KR20060096875A - Composition for inhibition of helicobacter pyroli infection containing acharan sulfate as an active component - Google Patents

Abstract

The present invention relates to a composition for inhibiting Helicobacter pylori infection containing acaran sulfuric acid as an active ingredient, and more particularly, to decomposing acaran sulfate oligomer obtained by enzymatically or chemically decomposing acaran sulfate or acaran sulfate. It relates to a composition for inhibiting Helicobacter pylori infection containing as a component. The composition of the present invention can be usefully used for the prevention and treatment of gastrointestinal diseases caused by Helicobacter pylori by inhibiting Helicobacter pylori infection.

Description

Composition for inhibition of Helicobacter pyroli infection containing acharan sulfate as an active component}

Figure 1 shows the identification of acaran sulfate sulfate oligomer produced by enzymatic method using SAX-HPLC The figure shown.

Figure 2 is a diagram showing the results confirmed by HPLC acaran sulfate oligomer fractions.

Figure 3 is a diagram showing the results of Capillary-electrophoresis (CE) analysis of the acaran sulfate oligomer fraction.

Figure 4 is a diagram showing the results confirmed by the FARA analysis of the acaran sulfate oligomer fraction.

5 is a diagram showing the results of confirming the molecular weight of an acaran sulfate oligomer (12mer, MW: 2754.4) using MALDI-MS.

6 is a diagram showing a decrease in molecular weight with a reaction time of acaran sulfuric acid produced by a chemical method.

7 is a diagram showing the inhibitory effect of Helicobacter pylori infection on KATO III cells of acaran sulfate oligomer (○: original acaran sulfate, ■: 2940 Da, Δ: 2380 Da, ▲: 1925 Da, ●: 1832 Da, □: 1773 Da).

8 is a diagram showing the Helicobacter pylori infection inhibitory effect on KATO III cells of cleaved acaran sulfate, represented by IC ₅₀ .

The present invention relates to a composition for inhibiting Helicobacter pyroli infection containing Acharan sulfate as an active ingredient.

Acharan sulfate is a type of glycosaminoglycan (GAG) represented by the following chemical formula and present in abundance in African snails (Korean Patent No. 10-0170064).

GAG, which contains acaran sulfate, is structurally diverse and complex through partial changes in the biosynthesis process. GAGs have a basic backbone that is partially sulfided by the repeated uronic acid and glucosamine, and these complex chemical structures allow various kinds of biological activity. As is known to date, such diverse bioactivity appears to be due to the presence of unique specific sequences.

Animal GAGs include hyaluronic acid, chondroitin sulfate, keratin sulfate, heparan sulfate, heparin, and heparin among these GAGs. It is isolated in mast cells along the arteries in the liver, lungs, and skin mucosa, and the rest of the GAGs are distributed in connective tissue. Chondroitin sulfate, used as a medicine, is obtained from shark cartilage and bovine bronchus. In addition, GAGs are also found in molluscs, which are inferior, such as the presence of GAGs with antithrombin binding sites with 3-0-sulfuric acid groups in shellfish (Pejler et al., J. Biol. Chem ., 262, 11413-11421, 1986), chondroitin sulfates substituted with sulfuric acid have also been found in sea cucumbers and sea urchins (Mourao et al., TIGG , 7, 235-246, 1995). It is also known that chondroitin sulfate is present in the cornea of cuttlefish (Karamanos et al ., Int. J. Biochem ., 23, 67-72, 1991).

GAGs exist in the form of proteoglycans in vivo, and these proteoglycans are cleaved by protease and glycosidase to release glycosides. The physiological role of GAGs is not known yet, but it seems to show physiological activity by binding to proteins in vivo. Proteins that bind to GAGs in vivo can be classified into five categories: protease inhibitors, plasma lipoproteins, growth factors, lipolytic enzymes, and extracelluar matrix proteins. In combination with GAGs, it acts on specific physiological activities such as anti-blood coagulation, regulation of atherosclerosis, regulation of cell growth and differentiation, regulation of cell adhesion and intercellular communication.

As such, GAGs may be used in various applications because they show various physiological activities in combination with proteins in vivo. As an example in which GAGs are used as drugs, chondroitin sulfate is also used in eye drops, arthritis drugs, and recently, tonic drinks. Hyaluronic acid is also widely used as an additive in cosmetics. Heparin is widely used as a glycan drug in the clinic, and heparin is widely used as a anticoagulant for thrombosis, renal dialysis, artificial blood vessels, extracorporeal circulation, and the like. Recently, various biological activities, such as complement activity of the immune system, inhibition of peripheral angiogenesis, and interaction of basic fibroblast growth factors, have been reported in addition to anticoagulant action.

The structure of acaran sulfate is similar to the other GAGs, heparin and heparan sulfate, and the disaccharide → 4) -α-D-GlcNAc (1 → 4) -α-L-IdoA2S (1). ¡Æ heparan sulphate has a monosulfated structure, primarily on the disaccharides N-acetyl-D-glucosamine and D-glucuronic acid. Heparin has a trisulfated structure mainly in the disaccharides N-sulfonyl-D-glucosamine and L-iduronic acid.

Acaran sulfate exhibits a variety of biological activities, including those of other GAGs, and anti-coagulants with fewer side effects when acaran sulfate is structurally modified such as deacetylation, sulfate, and new oligo GAG. In addition, sulfated oligosaccharides of acaran sulfate provide the structural features necessary for binding to fibroblast growth factors and thus play an important role in cell growth and differentiation. In fact, the desulfurized compound -NH2 after deacetylation is expected to increase the cell growth by 6 times compared to the control group, and thus the wound healing effect can be expected. Acaran sulfate is also ideal as a model compound for reactions using sulfate-based transferases because of its simple structure of repeating disaccharides. In addition, acaran sulfate is known to be very effective in menopausal disorders, including osteoporosis, liver function, anti-tumor effect, peripheral angiogenesis inhibitory effect.

Although acaran sulfate exhibits various pharmacological effects as described above, it is difficult to handle due to their large molecular weight and there is a problem of causing side effects. Therefore, there is a great need to prepare acaran sulfate having low molecular weight. It became. Recently, the inventors have discovered that the bacteroid stecolis, a microorganism that synthesizes GAG degrading enzymes in the human intestine HJ-15 was isolated and identified (Korean Patent Registration No. 10-0257168), and a new acaran sulfate degrading enzyme was isolated therefrom (Korean Patent Application No. 2000-75605).

Helicobacter pylori ( H. pylori ) was first isolated and identified from patients with gastritis by Warren and Marshall in 1983. The bacterium is a spiral gram bacilli, sheathed flagella wrapped with 4-6 proteins, about 0.5x3.0 ㎛ in size, with no sugar fermentation capacity and no aerobic conditions (5%). O ₂ , 15% CO ₂ , 80% N ₂ ). Helicobacter pylori is in the form of bacillus in vitro , but once infected in the stomach of the human, helicobacter is transformed into a motile spiral in the gastric mucosa, forming colonies in the gastric mucosa and gastric tissue, forming vacuolating toxin (VacA). To produce). Helicobacter pylori VacA toxic substances are known to cause apoptosis of the epithelial cells and to induce inflammation by the action of inflammatory mediators produced by inflammatory cells.

In addition, Helicobacter pylori has a strong urease (urease), more than 100 times the urease production capacity of Proteus bacteria, a pathogen of endogenous gastritis, and hydrolyze urea in the stomach to produce ammonia. The ammonia thus produced has direct cytotoxicity, which causes damage to the gastric mucosa, and ammonia promotes the production of gastrin in the gastric pyloric mucosa, which in turn causes excess gastric acid secretion in the cells, triggering gastric ulceration.

Although Helicobacter pylori is a difficult bacterium that cannot survive in the environmental conditions where ordinary bacteria can live, it can be assumed that it is because these bacteria have flagella and urease. do.

Helicobacter pylori infection rarely occurs before the age of 20 in developed countries such as the United States and Australia, and 40-60% of infections are reported after 60 years of age, while developing countries are reported to be infected by 80% before age 20. Is reported to be more prominent in children than in developed countries. In Korea, infection rates of 50% before age 5, 80% at age 8 and about 90% at age 20 are reported to be inversely related to socioeconomic levels in children.

In addition, several epidemiologic investigations have been made on the correlation between Helicobacter pylori infection and gastric cancer. Helicobacter pylori has been reported to increase the risk of stomach cancer by 2-10 times.

Therefore, there is a need for a method for effectively treating gastrointestinal diseases caused by Helicobacter pylori, and the growth, adhesion, urease and VacA toxicants of Helicobacter pylori are very important for the treatment.

Conventionally, antibiotics have been used to remove Helicobacter pylori and improve symptoms. Helicobacter pylori is proliferated in vitro by most antibiotics such as amoxycillin, tetratracycline, metronidazole, erythromycin, clarithromycin, ciprofloxacin, etc. Although suppressed, administration of these antibiotics alone does not effectively eliminate Helicobacter pylori in vivo . Therefore, combination therapy which selectively administers several kinds of drugs together is mainly used. Representatively, triple therapies using clarithromycin, amoxycillin, and proton pump inhibitors, triple theraphy and clarithromycin or amoxycillin and protons Dual therapy using a combination of proton pump inhibitors is widely used. Triple treatment with bismuth (bismuth, metronidazole, amoxicillin or tetracycline) has been reported, but side effects such as vomiting, taste disorders and diarrhea have been reported in 20-30% of patients receiving this product. Many types of Helicobacter pylori have been reported that are resistant to metronidazole. Dual or triple treatment with proton pump inhibitors is most widely used, with high rates of treatment reported for two weeks with less than 5% of adverse events occurring.

Nevertheless Antibiotics used to remove Helicobacter pylori should be taken for a long time. In the process, there are side effects such as resistance or the occurrence of mental illness caused by metronidazole. Therefore, the need for a new Helicobacter pylori infection inhibitor is proposed.

Therefore, the inventors of the present invention, while studying the function of the acaran sulfate, the acaran sulfate effectively inhibits Helicobacter pylori infection, acute gastritis, chronic active gastritis, liver, chronic atrophic gastritis, non-ulcer dyspepsia, gastric ulcer, duodenum The present invention has been completed by revealing that it can be usefully used for the prevention and treatment of gastrointestinal diseases including ulcers, gastric adenocarcinoma, lymphoma, and gastric cancer.

It is an object of the present invention to provide a Helicobacter pylori infection inhibitor containing acaran sulfate as an active ingredient.

It is also an object of the present invention to provide an agent for the prevention and treatment of diseases of the gastrointestinal tract containing acaran sulfate as an active ingredient.

In order to achieve the above object, the present invention provides a Helicobacter pylori (Helicobacter pylori) infection inhibitor containing ACCA is sulfuric acid as an active ingredient.

It is also an object of the present invention to provide an agent for preventing and treating gastrointestinal diseases containing acaran sulfate as an active ingredient.

Hereinafter, the present invention will be described in detail.

Acaran sulfate according to the present invention is a glycosaminoglycan-based material composed of a polymer having a molecular weight of about 135,000 and separated and purified through various steps such as ethanol precipitation from Achatina fulic from Africa. Kim YS et al., A New Glycosamineglycan From the Giant African Snail Achatina fulic , J. Biol. Chem ., 271 (20): 11750-11755, 1996).

The acaran sulfate according to the present invention is preferably a low molecular weight (LMW) acaran sulfate oligomer having a molecular weight of 1 to 10 kDa (kDaltons), more preferably 1.5 to 3 kDa acaran sulfate oligomer. Acaran sulfate oligomers can be obtained by enzymatic or chemical decomposition of acaran sulfate. Enzymatic methods are to decompose using heparin lyase, acharan sulfate lyase isolated from bacteroids (Kim BT et al., Purification and characterization of acharan sulfate lyases, two novel heparinases) , from Bacteroides stercoris HJ- 15.Eur . J. Biochem ., 268: 2635-2641, 2001). Chemical methods include controlled chemical depolymerization (N Volpi et al., Low molecular weight heparins (5 kDa) and oligoheparins (2) induced by free radicals from hydrogen peroxide in the presence of metal salts. kDa) produced by gel permeation enrichment or radical process: Comparison of structures and physicochemical and biological properties, Analytical Biochemistry , 200 (1): 100-107, 1992). This method is based on the generation of free radical OH using metal ions and hydrogen peroxide or peracids. The radical reaction of acaran sulfate leads to rearrangement of the structure and cleavage of glycosidic bonds.

The low molecular weight acaran sulfate oligomer having a molecular weight of 1 to 10 kDa having 2 to 30 monomers can be obtained by eluting from the acaran sulfate oligomer produced by the enzymatic or chemical method using HPLC.

In addition, acaran sulfate according to the present invention can be used in the form of sodium, calcium, lithium salts that can be conventionally provided.

Helicobacter pylori infection inhibitor containing acaran sulfate of the present invention as an active ingredient is a urease secreted by Helicobacter pylori compared to other GAGs and polysaccharides, including heparin, which is known to be effective in inhibiting infection of Helicobacter pylori. Its high inhibitory effect significantly reduces Helicobacter pylori infection.

Therefore, the Helicobacter pylori infection inhibitor containing acaran sulfate of the present invention as an active ingredient includes acute gastritis, chronic active gastritis, liver, chronic atrophic gastritis, non-ulcer dyspepsia, gastric ulcer, duodenal ulcer, gastric cancer, lymphoma, stomach cancer It can be usefully used for the prevention and treatment of diseases of the gastrointestinal tract.

The Helicobacter pylori infection inhibitor of the present invention may contain one or more active ingredients exhibiting the same or similar functions in addition to the acaran sulfate.

The Helicobacter pylori infection inhibitor of the present invention may be a pharmaceutical composition and may be used in the form of a general pharmaceutical formulation.

That is, the acaran sulfate of the present invention may be administered in various oral and parenteral dosage forms in actual clinical administration, and when formulated, diluents such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. that are commonly used Or using excipients. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose ( Sucrose) or lactose (Lactose), gelatin, etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used. In addition, calcium or vitamin D ₃ may be added to improve the efficacy as a preventive or therapeutic agent for gastrointestinal diseases.

The dosage of the pharmaceutical composition of the present invention varies depending on the body weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of the disease, the daily dosage is acaran sulfate 0.1 to 100 mg / kg based on the amount of can be administered 1 to 6 times a day.

The pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of gastrointestinal diseases.

Inhibitors of the present invention may be in the form of health foods for the purpose of improving gastrointestinal diseases. When the acaran sulfate of the present invention is used as a food additive, the acaran sulfuric acid can be added as it is or used with other food or food ingredients, and can be suitably used according to a conventional method. The blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment). However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. Is sure. There is no particular limitation on the kind of food.

The health food of the present invention may contain various flavors, natural carbohydrates, and the like as additional ingredients, as in general beverages. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The proportion of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.

In addition to the above, the health food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And a carbonation agent used for the carbonated beverage.

Hereinafter, preferred examples and experimental examples are presented to help understand the present invention. However, the following Examples and Experimental Examples are provided only to more easily understand the present invention, and the contents of the present invention are not limited by the examples.

Example 1: Preparation of Acaran Sulfate Oligomer by Enzymatic Method

Heparin lyase dissolved in acaran sulfate (10 mg / ml) in 50 mM sodium phosphate buffer (pH 7.0) and isolated from Bacteroides stercoris HJ-15 (KCCM-10096) , 7.5mU / mg) was added and reacted at 37 ° C. In order to determine the degree of decomposition of acaran sulfate during the reaction, it was measured at 232 nm using an anion exchange column by HPLC every 30 minutes. When it was confirmed that a high molecular weight acaran sulfate oligomer was produced, it was used for 5 minutes at 100 ℃ to eliminate the activity of the enzyme.

Separation and Purification of Strong Anion Exchange (SAX) -HPLC Using Low Molecular Weight Acaran Sulfate Oligomer

Enzymatically degraded low molecular weight acaran sulfate was separated via HPLC. For the separation process, a Phenosphere 5u SAX 80A column was used, and the solvent was distilled water (pH 3.5) and 2M NaCl (pH 3.5). The salt concentration gradient was 0 to 2M, and the flow rate was separated at 1.0 mL / min. Each of the separated 2 to 30 mer acaran sulfate oligomers was purified using a desalting column (FIGS. 1 and 2).

The separated acaran sulfate oligomers were separated and purified once again in the same manner as above.

As can be seen in Figures 1 and 2, it was possible to make oligomers by decomposing acaranic acid with enzyme, and separated by HPLC to separate only low molecular weight acaranic acid oligomer, purity through CE (Capillary-electrophoresis) analysis As a result, it was shown that the purity of 85 to 95% (Fig. 3).

Analysis of low molecular weight acaran sulfate oligomers using fluorophore-assisted carbohydrate electrophoresis (FACE) and Matrix-Assisted Laser Desorption Mass Spectrometry (MALDI-MS)

0.15M ANTS (8-aminonaphtalene-1,3,6-trisulfonate) dissolved in 15% acetic acid was added to the acaran oligomer isolated to 2-30 mer (mer) and labeled for 30 minutes preincubation at room temperature. Then 1M NaBH3CN dissolved in DMSO was added and reacted at 37 ° C. for 16 hours. After the reaction was completed, 60% sucrose was added to each of the acaran sulfate oligomers to which ANTS was bound, and 30% polyacrylamide gel was used for 1 hour at 20 ° C. at 4 ° C. with 1 × TBE buffer solution. Electrophoresis was performed for 30 minutes. After electrophoresis, it was confirmed using an ultraviolet analyzer (UV-Transilluminator), and the molecular weight of each fraction was measured using MALDI-MS.

As a result, it was clearly confirmed that an acaran sulfate oligomer of 30 mer or less was formed (FIG. 4), and the molecular weight of the 12 oligomer was measured to be 2754.4 Da, indicating the molecular weight of each oligomer. It was found that the molecular weight of the oligomers became 10 kDa or less (FIG. 5).

Example 2: Preparation of Acaran Sulfate Oligomer by Chemical Method

10 g of acaran sulfate and 5 g of sodium acetate are dissolved in 100 ml of distilled water and placed in a fixed vessel with a thermostatic bath, stirrer, calibrated drop funnels and a thermometer. Put in. Copper acetate monohydrate (0.46 g / 10 ml) dissolved in distilled water was added. The temperature was kept constant at 50 ° C. and the pH was maintained at 7.5 with 1N NaOH solution. For 6 hours (total reaction time) 25 ml of 9% hydrogen peroxide solution was added at a flow rate of 10 ml / h and kept 7.5 with 1N NaOH solution. Samples were collected at regular intervals to determine the molecular weight of the acaran sulfate fragments, and each biological activity was measured in vitro. At the end of the reaction (after 6 hours), chelating resin Chelex 100 (Bio-Rad) was used to remove the remaining copper from the product, and salt was removed using Bio gel P-2. .

Separation and Purification of Low Molecular Weight Acaran Sulfate Oligomers by HPLC

It was measured using HPLC on a TSK G6000SW column (4.6 × 300 mm, Tosh, Japan) equilibrated with 100 mM NaCl. The molecular weight was calculated by preparing a calibration curve with the acaran sulfate oligomer fraction and GAG of known molecular weight as a logarithm of the molecular weight relative to retention time.

As a result, after about 120 minutes at 50 ℃ radical depolymerization (radical depolymerization) produced a fragment of 2 kDa, the molecular weight decreased exponentially with the residence time (Fig. 6).

Experimental Example 1 Measurement of Helicobacter Pylori Inhibition Effect of Acaran Sulfate

In this experiment, the Helicobacter pylori ATCC 43504 cell line (US Cell Line Bank) was used. Cells were transplanted into Brucella agar with 7% heat inactivated horse serum and incubated at 37 ° C. under aerobic conditions (5% O 2, 15% CO 2, 80% N 2) for 3 days. Then, strains are collected by adding 2 ml of physiological saline to the plate on which each strain is grown. 0.5 ml of the strain collection solution was transplanted into 20 ml of Brucella broth in which 10% fetal bovine serum (FBS) was added, followed by aerobic conditions (5% O ₂ , 15% CO ₂ , Incubate for 3 days with 80% N ₂ ). The strain was stored at −70 ° C. with the addition of 10% DMSO (dimethyl sulfoxide) and used as an experimental strain.

Helicobacter pylori ATCC 43504 was centrifuged at 3000 rpm for 10 minutes, and then the supernatant was discarded and washed with PBS buffer. After centrifugation again at 3000 rpm for 10 minutes, the cells were suspended in 3 ml of PBS. 400 μl of GAG and polysaccharide samples including acaran sulfate were added and 400 μl of the bacteria were reacted in a water bath at 37 ° C. for 30 minutes, followed by treatment with tyrosine (trypsin) to collect KATO III cells (Korea Cell Line Bank) 5106. 200 µl was adjusted to pieces / ml and reacted in a 37 ° C water bath for 1 hour. 15% sucrose solution was placed in a tube, the reaction solution was placed in the base wall so as not to mix with the sucrose solution, and the cells were collected by centrifugation at 1000 rpm for 10 minutes. PBS buffer solution was added to the collected cells and washed, and then 300 µl of PBS buffer solution was added and suspended.

For urease inhibitory activity, 100 µl of bacterial culture suspension and 50 µl of 5M urea were reacted in a water bath at 37 ° C. for 20 minutes, and then 100 µl of H ₂ SO ₄ was added to stop the reaction. Solution I (5 g of phenol, 25 mg of sodium nitroprusside, 500 ml of distilled water) and Solution II (2.5 g of NaOH, 26.8 g of sodium phosphate dibasic), 10 ml of NaOCl, distilled water 1 ml each of 490 ml) was reacted in a water bath at 60 ° C. for 20 minutes and centrifuged to measure absorbance at 660 nm.

As a result, heparin, which is known to have an anti-infective effect of Helicobacter pylori, has an IC ₅₀ value of 2.1 mg / ml, which shows a 50% infection suppression effect, compared to 1.4 mg / ml of acaran sulfate. It was confirmed that the higher the value of heparin than the acaran sulfate sulfuric acid Helicobacter pylori infection inhibitory effect (Table 1).

Inhibitory Effect of Helicobacter Pylori Infection on KATO III Cells of GAGs and Polysaccharides sample IC ₅₀ (mg / ml) Heparin 2.1 Heparan sulfate > 5 Acharan sulfate 1.4 Chondroitin sulfate A > 5 Chondroitin sulfate C > 5 Ampicillin -a -a not measured.

In addition, in order to investigate the inhibitory effect of acaran sulfate according to the molecular size, the cleaved acaran sulfate was separated by molecular weight (2940, 2380, 1925, 1832 and 1773 Da (daltons)) to measure the inhibitory effect of Helicobacter pylori infection. It was.

As a result of the measurement, the compound prepared by cleavage was stronger than the original compound of acaran sulfate, and the IC ₅₀ of the oligomer having a molecular weight of 1925 Da showed the strongest inhibitory effect of 0.032. However, compounds with lower molecular weights had a lower infection inhibition effect (Table 2, Figure 7. 8).

Helicobacter Pylori Infection Inhibitory Effects of Acaran Sulfate Oligomers on Molecular Weight Molecular Weight (Da) IC ₅₀ (mg / ml) 1733 0.532 1832 1.076 1925 0.032 2380 0.146 2940 0.100

As described above, the composition containing acaran sulfate of the present invention as an active ingredient, in particular a composition containing an acaran sulfate oligomer having a molecular weight of 1.5 to 3 kDa as an active ingredient, inhibits the activity of the urease secreted by Helicobacter pylori Of gastrointestinal diseases including acute gastritis, chronic active gastritis, glabella, chronic atrophic gastritis, non-ulcer dyspepsia, gastric ulcer, duodenal ulcer, gastric adenocarcinoma, lymphoma, gastric cancer caused by Helicobacter pylori It can be usefully used for prevention and treatment.

Claims (7)

Helicobacter pylori infection inhibitor containing acaran sulfate as an active ingredient. According to claim 1, wherein the acaran sulfate is a Helicobacter pylori ( Helicobacter pylori ) infection inhibitor, characterized in that the acaran sulfate oligomer having a molecular weight of 1 ~ 10kDa. [Claim 2] The Helicobacter pylori infection inhibitor according to claim 1, wherein the acaran sulfate is an acaran sulfate oligomer having a molecular weight of 1.5 to 3 kDa. A gastrointestinal disease prevention and treatment containing acaran sulfate as an active ingredient. The method of claim 4, wherein the acaran sulfate is an acaran sulfate oligomer having a molecular weight of 1 to 10 kDa. The method of claim 4, wherein the acaran sulfate is an acaran sulfate oligomer having a molecular weight of 1.5 to 3 kDa. According to claim 4, wherein the gastrointestinal disease is selected from the group consisting of acute gastritis, chronic active gastritis, coccyx, chronic atrophic gastritis, non-ulcer dyspepsia, gastric ulcer, duodenal ulcer, gastric cancer, lymphoma, gastric cancer Prevention and treatment of diseases of the gastrointestinal tract.

Images