more preferably 1% by mass or more, and particularly preferably 1.5% by mass or more, based on the total amount of the processed myrobalan product (a), the lubricant (B), the excipient (C), and the plasticizer (D).

Preferably, the composition for oral administration of the present invention contains gallic acid or a salt thereof. The gallic acid or a salt thereof includes gallic acid or a salt thereof obtained by synthesis, gallic acid or a salt thereof extracted from a natural product, gallic acid or a salt thereof obtained by treating an extract with an enzyme or the like, and is not particularly limited, and from the viewpoint of an effect of suppressing an increase in blood glucose level and an effect of suppressing an increase in neutral fat, gallic acid or a salt thereof derived from a processed myrobalan is preferably contained. The content of gallic acid or a salt thereof in the composition of the present invention is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, and particularly preferably 0.1% by mass or more. In addition, gallic acid or a salt thereof 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 composition for oral administration of the present invention can be measured by an analytical method suitable for measuring the state of a sample among commonly known analytical methods for gallic acid or a salt thereof. For example, the analysis can be performed by liquid chromatography. In the measurement, an appropriate treatment for removing inclusions in the sample and the like may be performed as necessary in order to be suitable for the separation capability of the apparatus.

In the present invention, in addition to (a) the processed myrobalan, (B) the lubricant, and (C) the excipient, ingredients that can be used in the composition for oral administration may be used. Examples of the ingredients other than the processed product of myrobalan derived from animals and plants, binders, disintegrating agents, various carriers, stabilizing agents, surfactants, plasticizers, solubilizing agents, reducing agents, buffers, sweeteners, base agents, adsorbents, flavoring agents, antioxidants, brighteners, coating agents, paints, wetting agents, fillers, cooling agents, colorants, flavoring agents, perfumes, sugar coating agents, isotonic agents, softeners, emulsifiers, thickeners, thickening agents, foaming agents, pH adjusters, diluents, dispersants, disintegration aids, disintegration delaying agents, fragrances, desiccants, preservatives, solubilizers, dissolution aids, solvents, antistatic agents, humectants, moisturizers, and the like.

Examples of the form of the composition for oral administration of the present invention include tablets, granules, fine granules, powders, capsules such as soft capsules and hard capsules, chewable agents, granular agents, rods, tablets, blocks, solid agents, pills, caplets, rods and the like. Among them, the form of tablets, granules, powders, capsules, and chewables is preferable, and tablets and chewables are particularly preferable. The composition for oral administration of the present invention is preferably used as a food, a specific health food, a nutritional functional food, a functional marker food, or a health food.

III.Body fat accumulation retarder, body fat reducing agent, lipid absorption retarder, carbohydrate absorption retarder, α - Glucosidase inhibitor, blood glucose level increase inhibitor, visceral fat reducing effect, body weight reducing effect and anti-obesity agent Hereinafter, sometimes collectively referred to as "drugs for various uses") and production thereofThe term "drug for each use" in the present invention refers to a drug used for the purpose of the use, and is not limited to drugs, drinks and foods as long as it is an orally ingestible drug.

Accumulation of body fat occurs mainly when the balance between intake of lipid or carbohydrate and consumption of fat accumulated in the body in the form of energy is disrupted. For example, when intake of lipid or carbohydrate exceeds energy consumption, the ingested lipid or carbohydrate is accumulated in the body in the form of subcutaneous or visceral fat. The processed myrobalan product of the present invention can inhibit absorption of lipid or carbohydrate by at least the following inhibitory activity, and as a result, can inhibit accumulation of body fat or reduce body fat. From the viewpoint of effects, those other than myrobalan (Terminalia chebula) are preferable, and Terminalia bellirica (Terminalia bellirica) is preferably used.

Lipids ingested from food are broken down by lipases from the pancreas and absorbed from the gut. Therefore, inhibition of pancreatic lipase can block lipid absorption of ingested food, thereby promoting lipid excretion into the body. Therefore, inhibition of lipase inhibits absorption of excess lipids and thus inhibits accumulation of the lipids in the body as body fat, and further promotes decomposition of the lipids accumulated in the body. The processed product obtained from the fruit of myrobalan of the present invention can inhibit the activity of the pancreatic lipase, thereby inhibiting lipid absorption. From the viewpoint of effects, those other than myrobalan (Terminalia chebula) are preferable, and Terminalia bellirica (Terminalia bellirica) is preferably used.

Carbohydrates ingested from food are ingested as sugars of disaccharide or more, and in order to be absorbed in the body, these carbohydrates need to be decomposed into monosaccharides. The enzymes involved in this decomposition are alpha-amylase and alpha-glucosidase. Alpha-glucosidase is a generic name of enzymes (maltase, sucrase, lactase, etc.) which decompose saccharides of disaccharides and more into monosaccharides. For example, in the case of starch, after being decomposed into disaccharides by α -amylase, it is decomposed into glucose as a monosaccharide by maltase and absorbed into the body. In the case of sucrose, glucose and fructose, which are converted into monosaccharides by sucrase, are absorbed in the body. Thus, by blocking the α -amylase, α -glucosidase (maltase, sucrase, lactase, etc.) involved in the in vivo absorption of carbohydrates, the absorption of carbohydrates from the intestinal tract can be blocked. The processed product obtained from the fruit of myrobalan of the present invention has an excellent α -amylase inhibitory activity, and is also excellent in α -glucosidase inhibitory activity, particularly maltase inhibitory activity and sucrase inhibitory activity, and therefore, can inhibit the absorption of carbohydrates from the intestinal tract and promote the excretion of sugars into the body. As a result, the intake of excess energy into the body can be inhibited, the accumulation of fat in the body can be suppressed, and the fat accumulated in the body can be reduced. From the viewpoint of effects, those other than myrobalan (Terminaliachebula) are preferable, and a Terminalia bellirica (Terminalia bellirica) is preferably used.

In particular, as the α -glucosidase inhibitor and the blood glucose level increase inhibitor, it is preferable to use a belliri extract containing gallic acid or a salt thereof. The content of gallic acid is in the range of 4 mass% or more, preferably 8 mass% or more, more preferably 11 mass% or more, and particularly preferably 14 mass% or more in the Terminalia bellirica extract. The content of gallic acid can be measured by an analytical method suitable for measuring the state of a sample among commonly known analytical methods for gallic acid. For example, the analysis can be performed by liquid chromatography, and in the measurement, an appropriate treatment for removing impurities and the like in the sample can be performed as necessary in order to adapt the separation ability of the apparatus.

The Terminalia bellirica extract containing gallic acid or its salt, especially Terminalia bellirica extract containing gallic acid in an amount of the lower limit has excellent alpha-glucosidase inhibitory activity, and thus can inhibit sugar absorption from the intestinal tract and promote sugar excretion from the body. Further, by inhibiting the absorption of sugar into the body, the increase in blood glucose level can be inhibited, and the absorption of sugar after a meal can be stabilized. As described above, the above bellirie extract is particularly effective for the prevention of obesity and diabetes.

Further, the processed product of Terminalia chebula has effects of reducing visceral fat, reducing body weight, and preventing obesity by oral intake. Thus, the processed myrobalan product can be used for improving and preventing diseases caused by accumulation of visceral fat, such as metabolic syndrome, hyperuricemia, fatty liver disease, and menstrual disorder. A processed product of bellybia terminalis is preferable as a suitable processed product of myrobalan for exerting an effect of reducing visceral fat, an effect of reducing body weight, and an anti-obesity effect, and a bellybia terminalis extract is particularly preferable.

In order to exert the visceral fat reducing effect, the weight reducing effect, and the anti-obesity effect, when the processed myrobalan product is orally taken in a human, the processed myrobalan product is orally taken for preferably 4 weeks or more, more preferably 8 weeks or more, and particularly preferably 12 weeks or more.

In order to exert the above-mentioned effects, the processed myrobalan is preferably orally taken into a mammal, and particularly preferably taken into a human.

The intake amount and the amount to be added for obtaining these effects are not particularly limited, but the lower limit of the daily intake amount for an adult, for example, in the case of myrobalan extract, is preferably 5mg or more, more preferably 10mg or more, particularly preferably 15mg or more, and most preferably 20mg or more in terms of dry mass. The upper limit is preferably 10000mg or less, more preferably 5000mg or less, further preferably 1000mg or less, and particularly preferably 600mg or less. The amount of the pharmaceutical preparation for each application or the food containing the pharmaceutical preparation varies depending on the dosage form, and for example, in the case of a myrobalan extract, the lower limit of the amount is 0.0001% by mass or more, preferably 0.001% by mass or more in terms of dry mass, and particularly in the case of an extract containing the gallic acid or a salt thereof in the above amount, more preferably 0.005% by mass or more, and particularly preferably 0.01% by mass or more. The upper limit of the blending amount is 90% by mass or less, more preferably 80% by mass or less, and preferably 60% by mass or less.

In addition, in the case of the pulverized product of myrobalan, the lower limit of the daily intake of an adult is 100mg or more, preferably 200mg or more, and the upper limit thereof is preferably 10000mg or less, more preferably 6000mg or less in terms of dry mass, and the amount to be blended in a food varies depending on the dosage form, the lower limit of the amount to be blended in the pulverized product of myrobalan is 0.001 mass% or more, preferably 0.01 mass% or more in terms of dry mass, and the upper limit thereof is 90 mass% or less, preferably 60 mass% or less. In the case of paste or the like, the amount of the paste or the like may be equal to the amount of the pulverized product of myrobalan in terms of dry mass.

In the present invention, it is preferable to produce the pharmaceutical preparations for each of the above-mentioned uses so that the daily intake of gallic acid or a salt thereof for an adult becomes 20mg or more, from the viewpoint of improving the effects of these pharmaceutical preparations. From this viewpoint, it is more preferably 30mg or more, and particularly preferably 40mg or more. In particular, in order to obtain various effects of reducing visceral fat, reducing body weight, and preventing obesity, it is preferable to set the intake amount of gallic acid or its salt to the lower limit or more. The upper limit is preferably 600mg or less.

When the processed product obtained from myrobalan is formulated into, for example, an orally administrable dosage form, any additional component may be added as necessary, for example, royal jelly, propolis, vitamins (A, B1, B2, B6, B12, nicotinic acid, C, D, E, K, folic acid, pantothenic acid, biotin, derivatives thereof, and the like), minerals (iron, magnesium, calcium, zinc, and the like), selenium, chitin, chitosan, lecithin, polyphenols (flavonoids, derivatives thereof, and the like), carotenoids (lycopene, astaxanthin, zeaxanthin, lutein and the like), xanthine derivatives (caffeine and the like), proteins or peptides (soybean protein, collagen, elastin, silk, or decomposition products thereof, and the like), mucopolysaccharides (hyaluronic acid, chondroitin, dermatan, heparan, heparin, keratin, derivatives thereof, and the like), aminosugars (glucosamine, and the like), and the like, Acetylglucosamine, galactosamine, acetylgalactosamine, neuraminic acid, acetylneuraminic acid, hexosamine, salts thereof and the like), oligosaccharides (isomaltooligosaccharides, cyclic oligosaccharides and the like), phospholipids (phosphatidylcholine, phosphatidylserine and the like), sphingolipids and derivatives thereof (sphingomyelin, ceramide and the like), sulfur-containing compounds (alliin, sulfinyl disulfide (cepaenes and the like), taurine, glutathione, methylsulfonylmethane and the like), lignans (sesamin and the like), pearl powder, alpha-lipoic acid or derivatives thereof, coenzyme Q10, and animal and plant extracts, root vegetables (ginger and the like) containing the same, excipients, lubricants, plasticizers and the like. Among them, it is preferable to combine the lipid absorption-blocking component or the lipid metabolism-promoting component, the sugar absorption-blocking component or the sugar metabolism-promoting component described below.

(lipid absorption-retarding component, lipid metabolism-promoting component)

The addition of at least one of the lipid absorption-blocking component and the lipid metabolism-promoting component in the present invention can achieve a synergistic effect of blocking lipid accumulation or reducing body fat.

Examples of the lipid absorption-blocking component include components having a bile acid excreting effect such as chitosan and derivatives thereof, psyllium, proanthocyanidins, and the like, and components having a lipase inhibitory effect such as gallotannins, loquat leaves, and extracts thereof. For example, a plant extract containing a large amount of proanthocyanidin such as pine bark extract may be used as the proanthocyanidin.

Examples of the lipid metabolism-promoting component include riboflavin, catechin, isomerized linoleic acid, caffeine, capsaicin, carnitine, coenzyme Q10, α -lipoic acid and its derivatives, soybean peptide, branched amino acids, phosphatidylcholine, allyl thioether compounds, forskolin, bergenin, quercetin, astilbin, hydroxycitric acid, and salts thereof. Of course, plant extracts containing these lipid metabolism-promoting ingredients, for example, extracts of tea, pueraria flower, coleus forskohlii, cimicifuga foetida, engelhardtia chrysolepsis, soybean, capsicum, buckwheat, garlic, onion, coffee, and the like, may be used as the lipid metabolism-promoting ingredients.

The lipid absorption-blocking component and the lipid metabolism-promoting component may be appropriately combined according to the purpose. For example, only one of the lipid absorption-blocking component and the lipid metabolism-promoting component may be added, or both the lipid absorption-blocking component and the lipid metabolism-promoting component may be added. Of course, two or more lipid absorption-blocking components may be added, or two or more lipid metabolism-promoting components may be added.

The blend ratio of the processed product of the present invention to the lipid absorption-inhibiting component or the lipid metabolism-promoting component is not particularly limited. For example, the lower limit of the lipid absorption-blocking component or the lipid metabolism-promoting component (or a raw material containing these components) is 1 part by mass or more, preferably 5 parts by mass or more, based on 100 parts by mass of the processed product of the present invention. The upper limit of the lipid absorption-blocking component or the lipid metabolism-promoting component (or a raw material containing these components) is 5000 parts by mass or less, preferably 2500 parts by mass or less, based on 100 parts by mass of the processed product of the present invention.

(sugar absorption-retarding component or sugar metabolism-promoting component)

In the present invention, at least one of the sugar absorption-retarding component and the sugar metabolism-promoting component is blended together with the processed product of the present invention, and a synergistic effect can be expected in the same manner as when at least one of the lipid absorption-retarding component and the lipid metabolism-promoting component is added.

Examples of the raw material having a sugar metabolism-promoting component include thiamines (e.g., vitamin B1), pyridoxols, amino acids (e.g., isoleucine, leucine, valine, serine, proline, glycine, alanine, and threonine), citric acid, malic acid, molybdenum, phosphorus, sulfur, chromium, potassium, manganese, capsaicin, components such as tricaffeoylquinic acid, dicaffeoylquinic acid and derivatives thereof found in the stems and leaves of sweet potatoes, and caroteno saponins, and raw materials having these components, and litchi, black rice vinegar, soybean, jerusalem artichoke, beer yeast, and the like having the same effect. By blending these materials, accumulation of sugar in the body can be suppressed, and further, increase in body fat due to absorption of sugar can be suppressed.

Examples of the raw material having a sugar digestion/absorption-retarding component include a component itself having a sugar decomposition enzyme inhibitory action such as an α -amylase inhibitor and a glucosidase inhibitor, a raw material containing a component having such an inhibitory action, a component itself having a sugar absorption-retarding effect such as a water-soluble dietary fiber, and a raw material containing a component having such a sugar absorption-retarding effect. Specific examples of the raw material having a sugar metabolism-promoting component or a sugar digestion and absorption-promoting component include proteins having an α -amylase inhibitory activity and tannins. Alpha-amylase inhibiting proteins are included in wheat, rye, and the like. Tannins are contained in barley, tea, guava, loquat, etc.

Further, as a raw material having a sugar metabolism-promoting component or a sugar digestion and absorption-blocking component, an α -glucosidase inhibitor can be used. Examples of the α -glucosidase inhibitory substance include 1-deoxynojirimycin, sariluo (salacinol), 1-deoxynojirimycin, Salacia reticulata containing the same, and mulberry leaf. Other examples of the α -glucosidase inhibitory substance include moutan bark, polygonum multiflorum, Alpinia speciosa, mallotus japonicus, Citrus depressa, Passiflora edulis, Agrimonia pilosa, Catechu, sassafras, Rumex crispus, Filipendula ulmaria, and the like. Further, examples of the other α -glucosidase inhibitory substances include dihydrochalcone compounds or flavanone glycosides contained in citrus plants such as satsuma mandarin, citrus aurantium, citrus hassaku, mandarin orange, citrus reticulata, lemon, grapefruit, lime, and lime, quercus acutissima, commelina variety, peony, clove, apocynum venetum, cinnamon, eucalyptus leaf, caraway, chamomile, perilla, wild strawberry, fermented soybean, clove, hydroxyproline, and the like.

In addition, as a material having a sugar metabolism-promoting component or a sugar digestion/absorption-retarding component, a material having a carbohydrate digestive enzyme-inhibiting effect may be used. Examples of the substance having the carbohydrate-digesting-enzyme inhibitory effect include polyphenols contained in tea, guava, sweet tea, ginkgo leaf, grape seed, pine bark extract, and the like, ephedra, papaya, kidney bean, momordica cochinchinensis, persimmon leaf, puerh tea, hypericum erectum, apple tree, angelica sinensis, mallotus japonicus, dogwood, eucommia ulmoides leaf, and the like.

As the raw material having the sugar metabolism-promoting component or the sugar digestion and absorption-retarding component, a carbohydrate digestive enzyme inhibitor itself other than myrobalan, or a powder or an extract of a substance (plant, animal, or the like) containing the carbohydrate digestive enzyme inhibitor may be used.

Further, examples of the raw material having a sugar metabolism-promoting component or a sugar digestion and absorption-blocking component include a component which inhibits sugar absorption, saponin, conduritol a, gymnema sylvestre polypeptide, dietary fiber, and the like. In particular, gymnema sylvestre, angelica japonica, kochia scoparia, etc., saponins contained in gymnema sylvestre, pulegol a contained in gymnema sylvestre, gymnadenia sylvestre polypeptide, etc., may be used as a raw material having a sugar metabolism-promoting component or a sugar digestion absorption-retarding component. Examples of dietary fibers as raw materials having a saccharide metabolism-promoting component or a saccharide digestion-absorption-retarding component include indigestible dextrin, galactomannan, soluble sodium alginate, and inulin. In the case of dietary fiber, it is believed that it retards the absorption of sugar from the intestinal tract by gelling the food.

The blend ratio of the processed product of the present invention to the sugar absorption-retarding component or the sugar metabolism-promoting component is not particularly limited. For example, the lower limit of the sugar absorption-retarding component or the sugar metabolism-promoting component (or a raw material containing these components) is 1 part by mass or more, preferably 5 parts by mass or more, based on 100 parts by mass of the processed product of the present invention. The upper limit of the sugar absorption-retarding component or the sugar metabolism-promoting component (or a raw material containing these components) is 5000 parts by mass or less, preferably 2500 parts by mass or less, based on 100 parts by mass of the processed product of the present invention.

Of course, as other materials/components, excipients, extenders, binders, thickeners, emulsifiers, colorants, flavors, other food materials, pharmaceutical materials, and the like may be added together with the processed product of myrobalan as necessary.

The dosage forms of the above-mentioned drugs for various uses can be used in the form of drinks, granules, tablets, chewing gums, candies, troches, jellies, cornel, tea bags, and the like. Specifically, in addition to the various dosage forms exemplified for the oral composition, a liquid agent, a paste agent, a cream agent, a gel agent, and the like can be exemplified. Among them, the form of tablets, capsules, powders, granules, and liquids is preferable, and the form of tablets, powders, and granules is particularly preferable. Specifically, there are a supplement, a packaged beverage filled in a beverage bottle, can, bottle or the like, an instant beverage dissolved in water (hot water), milk, fruit juice, green juice or the like and drunk, and a food additive. In particular, supplements and instant drinks are preferable because they are convenient to drink at meals and can enhance palatability. The pharmaceutical agents for the above-mentioned respective uses are preferably prepared into various foods as exemplified above as the composition for oral administration.

Examples

The present invention will be described more specifically with reference to examples. It should be noted that the present invention is not limited to these examples.

I.Evaluation of composition for oral administration

The Terminalia bellirica extract was mixed with the respective ingredients as shown in Table 1, and then a tablet having a tablet diameter of 8mm was prepared in a tablet machine at a dose of 250 mg. In table 1, the unit of the amounts of (a) to (D) is part by mass,% means mass%. Commercially available products of calcium stearate, reduced palatinose and silica were used. As the belericae extract, an extract prepared by the following method was used.

(preparation of Terminalia bellirica extract)

Hot water was added to the remaining part of the Terminalia bellirica fruit from which the seeds were removed and mixed, and extraction was performed. After extraction, filtration was carried out, and the filtrate was concentrated. Drying the concentrated solution, pulverizing to obtain Terminalia bellirica extract (water extract of Terminalia bellirica fruit). The bellirish extract was analyzed by high performance liquid chromatography, and as a result, it contained 8.4 mass% of gallic acid.

[ Table 1]

(1) Evaluation of stability

The tablets of comparative examples 1 to 3 and comparative examples 1 to 3 were placed in a cup made of plastic and allowed to stand at 40 ℃ and 75% humidity for 15 hours. The properties of the tablets before and after storage were evaluated according to the items and evaluation criteria in table 2. The evaluation items are shown in table 2, and the evaluation results are shown in table 3.

[ Table 2]

[ Table 3]

In table 2, "+: slightly deformed "means deformed to a varying degree on the surface of the tablet; "++: the "distortion" indicates a distortion to the extent that the corners of the tablet come off; "+++: the "significant distortion" indicates a distortion of the tablet to the extent that the corners of the tablet fall off and the diameter of the tablet changes. According to Table 3, in comparative examples 1 to 3 in which the tablets were stored at 40 ℃ and 75% humidity for 15 hours, the diameter of the tablets was increased, the shape was largely deformed, and the adhesion to the container was generated. On the other hand, the tablets of examples 1 to 3 stored under the same conditions had almost no change in diameter and almost no change in shape was observed. Thus, the composition for oral administration of the present invention is a composition having high storage stability.

(2) Evaluation of Functionality

The tablets of comparative example 1 and examples 1,2 and 4 were subjected to a functionality evaluation. Specifically, whether or not bitterness is improved is judged by the following judgment based on comparative example 1. The evaluation results are shown in table 4.

0 minute: is not improved

1 minute: slightly improved

And 2, dividing: is improved

And 3, dividing: is obviously improved

[ Table 4]

Test substance	Evaluation results
		Comparative example 1	0
Example 1	2
		Example 2	3
Example 4	2

As can be seen from table 4, the orally administrable composition of the present invention is a composition in which bitterness derived from an extract of bellier is improved.

(3) Evaluation of manufacturability

The manufacturability was evaluated for comparative examples 1 to 3 and examples 1 to 4. Comparative example 1 it was difficult to put the raw materials into a mortar and to form a tablet. In comparative examples 2 and 3, the mixture of the raw materials was easier to handle than in comparative example 1, but the friction with the mortar during tabletting was observed, and tablets with partial defects were obtained. On the other hand, in examples 1 to 4, the mixture of the respective raw materials was easy to handle, and a complete tablet without a defect could be obtained.

Next, production examples 1 to 10 of the composition for oral administration of the present invention are shown. Can be manufactured by the same manufacturing method as in the example. The units of the values in table 5 are mass%.

[ Table 5]

The obtained composition has high storage stability, and can be used for oral administration with suppressed bitterness.

II.Evaluation of Effect of processed product of Terminalia chebula

Preparation example A mixture was prepared by mixing 50g of the remaining part of a fruit of Terminalia bellirica, from which seeds were removed, with 2L of water, and extracting under reflux at 100 ℃ for 30 minutes. After the extraction, the mixture was filtered to obtain a filtrate, the residue was further mixed with 2L of water, and the mixture was refluxed under heating in the same manner, and the filtrates obtained by the filtration were combined and freeze-dried to obtain 20g of extract A.

Production example B22 g of extract B was obtained in the same manner as in production example A except that the water in production example A was changed to a 50 vol% aqueous alcohol solution and the heating temperature was changed to 80 ℃.

Production example C the same procedure as in production example A was carried out except that 20g of seeds were used instead of the remaining part of the fruits of production example A after the seeds were removed, to obtain 4g of extract C.

Production example D the same procedure as in production example B was carried out except that 20g of seeds were used instead of the remaining portion of the fruits of production example B after the seeds were removed, to obtain 5.8g of extract C.

(example 5: evaluation of Lipase inhibitory Effect) the extracts A to D obtained in production examples A to D were dissolved in water, and the lipase inhibitory effect was evaluated as follows using a test solution adjusted to 30 mg/mL.

First, 1mL of each test solution was adjusted to pH8.5 with 10 mass/volume% sodium carbonate (Wako pure chemical industries, Ltd.), and the total amount was adjusted to 2mL with distilled water. To this solution were added 4mL of a substrate solution (a solution prepared by diluting milk 3-fold with distilled water and adjusting the pH to 8.5 with sodium carbonate) and 2mL of 0.04 mass/volume% of a lipase derived from porcine pancreas (Wako pure chemical industries, Ltd.). Immediately, the pH of the solution was measured, and after further reaction at 37 ℃ for 20 minutes, the pH was measured again to determine the difference in pH (as. DELTA.A). As a control, the same procedure as described above was carried out except that distilled water was used instead of each test solution, and the difference in pH (as Δ B) was determined. The lipase inhibition (%) was determined from the following formula (I) using. DELTA.A and. DELTA.B. The results are shown in Table 6. The values in the table are the average and standard deviation of three measurements.

[ mathematical formula 1]

[ Table 6]

Values are mean. + -. standard deviation

From the results in table 6, it is understood that the Terminalia bellirica extract exhibits an excellent lipase inhibitory effect particularly in the fruit parts other than the seeds. Namely, the Terminalia bellirica extract is known to have an excellent lipid absorption inhibitory effect.

In addition, when the results of d measurements were performed in the same manner as in example 5 using extracts obtained by manipulating the fruits of Terminalia catappa (Terminalia catappa) or Terminalia chebula as in production example A, the lipase inhibition efficiency of Terminalia catappa was 35.1. + -. 3.1, while the lipase inhibition efficiency of Terminalia chebula was 17.1. + -. 4.3, and the lipase inhibition effect was poor.

(example 6 evaluation of α -glucosidase inhibitory Effect) the extracts A to D obtained in production examples A to D were dissolved in water, and the α -glucosidase inhibitory effect was evaluated as follows using a test solution adjusted to 10 mg/mL.

First, dilutions of each test solution were prepared by diluting 3 times, 9 times, 27 times, and 81 times with purified water, and 80. mu.L of each dilution was added with 40. mu.L of a 0.02M aqueous base solution (base: p-nitrophenyl-. alpha. -D-glucopyranoside) and kept at 37 ℃ for 5 minutes. Then, 40. mu.L of ovalbumin-containing phosphate buffer solution of 0.2g/mL containing 0.2. mu.g/mL of α -glucosidase was added thereto, and the mixture was further kept at 37 ℃ for 15 minutes. Then, 160. mu.L of a 0.2M aqueous solution of sodium carbonate was added to the reaction solution, and the resulting solution was used as a test solution, and the absorbance at 400nm was measured (as a measurement value A). As a control, the absorbance (as a measured value B) of a test solution (control test solution) obtained in the same manner as described above was measured except that purified water was used instead of the above diluent. Further, as each blank of the test solution and the control test solution, the absorbance of each solution (blank) obtained by the same procedure as described above was measured except that a phosphate buffer solution containing ovalbumin was used in place of the α -glucosidase (the measurement value of the blank of the test solution was referred to as measurement value C, and the measurement value of the blank of the control test solution was referred to as measurement value D). After the α -glucosidase inhibition (%) was calculated using the following formula (II) using the above measured values a to D, the final concentration of each extract in the reaction solution showing 50% inhibition effect (IC50) as α -glucosidase inhibition was calculated.

[ mathematical formula 2]

The results are shown in Table 7. The values in table 7 were calculated from the average of the values obtained by three measurements, and the lower the concentration, the stronger the inhibitory activity.

[ Table 7]

From the results in table 7, it is understood that the burriella extract exhibits an excellent α -glucosidase inhibitory effect particularly in the parts other than the seeds. Namely, it is known that the Terminalia bellirica extract has an excellent carbohydrate absorption-retarding effect.

In addition, when the extract obtained by manipulating the fruit of Terminalia catappa or Terminalia chebula as in production example A was used and measured as in example 6, the Terminalia catappa IC50 was 0.2mg/mL and Terminalia chebula IC50 was 1.0mg/mL, and the alpha-glucosidase inhibitory effect was poor.

(example 7: evaluation of body fat accumulation retardation or body fat reduction effect) further, the extracts of production examples a and B, which were effective in examples 5 and 6, were used to evaluate their effects on body fat.

First, 21 female ICR-line mice, 27 weeks old, were acclimatized for 1 week with a standard feed (MF feed, oriental yeast industries, japan). Then, in addition to making the average body weight of each group uniform, three groups of 7 were randomly divided. Then, one of the groups was allowed to freely ingest test feed 1 containing 5 mass% of the extract of production example a, 40 mass% of beef tallow, and 9 mass% of granulated sugar. The other group of the remaining groups was allowed to freely ingest test feed 2 having the same composition except that the extract of production example B was contained instead of the extract of production example a of test feed 1. In addition, the other group was allowed to freely ingest a control feed of the same composition except that the extract of production example a of test feed 1 was not contained. Body weights were measured on day 25 from free intake of each group. After the measurement, the body weight gain (%) was measured by the following formula (III).

[ mathematical formula 3]

Furthermore, subcutaneous fat was measured by X-ray CT (trade name: LATheata, manufactured by Aroca, Japan) for experimental animals. Further, dissection was performed, retroperitoneal fat and periuterine fat were removed, and the total weight (weight of visceral fat) was measured. The results are shown in Table 8.

[ Table 8]

	Body weight gain (%)	Visceral fat (g)	Subcutaneous fat (g)
				Control feed	35.1±2.4	2.43±0.98	4.76±1.52
Test feed 1	32.0±2.1	1.40±0.71	3.15±1.45
				Test feed 2	31.1±1.8	1.26±0.78	3.04±1.69

Values as mean ± standard deviation according to the results of table 8, the group ingested with the test feed 1 or 2 containing the parishin extract of the present invention had lower subcutaneous fat, visceral fat than the control feed. That is, it is found that the Terminalia bellirica extract of the present invention has a body fat accumulation-retarding or body fat-reducing effect. In addition, it was found that the compound can be used as an anti-obesity agent because the increase in body weight is small as compared with the control feed and the test feed 2.

Example 8 extract a (2.4g) of production example a was isolated by column chromatography under the following conditions. At this time, the fraction recovered with the washing liquid (water) was dried to obtain extract E, and the fraction recovered with the eluent (ethanol) was subsequently dried to obtain extract F. Further, the polyphenol amounts of these extracts were measured by the fogdish method to obtain extract a (27 mass%), extract E (24 mass%), and extract F (55 mass%).

Column size: 1 x 7cm

Column carrier: DIAION HP-20 (Mitsubishi chemical corporation)

Cleaning solution: water (W)

Eluent: ethanol

Example 9 evaluation of sucrase inhibition the extract A, E, F obtained in example 8 was evaluated for the inhibition of maltase by the following method. First, rat intestinal acetone powder (manufactured by SIGMA) was homogenized with 9-fold volume of 56mM maleic acid buffer solution (pH6.0), and the solution was centrifuged. Subsequently, the obtained supernatant was further diluted 2-fold with 56mM maleic acid buffer solution (pH6.0) to obtain an enzyme solution.

The enzyme solution (10. mu.L), a 50mM sucrose solution (200. mu.L), and a solution (10. mu.L) of the extract A, E, F adjusted to each concentration with 56mM maleic acid buffer (pH6.0) were added to a 96-well plate. The reaction solution was kept at 37 ℃ for 30 minutes to effect a reaction, and then boiled for 2 minutes to stop the reaction.

The supernatant of the mixed solution after the reaction was stopped was collected, the amount of glucose produced by sucrase in the supernatant was measured with a measurement kit (glucose-CIITest Wako; Wako pure chemical industries, Ltd.), the sucrase inhibition rate (%) was calculated, and the final concentration of each extract in the reaction solution, which exhibited a 50% inhibition effect (IC50) as the sucrase inhibition rate, was determined. The results are shown in Table 9.

Comparative example 4 the final concentration of the guava leaf extract in the reaction solution, which showed 50% inhibitory effect (IC50) in terms of sucrase inhibition rate, was determined in the same manner as in example 9, except that the guava leaf extract (guava phenone; preproduction chemical company) was used in place of the extract A, E, F. The results are shown in Table 9.

[ Table 9]

From the results in table 9, it was found that extracts a and E of belericae had sucrase inhibitory effects at the same level as the guava leaf extract. Further, it is known that extract F obtained by separating extract a has a particularly excellent sucrase inhibitory activity, which is 6 times or more the activity of guava leaf extract. Therefore, it can be seen that the Terminalia bellirica extract of the present invention has an excellent sugar absorption-retarding effect.

Production example E500 mL of a beverage per bottle (unit is mass%) was prepared at the following blending ratio.

Production example F A tablet (unit is mg) of 200mg per tablet was prepared in the following compounding amounts.

Example 10 alpha-glucosidase inhibition assay

(1) Preparation of the samples

Hot water was added to the remaining part of the Terminalia bellirica fruit after removing the seeds, mixed, and extracted. After extraction, filtration was carried out, and the filtrate was concentrated. Drying the concentrated solution, and pulverizing to obtain Terminalia bellirica extract.

The obtained Terminalia bellirica extract (water extract of Terminalia bellirica fruit, manufactured by Toyo Seisakusho Co., Ltd.) was used for the alpha-glucosidase inhibition test. Specifically, inhibition tests were performed on maltase, sucrase and isomaltase. To 100mg of rat intestinal acetone powder (SIGMA corporation), 900. mu.L of 56mM maleic acid buffer (pH6.0) was added, and the resulting mixture was homogenized and centrifuged (3000rpm, 10 minutes, 4 ℃ C.) to obtain a supernatant as an enzyme solution. The inhibition test was performed using a diluted enzyme solution, the inhibition test was performed using an enzyme solution diluted 18 times, and the inhibition test was performed using an enzyme solution diluted 2 times. As the substrate, a 5mM maltose, sucrose, or isomaltose solution dissolved in a 56mM maleic acid buffer (pH6.0) was used. In addition, the content of gallic acid contained in the belchera extract used in the present experiment was analyzed by high performance liquid chromatography, and the result was 14.7 mass%.

The test substance solution was prepared by dissolving the Terminalia bellirica extract in a 0.1% DMSO solution to a predetermined concentration and then performing gradient dilution 2-fold each time.

(2) Activity assay

mu.L of the test substance solution and 15. mu.L of the enzyme solution were added thereto, and the mixture was preincubated at 37 ℃ for 5 minutes. Subsequently, 90. mu.L of the matrix solution was added and incubated at 37 ℃ for 30 minutes. After the reaction, the reaction mixture was treated at 98 ℃ for 2 minutes to stop the enzyme reaction. After the reaction was stopped, the absorbance at 550nm was measured using glucose Test Wako (manufactured by Wako pure chemical industries, Ltd.), and the glucose concentration was measured (as a measurement value A).

The procedure of the activity measurement was carried out in the same manner as in the above-described procedure except that a 0.1% DMSO solution was used instead of the above test substance solution, and the absorbance of the obtained test solution was measured (as a measurement value B).

The procedure was carried out in the same manner as in the above activity measurement except that an enzyme solution which was heat-inactivated by treatment at 98 ℃ for 2 minutes was used instead of the above enzyme solution, and the absorbance of the obtained test solution was measured (as measured value C).

The procedure of the activity measurement was carried out in the same manner as in the above-mentioned step, except that a 0.1% DMSO solution was used in place of the above test substance solution, and an enzyme solution that was heat-inactivated by treatment at 98 ℃ for 2 minutes was used in place of the above enzyme solution, and the absorbance of the obtained test solution was measured (as measured value D).

The alpha-glucosidase inhibition of the Terminalia bellirica extract was calculated by the formula (II) above.

An inhibition curve was prepared from the α -glucosidase inhibition rate obtained by the above formula (II) and the concentration of the test substance solution, and the final concentration of the test substance showing 50% inhibition effect was calculated (IC 50). For the IC50 of each enzyme, maltase was 61.1. mu.g/mL, sucrase was 103.1. mu.g/mL, and isomaltase was 335.1. mu.g/mL.

The above facts indicate that the Terminalia bellirica extract having a gallic acid amount of a specific amount or more exhibits an excellent α -glucosidase inhibitory effect.

Example 11 rat sucrose tolerance test

A sucrose tolerance test was performed in rats using a bellier extract (water extract of the fruit of bellier manufactured by toyoyo seiki co., ltd.). In addition, the content of gallic acid contained in the belchera extract used in the present experiment was analyzed by high performance liquid chromatography, and the result was 14.8 mass%.

SD male rats (SLC, Japan) aged 7 weeks were kept in a dead diet for 12 hours, and were divided into two groups, test and control, so that there was no difference between blood glucose and body weight. For the rats of the test group, the belericae extract was prepared to reach 1.0g/5mL/kg body weight, and orally administered into the stomach using a probe. Distilled water was similarly administered to rats in the control group. Then, 2.0g/5mL/kg body weight of sucrose solution was orally administered to each group of rats. Blood was collected from the tail vein of each rat before administration, 30 minutes and 60 minutes after administration, and the blood glucose concentration was measured using glutamest Ace R (ltd. iii and chemical research institute). The results are shown in FIG. 2.

According to fig. 2, the bellirish extract inhibited the increase in blood glucose level by 60 minutes after sucrose administration, as compared with the control group. As described above, the buerger's extract containing a specific amount of gallic acid or more has an excellent effect of suppressing the increase in blood glucose level.

Production example G

500mL of the beverage (unit is mass%) per bottle was prepared in accordance with the following blending ratio. The drink of production example G was taken before meals, and the effect of retarding the increase in blood glucose level was confirmed after meals.

Production example H

Tablets (unit is mg) of 200mg each were prepared in the following compounding amounts. After 2 tablets of production example H were taken before meals, the effect of suppressing the increase in blood glucose level after meals was confirmed.

Example 12 evaluation test of change in visceral fat/body weight/BMI in human

Object and method

1) Test food

As the test food, a food obtained by mixing reduced palatinose, microcrystalline cellulose, calcium stearate, and microsilica with a paris polyphylla extract (water extract of paris polyphylla fruit, manufactured by tokyo seiki co., ltd.) and tabletting was used. As a control food, a food obtained by replacing the belliri extract in the test food with a caramel pigment was used in order to make the control food not different from the test food in appearance. The test food and the control food are independently packaged in plain aluminum at a single intake (0.25g × 4 grains) to ensure blind detection of the subjects and the intervention operators. The calorie and nutrient content values of the test foods are shown in table 10. The amount of gallic acid contained in the test food was calculated from the results of quantitation by an HPLC method, and the standard intake amount per day was 41.6 mg.

[ Table 10]

Calorie and nutrient content values (daily standard intake) of test foods

¹⁾Energy conversion factor: protein 4; a lipid 9; carbohydrate 4

²⁾Nitrogen-protein conversion coefficient: 6.25

2) Test subject

The test-responsible physicians were assigned to the subjects 100 (male: 44; female: 56) subjects who satisfied the following inclusion criteria and did not conflict with the exclusion criteria.

And (3) inclusion standard: (1) healthy normal men and women aged 20 years or older and less than 65 years old (2) have a BMI of 23 or more and less than 30. Has a BMI of 25 or more and less than 30 and an abdominal visceral fat area of less than 100cm². (3) Persons who had received adequate instructions on the purpose, content, and ability to approve and voluntarily and in written form approve participation in the trial on an adequately understood basis.

Exclusion criteria: (1) a person (2) who frequently takes medicines cannot stop taking supplements/health foods (including specific health foods and functional marker foods) which may affect obesity, hyperlipidemia, lipid metabolism during a test period, (3) a person who cannot start drinking wine in two days before screening test and each test, (4) a person who suffers from severe kidney disease/digestive tract disease/heart disease/respiratory tract disease/endocrine disease or other metabolic diseases, a person who is being treated, (5) a person (7) who reports that allergy is caused to components of test foods, (6) a person who has drug dependence, past or present history of alcohol dependence, (7) a person (8) who has entered metal into a CT scanning measurement site by surgery or the like, (9) a person who has implanted medical equipment in vivo such as a pacemaker or implantable defibrillator, (10) a person who suffers from claustrophobia disorder during CT scanning shooting, (10) a shift operation person who shifts work, and (2) a person who cannot stop taking medicines during a test period, The night shift operator (11) has been diagnosed as a person with familial hyperlipidemia (12) a pregnant person, a person who intends to become pregnant during a test, a person who is nursing a mammal (13) who is participating in other food intake, a test using drugs, a test applying cosmetics, drugs, etc., a person who has agreed to participate in other clinical tests within one month, a person who wishes to participate in other clinical tests (14) and a person who is determined by other test responsible physicians to be unsuitable as a subject

3) Test method

This trial was conducted for a total of 16 weeks of placebo-controlled randomized double-blind parallel group comparison trial consisting of a pre-observation period (2 weeks), a period before intake start (2 weeks), and an intake period (12 weeks) (partition ratio: 1: 1). Statistical analysis subjects were assigned by group randomization (group size 4) with sex, age, weight, abdominal visceral fat area as adjustment factors. Both groups were divided into test and control food groups while ensuring blind detection of the groups. During the test period, the test food (test food in the test food group and control food in the control food group) was ingested twice daily, 1 bag (4) each time, together with 100mL of water or warm water before a meal.

During the trial, the following are described as notes throughout the trial to the subjects: drugs, health foods and the like which may have an influence on obesity, hyperlipidemia, lipid metabolism and the like are not used; the same life as before the start of the test was spent; does not consume a large amount of alcohol; after the meal, the patient does not go to bed within 2 hours; food including snacks was not ingested after 22 o' clock; the interval of each meal is more than 3 hours; avoid participating in other tests, etc. In addition, the following matters are described as matters to be taken into consideration in each examination: no X-ray examination using barium was performed within 1 week before the CT scan examination; controlling the intake of fruits, wild vegetables and carbonated drinks for inhibiting the generation of intestinal gas one day before CT scanning examination; avoid alcohol intake two days before the total examination; avoid diets other than water 21 o' clock the day before total examination; smoking is prohibited from getting up until the end of the examination on the day of all examinations.

4) Examination item

Physical examination

For body weight (BMI), the results of a total of four examinations before intake, 4 weeks after intake, 8 weeks after intake, and 12 weeks after intake were used for statistical analysis. The abdominal visceral fat, the abdominal subcutaneous fat area, and the abdominal total fat area evaluated by CT scanning (Supria manufactured by hitachi corporation and activin 16 manufactured by toshiba medical systems co., ltd.) were examined three times in total, except for 4 weeks after ingestion, in order to protect the subjects.

Meal/life/physical condition survey

The subjects were issued a meal log and a subject log, and the following survey items were logged every day throughout the intake period starting 2 weeks before the intake start day. In particular, meal contents were recorded in detail on the intake start day and three days before each examination during the intake period, and the nutrition intake was calculated by the dietician using the nutrition management software. In addition, the alcohol intake amount in the other mode is calculated.

Survey items: (1) test food intake (2) number of steps per day (measured value based on pedometer) (3) presence or absence of change in physical condition (4) presence or absence of change in living condition (5) bedtime (6) use of drugs (drugs other than nutritional drinks/newly-specified department of medicine/new-range department of medicine) (7) meal content (including supplement/health food/nutritional drink, alcohol)

Checks on Security

The examination of systolic pressure, diastolic pressure, pulse rate, blood examination, urine examination, and physician's inquiry are performed together with the physical examination. For blood tests, as hematology test items, white blood cell count, red blood cell count, hemoglobin, hematocrit, mean volume of red blood cells (MCV), mean hemoglobin content of red blood cells (MCH), mean hemoglobin concentration of red blood cells (MCHC), and platelet count are tested; total protein, albumin, aspartate Aminotransferase (AST), alanine Aminotransferase (ALT), lactate dehydrogenase (ld (ldh)), total bilirubin, alkaline phosphatase (ALP), serum gamma-glutamyl transpeptidase (gamma-GTP), urea nitrogen, creatinine, uric acid, sodium (Na), chlorine (Cl), potassium (K), calcium (Ca), phosphorus (P), fasting blood glucose, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, neutral fat, and phospholipids are examined as biochemical examination items. For urine test, as quantitative items, pH and specific gravity are checked; as qualitative items, protein characterization, sugar characterization, urobilinogen characterization, bilirubin characterization, ketone body in urine, occult blood reaction were examined.

5) Statistical analysis

The main evaluation item was abdominal visceral fat area. Abdominal subcutaneous fat area, abdominal total fat area, body weight, BMI were secondary evaluation items.

The analysis target group was a Protocol-compliant data Set (PPS), and when the interaction was confirmed, the actual measurement value and the change value before ingestion of each test were compared between groups by t-test which did not correspond to each test. In either test, the significance level was 5% in the two-sided test, and statistical analysis was performed using statistical analysis software (IBM: PASW Statistics 18). The missing data was treated as missing values, and the statistical data were expressed as mean ± standard deviation.

In addition to 1 out of 100 subjects who left due to withdrawal during the test due to a cause unrelated to the test food, 15 subjects who met the rejection criteria (intake of food or the like affecting long-term obesity, lipid metabolism, etc. with changed lifestyle habits, compared to before the start of the test) were confirmed after the end of the test. Therefore, 84 subjects (male; 35; female: 49; test food intake group: 43; control food intake group: 41) were analyzed. The test food group was 46.0 ± 9.3 years old with respect to the age of the subject; the control food group was 46.7 ± 8.8 years old; for height, the test food group was 163.8 ± 9.3 cm; the control food group was 161.8. + -. 8.2 cm. No differences between group nutritional intake (energy, protein, lipids, carbohydrates, dietary fibres) and exercise (walking) were observed throughout the experiment. No adverse events were observed as a result of ingestion of the test food.

[ Table 11] results of physical examination

Mean. + -. standard deviation (control: n ═ 41; test: n ═ 43)

A,: compared with the control food group, the food has significant difference (p is less than 0.05, p is less than 0.01, and p is less than 0.001)

#: the result of the two-way anova was that there was an interaction (p < 0.05)

As is clear from table 11, the test food group showed significantly lower values than the control food group in the change values of abdominal visceral fat area, body weight, and BMI with respect to before intake. Visceral fat and body weight (BMI) reduction by ingestion of a food product containing an extract of Terminalia bellirica is indicated.

In the following, effective formulations are shown below in order to obtain the above-mentioned visceral fat reducing, body weight reducing and anti-obesity effects. The following formula shows the preferred intake for one day. In the Terminalia bellirica extract used in formulation examples 1 to 11, the amount of gallic acid or a salt thereof is, for example, 8 to 19% by mass. Prescription examples 1,3, 10, and 11 correspond to the oral composition described in "composition for oral administration ii".

(Terminalia bellirica extract) the remaining part of Terminalia bellirica fruit from which the seeds were removed was extracted by adding hot water and mixing. After extraction, filtration was carried out, and the filtrate was concentrated. Drying the concentrated solution, and pulverizing to obtain Terminalia bellirica extract. The obtained Terminalia bellirica extract was used to prepare beverages and foods of formula examples 1 to 11.

(formulation example 1) the granules of the following composition were dissolved in 100ml of water at 6g per day (divided into two bags) and drunk.

[ Table 12]

Granules

(prescription example 2) Soft capsules (1 capsule 300mg) having the following composition were ingested 10 capsules per day.

[ Table 13]

Soft capsule

(prescription example 3) hard capsules (1 capsule 200mg) of the following composition were ingested 10 capsules per day.

[ Table 14]

Hard capsules

The coating material uses a gelatin hard capsule

(prescription example 4) A gel (1 piece 10g) having the following composition was ingested at 2 pieces per day.

[ Table 15]

Gel

1 piece 10g

(prescription example 5) the following composition of drink (1 bottle 100ml) was ingested in 2 bottles per day.

[ Table 16]

Beverage product

Internal volume 100ml

(prescription example 6) yogurt (1 yogurt with the following composition (100 g) was ingested 2 times per day.

[ Table 17]

Yoghurt

Internal volume 100g

(formulation examples 7 to 9) tea bags were prepared with the following compositions.

[ Table 18]

Tea bag

2 bags 6g

(unit: mass%)

Spraying Terminalia bellirica extract on black tea (or green tea, oolong tea).

(prescription examples 10 and 11) tablets (1 tablet 300mg) of the following composition were ingested at 10 tablets per day.

[ Table 19]

Tablet formulation

Each granule has a weight of 300mg

10 granules per day

	Prescription example 10	Prescription example 11
			Terminalia bellirica extract	20	20
Reducing maltose	63	53
			Cellulose, process for producing the same, and process for producing the same	15	15
Silicon dioxide	1	1
			Calcium stearate	1	1
Raw material mixture (folding 1)		10
			Total of	100	100

In addition, the method is as follows: the materials contained in the raw material mixture are as follows.

Zinc-containing yeast, green pepper fermented extract, black cohosh extract, white kidney bean extract, turmeric extract, oolong tea extract, barley young leaf powder, olive leaf powder, cocoa extract, persimmon tannin powder, licorice extract, chitosan, gymnema sylvestre extract, guava extract, black pepper extract black rice vinegar, chromium-containing yeast, chlorophyll, mulberry leaf extract powder, black tea extract, salacia extract, onion skin extract, corn stigma, eucommia bark leaf extract, crape myrtle leaf extract, pu' er tea extract, matcha, green tea extract, apple extract, lewis flower extract, L-isoleucine, L-valine, L-leucine, calcium pantothenate, vitamin B1, B2, B6, B12, C, D, folic acid (the materials are mixed in equal amount)

Industrial applicability

According to the present invention, an oral composition having high storage stability and suppressed bitterness can be provided by containing a processed myrobalan product and a lubricant and/or an excipient and making the total amount of the lubricant and/or the excipient 7 mass% or more based on the total amount of the processed myrobalan product, the lubricant, and the excipient.

Further, according to the present invention, a processed product obtained from myrobalan can also be used as an excellent body fat accumulation retardant, body fat reducing agent, lipid absorption retardant, carbohydrate absorption retardant, α -glucosidase inhibitor, blood glucose level increase retardant, visceral fat reducing agent, weight reducing agent, and anti-obesity agent.

Claims (12)

1. A composition for oral administration comprising:

(A) processed product of myrobalan, and

(B) a lubricant and/or (C) an excipient,

the total amount of (B) and/or (C) is 7% by mass or more based on the total amount of (A), (B) and (C).

2. The composition for oral administration according to claim 1, wherein the amount of the processed product of myrobalan (A) is 10% by mass or more based on the total amount of (A), (B) and (C).

3. Use of processed product of Terminalia chebula for producing body fat accumulation inhibitor or body fat reducing agent.

4. Use of processed product of fructus Chebulae in preparing lipid absorption inhibitor is provided.

5. Use of a processed product of myrobalan for the manufacture of a carbohydrate absorption retardant.

6. Use of a Terminalia bellirica extract comprising gallic acid or a salt thereof for the manufacture of an alpha-glucosidase inhibitor.

7. Use of a Terminalia bellirica extract containing gallic acid or a salt thereof for producing a blood glucose level increase retardant.

8. The use according to claim 7, wherein the content of gallic acid or a salt thereof in the Terminalia bellirica extract is 11% by mass or more.

9. Use of a processed product of myrobalan for producing a visceral fat reducing agent.

10. Use of a myrobalan processed product for the manufacture of a weight reducing agent.

11. Use of processed product of fructus Chebulae in preparing anti-obesity agent is provided.

12. The use of a processed myrobalan product according to any one of claims 9 to 11, wherein the medicament is produced such that an intake of gallic acid or a salt thereof per day for an adult is 20mg or more.

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