JP7359415B2 - urease inhibitor - Google Patents

Description

The present invention relates to urease inhibitors.

Urease is an enzyme that hydrolyzes urea to decompose it into carbon dioxide and ammonia, and is widely present in microorganisms such as bacteria and filamentous fungi, seed plants such as beans, and animals. It is known that urease from intestinal bacteria decomposes urea in the intestine into ammonia, and its cytotoxicity deteriorates the intestinal flora and causes diarrhea. Helicobacter pylori (hereinafter referred to as "H. pylori"), a typical urease-producing bacterium, lives in the stomach by generating ammonia with its own urease and neutralizing gastric acid. Helicobacter pylori damages the gastric mucosa and is the main cause of diseases such as gastritis, gastric ulcer, duodenal ulcer, and gastric cancer. As a measure against Helicobacter pylori, the removal of Helicobacter pylori using antibiotics is being carried out, but suppression of the urease activity of Helicobacter pylori with drugs is also being carried out. By the way, the administration of antibiotics not only affects the resident bacteria and the natural intestinal flora of the person, but also poses problems such as an increase in bacteria resistant to antibiotics.

In addition, since the generation of ammonia and its odor can be suppressed by suppressing urease activity, it is expected that suppressing urease activity will prevent the odor of pets and livestock, and suppress bad breath or body odor.

There are many reports regarding the suppression of urease activity, that is, urease inhibitory activity, such as carbostyril derivatives, especially 2-(4-chlorobenzoylamino)-3-quinolon-4-yl)propionic acid or its salts. The use of a urease inhibitor containing as an active ingredient for the prevention and treatment of diseases such as gastric mucosal disorders and hyperammonemia has been disclosed (see Patent Document 1). Also, for example, urease inhibitors, ammonia odor suppressants, and diapers caused by ammonia containing one or more compounds selected from the group consisting of flavones, flavonols, dihydroflavonols, and catechins as active ingredients. An anti-rash agent (see Patent Document 2) has been disclosed.
As a urease inhibitor containing a plant extract as an active ingredient, for example, a composition for inhibiting urease characterized by containing a solvent extract of evening primrose, and food/drinks and drugs containing the composition are provided (Patent Document 3) A urease activity inhibitor (see Patent Document 4) is disclosed, which is characterized by containing an extract of a plant belonging to the Sapindaceae family, such as Ganoderma and rambutan.

On the other hand, regarding enzyme inhibitors containing caramel as an active ingredient, hyaluronidase inhibitors containing caramel color as an active ingredient and elastase inhibitors containing caramel color as an active ingredient have been disclosed, and they have anti-aging, anti-skin aging, anti-inflammatory, etc. For this purpose, the use of these enzyme inhibitors in beverages, foods, cosmetics, quasi-drugs, pharmaceuticals, etc. has been disclosed (see Patent Document 5). In addition, palatinose thermal decomposition product (6-(α-D-glucopyranosyloxy)-1,3,4-trihydroxyhex-5-ene-2- and 5-[(α-D-glucopyranosyloxy)methyl]-2-furancarboxaldehyde) as active ingredients, and food and beverages, oral compositions, and toiletries containing the deodorant. An invention related to a product (see Patent Document 6) has been disclosed.
However, it is not known that caramel has urease inhibitory activity.

Japanese Unexamined Patent Publication No. 7-101862 Japanese Patent Application Publication No. 2004-91338 Japanese Patent Application Publication No. 2005-104888 Japanese Patent Application Publication No. 2011-6333 Japanese Patent Application Publication No. 2013-139398 Japanese Patent Application Publication No. 2001-521

An object of the present invention is to provide a highly safe and excellent urease inhibitor.

As a result of intensive research focusing on highly safe substances, the present inventor discovered that caramel has excellent urease inhibitory activity, and completed the present invention.

That is, the present invention relates to the following items (1) to (5). Item (1)
A urease inhibitor characterized by containing caramel as an active ingredient.
Section (2)
The urease inhibitor according to item (1), wherein the K610 of the caramel is in the range of 0.0001 to 1.0.
Section (3)
The urease inhibitor according to item (1) or item (2), wherein the caramel is obtained by heat treating one or more of sugar, glucose, fructose, isomerized sugar, and starch syrup.
Section (4)
The urease inhibitor according to any one of items (1) to (3), wherein the caramel is caramel I.
Section (5)
The urease inhibitor according to any one of items (1) to (4), which is in the form of a beverage, food, cosmetic, quasi-drug or pharmaceutical product, or feed.

The urease inhibitor of the present invention has excellent enzyme inhibitory activity and is excellent in safety and stability. Therefore, it is effective as a beverage, food, cosmetic, quasi-drug, pharmaceutical, feed, etc., for example, for the purpose of inhibiting urease produced by microorganisms such as Helicobacter pylori, or for the purpose of deodorizing by suppressing the generation of ammonia. It can be used for

In the present invention, caramel is obtained by heat-treating edible carbohydrates. Caramel includes caramel as a food and caramel as a coloring agent (caramel pigment).
Caramel as a food includes, for example, pudding wrap (syrup), caramel for pudding, pudding sauce (registered trademark), caramel syrup, caramel sauce, roasted sugar syrup, caramel aroma, roasted sugar, caramelization (caramelization), scorched sugar syrup, It is called charred sugar, brown sugar, caramel flavor, burnt sugar, caramel, etc. It has a low coloring effect and is used as a food with a brown sugar flavor.
Caramel (caramel pigment) is used as a food additive, and its component specifications are listed in the Japanese Food Additives Official Standards.
For example, when sugars are heated, their original taste changes, with the sweetness, bitterness, and sourness fading away, creating the unique flavor of brown sugar. By adjusting the degree of heating, you can create caramel with a variety of flavors and colors, from food caramel such as the pudding wrap (syrup), caramel syrup, caramel sauce, and burnt sugar to caramel (caramel pigment) as a coloring agent. can be made. When the degree of heat treatment is increased, the sweetness disappears, and both bitterness and sourness become weaker. Generally, caramel (caramel pigment) as a coloring agent does not impair the taste of foods when used in normal amounts. As a food, caramel has a slight residual sweetness from sugars, a bitter, sour taste, and is yellow to brown in color. In addition to making use of these unique scorched sugar flavors, they can also be used to provide a hidden flavor, richness, body, water retention, flavor enhancement, etc.

In the present invention, edible carbohydrates include starch hydrolysates, sugars or reduced products thereof, and molasses.
Starch hydrolysates are obtained by hydrolyzing starches such as corn starch, wheat starch, potato starch, sweet potato starch, tapioca starch, and rice, and examples thereof include starch syrup, corn syrup, dextrin, and starch sugar.
Examples of saccharides include monosaccharides such as glucose and fructose, disaccharides such as sugar, lactose, maltose, and trehalose, oligosaccharides, polysaccharides, high-fructose isomerization, honey, maple sugar, and brown sugar. Examples of oligosaccharides include maltooligosaccharides, fructooligosaccharides, xylooligosaccharides, and the like. Examples of polysaccharides include starch, modified starch, indigestible dextrin, dextran, inulin, polydextrose, mannan, and the like. The reduced product is usually a sugar alcohol, and examples thereof include sorbitol, maltitol, reduced starch syrup, and the like.
Molasses is a byproduct of the sugar refining process and is the residual liquid after sucrose is separated.
In the present invention, the edible carbohydrate is preferably one or more of sugar, glucose, fructose, high-fructose sugar syrup, and starch syrup.

In the present invention, caramel (caramel color) as a coloring agent is preferably a caramel classified as caramel I from the viewpoint of urease inhibitory activity and from the viewpoint that there is no upper limit for usage based on ADI (acceptable daily intake). The FAO/WHO Joint Expert Committee on Food Additives (JECFA) considered that there is no need to set an ADI for Caramel I, and designated it as "not specified."
In the ingredient specifications of the 9th edition of the Food Additives Official Standards, caramel (caramel color) as a coloring agent is listed under the names Caramel I, Caramel II, Caramel III, and Caramel IV, and the definitions of each are as follows. be.
Caramel I
This product is obtained by heat-treating edible carbohydrates such as starch hydrolyzate, molasses, or sugar, or by heat-treating edible carbohydrates by adding acid or alkali, and does not contain sulfite compounds or ammonium compounds. It's something that doesn't exist.
Caramel II
This product is obtained by heat-treating edible carbohydrates such as starch hydrolyzate, molasses, or saccharides by adding sulfite compounds, or adding acids or alkalis to these, and does not contain ammonium compounds. be.
Caramel III
This product is obtained by heat-treating edible carbohydrates such as starch hydrolyzate, molasses, or saccharide by adding ammonium compounds or adding acids or alkalis to this, and does not contain sulfite compounds. be.
Caramel IV
This product is obtained by adding sulfite compounds and ammonium compounds to edible carbohydrates such as starch hydrolyzate, molasses, or saccharides, or adding acids or alkalis to these and heat-treating them.
In addition, the above component standards stipulate confirmation tests and purity tests for each caramel.

In the present invention, the heat treatment of edible carbohydrates can be performed under atmospheric pressure, increased pressure, or reduced pressure. The heat treatment may be performed at a temperature and for a time that allows caramel to be obtained. Usually, under atmospheric pressure and pressurization, the temperature is 100° C. to 300° C., and the heating time is in the range of reaching temperature or 0.01 minutes to 24 hours, and can be set arbitrarily. The temperature and time for the heat treatment can be appropriately set depending on the heating device, the desired degree of heating, or the absorbance of caramel, which will be described later.

In the present invention, the apparatus or method for heat-treating edible carbohydrates is not particularly limited, and examples include a pot, a flat pot, an open oven, an open roasting oven, a pressurized heating reaction vessel, an extruder, a convection oven, a drum dryer, etc. Examples include methods such as apparatus, reduced pressure heating, steam heating, hot air heating, microwave heating, infrared heating, high frequency heating, high frequency dielectric heating, superheated steam heating, etc., and can be appropriately selected and set.

In the present invention, K610 is the absorbance obtained by measuring a 0.1% aqueous solution of caramel at a wavelength of 610 nm using a 10 mm cell in terms of solid matter.
In the present invention, K610 of caramel is preferably in the range of 0.0001 to 2.0, more preferably in the range of 0.0001 to 1.0, even more preferably , in the range of 0.0001 to 0.6, particularly preferably in the range of 0.0001 to 0.3, even more preferably in the range of 0.0005 to 0.2. In addition, according to the caramel color standard listed in the 11th edition of the Food Chemicals Codex (Food Chemicals Codex) in the United States, color strength A610 is defined as the color strength of a 0.1% aqueous solution at a wavelength of 610 nm and a 10 mm cell. A value of 0.01 to 2.0 is specified as the solid matter absorbance value.

Furthermore, in the present invention, the DE of the caramel is preferably in the range of 1 to 99, more preferably in the range of 5 to 95, even more preferably in the range of 10 to 80, from the viewpoint of urease inhibitory activity. , particularly preferably in the range from 20 to 80. Edible carbohydrates in caramel are decomposed by heat treatment, but the residual sugar content is directly measured as DE (%), which is reducing sugar, using measuring methods such as the Rijn-Einon method, Bertrand method, Willstetter-Schudel method, and HPLC method. be able to. In the present invention, the method for measuring DE of caramel is preferably the Bertrand method.

As shown in the Examples below, caramel has excellent urease inhibitory activity. Urease from intestinal bacteria hydrolyzes urea to produce ammonia, and its cytotoxicity in the intestines causes deterioration of intestinal flora and diarrhea. Furthermore, Helicobacter pylori, which lives in the stomach by producing ammonia through urease, damages the gastric mucosa and causes gastritis, gastric ulcer, duodenal ulcer, gastric cancer, and the like. Furthermore, the generation of ammonia by urease causes skin irritation (diaper rash, etc.) and odor.
Therefore, the urease inhibitor of the present invention can prevent, improve, or treat diseases and symptoms caused by urease and generated ammonia by inhibiting urease produced by microorganisms such as Helicobacter pylori. Suitably, it can be used to protect gastric mucosa, prevent diaper rash, suppress ammonia odor, prevent odor from pets and livestock, and suppress bad breath and body odor.

The urease inhibitor of the present invention only needs to contain at least caramel as an active ingredient. Moreover, the urease inhibitor of the present invention may be in the form of a mixture of caramel and other components. Such ingredients include those that do not impair the effects of the urease inhibitor of the present invention and have favorable effects on the processing and functions of beverages, foods, cosmetics, quasi-drugs, pharmaceuticals, feeds, etc. things can be used.
In the urease inhibitor of the present invention, the amount and concentration of caramel, which is an active ingredient, may be determined as appropriate based on the desired effect, method of use, etc.

The urease inhibitor of the present invention may be in the form of a solid, semi-solid, or liquid at room temperature (25°C), for example, a solution, powder, granule, paste, or emulsion.
Further, the urease inhibitor of the present invention may be in the form of a drink, food, cosmetic, quasi-drug or pharmaceutical product, or feed.
The form of the drink or food may be arbitrary, such as soft drinks, alcoholic drinks, milk drinks, health drinks, pickles, soy sauce, sauces, miso, fresh sweets, sweets, dessert foods, dairy products, processed foods, seasonings, and so-called Examples include health foods, foods for specified health uses, foods with functional claims, nutritional supplements, etc., and any of them may be used.
In addition to caramel, vitamins, animal and plant extracts, functional ingredients such as antioxidant ingredients, physiologically active substances, or other known urease-inhibiting ingredients can be appropriately blended into these beverages or foods.

Cosmetics can be in any form, including emulsions, creams, lotions, serums, packs, cleaning products, makeup cosmetics, dispersions, ointments, liquids, aerosols, patches, plasters, poultices, and liniments. , skin cleansers, deodorants, etc., and any of them may be used.
In addition to caramel, cosmetics include oils and fats such as vegetable oils, waxes such as lanolin and beeswax, plant extracts, hydrocarbons, fatty acids, higher alcohols, esters, various surfactants, pigments, fragrances, and vitamins. Those commonly used as raw materials for cosmetics can be suitably blended and used, such as animals, animal extracts, antioxidants, preservatives and bactericidal agents. Furthermore, the effect can be enhanced by using other components known to have a deodorizing effect.

The form of quasi-drugs or pharmaceuticals can be arbitrary; for example, oral administration in the form of tablets, capsules, granules, powders, troches, syrups, etc.; injections, suppositories, inhalants, transdermal absorption agents, etc. Parenteral administration using external preparations and the like may be mentioned, and either method may be used.
In addition to caramel, quasi-drugs or pharmaceuticals include excipients, binders, disintegrants, lubricants, solvents, solubilizing agents, suspending agents, isotonic agents, pH adjusters/buffers, Pharmaceutically acceptable carriers such as preservatives, antioxidants, coloring agents, flavoring/fragrant agents, and stabilizers can be appropriately blended and used.

The form of the feed is arbitrary, and includes, for example, livestock feed for cows, pigs, chickens, sheep, horses, etc., small animal feed for rabbits, rats, mice, etc., pet food for dogs, cats, small birds, etc. can be mentioned, and any of them may be used.
In addition to caramel, feed includes meat, protein, grains, bran, lees, sugars, vegetables, vitamins, minerals, gelling agents, preservatives, pH adjusters, seasonings, preservatives, and nutrients. Other feed materials such as reinforcing agents can be appropriately mixed and used.

When the urease inhibitor of the present invention is used as a beverage, food, cosmetic, quasi-drug or pharmaceutical product, feed, etc., the amount of caramel to be added to these should be determined by taking into account its purity, dosage form, etc. It may be determined based on the IC ₅₀ of the urease inhibitory activity of caramel, but is usually 0.001 to 100% by mass, preferably 0.001 to 50% by mass, more preferably 0.01 to 20% by mass of the total amount. , particularly preferably from 0.05 to 10% by weight.

When administering the urease inhibitor of the present invention to a living organism (human or non-human animal), the amount is:
Although it may vary according to the subject's condition, weight, sex, age, or other factors, there are no particular restrictions on caramel I among caramel as a food and caramel as a coloring agent (caramel color), and Regarding caramel color, it is preferable to limit the amount to 12 grams per day per adult (60 kg) in consideration of ADI (acceptable daily intake). In the present invention, it is preferable to divide the amount into one to multiple times a day and administer or ingest it repeatedly and continuously for one or more days. For ingestion, a product containing the urease inhibitor of the present invention may be ingested, or the caramel itself, which is the urease inhibitor of the present invention, may be ingested directly.
Furthermore, when the urease inhibitor of the present invention is used in a non-living body, the amount used may vary depending on the form of use, but is usually 0.001 to 100% by mass, preferably 0.001 to 100% by mass based on the total amount of the subject. 50% by weight, more preferably 0.01-20% by weight, particularly preferably 0.05-10% by weight.

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to examples, but the present invention is not limited to the following examples. In addition, in the present invention, all the blending percentages of each raw material and raw material are mass %.

A urease inhibitor containing caramel as an active ingredient, which is a product of the present invention, was obtained as follows. Then, using these as samples, urease inhibitory activity was measured.

Urease inhibitor (test product No. 1): Pudding syrup was obtained by heating sugar at 160°C. When its absorbance was measured, the K610 was 0.001 and the solid content DE was 72.
Urease inhibitor (test product No. 2): Caramel syrup was obtained by heating sugar at 190°C. When its absorbance was measured, the K610 was 0.005 and the solid content DE was 46.
Urease inhibitor (test product No. 3): Burnt sugar was obtained by heating sugar at 210°C. When its absorbance was measured, the K610 was 0.008 and the solid content DE was 41.
Urease inhibitor (test product No. 4): Burnt sugar was obtained by heating glucose at 140° C. for 3 hours. When its absorbance was measured, the K610 was 0.007 and the solid content DE was 45.
Urease inhibitor (test product No. 5): Burnt sugar was obtained by heating starch syrup at 140° C. for 4 hours. When its absorbance was measured, the K610 was 0.008 and the solid content DE was 54.
Urease inhibitor (test product No. 6): Burnt sugar was obtained by heat-treating isomerized sugar containing 42% fructose at 130° C. for 2 hours. When its absorbance was measured, the K610 was 0.008 and the solid content DE was 59.
Urease inhibitor (test product No. 7): Burnt sugar was obtained by mixing glucose and fructose at a ratio of 1:1 and heating the mixture at 130° C. for 2 hours. When its absorbance was measured, the K610 was 0.009 and the solid content DE was 55.
Urease inhibitor (test product No. 8): When the absorbance of the caramel color obtained by heating sugar was measured, the K610 was 0.015 and the solid content DE was 58.
Urease inhibitor (test product No. 9): When the absorbance of the caramel color obtained by heat-treating sugar was measured, the K610 was 0.060 and the solid content DE was 16.
Urease inhibitor (test product No. 10): When the absorbance of the caramel color obtained by heat treating sugar was measured, the K610 was 0.101 and the solid content DE was 14.

Urease inhibitor test product No. 8, No. 9 and no. When No. 10 was tested according to the definition and confirmation test for caramel listed in the 9th edition of the Food Additives Official Standards, they were classified as caramel I.

[Measurement of urease inhibitory activity]
Urease inhibitory activity was measured by the following method.
40 μL of samples at various concentrations were added to 40 μL of a nata bean-derived urease solution (0.8 U/mL, dissolved in 100 mM phosphate buffer (pH 6.9)) and left at 37° C. for 15 minutes. Subsequently, 80 μL of a 60 mM substrate urea solution (dissolved in the phosphate buffer) was added, and the mixture was allowed to stand at 37° C. for 15 minutes, and then 40 μL of 1N sulfuric acid was added to stop the reaction. 1 mL of solution A and 1 mL of solution B were added to the obtained reaction solution, and after standing at 65° C. for 20 minutes, the absorbance (A) at 630 nm was measured. The same enzyme reaction and absorbance measurement as above were carried out by adding the phosphate buffer solution instead of the sample solution, and the absorbance (C) was measured. Absorbance (B) and (D) were measured in the same manner as above and in each case by adding the phosphate buffer without adding enzyme. All reagents were manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.
Solution A: 5.0 g of phenol and 25 mg of sodium nitroprusside were dissolved in 500 ml of distilled water.
Solution B: Dissolve 2.2 g of disodium hydrogen phosphate and 2.5 g of sodium hydroxide in 300 mL of distilled water, add 3.0 mL of sodium hypochlorite with 10% or more available chlorine, and make up to 500 mL with distilled water. .
The samples were dissolved in the phosphate buffer, respectively, to give final concentrations of 0.5 mg/mL, 0.25 mg/mL, and 0.05 mg/mL in terms of solid matter.
The inhibition rate (%) was calculated using the following formula, and the results are shown in Table 1. The 50% inhibitory concentration (IC ₅₀ ) was determined from each inhibition curve, and the results are shown in Table 2.

Urease inhibition rate (%) = 100-100×[(AB)/(CD)]

A: Absorbance when sample solution is added, enzyme solution added B: Absorbance when sample solution is added, enzyme solution is not added C: Absorbance when sample solution is not added, enzyme solution is added D: Absorbance when sample solution is not added, enzyme solution is not added absorbance of

表中の数字は、ウレアーゼ阻害率（％）を示す。

The numbers in the table indicate the urease inhibition rate (%).

As shown in Table 1, the urease inhibition rate in terms of solid concentration according to the present invention was 45 to 95% at 0.5 (mg/mL) (500 ppm), indicating that it acts effectively. In particular, test item No. 1~No. 8 had a remarkable inhibitory activity of 69 to 95%, and even at 0.25 (mg/mL) (250 ppm) it was 56 to 89%.

As shown in Table 2, the IC ₅₀ (50% inhibition rate) of the urease inhibitor according to the present invention is 0.01 to 0.55 mg/mL (10 to 550 ppm), indicating that it has effective urease inhibitory activity in a small amount. Indicated. In particular, No. 1~No. 8 showed significant inhibitory activity at 0.01 to 0.16 mg/mL (10 to 160 ppm). When using the test article, for example, the amount used is usually 0.05% (500 ppm) to 5% (50,000 ppm), and in this case, effective urease inhibitory activity can be obtained. Therefore, the urease inhibitor of the present invention can be effectively used as drinks, foods, cosmetics, quasi-drugs or medicines, feeds, and the like.

Examples of using the urease inhibitor of the present invention as beverages, foods, quasi-drugs, and cosmetics are shown below.

[Formulation example 1]
A soft drink was produced by a conventional method using the following formulation example. By consuming this beverage, you can expect to suppress Helicobacter pylori and bad breath.
Stevia (High Stevia RA-700M
(manufactured by Ikeda Toka Kogyo Co., Ltd.) 0.018g
Erythritol 2.0g
Ascorbic acid 0.1g
Sodium ascorbate 0.04g
Fragrance Appropriate amount Invention product (test product No. 4) 1.0g
97mL water

[Formulation example 2]
A custard pudding was produced by a conventional method using the following formulation example. By eating this pudding, you can expect to suppress Helicobacter pylori and bad breath.
110g milk
40g whole egg
25g sugar
Vanilla fragrance Appropriate amount Invention product (test product No. 1) 4g

[Formulation example 3]
A pound cake was manufactured by a conventional method using the following formulation example. This cake has a rich flavor with a scorched sugar feel, and at the same time can be expected to suppress Helicobacter pylori and bad breath.
100g whole egg
50g sugar
30g salad oil
100g wheat flour (soft flour)
20g milk
baking powder 4g
salt 0.08g
Invention product (test product No. 6) 5g

[Formulation example 4]
Candies were manufactured in a conventional manner using the following formulation examples. This candy has a rich flavor with a burnt sugar taste, and is also expected to suppress Helicobacter pylori and bad breath.
300g sugar
250g starch syrup
Coffee extract appropriate amount Flavoring agent appropriate amount Invention product (test product No. 3) 5g

[Formulation example 5]
Gums were prepared in a conventional manner using the following formulation examples. This gum has a rich flavor with a scorched sugar taste, and is also expected to suppress Helicobacter pylori and bad breath.
Gum base 20g
45g sugar
Glucose 21g
10g starch syrup
Fragrance Appropriate amount Invention product (test product No. 2) 3g

[Formulation example 6]
500 mg of the product of the present invention (test product No. 7) was filled into gelatin capsules, and the cap portion was joined to prepare capsules for use as foods for suppressing Helicobacter pylori and suppressing bad breath.

[Formulation example 7]
60 parts by mass of dextrin was blended with 100 parts by mass of the product of the present invention (test product No. 5 (solid content 75%)), powdered using a spray dryer, then granulated according to the following formulation example, and then tableted. A health food was obtained in the form of tablets each weighing 1 g.
Test item No. 5. Spray dryer powder product 350g
Lactose 470g
Crystalline cellulose 140g
Hydroxypropylcellulose 30g
Magnesium stearate 1g
Talc 9g

[Formulation example 8]
A quasi-drug mouthwash was manufactured by a conventional method using the following formulation example.
(components and mass%)
Ethanol 18.0
Sodium lauryl sulfate 1.0
Glycerin 8.0
Sorbitol 7.0
Sodium citrate 0.5
Invention product (test product No. 6) 2.0
Fragrance Appropriate amount Water 63.5

[Formulation example 9]
A lotion was manufactured by a conventional method using the following formulation example.
(components and mass%)
Glycerin 5.0
Oleyl alcohol 0.1
Polyoxyethylene (20)
Sorbitan monolauryl phosphate 0.3
Invention product (test product No. 8) 0.5
Ethyl alcohol 10.0
Fragrance Appropriate amount Purified water 83.7

[Formulation example 10]
An O/W type cream was manufactured by a conventional method using the following formulation example.
(components and mass%)
Invention product (test product No. 9) 0.5
Stearyl alcohol 6.0
Stearic acid 2.0
Hydrogenated lanolin 4.0
Squalane 9.0
Octyldodecanol 10.0
1,3-butylene glycol 6.0
PEG1500 4.0
Polyexyethylene (25)
Cetyl alcohol ether 3.0
Glyceryl monostearate 2.0
Preservative: Appropriate amount Antioxidant: Appropriate amount Flavor: Appropriate amount Purified water 53.5

Claims (5)

A urease inhibitor containing caramel as an active ingredient, wherein the K610 of caramel is in the range of 0.0005 to 0.015 . A urease inhibitor containing caramel as an active ingredient, characterized in that the caramel has a DE of 20 to 80. The urease inhibitor according to claim 1 or 2, wherein the caramel is a heat-treated product of one or more edible carbohydrates selected from sugar, glucose, fructose, high fructose sugar, and starch syrup. The urease inhibitor according to any one of claims 1 to 3, wherein the caramel is caramel I. The urease inhibitor according to any one of claims 1 to 4, which is in the form of a drink, food, cosmetic, quasi-drug or pharmaceutical product, or feed.