JPH11106335A - Anti-helicobacter pylori agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject medicine having low toxicity, hardly causing adverse effects and safely usable while possessing anti-helicobacter pylori action by including hydroxycinnamic acid or its derivative as an active ingredient. SOLUTION: This medicine contains hydroxycinnamic acid or its derivative as an active ingredient. The hydroxycinnamic acid has three kinds of isomers of 2 hydroxycinnamic acid, 3-hydroxycinnamic acid and 4-hydroxycinnamic acid and all of these isomers can become active ingredients. The hydroxycinnamic acid is preferably derived from propolis. The medicine has preferably 0.01-100 wt.% hydroxycinnamic acid content. A food composition containing the medicine in general foods exhibits prophylaxis of disease or the like caused by infection of Helicobacter pylori or prevention of recurrence thereof and is useful as a food for retaining health of the stomach and intestines.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an anti-Helicobacter
Regarding the pylori agent, specifically, an anti-Helicobacter containing hydroxycinnamic acid or a derivative thereof as an active ingredient.
It relates to a pylori agent.

[0002]

2. Description of the Related Art The involvement of the microaerobic bacterium Helicobacter pylori is known to be a cause of gastric ulcer, duodenal ulcer and gastritis. Helicobacter pylori secretes urease so that it can grow under acidic conditions, produces ammonia from urea contained in stomach contents, neutralizes stomach acid,
It lives in the surface layer of the gastric mucosa. When infected with Helicobacter pylori, gastric acid is neutralized and gastric acid secretion is promoted, and ulcers are likely to occur. It is said that one in two healthy people is infected with Helicobacter pylori, and the number of people suffering from ulcers has recently increased due to the synergistic effect with stress. Prevention of gastric ulcer by removing Helicobacter pylori from the body is expected.

Conventionally, as one of the treatments for gastric ulcer and duodenal ulcer, there is a therapy in which an antibiotic is administered for the purpose of removing Helicobacter pylori from a patient. There is a problem that it is difficult to take.

[0004]

DISCLOSURE OF THE INVENTION In view of such circumstances, an object of the present invention is to provide an anti-Helicobacter pylori which exhibits a remarkable anti-Helicobacter pylori action, has low toxicity, hardly causes side effects, and is safe for ordinary use. -To provide a pylori agent and a food composition.

[0005]

Means for Solving the Problems In order to solve such problems, the present inventors have intensively studied various natural extracts, especially anti-Helicobacter pylori active substances in propolis extracts, and found that phenolic acid A kind of 4
Derivatives such as -hydroxycinnamic acid (alias; p-coumaric acid) and salts thereof have been found to have a remarkable anti-Helicobacter pylori action. Also, 2-hydroxycinnamic acid, which is an isomer of 4-hydroxycinnamic acid (also called o-coumaric acid)
It was also found that 3-hydroxycinnamic acid (also called m-coumaric acid) also had a remarkable anti-Helicobacter pylori effect.

The propolis extract contains antibacterial agents, anti-inflammatory agents,
It has long been used as a folklore drug as an antitumor agent. Recently, the biological effects of propolis extracts have come to the forefront of modern science, and many substances that exhibit antibacterial, anti-inflammatory, antitumor, and other effects, so-called physiologically active substances, have been isolated from propolis extracts. The structure has been clarified. 4-Hydroxycinnamic acid is also one of the compounds and is known to exhibit antibacterial activity against several kinds of microorganisms, but its effect on Helicobacter pylori was unknown. Similarly, the effects of 2-hydroxycinnamic acid and 3-hydroxycinnamic acid were unknown. When the antibacterial spectrum of 4-hydroxycinnamic acid was examined, it was surprisingly found that the antibacterial action was specifically strong against Helicobacter pylori.

The inventors of the present invention have conducted studies based on this finding and have found that an anti-Helicobacter pylori agent containing hydroxycinnamic acid or a derivative thereof as an active ingredient and a food composition containing such an anti-Helicobacter pylori agent The object was established and the present invention was completed.

That is, the present invention provides an anti-Helicobacter pylori agent containing hydroxycinnamic acid or a derivative thereof as an active ingredient, and a food composition containing such an anti-Helicobacter pylori agent.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The anti-Helicobacter pylori agent of the present invention comprises hydroxycinnamic acid or a derivative thereof as an active ingredient. Hydroxycinnamic acid has the structure shown in FIG. Hydroxycinnamic acid has three isomers, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid and 4-hydroxycinnamic acid, all of which exert a remarkable anti-Helicobacter pylori action. In the present invention, not only hydroxycinnamic acid as described above but also physiologically acceptable derivatives thereof can be advantageously used. As physiologically acceptable derivatives, for example, sodium salts, potassium salts, calcium salts, magnesium salts, salts such as ammonium salts, methanol esters,
Ethanol ester, 1-propanol ester,
Ester such as 2-propanol ester, and further, in the structure shown in FIG. 1, 1 or 2 selected from positions 2, 3, 4, 7, and 8 excluding the position to which a hydroxyl group is bonded.
Compounds in which hydrogen at the above positions has been substituted with a hydroxyl group, a sulfate group, and / or a phosphate group, and the like can be given.

As described above, the origin and origin of hydroxycinnamic acid or a derivative thereof used in the present invention (hereinafter, the hydroxycinnamic acid or a derivative thereof used in the present invention may be simply referred to as “the compound”) are not limited. . For example, the compound can be obtained by chemical synthesis or extraction from a natural product such as a plant containing the compound. Methods for preparing from natural products include a method for preparing from propolis and a method for preparing from pineapple stems. When prepared from these natural products, the compound does not necessarily have to be isolated as crystals, but is partially purified to such a degree that it exhibits an antibacterial action as an active ingredient, such as an extract. Such a partially purified product can be obtained by appropriately applying a general extraction method, purification method and the like in the art. For example, first, a natural product such as propolis is crushed as a raw material, extracted with an alcohol such as methanol or ethanol, or an extraction solvent such as a mixture of alcohol and water, and then concentrated by an ordinary method.
The obtained extract can be prepared by subjecting it to gel filtration column chromatography, reverse phase column chromatography, or the like, if necessary. The compound can also be prepared by chemical synthesis.

[0011] The content of hydroxycinnamic acid or a derivative thereof in the anti-Helicobacter pylori agent of the present invention may be such that it can exert an antibacterial effect on Helicobacter pylori in a living body. The minimum growth inhibitory concentration of the compound against Helicobacter pylori (hereinafter, may be abbreviated as "MIC"), usually 15 to 60 ppm or more, may be secured. The content of the compound in the anti-Helicobacter pylori agent of the present invention depends on the dosage form and the symptoms of the target disease, but is usually 0.01 to 100 w / w%, preferably 0.1 to 99%. .5w /
w%, more preferably 0.5 to 90 w / w%.

The anti-Helicobacter pylori agent of the present invention may be in the form of a composition containing the compound alone or other physiologically acceptable components together with the compound, in addition to the compound alone. Other physiologically acceptable components include non-toxic diluents, fillers, other known auxiliaries for prescription, and, if necessary, antioxidants, antacids and physiologically active substances. Used as appropriate. For example, excipients such as starch, maltose, trehalose, calcium carbonate, calcium phosphate, gum arabic, pullulan, used for solid preparations such as capsules, powders, granules, tablets,
Gelatin, binders such as hydroxypropylcellulose, lubricants such as magnesium stearate and talc, and distilled water, physiological saline, alcoholic water, and vitamin E, ascorbic acid,
Antioxidants such as glucosyl ascorbic acid, rutin, hesperidin, enzyme-treated rutin, enzyme-treated hesperidin, tocopherol, antacids such as aminoacetic acid, sodium bicarbonate, hydrotalcite, methyl methionine, sulfonium chloride, and aceglutamide aluminum,
Any physiologically active substance such as urogastron, sucralfate and secretin can be advantageously used.

The anti-Helicobacter pylori agent of the present invention as described above is usually used orally or parenterally after administration to animals including humans, and is used for the treatment of various diseases caused or related to Helicobacter pylori infection. Successful treatment, prevention and / or prevention of recurrence. For example, the Helicobacter pylori agent of the present invention is an anti-ulcer agent that is effective in treating and preventing ulcers such as gastric ulcer and duodenal ulcer and an anti-inflammatory agent that is effective in treating and preventing inflammation such as gastritis and enteritis. It is useful as an agent. Furthermore, the anti-Helicobacter pylori agent of the present invention is also useful as an agent for treating, preventing and / or preventing recurrence of various gastrointestinal-related diseases such as gastric cancer, which has been pointed out to be associated with Helicobacter pylori infection. The dose can be appropriately adjusted depending on the administration frequency, symptoms, body weight, age and the like. Usually, the administration of hydroxycinnamic acid or a derivative thereof in the range of about 1 to 200 mg per adult per day as a solid weight is suitable.

The present invention also provides a food composition comprising the above-mentioned anti-Helicobacter pylori agent in a general food. As foods, for example, candies, troches, jellies, gummy, chewing gum, chocolate, juice, soft drinks, alcoholic beverages,
Lactic acid bacteria drinks, jams, creams, cookies, biscuits, rice crackers, crackers, udon, buckwheat, sausage, ham, Kamaboko, bamboo rings, halves, tsukudani, instant juice, instant soup and the like can be mentioned. Such a food composition may be produced by appropriately adding and mixing the above-mentioned anti-Helicobacter pylori agent in the step of producing a desired food according to a conventional method. The content of the compound in such a food composition is not particularly limited. In particular, when the content is 0.01 to 5% by weight of the food, the original taste, flavor, and texture of the food are not impaired, and Is useful because it can obtain the effect of the period. In addition, since the compound is extremely safe, the food composition as described above can be routinely used with confidence. From these facts, the food composition containing an anti-Helicobacter pylori agent of the present invention is effective in preventing and preventing recurrence of various diseases caused or related to infection with Helicobacter pylori, Useful as a food to maintain health. The intake of such a food composition is appropriately adjusted depending on the frequency of intake, symptoms, body weight, age, form of food, and the like, and is generally in the range of 1 to 200 mg as a solid weight of the compound per adult per day. It is suitable.

Hereinafter, the present invention will be described in detail with reference to experimental examples.

[0016]

EXPERIMENTAL EXAMPLE 1 <Preparation of 4-hydroxycinnamic acid> 150 parts by weight of an original Brazilian propolis mass was pulverized and extracted with a 90% (v / v) aqueous ethanol solution. After leaving the extract at 4 ° C. overnight, it was filtered using diatomaceous earth, and the filtrate was concentrated and dried to obtain 70 parts by weight of a propolis extract as a solid.

This propolis extract was prepared in a volume ratio of 70: 3.
The mixture was dissolved in a hexane / ethyl acetate mixed solution of 0 and loaded on a column filled with silica gel "Kilica Gel 60 K650" manufactured by Katayama Chemical Industry at a rate of about 25 g of solids per liter of gel. Was applied at a flow rate of about 1.5 SV to give a linear gradient to the volume ratio, and column chromatography was carried out. The fraction eluted with a hexane / ethyl acetate mixed solution having a volume ratio of about 30:70 to 15:80 was collected and concentrated to dryness to obtain 18.4 parts by weight of a solid.

Next, this fraction was dissolved in a 40% (v / v) methanol aqueous solution, and about 15 g of a solid substance per liter of gel was applied to a column filled with octadecyl silica gel “silica gel ODS FS-1830” manufactured by Organo. The column chromatography was carried out by applying an aqueous methanol solution as an eluent at a flow rate of about 1.5 SV while giving a linear concentration gradient. About 60-90% concentration
The fraction eluted with the (v / v) aqueous methanol solution was collected, concentrated and dried to obtain 1.9 parts by weight of a solid.

Next, 1.5 parts by weight of this fraction was dissolved in a mixture of methanol, water and acetic acid at a volume ratio of 75: 25: 1, and the column “YMC Pack” manufactured by YMC was used.
ODS-A "was loaded at a rate of about 0.5 g of solids per liter of gel, and a methanol / water / acetic acid mixture of 75: 25: 1 by volume was passed as eluent at a flow rate of about 0.6 SV. And column chromatography was performed. The fraction eluted at an elution position in the vicinity of about 0.6 times the carrier volume of the column was collected to obtain 0.58 parts by weight as a solid. This fraction was concentrated to dryness, dissolved in methanol, and added with 0.5
The mixture was left at about 4 ° C. to precipitate crystals. The crystals were washed with methanol to obtain 0.37 parts by weight of a crystal sample.

The physicochemical properties of the compound obtained as a crystal sample above were examined. (1) Elemental analysis When the elemental composition was analyzed by an ordinary method using an elemental analyzer, C = 65.85%, H = 4.91%, and O = 2.
It was determined to be 9.24%. From these results, the chemical composition of this compound was estimated to be C: H: O = 9: 8: 3, and the theoretical values of the elemental composition were C = 65.57%, H = 5.02%, and O = 2.
It was determined to be 9.47%. (2) Molecular weight From the chemical composition estimated by the above-described elemental analysis and the result of carbon nuclear magnetic resonance analysis described later, the molecular formula of the present compound was represented by C ₉ H ₈ O.
Decided to be ₃ . From this molecular formula, the molecular weight of this compound is 16
4.16 was determined. (3) Melting point After filling a crystal sample with the tip of a capillary glass tube by about 1 mm according to a conventional method, the melting end temperature was measured by a melting point measuring instrument. As a result, the melting point of the present compound was 206 ° C. (4) Ultraviolet absorption The crystal sample was dissolved in methanol to a concentration of 6.0 μg / ml, and the ultraviolet absorption spectrum was measured by a conventional method. The results are shown in FIG. As is clear from FIG. 2, this compound had absorption maximums at 209 nm, 222 nm and 289 nm. (5) Infrared absorption spectrum A tablet was prepared by mixing 1.0 mg of the crystal preparation and 200 mg of dry KBr, and the infrared absorption spectrum was measured according to a conventional method. As shown in FIG.
^{80cm -1, 1670cm -1, 1625cm -1} , 160
It had absorption at 0 cm ^{-1 and the} like. These values are based on the infrared absorption spectrum of 4-hydroxycinnamic acid described in "The Aldrich Library of Infrared Spectra", 2nd edition (1975), page 834, issued by Aldrich Chemical Company. And matched. (6) Carbon Nuclear Magnetic Resonance Analysis ( ¹³ C-NMR) The crystal sample was subjected to carbon nuclear magnetic resonance analysis using tetramethylsilane as an internal standard according to a conventional method.
1 in 71.1 ppm, 1 in 161.1 ppm, 14
One at 6.7 ppm, two at 131.1 ppm, 12
One at 7.2 ppm, two at 116.8 ppm, and 1
One signal at 15.6 ppm was observed for a total of 9 carbons. From these results, it was considered that the number of carbon atoms per molecule of the present compound was 9. In addition, these values Aldrich Chemical Co. issue, "di-Aldrich Library of · ¹³ C · and · ¹ H · F. tea NV Em Earl Spectra", first edition, Vol. 2 (1
993), page 1,051, about 2 ppm of the chemical shift value of each carbon of 4-hydroxycinnamic acid, which is considered to be a value caused by a difference in internal standard and resolution.
Well matched with the value obtained by adding. (7) where the hydrogen nuclear magnetic resonance analysis of ⁽¹ H-NMR) crystal preparation according to a conventional method and subjected to hydrogen NMR analysis using tetramethylsilane as internal standard,
7.62 ppm (1H, d, J = 15.6 Hz);
45 ppm (2H, d), 6.83 ppm (2H, d)
And 6.30 ppm (1H, d, J = 15.6 Hz)
In total, signals for 6 hydrogen atoms were observed. From this result, it was considered that the number of hydrogens directly bonded to carbon in the present compound was 6 per molecule. (8) Chemical structure From these results, the compound obtained as a crystal sample above was identified as a known compound, 4-hydroxycinnamic acid. FIG. 4 shows the chemical structure of this compound.

[0021]

[Experimental example 2] <Antibacterial activity against Helicobacter pylori> Experimental example 1
The antibacterial activity of 4-hydroxycinnamic acid, which was isolated and identified as a crystal sample in Helicobacter pylori, was determined by Mitsuhashi,
Chemotherapy, Vol. 29, pp. 76-79 (198
1 year) according to the minimum inhibitory concentration (MIC) measurement method. For comparison, propolis extract extracted with 90% (v / v) ethanol, commercially available reagents 4-hydroxycinnamic acid (Funakoshi sales), 3-hydroxycinnamic acid (Funakoshi sales), 2-hydroxycinnamic acid (Funakoshi sales), The antibacterial activity of the antibiotics amoxicillin (Sigma) and metronidazole (Sigma) was also measured. Helicobacter pylori ATCC43504, NCTC11638, and 1576 strains and 2101 strains (obtained from Hyogo College of Medicine) isolated from clinical specimens were used as test strains.

The antibacterial activity was measured by adding 7% (w /
v), glucose 0.1% (w / v) and agar 1.5%
A test agar plate was prepared by adding a test medium to each of the above-mentioned test samples separately and appropriately to the basic medium to which (w / v) had been added, and the presence or absence of growth of the test strain on the test agar plate was determined. Was. The final concentration of each test sample on the test agar plate was 250 μg / ml, and the concentration was two-fold diluted sequentially.

First, while preparing the test agar plate described above, the agar plate was slightly aerobic using the above-described basic medium using a gas generating bag “CampyPak” manufactured by BB and placed in a culture chamber under high humidity conditions. At 37 ° C. for 5 days. One platinum loop of precultured cells was suspended in 1 ml of "brucella broth", and the suspension was streaked on a test agar plate, and then cultured according to the method of preculture. After 5 days of culture, the MIC was determined by observing the presence or absence of growth of the strain on each test agar plate. Table 1 shows the results.

[0024]

[Table 1]

As is evident from the results in Table 1, 4-hydroxycinnamic acid, 3-hydroxycinnamic acid and 2-hydroxycinnamic acid, although not as effective as the antibiotics amoxicillin and metronidazole, were all present in Helicobacter pylori. It was found to have strong antibacterial action. Separately, sodium salts and calcium salts of the above-mentioned 4-hydroxycinnamic acid, 3-hydroxycinnamic acid and 2-hydroxycinnamic acid were prepared in accordance with a conventional method, and the antibacterial activity of these salts was measured in this Experimental Example 2. The test was performed according to the method used in the above. As a result, it was confirmed that each of these salts exhibited almost the same antibacterial activity against Helicobacter pylori as described above. As described above, hydroxycinnamic acid and derivatives thereof all exert a remarkable anti-Helicobacter pylori effect, and the present invention comprising the compound as an active ingredient,
It shows that it is useful as an anti-Helicobacter pylori agent.

[0026]

[Experimental Example 3] <Antibacterial activity against various microorganisms> The antibacterial activity against various microorganisms of 4-hydroxycinnamic acid obtained as a crystal sample in Experimental Example 1 was examined in the same manner as in Experimental Example 2. The highest concentration of 4-hydroxycinnamic acid in the test agar plate was 2,000.
0 μg / ml. For culturing Helicobacter pylori, the same medium as in Experiment 2 was used as a basal medium. Bacillus cereus, Klebsiella pneumoniae, Escherichia.
Coli and Staphylococcus aureus with Nissui's "Agar Medium for Sensitive Discs-N", Lactobacillus brevis and Clostridium butyricum with Nissui's "Modified GAM Agar", Alsloderma Benhamie, "Potato dextrose agar" manufactured by Nissui was used for S. cerevisiae and Pifia anomala. Table 2 shows the results.

[0027]

[Table 2]

As is evident from the results in Table 2, 4-hydroxycinnamic acid showed an antibacterial activity against various microorganisms, but among the microorganisms examined, it has a strong antibacterial activity especially against Helicobacter pylori. I knew I was doing it. In addition, 3-hydroxycinnamic acid, 2-hydroxycinnamic acid and salts of these compounds used in Experimental Example 2 were separately tested in accordance with the method used in Experimental Example 3. As a result, almost all of the compounds were similarly Helicobacter
It showed strong antibacterial activity against H. pylori. The above results
Hydroxycinnamic acid or a derivative thereof is a Helicobacter
This shows that the present invention, which exhibits an antibacterial action specifically against H. pylori and uses the compound as an active ingredient, is useful as an anti-Helicobacter pylori agent.

[0029]

[Experimental Example 4] <Acute toxicity> The 4-hydroxycinnamic acid, 3-hydroxycinnamic acid, 2-hydroxycinnamic acid, sodium salt and calcium salt of these compounds used in Experimental Example 2 were separately sterilized physiological saline. It was appropriately dissolved or suspended in water. This was injected or intraperitoneally administered to ddy mice (10 mice / group) weighing 20 to 25 g or orally by gastric probe, and the progress was observed for 7 days. Regardless of the case of any of the compounds, no death was observed even in the case of administration of the compound at the maximum dose of about 0.1 g per kg of mouse body weight, which was the highest dose tried, by any of the administration routes. This indicates that the anti-Helicobacter pylori drug is safe even for regular use in animals including humans.

Hereinafter, embodiments of the present invention will be specifically described based on examples.

[0031]

Example 1 <Solution> 4-hydroxycinnamic acid 5 obtained by the method of Experimental Example 1
Parts by weight were dissolved in 95 parts by weight of 80 v / v% ethanol to obtain a liquid anti-Helicobacter pylori agent. This product is used as a raw material for manufacturing or diluting or suspending in a solvent containing water, and is used as a raw material for the treatment and prevention of diseases and symptoms caused or related to Helicobacter pylori infection. It is advantageously used as a liquid preparation. In particular, it is useful as an anti-ulcer agent which is effective in treating and preventing gastric ulcer and duodenal ulcer, and a liquid agent which is effective in preventing gastric cancer and preventing recurrence. Further, it is also advantageous to produce a solid preparation such as granules, capsules, tablets and the like by absorbing it into an excipient, and to use it by taking it internally.

[0032]

Example 2 <Solution> 50 parts by weight of the liquid anti-Helicobacter pylori agent obtained by the method of Example 1 and 2 parts by weight of ascorbic acid were added to water 4
5 parts by weight were mixed and adjusted to pH 7.4 with 1N-disodium phosphate to prepare a liquid anti-Helicobacter pylori agent. This product is used as it is, for diseases caused or related to Helicobacter pylori infection.
It is advantageously used as a liquid preparation that is effective in treating and preventing symptoms. In particular, it is useful as an anti-ulcer agent which is effective in treating and preventing gastric ulcer and duodenal ulcer, and a liquid agent which is effective in preventing gastric cancer and preventing recurrence. Further, similarly to Example 1, it can be advantageously carried out to produce another liquid preparation by further diluting, or to produce a solid preparation by absorbing it into an excipient.

[0033]

Example 3 <Solution> The procedure of Example 1 was repeated except that the 4-hydroxycinnamic acid sodium salt obtained in Experimental Example 2 was used instead of 4-hydroxycinnamic acid used in Example 1. A liquid anti-Helicobacter pylori agent was obtained. Next, 45 parts by weight of water was mixed with 50 parts by weight of this liquid anti-Helicobacter pylori agent, and the mixture was adjusted to pH with 1N-disodium phosphate.
The mixture was adjusted to 7.4 to prepare a liquid anti-Helicobacter pylori agent. The product is advantageously used as a liquid preparation that is used as it is, which is effective in treating and preventing diseases and symptoms caused or related to Helicobacter pylori infection.
In particular, it is useful as an anti-ulcer agent which is effective in treating and preventing gastric ulcer and duodenal ulcer, and a liquid agent which is effective in preventing gastric cancer and preventing recurrence. Further, similarly to Example 1, it can be advantageously carried out to produce another liquid preparation by further diluting, or to produce a solid preparation by absorbing it into an excipient.

[0034]

Example 4 <Powder> 9 parts by weight of 80 v / v% ethanol was added to 2 parts by weight of 3-hydroxycinnamic acid used in Experimental Example 2 to obtain a pH of 7.
The mixture was neutralized to 0, dissolved by heating, mixed with 8 parts by weight of cyclodextrin powder, and dried under reduced pressure to prepare a powdery anti-Helicobacter pylori agent. The product is advantageously used as a powder that is effective for the treatment and prevention of diseases and symptoms caused or related to Helicobacter pylori infection. In particular, it is useful as an anti-ulcer agent that is effective in treating and preventing gastric ulcer and duodenal ulcer, and a powder that is effective in preventing gastric cancer and preventing recurrence. Further, it can be advantageously carried out to produce and use another solid preparation by further processing, or to prepare and use a liquid preparation by dissolving or suspending in a solvent containing water.

[0035]

Example 5 <Granules> 1 part by weight of 2-hydroxycinnamic acid, 8 parts by weight of calyx, 6 parts by weight of Engosaku, Borei 6 used in Experimental Example 2
Parts by weight, 3 parts by weight of fennel, 2 parts by weight of liquorice, 2 parts by weight of shukusha, and 1 part by weight of Ryokyo were uniformly mixed to prepare a granular anti-Helicobacter pylori agent.
The product is advantageously used as a granule, which is used as it is, and is effective in treating and preventing diseases and symptoms caused or related to Helicobacter pylori infection. In particular, it is useful as an anti-ulcer agent that is effective in treating and preventing gastric ulcer and duodenal ulcer, and a granule that is effective in preventing gastric cancer and preventing recurrence. Further, it can be advantageously carried out to produce and use another solid preparation by further processing, or to prepare and use a liquid preparation by dissolving or suspending in a solvent containing water.

[0036]

Example 6 <Tablet> The same method as in Example 4 except that the calcium salt of 2-hydroxycinnamic acid obtained in Experimental Example 2 was used instead of the 3-hydroxycinnamic acid used in Example 4. To prepare a powder. 5 parts by weight of this powder, 5 parts by weight of trehalose powder and 5 parts by weight of lactose powder were uniformly mixed, and the mixture was uniformly mixed with a rotary tableting machine to a diameter of about 1 by a conventional method.
A tablet having a thickness of 0 mm and a thickness of about 2 mm was obtained. This product is advantageously used as a tablet that is used as it is, which is effective in treating and preventing diseases and symptoms caused or related to Helicobacter pylori infection. In particular, it is useful as an anti-ulcer agent that is effective in treating and preventing gastric ulcer and duodenal ulcer, and as a tablet that is effective in preventing gastric cancer and preventing recurrence.

[0037]

Example 7 <Chewing gum> 0.5 part by weight of the powder obtained by the method of Example 4, 2 parts by weight of glucose, 5 parts by weight of trehalose, and 2 parts by weight of a gum base heated and melted to a softness were added and mixed. After mixing an appropriate amount of mint flavor, the mixture was kneaded with a roll according to a conventional method and molded to produce a chewing gum. This product has excellent texture with a refreshing flavor in addition to mellow sweetness. This product is easy to eat and exerts an anti-Helicobacter pylori effect in vivo when eaten, so it is effective in preventing gastric ulcer, duodenal ulcer or gastritis caused by or related to Helicobacter pylori infection and preventing recurrence of gastric cancer. It can be used advantageously as a food that keeps your stomach healthy.

[0038]

Example 8 <Soft drink> 10 parts by weight of granules obtained by the method of Example 5,
Water was added to 20 parts by weight of isomerized sugar, 40 parts by weight of trehalose, 0.5 g by weight of citric acid, and 0.5 part by weight of L-ascorbic acid to make the total amount 1000 parts by weight, thereby producing a soft drink. This product is a product with excellent taste that exhibits a refreshing flavor in addition to a mild sweetness and a moderate bitterness. This product is easy to swallow and exhibits an anti-Helicobacter pylori effect when ingested in the body, so it is effective in preventing gastric ulcer, duodenal ulcer or gastritis caused by or related to Helicobacter pylori infection and preventing recurrence of gastric cancer. It can be advantageously used as a food that keeps the stomach healthy.

[0039]

Example 9 <Hard candy> To 300 parts by weight of trehalose-containing starch syrup, 800 parts by weight of reduced maltose syrup was added and mixed and dissolved. The mixture was concentrated under reduced pressure until the water content was less than 2%. Parts by weight and an appropriate amount of a lemon flavor and a colorant were mixed, and 10 parts by weight of 4-hydroxycinnamic acid sodium salt obtained by the method of Experimental Example 2 was added and mixed.
Subsequently, it was molded according to a conventional method to produce a hard candy. This product is a crisp hard candy that has an elegant sweetness, low hygroscopicity and is less likely to cause dripping. This product is easy to eat and exerts an anti-Helicobacter pylori effect in vivo when eaten, so it is effective in preventing gastric ulcer, duodenal ulcer or gastritis caused by or related to Helicobacter pylori infection and preventing recurrence of gastric cancer. It can be used advantageously as a food that keeps your stomach healthy.

[0040]

Industrial Applicability As described above, the present invention is based on the fact that hydroxycinnamic acid or a derivative thereof contained in propolis and the like, which exists as a natural product and has been eaten by humans, inhibits the growth of Helicobacter pylori well. It is based on unique knowledge. The anti-Helicobacter pylori agent of the present invention comprising such hydroxycinnamic acid or a derivative thereof as an active ingredient is useful for treating and / or preventing diseases caused or related to Helicobacter infection, for example, gastric ulcer, duodenal ulcer or gastritis. In addition, it can be advantageously used to prevent recurrence of gastric cancer. In addition, such anti-Helicobacter
The food composition of the present invention containing a pylori agent is effective in preventing and preventing recurrence of diseases caused or related to Helicobacter infection, and can be advantageously used as a food for maintaining stomach health.

[Brief description of the drawings]

FIG. 1 is a diagram showing the chemical structure of hydroxycinnamic acid used in the present invention by a general formula.

FIG. 2 is a view showing an ultraviolet absorption spectrum of a compound isolated from propolis used in the present invention.

FIG. 3 is a view showing an infrared absorption spectrum of a compound isolated from propolis used in the present invention.

FIG. 4 is a diagram showing the chemical structure of 4-hydroxycinnamic acid used in the present invention.

Claims (5)

[Claims] 1. An anti-Helicobacter pylori agent comprising hydroxycinnamic acid or a derivative thereof as an active ingredient. 2. Hydroxycinnamic acid or a derivative thereof is added to 0.1%.
The anti-Helicobacter pylori agent according to claim 1, which contains 1 w / w% or more. 3. The anti-Helicobacter pylori agent according to claim 1, wherein the hydroxycinnamic acid or a derivative thereof is derived from propolis. 4. The anti-Helicobacter pylori agent according to claim 1, 2 or 3 as an anti-ulcer agent. 5. A food composition comprising the anti-Helicobacter pylori agent according to claim 1, 2, 3 or 4.