JP2010059104A - Xanthine oxidase inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a xanthine oxidase inhibitor excellent in a xanthine oxidase inhibition action. <P>SOLUTION: The xanthine oxidase inhibitor contains as an active ingredient at least one polyphenol compound selected from among eriodictyol, hesperetin, naringenin, diosmetin, eriodictyol glycoside, hesperetin glycoside, naringenin glycoside, and diosmetin glycoside. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a xanthine oxidase inhibitor that inhibits the activity of xanthine oxidase, and specifically relates to a xanthine oxidase inhibitor containing a specific polyphenol as an active ingredient.

  Xanthine oxidase is an enzyme localized in the liver, small intestine and the like in mammals, and catalyzes an oxidation reaction from hypoxanthine to xanthine and an oxidation reaction from xanthine to uric acid in the metabolic process of purine compounds. Uric acid produced by this xanthine oxidase is excreted in urine as a final degradation product of purine compounds in humans.

  If metabolic abnormalities such as decreased uric acid excretion or increased production occur in the metabolic process of purine compounds, the uric acid level in the body (in the blood) rises to hyperuricemia, gouty arthritis (gout nodules), urine It is known that the risk of developing urolithiasis (uric acid calculus), gout kidney (renal disorder) and the like is increased. In recent years, it has been suggested that hyperuricemia is an independent risk factor for cardio-cerebral vascular disorders (eg, arteriosclerosis), and the importance of metabolic syndrome as a biomarker has been pointed out.

Conventionally, for treatment of hyperuricemia, for example, allopurinol, which is a uric acid production inhibitor, has been used. Allopurinol is a powerful inhibitor of xanthine oxidase, and has the effect of inhibiting the production of uric acid by inhibiting xanthine oxidase to lower the uric acid level in the blood. However, allopurinol has been reported to cause side effects such as liver damage. Therefore, attention has been focused on xanthine oxidase inhibitors derived from natural products with few side effects, particularly food components. As such a natural product-derived xanthine oxidase inhibitor, for example, those disclosed in Patent Documents 1 to 3 are known.
JP 2003-174857 A JP 2003-252776 A JP 2006-036787 A

  By the way, it is known that citrus fruits such as lemon contain a large amount of polyphenols such as eriocitrin, hesperidin and naringin. And it has been confirmed that these polyphenols have an effect of improving health functions such as an antioxidant action, an antiallergic action, an antiviral action and an anti-inflammatory action.

  This invention has been made based on the finding that specific polyphenols contained in lemon exert an xanthine oxidase inhibitory action as a result of intensive studies by the present researchers. The purpose is to provide a xanthine oxidase inhibitor excellent in xanthine oxidase inhibitory action.

  In order to achieve the above object, the xanthine oxidase inhibitor according to claim 1 is an eriodictiool, hesperetin, naringenin, diosmethine, eriodictinol glycoside, hesperetin glycoside, naringenin glycoside and diosmethine. It contains at least one polyphenol selected from glycosides as an active ingredient.

  The xanthine oxidase inhibitor according to claim 2 is characterized in that, in the invention according to claim 1, the polyphenol is eriodictiool, hesperetin, naringenin or diosmethine.

  The xanthine oxidase inhibitor according to claim 3 is the invention according to claim 1 or 2, wherein the polyphenols are blended as a lemon extract or an enzyme-treated product obtained by treating the lemon extract with β-glucosidase. It is characterized by.

The xanthine oxidase inhibitor according to claim 4 is used as a uric acid production inhibitor in the invention according to any one of claims 1 to 3.
The xanthine oxidase inhibitor according to claim 5 is used in the invention according to any one of claims 1 to 4 as a preventive or therapeutic agent for a disease caused by abnormal metabolism of uric acid. And

  ADVANTAGE OF THE INVENTION According to this invention, the xanthine oxidase inhibitor excellent in the xanthine oxidase inhibitory effect can be provided.

Hereinafter, an embodiment of a xanthine oxidase inhibitor embodying the present invention will be described in detail.
The xanthine oxidase inhibitor of this embodiment is at least one polyphenol selected from Eriodictiool, Hesperetin, Naringenin, Diosmethine, Eriodictiool glycoside, Hesperetin glycoside, Naringenin glycoside and Diosmethine glycoside. Is contained as an active ingredient. These active ingredients may be blended alone in the xanthine oxidase inhibitor, or may be blended in combination of two or more. Among these active ingredients, at least one polyphenol selected from eriodictiool, hesperetin, naringenin, and diosmethine is preferable because of its excellent xanthine oxidase inhibitory action.

Elio decrease-Thi-ol having a xanthine oxidase inhibitory activity (eriodictyol; 3 ', 4' , 5,7-tetrahydroxyflavanone; C 15 H 12 O 6), hesperetin (hesperetin; 3 ', 5,7- trihydroxy-4'-methoxyflavanone _{; C 16 H 14 O 6)} , naringenin (naringenin; 4 ', 5,7- trihydroxyflavanone; C 15 H 12 O 5) and diosmetin (diosmetin; 3', 5,7- trihydroxy-4'-methoxyflavone; C 16 H ₁₂ O ₆ ) is a kind of polyphenol, and as a natural product, it exists in the form of a glycoside in which sugar is bound with itself as an aglycon. These glycosides are eriodictiool, hesperetin, naringenin, or diosmethine as an aglycon, and a monosaccharide or disaccharide is linked by a glycosidic bond. It is a saccharide. And each said glycoside has a xanthine oxidase inhibitory effect similarly to Eriodictiool, Hesperetin, Naringenin, and Diosmethine. In addition, the structure of the monosaccharide and disaccharide contained in each said glycoside is not specifically limited.

  Examples of eriodictiool glycosides include eriocitrin, which is a glycoside of eriodictiool and rutinose (L-rhamnosyl-D-glucose), and glucoside of eriodictiool and glucose. Examples thereof include eriodictyol-7-glucoside which is a body. Examples of the hesperetin glycoside include hesperidin (vitamin P), which is a glycoside of hesperetin and rutinose. Examples of the naringenin glycoside include naringin, which is a glycoside of naringenin and neohesperidose, and narrutin, which is a glycoside of naringenin and rutinose. Examples of the diosmethine glycoside include diosmin, which is a glycoside of diosmethine and rutinose.

  These Eriodictiool, Hesperetin, Naringenin, Diosmethine, Eriodictiool Glycoside, Hesperetin Glycoside, Naringenin Glycoside, and Diosmethine Glycoside contain biosynthetic products, chemically synthesized products, and their components Either a natural product or a purified product obtained by extraction and purification using the natural product as a raw material may be used.

  Hereinafter, an example of a method for obtaining Eriodictiool, Hesperetin, Naringenin, Diosmethine, Eriodictiool glycoside, Hesperetin glycoside, Naringenin glycoside and Diosmethine glycoside from natural products will be described.

  Examples of natural products containing Eriodictiool glycoside, Hesperetin glycoside, Naringenin glycoside, and Diosmethine glycoside include citrus fruits such as lemon, lime, grapefruit and sudachi. And what contains these citrus leaves, a fruit, or a part of structural component of the fruit is used preferably as said raw material. In particular, it is preferable to use a peel (albedo, flavedo), an agate membrane, a sardine, or the like that constitutes a lemon fruit. Since eriocitrin is also contained in mint, mint leaves, fruits and the like can be used as raw materials in addition to citrus fruits.

  Each of these glycosides can be obtained by subjecting these raw materials to extraction treatment with a polar solvent (methanol, ethanol, water, etc.) and purification treatment by chromatography (for example, JP 2000-217560 A). No. and JP 2007-230878).

  Eriodictiool, hesperetin, naringenin and diosmethine can be obtained by subjecting an extract obtained by extracting the above raw materials to an enzyme-treated product treated with β-glucosidase, or by further purifying the enzyme-treated product. It can be obtained as a purified product. The β-glucosidase treatment is a treatment in which β-glucosidase is allowed to act on the extract, and an enzyme reaction is performed to cleave the glycoside bond of each glycoside contained in the extract. By this β-glucosidase treatment, the aglycones, eriodictiool, hesperetin, naringenin, and diosmethine, are generated from each glycoside. The β-glucosidase treatment can be performed using a known method such as a fermentation treatment using a microorganism or a glycosidase treatment using an enzyme (see, for example, JP-A-2007-230878).

  Fermentation treatment with microorganisms is a treatment performed by inoculating the extract with microorganisms belonging to the genus Aspergillus and culturing the microorganisms under predetermined fermentation conditions for a predetermined period. In this microbial fermentation treatment, aglycone is released from each glycoside by β-glycosidase produced by microorganisms (particularly vegetative mycelium). Examples of the microorganism include Aspergillus cytoii, Aspergillus niger, Aspergillus awamori, Aspergillus usami and other black koji molds, or Aspergillus oryzae, Aspergillus sojae, Aspergillus tamari and others Of jaundice. Among these microorganisms, black koji molds are preferably used because of the high efficiency of the aglyconization reaction, and Aspergillus cytoii, Aspergillus niger, Aspergillus awamori or Aspergillus usami are particularly preferably used.

  In addition, glycosidase treatment using an enzyme is a treatment in which β-glycosidase is allowed to act on the raw material to perform an enzymatic reaction that cleaves glycoside bonds of glycosides contained in the raw material. As this glycosidase treatment, in order to increase the efficiency of the treatment, it is preferable to add β-glycosidase to the extract to cause an enzyme reaction. Alternatively, the enzyme reaction may be performed by contacting a carrier on which β-glycosidase having enzyme activity is immobilized with the extract. As the β-glycosidase, the β-glycosidase produced by the Aspergillus microorganism or the β-glycosidase produced by Penicillium multicolor is preferably used. β-glycosidase may be either one extracted and purified from the above microorganism or a commercially available product.

  The xanthine oxidase inhibitor of the present embodiment is blended in compositions such as pharmaceuticals, quasi-drugs, health foods, foods for specified health use, health drinks, dietary supplements and the like that have xanthine oxidase inhibitory effects. Ingested by

  When the xanthine oxidase inhibitor of the present embodiment is used as a pharmaceutical product or used by being incorporated in a pharmaceutical product, for example, a method of administration by oral administration (oral administration), enteral administration, etc. (Enteral administration) and the like. Although it does not specifically limit as a dosage form, For example, a gum formulation, a powder, a powder, a granule, a tablet, a capsule, a pill, a suppository, a liquid agent, an injection, etc. are mentioned. In addition, excipients, bases, emulsifiers, solvents, stabilizers and the like as additives may be blended as long as the object of the present invention is not impaired.

  When using the xanthine oxidase inhibitor of this embodiment as a food or drink, by adding it to various food materials or beverage materials, for example, powder, tablets, granules, liquids (drinks, etc.) It can be processed into capsules, syrups, candies and the like and used as health food preparations, dietary supplements and the like. Specific examples of the above-mentioned food and drink include sports drinks, tea beverages extracted from tea leaves and herbs, dairy products such as milk and yogurt, foods containing gelling agents such as pectin and carrageenan, glucose, sucrose, and fructose. And beverages and foods containing sugars such as lactose and dextrin, flavorings, sweeteners such as stevia, aspartame, sugar alcohols, and fats and oils such as vegetable oils and animal fats. In addition, a substrate, an excipient, an additive, a secondary material, a bulking agent, and the like may be added as appropriate within a range that does not impair the object of the present invention.

  The dose (intake) of the xanthine oxidase inhibitor of the present embodiment is preferably 0.1 to 2500 mg / day for an adult when Eriodictiool, Hesperetin, Naringenin or Diosmethine is formulated as an active ingredient. kg body weight, more preferably 1 to 700 mg / kg body weight. If the daily dose (intake) is less than 0.1 mg / kg, the xanthine oxidase inhibitory action may not be sufficiently exhibited. Further, when the daily dose (intake) exceeds 2500 mg / kg, it is difficult to obtain further xanthine oxidase inhibitory action, which is uneconomical.

  In addition, the dose (intake) of the xanthine oxidase inhibitor when an Eriodictiool glycoside, hesperetin glycoside, naringenin glycoside or diosmethine glycoside is formulated as an active ingredient is as follows: Preferably it is 0.4-5000 mg / kg body weight, More preferably, it is 4-700 mg / kg body weight. If the daily dose (intake) is less than 0.4 mg / kg, the xanthine oxidase inhibitory action may not be sufficiently exhibited. Further, when the daily dose (intake) exceeds 5000 mg / kg, it is difficult to obtain a further xanthine oxidase inhibitory action, which is uneconomical.

Next, operational effects in the present embodiment will be described below.
(1) The xanthine oxidase inhibitor of this embodiment is at least selected from Eriodictiool, Hesperetin, Naringenin, Diosmethine, Eriodictiool glycoside, Hesperetin glycoside, Naringenin glycoside and Diosmethine glycoside A kind of polyphenols is contained as an active ingredient. Therefore, xanthine oxidase can be effectively inhibited.

  (2) In the xanthine oxidase inhibitor of this embodiment, preferably, eriodictiool, hesperetin, naringenin or diosmethine is applied as an active ingredient. In such a case, xanthine oxidase can be more effectively inhibited.

  (3) In the xanthine oxidase inhibitor of this embodiment, preferably, as the polyphenols that are active ingredients, an extract from a natural product such as lemon or an enzyme-treated product obtained by treating the extract with β-glucosidase is applied. Is done. In this case, since it is derived from a natural product, there are few side effects and it can apply more safely with respect to a biological body. Thereby, it can apply easily to a pharmaceutical and food-drinks.

  (4) The xanthine oxidase inhibitor of this embodiment effectively inhibits xanthine oxidase. Therefore, the production of uric acid in the living body can be suppressed. Therefore, it can be suitably used as a uric acid production inhibitor that controls the uric acid level in blood.

  (5) The xanthine oxidase inhibitor of the present embodiment can suppress uric acid production in vivo. Therefore, it can be suitably used as a prophylactic or therapeutic agent for diseases caused by abnormal metabolism of uric acid (for example, hyperuricemia).

In addition, this embodiment can also be changed and embodied as follows.
-In the xanthine oxidase inhibitor of this embodiment, when an eriodictiolol glycoside, hesperetin glycoside, naringenin glycoside or diosmethine glycoside is blended as an active ingredient, these active ingredients or these A natural material containing active ingredients and β-glucosidase may be ingested simultaneously.

  -You may use the xanthine oxidase inhibitor of this embodiment for animals other than humans, such as a horse and a cow, for example.

Next, the embodiment will be described in more detail with reference to each test example.
<Test on xanthine oxidase inhibitory action>
The xanthine oxidase inhibitory action of the xanthine oxidase inhibitor of this embodiment was evaluated. In this test, as the active ingredient of the xanthine oxidase inhibitor, Eriodictiool (manufactured by Extrasynthese SA), Hesperetin (manufactured by SIGMA), Naringenin (manufactured by SIGMA), Diosmethine (manufactured by SIGMA), Elio Citrine (manufactured by Extrasynthesis. SA), hesperidin (manufactured by SIGMA), naringin (manufactured by SIGMA), nariltin (manufactured by Extrasynthesis. SA), diosmine (manufactured by SIGMA), lemon extract and the same Eleven kinds of enzyme-treated products obtained by treating the lemon extract with β-glucosidase were used.

[Test Example 1-1: Test using various polyphenols]
First, a test using various polyphenols as an active ingredient of a xanthine oxidase inhibitor was performed. A test solution was prepared by dissolving polyiodies such as eriodictiool, hesperetin, naringenin and diosmethine in a 50% ethanol solution so as to be 100 μg / ml. Moreover, the test solution was obtained by dissolving polyphenols such as eriocitrin, hesperidin, naringin, narrudine and diosmine in a 50% ethanol solution so as to be 300 μg / ml. Further, a 50% ethanol solution without polyphenols was prepared and used as a control.

  Subsequently, 100 μl each of the above test solution and control was added to a solution prepared by mixing 1/15 M phosphate buffer (375 μl) adjusted to pH 7.5 and 1.8 mU xanthine oxidase [derived from bovine milk] (100 μl). A reaction solution was prepared. Each reaction solution was preincubated for 15 minutes at 25 ° C., and then a 0.15 mM xanthine solution (300 μl) was added as a substrate and incubated at 25 ° C. for 30 minutes. The concentration of polyphenols during the enzyme reaction is 11.4 μg / ml when the polyphenols are eriodictiool, hesperetin, naringenin and diosmethine. When the polyphenol is eriocitrin, hesperidin, naringin, narrudine and diosmine, the amount is 34.2 μg / ml.

  Thereafter, 1N HCl (125 μl) was added to the reaction solution to stop the enzyme reaction, and the amount of uric acid produced in the reaction solution was measured. The amount of uric acid produced was measured by measuring the absorbance at 290 nm with an absorptiometer. And based on the obtained uric acid production amount, the xanthine oxidase inhibition rate was computed with the following formula. The results are shown in Table 1 below.

Xanthine oxidase inhibition rate (%) = (1−A / B) × 100
A: Uric acid production when test sample is added B: Uric acid production when control is added

表１に示すように、エリオディクティオール、ヘスペレチン、ナリンゲニン、ジオスメチン、エリオシトリン、ヘスペリジン、ナリンジン、ナリルチン及びジオスミンのいずれもキサンチンオキシダーゼ阻害作用を示した。また、エリオディクティオールを添加した場合には、その配糖体であるエリオシトリンを添加した場合と比較して、質量比にして約１／３（モル比にして約２／３）程度の添加量であるにも拘らず、エリオシトリンよりも高いキサンチンオキシダーゼ阻害作用を示した。同様に、ヘスペレチン及びナリンゲニンも、それぞれの配糖体であるヘスペリジン、ナリンジン、ナリルジンと比較して高いキサンチンオキシダーゼ阻害作用を示した。これらの結果から、ポリフェノール類は、配糖体の状態よりも、糖部のない状態で配合することがより効果的であることが確認された。

As shown in Table 1, all of Eriodictiool, Hesperetin, Naringenin, Diosmethine, Eliocitrin, Hesperidin, Naringin, Narillin, and Diosmin showed xanthine oxidase inhibitory action. In addition, when eriodictyol is added, the mass ratio is about 1/3 (molar ratio is about 2/3) compared to the case where the glycoside eriocitrin is added. Despite the addition amount, it showed a higher xanthine oxidase inhibitory effect than eriocitrin. Similarly, hesperetin and naringenin also showed a higher xanthine oxidase inhibitory action than the respective glycosides hesperidin, naringin, and narrudine. From these results, it was confirmed that polyphenols are more effective when blended without a sugar moiety than with a glycoside.

[Test Example 1-2: Test using lemon extract and enzyme-treated product thereof]
Next, a test using a lemon extract and an enzyme-treated product as an active ingredient of a xanthine oxidase inhibitor was performed. The lemon peel was pulverized and subjected to an extraction process using distilled water as an extraction solvent, followed by a solid-liquid separation process to obtain a lemon extract. And while using this lemon extract for synthetic adsorption resin, the synthetic resin was washed with distilled water. Thereafter, the adsorbed component adsorbed on the synthetic resin is eluted with 30% ethanol, and the fraction containing the largest amount of eriocitrin is collected, concentrated and freeze-dried to obtain a powdered lemon extract. Obtained. The composition of the obtained lemon extract is shown in Table 2 below.

また、得られたレモン抽出物（２ｇ）を蒸留水（３５０ｍｌ）に溶解させた溶液（エリオシトリン濃度が６０００ｐｐｍ）に、β−グルコシダーゼ（２００ｍｇ）を添加し、４５℃にて１時間インキュベートした。その後、上記溶液と同量のエタノールを加え、遠心除去することにより不純物と共にβ−グルコシダーゼを除去した。このものを濃縮・凍結乾燥することにより粉末状の酵素処理物を得た。得られた酵素処理物の組成を下記表３に示す。

Further, β-glucosidase (200 mg) was added to a solution (eriocitrin concentration of 6000 ppm) in which the obtained lemon extract (2 g) was dissolved in distilled water (350 ml), and incubated at 45 ° C. for 1 hour. Thereafter, the same amount of ethanol as the above solution was added and centrifuged to remove β-glucosidase along with impurities. This was concentrated and freeze-dried to obtain a powdered enzyme-treated product. The composition of the obtained enzyme-treated product is shown in Table 3 below.

そして、得られたレモン抽出物及び酵素処理物を、それぞれ２５０、５００、７５０、１０００μｇ／ｍｌとなるように５０％エタノール溶液に溶解させ、試験試料を得た。そして、上記試験例１−１と同様の方法にて、キサンチンオキシダーゼ阻害率を算出した。その結果を下記表４に示す。なお、本試験例における酵素反応時の各実施例の濃度はそれぞれ８５．５、１１４．０μｇ／ｍｌである。

Then, the obtained lemon extract and enzyme-treated product were dissolved in a 50% ethanol solution so as to be 250, 500, 750, and 1000 μg / ml, respectively, to obtain test samples. And the xanthine oxidase inhibition rate was computed by the method similar to the said test example 1-1. The results are shown in Table 4 below. In addition, the density | concentration of each Example at the time of the enzyme reaction in this test example is 85.5 and 114.0 microgram / ml, respectively.

表４に示すように、レモン抽出物及び酵素処理物のいずれもキサンチンオキシダーゼ阻害作用を示した。この結果から、レモン抽出物の状態で配合した場合にもキサンチンオキシダーゼ阻害作用を得られることが確認された。また、β−グルコシダーゼ処理を行なった酵素処理物は、同処理を行なっていないレモン抽出物と比較してより高い阻害作用を示した。この結果から、β−グルコシダーゼ処理を行うことがより効果的であることが確認された。

As shown in Table 4, both the lemon extract and the enzyme-treated product showed xanthine oxidase inhibitory action. From this result, it was confirmed that the xanthine oxidase inhibitory action can be obtained even when blended in the lemon extract state. In addition, the enzyme-treated product that had been treated with β-glucosidase showed a higher inhibitory action than the lemon extract that had not been treated. From this result, it was confirmed that the β-glucosidase treatment was more effective.

<Test on uric acid level lowering action>
[Test Example 2-1: Test for mice]
In this test example, 5-week-old male ddy mice (purchased from Japan SLC) were used as test subjects. After the mice were preliminarily raised for 5 days, the lemon extract (see Table 2 above) and the enzyme-treated product (see Table 3 above) prepared by the same method as in Test Example 1-2 were each added to a 5% gum arabic solution. The suspension was orally administered. At that time, the lemon extract was administered at 175, 350, 700 mg / kg body weight. In addition, the enzyme-treated product was administered so as to be 700 mg / kg body weight. Moreover, what administered the 5% gum arabic solution without the lemon extract and enzyme-treated product was prepared and used as a control.

  Subsequently, 1 hour after administration, inosine monophosphate (manufactured by SIGMA) was administered into the abdominal cavity so that the body weight was 600 mg / kg, and blood was collected from the abdominal aorta under diethyl ether anesthesia 1 hour later. The supernatant obtained by centrifuging the collected blood was used as a blood sample, and the uric acid level of the blood sample was measured. This uric acid value was measured by uricase / TOOS method using uric acid-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) (measured at an absorbance of 555 nm). The results are shown in Table 5 below.

表５に示すように、キサンチンオキシダーゼ阻害剤であるレモン抽出物を投与した場合、同阻害剤を投与していないコントロールと比較して濃度依存的に血漿中尿酸値が減少した。また、酵素処理物を投与した場合においても、コントロールと比較して有意な血漿中尿酸値の低下を示した（ｔ検定における有意差：Ｐ＜０．０５）。

As shown in Table 5, when the lemon extract, which is a xanthine oxidase inhibitor, was administered, the plasma uric acid level decreased in a concentration-dependent manner as compared to the control not administered with the inhibitor. In addition, even when the enzyme-treated product was administered, it showed a significant decrease in plasma uric acid level compared to the control (significant difference in t test: P <0.05).

[Test Example 2-2: Test for human]
In this test example, three males (A, B, and C) whose plasma uric acid level was higher than the reference value (7 mg / dl) were used as subjects. Each subject was allowed to ingest a test sample (tablet sample) containing 600 mg of the above lemon extract every dinner, and this was continued for 2 months. Blood samples were collected on the intake start date (before intake) and 2 months after the intake start date (after intake), and the uric acid level in plasma was measured. The results are shown in Table 6 below. During the test period, the daily life such as eating habits, smoking and exercise was not changed as much as possible except that the test samples were taken at dinner. In order to avoid external influences such as meals, blood was collected after fasting for 12 hours.

表６に示すように、キサンチンオキシダーゼ阻害剤であるレモン抽出物を摂取した場合、被験者全員において血漿中尿酸値の減少が確認された。また、その平均値においても血漿中尿酸値の有意な減少が確認された（ｔ検定における有意差：Ｐ＜０．０５）。本実施形態のキサンチンオキシダーゼ阻害剤は、血漿中尿酸値の低下させることを目的とする尿酸産生抑制剤の有効成分として好適に配合することができることが確認された。

As shown in Table 6, when the lemon extract, which is a xanthine oxidase inhibitor, was ingested, a decrease in plasma uric acid level was confirmed in all subjects. In addition, a significant decrease in plasma uric acid level was also confirmed in the average value (significant difference in t test: P <0.05). It was confirmed that the xanthine oxidase inhibitor of this embodiment can be suitably blended as an active ingredient of a uric acid production inhibitor intended to reduce the plasma uric acid level.

Claims (5)

It contains at least one polyphenol selected from Eriodictiool, Hesperetin, Naringenin, Diosmethine, Eriodictinol Glycoside, Hesperetin Glycoside, Naringenin Glycoside, and Diosmethine Glycoside as an active ingredient A xanthine oxidase inhibitor. The xanthine oxidase inhibitor according to claim 1, wherein the polyphenol is eriodictiool, hesperetin, naringenin or diosmethine. The xanthine oxidase inhibitor according to claim 1 or 2, wherein the polyphenols are blended as a lemon extract or an enzyme-treated product obtained by treating the lemon extract with β-glucosidase. The xanthine oxidase inhibitor according to any one of claims 1 to 3, wherein the xanthine oxidase inhibitor is used as a uric acid production inhibitor. The xanthine oxidase inhibitor according to any one of claims 1 to 4, wherein the xanthine oxidase inhibitor is used as a preventive or therapeutic agent for diseases caused by abnormal metabolism of uric acid.