KR20170006971A - Composition for inhibiting urease activity of helicobater pylori and composition for preventing or treating damages of gastric mucosa - Google Patents

Abstract

The present invention relates to a composition for preventing and treating damage to gastric mucosa, and to a composition having a urease activity inhibiting function of Helicobacter pylori. The composition for preventing and treating damage to gastric mucosa includes components which are identical or similar to hot spring water of the Backam district or the Deokgu district. Moreover, the present invention relates to health functional food containing the components which are identical or similar to hot spring water of the Backam district or the Deokgu district. The composition according to the present invention inhibits a urease activity of Helicobacter pylori in the stomach, so the composition can be utilized in treating and preventing several sorts of stomach-related diseases, such as gastric cancer, gastric ulcer, and gastritis, caused by Helicobacter pylori; and can be useful in the functional food field including a functional beverage and health functional food which are effective in alleviating stomach diseases such as gastritis.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing and treating gastric mucosal damage, and a composition having an ability to inhibit the urease activity of Helicobacter pylori. BACKGROUND OF THE INVENTION 1. Field of the Invention [0001]

The present invention relates to a composition for the prevention and treatment of gastric mucosal injury, a composition having the ability to inhibit urease activity of Helicobacter pylori, and a health functional food containing the same.

Hot springs are defined as groundwater that is spontaneously released from the surface of the earth or artificially drilled and raised. The water temperature should be higher than the average annual temperature of the area or the groundwater temperature in the shallow strata of the area. Compared to this, it is said that less than that is a mineral spring that contains a large amount of inorganic substance or gas component irrespective of cold weather and water temperature.

The limit temperature of a hot spring varies according to the region. In Korea, the hot spring is prescribed as 25 ° C or more. In the United Kingdom, Germany, France, etc., the temperature is above 20 ° C.

In Korea, hot water is hot water of 25 ℃ or more, which is extracted from underground, and it is prescribed that the constituents are not harmful to human body. [Hot Spring Act (81.3.2. Law 3377), Hot Spring Act Enforcement Decree (81.6.18. ], Hot spring The narrow sense of hot springs is a phenomenon in which natural, special water, which is physically and chemically different from ordinary water, comes out from the ground to the surface.

The effects of the physical action of the hot spring water include general circulation enhancement effect, pain relief effect, soothing effect, and skin beauty effect.

Since Helicobacter pylori was first isolated from the gastric mucosa of humans by Marshall and Warren in Australia in 1982, it has been identified as a major cause of chronic gastritis and peptic ulcer. In 1994, It was identified as one of the carcinogenic factors in the research institute. This bacterium is a gram-negative bacillus with several flagella, and it grows in the surface layer or mucus of the gastric mucosal layer. It has the most characteristic microbiological characteristics and has strong motility and urease enzyme activity.

Helicobacter pylori secretes urease, a powerful urease, and hydrolyzes one molecule of H ₂ NCONH ₂ , urea in gastric juice to form two molecules of ammonia (NH ₃ ). The bacterium's urease has been reported to be closely related to Helicobacter pylori infection in human gastrointestinal epidermal cells and to help colonization (colonization). Specifically, it has been reported that the Helicobacter pylori strain inactivated with urease does not colonize gastric mucosal cells, and urease activity is essential for colonization of Helicobacter pylori (Eaton KA, et al., Infect Immun., 59, pp2470 -2475, 1991), ammonia produced by Helicobacter pylori urease increases pH in the gastric juice and damages the gastric mucosal layer (Sidebotham RL, et al., J. Clin. Pathol., 44, pp52-57, 1991) , Ammonia itself inhibits oxygen uptake in the gastric mucosal cells and ATP production in mitochondria (Tsujii M., et al., Gastroenterology, 102, pp1881-1888, 1992). Ultimately, ammonia forms monochloroamine (Reactive oxygen species), thereby causing cellular damage, causing chronic inflammation, and further damaging DNA, thereby promoting the development of cancer (Hah M. KB, et al., Am. J. Gastroenterol., 92, pp. 1853-1857, 1997).

Antibiotic therapy has been used to inhibit the activity of Helicobacter pylori urease as described above, but the efficiency is low due to the emergence of antibiotic resistant strains. Recently, a variety of vaccines have been developed as an effective method for eradicating Helicobacter pylori. Most of them are urease, VacA, CagA and Neutrophil-active protein known as antigens specific for the pathogenicity of Helicobacter pylori (NAP), which is known to be involved in the pathogenesis of cancer.

To date, the drinking of hot spring water has been known to increase the blood flow of the gastric mucosa and increase or inhibit the secretion of gastric juice. However, the drinking of hot spring water is parasitic on the human body and is caused by gastritis, peptic ulcer, Specific antimicrobial activity or anti-urease activity has not yet been reported.

DISCLOSURE OF THE INVENTION The present invention was conceived to solve the above-mentioned problems. The present inventors have conducted a study on white rats that were allowed to consume hot spring water in Baekam and Deokgu area, and found that the decrease in the degree of damage of the gastric mucosa and the inhibition of the activity of H. pylori- And the present invention has been completed on the basis thereof.

Accordingly, an object of the present invention is to provide a composition for preventing and treating gastric mucosal damage, which comprises the same or similar components as Baekam or Deokgu area hot spring water.

Another object of the present invention is to provide a composition having the ability to inhibit the urease activity of Helicobacter pylori, which comprises the same or similar components as the hot spring water of Baekam or Deokgu area.

Another object of the present invention is to provide a health functional food containing the same or similar components as the hot spring water of Baekam or Deokgu area.

However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.

In order to achieve the object of the present invention, the present invention provides a composition for prevention and treatment of gastric mucosal damage, which comprises the same or similar components as the hot spring water of Baekam or Deokgu area.

The present invention also provides a composition having the ability to inhibit the urease activity of gastric intestinal Helicobacter pylori, which comprises the same or similar components as the hot spring water of Baekam or Deokgu area.

In addition, the present invention provides a health functional food containing the same or similar components as the hot spring water of Baekam or Deokgu area.

In one embodiment of the present invention, the composition K 0.60 to 0.80 mg / L, Na 41.00 to 47.00 mg / L, Ca 1.9 to 3.0 mg / L, Cl 4.40 to 10.00 mg / L, SO ₄ 5.20 to 16.00mg / L, HCO ₃ 89.70 to 134.00 mg / L, SiO ₂ Those containing components of 34.00 to 87.00 mg / L, F 4.2 to 10.30 mg / L, Li 0.04 to 0.08 mg / L, Sr 0.03 or less mg / L, Zn 0.01 or less mg / L and Al 0.01 to 0.016 mg / desirable.

The composition according to the present invention reduces the degree of gastric mucosal damage and inhibits the urease activity of parasitic Helicobacter pylori from above, and is used for the treatment and prevention of various gastrointestinal diseases such as gastric cancer, gastric ulcer and gastritis caused by Helicobacter pylori. And can be usefully used in functional foods such as functional beverages and health functional foods effective for the improvement of gastrointestinal diseases such as gastritis.

FIG. 1 is a graph comparing the degree of gastric mucosal injury by administration of NSAID (Indomethacin) at the visual level when drinking white water in hot water.
FIG. 2 is a graph comparing the degree of gastric mucosal damage by administration of NSAID (Indomethacin) at the microscopic level when drinking white water in hot water.
FIG. 3 is a graph showing the results of comparing the degree of gastric mucosal damage by administration of NSAID (Indomethacin) when drinking white water in a hot spring water.
Fig. 4 is a graph showing the results of comparing the effect of inhibiting urease activity of Helicobacter pylori (26695) grown in hot spring water and distilled water and the upper part of the culture liquid.
FIGS. 5 and 6 show the inhibitory effects of Jack and Bean spa waters on Jack bean urease activity in vitro.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for preventing and treating gastric mucosal damage, which comprises the same or similar components as Baekam or Deokgu regional hot spring water. The present invention also provides a composition having the ability to inhibit urease activity of Helicobacter pylori, which comprises the same or similar components as Baekam or Deokgu regional hot spring water.

Wherein the composition comprises at least one of K 0.60-0.80 mg / L, Na 41.00-47.00 mg / L, Ca 1.9-3.0 mg / L, Cl 4.40-10.00 mg / L, SO ₄ 5.20-16.00 mg / L, HCO ₃ 89.70 to 134.00mg / L, SiO ₂ 34.00 to 87.00 mg / L, F 4.2 to 10.30 mg / L, Li 0.04 to 0.08 mg / L, less than Sr 0.03 mg / L, or less Zn 0.01 mg / L and 0.01 to 0.016 mg Al / L < / RTI >

The composition according to the present invention can be used for the treatment and prevention of various gastrointestinal diseases caused by Helicobacter pylori such as gastric cancer, gastric ulcer, gastritis and the like, and inhibits the production of ammonia caused by urease activity in the animal manure It can be applied as an environment improving agent.

The present invention also provides a health functional food containing a composition comprising the same or similar components as Baekam or Deokgu area spring water. That is, the composition of the present invention can be added to food or beverage for the purpose of improving gastrointestinal diseases. At this time, the amount of the composition including the hot spring water of the present invention in the food or beverage may be generally 10 to 90% by weight of the total food weight, and may be a functional beverage, a pill, a tablet, May be used in the form of a soft or hard capsule filled with a dry powder. The composition of the present invention may be added to the beverage composition at a ratio of 10 to 90 ml based on 100 ml.

The health beverage composition of the present invention is not particularly limited to a liquid ingredient other than the above-mentioned composition as an essential ingredient, and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose, polysaccharides such as maltose, sucrose and the like, such as dextrin, cyclodextrin and the like And sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and aging agents (cheese, chocolate etc.), pectic acid and its salts, , Organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination.

As used herein, NSAID formulations are non-steroidal anti-inflammatory agents and have been widely used worldwide for the treatment of various diseases. However, they are known to cause gastrointestinal diseases such as damaging the mucous membrane directly and inhibiting the synthesis of prostaglandins in the mucous membrane due to their acidic nature.

As used herein, PPI is an abbreviation for a proton pump inhibitor and is therefore intended to include omeprazole, or an alkaline salt thereof, or a hydrated form of any of them, as well as omeprazole, or an alkaline salt thereof, Including hydrated forms. The proton pump inhibitor is an agent for suppressing the secretion of gastric acid and has an effect of reducing symptoms of gastrointestinal diseases such as gastritis, gastric ulcer, duodenal ulcer.

Hereinafter, the structure of the present invention will be described in detail with reference to the following examples. However, the scope of the present invention is not limited by the following embodiments.

Example 1. Detecting the content of major elements in Baekam and Deokgu hot spring water

The contents of major elements of Baekam and Deokgu hot spring water were extracted from the present situation and utilization of Korean hot springs (Lee, Jong Tae, Korea Central Hot Spring Research Institute, December 2008 issue).

ingredient Baekam Hot Spring Water (mg / L) Deokgu hot spring water (mg / L) K 0.8 0.6 Na 47 41 Ca 1.9 3 Mg - 0.01 Cl 10 4.4 SO ₄ 16 5.2 CO ₃ - 5.8 HCO ₃ 134 89.7 SiO ₂ 87.0 34.0 F 4.2 10.3 Li 0.04 0.08 Sr - 0.03 Zn - 0.01 Al 0.01 0.016

Example 2. Measurement of the degree of damage of gastric mucosa

As experimental animals, 37 Sprague Dawley (SD) rats weighing 158g ~ 160g (6 weeks old, M) were used.

The 37 rats were divided into three groups: three in the tap water treatment group, four in the Deokgu hot spring water treatment group, four in the Baekam spring water treatment group, six in the NSAID treatment group (Indomethacin, 80 mg / kg), the NSAID (Indomethacin, 180 mg / kg) Six treatment groups, 6 NSAIDs (Indomethacin, 180 mg / kg) and Baekam spring water treatment group, and 6 NSAID and PPI treatment groups (omeprazole, 30 mg / kg + Indomethacin, 180 mg / kg)

In the group treated with hot spring water and NSAID, NSAID was administered after drinking hot spring water for 5 to 6 days. NSAID treatment was performed by dissolving indomethacin in Tris (pH 8.0) and once at a dose of 180 mg / kg. In PPI treatment, omeprazole was dissolved in physiological saline, subcutaneously injected at a dose of 30 mg / kg, and indomethacin was administered once intraperitoneally at a dose of 180 mg / kg.

After 24 hours, the rat was sacrificed and the stomach tissue was immobilized on 4% PFA, then embedded in paraffin, paraffin block was cut into 5 μm thick, and H & E stain was performed. And observation with an optical microscope are shown in Figs. 1 and 2, respectively.

In the group treated with only the NSAID of FIG. 1, the gastric mucosal papillary hemorrhage was shown to be black. In the group treated with only the NSAID shown in FIG. 2, the gastric mucosa was damaged due to the relatively white color. However, in the group treated with NSAID and hot water, it was found that the gastric mucosa was not damaged because the petechiae bleeding and white staining of the gastric mucosa were not observed.

Through this, it was confirmed that a composition comprising the same or similar components as Baekam or Deokgu hot spring water can prevent or treat gastric mucosal damage.

Example 3: Measurement of urease inhibitory activity of Helicobacter pylori

First, 18.5 g of Brain-Heart Infusion (BD) was sufficiently dissolved in 465 ml of distilled water and hot spring water, respectively, followed by autoclaving. Subsequently, 35 ml of 7% serum was mixed to prepare a culture medium. Then, Helicobacter pylori was inoculated and cultured in a CO ₂ incubator at 37 ° C.

Each sample of Helicobacter pylori was then harvested from three different mediums cultured for 5 days, 1.5-2 ml of soy agar was inoculated with a 20% urease solution at a ratio of 1: 1, and a McFarland value of 0.08-0.12 I set it to 0.1 in range. The number of colonies of Helicobacter pylori was measured every 30 minutes and is shown in Table 2. After the feeding of distilled water (DW), Deokgu hot spring water, and Baekam hot spring water for 30 days, the gastric mucosa was collected from rats fed with distilled water and hot spring water and cultured in anaerobic condition.

As shown in Table 2, it was confirmed that inhibition of urease activity of Helicobacter pylori was inhibited in mice in which Deokgu and Baekam hot spring water were consumed compared with distilled water, thereby inhibiting colonization of Helicobacter pylori. As shown in FIG. 4, the urease activity of the bacteria and culture supernatant cultured in Deokgu and Baekam hot spring water was also decreased compared with that in the distilled water.

Immediately (cfu / ml) After 30 minutes (cfu / ml) After 60 minutes (cfu / ml) After 90 minutes (cfu / ml) Distilled water 7906.7 7323.3 7423.3 8196.7 Deokgu hot spring water 7170.0 3870.0 3990.0 4030.0 Baekam Hot Spring Water 6935.0 3865.0 3960.0 4005.0

Through this, it was confirmed that the composition comprising the same or similar components as Baekam or Deokgu hot spring water inhibited the urease activity of Helicobacter pylori bacteria and inhibited the colonization of Helicobacter pylori bacteria.

Example 4. Measurement of jackin urease inhibitory activity

The urease inhibitory activity of each of the distilled water (DW), Deokgu hot spring water, and Baekam hot spring water was measured by the following method, and the results are shown in FIG. 5 and FIG.

0.1 ml of a jack bean urease (Sigma type III, Sigma Co.) enzyme solution (5 μl) was added to 2.5 ml of a 3 mM phosphate buffer solution (pH 6.8), 0.1 ml of phenol red (SpectronicGenesys, Spectronic Inc., USA) was used to examine the change of OD560 over time to determine the time course of OD560. Min. The velocity was calculated from the slope of the straight line portion of the curve (0.15-0.5 OD unit).

As shown in FIG. 5 and FIG. 6, it was found that each of Deokgu and Baekam hot spring water exhibited Jackin urease inhibitory activity.

Claims (3)

K 0.60-0.80 mg / L, Na 41.00-400.00 mg / L, Ca 1.9-3.0 mg / L, Cl 4.40-10.00 mg / L, SO ₄ 5.20-16.00 mg / L, HCO ₃ 89.70-134.00 mg / Containing components of 34.00 to 87.00 mg / L of SiO ₂ , 4.2 to 10.30 mg / L of Li, 0.04 to 0.08 mg / L of Li, 0.03 mg / L of Sr or less, 0.01 or less mg / L of Zn and 0.01 to 0.016 mg / Health functional foods.

K 0.60-0.80 mg / L, Na 41.00-400.00 mg / L, Ca 1.9-3.0 mg / L, Cl 4.40-10.00 mg / L, SO ₄ 5.20-16.00 mg / L, HCO ₃ 89.70-134.00 mg / Containing components of 34.00 to 87.00 mg / L of SiO ₂ , 4.2 to 10.30 mg / L of Li, 0.04 to 0.08 mg / L of Li, 0.03 mg / L of Sr or less, 0.01 or less mg / L of Zn and 0.01 to 0.016 mg / Or a pharmaceutically acceptable salt thereof, for the prevention and treatment of gastric mucosal injury.

K 0.60-0.80 mg / L, Na 41.00-400.00 mg / L, Ca 1.9-3.0 mg / L, Cl 4.40-10.00 mg / L, SO ₄ 5.20-16.00 mg / L, HCO ₃ 89.70-134.00 mg / Containing components of 34.00 to 87.00 mg / L of SiO ₂ , 4.2 to 10.30 mg / L of Li, 0.04 to 0.08 mg / L of Li, 0.03 mg / L of Sr or less, 0.01 or less mg / L of Zn and 0.01 to 0.016 mg / Wherein the composition has a urease inhibiting ability of Helicobacter pylori.

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