JP2003048844A - Urease activity inhibitor - Google Patents

Abstract

(57) [Problem] To provide a safe drug which inhibits the activity of urease instead of a conventional chemotherapeutic agent. SOLUTION: Klempi (disconnecting skin) extract, Koboku (thick) extract, Kobushi (Kabushiko) extract, Sunhaengs (Yamaboshi) extract, Hikai (basic solution) extract, Butterfly (chotocho) ) Extract, kayak extract, citrus (persimmon) extract, gokahi (five skin) extract, Kashu (Hanshu crow) extract, Sappan (Sappan) extract, Taiwan Goto extract, sea breeze extract, Jurema-Pret
a) One of the plant extracts selected from the extract, red wisteria extract, Nankyo extract, walnut extract and tea tree extract
A urease activity inhibitor comprising a species or two or more species as an active ingredient.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a urease activity inhibitor containing a plant extract as an active ingredient, and more specifically, it inhibits urease mainly produced by microorganisms as a drug or an additive for foods to produce urease. The present invention relates to a urease inhibitor capable of erasing a disease caused by the disease and a urease-producing microorganism itself.

[0002]

BACKGROUND OF THE INVENTION Urease is an enzyme that catalyzes the hydrolysis of urea, whereby urea becomes carbon dioxide and ammonia. This urease is bacteria, microorganisms such as filamentous fungi, higher plants such as nata beans, lower animals, the oral cavity of mammals such as humans,
It is found in gastric mucosa, red blood cells, etc.

By the way, it goes without saying that the urease found in a microorganism is a urease derived from the microorganism. For example, the urease found in an animal is also parasitic on the animal. Often derived from microorganisms. In addition, some of the urease-producing microorganisms are one of the causes of diseases of animals such as hosts.

[0004] For example, it has been reported that Helicobacter pylori (hereinafter referred to as "H. pylori") is detected at a high rate in gastric biopsy material of patients with gastritis or gastric ulcer (Wall).
en et.al., Lancet, 1273-1275, 1993), it has been revealed that it is gradually involved in the development of gastritis and gastric or duodenal ulcer, but this microorganism is also known to produce urease. .

Various studies have been conducted on the mechanism by which the H. pylori damages gastric mucosal cells.
It is almost as follows. That is, H. pylori, like other Escherichia coli, enters the mouth and reaches the stomach, and uses its flagella to swim in the mucus layer to reach the gastric mucosal layer and adhere to gastric mucosal cells. Then, urea is decomposed by urease produced by itself, and the resulting ammonia neutralizes the gastric acid to establish a favorable living environment and start proliferation. According to the adhesion (infection) of the Helicobacter pylori to the gastric mucosal epithelial cells, first, IL-8, which is a chemoattractant factor for neutrophils, is released from the gastric mucosal cells and is favored at the site of infection. The spheres gather.
Second, H. pylori produces and releases neutrophil activators,
The activated neutrophils are more likely to adhere to the endothelial cells of blood vessels, which causes microcirculatory disorders of the mucous membrane, and a protease, which is known as a causative agent of the microcirculatory disorders, is free. Produces radicals (active oxygen) and leukotrienes. Thirdly, the ammonia produced by the action of urease produced by H. pylori reacts with the above free radicals to produce monochloramine, which is a substance that damages gastric mucosal cells and the like. Thus, inflammation is triggered and progresses.

[0006] In addition to the above-mentioned inflammatory reaction, gastric mucosal injury caused by Helicobacter pylori includes, for example, attack of ammonia itself produced by the action of urease on gastric mucosa, and cytotoxin (vacuumization) produced by Helicobacter pylori itself. It is also considered that the vacuolar degeneration of mucosal cells due to (toxin) is also a factor.

[0007] As described above, since the urease of H. pylori is a cause of several diseases in addition to gastrointestinal tract-related diseases, suppression of the urease is required.

On the other hand, a modified Proteus bacterium is known as a urease-producing microorganism. This microorganism decomposes urea in urine into ammonia by urinary tract infection,
It is considered to induce phospholithiasis and pyelonephritis (JP-A-52-151158).

Some intestinal microorganisms also produce urease, which decomposes urea in the digestive tract contents and mucus components to produce ammonia. The generated ammonia is absorbed from the intestinal tract and enters the blood. However, when there is a liver dysfunction, these ammonia are not metabolized and may induce hyperammonemia. Therefore, urease is considered to indirectly contribute to these pathological conditions.

Further, it has been known that urease derived from microorganisms in manure causes ammonia and carbon dioxide gas from manure to cause a strong unpleasant odor (Japanese Patent Laid-Open No. 2000-125779), and this urease is also known. It is also known that the ammonia generated by the action of increases the skin pH, and as a result, the activity of protease and lipase is increased, which causes diaper rash in infants.

In order to suppress the growth of such urease-producing microorganisms, antibacterial agents have been mainly used conventionally. As this antibacterial agent, the use of antibiotics has been mainly attempted. For example, in the case of H. pylori, amoxicillin and clarithromycin have recently been used as antibacterial agents, and a proton pump inhibitor (PPI) has been added to these three types. The three-drug combination sterilization therapy that combined the above chemotherapeutic agents was covered by insurance. However, since the above eradication therapy requires administration of a relatively large amount of drug, its side effects, especially the emergence of resistant bacteria, become a problem that cannot be ignored.

[0012] On the other hand, it has been studied to inhibit the activity of urease produced by microorganisms, instead of killing the microorganisms. As a drug used for this purpose, hydroxyurea, hydroxamic acid derivatives, lamprazole and its derivatives, etc. are known (JP-A-7-118153), but some have serious side effects. A highly safe drug has been demanded.

[0013]

DISCLOSURE OF THE INVENTION The present invention has been made under the circumstances described above, and is intended to provide a highly safe urease inhibitor which can sufficiently inhibit the activity of urease produced by microorganisms. The challenge is to provide.

[0014]

Means for Solving the Problems The inventors of the present invention have conducted an intensive search for natural substances having urease inhibitory activity and found that some plant extracts have a high urease activity inhibitory activity.

The activity of the plant extract for inhibiting the urease activity is high enough to suppress the growth of urease-producing microorganisms such as H. pylori, and is effective in preventing diseases associated with the microorganism. It has been found that it can be used as a drug or therapeutic drug. Further, they have found that even if the above plant extract is used as a food form, its urease inhibitory activity is not impaired, and that it can be used as a prophylactic / therapeutic agent for diseases by ingesting it, and completed the present invention.

That is, the present invention is based on Kurempi (bitter skin).
Extract, Koboku (Koboku) extract, Kobushi (Kabushi)
Extract, Sanhens extract, Hikai (basic)
Extract, Choengkou extract, Kayanomi extract, Citiate extract, Gokahi extract, Kashu extract, Sappan extract, Taiwanese hook Effectively one or more plant extracts selected from wisteria extract, sea breeze wisteria extract, Jurema-Preta extract, red wisteria extract, radish extract, walnut extract and chanterelle extract The present invention provides a urease activity inhibitor characterized by being contained as a component.

The present invention also provides a pharmaceutical product characterized by containing the above-mentioned urease activity inhibitor.

Furthermore, the present invention provides a food or drink containing the above-mentioned urease activity inhibitor.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION In the present specification, the name of the plant used as a raw material for the plant extract is “Handbook of Natural Products” published by Food and Science Co. in 1992.

[Twelfth Edition], "Japanese and Chinese Encyclopedia," published by a nursery school (I)
And (II), "Primary color Japanese medicinal plant picture book" issued by a nursery company
Or, it is based on the description in the "Chinese Medicine Dictionary" issued by Shanghai Science and Technology Publishing Company or in accordance with these.

In the urease activity inhibitor of the present invention,
Used as an active ingredient, Krempi (bitter bite) extract, Koboku (koboku) extract, Rhododendron (kabushi) extract, Sanhens (Yamaboshi) extract, Hikai (Understood) extract, Choengkou ( Choto Hou extract, Kayano extract, Citiate extract, Gokahi extract.
Kash extract, Sappan extract, Taiwan hangou extract, Haifu extract, Jurema-Preta extract, Benito extract, Antarcticus extract, walnut extract and tea tree extract The products are known per se as Kampo medicines and food additives, and in use as the urease inhibitor of the present invention, there is no particular limitation on the origin, manufacturing method, form, composition of ingredients, etc. What is marketed as an additive can be used as it is as an active ingredient in the present invention. However, it has not yet been known that each of these plant extracts exhibits an inhibitory effect on urease.

The plant extract used in the present invention is already known as described above. The examples of the extraction method are as follows.

The Krempi extract is a root bark or bark of Melia toosendan or Melia azedarach, or a fruit (also known as Senrenshi (kawaryuko)), a hydrophilic solvent such as water, ethanol, or the like. It is obtained by extraction with the organic solvent of. The obtained Krempi extract contains triterpenes and the like as components.

The extract of Koboku (Koboku) is a magnolia family honoki (Japanese Atsugi, Magnolia obovata), Karahoo (Hohoku Atsugi, Magnolia officinalis), or Wenshu Atsugi (Magnus).
Oliaofficinalis var. biloba) can be obtained by extracting the bark or flowers (flower thickwood) of the trunk and branches with water, a hydrophilic solvent such as ethanol, or another organic solvent. The obtained Komoku extract contains sesquiterpenes such as β-oedesmol, phenylpropanols such as magnolol and honokiol, and glycosides thereof as components.

[0024] The Rhizoma japonicus extract is Cyperus rotundus or C. frabe of the same genus.
lliformis, C. difformis, C. glomeratus, C. iria,
It is obtained by extracting the rhizome of C. michelianus, C. rotundus, etc. with water, a hydrophilic solvent such as ethanol, or other organic solvent. The obtained kobushi extract contains sesquiterpenes such as cyperene as components.

Sanhens extract is Cassia nomame or its genus, Cas.
It is obtained by extracting seeds of sia nictitans with water, a hydrophilic solvent such as ethanol, or another organic solvent.
The obtained sunhens extract contains anthraquinones and the like as components.

[0026] The Hikai (basic) extract is a powdered yam powder (Dioscrea hypoglauca) or a plant belonging to the same family, D. collettii and Fukushu yam (D. fatschauensi).
s), Onidokoro (D. tokoro), Tachidokoro (D. graci
llima), or roots or rhizomes of which are extracted with a hydrophilic solvent such as water or ethanol, or other organic solvent. The obtained calyx (basic) extract contains triterpenes such as diosgenin and triterpene glycosides such as dioscin as components.

[0027] The extract of Chotokkou (Fishing hook) is Uncaria sinensis, Rubiaceae (U. macrophylla), or a member of the same family, U. macrophylla (U. macrophylla).
rhynchophylla) can be obtained by extracting with water, a hydrophilic solvent such as ethanol, or other organic solvent. The obtained Ginkgo biloba extract contains indole alkaloids such as lincophilin as a component.

[0028] Kaya flea extract is a product of the yew family Kaya (Torrey).
a nucifera) or a seed of T. grandis, which is a homologous plant, with water, a hydrophilic solvent such as ethanol, or another organic solvent. The obtained Kayanomi extract contains essential oils such as nuciferol and fatty oils as components.

The citrus extract is based on the oyster family Oyster (Di
ospyros kaki) or its homologous plants, D. morrisiana, and D. eriantha, which are plants belonging to the same genus, are extracted with a hydrophilic solvent such as water or ethanol, or another organic solvent. The obtained City extract contains a triterpene such as ursolic acid as a component.

The extract of Gokahi (five-skin bark) is produced by Acanthopanax gracilistylus, A. siebold.
ianus) or its cognate plant, A. senticosu
s), Mansyuu Kogi (A. sessiliflorus), Yamakogi (A. spinosus), Leaf Goka (A. henryi), Umbrella Goka (A.verticillatus), Takagi Goka (A. evodiaefoliu)
m), Goka (A. setchuenensis), Goka Fuji (A. leucor
It is obtained by extracting the root bark or leaves of rhyzus) with a hydrophilic solvent such as water or ethanol, or another organic solvent. The obtained Gokahi extract contains lignans, saponins and the like as components.

[0031] The Kashi extract is obtained by extracting tuberous roots of Polygonum multiflorum (Polygonum multiflorum) with water, hydrophilic solvents such as ethanol, or other organic solvents. The obtained Kashi extract contains anthraquinones such as chrysophanol as a component.

The Sappan extract is obtained by extracting the heartwood of the legume family Caesalpinia sappan with water, a hydrophilic solvent such as ethanol, or another organic solvent.

[0033] The Taiwan Hangfuji extract can be obtained by extracting the hooks of Uncaria kawakamii with water, a hydrophilic solvent such as ethanol, or another organic solvent. The obtained Taiwanese ginseng extract contains indole alkaloids such as lincophylline as a component.

The sea breeze wisteria is a pepper family, Futtokazura (Pi
per kadsura) is obtained by extracting with water, a hydrophilic solvent such as ethanol, or other organic solvent. The seaweed extract obtained contains fuftoxide as a component.

The Jurema-Preta extract is obtained by extracting the bark of the legume Acacia jurema with water, a hydrophilic solvent such as ethanol, or another organic solvent.

The red widow extract is from Sargento.
It is obtained by extracting the stem of doxa cuneata) with water, a hydrophilic solvent such as ethanol, or another organic solvent. The obtained red bean extract contains tannin and the like as a component.

The radix root extract can be obtained by extracting the roots of the ginger family Alpinia galanga with a hydrophilic solvent such as water or ethanol, or another organic solvent.

The walnut extract is a walnut family walnut (Juglan
s mandshurica var.sachalinensis) with water, hydrophilic solvents such as ethanol, or other organic solvents.

The tea tree extract is a tea tree of the Camelliaceae family (Th
ea sinensis) stems are extracted with water, hydrophilic solvents such as ethanol, or other organic solvents. The obtained tea tree extract contains catechins as a component.

The urease activity inhibitor of the present invention is prepared by using each of the above plant extracts as an active ingredient and combining this with an appropriate pharmaceutical carrier. When the urease activity inhibitor of the present invention is used as a medicine, it may be generally used in the form of a general medicinal preparation by using the above-mentioned plant extract and a pharmaceutically acceptable carrier.

The blending ratio of the urease activity inhibitor to the drug is appropriately determined by those skilled in the art according to the kind of the plant extract used for the urease activity inhibitor and the pharmacological action of the plant. In the case of a radish extract, the amount is about 50 to 300 mg.

Various forms can be selected as the dosage unit form of the above-mentioned pharmaceutical agent according to the present invention according to the therapeutic purpose, and typical examples thereof include tablets, pills, powders, solutions, suspensions, emulsions and granules. Agent, capsule, suppository, injection (solution,
Suspensions, etc.), ointments and the like.

Further, as a pharmaceutically acceptable carrier for the drug, a filler, a bulking agent, a binder, a moisturizer, a disintegrant, a surface, which is usually used, depending on the above-mentioned formulation form. Diluents or excipients such as activators and lubricants can be used.

When the form of the preparation is a tablet, it may be a tablet which is coated with a usual coating as required, for example, a sugar-coated key, a gelatin encapsulated tablet, or an enteric coated tablet. When the agent of the present invention is prepared as an injection such as a solution, emulsion or suspension, it is preferable that these are sterilized and isotonic with blood, and an amount sufficient to prepare an isotonic solution. Sodium chloride, glucose or glycerin may be contained in the drug of the present invention, and a usual solubilizing agent, buffer, soothing agent and the like may be added. Furthermore, in the drug of the present invention, a colorant, a preservative, a fragrance, a flavoring agent, a sweetening agent and the like and other medicinal products can be contained, if necessary.

There are no particular restrictions on the method of administration of the above-mentioned pharmaceuticals,
It is determined according to various formulation forms, patient's age, sex and other conditions, degree of disease and the like. For example, tablets, pills, liquids,
Suspensions, emulsions, granules and capsules are administered orally,
Injections are administered intravenously alone or mixed with a normal replacement fluid such as glucose or amino acid, and further, if necessary, they are administered intramuscularly, intradermally, subcutaneously or intraperitoneally alone, and suppositories are administered rectally. .

The dose of the above-mentioned medicinal product is appropriately selected depending on the usage, age of the patient, sex and other conditions, mildness of the disease, etc., but is about dry weight of each plant extract which is usually an active ingredient per 1 kg of body weight. The dose is preferably about 0.5 to 20 mg / day, and the preparation can be administered in 1 to 4 divided doses per day.

The urease activity inhibitor of the present invention is
It can also be in the form of a food additive, which is added to breads, confectioneries, drinks and the like. This food additive can be added to other generally known food materials (raw material components) according to a conventional method to obtain a food or drink having an inhibitory activity against urease activity.

There are no particular restrictions on the other ingredients for food ingredients used in the preparation of the above foods and drinks, and any ingredients commonly used in the food industry may be used, including, for example, wheat flour, starch, sugar, fats and oils. The various proteins, lipids, sugar raw materials and other vitamins, minerals, etc. can be exemplified.

Further, the urease activity inhibitor of the present invention is
In a commonly used amount range, a combination of a foaming agent such as sodium hydrogencarbonate and / or sodium carbonate and an organic acid (neutralizing agent) such as citric acid, tartaric acid, fumaric acid, ascorbic acid, etc., It is also possible to prepare a food or drink in the form of a foaming agent according to a conventional method, for example, a direct powder compression method, a dry or wet granule compression method.

[0050]

EFFECT OF THE INVENTION The urease activity inhibitor of the present invention can inhibit the activity of urease produced by urease-producing microorganisms such as H. pylori and modified Proteus, and prevent diseases and lesions caused by these. It is a thing.

Not only that, it also acts as a disinfectant for H. pylori in the stomach, for example. That is, H. pylori replaces urea with ammonia by urease activity, and thereby suppresses the action of hydrochloric acid in gastric acid and survives in the stomach, but since H. pylori inhibits this urease activity, H. pylori mediates hydrochloric acid with ammonia. They cannot be harmed and eventually die.

Due to such an action, the urease activity inhibitor of the present invention is a preventive or therapeutic agent for a disease caused by one of the urease-producing microorganisms, for example,
It can be used as a prophylactic or therapeutic agent for diseases such as gastritis, gastric ulcer, duodenal ulcer, etc., which are caused by Helicobacter pylori and modified Proteus bacterium.

[0053]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Production Example 1 Plant Extract and Preparation Thereof: As a plant extract, krenpi (bitter bite bark) extract, sengren (kawatsuko) extract, koboku (koboku) extract, kobushi (kabushi) extract Products, sun hens extract, hikai extract, chopstick extract, kayanomi extract, citrus extract, gokahi extract, kashu (Shouban) extract, Sappan extract, Taiwan Houfu extract, Haifu wisteria extract, Jurema-P (Jurema-P)
reta) extract, Benito extract, Ranunculaceae extract, walnut extract and tea tree extract. These plant extracts were prepared by the method described below in "Handbook of Natural Products (Twelfth Edition)" published by Foods and Science Co., Ltd. in 1992 or in accordance with the following method.

(1) Preparation of cold methanol extract The dried crude drug was used as it was or crushed, methanol was added thereto, and the mixture was chilled at room temperature for about 1 week to obtain a cold methanol extract. Then, the solid content of this extract was filtered off, concentrated under reduced pressure and dried to obtain a cold methanol extract. Table 1 shows the weight of each crude drug used for extraction, the amount of solvent, and the amount of extract. Each crude drug is a marketed product unless otherwise specified.

[0056]

[Table 1]

(2) Preparation of Cold Acetone Extract The dried crude drug was used as it was or crushed, acetone was added, and the mixture was cold shaken at room temperature for about 1 week to obtain a cold acetone extract.
Then, the solid content of this extract was filtered off, concentrated under reduced pressure and dried to obtain a cold acetone extract. Table 2 shows the weight, solvent amount, and extract amount of each crude drug used for extraction.
Each crude drug is a marketed product.

[0058]

[Table 2]

(3) Preparation of hot water extract Dried crude drug as it is or crushed, and water is added to about 3
Reflux for hours. The solid content was removed by filtration, concentrated under reduced pressure, and freeze-dried to obtain an extract. Table 3 shows the weight, amount of solvent, and amount of extract of each crude drug used for extraction. Each crude drug is a marketed product.

[0060]

[Table 3]

Example 1 Jack Bean-Derived Urease Activity Inhibition Test: Among the plant extracts obtained in Production Example 1, the plant extract shown in Table 4 was tested for inhibitory activity against urease activity using a jack bean-derived urease. . In addition, the cold methanol extract of the pod flea was used as the pod flea extract. First, to an Eppendorf tube, 20 μl of 100 mM PBS (pH 7.4), 30 μl of each sample solution prepared in Production Example 1, and 50 μl of jack bean urease (manufactured by Sigma) solution (2 U / ml) were added, and the mixture was allowed to stand at 37 ° C. for 10 minutes. Allowed to react. To this reaction solution, 50 μl of a 25 mM urea solution was added and reacted at 37 ° C. Exactly 30 minutes later, 600 μl of 4% trichloroacetic acid (TCA) solution was added to this reaction solution,
It was centrifuged at 00 rpm for 5 minutes. 20 μl of the supernatant was transferred to a 96-well microplate, and the color-developing reagents A, B, and C of the urease test kit (manufactured by Wako Pure Chemical Industries, Ltd.) were each added to 20 μl.
The reaction product ammonia was developed by adding μl, 10 μl and 20 μl. A 2000-fold diluted solution (70 μg / ml) of a concentrated ammonia solution was used as a standard solution, which was serially diluted and added instead of the supernatant. After the reaction, 630
Absorbance value in nm was measured. In addition, the same measurement was performed for a control to which no sample was added as a control. The inhibitory activity (%) was calculated by the following formula. Also,
The concentration of each sample solution having an IC ₅₀ was evaluated as urease inhibitory activity according to the following evaluation criteria. The results are shown in Table 4.

[0062]

[Formula 1] Inhibitory activity (%) = (absorbance _{control group} -absorbance
_{Exposed group} ) / Absorbance _{control group} X100

[0063] <Evaluation>_{<contents> +++: IC 50 <0.16mg /} ml ++: IC 50 <0.8mg / ml +: IC 50 <2mg / ml

[0064]

[Table 4]

From Table 4, it was found that the plant extract of the present invention exerted an excellent urease activity inhibitory effect.

Example 2 Helicobacter pylori-derived urease activity inhibition test: (1) Preparation of H. pylori-derived urease The inhibitory activity of each plant extract obtained in Production Example 1 was tested using the H. pylori-derived urease. did. First, the Helicobacter pylori standard strain (ATCC4350
4) under microaerobic conditions, Brucella Broth (BECT) containing 10% fetal bovine serum
After culturing for 24 hours in ON DICKINSON), the cells were collected by centrifugation at 3,000 rpm for 10 minutes,
Washed once with cold PBS. Add deionized water to this and add 1
It was treated with ultrasonic waves for 5 minutes (5 seconds x 6, 5 seconds interval). Protease Inhibitor Cocktail 1 in bacterial lysate
After adding a tablet (made by Boehringer) and dissolving it, 15,000 r
After centrifugation at pm for 30 minutes, the supernatant was filtered through a 0.22 μm filter. The treatment liquid was treated with a desalting column (PD-10, Pharmacia), the solvent was replaced with PBS, and MW was used.
It was concentrated at a molar cut of 10,000. Glycerol was added to this concentrated solution so that the final concentration was 50%, and the solution was stored at 4 ° C.

(2) Method for measuring urease inhibitory activity In an Eppendorf tube, 100 mM PBS (pH 7.
4), 20 μl, of the samples prepared in Preparation Example 1, Koboku, Kashu, Sappan, Kaifuto, Jurema Preta,
30 μl of each sample solution of radish, walnut, chanoki,
Helicobacter pylori-derived urease solution (urease activity 2 U / m
50 μl (corresponding to 1) was added and the mixture was allowed to stand at 37 ° C. for 10 minutes. Add 50 μl of 25 mM urea solution to the reaction solution,
Reacted at 7 ° C. Exactly 30 minutes later, 600 μl in the reaction solution
4% TCA solution was added and the mixture was centrifuged at 10,000 rpm for 5 minutes. 20 μl of the supernatant was transferred to a 96-well microplate, and 20 μl, 10 μl of the color-developing reagents A, B and C of the urease test kit (manufactured by Wako Pure Chemical Industries, Ltd.),
The reaction product, ammonia, was developed by the addition of 20 μl. A 2000-fold diluted solution (70 μg / ml) of a concentrated ammonia solution was used as a standard solution, which was serially diluted and added instead of the supernatant. After the reaction, the absorption value at 630 nm was measured. The inhibitory activity (%) was calculated in the same manner as in Example 1 and evaluated by the same evaluation criteria. The results are shown in Table 5.

[0068]

[Table 5]

From Table 5, it is confirmed that the extract of Koubo, the extract of Kashi, the extract of Sappan, the extract of Kaifuto, the extract of Jurema preta, the extract of Pleurotus cornucopiae, the extract of walnut, and the extract of Chacobium have excellent inhibitory activity against H. pylori urease. I found out.

Example 3 Bread production: As a plant extract, among the samples prepared in Production Example 1, Klempi, Koboku, Kashu, Kayanomi,
Extracts from Sappan and Umifuto were used. Bread was produced according to a conventional method with the following formulation.

[0071] <Compounding> <Parts by weight> Flour 52 White sugar 3 Condensed milk 4 Unsalted butter 3 Egg 3 Purified salt 1 Raw yeast 1.5 Water 31.5 Plant extract 1

Each of these breads had a characteristic herb flavor and a good taste, and was comparable to ordinary bread.

Example 4 Production of Tea-Like Beverage: Among the samples prepared in Production Example 1, extracts of Klempi, Koboku, Kobushi, Kashu, Kayanomi, Sappan, and Kaifufuji were used as plant extracts. According to the conventional method, 70 g of oolong tea leaves are deionized water of 1 kg at 90 ° C.
And stirred for 5 minutes to perform extraction with stirring. After filtering the obtained oolong tea using a 150 mesh stainless steel filter,
Cool the extract below 30 ° C and run at 3,000 rpm for 10
It was processed for a minute to obtain a clear liquid. This was diluted 8 times with water, sodium ascorbate 0.03% was added, and sodium bicarbonate was added to adjust the pH to about 6.5. After the adjustment, each plant extract was added in an amount of 0.05% to make a tea-like beverage.

Each of the obtained tea-like beverages had a characteristic herbal flavor and had a good taste, and had a preferable flavor as a tea beverage.

Example 5 Production of Preparation: As a plant extract, among the samples prepared in Production Example 1, Klempi, Koboku, Kashu, Kayanomi,
Sappan and Umifuto were used. Take the required amount of the plant extract, and use it as an excipient, a disintegrant, and a lubricant, Avicel (Asahi Kasei Co., Ltd.), fibrin calcium glycolate (EC
G), Sanalmine (manufactured by Kyowa Chemical Industry Co., Ltd.), magnesium stearate, and soft anhydrous silicic acid were mixed according to a conventional method in the following formulation to give a direct compression tablet.

[0076] <Blending> <Weight (g)> Plant extract 1350 Magnesium stearate 45 ECG 120 Avicel 375 Light anhydrous silicic acid 60 Sanalmin 300

[0077]

Industrial Applicability The plant extract used in the urease inhibitor of the present invention, that is, the krempi (bitter bite) extract, the koboku (koboku) extract, the kobushi (kabushi) extract, the sun henz (yamasen) extract. , Hikai (basic) extract, Choengkou (fishing hook) extract, Kayanomi extract, Shiti (persimmon vine) extract, Gokahi (five-skin) extract, Kashu extract, Sappan (Sappan) ) Extract, Taiwan Houfu extract, Haifu extract, Jurema-
Preta) extract, Benito extract, Antarcticus extract, walnut extract and tea tree extract are active ingredients, and these plant extracts themselves are herbal medicines / food ingredients It is safe by (administration) and has very few side effects.

Further, since the urease inhibitor of the present invention can inhibit the activity of the microorganism-derived urease, it is possible to eradicate the microorganism which cannot survive if the activity of the urease is inhibited.

Therefore, medicines and foods and drinks containing this urease inhibitor as an active ingredient are used for the prevention and treatment of diseases caused by urease produced by microorganisms and the eradication of the urease-producing microorganisms themselves. It can be preferably used for the purpose. that's all

Front page continuation (51) Int.Cl. ⁷ Identification code FI theme code (reference) A23L 1/30 A23L 1/30 B 2/38 2/38 C 2/52 A61P 1/04 A61P 1/04 31/04 31/04 43/00 111 43/00 111 A23L 2/00 F (72) Inventor Hiroshi Tadano 1-1-19 Higashishimbashi, Minato-ku, Tokyo Yakult Honsha Co., Ltd. (72) Inventor Mako Nakazawa Tokyo Yakult Honshinbashi, 1-119, Minato-ku, Yakult Honsha Co., Ltd. (72) Inventor Sachiko Matsumoto Tokyo, Higashishimbashi 1-1-19, Minato-ku, Yakult Honsha, Ltd. (72) Inventor Tominaga, Eitaka Tokyo Higashi-Shimbashi 1-1-19 Minato-ku, Yakult Honsha Co., Ltd. (72) Inventor Ritsuo Aiyama 1-1-19 Higashi-Shimbashi, Minato-ku Yakult Honsha (72) Inventor Teruo Yokokura Tokyo 1-19 Higashi-Shimbashi, Minato-ku, Tokyo Yakult Honsha F-term (reference) 4B017 LC03 LG15 4B018 MD61 ME11 4C088 AB03 AB12 AB14 AB16 AB24 AB36 AB42 AB43 AB4 5 AB59 AB65 AB79 AB81 AB84 AC03 AC04 AC05 AC06 AC11 AC13 BA08 BA09 BA10 CA06 CA07 NA14 ZA68 ZB35 ZC20

Claims (8)

[Claims] Claims: 1. Krempi extract, Koboku extract, Kobushi extract, Sanhens extract, Hikai extract, Chokkou extract. Hang extract, Kayanomi extract, Shiti extract, Gokahi extract, Kashu extract, Sappan extract, Taiwan Koufuji extract, Kaifu widow extract , Jurema-Pret
a) 1 of a plant extract selected from an extract, a red bean extract, an algal extract, a walnut extract and a tea tree extract
A urease activity inhibitor comprising one or more species as an active ingredient. 2. The urease activity inhibitor according to claim 1, wherein the urease to be inhibited is derived from a microorganism. 3. The urease which inhibits Helicobacter
The urease activity inhibitor according to claim 1, which is derived from Helicobacter pylori. 4. A medicinal product comprising the urease activity inhibitor according to claim 1. 5. The medicine according to claim 4, which is an antibacterial agent. 6. The pharmaceutical according to claim 4, which is a preventive or therapeutic agent for gastritis. 7. The medicine according to claim 4, which is a preventive or therapeutic agent for gastric ulcer or duodenal ulcer. 8. A food or drink comprising the urease activity inhibitor according to claim 1.