JP2021014414A - Method for producing composition having uric acid level reducing effect and pharmaceutical product - Google Patents

Abstract

To provide a method for producing a composition having a uric acid level reducing effect, which is derived from a natural product, and a method for producing a pharmaceutical product comprising the composition obtained by the method as an active ingredient.SOLUTION: A method for producing a composition having a uric acid level reducing effect prepares an extract containing a substance having a uric acid level reducing action by eluting from coffee grains into a solvent containing ethanol. A method for producing a pharmaceutical product having a uric acid level reducing effect produces a composition having a uric acid level reducing action by the method for producing a composition having a uric acid level reducing action and then produces a pharmaceutical product containing the above composition as an active ingredient.SELECTED DRAWING: None

Description

The present invention relates to a method for producing a composition having a uric acid level reducing action derived from a natural product, and a method for producing a pharmaceutical product containing the composition obtained by the method as an active ingredient.

Gout, which is known as one of the lifestyle-related diseases, is a disease that causes severe pain in joints such as the big toe due to hyperuricemia due to abnormal metabolism of purines. Such pain occurs because the increased uric acid in the fluid crystallizes and deposits in the joints. In recent years, dietary habits have changed rapidly, and more and more people are eating high-calorie, high-protein, high-fat diets. The number of patients with gout is increasing year by year due to this change in eating habits, and there is increasing interest in the prevention and treatment of gout and hyperuricemia.

Gout is a disease caused by an increase in uric acid in the blood, and controlling uric acid in the blood within a normal value is the basis of prevention and treatment for diseases such as gout and hyperuricemia. Xanthine oxidase is an enzyme that plays an important role in in vivo uric acid synthesis, and a drug that inhibits this xanthine oxidase is useful as a prophylactic and therapeutic drug for gout, hyperuricemia, and the like.

However, the uric acid synthesis inhibitor "allopurinol", which has been conventionally used as a drug for adjusting the blood uric acid level, has problems such as transient xanthine oxidase inhibitory activity and side effects. Therefore, there is a demand for a uric acid level reducing agent derived from a natural product having no or few side effects and derived from foods and drinks that are ingested daily. For example, Non-Patent Document 1 reports that chlorogenic acid lactone contained in a hot water extract of roasted coffee beans has xanthine oxidase inhibitory activity. Further, Patent Document 1 states that feroil quinic acid lactones and kumaroyl quinic acid lactones contained in a hot water extract of roasted coffee beans have strong xanthine oxidase inhibitory activity, and these substances are roasted. It is described that it can be efficiently recovered by extracting from the hot water extract of roasted coffee beans with a fat-soluble organic solvent.

JP-A-2017-48185

Honda, et al., Bioscience, Biotechnology, and Biochemistry, 2014, vol.78 (12), p.2110-2116.

Non-Patent Document 1 does not describe anything other than chlorogenic acid lactone as a substance having xanthine oxidase inhibitory activity contained in a hot water extract of roasted coffee beans. In addition, it is a verification at the test tube level, and its usefulness in vivo has not been confirmed. On the other hand, the substance having xanthine oxidase inhibitory activity described in Patent Document 1 is recovered from a hot water extract of roasted coffee beans that can be a beverage. From the viewpoint of effective utilization of resources, it is preferable that a substance having xanthine oxidase inhibitory activity can be obtained from a residue generated during processing, rather than being directly used as a food or drink. In particular, the extraction residue of roasted coffee beans is generated in a large amount during the production of instant coffee and liquid coffee, and is generally used as fuel and compost, but more advanced effective utilization is required.

The present invention is a method for producing a composition having a uric acid level reducing action derived from an extract slag of a natural product, particularly coffee roasted beans, which is the most used favorite beverage in the world, and a composition obtained by the method. It is an object of the present invention to provide a method for producing a pharmaceutical product containing the active ingredient.

As a result of diligent research to solve the above problems, the present inventors have found that an ethanol extract from coffee extract has a strong uric acid level reducing effect, and further search for an active ingredient in the extract. We have found that caffe oil tryptophan and cafestol have high uric acid level reducing activity, and completed the present invention.

[1] The method for producing a composition having a uric acid level reducing action according to the first aspect of the present invention is an extract containing a substance having a uric acid level reducing action, which is eluted from a coffee extract slag into a solvent containing ethanol. To prepare.
[2] In the production method of the above [1], it is preferable that the solvent containing ethanol is ethanol or a mixed solvent of ethanol and water.
[3] The method for producing a pharmaceutical product having a uric acid level reducing effect according to the second aspect of the present invention has a uric acid level reducing effect according to the method for producing a composition having a uric acid level reducing effect according to the above [1] or [2]. A composition having the composition is produced, and a pharmaceutical product containing the composition as an active ingredient is produced.
[4] As the production method of the above [3], it is preferable that the drug is a therapeutic agent for gout or hyperuricemia.
[5] The uric acid level reducing agent according to the third aspect of the present invention contains caffe oil tryptophan or cafestol as an active ingredient.
[6] The pharmaceutical product according to the fourth aspect of the present invention contains caffeoyl tryptophan or cafestol as an active ingredient.
[7] The drug according to [6] is preferably a therapeutic agent for gout or hyperuricemia.

By the method for producing a composition having a uric acid level reducing action according to the present invention, a substance having a uric acid level reducing action is efficiently extracted from the extraction slag of roasted coffee beans, and a composition having a very high uric acid level reducing action is produced. can do. In addition, the composition produced by the method for producing the composition and the uric acid level reducing agent according to the present invention both have a high uric acid level reducing effect and are derived from coffee beans and are relatively safely administered. It is possible. Therefore, these are suitable as active ingredients of functional foods such as supplements and active ingredients of pharmaceuticals, and in particular, they are active ingredients of pharmaceuticals for prevention and treatment of gout and hyperuric acidemia, and in serum. It is suitable as an active ingredient of functional foods for reducing uric acid levels.

It is a figure which showed the measurement result of the uric acid production inhibition rate (%) in the liver-derived cultured cell maintained in the presence of each concentration of cafe oil tryptophan in Example 2. FIG. It is a figure which showed the measurement result of the uric acid production inhibition rate (%) in the liver-derived cultured cells maintained in the presence of each concentration of cafestol in Example 3. FIG. It is a figure which showed the measurement result of the plasma uric acid concentration (mg / dL) in the mouse which administered the coffee grounds ethanol extract in Example 4. FIG.

In the present invention and the present specification, the coffee extraction slag means the residue obtained by hot water extraction of roasted coffee beans. In other words, it is the remainder of the roasted coffee beans from which at least a portion of the water-soluble solids has been removed. The coffee grounds may contain water-soluble solids of roasted coffee beans.

The method for producing a composition having a uric acid level reducing effect according to the present invention (hereinafter, may be referred to as "method for producing a composition according to the present invention") is such that the coffee extract slag is eluted with a solvent containing ethanol. , A method for preparing an extract containing a substance having a uric acid level reducing action. An extract of an ethanol-containing solvent from a coffee grounds (hereinafter, may be referred to as “coffee grounds ethanol extract”) is a composition having a uric acid level reducing action. The compound having a uric acid level reducing action, which is known to be contained in the hot water extract of roasted coffee beans, is also contained in the coffee extract slag, and the solvent containing ethanol makes it more efficient from the coffee extract slag. It can be extracted well. In addition, coffee grounds contain abundant substances having a uric acid level reducing action that are difficult to extract with hot water, and some of these substances are extracted with an ethanol-containing solvent. The composition produced by the method for producing the composition according to the present invention comprises a substance contained in roasted coffee beans having a uric acid level reducing effect, which is a substance that can be extracted with hot water and a substance that is difficult to be extracted with hot water. Both are included and have a high uric acid level reducing effect.

The coffee grounds used as a raw material are residues obtained after contacting roasted coffee beans or crushed products with heated water to extract water-soluble solids. The method for extracting water-soluble solids is a method generally used for brewing coffee, or a method used for extracting soluble solids from crushed roasted coffee beans when producing instant coffee. Can be done by Specifically, any of a drip type, an espresso type, a siphon type, a percolator type, a coffee press (French press) type, a column type and the like may be used. The extraction may be a normal pressure type or a pressurized type. Further, the coffee slag may be a residue after hot water extraction is performed only once, or a residue after repeated hot water extraction a plurality of times.

The roasted coffee beans for obtaining the coffee extract slag as a raw material are not particularly limited in the type and production area of the coffee beans, and may be arabica or lobaster, and may be of two or more varieties. It may be a blend of coffee beans. Further, the roasting method is not particularly limited, and any method generally used for roasting coffee beans may be used. Examples of the method for roasting coffee beans include a direct fire roasting method, a hot air roasting method, a far infrared roasting method, a charcoal fire roasting method, and microwave roasting Coffea liberica seeds.

The degree of roasting of roasted coffee beans for obtaining coffee grounds used as a raw material is not particularly limited, and may be extremely light roasted, lightly roasted, or medium roasted. It may be deep roasted. The degree of crushing of the roasted coffee beans is not particularly limited, and various shapes of roasted coffee beans such as coarsely ground, medium coarsely ground, mediumly ground, mediumly finely ground, and finely ground can be used.

The coffee grounds are preferably ground before being extracted with a solvent containing ethanol. The crushing can be performed using a general crusher such as a roll mill.

The solvent containing ethanol, which is the extraction solvent used in the present invention, is not particularly limited as long as it is a solvent containing ethanol, but since the coffee extraction slag usually contains a large amount of water, the ethanol concentration at the time of extraction is high. It is preferable that the ethanol concentration of the extraction solvent is high so that the concentration does not decrease too much. The ethanol concentration of the extraction solvent is preferably 50% by volume or more, more preferably 75% by volume or more, further preferably 90% by volume or more, and further preferably 95% by volume or more. Preferably, a solvent consisting only of ethanol is particularly preferable.

When the solvent for extraction contains a solvent other than ethanol, the other solvent is preferably a polar solvent, more preferably alcohol other than ethanol such as methanol, propanol and isopropanol, and water, and extraction efficiency and safety to the human body. Water is particularly preferable from the viewpoint of sex. By using ethanol or a mixed solvent of ethanol and water as the extraction solvent, the obtained extract can be ingested as it is by humans. When the other solvent is not an edible solvent, it is preferable to remove the obtained ethanol extract by vacuum drying or the like and then ingest it to an animal such as a human.

A liquid coffee ground ethanol extract can be obtained by mixing the coffee grounds and an extraction solvent containing ethanol and then removing the solid content. The coffee grounds and the extraction solvent may be mixed at any temperature below the boiling point of the extraction solvent, and may be performed at room temperature. The solid content removal treatment may be performed immediately after mixing the coffee extract slag and the extraction solvent, or the solid content removal treatment may be performed after holding the mixture of the coffee extract slag and the extraction solvent for a certain period of time. When holding the mixture, it may be held still or may be held while stirring.

The method for removing the solid content from the mixture of the coffee residue and the extraction solvent is not particularly limited, and can be performed by, for example, a filtration treatment using a filter paper, a filtration filter or the like. As the filtration filter used, for example, the same filter as that used for removing the solid content from the extract obtained by hot-water-extracting the water-soluble solid content from the crushed product of roasted coffee beans can be used. ..

The liquid coffee grounds ethanol extract thus obtained can be concentrated by removing liquid components such as ethanol. Further, by completely removing the liquid component from the coffee grounds ethanol extract, a solid coffee grounds ethanol extract can be obtained. For the removal of liquid components such as ethanol, a method generally used for removing an organic solvent such as a vacuum distillation method using an evaporator can be appropriately used.

The obtained coffee slag ethanol extract contains roasted coffee beans such as chlorogenic acids, chlorogenic acid lactones, feroil quinic acid lactones, kumaroyl quinic acid lactones, and pyrogallol (1,2,3-Benzenetriol). It contains a known component having xanthin oxidase inhibitory activity contained in the hot water extract. The coffee grounds ethanol extract also contains cafe oil tryptophan and cafe stol. Café oil tryptophan and cafestol are coffee-derived uric acid level reducing components newly discovered by the present inventors.

The coffee slag ethanol extract produced by the method for producing the composition according to the present invention is a substance contained in roasted coffee beans and can be taken relatively safely. Therefore, these are suitable as raw materials for foods and drinks, feeds, cosmetics, pharmaceuticals, etc., and in particular, foods and drinks, feeds, cosmetics, pharmaceuticals taken to suppress the influence of the production or accumulation of uric acid in the body. It is suitable as an active ingredient such as. Specifically, the coffee slag ethanol extract is useful as an active ingredient of functional foods such as pharmaceuticals and supplements used for the prevention or treatment of various diseases caused by the production or accumulation of uric acid.

For example, the solvent-removed coffee ground ethanol extract can be used as it is by adding it to liquid coffee, instant coffee, coffee mix and the like. Here, examples of the liquid coffee include coffee beverages (or beverages containing coffee) that are put on the market in cans or so-called PET bottle containers. Further, as the instant coffee, there is a coffee called soluble powder coffee in which water is removed by spraying or freeze-drying an extract obtained by extracting roasted crushed coffee with boiling water. Examples of the coffee mixed beverage include a beverage obtained by adding sugar, creaming powder, or the like to soluble powdered coffee and mixing them. In addition, the coffee ground ethanol extract can be directly filled in capsules or the like and applied as a supplement.

In particular, by using the coffee ground ethanol extract as an active ingredient, a pharmaceutical product having a uric acid level reducing effect can be produced. The manufactured drug having a uric acid level reducing action can be a therapeutic agent for gout or hyperuricemia.

The dosage form of the drug containing the coffee ground ethanol extract as an active ingredient is not particularly limited, and various dosage forms can be applied. Examples of the dosage form include tablets, capsules, granules, powders, syrups, sprays, injections, suppositories, eye drops, nasal drops and the like. Since it is easy to take, the dosage form of the drug containing the coffee slag ethanol extract as an active ingredient is preferably one suitable for oral administration such as tablets, capsules, granules, powders and syrups.

Café oil tryptophan and cafestol are suitable as active ingredients of uric acid level reducing agents. As the caffe oil tryptophan and cafestol, which are the active ingredients of the uric acid level reducing agent, those isolated and purified from the coffee slag ethanol extract by a column chromatography method or the like may be used, or chemically synthesized ones may be used. Good.

Café oil Tryptophan and cafestol are both coffee-derived substances and can be taken relatively safely. Therefore, these are suitable as raw materials for foods and drinks, feeds, cosmetics, pharmaceuticals, etc., like coffee slag ethanol extract, and are particularly suitable for the prevention and treatment of gout and hyperuricemia. It is useful as a raw material for.

The uric acid level reducing agent according to the present invention may consist only of the active ingredient, caffe oil tryptophan or cafestol, or may contain other ingredients. The other component may be any as long as it does not impair the uric acid level reducing action of caffe oil tryptophan or caffe stall, for example, excipients, binders, fluidity improvers (anticaking agents), stabilizers, etc. Various substances used as preservatives, pH adjusters, solubilizers, suspending agents, emulsifiers, thickeners, flavoring agents, sweeteners, acidulants, fragrances, coloring agents, etc. can be added to the desired product quality. It may be appropriately contained depending on the circumstances. In addition, the dosage form of the uric acid level reducing agent can take various dosage forms, and those suitable for oral administration of tablets, capsules, granules, powders, syrups and the like are preferable.

Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples and the like.

[Example 1]
The uric acid production reducing effect of the coffee grounds ethanol extract extracted from the coffee grounds (coffee grounds) with a mixed solvent of ethanol and water was evaluated by a method using cultured cells. Instant coffee was compared.

<Preparation of coffee grounds ethanol extract>
To 100 g of coffee grounds having a solid content of about 30%, 166.5 mL of 95% by volume ethanol was added, stirred to prepare a slurry, and then fine powder was removed by filter filtration using a glass filter. The filter-filtered extract was distilled under reduced pressure for 3 hours to remove water and concentrate. The concentrated extract was then cooled in a cooler at about −40 ° C. for 30 minutes and then at −80 ° C. for 30 minutes. A coffee grounds ethanol extract was obtained by powdering the cooled extract by drying under reduced pressure.

<Cell culture>
AML12 cells, which are cultured cells derived from the liver, were purchased from ATCC (American Type Culture Collection, Manassas, VA, USA) and used in the experiment. 10% FBS (bovine fetal serum, Hyclone, Logan), 5 μg / mL recombinant human insulin (human recombinant, Wako Pure Chemical Industries, Ltd.), 5 μg / mL transferase (Wako Pure Chemical Industries, Ltd.), 3 ng DMEM / F-12 medium (Life Technologies) containing / mL selenium (manufactured by Sigma Aldrich), 40 ng / mL dexamethasone (manufactured by Wako Pure Chemical Industries, Ltd.), 100 IU / mL penicillin and 100 μg / mL streptomycin (manufactured by Nakaraitesk) Was cultured at 37 ° C. under the condition of 5% CO ₂ .
The AML12 cells were seeded such that a 24-well multiplate 1.0 × 10 ⁵ cells / well (400 [mu] L), were cultured in 10% FBS / DMEM / F- 12 medium. 72 hours after seeding, the medium was replaced with serum-free DMEM / F-12 medium and cultured for 24 hours. Next, AML12 cells were washed with a phosphate buffered saline solution (PBS (−), manufactured by Wako Pure Chemical Industries, Ltd.). In the following experiments, "PBS (-)" indicates a phosphate buffered saline solution containing no calcium or magnesium.

<Cell maintenance in the presence of specimen>
As a cell maintenance solution, a buffer salt solution containing guanosine and inosin (188 mM NaCl, 5 mM KCl, 1 mM MgCl ₂ , 0.8 mM CaCl ₂ , 25 mM NaHCO ₃ , 1 mM NaH ₂ PO ₄ , 10 mM HEPES, 5 mM glucose, 100 μM guanosine and 100 μM inosin (all manufactured by Wako Pure Chemical Industries, Ltd.) (hereinafter, BSS) were used. Coffee ground ethanol extract and instant coffee (trade name: <<Blendy> instant coffee>, manufactured by Ajinomoto AGF Co., Ltd.) were used as samples.
200 μL of a sample solution prepared by adding a sample dissolved in DMSO to BSS so that the final concentration becomes 0 μM or 100 μM (the final concentration in the sample solution as DMSO is 0.15% by volume) is added to PBS ( It was added to AML12 cells after washing with −) and maintained at 37 ° C. for 2 hours.

<Measurement of uric acid production>
After maintenance for 2 hours, the AML12 cells after collecting the supernatant were washed with PBS (-), and 300 μL of Tris buffer (1 mM sodium phosphate (manufactured by Wako Pure Chemical Industries, Ltd.), 50 mM Tris (manufactured by Sigma-Aldrich)). ), pH 7.5), scraped out with a cell scraper and recovered. The recovered cells were ultrasonically decomposed and centrifuged at 12000 × g for 5 minutes at 4 ° C.

The uric acid concentration in the recovered supernatant was measured using the uricase colorimetric method (product name: <uric acid C-testwaco>, manufactured by Wako Pure Chemical Industries, Ltd.). The amount of protein in the recovered AML12 cells was measured using the bicinchoninic acid method (product name: <Pierce BCA protein assay kit>, manufactured by Thermo Fisher Scientific Co., Ltd.). It was calculated as the amount of uric acid produced per 1 mg of cellular protein per 2 hours (nmol / 2h / mg protein).

The uric acid production inhibition rate of each cell was calculated by the following formula.

[Uric acid production inhibition rate (%)] = ([Uric acid production amount of cells without sample addition (control)]-[Uric acid production amount of cells with sample addition]) × 100 / [Control uric acid production amount]

As a result, the uric acid production inhibition rate of AML12 cells cultured in the presence of 100 μM instant coffee was 19%, whereas the uric acid production inhibition rate of AML12 cells cultured in the presence of 100 μM coffee slag ethanol extract was 19%. The rate was 73.3%. From these results, it was found that the coffee ground ethanol extract significantly inhibits the production of uric acid level as compared with instant coffee.

[Example 2]
The effect of reducing the amount of uric acid produced by cafe oil tryptophan was investigated.
Specifically, instead of the coffee ground ethanol extract, caffe oil tryptophan (synthetic product by Sumika Chemical Analysis Service) was used as the sample, and the final concentration of each sample in the sample solution used for cell maintenance was 0 μM. The uric acid production inhibition rate in the liver-derived cultured cells was measured in the same manner as in Example 1 except that the values were 10 μM, 30 μM, and 100 μM.

The measurement results are shown in FIG. In the figure, each measured value indicates an average value ± standard error (n = 6). It shows that there is a statistically significant difference between the numbers with different alphabets. As shown in FIG. 1, a significant effect of reducing the amount of uric acid produced was observed in cells to which caffeoyl tryptophan was added at 10 μM or more.

[Example 3]
The effect of reducing the amount of uric acid produced by cafestol was investigated.
Specifically, instead of the coffee slag ethanol extract, cafestol (manufactured by Funakoshi Co., Ltd.) was used as the sample, and the final concentration of each sample in the sample solution used for cell maintenance was 0 μM, 10 μM, 30 μM, 100 μM. The uric acid production inhibition rate in the liver-derived cultured cells was measured in the same manner as in Example 1 except that.

The measurement results are shown in FIG. In the figure, each measured value indicates an average value ± standard error (n = 6). It shows that there is a statistically significant difference between the numbers with different alphabets. As shown in FIG. 2, in the cells to which 100 μM of cafestol was added, a significant effect of reducing the amount of uric acid produced was observed.

[Example 4]
The effect of the coffee ground ethanol extract prepared in Example 1 on reducing uric acid levels obtained by administration to animals was examined.

<Animal experiment>
Male ICR mice 4 weeks old (purchased from Charles River Laboratories, Japan) were preliminarily bred on a normal diet (product name: <CRF-1>, manufactured by Oriental Yeast Co., Ltd.) for 1 week. After that, the mice were divided into 5 groups as follows so that the average weight of each group was about the same, and subjected to the test: normal mouse group (8 animals / group), hyperuric acidemia model mouse. Group (10 animals / group), alloprinol group (8 animals / group), coffee slag ethanol extract low dose group (8 animals / group), and coffee slag ethanol extract high dose group (8 animals / group).

After the preliminary breeding, the mice were fasted for 4 hours, and the coffee slag ethanol extract suspended in a 0.5% (w / v) sodium carboxymethyl cellulose (CMC-Na, manufactured by Wako Pure Chemical Industries, Ltd.) solution was used. The low dose group was orally administered at 300 mg / kg body weight, and the high dose group was orally administered at 600 mg / kg body weight. To the allopurinol group, 10 mg of allopurinol suspended in a 0.5% (w / v) CMC-Na solution was orally administered per kg of body weight. Only 0.5% (w / v) CMC-Na solution was orally administered to the normal mouse group and the hyperuricemia model mouse group. Oral administration of the sample was performed 3 times a day for 3 consecutive days, and then 1 hour later (after administration on the 3rd day), guanosine 5'-monoline dissolved in PBS (-) in mice other than the normal mouse group. Both acid (GMP, manufactured by Tokyo Kasei Kogyo Co., Ltd.) and inosine 5'-monophosphate (IMP, manufactured by Tokyo Kasei Kogyo Co., Ltd.) were intraperitoneally administered at 300 mg / kg, respectively. Only PBS (-) was administered to the normal mouse group. One hour after the intraperitoneal administration, the mice were laparotomized under isoflurane (manufactured by Pfizer) anesthesia, and blood was collected from the inferior vena cava. The collected blood was allowed to stand on ice. The blood after standing was centrifuged at 5000 × g for 10 minutes at 4 ° C. to obtain a plasma sample.

The uric acid concentration (plasma uric acid concentration: mg / dL) of the obtained plasma sample was measured by using the uricase colorimetric method (product name: <uric acid C-testwaco>, manufactured by Wako Pure Chemical Industries, Ltd.). The measurement results are shown in FIG. In the figure, "Normal Control" shows the result of the normal mouse group, and "Model Control" shows the result of the hyperuricemia model mouse group. In addition, each measured value indicates an average value ± standard error. Numbers with an asterisk indicate that there is a statistically significant difference from the hyperuricemia model mouse group. As shown in FIG. 3, in the mice to which 600 mg / kg of coffee slag ethanol extract was administered (coffee slag ethanol extract high dose group), a significant effect of reducing the amount of uric acid produced was observed.

Claims (7)

A method for producing a composition having a uric acid level reducing action, which comprises eluting the coffee grounds into a solvent containing ethanol to prepare an extract containing a substance having a uric acid level reducing action. The method for producing a composition having a uric acid level reducing action according to claim 1, wherein the solvent containing ethanol is ethanol or a mixed solvent of ethanol and water. A composition having a uric acid level reducing action is produced by the method for producing a composition having a uric acid level reducing action according to claim 1 or 2.
A method for producing a drug having a uric acid level reducing action, which comprises producing a drug containing the composition as an active ingredient. The method for producing a drug having a uric acid level reducing action according to claim 3, wherein the drug is a therapeutic agent for gout or hyperuricemia. Café oil A uric acid level reducing agent containing tryptophan or cafestol as an active ingredient. Café oil A drug containing tryptophan or cafestol as an active ingredient. The drug according to claim 6, which is a therapeutic agent for gout or hyperuricemia.

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