阅读说明：本技术 尿酸排出促进用组合物、urat1抑制用组合物及血液中尿酸值降低用组合物 (Composition for promoting uric acid excretion, composition for inhibiting URAT1, and composition for lowering uric acid level in blood ) 是由 山村淳贵 辰草太郎 于 2019-08-05 设计创作，主要内容包括：本发明的目的在于提供一种尿酸排出促进用组合物,尤其为通过抑制URAT1来促进尿酸排出的尿酸排出促进用组合物、URAT1抑制用组合物及血液中尿酸值降低用组合物以及促进尿酸排出的方法、抑制URAT1的方法及降低血液中尿酸值的方法。本发明涉及一种含有选自不具有或具有1个甲氧基的黄烷酮及黄烷酮糖苷中的1种以上的黄烷酮化合物作为有效成分的尿酸排出促进用组合物等。(The purpose of the present invention is to provide a composition for promoting uric acid excretion, in particular, a composition for promoting uric acid excretion, a composition for inhibiting URAT1, a composition for reducing uric acid level in blood, a method for promoting uric acid excretion, a method for inhibiting URAT1, and a method for reducing uric acid level in blood, which promote uric acid excretion by inhibiting URAT 1. The present invention relates to a composition for promoting uric acid excretion, which contains, as an active ingredient, at least one flavanone compound selected from the group consisting of flavanones having no or 1 methoxy group and flavanone glycosides.)

1. A composition for promoting uric acid excretion, which comprises 1 or more flavanone compounds selected from flavanones and flavanone glycosides having no or 1 methoxy group as an active ingredient.

2. The composition for promoting uric acid excretion according to claim 1, wherein the flavanone compound is at least 1 compound selected from the group consisting of isoxanthohumol, naringenin, hesperidin and eriodictyol.

3. The composition for promoting uric acid excretion according to claim 1 or 2, wherein the flavanone compound is isoxanthohumol.

4. The composition for promoting uric acid excretion according to any one of claims 1 to 3, wherein uric acid excretion is promoted by inhibiting URAT 1.

5. A composition for inhibiting URAT1 contains 1 or more flavanone compounds selected from flavanone and flavanone glycoside having no or 1 methoxy group as active ingredient.

6. The URAT1 inhibitory composition according to claim 5, wherein the flavanone compound is at least one compound selected from the group consisting of isoxanthohumol, naringenin, hesperidin and eriodictyol.

7. A composition for lowering uric acid level in blood, which comprises isoxanthohumol as an active ingredient.

8. The composition for reducing uric acid level in blood according to claim 7, which is used for preventing or ameliorating hyperuricemia.

9. The composition for reducing uric acid level in blood according to claim 7, which is used for the prevention or amelioration of gout.

10. The composition according to any one of claims 1 to 9, which is a food, drink or medicine.

11. A method for promoting uric acid excretion, which comprises administering to a subject or allowing the subject to take 1 or more flavanone compounds selected from the group consisting of flavanones and flavanone glycosides having no or 1 methoxy group.

12. A method for inhibiting URAT1, which comprises administering to a subject or allowing the subject to ingest at least 1 flavanone compound selected from the group consisting of flavanones and flavanone glycosides having no or 1 methoxy group.

13. A method for reducing uric acid level in blood, characterized by administering to a subject or allowing the subject to ingest isoxanthohumol.

14. The use of a flavanone compound, wherein the flavanone compound is selected from the group consisting of flavanones having no or 1 methoxy group and flavanone glycosides, and wherein the flavanone compound is used for promoting uric acid excretion.

15. A flavanone compound is characterized by comprising 1 or more flavanone compounds selected from flavanone and flavanone glycoside having no or 1 methoxy group, and is used for inhibiting URAT 1.

16. Use of isoxanthohumol for the reduction of uric acid levels in blood.

Technical Field

The present invention relates to a composition for promoting uric acid excretion, a composition for inhibiting URAT1, and a composition for lowering uric acid level in blood. The present invention also relates to a method for promoting uric acid excretion, a method for inhibiting URAT1, and a method for reducing uric acid level in blood. In addition, the invention also relates to the application of the flavanone compound for promoting uric acid excretion or inhibiting URAT1, and the application of Isoxanthohumol (Isoxanthohumol) for reducing uric acid level in blood.

Background

Uric acid is produced in humans and the like by decomposition of purine bodies taken from food. Uric acid is dissolved in body fluids such as blood, circulates, and is excreted into urine. However, when metabolic abnormalities such as increased uric acid production and decreased uric acid excretion ability occur for some reasons, uric acid levels in the body may increase and hyperuricemia may occur. Hyperuricemia is a state in which the uric acid level in blood (serum uric acid level) is high, and is known to be a cause of gout, urinary calculi, renal disorder, and the like.

As a therapeutic agent for hyperuricemia, there are drugs such as benzbromarone which promotes uric acid excretion by inhibiting the activity of URAT1, which is a renal uric acid transporter, and drugs such as allopurinol which inhibits uric acid synthesis by inhibiting xanthine oxidase, which is a uric acid producing synthase, and these drugs are prescribed according to the type of hyperuricemia of a patient. These drugs, although having high efficacy, have many problems associated with side effects such as liver disorders. In addition, hyperuricemia is difficult to treat, and the patient returns to the hyperuricemia state again when the administration of the drug is discontinued. Therefore, in order to fundamentally treat hyperuricemia, long-term continuous administration of the drug is required.

Therefore, a component which is effective for improving hyperuricemia and can be safely ingested for a long period of time, for example, a component derived from a natural product ingested daily since ancient times, is desired.

As a method for improving hyperuricemia using a natural product-derived component, patent document 1 describes a blood uric acid level-lowering agent containing xanthohumol as an active ingredient. Patent document 2 proposes a xanthine oxidase inhibitor containing polyphenol components derived from apple and/or hop. Patent document 3 describes a uric acid excretion promoter containing ellagic acid as an active ingredient. Patent document 4 proposes a uric acid excretion promoting composition containing, as an active ingredient, a mixture of a squeezed liquid or a crushed liquid of Citrus depressa peel, a lactic acid fermentation product of Citrus depressa peel, and a lactic acid fermentation product of papaya fruit.

Patent document

Patent document 1: japanese patent laid-open publication No. 2017-61436

Patent document 2: japanese patent laid-open No. 2006 and 16927

Patent document 3: japanese patent laid-open publication No. 2006-273762

Patent document 4: japanese patent laid-open publication No. 2016-155825

Disclosure of Invention

URAT1(ura Transporter 1) is expressed in the proximal tubule of the kidney and is a Transporter for reabsorption of uric acid. With respect to uric acid in blood, almost 100% is filtered in the glomerulus, most is reabsorbed in the tubules by URAT1, and the residue is excreted into urine. Thus, by inhibiting the activity of URAT1, uric acid excretion from urine can be enhanced. Patent documents 1 to 4 do not describe that flavanones and flavanone glycosides having no or 1 methoxy group have an inhibitory activity of URAT1 or an uricosuric action.

The purpose of the present invention is to provide a composition for promoting uric acid excretion, particularly a composition for promoting uric acid excretion that promotes uric acid excretion by inhibiting URAT 1. The present invention also aims to provide a composition for inhibiting URAT 1. It is another object of the present invention to provide a composition for reducing uric acid level in blood. It is another object of the present invention to provide a method for promoting uric acid excretion, a method for inhibiting URAT1, and a method for lowering uric acid level in blood.

The present inventors have intensively studied to solve the above problems and, as a result, have found that a specific flavanone compound contained in a plant such as hop, which has been experienced in a large number of diets since ancient times, has a URAT 1-inhibiting effect, and have completed the present invention based on this finding.

That is, the present invention relates to the following uric acid excretion promoting composition, URAT1 inhibiting composition, composition for lowering uric acid level in blood, method for promoting excretion of uric acid, and the like, though not limited thereto.

[1] A composition for promoting uric acid excretion, which comprises 1 or more flavanone compounds selected from flavanones and flavanone glycosides having no or 1 methoxy group as an active ingredient.

[2] The composition for promoting uric acid excretion according to the above [1], wherein the flavanone compound is at least 1 compound selected from the group consisting of isoxanthohumol, naringenin, hesperidin and eriodictyol.

[3] The composition for promoting uric acid excretion according to [1] or [2], wherein the flavanone compound is isoxanthohumol.

[4] The uric acid excretion promoting composition according to any one of the above [1] to [3], wherein uric acid excretion is promoted by inhibiting URAT 1.

[5] A composition for inhibiting URAT1 contains 1 or more flavanone compounds selected from flavanone and flavanone glycoside having no or 1 methoxy group as active ingredient.

[6] The URAT1 inhibitor composition according to the above [5], wherein the flavanone compound is at least 1 compound selected from the group consisting of isoxanthohumol, naringenin, hesperidin and eriodictyol.

[7] A composition for lowering uric acid level in blood, which comprises isoxanthohumol as an active ingredient.

[8] The composition for lowering uric acid level in blood according to the above [7], which is used for preventing or ameliorating hyperuricemia.

[9] The composition for reducing uric acid level in blood according to the above [7], which is used for preventing or ameliorating gout.

[10] The composition according to any one of the above [1] to [9], which is a food, drink or medicine.

[11] A method for promoting uric acid excretion, which comprises administering to a subject or allowing the subject to take 1 or more flavanone compounds selected from the group consisting of flavanones and flavanone glycosides having no or 1 methoxy group.

[12] A method for inhibiting URAT1, which comprises administering to a subject or allowing the subject to ingest at least 1 flavanone compound selected from the group consisting of flavanones and flavanone glycosides having no or 1 methoxy group.

[13] A method for reducing uric acid level in blood, characterized by administering to a subject or allowing the subject to ingest isoxanthohumol.

[14] The use of a flavanone compound, wherein the flavanone compound is selected from the group consisting of flavanones having no or 1 methoxy group and flavanone glycosides, and wherein the flavanone compound is used for promoting uric acid excretion.

[15] A flavanone compound is characterized by comprising 1 or more flavanone compounds selected from flavanone and flavanone glycoside having no or 1 methoxy group, and is used for inhibiting URAT 1.

[16] Use of isoxanthohumol for the reduction of uric acid levels in blood.

The present invention provides a uric acid excretion promoting composition that promotes uric acid excretion by inhibiting URAT 1. Further, the present invention provides a composition for inhibiting URAT1 and a composition for reducing uric acid level in blood. The present invention provides a method for promoting uric acid excretion, a method for inhibiting URAT1, and a method for lowering uric acid level in blood.

Drawings

Fig. 1 is a graph showing the URAT1 inhibition ratios of isoxanthohumol and xanthohumol.

Fig. 2 is a graph showing the rate of URAT1 inhibition of naringenin.

Fig. 3 is a graph showing the rate of URAT1 inhibition by hesperidin.

Fig. 4 is a graph showing the inhibitory rate of URAT1 of eriodictyol.

Detailed Description

The composition for promoting uric acid excretion according to the present invention contains 1 or more flavanone compounds selected from flavanones and flavanone glycosides having no or 1 methoxy group as an active ingredient.

The composition for inhibiting URAT1 of the present invention contains 1 or more flavanone compounds selected from flavanones and flavanone glycosides having no or 1 methoxy group as an active ingredient.

Hereinafter, the above-mentioned flavanone compound used in the present invention is simply referred to as a flavanone compound. In the uric acid excretion promoting composition and URAT1 inhibiting composition of the present invention, 1 flavanone compound or 2 or more flavanone compounds may be used as the active ingredient.

The flavanone compound used in the present invention is a flavanone and/or a flavanone glycoside having no or 1 methoxy group (having 0 or 1 methoxy group). The flavanone and flavanone glycoside have URAT1 inhibiting effect.

Examples of the flavanone having no or 1 methoxy group include compounds represented by the following general formula (1).

[ chemical formula 1]

In the above general formula (1), R¹Represents a hydrogen atom or a methyl group. R²Represents a hydrogen atom, a dimethylallyl group or a geranyl group. R³Represents a hydrogen atom or a hydroxyl group. R⁴Represents a hydrogen atom or a methyl group. Wherein R is¹And R⁴At least 1 of (a) represents a hydrogen atom.

R²Preferably a hydrogen atom orDimethylallyl.

Examples of flavanones having no or 1 methoxy group include isoxanthohumol, naringenin, hesperetin, eriodictyol, and the like. Examples of flavanone glycosides having no or 1 methoxy group include isoxanthohumol glycoside, naringenin glycoside, hesperetin glycoside (such as hesperidin), eriodictyol glycoside, and the like.

The flavanone compound in the present invention is preferably at least 1 compound selected from isoxanthohumol, isoxanthohumol glycoside, naringenin glycoside, hesperetin glycoside (e.g., hesperidin), eriodictyol and eriodictyol glycoside, and more preferably at least 1 compound selected from isoxanthohumol, naringenin, hesperidin and eriodictyol. These flavanones and flavanone glycosides have high URAT1 inhibitory effect. Among them, isoxanthohumol is more preferable as the flavanone compound because of its high inhibitory action against URAT 1.

The source and preparation method for obtaining the flavanone compound in the present invention are not particularly limited. The flavanone compound can be natural or synthetic. Further, if there is a commercially available product, the commercially available product can be used.

For example, isoxanthohumol can be prepared from an extract of Humulus lupulus (Humulus lupulus) belonging to the family Cannabaceae by a process such as heating. By heating the hop extract, isoxanthohumol can be formed in the extract. The hop extract can be obtained by extracting hop pellets with a solvent, and can be prepared by a process related to purification, if necessary, or by a known method for preparing a hop extract. Examples of the extraction method include an extraction method using an ethanol solvent, which is used as a method for producing a hop extract used in beer brewing. Hop extracts are commercially available, and commercially available hop extracts may also be used. The heating of the hop extract to produce isoxanthohumol is preferably carried out at 80 to 140 ℃ (more preferably at 85 to 100 ℃) for 15 minutes to 5 hours (more preferably 20 minutes to 3 hours). The purification of the hop extract for the preparation of isoxanthohumol is carried out in a known manner. Examples of the purification method include a method using HPLC, an adsorption column, or the like, or a method using precipitation due to a change in solubility. In addition, isoxanthohumol can also be produced by heating xanthohumol to isomerize. The heating temperature in this case is preferably 80 to 140 ℃ (more preferably 85 to 100 ℃) for 15 minutes to 5 hours (more preferably 20 minutes to 3 hours). If necessary, isoxanthohumol obtained by the isomerization treatment can be concentrated and purified by a known method (for example, filtration, concentration under reduced pressure, freeze-drying, etc.).

Isoxanthohumol is reported to be stable also at high temperatures, e.g., 100 ℃. In the food sanitation act of japan, sterilization conditions are defined as standards for refreshing beverages such as water, and for example, a substance having a ph of 4.0 or more (excluding a substance having a ph of 4.6 or more and a water activity of more than 0.94) needs to be heated at 85 ℃ for 30 minutes. When the conversion of the components in the sterilization step is considered, it is considered that isoxanthohumol has a high beverage suitability.

According to one embodiment of the present invention, various functional foods, functional beverages, and the like can be provided which are stable to heat and contribute to maintenance and improvement of health.

Naringenin, hesperetin, eriodictyol and their glycosides are contained in citrus such as lemon, lime, grapefruit, satsuma mandarin, and sour orange. Naringenin glycoside, hesperetin glycoside or eriodictyol glycoside can be obtained, for example, by the following procedure: the leaf, fruit or pericarp of these citrus fruits is used as a raw material, extracted with a polar solvent (methanol, ethanol, water, etc.), and the obtained extract is purified by chromatography or the like. Naringenin, hesperetin or eriodictyol can be obtained as an enzyme-treated product obtained by treating an extract obtained by extracting the above raw materials with β -glucosidase, or by further purifying the enzyme-treated product. Naringenin, hesperetin or eriodictyol as its aglycone is produced from the glycoside by β -glucosidase treatment. Extraction, purification and enzymatic treatment of a material derived from citrus can be carried out by a known method.

In the present invention, the composition of the present invention may contain, as a flavanone compound source, the following components: extracts of plant-derived materials containing flavanone compounds, and the like.

As shown in the examples, flavanones and flavanone glycosides (flavanone compounds) having no or 1 methoxy group such as isoxanthohumol have an effect of inhibiting URAT1 activity (URAT1 inhibitory effect). In addition, xanthohumol is also high with respect to the URAT1 inhibitory effect of the flavanone compounds of the present invention.

When the activity of uric acid transporter URAT1 is inhibited, uric acid excretion from urine is promoted. The flavanone compound of the present invention has URAT1 inhibitory activity, and therefore, is suitably used for inhibiting URAT1 or promoting uric acid excretion. The flavanone compound of the present invention is used as an active ingredient of a composition for promoting uric acid excretion and a composition for inhibiting URAT1, and can be used for the production of these compositions.

The composition for promoting uric acid excretion of the present invention can promote uric acid excretion by inhibiting URAT 1. The uric acid excretion promoting composition of the present invention is suitably used for promoting uric acid excretion by inhibiting URAT 1.

The present invention also encompasses a composition for lowering uric acid level in blood, which contains isoxanthohumol as an active ingredient.

Isoxanthohumol has excellent inhibitory effect on URAT 1. As described above, when the activity of uric acid transporter URAT1 is inhibited, excretion of uric acid from urine is promoted. This can be expected to reduce the uric acid level in blood. The composition for lowering blood uric acid level of the present invention can be used for lowering blood uric acid level by promoting uric acid excretion.

Hereinafter, the uric acid excretion promoting composition, URAT1 inhibiting composition, and blood uric acid level lowering composition of the present invention will be collectively referred to as uric acid excretion promoting composition, and the like.

The composition for promoting uric acid excretion and the like of the present invention are useful for the prevention or amelioration of a disease or a condition in which a prophylactic or ameliorating effect is exhibited by promoting uric acid excretion or lowering uric acid level in blood. Examples of such conditions and diseases include hyperuricemia, gout, and urinary calculi. In one embodiment, the composition for lowering blood uric acid level of the present invention is used for preventing or ameliorating hyperuricemia and gout. In the present specification, the prevention of a condition or disease means prevention of occurrence of a condition or disease, delay of occurrence of a condition or disease, reduction of the rate of occurrence of a condition or disease, reduction of the risk of occurrence of a condition or disease, and the like. The improvement of a condition or disease refers to recovery of a subject from a condition or disease, alleviation of symptoms of a condition or disease, delay or prevention of progression of a condition or disease, and the like.

The flavanone compound used in the present invention is contained in a natural product or a food or drink, and is a compound having a dietary experience. Therefore, from the viewpoint of safety, for example, it is considered that the flavanone compound has few problems even when taken daily. Thus, the present invention can provide a composition for promoting uric acid excretion, which contains a highly safe component as an active ingredient.

The uric acid excretion promoting composition of the present invention and the like can be suitably used for any of therapeutic use (medical use) and non-therapeutic use (non-medical use).

The uric acid excretion promoting composition of the present invention can be provided in the form of a food, drink, medicine, quasi-drug, feed, or the like. The uric acid excretion promoting composition of the present invention may be a food, drink, medicine, quasi-drug, feed, etc. for promoting excretion of uric acid, inhibiting URAT1, or lowering uric acid level in blood, or may be a raw material or a preparation blended with these.

The uric acid excretion promoting composition and the like may be provided in the form of a preparation as an example, but is not limited to this form. The formulation may be provided as a composition directly, or as a composition containing the formulation. The uric acid excretion promoter composition, URAT1 inhibitor composition, and blood uric acid level lowering composition of the present invention can be referred to as a uric acid excretion promoter, a URAT1 inhibitor, and a blood uric acid level lowering agent, respectively. The uric acid excretion promoting composition of the present invention may be in any form of solid, liquid, paste, and the like.

In one embodiment, the uric acid excretion promoting composition or the like of the present invention is preferably an oral composition. The composition for oral administration includes foods and drinks, orally administered medicines, quasi drugs, and feeds, preferably foods and drinks or orally administered medicines, and more preferably foods and drinks.

The uric acid excretion promoting composition of the present invention and the like may contain any additives and any components other than the flavanone compound as long as the effects of the present invention are not impaired. These additives and components can be selected according to the form of the composition, and substances that can be used in general foods and drinks, medicines, quasi drugs, feeds, and the like can be used.

The uric acid excretion promoting composition of the present invention can be produced by a general method, and the production method is not particularly limited, and can be used for producing foods, drinks, medicines, quasi drugs, feeds, and the like. In the production of the composition for promoting uric acid excretion according to the present invention and the like, as the flavanone compound, a purified compound can be used, and as the flavanone compound source, an extract of a plant-derived material containing the flavanone compound described above can be used, as long as the effects of the present invention can be exerted. In addition, for example, a uric acid excretion promoting composition containing isoxanthohumol can be produced by a step of mixing a hop extract and heating the hop extract.

For example, when the composition for promoting uric acid excretion according to the present invention is prepared into foods and beverages, various foods and beverages can be prepared by blending components that can be used in foods and beverages (e.g., food materials, food additives that can be used as needed, etc.) into the flavanone compound. The food or drink is not particularly limited, and examples thereof include general foods or drinks, health foods, health drinks, functional foods, specific health foods, and foods or drinks for patients. The health food, functional marker food, specific health food, etc. can be made into various preparations such as fine granule, tablet, granule, powder, capsule, chewable agent, syrup, liquid, etc.

As an example of a preferable embodiment of the composition for promoting uric acid excretion of the present invention, a beverage can be mentioned. For example, isoxanthohumol is stable to heat, and therefore, a composition for promoting uric acid excretion containing isoxanthohumol is suitable for beverages.

The beverage may be nonalcoholic beverage or alcoholic beverage. Examples of the nonalcoholic beverage include tea beverages, coffee beverages, nonalcoholic beer-flavored beverages, carbonated beverages, functional beverages, fruit and vegetable beverages, milk beverages, soy milk beverages, and flavored water. In one embodiment, the uric acid excretion promoting composition and the like of the present invention are preferably such a nonalcoholic beverage or alcoholic beverage.

When the uric acid excretion promoting composition of the present invention is a tea beverage, a black tea beverage or a sugar-free tea beverage is preferable. Examples of the sugar-free tea beverage include green tea beverage, oolong tea beverage, barley tea beverage, brown rice tea beverage, coix seed tea beverage, and sugar-free black tea beverage.

When the uric acid excretion promoting composition of the present invention is a coffee beverage, it is preferably coffee in a container or liquid coffee.

The term "nonalcoholic beer-flavored beverage" as used herein refers to a carbonated beverage having a beer-like flavor, and is usually of a non-fermented nonalcoholic type and contains substantially no alcohol. Here, the non-alcoholic beer-flavored beverage does not exclude a beverage containing an undetectable amount of alcohol.

When the composition for promoting uric acid excretion according to the present invention is a carbonated beverage, it is preferably a cola-flavored beverage, a clear carbonated beverage, a ginger-flavored carbonated beverage, a fruit-juice-based carbonated beverage, a milk-containing carbonated beverage or a sugar-free carbonated beverage.

When the composition for promoting uric acid excretion of the present invention is a functional beverage, a sports drink, an energy drink, a health supplement drink, or a jelly drink in a pouch is preferable.

When the composition for promoting uric acid excretion according to the present invention is a fruit or vegetable beverage, a 100% fruit beverage, a fruit-containing beverage, a low-content fruit juice refreshing beverage, a fruit-containing beverage or a fruit pulp beverage is preferable.

When the uric acid excretion promoting composition of the present invention is a milk-based drink, milk, drinking yoghurt, lactic acid bacteria drink, or milk-containing refreshing drink is preferable.

When the uric acid excretion promoting composition of the present invention is a soybean milk beverage, soybean milk or a soybean beverage is preferable.

Examples of the alcoholic beverages include beer, beer-like beverages, and alcoholic beverages other than beer and beer-like beverages.

When the composition for promoting uric acid excretion of the present invention is a beer-based beverage, low-malt beer or third beer is preferable.

When the composition for promoting uric acid excretion of the present invention is an alcoholic beverage other than beer and beer-like beverages, distilled liquor, carbonated distilled liquor, liqueur, cocktail, spirit, and whisky are preferable.

The form of the beverage is not particularly limited, and the beverage can be made into a packaged beverage. The container for the packaged beverage is not particularly limited, and any type and material of the container can be used, for example, a metal container such as an aluminum can or a steel can; resin containers such as PET bottles; paper containers such as cartons; glass containers such as glass bottles; any of commonly used containers such as wooden barrels. By filling and sealing the beverage into such a container, a container-packaged beverage can be obtained.

When the uric acid excretion promoting composition of the present invention is prepared into a medicine or quasi-drug, for example, a pharmaceutically acceptable carrier, an additive added as needed, or the like may be blended with the flavanone compound to prepare a medicine or quasi-drug in various dosage forms. Such carriers, additives and the like may be those which are pharmacologically acceptable and usable in medicines or quasi drugs, and examples thereof include 1 or 2 or more kinds of excipients, binders, disintegrants, lubricants, antioxidants, colorants and the like. As the administration (intake) form of the medicine or quasi-medicine, the oral administration form is preferable from the viewpoint of more sufficiently obtaining the effect of the present invention. When the composition for promoting uric acid excretion is formulated into a medicine, it is preferably formulated into a medicine for oral administration. Examples of dosage forms of preparations for oral administration include liquid, tablet, powder, fine granule, sugar-coated tablet, capsule, suspension, emulsion, and chewable agent. The medicament may be a medicament for a non-human animal.

When the composition for promoting uric acid excretion of the present invention is prepared into a feed, for example, a flavanone compound may be mixed with a component usable for a feed to prepare a feed. The feed may also contain feed additives. Examples of the feed include livestock feeds; a feed for small animals such as rats and mice; pet foods for dogs, cats and the like.

The content of the flavanone compound in the uric acid excretion promoting composition of the present invention may be appropriately set according to the form of the composition. In one embodiment, the total content of the flavanone compounds in the uric acid excretion promoting composition of the present invention is preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and further preferably 90% by weight or less of the total content of the flavanone compounds in the uric acid excretion promoting composition and the like. In one embodiment, the total content of flavanone compounds in the composition is preferably 0.0001 to 90% by weight, more preferably 0.001 to 90% by weight. The total content of the flavanone compounds is the total content of 2 or more flavanone compounds. In one embodiment, when the composition for promoting uric acid excretion according to the present invention is prepared into foods, drinks, medicines, quasi drugs, feeds, or the like, the total content of the flavanone compound in the composition is preferably set to the above range.

The content of the flavanone compound can be measured by a known method, and for example, can be measured by High Performance Liquid Chromatography (HPLC), LC-MS/MS, or the like.

The uric acid excretion promoting composition of the present invention and the like can be ingested or administered in an appropriate manner depending on the form. The uric acid excretion promoting composition and the like of the present invention are preferably orally ingested (orally administered) from the viewpoint of sufficiently obtaining the effects of the present invention.

The intake amount (also referred to as an administration amount) of the uric acid excretion promoting composition and the like of the present invention is not particularly limited, and may be an amount (effective amount) that can obtain a uric acid excretion promoting effect, a URAT1 inhibitory effect, or a blood uric acid level lowering effect, and may be appropriately set according to the administration form, the administration method, the body weight of the subject, and the like. In one embodiment, when orally taken or administered to a human (adult), the uric acid excretion promoting composition of the present invention is preferably administered in an amount of 60kg body weight per 1 day, more preferably 1 to 200mg, and most preferably 5 to 60mg, based on the total amount of flavanone compounds ingested. The total intake of flavanone compounds means the total intake of 2 or more flavanone compounds when they are ingested. The amount is preferably 1 or more times a day, and is taken 1 to several times (e.g., 2 to 3 times) a day, for example. In one embodiment, the uric acid excretion promoting composition of the present invention and the like may be an oral composition for making an adult ingest or administer the flavanone compound in an amount of 60kg body weight per 1 day.

The subject to be ingested (may also be referred to as administration subject) of the uric acid excretion promoting composition of the present invention is not particularly limited. The subject is preferably a mammal (human or non-human mammal), more preferably a human. In addition, as a subject to be ingested with the uric acid excretion promoting composition of the present invention and the like, for example, a subject in need or desire of promoting uric acid excretion is preferable. In addition, as the subject to be ingested with the composition for lowering blood uric acid level of the present invention, a subject that needs or desires to lower blood uric acid level is preferable. Such subjects include not only subjects with high uric acid levels in blood such as hyperuricemia but also subjects with low uric acid levels in blood, who are interested in the increase of uric acid levels in blood, subjects who are expected to prevent hyperuricemia, subjects who are expected to prevent gout, subjects with high intake of foods and beverages that increase uric acid levels in blood, and the like, and it is desired to prevent the increase of uric acid levels in blood.

In one embodiment, the uric acid excretion promoting composition and the like of the present invention can be used for a subject in a healthy state for the purpose of promoting uric acid excretion and preventing a disease in a state expected to be improved.

The uric acid excretion promoting composition of the present invention may be in the form of 1 or 2 or more types, for example, in the form of a package, container, instructions, or the like, indicating the intended use, the type of active ingredient, the above-mentioned effects, and the method of use (e.g., method of ingestion or method of administration). The uric acid excretion promoting composition of the present invention and the like may be labeled to have URAT1 inhibitory activity, uric acid excretion promoting activity, or an activity based on these activities. Such a marker may be accompanied by a marker indicating that the uric acid level in blood is lowered.

The present invention also encompasses the following methods for promoting uric acid excretion, method for inhibiting URAT1, and method for reducing uric acid level in blood.

A method for promoting uric acid excretion, which comprises administering to a subject or allowing the subject to take 1 or more flavanone compounds selected from the group consisting of flavanones and flavanone glycosides having no or 1 methoxy group.

A method for inhibiting URAT1, which comprises administering to a subject or allowing the subject to ingest at least 1 flavanone compound selected from the group consisting of flavanones and flavanone glycosides having no or 1 methoxy group.

A method for reducing uric acid level in blood, characterized by administering to a subject or allowing the subject to ingest isoxanthohumol.

The methods described above may be therapeutic or non-therapeutic. By "non-therapeutic" is meant a concept that does not include medical acts, i.e., surgery, treatment, or diagnosis in humans. In the above method, the subject is preferably a mammal (human or non-human mammal), more preferably a human.

The present invention also includes the following applications and the like.

The use of a flavanone compound, wherein the flavanone compound is selected from the group consisting of flavanones having no or 1 methoxy group and flavanone glycosides, and wherein the flavanone compound is used for promoting uric acid excretion.

A flavanone compound is characterized by comprising 1 or more flavanone compounds selected from flavanone and flavanone glycoside having no or 1 methoxy group, and is used for inhibiting URAT 1.

Use of isoxanthohumol for the reduction of uric acid levels in blood.

The application may be therapeutic or non-therapeutic. The above-mentioned use is preferably a mammalian (human or non-human mammal), more preferably a human use.

In the above-mentioned method and application, the flavanone compound may be administered to or ingested by the subject in an amount (i.e., an effective amount) to obtain a uric acid excretion promoting effect, a URAT1 inhibiting effect, or a uric acid level lowering effect in blood. The flavanone compound and preferred embodiments thereof are the same as those in the composition for promoting uric acid excretion and the like. The preferable intake amount and administration object of the flavanone compound are the same as in the case of the uric acid excretion promoting composition of the present invention described above. The flavanone compound can be administered or ingested directly, or as a composition containing the flavanone compound. For example, the uric acid excretion promoting composition of the present invention can be administered or ingested.

The present invention also encompasses, in one embodiment, the use of a flavanone compound selected from the group consisting of flavanones having no or 1 methoxy group and flavanone glycosides for producing a composition for promoting uric acid excretion or a composition for inhibiting URAT 1. The present invention also encompasses the use of isoxanthohumol, which is characterized by being used for producing a composition for lowering uric acid level in blood. The flavanone compound and preferred embodiments thereof are the same as those of the uric acid excretion promoting composition and the like.

Examples

The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited thereto.

< example 1 >

The test substances used were isoxanthohumol (manufactured by Fujioshi Kagaku K.K.), naringenin (Funakoshi Co., Ltd.), hesperidin (Tokyo Kasei Co., Ltd.), and eriodictyol (Funakoshi Co., Ltd.).

MDCK2 cells derived from porcine kidney (Shin et al, neuroprology 16(2011)156-163) which stably express human URAT1 were washed with Hank's Balanced Salt Solution (HBSS) (Nacalai Co., Ltd.), and then cultured in HBSS containing a test substance and 14C-labeled uric acid for 10 minutes. Each test substance was dissolved in dimethyl sulfoxide (DMSO) and added to HBSS so that the concentration of the test substance was 1, 5, 10, 15, 20, 40, 60, 80, 100, or 200 μ g/mL. At this time, the DMSO concentration in HBSS was 1.5% or less. Uric acid was added to HBSS to 20 μ M. After the cells were washed again with HBSS, the cells were dissolved with a 0.1N aqueous solution of sodium hydroxide, and the 14C radiation amount in the solution was measured by a liquid scintillation counter to measure the amount of uric acid absorbed into the cells. As a positive control, a group to which 30. mu.M benzbromarone was added was set. In the control analyte-non-added group, DMSO was added only to HBSS (DMSO concentration: 1%). The control and the test substance at each concentration were each tested with n-3. The inhibition rate (%) of URAT1 was calculated by assuming the uric acid absorption amount of the test substance-free group as the uric acid absorption amount of the test substance-added group at 100%. The uric acid absorption amount was calculated by taking the average value of n-3. The formula for calculating the URAT1 inhibition (%) is shown below. The control group is a test substance-free group.

Inhibition rate (%) < 100 × { (uric acid absorption amount of control group-uric acid absorption amount of test substance-added group)/uric acid absorption amount of control group }

< comparative example 1 >

The inhibition (%) of URAT1 was determined in the same manner as in example 1, except that xanthohumol (Alexis biochem, inc.) was used as the test substance.

The results of evaluating the effect of the addition culture of each test substance in example 1 and comparative example 1 on URAT1 activity are shown in fig. 1 to 4. Fig. 1 is a graph showing the URAT1 inhibition ratio of isoxanthohumol. Fig. 1 also shows, for comparison, the URAT1 inhibition ratio of xanthohumol of comparative example 1. In fig. 1, IXN (black circles) is isoxanthohumol and XN (white circles) is xanthohumol.

Fig. 2 is a graph showing the inhibitory rate of URAT1 of naringenin, fig. 3 is a graph showing the inhibitory rate of URAT1 of hesperidin, and fig. 4 is a graph showing the inhibitory rate of URAT1 of eriodictyol.

The remarkable improvement of the inhibition rate is confirmed by the addition culture of the flavanone compound of isoxanthohumol, naringenin, hesperidin or eriodictyol. On the other hand, no significant increase in the inhibition rate was observed in the addition culture of xanthohumol (comparative example 1) which is a flavonoid but belongs to the chalcone group among them. The inhibition rate of benzbromarone (30 mu M) is 99-100%. The concentration of the test substance used in example 1 (IC) at 50% inhibition of URAT1 was calculated as an index of the effectiveness of the biological or biochemical inhibitory action of the compound₅₀)。IC₅₀Is calculated and knotThe results are shown in Table 1.

[ Table 1]

Substance to be measured	IC50(μg/mL)
		Isoxanthohumol	8.90
Naringenin	11.40
		Hesperidin	16.97
Eriodictyol	12.53

Isoxanthohumol exhibits the lowest IC among the test substances₅₀And thus is considered to have the highest URAT1 inhibitory activity.

Industrial applicability

The present invention is useful in the fields of foods and beverages, medicines, and the like.