KR20180063597A - Composition for inhibiting a growth of Helicobacter Pylori - Google Patents

Abstract

The present invention relates to a Helicobacter pylori composition that inhibits the growth of (also called Helicobacter Pylori, the "H. pylori") including a gallate, by containing more specifically, catechin, epicatechin, caffeine, gallate, etc. to a specific combining ratio And a health functional food composition capable of improving, alleviating, treating, or preventing gastrointestinal diseases such as gastric ulcer and gastric cancer caused by abnormal hyperplasia of Helicobacter by suppressing the growth of Helicobacter.

Description

Composition for inhibiting growth of Helicobacter pylori {

The present invention relates to a composition for inhibiting the growth of Helicobacter pylori (hereinafter referred to as " Helicobacter ") comprising gallic acid or a salt or derivative thereof as an active ingredient, and more particularly to a composition inhibiting the growth of Helicobacter pylori A composition for preventing, ameliorating, treating, or preventing gastrointestinal diseases such as gastric ulcer and gastric cancer caused by excessive hyperplasia of Helicobacter by suppressing the growth of Helicobacter by containing as a active ingredient in combination with catechin, epicatechin, And / or a health functional food composition.

Helicobacter pylori, which was found in 1983, is known to cause gastritis, gastric ulcer, low-grade mucosal-associated lymphoid tissue lymphoma, gastric cancer, etc. It is known that most human beings are infected from childhood. In Korea, more than 60% Have been reported to be infected.

Infected helicobacter causes inflammation. When the inflammation spreads to the stomach submucosa, gastric ulcer occurs, which is known to increase the prevalence of gastric cancer by 3 to 5 times. According to the US National Institutes of Health, the use of antibiotics targeting Helicobacter is permitted for the treatment of gastric ulcers and peptic diseases, but the long-term use of antibiotics targeting all Gram-negative bacteria including Helicobacter are not only harmful bacteria, The emergence of resistant bacteria, bacterial bacteremia disturbance in the intestines, and so on.

Therefore, it is urgent to find alternative therapies that can effectively treat the digestive system-related diseases by effectively inhibiting the growth of Helicobacter but the side effects are small compared to the use of existing antibiotics.

1. Domestic registered patent No. 10-0673605 (Notice of January 24, 2007) 2. Domestic Registered Patent No. 10-0602841 (Announced on July 19, 2006) 3. Domestic Registered Patent No. 10-0474942 (Announcement of Mar., 2005)

The present inventors searched for a substance which can effectively inhibit the growth of Helicobacter, by effectively acting on Helicobacter, a harmful bacteria in the intestine, without affecting the intestinal beneficial bacteria. It has been found that an effective inhibitory effect on the growth of Helicobacter can be obtained by combining at least one species in a specific ratio.

Accordingly, the present invention relates to gallic acid, or a salt or derivative thereof; And a composition capable of effectively inhibiting the growth of Helicobacter by incorporating at least one of catechin, epicatechin and caffeine in a specific ratio in combination.

In order to accomplish the above object, the present invention provides a method for inhibiting Helicobacter pylori, And a health functional food composition containing at least one of catechin, epicatechin and caffeine as an active ingredient for improving, alleviating, treating, or preventing gastric function disorders.

The composition of the present invention contains a specific combination ratio of gallic acid or a salt or derivative thereof and a combination of other ingredients that have not previously been studied for their action in the digestive system so that they act safely and effectively on the helicobacter, Thereby inhibiting growth, thereby preventing and treating gastrointestinal-related diseases.

FIG. 1 is a graph showing the results obtained by orally administering the growth inhibition rate of Helicobacter in Examples 1 to 13, Comparative Examples 1 to 4, and Reference Example 2 to mice, and then detecting the presence of Helicobacter pylori by PCR .
FIG. 2 is a graph showing the cytotoxicity test results of the components used in the present invention.
FIG. 3 shows the results of oral administration of the growth inhibiting rate of Helicobacter by long-term administration to mice in Examples 1 to 13, Comparative Examples 1 to 4, and Reference Example 2 for 8 weeks, and then the gastric DNA was extracted to determine the presence or absence of Helicobacter pylori The results obtained by PCR are shown in a graph.

The composition according to the present invention may be gallic acid, or a salt or derivative thereof; And at least one of catechin, epicatechin and caffeine as effective ingredients to improve, alleviate, cure or prevent stomach dysfunctions such as gastritis, gastric ulcer, low-grade mucosal-associated lymphoid tissue lymphoma and gastric cancer caused by Helicobacter pylori Can be used.

The gallic acid used in the present invention is a phenolcarboxylic acid obtained by alkali hydrolysis of tannin, which is also called gallic acid. A compound having the formula C ₇ H ₆ O ₅ and a molecular weight of 170, and has a structure represented by the following formula (1).

[Chemical Formula 1]

Glycans are generally present in plants such as leaves, fruits, stems, roots, etc., but galantanin forms a sugar and a debod seed and contains plants at very high concentrations.

The salt of gallic acid used in the present invention may be in the form of a salt of, for example, a metal salt, particularly an alkali metal or an alkaline earth metal. Specifically, it may be in the form of a salt such as Li, Na, K, Ca or Mg, It is not.

The gallic acid derivatives used in the present invention include, but are not limited to, epigallocatechin gallate (EGCG), gallocatechin gallate (GCG), epicatechin gallate (ECG), catechin gallate .

In the composition of the present invention, gallic acid, or a salt or derivative thereof, is contained in combination with other ingredients such as catechin, epicatechin, caffeine and the like in a specific ratio, and the combination ratio differs depending on the components to be combined.

Specifically, the gallic acid or a salt or derivative thereof is combined with catechin in a weight ratio of 1: 1 to 3, preferably 1: 2 to 2.5, more preferably 1: 2.1 to 2.3, with epicatechin at a ratio of 1: 2.5 to 4.5 , Preferably from 1: 2 to 3, more preferably from 1: 2.6 to 3.6, in a weight ratio of 1: 3 to 4, preferably 1: 3.5 to 3.6, ≪ / RTI > to 2.7. Preferably, the present invention relates to gallic acid, or a salt or derivative thereof, as an active ingredient; Catechin; Epicatechin; And caffeine. Particularly, the combination ratio of these components is 1: 1 to 3: 2.5 to 4.5: 1.5 to 3.5, more preferably 1: 2 to 2.5: 3 to 4: Can be from 1: 2.1 to 2.3: 3.5 to 3.6: 2.6 to 2.7, or 1: 2: 4: 3.

The gallic acid, salt or derivative thereof, and other ingredients used in the present invention may be extracted from plants, synthesized according to methods known in the art, or commercially available ones may be used. Alternatively, an extract of fermented green tea may be used. In the case of fermented green tea prepared according to the manufacturing method of the fermented green tea described below, since the extract contains gallate, catechin, epicatechin and caffeine in the ratio described above, it can be applied to the composition of the present invention Do.

The post-fermented green tea which can be used in the present invention can be produced by the following method.

The method for producing a post-fermented green tea according to the present invention can be used to produce a fermented tea by inoculating a strain derived from a green tea into a green tea leaf and fermenting it for a certain period of time.

The soybean-derived strain may be a soybean fermented soybean paste prepared by using Meju, a soybean paste produced from soybean paste, soybean paste, soybean paste or soybean fermented soybean produced using soybean. The strains derived from the genus include, for example, Bacillus subtilis, Bacillus licheniformis, Bacillus megateriums, Bacillus natto, Bacillus citrus ( Bacillus citreus, Bacillus circulans, Bacillus mesentricus, Bacillus pumilus, and the like.

In addition, the process of fermenting the fermented broth inoculated with the strain may take 14 to 28 days. The fermentation temperature may be 20 to 70 ° C, specifically 40 to 60 ° C. If the fermentation temperature exceeds 40 ° C, the growth of the remaining bacteria other than the Bacillus subtilis bacteria is inhibited or killed. If the fermentation temperature becomes too high, the growth of Bacillus subtilis bacteria is inhibited. Therefore, The fermentation can not proceed.

Hereinafter, a method for manufacturing a post-fermented green tea according to an embodiment of the present invention will be described in more detail.

Bacillus subtilis (Bacillus subtilis) cultured at 30 ° C for 72 hours in a vibrating incubator is recovered, and the strain and the active medium are separated using a centrifuge. After washing the strains isolated with 1.0% physiological saline, 2.5% by weight of sugar and 2.0% by weight of fructose were mixed with purified water, and sterilized at 120 ° C for 3 hours under high pressure for 15 minutes. And the number of fermentation strains is 10 ³ to 10 ⁸ CFU / ml. In the sterilized reaction tank, mix the green tea leaves with the fermentation broth (60% by weight based on the green tea leaf weight) and mix well for 20 minutes. After the completion of the stirring, the fermentation process is carried out at 42 ° C for 14 days in a state where it is transferred to a constant temperature fermenter and the inflow of the outside air is prevented. When the fermentation is completed, it may be subjected to a drying process through hot air drying.

After fermentation is complete, the fermented green tea can be extracted through a variety of methods, including, but not limited to, hot water or C ₁ to C ₅ lower alcohols as extraction solvents. Specifically, hot water or ethanol (particularly, 50% (v / v) ethanol) can be used.

The composition of the present invention contains the active ingredient in an amount of 0.1 to 50% by weight based on the total weight of the composition. If it is contained in an amount of less than 0.1% by weight, the growth inhibition effect of Helicobacter is not exhibited. If it is contained in an amount of more than 50% by weight, heartburn may be felt at the time of fasting.

In addition to reducing the inflammation caused by the infected Helicobacter, the composition of the present invention can prevent inflammation from being caused by the Helicobacter by inhibiting the live bacteria of Helicobacter, thereby effectively preventing the disease from occurring.

Therefore, the composition of the present invention can improve gastric dysfunction, and more specifically, can be used to prevent or treat digestive-related diseases such as gastritis, gastric ulcer, low-grade mucosa-associated lymphoid tissue gastric lymphoma, stomach cancer and the like.

The composition of the present invention may be formulated into a health functional food or a pharmaceutical composition.

The pharmaceutical composition according to the present invention may further contain a preservative, a stabilizer, a wetting agent or an emulsifying accelerator, a pharmaceutical adjuvant such as a salt and / or a buffer for controlling osmotic pressure, and other therapeutically useful substances, Orally, orally, or parenterally, intravenously, or the like in the form of solid, semi-solid or liquid form, with or without an organic carrier.

Examples of the oral administration agent include tablets, pills, hard and soft capsules, liquids, suspensions, emulsions, syrups, granules, etc. These formulations may contain, in addition to the active ingredient, a diluent such as lactose, dextrose, Sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (e.g., silica, talc, stearic acid and magnesium or calcium salts thereof and polyethylene glycols). Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally mixed with starch, agar, alginic acid or its sodium salt Such as disintegrants, absorbents, coloring agents, flavoring agents, and sweetening agents. The tablets may be prepared by conventional mixing, granulating or coating methods.

The parenteral administration agent may be, for example, a formulation such as Ringer's solution, suppository, etc., but is not limited thereto.

The health functional food composition may be formulated into, for example, a pill, a capsule, a tablet, a granule, a drink, and the like, although the formulation is not particularly limited. The health food composition of each formulation may be formulated by those skilled in the art without difficulty, depending on the purpose of formulation or use, in addition to the active ingredient, and the synergistic effect may occur when the composition is applied simultaneously with other ingredients .

The dosage of the active ingredient is within the level of those skilled in the art, and the daily dose of the drug depends on various factors such as the degree of progress of the subject to be administered, the age of onset, age, health condition, As a standard, it is generally possible to administer 1 to 2500 mg / kg of the composition, preferably 50 to 1000 mg / kg, once or twice a day, and the dose may be administered in any manner within the scope of the invention It is not limited.

Hereinafter, the present invention will be described more specifically with reference to examples and test examples. It is to be understood that the scope of the present invention is not limited to these embodiments and that variations, substitutions, and insertions conventionally known in the art can be carried out, And this is included in the scope of the present invention.

[Referential Example 1] Preparation of active ingredient

Glycans, catechins (GC and GCG and others) for testing the efficacy of the compositions of the present invention were obtained from Sigma Aldrich, EGCG among epicatechins was purchased from Wako, and EGC was purchased from Sigma-Aldrich. Caffeine was also obtained from Sigma-Aldrich.

[Reference Example 2] Preparation of an extract of green tea after fermentation

Bacillus subtilis (Bacillus subtilis) cultured at 30 ° C for 72 hours in a vibrating incubator was recovered and the strain and active medium were separated using a centrifuge. After washing the strains isolated with 1.0% physiological saline, 2.5% by weight of sugar and 2.0% by weight of fructose were mixed with purified water, and sterilized at 120 ° C for 3 hours under high pressure for 15 minutes. , So that the number of fermentation strains, i.e., Bacillus subtilis, was 10 ³ to 10 ⁸ CFU / ml. In the sterilized reaction tank, the green tea leaves and the fermenter solution (60% by weight based on the green tea leaf weight) were mixed and stirred for 20 minutes. After the completion of stirring, the fermentation process was carried out at 42 ° C for 14 days in a state where it was transferred to a constant-temperature fermenter and prevented the influx of external air. After fermentation, the post-fermented tea mixture was hot-air dried at 80 ° C for 5 hours.

1 kg of the fermented tea was immersed in 15 L of a 50% (v / v) ethanol solution, refluxed at 70 ° C for 3 hours, and then extracted at room temperature for 12 hours. The extract was filtered, concentrated under reduced pressure to a vacuum, and lyophilized to give a powdery post-fermented tea extract. The yield was 15 ~ 20% and the prepared powder was stored at 4 ℃ until use.

[Reference Example 3] Culture of Helicobacter pylori

H. pylori (KCCM 41351) was cultured using cotton blood or Brucella medium, and Mueller-hinton broth or Mueller-Hinton agar medium was used for antibacterial activity. Bacteria were cultured for 3 days in a 10% CO ₂ incubator maintained at 100% humidity.

[Reference Example 4] Analysis of components of green tea extract

In order to confirm the differences in components contained in the green tea leaves used in the preparation of the post-fermentation green tea in Reference Example 2 and in the fermented green tea prepared in Reference Example 2, the content of ingredients was compared with respect to the catechins. Each sample was analyzed by Waters 2695 HPLC from Alliance and analyzed using ODS (C18) column. The analytical results are shown in Table 1 below, and the content of each component in Table 1 is% (w / w) by weight.

Composition Catechin Epicathein Caffeine Galate Fermented green tea extract 2.78 4.46 3.32 1.26 Green tea extract 21.74 24.27 3.57 0.02

As can be seen from Table 1, the post-fermented green tea extract contained significantly lower catechins than the green tea extract, while the gallate content was increased by several tens of times.

The composition of post-fermented green tea extract is completely different from that of general green tea extract.

[Test Example 1] Evaluation of growth inhibitory effect of Helicobacter

The inhibitory effect of the components of Reference Examples 1 and 2 on the growth of Helicobacter was confirmed. At this time, the components obtained in Reference Example 1 were used in combination ratio shown in the following Table 2, and the total concentration of the combined ingredients was 0.01, 0.05, 0.1, 0.5, 1, 5, 10, 50, 100 and 500 g / ml Respectively.

Example Comparative Example One 2 3 4 5 6 7 8 9 10 11 12 13 One 2 3 4 Galate One One One One One One One One One One One One One One Catechin 2 2.2 2.5 2.2 2.2 2.2 2.2 Epicathein 3 3.5 4 3.5 3.5 3.5 3.5 Caffeine 2 2.6 3 2.6 2.6 2.6 2.6

After the suspension of Helicobacter KCCM 41351 in 0.9% physiological saline to a concentration of 10 ⁹ CFU / ml, the combination as shown in Table 2 or the post-fermented green tea extract of Reference Example 2 was diluted with 0.01, 0.05, 0.1, 0.5, 1 , 5, 10, 50, 100, and 500 g / ml, and then incubated for 30 minutes in 9 ml of sterilized 100 mM phosphate-buffered saline (pH 7) supplemented with 1 ml of the diluted solution. After the culture was completed, the culture was continuously diluted with sterile physiological saline, and 0.1 ml of the diluted solution was inoculated into the blood culture medium of Columbia blood and cultured at 37 ° C for 72 hours in a microorganism. As a control group, a phosphate buffer solution not containing Reference Examples 1 and 2 was used. The ratio of the number of bacteria to the control group was calculated as a growth inhibition rate, and the results are shown in Table 3 below.

Helicobacter growth inhibition rate (%) by composition density
(g / ml) Example Comparative Example Reference example One 2 3 4 5 6 7 8 9 10 11 12 13 One 2 3 4 2 0.01 3.4 3.4 4.5 5.7 6.9 7.4 1.2 1.5 1.5 12.4 3.9 7.9 14.7 1.1 2.6 2.8 0.1 15.3 0.05 4.3 4.5 5.7 7.9 9.3 10.8 1.6 1.9 1.9 18.6 5.7 11.4 31.3 1.3 2.9 3.7 0.1 33.2 0.1 5.3 5.8 7.1 10.5 13.4 14.3 2.9 3.4 3.5 25.8 7.7 16.6 39.7 1.6 3.6 4.6 0.5 42.3 0.5 8.3 8.9 10.5 16.3 19.6 20.1 4.8 5.3 5.4 38.7 12.8 28.3 53.9 2.8 5.7 6.8 0.8 55.7 One 10.2 11.4 13.3 18.9 22.8 23.4 5.7 6.6 6.5 46.6 16.1 32.8 61.6 3.5 6.6 8.1 1.3 60.8 5 13.7 14.8 18.6 24.4 27.6 27.9 7.8 8.5 8.7 55.3 21.3 38.7 74.7 4.7 8.1 10.7 1.8 73.6 10 15.6 16.6 21.7 27.6 30.8 30.6 9.5 10.7 10.9 59.8 24.6 41.6 79.4 5.8 8.9 11.8 2.5 80.9 450 18.9 20.7 25.3 30.1 32.6 33.5 11.9 13.2 13.3 61.5 28.9 44.4 83.8 6.8 9.5 13.1 3.7 84.2 100 21.4 23.5 27.7 30.7 33.1 33.3 12.9 13.6 13.5 62.4 30.5 46.6 84.2 7.6 9.7 13.7 3.9 85.3 500 21.8 24.4 27.3 30.8 33.5 30.6 12.6 13.7 13.2 63.9 31.4 46.7 84.6 7.9 9.6 14.3 3.8 85.5

From the results shown in the above Table 3, it can be seen that, in the case of Comparative Examples 1 to 4 containing only one of gallate, catechin, epicatechin and caffeine, the degree of decrease in the growth of Helicobacter is not so great, but at least one of catechin, epicatechin and caffeine Fermented green tea extract of Examples 1 to 13 and Reference Example 2 used in combination with gallate showed that the growth of Helicobacter was effectively reduced as the content of the combination or post-fermented green tea extract was increased have.

[Test Example 2] Evaluation of helicobacter reduction in mouse stomach

8 weeks old male C57BL / 6 mice (n = 5) were inoculated with 22 G gastric gavage needle at a concentration of 10 ⁹ CFU / ml, The post-fermented green tea extract of Reference Example 2 was orally administered at 100 mg / kg for 5 days. After 5 days, the stomach was removed and the DNA was extracted using a QIAmp Tissue Kit. The presence or absence of Helicobacter pylori was detected by PCR using Helicobacter pylori CagA primer (sense 5'-AGTAAGGAGAAACAATCA-3 ', antisense 5'-AATAAGCCTTAGAGTCTTTTTGGAAATC-3' Respectively. The results are shown in Fig.

1, the growth inhibition rate of Helicobacter was low in Comparative Examples 1 to 4, which contained only one of gallate, catechin, epicatechin and caffeine. However, at least one of catechin, epicatechin, In the case of Examples 1 to 13 and in the case of treating the after-fermented green tea extract of Reference Example 2, the growth of Helicobacter was effectively inhibited as the content of the combination or post-fermented green tea extract was increased. Especially, about 97% of Helicobacter was killed by post fermented green tea extract.

[Test Example 3] Cytotoxicity assay

KATO Ⅲ, a gastrointestinal cell line, was treated with 1 mg / ml of the post-fermented green tea extract of Examples 1 to 13 and Reference Example 2 for 48 hours. (Necrosis, apoptosis-inducible cell death) based on the test method of 3- [4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide (MTT) The results are shown in Fig.

The results showed that the components used in the present invention did not induce apoptosis (including apoptosis).

[Test Example 4] Preclinical experiments related to the treatment of animals infected with Helicobacter pylori by long-term administration

(SS1) concentration of 10 ⁹ CFU / ml in 7-week-old male C57BL / 6 mice (n = 5) two weeks before the administration of the post-fermented green tea extracts of Examples 1 to 13, Comparative Examples 1 to 4 and Reference Example 2, (50 mg / kg) of the fermented green tea extracts of Examples 1 to 13, Comparative Examples 1 to 4, and Reference Example 2 were administered to the animals infected with Helicobacter pylori through oral administration for a total of 8 weeks, (10 mg / kg). After the end of the experiment, the stomach was removed and the DNA was extracted using the QIAmp Tissue Kit. The presence or absence of Helicobacter pylori was detected by PCR using Helicobacter pylori CagA primer (sense 5'-AGTAAGGAGAAACAATCA-3 ', antisense 5'-AATAAGCCTTAGAGTCTTTTTGGAAATC-3' Respectively. The results are shown in FIG.

After infection with Helicobacter pylori, in the groups to which Comparative Examples 1 to 4 were administered, a large number of Helicobacter remained in the stomach. However, in the group treated with the post-fermented green tea extract of Examples 1 to 13 and Reference Example 2, the Helicobacter disappeared And it was confirmed that Helicobacter was almost completely eliminated in the group administered with the post-fermented green tea extract.

[Formulation Example 1] Powder

Example 13 100 mg

Lactose 100 mg

Talc 10 mg

maintain 5 mg

The above components are mixed and filled in airtight bags to prepare powders.

[Formulation Example 2] Tablets

Example 13 50 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

Vitamin C 50 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

[Formulation Example 3]

Example 13 50 mg

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

Vitamin C 50 mg

Serine 50 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

[Formulation Example 4] Liquid preparation

Example 13 100 mg

Isomer 10 g

Mannitol 5 g

Vitamin C 50 mg

Serine 50 mg

maintain Suitable amount

Purified water Suitable amount

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

[Formulation Example 5] Health food (granule)

Example 13 1000 mg

Vitamin mixture

Vitamin A acetate 70 [mu] g

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

Vitamin B12 0.2 [mu] g

Vitamin C 10 mg

Biotin 10 [mu] g

Nicotinic acid amide 1.7 mg

Folic acid 50 [mu] g

Calcium pantothenate 0.5 mg

Mineral mixture

Ferrous sulfate 1.75 mg

Zinc oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dicalcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

[Formulation Example 6] Health drinks

Example 13 1000 mg

Citric acid 1000 mg

oligosaccharide 100 g

Plum concentrate 2 g

Taurine 1 g

Purified water is added to the entire 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered and sterilized in a sterilized 2 DEG C container, It is used in the production of the health beverage composition of the invention.

Although the composition ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the blending ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (7)

Gallic acid, or a salt or derivative thereof, as a helicobacter inhibitor; And at least one of catechin, epicatechin and caffeine as an active ingredient. The method according to claim 1, wherein the gallic acid or a salt or a mixture of the derivative or the catechin as the active ingredient is mixed at a weight ratio of 1: 1 to 3; the mixture of gallic acid or a salt or derivative thereof and epicatechin is mixed at a ratio of 1: 4.5; Wherein the mixture of gallic acid, or a salt or derivative thereof, and caffeine is mixed in a weight ratio of 1: 1.5 to 3.5. The composition according to claim 1, wherein the content of the active ingredient is 0.1 to 50% by weight based on the total weight of the composition. 3. The composition of claim 2, wherein each of the mixtures is prepared using a post fermented green tea extract. The composition of claim 1, wherein the composition is formulated as a pill, capsule, tablet, granule, or drink. Gallic acid, or a salt or derivative thereof, as a helicobacter inhibitor; And at least one of catechin, epicatechin, and caffeine as an effective ingredient for improving, alleviating, treating, or preventing gastric dysfunction. [Claim 7] The composition according to claim 6, wherein the gastric dysfunction is at least one selected from the group consisting of gastritis caused by Helicobacter pylori, gastric ulcer, low-grade mucosa-associated lymphoid tissue gastric lymphoma and gastric cancer.

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