KR101521125B1 - Complex plant extracts containing anti-Helicobacter pylori substance treating gastritis and preventing gastric diseaes - Google Patents

Abstract

The present invention relates to an antimicrobial composition for Helicobacter pylori , which comprises an immature, bacterium extract and an effective component of an extract from the root. The double natural compound according to the present invention has antimicrobial activity against Helicobacter pylori unlike the case of treating a single extract with a synergistic effect of antimicrobial inhibition and has no side effects and is safe for the human body, And gastrointestinal diseases including gastritis caused by gastrointestinal bleeding.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for treating and preventing gastrointestinal diseases including anti-Helicobacter pylori (Gastrointestinal tract)

The present invention relates to the development of an antimicrobial composition for the treatment and prevention of gastrointestinal diseases including Helicobacter pylori, which exhibits an elevated anti-helicobacterial effect, comprising the complex natural products (crude asparagus, extracts and extracts from Aspergillus) as active ingredients.

Helicobacter is firstly found in the gastric mucosa of humans by Dr. Marshall and Warren of Australia in 1980 and it affects the normal cell apoptosis of the surrounding cells by attaching to the gastric epithelial layer. The urease secretes urease, which has a strong enzyme activity. The urease decomposes urea to produce a large amount of ammonia and carbon dioxide, neutralizing the gastric juice around the helicobacter, thereby reducing mucous membrane function and causing gastric acid reflux. Helicobacter is the most common cause of gastritis and gastric ulcers in humans. In the case of Helicobacter, prevention is important because immune reaction in the body is useless because it lives on the gastric mucosa, and once it is infected, it is difficult to treat and even if it is treated, the possibility of recurrence is high.

To date, methods for removing Helicobacter pylori include proton pump inhibitors such as omeprazole, and triple therapy for treating two antibiotics such as amoxicillin, clarithromycin and tetracycline. However, Helicobacter is resistant to eradication because it is resistant to drugs and has a good mutation. In addition, these antibiotics have resistance to drugs when they are taken over a long period of time, and they are frequently accompanied by various side effects such as constipation, rash, and reflux esophagitis. To overcome these shortcomings, the present invention uses two natural substances having harmless components to inhibit Helicobacter pylori to prevent Helicobacter pylori and gastric ulcer.

Rubus coreanus ( Rubus coreanus MIq.) Is a deciduous broad-leaved shrub belonging to Rosaceae. It is a deciduous tall tree that grows mainly in the valleys and mountains with good sunlight and good soil. It is cultivated much in Chonbuk area (Gochang, Jeongeup, Sunchang, Gimje) and Jeju island in Korea, and it usually blooms in May ~ June and it is harvested in July ~ August. It is used for medicinal purposes as well as for the fruit of bokbunja. The raw fruit of bokbunja strawberry, that is, it is called bokbunja and it is widely used as herb medicine. In other words, the ' Rubi Fructus ' used in the present invention refers to unripe green fruit, and a lot of efficacy in disease has been specified in various ear buds .

The Korean traditional botanical bacterium referred to in Dongbok-bong, Ganbonghwa, and Honsho-jong new green refers to immature fruit which is used in the present invention, and its efficacy is to help the kidney function, to strengthen the energetic ability, It is said that it protects, brightens eyes and has efficacy in infertility. In addition, it has been recorded that the bokbunja immature group protects the above functions and strengthens the stomach wall.

It is a deciduous broad-leaved arboreous tree of Ulmus davidiana var. Japonica . The country of origin is Korea, China, and Japan, and it is said that it grows near the mountain valley and the valley in the middle of the central part of Korea. Elm trees are about 10m in height, similar in appearance to zelkova trees, and have a variety of species. Elm trees are called hu (楡), hulls are skin or whitish bark (楡 白), and root hulls are uk root (楡 根 hide). Root bark peeled off in early spring, dried in the shade, usually used, but the skin is yellowish.

According to Donguibogam, it is good for swelling or swelling of inflammation, tumor, etc. Especially among all diseases of gastric ulcer, gastritis, gastric ulcer, duodenal ulcer, small intestine ulcer, rectal ulceration, esophageal ulcer and ulcer symptoms such as ulceration is effective. It contains a powerful analgesic agent and has insecticidal effects. It is widely used as a medicine, and it has a great advantage that it is not harmful to the human body even if taken for a long time because it is not addictive. It is a natural herbal medicine which can be used variously through single or mixed prescriptions.

The extracts used in the present invention were selected from the database of the native plant extract bank of the Korea Biotechnology Research Institute as the target plants. This native plant is a naturally occurring native plant with safety because it is regulated as an edible plant in Korea Food Code.

Until now, the treatment of H. pylori infection has mainly been performed using antibiotics, and the amount of antibiotics is mostly longer than that of other pathogenic bacteria. Antibiotics are accompanied by side effects and are resistant to regularly changing medications. In order to solve such problems, the present invention has developed an antimicrobial composition for an anti-Helicobacter, which comprises two natural complexes having no synergistic effect on elimination of strong anti-helicobacter, And to provide a pharmaceutical material and a functional material capable of inhibiting gastrointestinal diseases including gastritis.

To prove the present invention, 13 H. pylori strains were supplied from KNRRC of Gyeongsang National University Medical School and the antibacterial effect was measured by using the minimum inhibitory concentration method (MIC).

The present invention relates to an antimicrobial composition for an anti-helicobacter containing an active ingredient of a bimodal extract and a rhizome extract, and relates to the development of a composition for the treatment and prevention of anti-helicobacterial gastritis and gastrointestinal diseases.

Figure 1 shows DPPH scavenging activity and reducing power of Rubus coreanus L. and U. keisai.
Figure 2 shows the Helicobacter antimicrobial activity test for a single extract in a minimal inhibitory concentration assay (MIC test). FIG. 2 is a photograph showing the antimicrobial activity of Helicobacter pylori against the test group treated with the control and the extract (left), and the degree of colony formation based thereon (Right). The inhibition of anti-helicobacter growth inhibition was not observed even at 150 μg / ml and 200 μg / ml of bokbunja extract and extracts.
FIG. 3 shows the antimicrobial activity of Helicobacter against the double-complex extract by the minimum inhibitory concentration method (MIC test). As shown in FIG. 2, the inhibition of anti-helicobacter growth was not observed even at 150 μg / ml and 200 μg / ml of the extracts of the immature and extracts and the extracts of acanthin gum, respectively. However, 75 μg / ml of bokbunja extract And 75 μg / ml, respectively, were inhibited by 90% or more of Helicobacter spp. This indicates that the anthelmintic effect of antibiotics and antioxidants in the extracts and extracts of the bokbunjae showed the synergistic effect.
Figure 4 shows the suitability test of antibiotics and biosynthetic complexes according to the characteristics of each Helicobacter strain. As shown in FIG. 3, the synergistic effect of anti-helicobacter was shown when the extracts of Bombyx mori and extracts were combined. Compared with antibiotics (amoxicillin 0.5 μg / ml, clarithromycin 1 μg / ml), proton pump inhibitor (omeprazole 150 μg / ml) and triacetin (OAC, amoxicillin + clarithromycin + omeprazole) used for eradication of Helicobacter (Fig. 4A, B) . ≪ / RTI >
Figure 4C is a plot of the antibiotic susceptibility characteristics of Helicobacter strains. Thirteen Helicobacter strains were shown to respond positively when treated with antibiotics amoxicillin (0.5 μg / ml), clarithromycin (1 μg / ml), and omeprazole (150 μg / ml) Giving.
Based on FIG. 4 , it was found that the antibiotic triple therapy used in the treatment of Helicobacter pylori gastritis in the clinic and the helicobacter-suppressing ability of the dual-complex extracts used in the present invention Compared with antibiotics, the combined extract is not harmless to the human body and is not resistant enough to prevent and treat Helicobacter pylori (gastritis, gastric ulcer).

Preferred embodiments of the present invention will be described. The following examples are illustrative of the present invention and are not intended to limit the scope of the present invention.

Preparation of Bokbunja Extract and Root Root Extract

The brambly matured seeds of the present invention were obtained from Kyungdong Market (Seoul, Korea) and were extracted with water and extracted with alcohol.

Preparation for experiment (preparation of Helicobacter bacteria)

The Helicobacter fungi used in the present invention were tested for the isolates of Helicobacter spp. Isolated from Koreans through microbial base bank KNRRC (Institute of Microbiology, Gyeongsang Univ.). The Helicobacter pylori strains used in the present invention can be used as strains of 26695 (a), 92-157 (b), 92-354-4 (c), 95-113 (d), 95-307 , 92-20 (g), 92-30 (h), 92-33-1 (i), 92-82-1 (j), F444-12-1 (k) As a control, two lines were additionally used as standard strain ATCC43504 (A) and SS1 (S), which is frequently used in in vivo experiments. Helicobacter pylori strains were inoculated onto Brucella agar medium containing 10% FBS and cultured at 37 ° C in 10% CO ₂ .

Antimicrobial activity of Helicobacter pylori using natural plant extracts

(Minimum inhibitory concentration, MIC)

The inhibition experiment of Helicobacter was carried out by the minimum inhibitory concentration (MIC) experiment. Control broth and extracts were prepared for each concentration and then treated with 1 × ^{10 8} CFU / ml of Helicobacter per ml. After culturing for 3 days, the lowest concentration at which no colonies were formed was confirmed.

As a result, the inhibition of anti-helicobacter growth was not observed even when 150 μg / ml and 200 μg / ml of brambone extract, extract and root extract were treated, respectively. However, 75 μg / ml of bokbunja extract and 75 μg / Were inhibited by 90% or more of Helicobacter bacteria. In the current clinical trial, antibiotics (amoxicillin 0.5 μg / ml, clarithromycin 1 μg / ml) and proton pump inhibitor (omeprazole 150 μg / ml), which are used in eradication of Helicobacter pylori, ml), and triple therapy (OAC, amoxicillin + clarithromycin + omeprazole).

[Manufacturing Example]

Hereinafter, a preparation example of the brambloria japonica extract, an extract, a carrot leaf extract and fractions thereof according to the present invention will be described, but the present invention is not intended to be limited thereto but will be specifically described.

[Preparation Example 1] Preparation of pharmaceutical preparation

<1-1> Preparation of powder

2 g of the extract of Bokbunja and the extract +

Lactose 1 g

The above components were mixed and packed in airtight bags to prepare powders.

<1-2> Preparation of tablets

100 mg of the extract of Bokbunja and the extract +

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

&Lt; 1-3 &gt; Preparation of capsules

100 mg of the extract of Bokbunja and the extract +

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.

&Lt; 1-4 &gt;

1 g of the extract of Bokbunja and the extract +

Lactose 1.5 g

Glycerin 1 g

0.5 g of xylitol

After mixing the above components, they were prepared so as to be 4 g per one ring according to a conventional method.

<1-5> Preparation of granules

150 mg of the extract of Bokbunja and the extract +

Soybean extract 50 mg

Glucose 200 mg

Starch 600 mg

After mixing the above components, 100 mg of 30% ethanol was added and the mixture was dried at 60 ° C to form granules, which were filled in a capsule.

[Preparation Example 2] Preparation of health food

1000 mg of the extract of Bokbunja and the extract +

Vitamin mixture quantity

Vitamin A acetate 70 μg

Vitamin E 1.0 mg

0.13 mg of vitamin

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

Vitamin B12 0.2 μg

Vitamin C 10 mg

Biotin 10 μg

Nicotinic acid amide 1.7 mg

Folic acid 50 μg

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium 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.

[Manufacturing Example 3] Production of food

<3-1> Production of flour food

Bread, cake, cookies, crackers and noodles were prepared using the mixture of wheat bran with 0.5-4.0 wt.

<3-2> Manufacture of soups and gravies

0.1 ~ 5.0 parts by weight of the extract of Bokbunja and the extract of Bokbunja were added to soup and juice to produce health promotion meat product, noodle soup and juice.

<3-3> Preparation of ground beef

The ground beef for health promotion was prepared by adding the brambles of the present invention and 10 parts by weight of the extract and the extract of Root cane to the ground beef.

<3-4> Manufacture of dairy products

5 to 10 parts by weight of the extract of Bokbunja and 5 ~ 10 parts by weight of the extract of Bokbunja were added to milk and various dairy products such as butter and ice cream were prepared using the milk.

&Lt; 3-5 &gt;

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh. Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer.

The brambled granules and extracts of the present invention were concentrated under reduced pressure in a vacuum concentrator, dried by spraying and dried in a hot air drier, and pulverized to a size of 60 mesh by a pulverizer to obtain a dry powder.

The above-prepared cereals, seeds and the present invention were prepared in the following proportions.

(3 parts by weight) of the brambles of the present invention and the extracts (3 parts by weight) of the present invention, cereals (30 parts by weight of brown rice, 15 parts by weight of yulmu, 20 parts by weight of barley) (3 parts by weight), Ganoderma lucidum (0.5 part by weight) and Rhizophora (0.5 part by weight).

<3-6> Production of chewing gum

Gum base 20%

Sugar 76.36 ~ 76.76%

Extract of Bokbunjae and Extract + Root Extract

Fruit flavor 1%

Water 2%

Chewing gum was prepared using the above-mentioned composition and content by a conventional method.

<3-7> Manufacture of candy

Sugar 50-60%

Syrup 39.26 ~ 49.66%

Extract of Bokbunjae and Extract + Root Extract

Orange fragrance 0.1%

The composition and the content of the candy were prepared using a conventional method.

[Manufacturing Example 4] Preparation of beverage

<4-1> Production of health drinks

(50%), water (75%), and 5 g of the extract of Bokbunja and extracts of the present invention were mixed homogeneously And then sterilized and packaged in glass bottles, plastic bottles, etc.

<4-2> Production of vegetable juice

Vegetable juice was prepared by adding 5 g of the bramblymia japonica extract and the extract and Rootgrass extract of the present invention to 1,000 ml of tomato or carrot juice.

<4-3> Preparation of fruit juice

Fruit juice was prepared by adding 1 g of the extract of Bokbunja, the extract of Extract of Bokbunja and the extract of Rootgrass, to 1,000 ml of apple or grape juice.

Claims (16)

A pharmaceutical composition for preventing or treating Helicobacter pylori infection, which comprises a Rubi Fructus and Ulmus davidiana var. Japonica extract as an active ingredient and exhibits a synergistic effect on the inhibition of Helicobacter pylori. The pharmaceutical composition according to claim 1, for the prophylaxis and treatment of Helicobacter pylori infection according to the anti-helicobacter growth inhibitory effect. [Claim 2] The method according to claim 1, wherein the brambly matured and extracts and the extracts are extracted by using water, a lower alcohol of C ₁ to C ₂ or a mixture thereof as a solvent to prevent and treat Helicobacter pylori A pharmaceutical composition for therapeutic use. [Claim 5] The pharmaceutical composition according to claim 3, wherein the lower alcohol is ethanol or methanol, wherein the pharmaceutical composition is for preventing and treating Helicobacter pylori by anti-helicobacter. A pharmaceutical composition for the prevention and treatment of Helicobacter pylori infection by an anti-helicobacter containing an organic solvent fraction prepared by extracting bokbunja matured, extract and rhizome extract with an organic solvent. 6. The pharmaceutical composition according to claim 5, wherein the organic solvent is selected from the group consisting of n-nucleic acids, methylene chloride, chloroform, ethyl acetate, dichloromethane and butanol. Gt; The pharmaceutical composition according to claim 1, which is used for preventing and treating anti-Helicobacter pylori (gastric ulcer) including bramble ingrown immature and rhizome extract. The composition of claim 3, wherein the dose of the anti-helicobacter composition is from 1 mg to 10000 mg based on the effective ingredient once, the mass composition ratio of the brambles and rootstocks is in the range of 100: 1 to 1: 100, The present invention relates to a pharmaceutical composition for the prevention and treatment of Helicobacter pylori (gastritis), which comprises 100 mg of bokbunja and 9900 mg of mugwort (9900 mg / 100 mg / 100 mg / 100 mg to 9900 mg) A health functional food composition for preventing or ameliorating Helicobacter pylori gastritis which contains a Rubi Fructus and Ulmus davidiana var. Japonica extract as an active ingredient and has a synergistic effect on the inhibition of Helicobacter pylori. The health functional food composition according to claim 9, for the prevention or amelioration of Helicobacter pylori infection according to the anti-helicobacter growth inhibitory effect. 10. The method of claim 9, wherein bokbunja immature and extract yugeunpi extract prevention of water, C ₁ to pylori gastritis by the anti-Helicobacter pylori characterized in that the extraction by using the lower alcohol or a solvent mixture thereof in the C ₂ or A health functional food composition for improvement. 12. The health functional food composition according to claim 11, wherein the lower alcohol is ethanol or methanol, for preventing or ameliorating Helicobacter pylori. A health functional food composition for preventing or ameliorating Helicobacter pylori infection by an anti-helicobacter containing an organic solvent fraction prepared by extracting an extract of Bokbunja, an extract and a root extract with an organic solvent. 14. The anti-helicobacter according to claim 13, wherein the organic solvent is selected from the group consisting of n-nucleic acids, methylene chloride, chloroform, ethyl acetate, dichloromethane and butanol. Functional food composition. 12. The method of claim 11, wherein the dose of the anti-helicobacter composition is from 1 mg to 10000 mg based on the active ingredient once, and the mass composition ratio of the brambles and rootstocks is in the range of 100: 1 to 1: 100, The present invention relates to a health functional food composition for preventing or ameliorating Helicobacter pylori (gastritis) caused by anti-helicobacter in the range of 100 mg of bokbunja and 9900 mg of mugwort (9900 mg to 100 mg / 100 mg to 90 mg). delete

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