JP2013209363A - Xanthine oxidase inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a safe xanthine oxidase inhibitor effective for treating gout and hyperuricemia.SOLUTION: A xanthine oxidase inhibitor including an extract of water caltrop is provided. An agent for suppressing the blood urate level increase that includes extract of water caltrop is also provided. The xanthine oxidase inhibitor or the agent for suppressing the blood urate level increase is safe and is useful as a drug, drink and food for treating, alleviating and preventing diseases resulting from overproduction of urate (for example, gout, hyperuricemia or the like).

Description

  The present invention relates to xanthine oxidase inhibitors.

Xanthine oxidase (xanthine
Oxidase, XO, XAO) is one type of xanthine oxidoreductase that generates reactive oxygen species. It is an enzyme that oxidizes hypoxanthine to xanthine and then catalyzes oxidation to uric acid. It plays an important role in purine catabolism in many organisms, including humans. Xanthine oxidase can be reversibly converted to xanthine dehydrogenase by oxidation of a sulfhydryl group.

  Increased blood uric acid concentration causes various diseases such as hyperuricemia and gout. In order to treat such diseases, uric acid production inhibitors or xanthine oxidase inhibitors are administered. Xanthine oxidase inhibitors include allopurinol, oxypurinol, phytic acid, febuxostat and the like.

  From the viewpoint of safety to the human body, xanthine oxidase inhibitors derived from natural products have been developed. For example, the extract of Prunus cranata (Banaba) (patent document 1); Pimenta (Pimenta officinalis), marjoram (Origanum majorana), guava (Psidium guajava), anise (Pimpinella anisum), olive (Olea europaea), Toshikimi (Illicium verum) , Peanut (Canavalia gladiata), hyssop (Hyssopus officinalis), black currant (Ribes nigrum), bilberry (Vaccinium myrtillus), mugwort (Artemisia princeps) or Campesiaboku (Haematoxylon campechianum L.) extract (Patent Document 2); Extract or dried powder of turmeric (Kaempferia parviflora) (patent document 3); dried or extracted extract of sunflower, cinnamon, cedron, wabenkei, red scenic, galangal, nutmeg, hypericum or grape (patent document 4) ; Dokuju, Sekikouju, Naginata Kouji , Lemon balm, rosemary, spearmint, peppermint, winter savory, betel or fukumangi plant body or extract (Patent Document 5); Artemisia, Settsurenka, Chrysanthemum, Guava, Boxworm, Blue Mallow, Oregano, Kakidooshi, Hakka, Murasaki Kinafuji Or, an extract of peanut (Patent Document 6); and an extract of natural lichen or lichen culture (Patent Document 7) have been reported.

  By the way, rhinoceros is an aquatic annual plant that grows naturally in ponds and lakes, and is actually the world's medicinal product such as nutritional tonic and improved gastrointestinal function. It was used for food in various places. Furthermore, in recent years, many existences of medicinal effects of cancer suppression have been reported, and they are often used as a medicinal shell material (Patent Document 8). As for the use or action of Hishimi, the use of Hishimi extract for cosmetics (Patent Document 9), the antiplasmin action of Hishimi extract (Patent Document 10), and the collagen synthesis promoting action (Patent Document 11). ), Cell activation effect (Patent Document 12), atopic dermatitis improving action (Patent Document 13), leukocyte cell adhesion inhibitory action (Patent Document 14), and histamine release inhibitory action (Patent Document 15).

JP 2000-290188 A JP 2010-37335 A JP 2011-236133 A JP 2002-121145 A JP 2003-252776 A International Publication No. 2009/093584 JP-A-5-244963 JP 2011-111394 A JP-A-5-306214 JP-A-7-188045 Japanese Patent Laid-Open No. 7-316063 JP-A-8-333270 JP 11-199500 A JP-A-11-236334 JP 2001-48766 A

  An object of the present invention is to provide a xanthine oxidase inhibitor that is highly safe and useful for the treatment, amelioration, or prevention of gout or hyperuricemia.

  The present invention provides a xanthine oxidase inhibitor containing a honey extract as an active ingredient.

  In one embodiment, the Hishimi extract is an extract obtained by hot water extraction of Hishimi.

  In a further embodiment, the temperature of the hot water set in the hot water extraction is 40 ° C to 100 ° C.

  The present invention also provides a blood uric acid level increase inhibitor containing the xanthine oxidase inhibitor.

  According to the present invention, a xanthine oxidase inhibitor and a blood uric acid level increase inhibitor that are highly safe and useful for preventing or ameliorating diseases caused by excessive production of uric acid (for example, gout, hyperuricemia, etc.) are provided. Is done.

The serum uric acid density | concentration when a Rhijin hot water extract is intragastrically administered to a hyperuricemia induction model rat is shown.

  In the present specification, “rhino” refers to an aquatic annual plant belonging to the genus Trapaceae (Trapaceae). Examples of the “rhino” include seeds such as Onibishi (Trapa natans), Japanese cypress (Trapa japonica), Japanese tiger shrimp (Trapa incisa), and Japanese tiger shrimp (Trapa bicornis). Any species can be used. Shrimp is a large variety and is particularly suitable as an extraction material because the harvested fruits are larger than other types of diamonds.

  Hishimi has a substantially triangular appearance. The actual size depends on the type, but in the case of Onibishi, the longest side is about 5 cm and the thickness is about 1 cm. The diamonds used for the extraction may be those that have just been harvested or have been stored under normal storage conditions and periods for the diamonds. Hishimi has a hard outer shell. Examples of the ingredients contained in Rhizomi include starch and polyphenols.

  Hishimi may be used after being pulverized to an appropriate size without removing the outer shell. Alternatively, Roshimi may use only the outer shell separated, and only the separated outer shell crushed to an appropriate size. In addition, when using only the outer shell of the diamond fruit, the moisture contained may be removed by performing drying using means well known to those skilled in the art before or after pulverization. The pulverization method includes means such as pulverization or atomization using a pulverizer or an attritor. If necessary, wash before crushing. Sonication can be performed before extraction, especially if the material after crushing aggregates.

  Examples of the extract in the present invention include squeezed juice obtained by pressing and extracting the crushed rhinoceros, a crude extract using an extraction solvent, and various chromatographs (distribution chromatography, adsorption chromatography, high performance liquid). Chromatography and the like), extract fractions obtained by concentration or purification by ultrafiltration and the like can be used. These may be used alone or in combination of two or more.

  Examples of the extraction solvent include water, hydrophilic organic solvents, hydrous organic solvents, and lipophilic organic solvents. Examples of the hydrophilic organic solvent include methanol, ethanol, acetone, dioxane, tetrahydrofuran, and isopropanol. Examples of the water-containing organic solvent include water-containing methanol, water-containing ethanol, water-containing acetone and the like. Examples of the lipophilic organic solvent include n-butanol, n-hexanol, n-amyl alcohol, ethyl acetate, propyl acetate, butyl acetate, methylene chloride, diethyl ether, benzene, toluene, xylene and the like. Preferably, an extract obtained from the ground product of Rhizomi using water, alcohol, or a mixture thereof can be used. More preferably, an extract obtained by using water from the pulverized product of Rhizomi can be used. Examples of water include tap water, pure water, ion exchange water, and distilled water, but are not particularly limited.

  There are no particular restrictions on the volume of the solvent used for extraction (in the case of a water-containing organic solvent, the concentration of the organic solvent in water), the processing temperature and time of extraction, and the like. When water is used as the extraction solvent, examples of the method include a hot water extraction method and a cold water extraction method. Examples of the hot water extraction method include a method of immersing the material in hot water or a method of steaming with steam. The temperature of hot water is preferably 40 to 100 ° C., more preferably 70 to 100 ° C., and the treatment time of hot water is preferably 10 to 120 minutes, more preferably 20 to 40 minutes. In the case of hot water treatment, high pressure treatment may be used in combination. In the case of steaming with steam, the steaming time with boiling hot water is preferably 10 to 120 minutes, more preferably 30 to 60 minutes. Examples of the cold water extraction method include a method of immersing the material in an aqueous solution to which cold water or other components are added. The temperature of cold water becomes like this. Preferably it is 0-40 degreeC, More preferably, it is 10-40 degreeC, Processing time becomes like this. Preferably it is 10-240 minutes, More preferably, it is 60-120 minutes.

  After the extraction, the precipitate or the insoluble fraction can be removed by an appropriate separation means such as centrifugation or filtration, and the supernatant or the soluble fraction can be recovered. Furthermore, the same extraction process can be performed again on the precipitate or insoluble fraction after the extraction, and the supernatant or the soluble fraction can be recovered.

  The Hishimi extract may be further subjected to treatments such as drying and pulverization. As the drying method, any known method can be used, and examples thereof include an air drying method, a heat drying method, a spray drying method, and a freeze drying method. For example, what is obtained by adding an excipient (for example, dextrin) to the Rishimi extract can be dried by spray drying or the like. The pulverization method is as described above.

  The Rhishin extract can be used in any form of liquid or solvent-removed solid.

  Inhibiting xanthine oxidase as it is or by adding an appropriate liquid or solid excipient or extender such as titanium oxide, calcium carbonate, distilled water, lactose, starch, etc. It can be used as an agent. In the present specification, the “xanthine oxidase inhibitor” refers to a substance or composition that inhibits the action of xanthine oxidase. Alternatively, it can be used as a blood uric acid level increase inhibitor. “Blood uric acid levels” can be expressed as serum uric acid levels (mg / dL). In the present specification, the “blood uric acid level increase inhibitor” refers to a substance or composition having an action of suppressing an increase in blood uric acid level or reducing the amount of overproduced uric acid. Alternatively, it can be used as an active oxygen production inhibitor. In the present specification, the “reactive oxygen production inhibitor” refers to a substance or composition having an action of suppressing an increase in active oxygen in blood, tissue, or organ. It can also be used as a prophylactic agent or symptom improving agent for diseases caused by excessive production of uric acid (for example, gout, hyperuricemia, etc.). In the present specification, in the present specification, “prevention” of a disease refers to an action that reduces the possibility of causing symptoms, and “prophylactic agent” refers to a substance or composition having such an action. Say. “Symptom improvement” of a disease refers to the action of improving the symptoms that occur, and “symptom improvement” refers to a substance or composition having such action. Xanthine oxidase inhibitor containing Rhijin extract, blood uric acid level increase inhibitor, active oxygen production inhibitor, preventive agent or symptom ameliorating agent for diseases caused by excessive uric acid production (hereinafter collectively referred to as “xanthine oxidase inhibitor, etc. The amount of Rhizomi extract is not particularly limited, but it is preferably 0.01 to 100% by mass, more preferably 0.1 to 50% by mass, Even more preferably, 0.5 to 30% by mass is contained.

  A xanthine oxidase inhibitor containing Rhizomi extract can be used as a material for foods and drinks and pharmaceuticals. A xanthine oxidase inhibitor containing Rhizomi extract and the like can be contained in food and drink compositions (for example, health foods such as oral supplements) and pharmaceutical compositions. These food-drinks composition and pharmaceutical composition can be used especially for the prevention or improvement of the disease (for example, gout, hyperuricemia etc.) resulting from uric acid overproduction, for example.

  The food and drink composition is glucose, fructose, sucrose, maltose, maltitol, sorbitol, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, casein, gelatin, pectin, agar, amino acids, excipients, A bulking agent, a binder, a thickener, an emulsifier, a coloring agent, a fragrance, a food additive, a seasoning, a preservative, and the like can be further contained as appropriate. Such a food / beverage composition can be formed into a powder, granule, capsule, tablet, syrup, suspension, or the like, and can be processed into a candy, a troche, a gum, or the like depending on the application. Manufacture of the food-drinks composition (for example, oral supplement) may be performed by the method normally used by those skilled in the art. A blending amount, a blending method, and a blending time of the xanthine oxidase inhibitor and the like in the food / beverage product composition can be appropriately selected.

  The xanthine oxidase inhibitor of the present invention and a food or beverage composition containing the same can be taken as they are, and can be taken even if dissolved or suspended in a solvent such as water, before and after a meal, or Can be taken orally between meals. A xanthine oxidase inhibitor or the like or a food or drink composition can be added to the food or drink to eat or drink. Alternatively, the xanthine oxidase inhibitor of the present invention and the food and beverage composition containing the same can be used as so-called Hishimi tea drinks by obtaining Hishimi extract with hot water.

  A xanthine oxidase inhibitor or the like comprising the Rhizomi extract of the present invention or a food or drink composition, or a food or drink containing the xanthine oxidase inhibitor has a xanthine oxidase inhibitory effect and a blood uric acid level increase inhibitory effect, Furthermore, it can have effects such as improvement and prevention of symptoms of diseases caused by excessive production of uric acid (for example, gout, hyperuricemia, etc.). Here, the term “suppression of increase in blood uric acid level” used in the present specification is not limited to suppression of increase in blood uric acid level over time, but in addition to such suppression. It also includes the case where there is no change in the blood uric acid level with the passage of time (that is, the uric acid level becomes substantially constant, for example), and the case where the blood uric acid level decreases with the passage of time. Therefore, foods and drinks containing a xanthine oxidase inhibitor containing Rhizomi extract are effective in inhibiting xanthine oxidase, suppressing blood uric acid level elevation, diseases caused by excessive production of uric acid (eg gout, hyperuricemia, etc. ) Can be applied to functional foods, foods for the sick, and foods for specified health use for the purpose of improving and / or preventing the symptoms of .

  Specific food and drink forms include, for example, cooked rice products, wheat products, fermented products, vegetable products, dairy products, confectionery, fermented beverages, fruit juice beverages, carbonated beverages, soft drinks, milk, whey beverages, and lactic acid bacteria beverages. However, it is not limited to these. Addition or processing of a xanthine oxidase inhibitor or the like or a food / beverage composition to a food / beverage product can be performed by a method commonly used by those skilled in the art, and the blending amount, blending method, blending time can be appropriately selected, and if necessary, Various additives as described above may be blended. Addition to feed for animals other than humans, such as livestock or pets, is also possible.

  In the food / beverage composition or food / beverage product, the content of the xanthine oxidase inhibitor of the present invention or the like is not particularly limited as long as the effect of xanthine oxidase inhibition or the like in the present invention is exerted. Can depend on the effect. The xanthine oxidase inhibitor or the like or Rhizomi extract of the present invention is preferably 0.1 to 100% by mass, more preferably based on the solid content concentration of the Rhizomi extract with respect to the total amount of the food or drink composition or food or drink. Is contained in an amount of 1 to 50% by mass.

  A pharmaceutical composition containing a xanthine oxidase inhibitor containing the Rhizomi extract of the present invention has a xanthine oxidase inhibitory effect, a blood uric acid level increase inhibitory effect, and an active oxygen production inhibitory effect. The symptom of the disease (for example, gout, hyperuricemia etc.) resulting from the improvement and the preventive effect can be show | played. A pharmaceutical composition containing a xanthine oxidase inhibitor containing Rhizomi extract has a xanthine oxidase inhibitory effect, a blood uric acid level increase inhibitory effect, an active oxygen production inhibitory effect, a disease caused by uric acid overproduction (for example, gout, It may be aimed at improving and / or preventing the symptoms of hyperuricemia and the like, or may utilize these effects.

  The pharmaceutical composition includes various pharmaceutically acceptable carriers, binders, stabilizers, excipients, diluents, pH buffers, disintegrants, solubilizers, solubilizers, isotonic agents, and the like. It may further contain a compounding component for dispensing. These pharmaceutical compositions can be administered orally, tube, or transdermally in dosage forms such as powders, granules, capsules, syrups, suspensions, ointments and the like. The production of the pharmaceutical composition can be carried out by methods commonly used by those skilled in the art, and the blending amount, blending method, and blending time can be appropriately selected. The content of the xanthine oxidase inhibitor of the present invention or the like in the pharmaceutical composition of the Rishimi extract is not particularly limited as long as the effect of xanthine oxidase inhibition and the like in the present invention is exhibited. The xanthine oxidase inhibitor or the like or the Rishimi extract of the present invention is preferably 10 to 100% by mass, more preferably 60 to 100% by mass, based on the solid content concentration of the Rishimi extract, based on the total amount of the pharmaceutical composition. Contained.

  The dosage of the pharmaceutical composition can be appropriately selected according to the patient's age, weight, symptoms, patient grade, administration route, administration schedule, formulation form, desired inhibitory activity and the like. The pharmaceutical composition can be administered as it is, or can be administered by dissolving, suspending or diluting in a solvent such as water. For example, in the case of oral administration, generally 0.01 to 1 g / kg body weight per day is preferable, and the dose may be divided into several times a day.

  Extracts that exhibit other xanthine oxidase inhibitory effects or blood uric acid level elevation-inhibiting effects when preparing food-drinks compositions or food-drinks or pharmaceutical compositions containing xanthine oxidase inhibitors containing Rishimi extract as active ingredients You may use a thing together. In this case, there is no particular limitation on the blending ratio of the Hishimi extract and the other extracts, but the mass ratio is usually about 1: 9 to 9: 1 as the solid content of the Hishimi extract.

  EXAMPLES Hereinafter, although an Example demonstrates this invention more concretely, this invention is not limited by these Examples.

(Preparation Example 1: Onishibushi-derived Hishimi hot water extract)
Shrimp (Yanakawa City, Fukuoka Prefecture) was thoroughly washed with clean water and then ground with a mixer. Next, pure water having a mass 5 times the mass of the actual mass was added to the pulverized fruit and sonicated for 5 minutes. After sonication, this was heated to 95 ° C. or higher to boil and then heated for 1 hour. This was then cooled. This was centrifuged at 3000 rpm for 20 minutes, and the resulting supernatant was collected and lyophilized (“whole fruit extract”).

  The supernatant was applied to a spin-type ultrafiltration device (Vivaspin; manufactured by GE Healthcare), and a fraction having a molecular weight exceeding 30000 was collected and freeze-dried (“Rishimi extract MW> 30000”). Further, a solution having a molecular weight exceeding 10,000 was collected from the filtrate and freeze-dried (“Rhizomi extract 10000 <MW ≦ 30000”). Further, the filtrate was separated into a fraction having a molecular weight of more than 3000 and a fraction having a molecular weight of 3000 or less, and the respective solutions were freeze-dried (respectively “Rishimi extract 3000 <MW ≦ 10000” and “Rishimi extract MW”, respectively. ≦ 3000 ”).

(Preparation Example 2: Himebishi-derived Hishimi hot water extract)
Extracts of the whole and various molecular weight fractions were obtained in the same manner as in Example 1 except that Japanese persimmon fruits (produced in Yanagawa City, Fukuoka Prefecture) were used as starting materials.

(Example 1: Xanthine oxidase inhibitory effect of Rhijin hot water extract)
Extracts of the whole of Preparation Example 1 and various molecular weight fractions (“Hishimi extract”, “Hishimi extract MW ≦ 3000”, “Hishimi extract 3000 <MW ≦ 10000”, “Hishimi extract 10000 <MW ≦ 30000 "and" Hishimi extract MW> 30000 ") were used to prepare 100 mg / mL solutions (hereinafter referred to as" 100 mg / mL Hishimi extract "for convenience).

  100 mg / mL Rhizomi extract is either 1, 10, or 25 μL, 10 mmol / L xanthine 12 μL and 0.1 mmol / L Tris-HCl buffer (pH 8.1) (volume that makes the final total volume of the reaction solution 1000 μL: 973, 964 or 949 μL) was first placed in a test tube, and then 14 μL of 0.1 Unit / mL buttermilk-derived xanthine oxidase was added to initiate the reaction (all reagents used were purchased from Wako Pure Chemical Industries, Ltd.). Therefore, the final concentration of each component in the reaction solution is Rhijin extract 0.1, 1.0, or 2.5 mg / mL, xanthine 0.12 mmol / L, and xanthine oxidase 0.0014 Unit / mL. As a positive control, 1 mmol / L allopurinol (purchased from Wako Pure Chemical Industries, Ltd.) was used. This reaction was carried out at 37 ° C. for 15 minutes. The test tube was placed on ice to stop the reaction, and ultraviolet absorbance was measured at 292 nm.

  The results are shown in Table 1 below. The results are expressed as a ratio when the xanthine oxidase inhibition of 1 mmol / L allopurinol, which is a positive control, is 100.

  Xanthine oxidase inhibitory effect was observed in “Hishimi extract”. From the results of the molecular weight fraction, a high xanthine oxidase inhibitory effect was observed particularly with “Rishimi extract 10000 <MW ≦ 30000”.

  Similar results were obtained when the xanthine oxidase inhibitory effect was similarly examined using the whole of Preparation Example 2 and extracts of various molecular weight fractions.

(Example 2: inhibitory effect of Rishimi hot water extract on blood uric acid level increase)
Male SD rats (6 weeks old: purchased from Clea Japan) were acclimated for 1 week. From 12 hours before the start of the experiment, the rats were fasted and allowed to drink freely. A method using oxonic acid was used to induce hyperuricemia in rats. That is, the rats were divided into a control group (non-oxonic acid treatment group), an oxonic acid treatment group (oxonic acid-treated test substance non-administration group), a test substance administration group (allopurinol administration group, “Rishimi extract” in Preparation Example 1, “Rhizomi extract MW ≦ 3000”, “Rhizomi extract 3000 <MW ≦ 10000”, “Rhizomi extract 10000 <MW ≦ 30000” and “Rhizomi extract MW> 30000” administration groups). Rats in the oxonic acid-treated group and the test substance-administered group were administered subcutaneously with potassium oxonate (purchased from Wako Pure Chemical Industries, Ltd.) at a dose of 250 mg / kg body weight. A similar amount of physiological saline (PBS) was subcutaneously administered to the rats in the control group. One hour after the administration of oxonic acid, the test substance administration group (10 mg / kg-body weight for allopurinol, 100 mg / kg-body weight for Rishimi test substance) was intragastrically administered to rats in the test substance administration group. Two hours after the intragastric administration of the test substance, each group of mice was bled from the abdominal aorta under ether inhalation anesthesia. The collected blood was separated into serum by centrifugation, and the serum uric acid concentration of each individual was measured with a uric acid measurement kit (uric acid C-Test Wako: Wako Pure Chemical Industries, Ltd.). The result is shown in FIG.

  FIG. 1 shows the concentration of uric acid in serum when Rhijin hot water extract was intragastrically administered to a hyperuricemia-induced model rat. The vertical axis represents the serum uric acid concentration (mg / dL), and the horizontal axis, in order from the left, the control group, the oxonic acid treatment group, the allopurinol administration group, the Rishimi extract whole administration group, the Rishimi extract MW ≦ 3000 administration group. , Hishimi extract 3000 <MW ≦ 10000 administration group, Hishimi extract 10000 <MW ≦ 30000 administration group, and Hishimi extract MW> 30000 administration group (*: p <0.05, **: p <0. 01).

  As is clear from FIG. 1, the serum uric acid concentration increases by administering potassium oxonate, which is a hyperuricemia-inducing agent, but the increase in serum uric acid concentration is suppressed by administering Rishimi test substance. It was done. From the results of the molecular weight fraction, a high inhibitory effect on the increase in serum uric acid concentration was observed, particularly in the Rhizomi Extract 10000 <MW ≦ 30000 administration group.

  The same results were obtained when the effect of suppressing the increase in blood uric acid level using the hyperuricemia-induced model rat was examined using the whole fruit of Preparation Example 2 and extracts of various molecular weight fractions. .

(Example 3: Production of Hishimi-cha)
The shell of Onibishi (produced in Fukuoka Prefecture) was peeled off and the shell was thoroughly washed. Then, this shell part was cut into 0.5 cm to 1.0 cm square. On a hot plate having a surface temperature heated to 250 ° C., 100 g of the above-mentioned sea urchin shell was put on the lid, heated for 5 minutes and steamed. Next, the roasted and steamed sea urchin shell was spread on a paper towel and allowed to cool, and was then stirred on the plate for 10 minutes to squeeze the water present inside the sea urchin shell onto the surface. The scallop shell squeezed out on a hot plate adjusted to a surface temperature of 150 ° C. was put into the hot plate with constant chopsticks and taken out three times in the middle, and dried for 30 minutes while squeezing. Thereafter, the snail shell was once taken out, a paper towel was laid on the hot plate, the snail shell was spread, and further dried on the hot plate for 20 minutes. In this manner, 1.5 g of Onibibushi husk tea treated in this manner was placed in 200 mL of hot water (100 ° C.) and steamed for 30 minutes to obtain a potable Hishimi tea.

(Example 4: Human clinical trial with Hishimi-cha)
Healthy adult males and females (excluding those undergoing treatment such as medication) (age 21.4 ± 3.8 years old) are selected as candidate subjects, and they are healthy from prior candidates (height, weight, blood pressure, blood tests and interviews). Thirty-two people confirmed to be present were selected as subjects.

  The subject was prohibited from taking anything other than water 12 hours before the start of the trial. Water intake was also prohibited from 1 hour before the start of the trial. The selected 32 subjects were randomly assigned to 2 groups (16 in each group), and pre-bleeding was performed in each group. Thereafter, 200 ml of water in the control group and 200 ml of Hishimi tea (Onibishi husk tea) obtained in Example 3 in the Hishi-no-tea group, together with one hamburger (Mega Macdon (754 kcal) manufactured by McDonald's Japan) for 15 minutes. Ingested over time. Thereafter, blood was collected from each subject in both groups at 1 hour and 3 hours after ingestion, and the uric acid level was measured. The measurement of the uric acid level in the collected blood was entrusted to SRL Inc. This clinical trial was conducted with the approval of Keio University Clinical Examination Committee.

  The obtained results are shown in Table 2.

  As shown in Table 2, compared to the results of the subjects in the control group who ingested water and hamburgers, the subjects in the shinmi group who ingested hamburgers together with the shinmi tea obtained in Example 3 1 hour and 3 hours after ingestion, the uric acid level decreased, and it can be seen that Hishimi tea obtained in Example 3 has an excellent blood uric acid level increase suppressing effect.

  The xanthine oxidase inhibitor or the blood uric acid level elevation inhibitor of the present invention contains a honey extract. Hishimi extract is derived from natural products, and uses what has been conventionally taken for food. The xanthine oxidase inhibitor or blood uric acid level elevation inhibitor containing the Rhizomi extract of the present invention is highly safe and treats and improves diseases caused by excessive production of uric acid (eg gout, hyperuricemia). Or it is useful for the pharmaceutical and food-drinks which show a preventive effect.

Claims (4)

  A xanthine oxidase inhibitor containing Rhizomi extract as an active ingredient.   The xanthine oxidase inhibitor according to claim 1, wherein the Rhizomi extract is an extract obtained by hot water extraction of Rishimi.   The xanthine oxidase inhibitor of Claim 2 whose temperature of the hot water set by the said hot water extraction is 40 to 100 degreeC.   A blood uric acid level increase inhibitor comprising the xanthine oxidase inhibitor according to any one of claims 1 to 3.

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