KR102682331B1 - A Composition For Preventing, Improving Or Treating Gastrointestinal Disorders Including Eucommia ulmoides Oliver Extract And Red Ginseng Extract - Google Patents

Abstract

The present invention provides a composition for preventing, improving, or treating gastrointestinal disorders, comprising a cephalic herb extract and a red ginseng extract. The composition for preventing, improving or treating gastrointestinal disorders of the present invention is excellent in suppressing excessive gastric acid secretion and alleviating the degree of gastric damage by containing the extract of eucommia and red ginseng extract in a specific weight ratio. In addition, the composition for preventing, improving or treating gastrointestinal disorders of the present invention contains extracts derived from natural substances, so it has low toxicity and has the advantage of being able to achieve the effect of preventing, improving or treating gastrointestinal disorders by drinking it on a daily basis.

Description

Composition for preventing, improving or treating gastrointestinal disorders including Eucommia ulmoides Oliver Extract And Red Ginseng Extract}

The present invention relates to a composition for preventing, improving, or treating gastrointestinal disorders, comprising a cephalic extract and a red ginseng extract.

Hyperacidity is a symptom of excessive secretion of gastric acid within the stomach and is a common gastrointestinal disorder that can occur even in normally healthy people. It can occur even in chronic gastrointestinal diseases, but it can also occur temporarily when the rhythm of life is broken due to mental anxiety, stress, or irregular eating. Symptoms of excessive gastric acid mainly include pain in the solar plexus, pain on an empty stomach (symptoms temporarily disappear after eating food), stomach pain, burping, sores, rumination, and bowel movements. When these symptoms accumulate, they lead to gastritis and peptic ulcer. It can progress to various diseases such as reflux esophagitis.

Peptic ulcer commonly refers to a stomach ulcer or duodenal ulcer, and refers to a condition in which the mucous membrane of the stomach or duodenum is damaged or lost due to some cause, exposing the submucosal tissue. If the lesion is limited to the mucous membrane, it is called erosion, and the terms gastritis or duodenitis are also used to refer to the destruction of the stomach or duodenum. Peptic ulcer is a common disease that occurs in 5-10% of the world's population, and it is known to be 2-3 times more common in men than in women. Duodenal ulcers often occur at a younger age than gastric ulcers. Duodenal ulcers commonly occur between the ages of 30 and 50, and gastric ulcers commonly occur between the ages of 40 and 60.

For the treatment of gastrointestinal disorders, antacids and histamine receptor antagonists are mainly used, but even if gastritis or peptic ulcers are cured, they often recur or reappear, so long-term maintenance therapy is necessary even after complete healing. Accordingly, research is continuously being conducted on compositions that can prevent or improve gastrointestinal disorders by suppressing excessive secretion of gastric acid and that can be consumed on a daily basis.

Ginseng ( Panax ginseng ) is a perennial shade-loving herb belonging to the Panax genus of the Araliaceae family, and has long been used as an important medicinal herb in oriental medicine. Ginseng is generally divided into white ginseng and red ginseng depending on the processing method. White ginseng refers to unprocessed ginseng mined from the field, that is, dried fresh ginseng, and red ginseng refers to fresh ginseng that is steamed, dried, and processed, and saponin is modified and processed during the manufacturing process. It involves several chemical changes, including amino acid changes. Red ginseng produces saponin components such as ginsenosides Rg2, Rg3, Rh1, and Rh2, which do not exist in ginseng, due to the heat applied during the manufacturing process. Red ginseng's unique active ingredients prevent cancer, inhibit cancer cell growth, and lower blood pressure. , It is excellent in protecting brain nerve cells, improving learning ability, anti-thrombotic activity, and antioxidant activity.

Eucommia ulmoides oliver refers to a deciduous tree belonging to the Eucommia ulmoides oliver family or a herbal medicine made from dried bark. The stems and leaves of Duchung have been consumed as tea since ancient times. They contain a lot of vitamin C and are known to have blood pressure lowering and diuretic effects. The stems and leaves are useful herbal medicine for various diseases such as stress and hangovers. Not only has it been consumed as a tea, but recently, as the pharmacological mechanisms of various ingredients contained in eucalyptus have been gradually revealed through clinical experiments, its value is being re-recognized, and it is widely consumed as a health tea.

The present inventors studied whether materials derived from natural products could be used to improve gastrointestinal disorders. Among the natural products, mixing red ginseng extract and Eucommia extract in a specific ratio prevented gastrointestinal disorders by suppressing excessive gastric acid secretion and alleviating the degree of gastric damage. The present invention was completed after confirming that the improvement or treatment effect was excellent.

Korean Patent Publication No. 10-2009-0046425 (May 11, 2009)

The purpose of the present invention is to provide a composition that is effective in preventing, improving, or treating gastrointestinal disorders.

One aspect of the present invention provides a pharmaceutical composition for preventing, improving, or treating gastrointestinal disorders, comprising a cephalic extract and a red ginseng extract.

Another aspect of the present invention provides a health functional food composition for preventing or improving gastrointestinal disorders, comprising a cephalic herb extract and a red ginseng extract.

The composition for preventing, improving, or treating gastrointestinal disorders of the present invention is excellent in suppressing excessive gastric acid secretion and alleviating the degree of gastric damage by containing natural substances such as eucommia extract and red ginseng extract in a specific weight ratio. Therefore, the composition for preventing, improving or treating gastrointestinal disorders of the present invention contains extracts derived from natural substances, so it has low toxicity and can be consumed on a daily basis, thereby effectively achieving the effect of preventing, improving or treating gastrointestinal disorders. there is.

Figure 1 shows the results of confirming the cAMP level (%) of the experimental group compared to the control group.
Figure 2 shows the results of confirming the H+/K+ ATPase activity (%) of the experimental group compared to the control group.
Figure 3 shows the results of confirming the gastric juice secretion amount (%) of the experimental group compared to the control group.
Figure 4 shows the results of confirming the gastric wall damage index (%) of the experimental group compared to the control group.
Figure 5 shows the results of confirming the blood histamine level (%) of the experimental group compared to the control group.

Hereinafter, the present invention will be described in more detail to facilitate understanding of the present invention. At this time, the terms or words used in this specification and claims should not be construed as limited to their usual or dictionary meanings, and the inventor should appropriately define the concept of the term in order to explain his or her invention in the best way. It must be interpreted with meaning and concept consistent with the technical idea of the present invention based on the principle that it can be done.

1. Preparation of Duchung extract and red ginseng extract

In the present invention, the leaves, young shoots, body, body shell, stem, stem bark, root, root bark, rhizome, seed, fruit, immature fruit, mature fruit, flesh, pericarp, flower, and stamen group (androecium) of the plant are used. ), gynoecium, sepals, stamens, petals, sepal pieces, carpels, and combinations thereof. Preferably, stem bark can be used.

In the present invention, red ginseng is made by steaming, cooking, and drying raw ginseng, and a browning reaction occurs during the drying process, resulting in a light yellow-brown to reddish-brown color. Additionally, the ginseng can be used without limitation, whether cultivated or commercially available.

In the present invention, 'extract' refers to a substance extracted from a raw material by any method, and is used to include, without limitation, the extract thus extracted, the concentrate obtained therefrom, and the dried product and powder of the concentrate.

When obtaining the extract from raw materials, all conventionally known extraction methods such as solvent extraction, ultrasonic extraction, filtration, and reflux extraction can be used. Preferably, solvent extraction or reflux extraction are used. can do. The extraction process can be repeated several times, and then additional steps such as concentration or freeze-drying can be performed. Specifically, the obtained extract can be concentrated under reduced pressure to obtain a concentrate, the concentrate can be freeze-dried, and then a high-concentration extract powder can be prepared using a grinder. The extract also includes fractions obtained by further fractionating the extract.

The extract may use at least one selected from the group consisting of water, organic solvent, supercritical fluid, and mixtures thereof as an extraction solvent. The organic solvent is alcohol, preferably C1-C4 lower alcohol, hexane (n-hexane), ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, ethyl acetate, benzene, and It may be any one selected from the group consisting of mixed solvents thereof, and is preferably ethanol. For example, when using a mixture of water and an organic solvent as an extraction solvent, the mixture of water and an organic solvent may preferably be a mixture of water and a C1-C4 lower alcohol, more preferably a mixture of water and ethanol. It may be a mixture.

The mixture of water and ethanol may be a 3% (v/v) to 70% (v/v) ethanol aqueous solution, such as a 5% (v/v) to 50% (v/v) ethanol aqueous solution, preferably It may be a 10% (v/v) to 45% (v/v) ethanol aqueous solution, more preferably a 15% (v/v) to 40% (v/v) ethanol aqueous solution, and even more preferably may be a 20% (v/v) to 35% (v/v) ethanol aqueous solution, but is not limited thereto.

The solvent used in the preparation of the Eucommia extract may be water or a C1-C4 alcohol, preferably ethanol or an aqueous ethanol solution, more preferably 20% (v/v) to 35% (v/v). It may be an ethanol aqueous solution. If the concentration of the ethanol aqueous solution is less than the lower limit when preparing the eucalyptus extract, it may be difficult to extract the active ingredient that shows the effect of preventing, improving, or treating gastrointestinal disorders, making it difficult to obtain the desired level of prevention, improvement, or treatment effect of gastrointestinal disorders.

The solvent used in preparing the red ginseng extract may be water.

Extraction may be performed at 60°C to 100°C, preferably at 65°C to 95°C, and more preferably at 70°C to 90°C, but is not limited thereto. Extraction may be performed for 4 hours to 24 hours, preferably for 4 hours to 16 hours, and more preferably for 4 hours to 12 hours, but is not limited thereto.

Extraction may be performed 1 to 7 times, preferably 1 to 5 times, and more preferably 1 to 3 times, but is not limited to this, and the extract is obtained from each extraction. It may be a single extract or a mixed extract of extracts obtained from each extraction.

In order to obtain specific active ingredients that are highly effective in preventing, improving, or treating gastrointestinal disorders from each of the above extracts, the fractions obtained by additionally performing a conventional fractionation process can be used. For example, fractions obtained by passing the extract obtained according to the above extraction through an ultrafiltration membrane with a certain molecular weight cut-off value, by various chromatographs (designed for separation according to size, charge, hydrophobicity or affinity). Active fractions obtained through various purification methods, such as separation, are also included in the extract of the present invention. Extracts containing a mixture of various ingredients can be separated according to the properties of the active ingredients through concentration gradient column chromatography, etc. to prepare specific active fractions with better effects for preventing, improving, or treating gastrointestinal disorders.

The chromatography may be, for example, one or more types selected from the group consisting of column chromatography, high performance liquid chromatography (HPLC), ion exchange chromatography, affinity chromatography, and size exclusion chromatography.

The column chromatography is performed using a filler selected from the group consisting of silica gel, Sephadex, LH-20, ODS gel, RP-18, polyamide, Toyopearl, and XAD resin to separate the active fraction. and purification, and column chromatography can be performed several times by selecting an appropriate filler as needed, but is not limited thereto. When using the chromatography, the elution solvent, elution rate, and elution time may be solvents, rates, or times commonly used in the art.

Additionally, in order to obtain specific active ingredients that are highly effective in preventing, improving, or treating gastrointestinal disorders, fractions obtained by fractionating each of the above extracts with an organic solvent can be used. The organic solvent includes alcohol, hexane (n-hexane), ether, glycerol, propylene glycol, butylene glycol, ethyl acetate, methyl acetate, dichloromethane, chloroform, ethyl acetate, benzene, acetone, acetonitrile, and mixed solvents thereof. It may be any one selected from the group consisting of, but is not limited to this.

2. Pharmaceutical composition for preventing, improving or treating gastrointestinal disorders containing Eucommia extract and red ginseng extract

One aspect of the present invention provides a pharmaceutical composition for preventing, improving, or treating gastrointestinal disorders, comprising a cephalic extract and a red ginseng extract.

The manufacturing method of the Duchung extract and the red ginseng extract is the same as that mentioned in “ 1. Preparation of the Duchung extract and the red ginseng extract ” above, so description is omitted.

The above gastrointestinal disorder may be caused by excessive secretion of gastric acid, and may be used to include heartburn, gastritis, peptic ulcers such as gastric or duodenal ulcers, and reflux esophagitis. Additionally, symptoms of excessive gastric acid secretion may occur due to mental anxiety, stress, irregular lifestyle, or chronic gastrointestinal disease, but are not particularly limited thereto.

In the present invention, “prevention” refers to all actions that suppress or delay gastrointestinal disorders by administration of the composition, and “treatment” refers to all actions that improve or beneficially change the symptoms of gastrointestinal disorders by the composition.

The pharmaceutical composition for preventing, improving or treating gastrointestinal disorders of the present invention is prepared by mixing the Eucommia extract and the red ginseng extract at a weight ratio of 1:2 to 1:3.5, or 1:2.5 to 1:3.5, or 1:2 to 1. It can be included in a weight ratio of :3. If the ratio of the Eucommia extract and the red ginseng extract is outside the above range, the effectiveness of preventing, improving, or treating gastrointestinal disorders may be reduced.

In addition, the mixture of the Eucommia extract and the red ginseng extract is 0.005 to 20.0% by weight, or 0.01 to 10.0% by weight, or 0.01 to 5% by weight, or It may be contained in an amount of 0.01 to 3% by weight, or 0.1 to 2% by weight, or 0.5 to 1.5% by weight, but is not limited thereto. If the effective content of the mixture of the Eucommia extract and red ginseng extract is less than 0.005% by weight, the effect of preventing, improving, or treating gastrointestinal disorders is lowered, and if it exceeds 20% by weight, the effect of increasing the effective efficacy due to the increase in content decreases. It can be economical.

The pharmaceutical composition of the present invention can provide a synergistic effect on the effect of the mixture of the Eucommia extract and the red ginseng extract, within a range that does not impair the effect aimed at by the present invention, in addition to the mixture of the Eucommia extract and the red ginseng extract. It may additionally contain other ingredients. For example, it may include antioxidants, stabilizers, solubilizers, wetting agents or emulsification accelerators, vitamins, auxiliaries such as salts and/or buffers for adjusting osmotic pressure, and other therapeutically useful substances.

The pharmaceutical composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, external preparations, suppositories, and sterile injection solutions according to conventional methods.

Solid preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills, etc. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. there is.

Preparations for parenteral administration include external preparations such as powders, granules, tablets, capsules, sterilized aqueous solutions, solutions, non-aqueous solvents, suspensions, emulsions, syrups, suppositories, and aerosols, and sterilized injection preparations according to conventional methods. It can be formulated and used in the form of a cream, gel, patch, spray, ointment, warning agent, lotion, liniment agent, pasta agent, or cataplasma agent. It can be prepared and used as a pharmaceutical composition for external use on the skin. , but is not limited to this. Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurin, glycerogeratin, etc. can be used.

The route of administration of the pharmaceutical composition of the present invention includes oral, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal administration, for example, topical administration by application. application) method. The parenteral includes subcutaneous, intradermal, intravenous, intramuscular, and intralesional injection or infusion techniques.

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount.

In the present invention, “pharmaceutically effective amount” means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type and severity of the individual, age, gender, type of disease, It can be determined based on factors including the activity of the drug, sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used simultaneously, and other factors well known in the medical field. The pharmaceutical composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And it can be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects, and can be easily determined by a person skilled in the art.

The dosage of the pharmaceutical composition of the present invention may vary depending on various factors, including the subject's age, weight, general health, gender, administration time, administration route, excretion rate, drug combination, and severity of a particular disease.

Additionally, the pharmaceutical composition of the present invention can be used alone or in combination with surgery, radiation therapy, hormone therapy, chemotherapy, and methods using biological response regulators. In addition, the pharmaceutical composition of the present invention can be administered in a dosage range of 0.001 to 200 mg/kg for adults, 70 to 200 mg/kg, or 80 to 170 mg/kg, or 130 to 160 mg/kg, Alternatively, it may be administered at a dosage of 145 to 155 mg/kg. When the pharmaceutical composition is for external use, it is recommended to apply it once to five times a day in an amount of 1.0 to 3.0 ml for adults and continue for more than one month, but the dosage does not limit the scope of the present invention.

In addition, the pharmaceutical composition of the present invention is not particularly limited and can be applied to any subject as long as it is intended for the prevention, improvement or treatment of gastrointestinal disorders. For example, the pharmaceutical composition of the present invention can be used not only on humans, but also on non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cows, sheep, pigs, goats, birds, and fish. do.

3. Health functional food composition for preventing or improving gastrointestinal disorders containing Eucommia extract and red ginseng extract

One aspect of the present invention provides a health functional food composition for preventing or improving gastrointestinal disorders comprising a cephalic herb extract and a red ginseng extract.

The manufacturing method of the Duchung extract and the red ginseng extract is the same as that mentioned in “ 1. Preparation of the Duchung extract and the red ginseng extract ” above, so description is omitted.

The above gastrointestinal disorder may be caused by excessive secretion of gastric acid, and may be used to include heartburn, gastritis, peptic ulcers such as gastric or duodenal ulcers, and reflux esophagitis. Additionally, symptoms of excessive gastric acid secretion may occur due to mental anxiety, stress, irregular lifestyle, or chronic gastrointestinal disease, but are not particularly limited thereto.

In the present invention, prevention or improvement of gastrointestinal disorders can be achieved by suppressing excessive secretion of gastric acid.

The health functional food composition for preventing or improving gastrointestinal disorders of the present invention contains the Eucommia extract and the red ginseng extract at a weight ratio of 1:2 to 1:3.5, or 1:2.5 to 1:3.5, or 1:2 to 1: It can be included in a weight ratio of 3. If the ratio of the Eucommia extract and the red ginseng extract is outside the above range, the effect of preventing or improving gastrointestinal disorders may be reduced.

In addition, the mixture of the Eucommia extract and the red ginseng extract is 0.005 to 20.0% by weight, or 0.01 to 10.0% by weight, or 0.01 to 5% by weight, or 0.01% by weight, based on the total weight of the health functional food composition for preventing or improving gastrointestinal disorders. It may be contained in an amount of 3 to 3% by weight, or 0.1 to 2% by weight, or 0.5 to 1.5% by weight, but is not limited thereto. If the effective content of the mixture of Eucommia extract and red ginseng extract is less than 0.005% by weight, the effect of preventing or improving gastrointestinal disorders is lowered, and if it exceeds 20% by weight, the effect of increasing the effective efficacy due to the increase in content is reduced, making it uneconomical. You can.

The health functional food composition, in addition to the mixture of the eucommia extract and the red ginseng extract of the present invention, preferably provides a synergistic effect on the effect of the mixture of the eucommia extract and the red ginseng extract within the range that does not impair the effect aimed at by the present invention. It may additionally contain other ingredients. For example, it may include conventional auxiliaries such as stabilizers, solubilizers, vitamins, pigments and flavors, or carriers.

It may also contain ingredients commonly added when manufacturing a health functional food composition, including, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. Examples of such carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, oligosaccharides, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, natural flavoring agent thaumatin, stevia extract, and synthetic flavoring agent may be used. For example, when the health functional food composition of the present invention is manufactured as a drink, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, malic acid, fruit juice, natural extract, etc. may be additionally included in addition to the Eucommia extract and red ginseng extract of the present invention.

Health functional foods to which the mixture of Eucommia extract and red ginseng extract of the present invention can be added are not particularly limited, but include, for example, meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, It includes dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and vitamin complexes, and includes all foods in the conventional sense.

The health functional food can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of preventing or improving gastrointestinal disorders.

For example, health functional food in the form of tablets is made by granulating a mixture of the health functional food composition with excipients, binders, disintegrants, and other additives in a conventional manner, adding a lubricant, etc., and compression molding, or The mixture can be directly compression molded. Additionally, the health functional food in the form of tablets may contain flavoring agents, etc., if necessary.

Among capsule-type health functional foods, hard capsules can be manufactured by filling a regular hard capsule with a mixture of the health functional food composition mixed with additives such as excipients, and soft capsules can be manufactured by mixing the health functional food composition with additives such as excipients. It can be manufactured by filling the mixture with a capsule base such as gelatin. The soft capsule may contain plasticizers such as glycerin or sorbitol, colorants, preservatives, etc., if necessary.

The health functional food in the form of a pill can be prepared by molding a mixture of the health functional food composition and excipients, binders, disintegrants, etc. using a known method. If necessary, it can be coated with white sugar or other coating agents. , or the surface can be coated with substances such as starch or talc.

Health functional food in the form of granules can be manufactured into granules by mixing the above-mentioned health functional food composition with excipients, binders, disintegrants, etc., using a known method. If necessary, it may contain flavoring agents, flavoring agents, etc. You can.

Hereinafter, the present invention will be described in detail through preparation examples and examples.

However, the following preparation examples, experimental examples, and examples are only for illustrating the present invention, and the content of the present invention is not limited by the following preparation examples and examples.

Preparation Example 1. Preparation of Eucommia extract

Add 30% (v/v) ethanol solution 10 to 15 times the weight to 2 kg of Eucommia ulmoides Oliver ( stem bark), extract 1 to 3 times at 80°C for 4 to 12 hours, and filter the extract through a 5㎛ filter. It was filtered using. The filtrate was concentrated at 50-60°C using a rotary vacuum concentrator (BUCHI, R-220), and finally the concentrate was diluted to 15°Brix by adding sterilized distilled water and then freeze-dried (OPERON, FDT-12012). 255.9 g of Euchung extract powder was obtained.

Preparation Example 2. Preparation of red ginseng extract

500 g of 6-year-old red ginseng ( P. ginseng CA Meyer, 75% root, 25% residue) was dried at 100-120°C for 15-20 minutes using a far-infrared dryer (Korea Energy Technology Co., Ltd., HKD-LAB) and then cut into pieces. . 4 to 8 times the amount of distilled water was added to dried red ginseng and extracted at 85°C for 8 to 12 hours. The extract was filtered and cooled to 0 to 10°C. For the residue, 4 to 8 times more distilled water was added and extraction was performed 1 to 4 additional times for 8 to 12 hours. The extracts were filtered, combined and cooled to 0 to 10°C. The cooled extract was centrifuged at 5,000 to 8,000 rpm for 10 to 20 minutes at 4°C (Hanil Cymed Co., Ltd., Supra 22K) to remove precipitates, and then concentrated to 50 rpm using a rotary vacuum concentrator (BUCHI, R-220). Concentrated to 71°Brix at ~60°C. Finally, sterilized distilled water was added to the concentrate, diluted to 15°Brix, and then freeze-dried (OPERON, FDT-12012) to obtain 230g of red ginseng concentrate powder.

Preparation Example 3. Preparation of a complex of Eucommia extract and red ginseng extract

Five types of complexes were prepared by mixing the individual extracts obtained in Preparation Example 1 and Preparation Example 2 in different ratios. In each complex, the weight ratio of Duchung:red ginseng was 4:1, 3:1, 1:1, 1:3, and 1:4.

Example 1. Testing the efficacy of improving gastric acid hypersecretion in histamine-induced gastric parietal cells

1-1. Measurement of gastric acid secretion factor cAMP level

After treating the gastric parietal cells with the single extracts and complexes of Preparation Examples 1 to 3 at a concentration of 100 μg/ml, histamine (Sigma, H7125, USA) was treated with the gastric parietal cells at a concentration of 100 μM, and cultured for 24 hours using the cAMP ELISA kit ( Cell biolabs) was used according to the standard reagents and analysis procedures provided by the manufacturer. After selecting the non-acetylated version and removing the media, 1 ml of lysis buffer is dispensed per 35 cm ² . At this time, the lysis buffer is dispensed in proportion to the area. After dispensing the lysis buffer, the plate was reacted at 4°C for 20 minutes, the surface of the plate was scraped with a cell scraper, homogenized using a pipette, centrifuged for 10 minutes, and the supernatant was used as a sample for the experiment. Dispense 50 μl of supernatant and 50 μl of cAMP standard reagent at each concentration onto the goat anti-rabbit antibody coated plate. Afterwards, 25 ㎕ of the diluted peroxidase cAMP tracer conjugate was dispensed, covered with a plate cover, and reacted at room temperature while shaking with an orbital shaker for 2 hours. After 2 hours, dispense 250 ㎕ of 1 After that, 50 μl of the stop solution was dispensed, the OD value was measured using an ELISA reader, and the amount was calculated using the standard curve, which is shown in Table 1 below.

cAMP level (pmol/ml) Normal group (NC) 0.49 Control group (C) 2.39 Euchung 2.01 Du Hong (4:1) 1.95 Duhong (3:1) 1.77 Duhong (1:1) 1.70 Duhong (1:3) 1.40 Duhong (1:4) 1.93 red ginseng 2.05

From the results in Table 1, the cAMP level of the control group that did not process the sample was set as 100%, and the results of confirming the cAMP level (%) of the experimental group are shown in Figure 1.

From the above results, it can be seen that the group treated with 100 μg/ml of a mixture of Eucommia extract and red ginseng extract in a 1:3 ratio significantly improved cAMP levels.

1-2. Measurement of gastric acid secretion factor H+/K+ ATPase activity

After treating the gastric parietal cells with the single extracts and complexes of Preparation Examples 1 to 3 at a concentration of 100 μg/ml, histamine (Sigma, H7125, USA) was treated with the gastric parietal cells at a concentration of 100 μM, and after incubation for 24 hours, H+/K+ ATPase The analysis was performed using an analysis kit (Elabscience) according to the standard reagents and analysis procedures provided by the manufacturer.

Prepare reagents 1 to 11 included in the kit so that they can be used in the experiment after pretreatment according to the protocol, and add each reagent to the sample tube and sample control tube to exclude the experimental value by identifying the unique degree of color development of the sample. . Dispense 130 ㎕ of reagent No. 1 into the sample control tube and the sample tube, 80 ㎕ of reagent No. 2 into the sample tube, 120 ㎕ of reagent No. 3 into the sample control tube, and 120 ㎕ of reagent No. 4 into the sample control tube and sample tube. Dispense 40 ㎕ each of reagent No. 5 into the sample control tube and sample tube, 40 ㎕ each of reagent No. 6 into the sample tube, and dispense 100 ㎕ of the sample to be tested into each sample tube, mix, and then mix. React in a water bath at ℃ for 10 minutes. After that, 50 ㎕ of reagent No. 7 was dispensed into the sample control tube and the sample tube, and 100 ㎕ of the sample to be tested was dispensed into the sample control tube, centrifuged at 3500 rpm for 10 minutes, and the supernatant was used for phosphorus analysis. use. Dispense 400 μl of the 0.5 μmol/ml standard phosphorus application solution into the standard tube, dispense 400 μl of the sample control tube supernatant reacted into a new sample control tube, and dispense 400 μl of the sample tube supernatant reacted into a new sample tube. Dispense 2000 ㎕ each of the phosphorus analysis reagent into a new sample control tube and a sample tube, react in a water bath at 45°C for 5 minutes, and use an ELISA reader to calculate the activity using an O.D value of 660 nm measured as shown in the table below. Shown in 2.

H+/K+ ATPase activity
(U/mg prot) Normal group (NC) 1.70 Control group (C) 8.11 Euchung 6.43 Du Hong (4:1) 6.30 Duhong (3:1) 7.30 Duhong (1:1) 6.30 Duhong (1:3) 4.00 Duhong (1:4) 4.70 red ginseng 5.50

From the results in Table 2, the H+/K+ ATPase activity of the control group that did not treat the sample was set as 100%, and the results of confirming the H+/K+ ATPase activity (%) of the experimental group are shown in Figure 2.

From the above results, it can be seen that the H+/K+ ATPase activity was significantly improved in the group treated with 100 ㎍/ml of a mixture of Eucommia extract and red ginseng extract in a 1:3 ratio.

Example 2. Testing the efficacy of improving gastric acid secretion in an alcoholic gastric injury animal model

2-1. Composition of the experimental group

To confirm the effect of the single extracts and complexes of Preparation Examples 1 to 3 on alleviating gastric acid secretion in an alcoholic gastric injury animal model (7 weeks old, SD rat, male), Nam et al., J. Korean Soc. Food Sci. Nutr. , 43 (10), 150-1509 (2014) The experiment was performed by applying the method disclosed in the literature. The normal and experimental groups were supplied with 7-week-old male, SD rats from Saeron Bio Co., Ltd. (Gyeonggi-do, Korea), acclimatized for 7 days, and allowed to freely consume water and food. Temperature (23 ± 2°C) and humidity were maintained. (55±10%) and light/dark cycle (12 hours) were adjusted automatically. After stabilization, body weight was measured, groups were separated, and experiments were conducted (Table 3).

number label Number of horses Sample dosage stomach damaging substances One Normal group (NC) 6 - - 2 Control group (C) 6 - 40% EtOH / 100 mM HCl, 1 ml each 3 Euchung 6 Eucommia 100 mg/kg 4 red ginseng 6 Red ginseng 100 mg/kg 5 Duhong (3:1) 6 Eucommia + Red Ginseng (3:1) 100 mg/kg 6 Duhong (1:1) 6 Eucommia + Red Ginseng (1:1) 100 mg/kg 7 Duhong (1:3) 6 Eucommia + Red Ginseng (1:3) 100 ㎎/㎏

After group separation, once a day for two weeks, the single extracts and complexes of Preparation Examples 1 to 3 and 40% ethanol were orally administered to each animal in an amount of kg/bw as shown in Table 3 using an oral sonde. When oral administration for a total of 2 weeks was completed, the subjects were fasted for 24 hours and administered 100mM HCl. An autopsy was performed 1 hour later, blood was collected from the hepatic vein, and stomach tissue was removed.

2-2. Measurement of gastric juice secretion

Before taking pictures of the extracted stomach, a small incision was made in the pylorus, gastric fluid was collected in a 50 ml conical tube, centrifuged at 3,000 rpm for 20 minutes, the supernatant was collected, and the amount of gastric fluid secreted (ml) was measured. The results are shown in Table 4. showed.

Gastric juice secretion volume (ml) Normal group (NC) 0.31 Control group (C) 4.20 Euchung 3.33 Duhong (3:1) 3.78 Duhong (1:1) 3.80 Duhong (1:3) 1.62 red ginseng 2.80

In addition, from the results in Table 4, the gastric juice secretion amount of the control group that did not process the sample was set as 100%, and the results of confirming the gastric juice secretion amount (%) of the experimental group are shown in Figure 3.

From the above results, it can be seen that the group administered 100 ㎍/kg of a mixture of eucommia extract and red ginseng extract in a 1:3 ratio significantly improved the amount of gastric juice secretion.

2-3. Gastric wall damage index measurement

The extracted stomach was incised along the greater part of the stomach, the surface of the stomach wall was washed with saline, spread well on a 6-well plate using a cotton swab or tweezers, fixed with formalin, and then photographed. For the taken photos, the area of stomach damage and the total area of the stomach were measured using an image program (Image J, USA), and then the gastric wall damage index (Ulcer Index) (%) was calculated according to the following equation, and the results are shown in Table 5. .

Gastric wall damage index (%) = damaged area/total area.

Stomach wall damage index (%) Normal group (NC) 1.64 Control group (C) 7.23 Euchung 6.53 Duhong (3:1) 6.76 Duhong (1:1) 6.01 Duhong (1:3) 3.08 red ginseng 6.50

In addition, from the results in Table 5, the gastric wall damage index of the control group that did not process the sample was set as 100%, and the results of confirming the gastric wall damage index (%) of the experimental group are shown in Figure 4.

From the above results, it can be seen that the group administered 100 ㎍/kg of a mixture of Eucommia extract and red ginseng extract in a 1:3 ratio significantly improved gastric wall damage.

2-4. Measurement of histamine levels in the blood

Measurement of blood histamine levels was performed using the Histamine Elisa Kit (Abcam) according to the standard reagents and analysis procedures provided by the manufacturer. After preparing 500 ㎕ of serum, it was dried using a centrifugal concentrator, and then treated with 500 ㎕ analysis buffer and used as a sample for the experiment. After dispensing 100 ㎕ of sample into the microplate, 50 ㎕ of 1x histamine tracer was dispensed each. Afterwards, 50 ㎕ of 1x histamine antibody was dispensed and reacted by mixing for 1 hour using an orbital shaker. After washing three times using washing buffer, 200 ㎕ of SA-HRP was dispensed and reacted by mixing for 30 minutes using an orbital shaker. After washing three times using washing buffer, 200 ㎕ of TMB substrate solution was dispensed and reacted by mixing for 30 minutes using an orbital shaker. After 30 minutes, 50 ㎕ of the stop solution was dispensed, the O.D. value was measured and calculated using an ELISA reader at a wavelength of 450 nm, and the results are shown in Table 6.

Blood histamine content (㎍/㎖) Normal group (NC) 1.46 Control group (C) 4.05 Euchung 3.19 Duhong (3:1) 4.37 Duhong (1:1) 3.21 Duhong (1:3) 1.92 red ginseng 3.30

In addition, from the results in Table 6, the blood histamine level of the control group that did not process the sample was set as 100%, and the results of confirming the blood histamine level (%) of the experimental group are shown in Figure 5.

From the above results, it can be seen that the group administered 100 ㎍/kg of a mixture of Eucommia extract and red ginseng extract in a 1:3 ratio significantly improved the histamine content in the blood.

Preparation Example 4. Preparation of pharmaceutical composition

4-1. manufacture of powders

2 g of a mixture of the Eucommia extract and the red ginseng extract of the present invention

1 g lactose

The above ingredients were mixed and filled into an airtight bubble to prepare a powder.

4-2. manufacture of tablets

100 mg of mixture of Eucommia extract and red ginseng extract of the present invention

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above ingredients, tablets were manufactured by tableting according to a conventional tablet manufacturing method.

4-3. Manufacturing of capsules

100 mg of mixture of Eucommia extract and red ginseng extract of the present invention

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above ingredients, a capsule was prepared by filling a gelatin capsule according to a typical capsule manufacturing method.

4-4. manufacturing of pills

1 g of mixture of Eucommia extract and red ginseng extract of the present invention

1.5 g lactose

1 g glycerin

0.5 g xylitol

After mixing the above ingredients, it was prepared in an amount of 4g per pill according to a conventional method.

4-5. Preparation of granules

150 mg of mixture of Eucommia extract and red ginseng extract of the present invention

Soybean extract 50 mg

Dextrose 200 mg

Starch 600 mg

After mixing the above ingredients, 100 mg of 30% ethanol was added and dried at 60°C to form granules, which were then filled into bags.

Manufacturing Example 5. Manufacturing of health functional food

5-1. Manufacturing of flour foods

0.5 to 5.0 parts by weight of the mixture of the Eucommia extract and the red ginseng extract of the present invention was added to flour, and bread, cakes, cookies, crackers, and noodles were manufactured using this mixture.

5-2. Preparation of soups and gravies

0.1 to 5.0 parts by weight of a mixture of the Eucommia extract and the red ginseng extract of the present invention was added to soup and gravy to prepare soup and gravy of processed meat products and noodles.

5-3. Manufacturing of ground beef

Ground beef was prepared by adding 10 parts by weight of a mixture of the Eucommia extract and the red ginseng extract of the present invention to ground beef.

5-4. Manufacturing of dairy products

5 to 10 parts by weight of the mixture of the Eucommia extract and the red ginseng extract of the present invention was added to milk, and various dairy products such as butter and ice cream were manufactured using the milk.

5-5. Manufacturing of Seonsik

Brown rice, barley, glutinous rice, and coix seed were gelatinized and dried using a known method, roasted, and then made into powder with a particle size of 60 mesh using a grinder.

Black beans, black sesame seeds, and perilla seeds were steamed and dried using a known method, roasted, and then made into powder with a particle size of 60 mesh using a grinder.

The mixture of the Eucommia extract and the red ginseng extract of the present invention was concentrated under reduced pressure in a vacuum concentrator, dried with a spray and hot air dryer, and the dried product was pulverized with a grinder to a particle size of 60 mesh to obtain a dried powder.

The mixture of the grains, seeds, and Eucommia extract of the present invention and the red ginseng extract prepared above was mixed in the following ratio.

Grains (30 parts by weight of brown rice, 15 parts by weight of coix, 20 parts by weight of barley), seeds (7 parts by weight of perilla seeds, 8 parts by weight of black beans, 7 parts by weight of black sesame seeds), a mixture of the Eucommia extract and the red ginseng extract of the present invention (3) parts by weight), Reishi (0.5 parts by weight), Rehmannia glutinosa (0.5 parts by weight)

5-6. Manufacturing of health functional beverages

Homogenously mix 5 g of a mixture of the eucommia extract and red ginseng extract of the present invention with auxiliary ingredients such as high fructose corn syrup (0.5%), oligosaccharide (2%), sugar (2%), table salt (0.5%), and water (75%). After instantaneous sterilization, it was manufactured by packaging it in small containers such as glass bottles and plastic bottles.

5-7. Preparation of Vegetable Juice

Vegetable juice was prepared by adding 5 g of the mixture of the Eucommia extract and the red ginseng extract of the present invention to 1,000 ml of tomato or carrot juice.

5-8. manufacturing of fruit juice

Fruit juice was prepared by adding 1 g of a mixture of the Eucommia extract and the red ginseng extract of the present invention to 1,000 ml of apple or grape juice.

Claims (11)

A pharmaceutical composition for preventing, improving, or treating gastrointestinal disorders comprising a eucommia extract and a red ginseng extract in a weight ratio of 1:2 to 1:3.5,
The composition, wherein the gastrointestinal disorder includes at least one selected from the group consisting of heartburn, gastritis, gastric ulcer, duodenal ulcer, and reflux esophagitis. delete In claim 1,
A composition comprising the Duchung extract and the red ginseng extract in a weight ratio of 1:2.5 to 1:3.5. In claim 1,
A composition comprising the Duchung extract and the red ginseng extract in a weight ratio of 1:3. In claim 1,
A composition in which the extraction solvent for preparing the Eucommia extract is water or C1-C4 alcohol. In claim 1,
When preparing the red ginseng extract, the extraction solvent is water. In claim 1,
A composition in which the prevention, improvement or treatment of the gastrointestinal disorder is achieved by suppressing excessive secretion of gastric acid. delete A health functional food composition for preventing or improving gastrointestinal disorders, comprising a eucommia extract and a red ginseng extract in a weight ratio of 1:2 to 1:3.5. delete In claim 9,
A composition wherein the gastrointestinal disorder includes at least one selected from the group consisting of heartburn, gastritis, gastric ulcer, duodenal ulcer, and reflux esophagitis.