Composition for suppressing postprandial increase in uric acid level

Abstract

To provide compositions having excellent action of inhibiting postprandial increase in uric acid level.SOLUTION: Provided is a composition for suppressing postprandial increase in uric acid level, comprising gallic acid or a salt thereof.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for suppressing postprandial increase in uric acid level, a composition for suppressing purine absorption, and a composition for inhibiting purine nucleotidase, each of which contains gallic acid or a salt thereof. [Background technology]

[0002] Gout and hyperuricemia, the underlying disease of gout, are diseases caused by high serum uric acid levels. In Japan, the number of patients with gout and hyperuricemia is on the rise due to changes in dietary habits, and there is growing interest in the prevention and treatment of gout and hyperuricemia.

[0003] It is considered important to appropriately control serum uric acid levels for the prevention and treatment of gout and hyperuricemia. There are four main methods of control: restricting the intake of purines, which are the raw material of uric acid, by restricting dietary intake; inhibiting the absorption of purines from the outside of the body; inhibiting uric acid synthesis by inhibiting xanthine oxidase; and promoting excretion of uric acid from the kidney or other organs. It has been reported that if a healthy person takes in 4 g of purines per day for several days, the serum uric acid level rises and hyperuricemia occurs (Non-Patent Document 1), so it is considered that the effect of diet on serum uric acid levels is large. Therefore, it is desirable to continue restricting the intake of purines by restricting dietary intake, but it is not easy to continue restricting the intake of purines every day in daily life. In order to suppress the increase in uric acid levels due to diet, it is very important to inhibit the absorption of purines from the outside of the body, and efforts have been made to develop foods that can effectively reduce the absorption of purines into the body and suppress the increase in uric acid levels after meals. For example, it is known that the intake of inositol phosphate exerts an effect of inhibiting purine absorption and an effect of inhibiting purine nucleotide metabolism (Patent Document 1). However, the compositions developed so far have not necessarily been sufficiently effective, and there is a demand for the development of new compositions that have an excellent effect of suppressing the rise in postprandial uric acid levels. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. WO2019 / 082335 [Non-patent literature]

[0005] [Non-Patent Document 1] Yu TF,Berger L.Impaired renal function in gout:its association with hypertensive vascular disease and intrinsic renal disease.Am J Med 1982;72:95-100 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide an oral composition which has an excellent effect of suppressing an increase in postprandial uric acid level.

[0007] The present inventors have conducted extensive research to solve the above problems and have surprisingly found that by containing gallic acid or a salt thereof, a composition having excellent effects of suppressing a postprandial increase in uric acid level, suppressing purine absorption, and inhibiting purine nucleotidase can be obtained. The present invention has been completed based on such findings.

[0008] The outline of the present invention is as follows. [1] A composition for suppressing postprandial increase in uric acid level, comprising gallic acid or a salt thereof. [2] A composition for inhibiting purine absorption, comprising gallic acid or a salt thereof. [3] A composition for inhibiting purine nucleotidase, comprising gallic acid or a salt thereof. Effect of the Invention

[0009] The composition of the present invention contains gallic acid or a salt thereof and thus effectively inhibits purine nucleotidase, and is therefore excellent in suppressing purine absorption and exerts the effect of suppressing a postprandial increase in uric acid level. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The present invention will be described in detail below. Note that the present invention is not limited to the following embodiments.

[0011] The present invention uses gallic acid or a salt thereof as an essential component. Gallic acid is 3,4,5-trihydroxybenzene carboxylic acid, and is widely present in the roots, stems, leaves, fruits, etc. of plants. The salt of gallic acid used in the present invention is not particularly limited, and examples thereof include alkali metal salts. As the gallic acid or a salt thereof used in the present invention, gallic acid is preferred from the viewpoint of the effect of suppressing the rise in uric acid level after meals.

[0012] Gallic acid or a salt thereof used in the present invention is not particularly limited, and examples thereof include synthetic products synthesized by methods generally known to those skilled in the art, natural products containing gallic acid or a salt thereof, and processed products of the natural products. In the present invention, synthetic products synthesized by methods generally known to those skilled in the art, natural products containing gallic acid or a salt thereof, and processed products of the natural products are preferred, natural products containing gallic acid or a salt thereof, and processed products of the natural products are more preferred, and processed products of the natural products containing gallic acid or a salt thereof are particularly preferred from the viewpoint of the effect of suppressing the rise in postprandial uric acid level. In the present invention, only one type of gallic acid or a salt thereof may be used, or two or more types may be used. In the present invention, commercially available products of gallic acid or a salt thereof may be used.

[0013] The natural product containing gallic acid or a salt thereof used in the present invention is not particularly limited, and examples thereof include plants of the Anacardiaceae family, Fagaceae family, Fabaceae family, Theaceae family, and Combriaceae family, with Fabaceae, Theaceae and Combriaceae plants being preferred, and Theaceae and Combriaceae plants being more preferred.

[0014] The processed natural product containing gallic acid or a salt thereof is not particularly limited, but may be, for example, a crushed product, a squeezed juice, an extract, etc. Crushed products include powders, granules, etc. The extract is obtained by extracting a natural product with a solvent. The solvent is not particularly limited, but may be, for example, water, an organic solvent, or a water-containing organic solvent (water-containing alcohol such as water-containing ethanol). The extraction method is not particularly limited as long as it is a method that is usually acceptable for extracting natural product components, but may be, for example, a solid-liquid extraction method such as a heating extraction method or a supercritical fluid extraction method. The squeezed juice or extract may be in a liquid form, but may also be used as a paste or a dry powder. When it is made into a paste or a dry powder, it may be produced by using only the product itself, or may be processed together with an excipient. The obtained processed product may be further subjected to a chemical treatment, an enzyme treatment, or a purification treatment.

[0015] The blending ratio of gallic acid or a salt thereof in the composition of the present invention is not particularly limited, and the content can be appropriately set within a wide range depending on various conditions such as the purpose, shape, and subject of use. For example, when the composition of the present invention is a solid preparation (powder, granule, tablet, capsule, chewable, etc.), the content is preferably 0.001 to 50% by mass, more preferably 0.01 to 30% by mass, and particularly preferably 0.1 to 10% by mass from the viewpoint of the effect of suppressing the rise in uric acid level after meals. Also, for example, when the composition of the present invention is a liquid preparation (liquid, gel, jelly, paste, etc.), the content is preferably 0.0001 to 10% by mass, more preferably 0.001 to 5% by mass, and particularly preferably 0.01 to 1% by mass from the viewpoint of the effect of suppressing the rise in uric acid level after meals.

[0016] The content of gallic acid or its salt in the composition of the present invention can be measured by an analytical method suitable for the condition of the measurement sample among commonly known analytical methods for gallic acid or its salt. For example, it can be analyzed by liquid chromatography. As an example, it can be measured by a high performance liquid chromatograph equipped with an ultraviolet absorption detector, and the analytical column is Unison UK-C18HT (3×100 mm) manufactured by Imtakt, and the mobile phase is a 1 volume % formic acid aqueous solution (mobile phase A) and a 1 volume % formic acid acetonitrile solution (mobile phase B). The column temperature can be 45° C. and the flow rate can be 0.7 mL / min. The gradient conditions can be as follows. In addition, when measuring, appropriate treatment such as removing impurities in the sample to match the separation ability of the device may be performed as necessary.

[0017] [Table A]

[0018] The daily intake of the composition of the present invention per body weight is not particularly limited, and can be appropriately set depending on the mode of use and the contents of use by the user. For example, when the composition of the present invention is a solid formulation (powder, granule, tablet, capsule, chewable, etc.), the intake is preferably 2 to 1000 mg / kg, more preferably 4 to 200 mg / kg, based on the body weight of the user, and particularly preferably 10 to 100 mg / kg, from the viewpoint of the effect of suppressing the increase in uric acid level after meals. Also, for example, when the composition of the present invention is a liquid formulation (liquid, gel, paste, etc.), the intake is preferably 200 to 20000 mg / kg, more preferably 600 to 15000 mg / kg, based on the body weight of the user, and particularly preferably 1000 to 10000 mg / kg, from the viewpoint of the effect of suppressing the increase in uric acid level after meals.

[0019] Similarly, the amount of the composition of the present invention taken per time per body weight is not particularly limited. For example, when the composition of the present invention is a solid preparation (powder, granule, tablet, capsule, chewable, etc.), it is preferably 0.6 to 1000 mg / kg, more preferably 1.3 to 200 mg / kg, based on the body weight of the user, and particularly preferably 3.3 to 100 mg / kg, from the viewpoint of the effect of suppressing the rise in uric acid level after meals. Also, for example, when the composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), it is preferably 66 to 20000 mg / kg, more preferably 200 to 15000 mg / kg, based on the body weight of the user, and particularly preferably 333 to 10000 mg / kg, from the viewpoint of the effect of suppressing the rise in uric acid level after meals.

[0020] The daily intake of the composition of the present invention is not particularly limited, and for example, when the composition of the present invention is a solid preparation (powder, granule, tablet, capsule, chewable, etc.), the daily intake is preferably 0.1 to 50 g, more preferably 0.2 to 10 g, and particularly preferably 0.5 to 5 g from the viewpoint of the effect of suppressing the rise in uric acid level after meals. For example, when the composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the daily intake is preferably 10 to 1000 g, more preferably 30 to 750 g, and particularly preferably 50 to 500 g from the viewpoint of the effect of suppressing the rise in uric acid level after meals.

[0021] The amount of the composition of the present invention taken at one time is not particularly limited, and for example, when the composition of the present invention is a solid preparation (powder, granule, tablet, capsule, chewable, etc.), the amount is preferably 0.03 to 50 g, more preferably 0.06 to 10 g, and particularly preferably 0.16 to 5 g from the viewpoint of the effect of suppressing the rise in uric acid level after meals. Also, when the composition of the present invention is a liquid preparation (liquid, gel, paste, etc.), the amount is preferably 3.3 to 1000 g, more preferably 10 to 750 g, and particularly preferably 16 to 500 g from the viewpoint of the effect of suppressing the rise in uric acid level after meals.

[0022] The composition of the present invention may contain only gallic acid or its salt, or may contain other components in addition to gallic acid or its salt. Examples of the other components include proteins, dietary fibers such as water-soluble dietary fiber and insoluble dietary fiber, minerals, plants or processed plant products, algae, lactic acid bacteria, yeasts, and other microorganisms. If necessary, the composition may further include sugars such as dextrin and starch, oligosaccharides, sweeteners, acidulants, colorants, thickeners, gloss agents, excipients, vitamins, nutritional supplements, binders, lubricants, stabilizers, diluents, bulking agents, emulsifiers, food additives, and seasonings that are commonly used in the food industry. The content of these other components may be appropriately selected depending on the form of the composition of the present invention.

[0023] The composition of the present invention can be used as, for example, medicines (including quasi-drugs), so-called health foods such as functional foods whose efficacy has been approved by a designated organization, such as foods for specified health uses, foods with nutritional functions, and foods with functional claims, as well as general foods, food additives, feed, etc. The composition of the present invention may be taken before meals, between meals, after meals, or simultaneously with meals, but from the viewpoint of the effect of suppressing an increase in uric acid level after meals, it is preferable to take the composition before meals, after meals, or simultaneously with meals, and more preferably before meals.

[0024] The composition of the present invention can be used as a composition for suppressing an increase in uric acid level after a meal. Most of the purines contained in food are present as nucleic acids, and are absorbed into the body from the intestinal tract through a process of being decomposed into nucleosides by purine nucleotidase. Therefore, by inhibiting purine nucleotidase, it is possible to suppress the absorption of purines into the body from the intestinal tract, and thus to suppress an increase in uric acid level after a meal.

[0025] The composition of the present invention is not particularly limited as long as it can be distinguished from other products as a product in terms of its use in suppressing postprandial uric acid level rise, suppressing purine absorption, and inhibiting purine nucleotidase. For example, the present invention includes a product that displays the function of suppressing postprandial uric acid level rise, suppressing purine absorption, or inhibiting purine nucleotidase on the main body, packaging, instructions, or advertising material of the product of the present invention. Examples of the product include so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods such as specified health foods, nutritional functional foods, and functional food whose efficacy has been approved by a designated organization, and feeds. Examples of so-called health foods include those that display "suppresses postprandial uric acid level rise", "suppresses uric acid level rise due to purines in meals", "suppresses absorption of purines contained in meals", and "suppresses absorption of purines".

[0026] The form of the composition of the present invention is not particularly limited, and can be any form. For example, forms suitable for oral use, specifically, powder, granule, tablet, liquid, gel, paste, capsule such as hard capsule or soft capsule, caplet, tablet, gel, jelly, gummy, wafer, biscuit, cookie, cake, chewable, syrup, stick, etc., can be mentioned, and various excipients, binders, lubricants, stabilizers, diluents, bulking agents, thickeners, gelling agents, emulsifiers, colorants, flavors, sweeteners, additives, etc. can be blended according to the form used. From the viewpoint of the postprandial uric acid level increase suppression effect, the composition of the present invention is preferably in the form of granules, tablets, capsules, or liquid, and more preferably in the form of granules, tablets, or capsules. Here, granules refer to a composition obtained by granulating powder, and may be directly consumed, or may be dissolved in a liquid such as water and consumed. Moreover, the term "gel-like" refers to a composition that contains water and a gelling agent and has viscosity or elasticity.

[0027] The packaging form of the composition of the present invention is not particularly limited and can be appropriately selected depending on the dosage form, etc., and examples thereof include blister packs such as PTPs, strip packaging, heat seals, aluminum pouches, film packaging using plastics, synthetic resins, etc., glass containers such as vials, and plastic containers such as ampoules. EXAMPLES

[0028] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to these examples, and the present invention can take various forms as long as the object of the present invention can be achieved.

[0029] <Test: Evaluation of purine nucleotidase inhibitory activity> In order to confirm that the ingestion of the composition of the present invention exerts a purine nucleotidase inhibitory effect, the following test was carried out. Specifically, taking advantage of the fact that rat small intestine powder contains 5'-nucleotidase as a digestive enzyme, the inhibition of metabolism of purine nucleotides to purine nucleosides by gallic acid was investigated.

[0030] [Test Method] Rat small intestine acetone powder (Sigma-Aldrich) was mixed with assay buffer (0.01M MgCl2, 0.1M Tris-maleate (pH 6.8) and adjusted to pH 6.8) to 100mg / ml to prepare the enzyme solution. The enzyme solution was heated to inactivate it to prepare the inactivated enzyme solution. Inosine monophosphate (IMP) (Tokyo Chemical Industry Co., Ltd.) was adjusted to 9mM in assay buffer to prepare the substrate solution. Gallic acid and assay buffer were mixed so that the concentration of gallic acid was 13.56mg / ml to obtain the specimen solution. Gallic acid manufactured by Kishida Chemical Co., Ltd. was used. The assay buffer was used as the control solution, and the enzyme reaction was carried out by the following method.

[0031] 100 μL of the sample solution or control solution, 100 μL of the substrate solution, and 100 μL of the enzyme solution or the inactivated enzyme solution were mixed, and the enzyme reaction was carried out at 37°C for 30 minutes. The concentration of gallic acid during the enzyme reaction was 4.52 mg / ml. After the enzyme reaction, 60 μL of the reaction solution was taken out, and 540 μL of a stop solution (0.33 M HClO4) was added to stop the reaction. The solution was transferred to a spin filter (Nacalai Tesque, Inc.) and centrifuged (1080 × g, 10 minutes, room temperature), and the filtrate was subjected to high performance liquid chromatography (HPLC) to measure the amount of inosine monophosphate and inosine. The HPLC analysis conditions are shown below. Column: ZORBAX SB-C185μm, 4.6×150mm (Agilent) Mobile phase: 50mM KH2PO4 (pH7.5) Flow rate: 1.0mL / min Detection wavelength: 254 nm Column temperature: 35℃ Sample injection volume: 10 μL

[0032] The metabolic inhibition rate from inosine-phosphate to inosine was calculated by the following formula 1.

[0033]

number

[0034] [Results (purine nucleotidase inhibitory effect)] The test results are shown in Table 1.

[0035] [Table 1]

[0036] As shown in Table 1, it has been revealed that gallic acid has an excellent purine nucleotidase inhibitory effect. Therefore, since gallic acid or a salt thereof has an excellent purine nucleotidase inhibitory effect, the composition of the present invention is excellent in suppressing purine absorption, and can exert an excellent effect in suppressing a postprandial increase in uric acid level.

[0037] [Production Example] Based on the results of the Examples, Production Examples of the present invention are given below.

[0038] [Production Example 1-4: Granules] According to the formulation in Table 2, gallic acid was mixed with other raw materials, and then fluidized bed granulation was performed using a granulator to produce the granules described in Production Example 1-4. The granules described in Production Example 1-4 may be taken by dissolving 3 g per day in 100 ml of a solvent such as water, or may be taken as is without dissolving. All of the granules in Production Example 1-4 are effective in suppressing the rise in uric acid levels after meals.

[0039] [Table 2]

[0040] [Production Example 5-8: Tablets] According to the composition of Table 3, gallic acid and other raw materials were mixed, and then tableted using a rotary tablet press to produce tablets of Production Example 5-8. The tablets were produced with a tablet diameter of 8 mmφ, tablet thickness of 4.5 mm, weight of 300 mg, and hardness of 5 kgf or more. One to two tablets of the tablets described in Production Example 5-8 may be taken per day with 100 ml of water or the like. All tablets of Production Example 5-8 are effective in suppressing an increase in uric acid level after meals.

[0041] [Table 3]

[0042] [Production Example 9-12: Hard Capsule] According to the composition in Table 4, gallic acid was mixed with other raw materials and encapsulated with a film containing gelatin or hydroxypropyl cellulose to produce hard capsules. Each hard capsule was produced at 300 mg. One to two capsules per day can be taken with 100 ml of water or the like. All of the hard capsules in Production Examples 9 to 12 are effective in suppressing the rise in uric acid levels after meals.

[0043] [Table 4]

[0044] [Manufacturing example 13-16: PET beverage] According to the formula in Table 5, a liquid preparation containing gallic acid and other ingredients was packed in a PET container to produce a PET beverage. Each PET beverage was produced in a volume of 500 ml. One bottle should be consumed per day. In addition, all of the PET beverages in Production Examples 13-16 are effective in suppressing the rise in uric acid levels after meals.

[0045] [Table 5] [Industrial Applicability]

[0046] INDUSTRIAL APPLICABILITY The composition of the present invention exhibits an inhibitory effect on purine absorption and an excellent inhibitory effect on postprandial increase in uric acid level due to its purine nucleotidase inhibitory effect, and is therefore highly industrially useful.

Claims

1. A composition for suppressing a postprandial increase in uric acid level, characterized in that gallic acid or a salt thereof (excluding those derived from tea, red wine or grapes) is contained as an active ingredient.

2. A composition for inhibiting purine absorption, comprising gallic acid or a salt thereof (excluding those derived from tea, red wine or grapes) as an active ingredient.

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