JP6719475B2 - Urease activity inhibitor - Google Patents

Description

The present invention relates to a urease activity inhibitor. More specifically, a urease activity inhibitor containing a cyclic dipeptide as an active ingredient, a gastric mucosa protective agent, a urinary stone formation inhibitor, an ammonia odor inhibitor, a diaper rash inhibitor, a livestock deodorant, a halitosis or body odor inhibitor, and , A composition containing these agents, and a function exerted by using the cyclic dipeptide.

Urease produced by various bacteria including Pseudomonas aeruginosa, Spirochaeta, and Helicobacter pylori, which live in the gastric mucosa, is known to be resident in the oral cavity. And produce ammonia. Especially for Helicobacter pylori, urease produced by the bacterium produces ammonia in the gastric mucosa, which damages the gastric mucosa and neutralizes gastric acid to create an environment favorable for the survival of the bacterium. There are reports that it is associated with the development of gastric ulcer, duodenal ulcer, and chronic urticaria.

On the other hand, in the treatment of diseases caused by Helicobacter pylori, such as gastric ulcer and duodenal ulcer, sterilization using an antibiotic and treatment using a proton pump inhibitor are generally performed. However, with regard to antibiotics, a reduction in the eradication rate was observed due to the emergence of resistant bacteria, and with proton pump inhibitors, when the gastric wall was weakened, gastric ulcers could be induced, and reflux esophagitis could be caused. The existence of side effects has become a problem.

In addition, urea contained in human or livestock excrement reacts with urease to generate ammonia and give off a foul odor, or the pH of stool is increased by the stimulation or ammonia generated by ammonia itself, and enzymes such as lipase. It is known that the increased activity induces skin inflammation (for example, diaper rash) and diarrhea, which poses a problem in the fields of livestock, the environment, and health. In recent years, the control of bad breath and body odor caused by ammonia has been increasing in interest.

Furthermore, in urolithiasis associated with urinary tract infection, it is known that urinary calculi are formed by infection with Proteus mirabilis which is a urease-producing bacterium.

Therefore, conventionally, urease activity inhibitors were used to suppress the activity of urease, suppress the generation of ammonia, suppress the onset or progression of gastric ulcer, duodenal ulcer, urolithiasis, suppress the smell of ammonia caused by excrement, and diapers. It is being studied to prevent rashes, deodorize livestock, and control bad breath and body odor.

For example, as a technique applied to diapers and the like, in Patent Document 1, a hydroxamic acid compound having a strong anti-urease action and a cationic surfactant are used in combination to provide an excellent ammonia suppressing effect and a softening effect. It is stated that diapers can be obtained. Here, as the hydroxamic acid compound, a commercially available animal drug is used.

Patent Document 2 reports that a chlorogenic acid derivative contained in an extract of coffee or Citrus serrata has a urease inhibitory action and is used for an antiperspirant or an antidiaper rash composition. In Patent Document 3, an extract of luscus, guava, maikai, rubus, mugwort, tamarind, yukinoshita, loquat, or persimmon has an inhibitory effect on urease activity, and is useful for preventing foul odors from feces and diaper rash. Is described. It is speculated that the main body of these agents may be polyphenolic compounds.

In Patent Document 4, flavones, flavonols, dihydroflavonols, and catechins have a strong urease activity-inhibiting effect. These are olives (Olea europaea), parsley (Petroselinum sativum), Scutellaria baicalensis, It is disclosed that the extract can be extracted from oleracea (Reseda luteola), honeysuckle (Lonicera japonica), yellow mullet (Engelhardtia chrysolepis), wisteria tea (Ampelopsis grossedentata), tea (Thea sinensis), white whale (Quercus salicina) and the like. Then, examples in which these compounds are contained in diapers, wipes for wipes, hygiene sheets, and wet tissues are disclosed.

In addition to the above-mentioned applications, in Patent Document 5, a fatty acid, which is a methanol extract of konjac fly powder generated during milling of konjac potato, has a urease activity inhibitory effect, and the longer the carbon chain length of the fatty acid is, the urease activity is increased. It is described that the inhibitory effect also becomes stronger. It has been shown that the urease activity inhibitor produced from this konjac fly powder can be used as a fertilizer, a soil conditioner, or as a constituent element of a catheter that can be used for treating urinary tract infections.

In Patent Document 6, pectin and pectic acid contained in fruit juices of tomato, lemon, apple or extracts thereof have urease activity inhibitory effect and are used for treatment or prevention of gastric ulcer, duodenal ulcer, gastric cancer, gastritis and the like. It is disclosed.

Further, in Patent Document 7, an extract obtained by extracting cinnamon leaves with a water-methanol mixed solution at 40°C to 90°C has a urease activity inhibitory effect and is used as a feed for deodorizing animal manure odor. It has been reported.

As other substances having an inhibitory effect on urease activity, plant-based unused resources such as buckwheat hulls, cowpea hulls and broccoli bases have been reported (see Non-Patent Document 1).

JP-A-58-104276 JP, 6-183989, A JP-A-8-19595 Japanese Patent No. 4450355 JP, 2011-63571, A JP2012-6889A JP 2001-258480 A

Proceedings of 2009 Annual Meeting of the Japanese Society of Agricultural Chemistry: 227-2009

A "dipeptide" in which two amino acids are linked has been attracting attention as a functional substance. Dipeptides can add physical properties and new functions not present in a single amino acid, and are expected to have a range of applications beyond amino acids. Among them, diketopiperazine, which is a cyclic dipeptide, is known to have various physiological activities, and various studies have been conducted.

However, it is not yet known whether or not the cyclic dipeptide can be used as an inhibitor of urease activity.

The subject of the present invention is a urease activity inhibitor containing a cyclic dipeptide as an active ingredient, a gastric mucosa protective agent, a urinary stone formation inhibitor, an ammonia odor inhibitor, a diaper rash inhibitor, a livestock deodorant, a halitosis or body odor inhibitor. And to provide a composition containing these agents and a function exerted by using the cyclic dipeptide.

The present invention relates to the following [1] to [11].
[1] A urease activity inhibitor containing a cyclic dipeptide or a salt thereof as an active ingredient.
[2] A gastric mucosa protective agent containing a cyclic dipeptide or a salt thereof as an active ingredient.
[3] A urolithiasis inhibitor containing a cyclic dipeptide or a salt thereof as an active ingredient.
[4] An ammonia odor inhibitor containing a cyclic dipeptide or a salt thereof as an active ingredient.
[5] A diaper rash preventing agent comprising a cyclic dipeptide or a salt thereof as an active ingredient.
[6] A livestock deodorant containing a cyclic dipeptide or a salt thereof as an active ingredient.
[7] A halitosis or body odor inhibitor containing a cyclic dipeptide or a salt thereof as an active ingredient.
[8] The urease activity inhibitor according to [1], the gastric mucosa protective agent according to [2], the urinary tract stone formation inhibitor according to [3], the ammonia odor inhibitor according to [4], A composition comprising the diaper rash inhibitor according to [5], the livestock deodorant according to [6] above, or the breath or body odor suppressor according to [7] above.
[9] A method for suppressing ammonia odor, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient.
[10] A method for suppressing odor of livestock, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient.
[11] A method for suppressing halitosis or body odor, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient.

Urease activity inhibitor of the present invention, since the cyclic dipeptide as an active ingredient has resistance to the action of various peptide degrading enzymes secreted in the digestive tract, without being decomposed in the stomach or duodenal lumen, It can exert an excellent urease activity inhibitory effect in the duodenum, gastric mucosa, urine and the like. As a result, a gastric mucosa protecting action, a urinary tract stone formation inhibiting action, an ammonia odor inhibiting action, a diaper rash preventing action, a deodorizing action for livestock, a bad breath or body odor inhibiting action, etc. can be brought about. Further, it is applicable not only to humans but also to pets such as dogs and cats and domestic animals for the purpose of suppressing urinary stone formation and deodorization.

The urease activity inhibitor of the present invention contains a cyclic dipeptide or a salt thereof as an active ingredient. Hereinafter, the cyclic dipeptide or a salt thereof used to inhibit urease activity may be collectively referred to as the cyclic dipeptide of the present invention. As a result of comprehensive analysis of cyclic dipeptides composed of a combination of natural amino acids, the present inventors have found for the first time that cyclic dipeptides have urease activity inhibitory activity. It is speculated that the reason why such an effect is exhibited is that the cyclic dipeptide of the present invention approaches the active site of urease and inhibits the activity of urease. In addition, since the cyclic dipeptide is characterized by being less likely to be decomposed by peptidase and the like, it is considered that the effect that urease activity in the digestive tract can be sufficiently inhibited is also exhibited. However, these speculations do not limit the present invention. In the present invention, “inhibiting urease activity” means that urease inhibits the reaction of hydrolyzing urea to produce carbon dioxide and ammonia.

Examples of the cyclic dipeptide of the present invention include cyclotryptophanylproline [Cyclo(Trp-Pro)], cycloarginylphenylalanine [Cyclo(Arg-Phe)], cycloisoleucyl leucine [Cyclo(Ile-Leu)]. , Cycloglutamyllysine [Cyclo(Glu-Lys)], cyclomethionylserine [Cyclo(Met-Ser)], cycloarginyl glutamic acid [Cyclo(Arg-Glu)], cycloasparaginyl asparagine [Cyclo(Asn-Asn] )], cycloglutaminyl glutamine [Cyclo(Gln-Gln)], cycloglutamylglutamic acid [Cyclo(Glu-Glu)], and the like. You may use these individually by 1 type or in combination of 2 or more types. In the present specification, as long as the amino acid composition in the cyclic dipeptide is the same, the order in which they are described may be any, for example, Cyclo(Trp-Pro) and Cyclo(Pro-Trp) are the same cyclic dipeptide. It is.

In the present specification, a salt of a cyclic dipeptide refers to any pharmacologically acceptable salt of the cyclic dipeptide (including an inorganic salt and an organic salt), for example, a sodium salt of the cyclic dipeptide, a potassium salt, Calcium salt, magnesium salt, ammonium salt, hydrochloride, sulfate, nitrate, phosphate, organic acid salt (acetate, citrate, maleate, malate, oxalate, lactate, succinate, Fumarate, propionate, formate, benzoate, picrate, benzenesulfonate, trifluoroacetate, etc.) and the like.

The cyclic dipeptide of the present invention can be prepared according to methods known in the art. For example, it may be produced by a chemical synthesis method, an enzymatic method or a microbial fermentation method, or may be synthesized by subjecting a linear peptide to a dehydration/cyclization reaction. For example, a heat-treated product obtained by heat-treating a plant-derived component and/or an animal-derived component containing a linear dipeptide, tripeptide, or oligopeptide can be preferably used.

The plant-derived component is not particularly limited as long as it contains a linear dipeptide, tripeptide, or oligopeptide. Specific examples thereof include extracts of one or more plants selected from the group consisting of soybean, malt, barley, wheat, flower, and tea. In the present specification, barley malt may be simply referred to as malt. Since these are derived from food materials, they are considered to have high biosafety. Note that there is no limitation on the place of origin or variety of the plant used, and the part used for extraction is also not particularly limited. As the extraction method, a known method can be used, and the extract may contain a linear dipeptide, tripeptide, or oligopeptide by a known method such as enzyme treatment or heat treatment. Moreover, a commercial item can be used.

The animal-derived component is not particularly limited as long as it contains a linear dipeptide, tripeptide, or oligopeptide. Specific examples thereof include one or more selected from the group consisting of collagen, albumin, casein, placenta, and globulin, and among them, collagen is preferable. These origin animals are also not particularly limited. These animal components may be prepared according to known techniques, or commercially available products may be used.

Examples of the method for heat-treating the plant-derived component and/or animal-derived component containing the linear dipeptide, tripeptide, or oligopeptide include a method of heating these components in a solution or a solid phase.

The medium of the solution used in the heat treatment includes water, an organic solvent, and a mixture thereof. Examples of the organic solvent include ethanol and hexane. The mixing ratio when mixing with water is not particularly limited.

The pH of the solution during the heat treatment and the concentration of the raw material used for heating are not particularly limited, and can be appropriately set according to the type of medium as long as the heating can be performed.

The heating temperature is not generally set depending on the type of raw material or medium used for heating, but is 100 to 170° C. for both heating in a solution and heating in a solid phase. 110-150 degreeC is preferable. The heating time can be appropriately set depending on the heating temperature, and is, for example, 0.25 to 10 hours.

For example, when a soybean extract is used as a plant-derived component, the soybean peptide is prepared in an aqueous solution having an arbitrary concentration and then heated at 100 to 170° C. for about 0.25 to 10 hours to contain a cyclic dipeptide. Material is obtained. When such a material is liquid, the content of cyclic dipetide or its salt per Brix in the liquid is 0.2 to 1.0 ppm/Brix, Cyclo(Arg-Phe) for Cyclo(Trp-Pro). 10-50 ppm/Brix, Cyclo(Ile-Leu) 2.0-10 ppm/Brix, Cyclo(Gln-Gln) 1.0-5.0 ppm/Brix, Cyclo(Glu-Glu) 20-100 ppm/Brix Is. In the present specification, "amount per Brix" means an amount determined by a value corresponding to a mass percentage of a sucrose solution (aqueous solution containing only sucrose as a solute) at 20°C. Unless otherwise specified, "ppm" used in the present specification means ppm of weight/volume (w/v), and 1.0 ppm/Brix is 0.1 mg/in the case where the specific gravity of the solvent is 1. It is converted into mL and converted into 0.01% by weight. The content (w/w%) of cyclic dipetide or a salt thereof can be measured by, for example, an HPLC method, and the content of cyclic dipetide or a salt thereof per Brix can be measured, for example, by using an HPLC or a saccharimeter. Can be measured.

When a tea leaf extract is used as a plant-derived component, a tea-derived low-molecular peptide obtained by subjecting a tea (including tea leaves and tea leaves) extract to an enzyme treatment or a heat treatment to lower the protein molecular weight. Is prepared in an aqueous solution having an arbitrary concentration and then heated at 100 to 170° C. for about 0.25 to 10 hours to obtain a material containing a cyclic dipeptide. When such a material is liquid, the content of cyclic dipetide or its salt per Brix in the liquid is 0.2 to 1.0 ppm/Brix, Cyclo(Arg-Phe) for Cyclo(Trp-Pro). 2.0-10 ppm/Brix, Cyclo(Ile-Leu) 2.0-10 ppm/Brix, Cyclo(Gln-Gln) 1.0-5.0 ppm/Brix, Cyclo(Glu-Glu) 10-50 ppm /Brix.

When using a malt extract as a plant-derived component, the malt-derived low-molecular peptide obtained by subjecting the extract obtained from the malt or a crushed product thereof to enzymatic treatment or heat treatment to reduce the molecular weight of the protein is optional. After being prepared into an aqueous solution having the above concentration, the material containing the cyclic dipeptide is obtained by heating at 100 to 170° C. for about 0.25 to 10 hours. When such a material is liquid, the content of cyclic dipetide or its salt per Brix in the liquid is 0.2 to 1.0 ppm/Brix, Cyclo(Arg-Phe) for Cyclo(Trp-Pro). 2.0-10 ppm/Brix, Cyclo(Ile-Leu) 2.0-10 ppm/Brix, Cyclo(Glu-Lys) 5-50 ppm/Brix, Cyclo(Gln-Gln) 1.0-10 ppm/Brix , Cyclo(Glu-Glu) is 5 to 50 ppm/Brix.

When collagen is used as the animal-derived component, a commercially available collagen peptide is prepared in an aqueous solution having an arbitrary concentration and then heated at 100 to 170° C. for about 0.25 to 10 hours to obtain a material containing a cyclic dipeptide. When such a material is liquid, the content of cyclic dipetide or salt thereof per Brix in the liquid is 10 to 50 ppm/Brix for Cyclo(Arg-Glu) and 1.0 to Cyclo(Glu-Glu). It is 5.0 ppm/Brix.

Thus, a urease activity inhibitor containing the cyclic dipeptide of the present invention is obtained. The total content of the cyclic dipeptide of the present invention in the urease activity inhibitor of the present invention is not particularly limited and is usually about 0.1 to 100 w/w%.

The obtained urease activity inhibitor of the present invention is treated with one or more selected from the group consisting of filtration, centrifugation, concentration, ultrafiltration, freeze-drying, pulverization, and fractionation. May be prepared according to a known method, or may be directly formulated or prepared into a form that can be used as a raw material such as pharmaceuticals, quasi drugs, cosmetics, hygiene products, daily necessities, clothes, cleaning products, or feed. May be. Therefore, the treated product is included as one embodiment of the urease activity inhibitor of the present invention.

Further, since the cyclic dipeptide of the present invention inhibits the activity of urease and suppresses the production of ammonia, the urease activity inhibitor of the present invention is suitably used for applications where it is expected to suppress the generation of ammonia. There are no particular limitations on the use for which the suppression of the generation of ammonia is expected, as long as the effect is suppressed by suppressing the generation of ammonia. Specifically, for example, it is preferably used in anticipation of gastric mucosa protective action, urinary calculus formation inhibiting action, ammonia odor inhibiting action, diaper rash preventing action, deodorizing action for livestock, and bad breath or body odor inhibiting action. Therefore, as another aspect of the urease activity inhibitor of the present invention, the cyclic dipeptide of the present invention or a salt thereof as an active ingredient, a gastric mucosa protective agent, a urinary calculus formation inhibitor, an ammonia odor inhibitor, a diaper rash inhibitor, A deodorant for livestock, or a breath odor or body odor suppressor. Regarding the cyclic dipeptides or salts thereof contained in these agents, the amounts thereof used, and the shapes and forms of the agents, the section of the urease activity inhibitor of the present invention can be referred to.

Furthermore, the urease activity inhibitor of the present invention is preferably used for prevention or treatment of diseases caused by urease-producing microorganisms. As urease-producing microorganisms, Helicobacter pylori, Pseudomonas aeruginosa, spirochete, Proteus mirabilis, etc. are known, for example, Helicobacter pylori survives in the gastric mucosa to produce urease, and produced by urease. The resulting ammonia damages the gastric mucosa and induces gastric and duodenal ulcers. Therefore, it is considered that by inhibiting the activity of urease with the cyclic dipeptide of the present invention or a salt thereof, it is possible to prevent or treat the diseases caused by the urease-producing microorganism. In the present specification, examples of diseases caused by urease-producing microorganisms include gastric ulcer, duodenal ulcer, chronic gastritis, gastric cancer, urinary calculi and the like.

The cyclic dipeptide of the present invention or its salt used for the prevention or treatment of a disease caused by a urease-producing microorganism may be used in an amount such that the desired effect of the present invention can be obtained. The form, the method of administration, the purpose of use, and the age, body weight, and symptom of the patient to whom the agent is administered are appropriately set and are not constant. For example, in the case of oral ingestion, the dose is usually about 100 μg to 1 g/day for an adult body weight of about 50 kg. The administration may be performed within a desired dose range, in a single dose, or in several doses. The administration period is also arbitrary.

The present invention also comprises a urease activity inhibitor of the present invention, a gastric mucosa protective agent, a urinary stone formation inhibitor, an ammonia odor inhibitor, a diaper rash inhibitor, a livestock deodorant, or a composition containing a bad breath or body odor inhibitor. Provide things. Since these compositions contain the cyclic dipeptide of the present invention or a salt thereof, they have a urease activity-inhibiting action, and by suppressing ammonia generation based on the action, they have a gastric mucosa-protecting action and a urinary tract. Calcium formation suppressing action, ammonia odor suppressing action, diaper rash preventing action, deodorizing action for livestock, halitosis or body odor suppressing action, or as a composition that brings effects such as prevention or treatment of diseases caused by urease-producing microorganisms It can be preferably used, for example, in the form of pharmaceuticals, quasi drugs, cosmetics, hygiene products, daily necessities, clothes, cleaning products, or foods and drinks or feeds.

Hereinafter, each composition will be described.

(Composition that provides urease activity inhibitory action)
Examples of the composition that exerts an activity of inhibiting urease activity include a composition that can inhibit the activity of urease by the cyclic dipeptide of the present invention or a salt thereof. Therefore, the composition is one aspect of the urease activity inhibitor of the present invention.

When the composition is a known pharmaceutical product, quasi drug, cosmetics, hygiene product, daily necessities, cleaning product, or food or drink or feed, the cyclic dipeptide of the present invention is used as a raw material for the known production. It can be prepared according to the method. Specifically, for example, to the cyclic dipeptide of the present invention or a salt thereof, if desired, a solvent, a dispersant, an emulsifier, a buffer, a stabilizer, an excipient, a binder, a disintegrating agent, a lubricant, etc. are added, According to a known method, it can be formulated into a solid preparation such as tablets, granules, powders, powders and capsules, and liquid preparations such as normal solutions, suspensions and emulsions. Further, for example, carbonated drinks, natural fruit juices, fruit juice drinks, soft drinks (including fruit juice containing), pulp drinks, fruit foods containing fruit grains, vegetable drinks, soy milk/soy milk drinks, coffee drinks, tea drinks, jelly drinks, Powdered beverages, concentrated beverages, sports beverages, nutritional beverages, favorite beverages such as alcoholic beverages, nutritional foods, supplements and other raw materials may be mixed with the cyclic dipeptide of the present invention or a salt thereof and prepared according to known methods. .. Furthermore, for example, the cyclic dipeptide of the present invention or a salt thereof is optionally mixed with a solvent, a dispersant, an emulsifier, a buffer, a stabilizer and the like according to a known technique to form an aerosol, a spray, a spray, a mousse or a coating. It can also be prepared into a liquid product such as an agent. The content of the cyclic dipeptide of the present invention or a salt thereof in these compositions can be appropriately set depending on the form and purpose.

When the composition is ingested into the body, it exerts an action of inhibiting the activity of urease present in the body. In particular, inhibiting the activity of urease is extremely useful for ameliorating and preventing the symptoms of a disease caused by Helicobacter pylori. That is, the composition of the present invention, as a food for specific health, which is intended to prevent or ameliorate the above-mentioned diseases, nutritionally functional food, special-purpose food, food with functional claims, dietary supplement (supplement), for example, , "Protect gastric mucosa", "Prevent gastric ulcer or duodenal ulcer", "Reduce gastric ulcer or duodenal ulcer", "Reduce chronic gastritis" as indication of the function exerted by inhibiting the activity of urease Yes, "Prevent the formation of urinary stones", "Reduce ammonia odor", "Reduce halitosis", "Reduce body odor", "Prevent diaper rash", or these It will be possible to provide with a label that can be interpreted as the same meaning as, and those who suffer from symptoms such as anorexia and gastric reflex caused by gastritis, those who suffer from urinary tract stones, bad breath and body odor caused by ammonia It is an extremely useful composition for those who suffer from rash, diaper rash and the like. The content of the cyclic dipeptide of the present invention or a salt thereof in such a composition cannot be unconditionally set depending on the type of the cyclic dipeptide, its preparation conditions and post-treatment conditions, etc., but from the viewpoint of exerting its effect, it is preferable. Is 0.01 w/w% or more, more preferably 0.1 w/w% or more, still more preferably 1.0 w/w% or more. The upper limit is not particularly set, but is, for example, about 50 w/w%.

(Composition that provides gastric mucosal protection and composition that provides urolithiasis inhibition)
As a composition providing a gastric mucosa-protecting effect, by administering the cyclic dipeptide of the present invention or a salt thereof to the body, the generation of ammonia in the gastric mucosa is suppressed, thereby suppressing the neutralization of gastric acid by ammonia and suppressing the gastric mucosa. A composition that protects the skin can be exemplified. In addition, as a composition having an effect of inhibiting the formation of urinary calculi, for example, when Proteus mirabilis, which produces urease, infects the urinary tract, etc., urine is alkalized by ammonia, which is a reaction product of urease, and phosphorus is introduced into the urinary tract. Although acid salt stones are easily formed, by administering the cyclic dipeptide of the present invention or a salt thereof to the body, it is possible to suppress the alkalization of urine by suppressing the generation of ammonia in the urinary tract, thereby forming urinary tract stones. Can be suppressed. The cyclic dipeptide of the present invention or a salt thereof in these compositions is hard to be decomposed in the stomach or duodenum upon oral administration, and most of them exhibit the above-mentioned action as unchanged form.

The composition, when preparing a known drug, quasi drug, food or drink, or feed, by mixing the cyclic dipeptide of the present invention to the raw material thereof, may be prepared according to a known production method, Alternatively, it may be prepared by adding the cyclic dipeptide of the present invention to an already known food or drink or a feed, and dissolving and/or suspending the cyclic dipeptide. Specifically, for example, to the cyclic dipeptide of the present invention or a salt thereof, if desired, a solvent, a dispersant, an emulsifier, a buffer, a stabilizer, an excipient, a binder, a disintegrating agent, a lubricant, etc. are added, According to a known method, it can be formulated into a solid preparation such as tablets, granules, powders, powders and capsules, and liquid preparations such as normal solutions, suspensions and emulsions.

Further, for example, carbonated drinks, natural fruit juices, fruit juice drinks, soft drinks (including fruit juice containing), pulp drinks, fruit foods containing fruit grains, vegetable drinks, soy milk/soy milk drinks, coffee drinks, tea drinks, jelly drinks, Powdered beverages, concentrated beverages, sports beverages, nutritional beverages, favorite beverages such as alcoholic beverages, nutritional foods, supplements and other raw materials may be mixed with the cyclic dipeptide of the present invention or a salt thereof and prepared according to known methods. .. Such a composition, by containing the cyclic dipeptide of the present invention or a salt thereof, brings about a gastric mucosa protective action or a urolithiasis formation inhibiting action, and therefore requires a gastric mucosa protective action or a urolithiasis formation inhibiting action. It is extremely useful for ameliorating symptoms and preventing diseases. That is, the composition of the present invention, as a food for specific health, which is intended to prevent or ameliorate the above-mentioned diseases, nutritionally functional food, special-purpose food, food with functional claims, dietary supplement (supplement), for example, , "Protect gastric mucosa", "prevent gastric ulcer or duodenal ulcer", as an indication of the function exerted by protecting the gastric mucosa and the function exerted by suppressing the formation of uroliths It becomes possible to provide with indications such as "Relieve gastric ulcer or duodenal ulcer", "Reduce chronic gastritis", "Prevent the formation of urinary tract stones", and reduce appetite caused by gastritis, etc. The composition is extremely useful for those who suffer from symptoms such as stomach upset and those who suffer from urinary tract stones. In the present specification, examples of the diseases requiring the protective effect on the gastric mucosa and the inhibitory effect on urolith formation include gastric ulcer, duodenal ulcer, chronic gastritis, obesity, hypertension, hyperuricemia and the like.

The content of the cyclic dipeptide of the present invention or a salt thereof in the composition, the type of the cyclic dipeptide, can not be unconditionally set by the preparation conditions and post-treatment conditions, etc., from the viewpoint of exerting its effect, preferably Is 0.01 w/w% or more, more preferably 0.1 w/w% or more, still more preferably 1.0 w/w% or more. The upper limit is not particularly set, but is, for example, about 50 w/w%.

(Composition that has an ammonia odor suppressing effect)
The composition having an ammonia odor suppressing effect is sprayed, sprayed, or applied directly to a place where elimination of an ammonia odor is desired, a place where humans, pets, livestock, etc. have feces and urine, or the surrounding area. As a result, the cyclic dipeptide of the present invention or a salt thereof suppresses the decomposition of urea and suppresses the generation of ammonia, which in turn has the effect of reducing or eliminating the unpleasant ammonia odor. As the form of such a composition, for example, the cyclic dipeptide of the present invention or a salt thereof is optionally mixed with a solvent, a dispersant, an emulsifier, a buffer, a stabilizer and the like according to a known technique, and then an aerosol agent, a spray agent, a spray agent. It is also possible to prepare liquid products such as mousses and coating agents.

The content of the cyclic dipeptide of the present invention or a salt thereof in the composition, the type of the cyclic dipeptide, can not be unconditionally set by the preparation conditions and post-treatment conditions, etc., from the viewpoint of exerting its effect, preferably Is 0.01 w/v% or more, more preferably 0.1 w/v% or more, still more preferably 1.0 w/v% or more. The upper limit is not particularly set, but is, for example, about 50 w/v%.

(Composition that provides diaper rash prevention action)
A composition that provides a diaper rash prevention effect is prepared by, for example, directly spraying, coating, or immersing the diaper (cloth, paper, non-woven fabric, etc.) on the diaper to dry the composition and attaching the cyclic dipeptide of the present invention or a salt thereof to the diaper. It is possible to suppress the generation of ammonia from urea in the incidental manure, suppress skin irritation due to ammonia, and prevent diaper rash. As the form of such a composition, for example, the cyclic dipeptide of the present invention or a salt thereof is optionally mixed with a solvent, a dispersant, an emulsifier, a buffer, a stabilizer and the like according to a known technique, and then an aerosol agent, a spray agent, a spray agent. It can also be prepared into a liquid product such as mousse. Further, in addition to the diaper, it can be contained in advance in a wet tissue, a wipe of a butt, a sanitary sheet, a cleaning agent, or the like.

The content of the cyclic dipeptide of the present invention or a salt thereof in the composition, the type of the cyclic dipeptide, can not be unconditionally set by the preparation conditions and post-treatment conditions, etc., from the viewpoint of exerting its effect, preferably Is 0.01 w/v% or more, more preferably 0.1 w/v% or more, still more preferably 1.0 w/v% or more. The upper limit is not particularly set, but is, for example, about 50 w/v%.

(Composition providing deodorant action for livestock)
The composition that provides the deodorizing effect for livestock can be obtained by spraying, spraying, or applying it to a livestock barn or its litter, or by mixing it with feed to suppress the generation of ammonia and obtain the deodorizing effect. .. As the form of such a composition, for example, the cyclic dipeptide of the present invention or a salt thereof is optionally mixed with a solvent, a dispersant, an emulsifier, a buffer, a stabilizer and the like according to a known technique, and then an aerosol agent, a spray agent, a spray agent. It can be prepared into liquid products such as mousses and coating agents. In addition, the feed may be mixed with the cyclic dipeptide of the present invention or a salt thereof as it is, and if desired, a solvent, a dispersant, an emulsifier, a buffer, a stabilizer, a shaping agent may be added to the cyclic dipeptide of the present invention or a salt thereof. By adding agents, binders, disintegrating agents, lubricants and the like, it is possible to formulate and mix into solid agents such as tablets, granules, powders, powders and capsules according to known methods.

The content of the cyclic dipeptide of the present invention or a salt thereof in the composition, the type of the cyclic dipeptide, can not be unconditionally set by the preparation conditions and post-treatment conditions, etc., from the viewpoint of exerting its effect, preferably Is 0.01 w/v% or more, more preferably 0.1 w/v% or more, still more preferably 1.0 w/v% or more. The upper limit is not particularly set, but is, for example, about 50 w/v%.

(Composition that suppresses bad breath or body odor)
The composition which brings about the effect of suppressing bad breath or body odor, for example, can be sprayed or applied directly to the oral cavity or a part of the body where elimination of ammonia odor is desired, whereby the generation of ammonia can be suppressed and the deodorizing effect can be obtained. .. As the form of such a composition, for example, the cyclic dipeptide of the present invention or a salt thereof is optionally mixed with a solvent, a dispersant, an emulsifier, a buffer, a stabilizer and the like according to a known technique, and then an aerosol agent, a spray agent, a spray agent. It is also possible to prepare liquid products such as mousses and coating agents.

The content of the cyclic dipeptide of the present invention or a salt thereof in the composition, the type of the cyclic dipeptide, can not be unconditionally set by the preparation conditions and post-treatment conditions, etc., from the viewpoint of exerting its effect, preferably Is 0.01 w/v% or more, more preferably 0.1 w/v% or more, still more preferably 1.0 w/v% or more. The upper limit is not particularly set, but is, for example, about 50 w/v%.

The present invention also provides various methods characterized by using the cyclic dipeptide of the present invention or a salt thereof. That is, as the method of the present invention, having the above characteristics, a method of inhibiting the activity of urease, a method of protecting the gastric mucosa, a method of suppressing the formation of urinary tract stones, a method of suppressing the smell of ammonia, prevent diaper rash A method of suppressing odor of livestock, and a method of suppressing halitosis or body odor. For the cyclic dipeptides or salts thereof that can be used in these methods, the amounts thereof to be used, and the methods for using the same, refer to the sections of the urease activity inhibitor of the present invention and the compositions corresponding to various methods.

Furthermore, the present invention provides a method for producing various compositions, which comprises using the cyclic dipeptide of the present invention or a salt thereof as a raw material for the composition of the present invention. That is, as the production method of the present invention, a method of producing a composition having the above-mentioned characteristics, which exerts a urease activity inhibitory action, a method of producing a composition which exerts a gastric mucosal protective action, and a composition which exerts a urinary calculus formation inhibiting action Manufacturing method, method for producing composition having ammonia odor suppressing effect, method for producing composition providing diaper rash preventing effect, method for producing composition providing livestock deodorizing effect, and composition providing oral malodor or body odor suppressing effect Mention may be made of a production method and a method for producing a composition which brings about effects such as prevention or treatment of diseases caused by Helicobacter pylori.

The production method of the present invention, if the cyclic dipeptide of the present invention or a salt thereof is used as a raw material of a composition, the amount used, the timing of addition, the addition method are not particularly limited, and other components to be added and blended are also not limited. They can be used, and the amount used and the method of addition can be appropriately selected according to known techniques. Specifically, for example, a carrier, a base, and/or an additive or the like usually used in the fields of formulation, food, etc. can be appropriately blended within the range to achieve the object of the present invention.

With regard to the embodiments described above, the present invention further discloses the following agents and compositions, their use.
<1> A urease activity inhibitor containing a cyclic dipeptide or a salt thereof as an active ingredient.
<2> The cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and The urease activity inhibitor according to <1>, which comprises one or two or more selected from the group consisting of cycloglutamylglutamic acid.
<3> The urease activity inhibitor according to <1> or <2>, wherein the cyclic dipeptide or a salt thereof is contained in a plant-derived component and/or an animal-derived component.
<4> The urease activity inhibitor according to <3>, wherein the plant-derived component is one or more kinds of extracts selected from the group consisting of soybean, malt, barley, wheat, flower and tea.
<5> The urease activity inhibitor according to <3>, wherein the animal-derived component is one or more selected from the group consisting of collagen, albumin, casein, placenta, and globulin.
<6> Urease activity according to any one of <1> to <5>, which is used for gastric mucosa protection, urinary tract stone formation suppression, ammonia odor suppression, diaper rash prevention, livestock deodorization, or halitosis or body odor suppression. Inhibitor.
<7> The urease activity inhibitor according to any one of <1> to <5>, which is used for preventing or treating a disease caused by a urease-producing fine substance.
<8> A gastric mucosa protective agent containing a cyclic dipeptide or a salt thereof as an active ingredient.
<9> The cyclic dipeptide is cyclotryptophanyl proline, cycloarginyl phenylalanine, cycloisoleucyl leucine, cycloglutamyllysine, cyclomethionyl serine, cycloarginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and The gastric mucosa protective agent according to <8>, which contains one or more selected from the group consisting of cycloglutamylglutamic acid.
<10> The gastric mucosa protective agent according to <8> or <9>, wherein the cyclic dipeptide or a salt thereof is contained in a plant-derived component and/or an animal-derived component.
<11> A urolithiasis inhibitor, which comprises a cyclic dipeptide or a salt thereof as an active ingredient.
<12> The cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and The urolithiasis inhibitor according to <11>, which comprises one or two or more selected from the group consisting of cycloglutamylglutamic acid.
<13> The urinary tract stone formation inhibitor according to <11> or <12>, wherein the cyclic dipeptide or a salt thereof is contained in a plant-derived component and/or an animal-derived component.
<14> An ammonia odor inhibitor containing a cyclic dipeptide or a salt thereof as an active ingredient.
<15> The cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and The ammonia odor suppressor according to <14>, which contains one or more selected from the group consisting of cycloglutamylglutamic acid.
<16> The ammonia odor suppressor according to <14> or <15>, wherein the cyclic dipeptide or a salt thereof is contained in a plant-derived component and/or an animal-derived component.
<17> A diaper rash preventing agent which comprises a cyclic dipeptide or a salt thereof as an active ingredient.
<18> Cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and The diaper rash inhibitor according to <17> above, which comprises one or more selected from the group consisting of cycloglutamylglutamic acid.
<19> The diaper rash inhibitor according to <17> or <18>, wherein the cyclic dipeptide or a salt thereof is contained in a plant-derived component and/or an animal-derived component.
<20> A livestock deodorant containing a cyclic dipeptide or a salt thereof as an active ingredient.
<21> Cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and The livestock deodorant according to <20>, which contains one or more selected from the group consisting of cycloglutamylglutamic acid.
<22> The livestock deodorant according to <20> or <21>, wherein the cyclic dipeptide or a salt thereof is contained in a plant-derived component and/or an animal-derived component.
<23> A halitosis or body odor inhibitor containing a cyclic dipeptide or a salt thereof as an active ingredient.
<24> The cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and The breath odor or body odor inhibitor according to <23>, which contains one or two or more selected from the group consisting of cycloglutamylglutamic acid.
<25> The halitosis or body odor inhibitor according to <23> or <24>, wherein the cyclic dipeptide or a salt thereof is contained in a plant-derived component and/or an animal-derived component.
<26> The urease activity inhibitor according to any of <1> to <7>, the gastric mucosa protective agent according to any of <8> to <10>, and the urine according to any of <11> to <13>. Road stone formation inhibitor, ammonia odor inhibitor according to any of <14> to <16>, diaper rash inhibitor according to any of <17> to <19>, any of <20> to <22> A composition comprising the livestock deodorant according to any one of claims 1 to 3 or the breath or body odor suppressor according to any one of the items <23> to <25>.
<27> The composition according to <26> above, which is labeled with at least one of the function exhibited by inhibiting the activity of urease, gastric mucosa protection, urinary tract stone formation suppression, and halitosis or body odor suppression.
<28> A method for suppressing ammonia odor, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient.
<29> A method for suppressing odor of livestock, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient.
<30> A method for suppressing halitosis or body odor, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient.
<31> Use of a cyclic dipeptide or a salt thereof in the preparation of a composition for inhibiting urease activity.
<32> Use of a cyclic dipeptide or a salt thereof in the preparation of a composition for protecting gastric mucosa.
<33> Use of a cyclic dipeptide or a salt thereof in the preparation of a composition for suppressing the formation of urinary tract stones.
<34> Use of a cyclic dipeptide or a salt thereof for suppressing ammonia odor.
<35> Use of a cyclic dipeptide or a salt thereof in the preparation of a composition for preventing diaper rash.
<36> Use of a cyclic dipeptide or a salt thereof for suppressing the odor of livestock.
<37> Use of a cyclic dipeptide or a salt thereof for suppressing halitosis or body odor.

Hereinafter, the present invention will be specifically described with reference to examples, but the present invention is not limited to the following examples.

Example 1 Urease activity inhibitory effect Urease activity inhibitory evaluation was examined according to the following protocol. The cyclic dipeptide was chemically synthesized by Kobe Natural Products Chemical Co., Ltd. and used in the following experiment.

<Preparation of urease solution>
15 mg of urease powder (151 U/mg, manufactured by Toyobo Co., Ltd.) was dissolved in 100 mL of pure water and frozen and used as a stock. Before use, the stock was diluted 10-fold with pure water and used for the test.

<Preparation of acetate buffer>
Aqueous acetic acid solution (71.5 mL of acetic acid (Nacalai Tesque) dissolved in pure water to 1000 mL) and sodium acetate aqueous solution (51.3 g of sodium acetate (Nacalai Tesque) dissolved in pure water to 500 mL ) Was mixed and adjusted to pH 4.1. When this was used, it was diluted 10 times with pure water and mixed with ethanol (manufactured by Nacalai Tesque, Inc.) at a ratio of 4:1 to obtain a 0.1 mol/L acetic acid buffer.

<Preparation of substrate solution>
0.3 g of urea (manufactured by Nacalai Tesque, Inc.) was dissolved in 50 mL of pure water to prepare a substrate solution.

<Preparation of coloring reagent>
Coloring reagents A and B were prepared as follows.
Solution A: 5 g of phenol (manufactured by Nacalai Tesque) and 25 mg of sodium nitroprusside (manufactured by Nacalai Tesque) were dissolved in 500 mL of water to prepare a solution A.
Solution B: 1% sodium hydroxide aqueous solution (prepared by diluting 4 mol/L sodium hydroxide with water, manufactured by Nacalai Tesque, Inc.) and 19.7 mL of sodium hypochlorite (manufactured by Nacalai Tesque, Inc.) 0.3 mL were mixed. To prepare a liquid B.

<Preparation of evaluation compound solution>
Depending on the solubility of the evaluation compound, the cyclic dipeptide dissolved in water or an aqueous solution containing 1% DMSO was used for the test. Instead of the evaluation compound solution, water containing no evaluation compound or an aqueous solution containing 1% DMSO was used as a control group.

<Evaluation of urease activity inhibition>
The following reactions were all carried out in a constant temperature bath at 37°C. To each well of a 96-well plastic plate (Greiner, transparent), 125 μL of the acetate buffer prepared above, 20 μL of the urease solution, and 5 μL of the evaluation compound solution were added, mixed by pipetting, and then preincubated. Next, 50 μL of the substrate solution which had been kept warm was added, and the reaction was started by mixing by pipetting. On the other hand, a 96-well plate other than this was prepared as a measurement plate, and 90 μL of water and 50 μL of solution A were added to each well and kept warm. 10 minutes after the start of the reaction, 10 μL of the reaction solution was transferred to a measurement plate and mixed by pipetting to stop the reaction with urease. After 15 minutes, 50 μL of solution B was added to the measurement plate, mixed in the same manner, and allowed to stand for 30 minutes or more. Thereafter, the absorbance at 640 nm was measured for all the wells, and the urease activity inhibition rate (%) was calculated using the following (formula 1). Acetohydroxamic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was used as a positive control for the inhibitor, and it was confirmed that 50% or more inhibition was observed at 100 μM. The results are shown in Table 1 (n=3). The concentration shown here indicates the final concentration (μM) in the reaction solution.
(Equation 1)
Activity inhibition rate (%)=100×(1-absorbance in evaluation compound solution added group/absorbance in control group)

From the above results, it can be seen that the cyclic dipeptides shown in Table 1 have urease activity inhibitory action.

Hereinafter, specific formulations of the composition containing the cyclic dipeptide of the present invention or a salt thereof will be exemplified. These compositions can be prepared according to known methods.

(Prescription example)
Production examples of various drugs, quasi drugs, cleansing cosmetics and foods using the urease inhibitor of the present invention are shown below, but the present invention is not limited thereto.

(Prescription example 1) Gastric mucosa protective agent
Heat-treated soybean peptide containing cyclic dipeptide 15.0 g
Magnesium ascorbate 0.5g
DL-α-tocopherol acetate 0.5g
Silicone oil 30.0g
Tween 80 0.05g
Corn starch 48.95g
The above ingredients were uniformly mixed and 200 mg was filled in a gelatin capsule to prepare a capsule.

(Prescription example 2) Urolithiasis inhibitor
Heat-treated tea peptide containing cyclic dipeptide 20.0 mg
Corn starch 50.0mg
Hydroxypropyl methylcellulose 150.0 mg
Carboxymethyl chitin 30.0 mg
The above components were uniformly mixed and compressed into tablets.

(Prescription example 3) Halitosis inhibitor
Heat-treated malt peptide containing cyclic dipeptide 100.0 mg
Corn starch 80.0mg
Methylcellulose 40.0mg
Magnesium stearate 20.0 mg
Talc 10.0 mg
The above components were uniformly mixed and compressed into tablets.

(Prescription example 4) Body odor suppressant mass%
Heat-treated tea peptide containing cyclic dipeptide 1.8
Sodium citrate 2.0
Potassium laurate 15.0
Potassium myristate 5.0
Propylene glycol 5.0
Sorbitol 3.0
Polyethylene powder 0.5
Hydroxypropyl chitosan solution 0.5
Preservative Suitable amount
pH adjuster Proper amount Perfume Proper amount Purified water 100 Residue

(Prescription example 5) Baby powder for prevention of diaper rash mass%
Heat-treated tea peptide 2.0 containing cyclic dipeptides
Heat-treated malt peptide 2.0
Zinc oxide 35.0
Betaine 2.0
Eucalyptus leaf oil 1.5
Menthol 3.2
Polyethylene powder 15.5
Fragrance Residual amount of talc 100

(Prescription example 6) Sheet for wipes of the buttocks Mass%
Heat-treated tea peptide containing cyclic dipeptide 1.2
Plum extract 0.8
Ethanol 8.0
Propylene glycol 12.0
Preservative A suitable amount of purified water 100 Residual mixture The above components were mixed and sprayed uniformly on gauze in an amount of 1.4% by mass to obtain a sheet for wipes for wipes.

The urease activity inhibitor of the present invention has a characteristic that the contained cyclic dipeptide is difficult to be decomposed in the stomach and duodenum, and inhibits the activity of urease in the living body, for example, gastric mucosa protective action, urinary tract stones. Formation inhibitory action, or the possibility of bringing about actions such as the prevention or treatment of diseases caused by urease-producing microorganisms, ammonia odor suppressing action from manure and diaper rash preventing action, deodorizing action for livestock, bad breath or body odor It can be used in the expectation that it will bring about an inhibitory action.

Claims (25)

A cyclic dipeptide or a salt thereof as an active ingredient, a urease activity inhibitor , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cyclo A urease activity inhibitor comprising one or more selected from the group consisting of arginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . Cyclic dipeptides or salts thereof, made be contained in the plant-derived component and / or animal-derived components, urease activity inhibitor according to claim 1 Symbol placement. The urease activity inhibitor according to claim 2 , wherein the plant-derived component is an extract of one kind or two or more kinds selected from the group consisting of soybean, malt, barley, wheat, flower and tea. The urease activity inhibitor according to claim 2 , wherein the animal-derived component is one or more selected from the group consisting of collagen, albumin, casein, placenta, and globulin. The urease activity inhibitor according to any one of claims 1 to 4, which is used for gastric mucosa protection, urinary tract stone formation suppression, ammonia odor suppression, diaper rash prevention, livestock deodorization, or halitosis or body odor suppression. Used in the prevention or treatment of diseases caused by urease-producing microorganisms, urease activity inhibitor according to any one of claims 1-4. The urease activity inhibitor according to claim 6 , wherein the microorganism is Helicobacter pylori, Pseudomonas aeruginosa, spirochete, or Proteus mirabilis. A gastric mucosa protective agent comprising a cyclic dipeptide or a salt thereof as an active ingredient , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cyclo A gastric mucosa protective agent containing one or more selected from the group consisting of arginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . A urolithiasis inhibitor , which comprises a cyclic dipeptide or a salt thereof as an active ingredient , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine. , A urinary calculus inhibitor containing one or more selected from the group consisting of cycloarginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . A cyclic dipeptide or a salt thereof as an active ingredient, an ammonia odor suppressor , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cyclo An ammonia odor suppressor containing one or more selected from the group consisting of arginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . Using a cyclic dipeptide or a salt thereof as an active ingredient, a diaper rash inhibitor , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cyclo A diaper rash inhibitor, which comprises one or more selected from the group consisting of arginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . A cyclic dipeptide or a salt thereof as an active ingredient, a domestic animal deodorant , wherein the cyclic dipeptide is cyclotryptophanyl proline, cycloarginyl phenylalanine, cycloisoleucyl leucine, cycloglutamyllysine, cyclomethionyl serine, cyclo A livestock deodorant containing one or more selected from the group consisting of arginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . A cyclic dipeptide or a salt thereof as an active ingredient, a breath or body odor inhibitor , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, A halitosis or body odor inhibitor containing one or more selected from the group consisting of cycloarginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . From the group consisting of cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and cycloglutamylglutamic acid. comprising one or more cyclic dipeptide or a salt thereof selected, for urease activity inhibition, gastric mucosa protective, for urinary calculus formation inhibition, for ammonia odor suppression, Contact Mutsukabure for preventing, livestock deodorant use, or for mouth odor or body odor suppression composition. 15. The composition according to claim 14 , which is labeled with at least one of a function exerted by inhibiting the activity of urease, gastric mucosal protection, suppression of urinary stone formation, and suppression of halitosis or body odor. A method for suppressing ammonia odor, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine. , Cyclomethionyl serine, cycloarginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid, or one or more selected from the group consisting of cycloglutamyl glutamic acid . A method for suppressing odor of domestic animals, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyl. A method comprising one or more selected from the group consisting of lysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and cycloglutamylglutamic acid . A method for suppressing halitosis or body odor, which comprises using a cyclic dipeptide or a salt thereof as an active ingredient , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyl. A method comprising one or more selected from the group consisting of lysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and cycloglutamylglutamic acid . Use of a cyclic dipeptide or a salt thereof in the preparation of a composition for inhibiting urease activity , wherein the cyclic dipeptide is cyclotryptophanyl proline, cycloarginyl phenylalanine, cycloisoleucyl leucine, cycloglutamyl lysine, cyclo Use, which contains one or more selected from the group consisting of methionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and cycloglutamylglutamic acid . Use of a cyclic dipeptide or a salt thereof in the preparation of a composition for protecting gastric mucosa , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclo Use, which contains one or more selected from the group consisting of methionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and cycloglutamylglutamic acid . Use of a cyclic dipeptide or a salt thereof in the preparation of a composition for inhibiting the formation of uroliths, wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyl. Use, which contains one or more selected from the group consisting of lysine, cyclomethionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and cycloglutamylglutamic acid . Use of a cyclic dipeptide or a salt thereof for suppressing ammonia odor , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, cyclo Use, which comprises one or more selected from the group consisting of arginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . Use of a cyclic dipeptide or a salt thereof in the preparation of a composition for preventing diaper rash , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclo Use, which contains one or more selected from the group consisting of methionylserine, cycloarginylglutamic acid, cycloasparaginylasparagine, cycloglutaminylglutamine, and cycloglutamylglutamic acid . In order to suppress the odor of livestock, the use of a cyclic dipeptide or a salt thereof , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, Use, which comprises one or more selected from the group consisting of cycloarginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid . Use of a cyclic dipeptide or a salt thereof for suppressing halitosis or body odor , wherein the cyclic dipeptide is cyclotryptophanylproline, cycloarginylphenylalanine, cycloisoleucylleucine, cycloglutamyllysine, cyclomethionylserine, Use, which comprises one or more selected from the group consisting of cycloarginyl glutamic acid, cycloasparaginyl asparagine, cycloglutaminyl glutamine, and cycloglutamyl glutamic acid .