WO2019117486A1 - Pharmaceutical composition for preventing or treating gastrointestinal disorders, containing, as active ingredient, mixture of extract of rubi fructus of rubus crataegifolius and extract of ulmi cortex of ulmus macrocarpa - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating gastrointestinal disorders, containing, as an active ingredient, a mixture of an extract of Rubi Fructus of Rubus crataegifolius and an extract of Ulmi cortex of Ulmus macrocarpa. The mixture exhibits antibacterial effects against Helicobacter pylori, and can be effectively usable in the prevention or treatment of gastrointestinal disorders since an extract of Gardenia jasminoides or a lactobacillus strain is additionally mixed in the mixture so as to promote the recovery of damaged tissue in an animal model having a Helicobacter pylori infection and alcohol, stress or non-steroid-induced gastric damage.

Description

A pharmaceutical composition for prevention or treatment of gastrointestinal diseases, which comprises as an active ingredient, a mixture of an unripe raspberry, an extract, and a milky oil extract of royal elm

The present invention relates to a process for the production of Rubus The present invention relates to a pharmaceutical composition for the prevention or treatment of gastrointestinal diseases, which comprises as an active ingredient, a mixture of Crataegifolius Rubi Fructus extract and Ulmus macrocarpa frankincense extract.

Gastrointestinal diseases include stomach injuries caused by gastric mucosal damage caused by Helicobacter, atrophic gastritis, gastric ulcer, and gastric cancer. There are also gastrointestinal (gastritis, stomach, atrophic gastritis) caused by chemicals such as ethanol, methanol, smoking, gastric acid, NASIDs (Non-Steroidal Anti-Inflammatory Drugs)

Helicobacter is firstly found in the gastric mucosa of the human body and adheres to the gastric epithelial layer and interferes with normal cell apoptosis of surrounding cells. This urease secretes urease which has strong enzyme activity. This urea decomposes urea to produce a large amount of ammonia and carbon dioxide, neutralizing the gastric juice around the helicobacter to lower mucous membrane function and cause 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 not useful because it lives on the gastric mucosa, and once it becomes infected, it is difficult to treat and even if it is treated, it is highly likely to recur.

Up to now, 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 Has been widely used. 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.

Gastritis is inflammation in the stomach mucosa of the stomach, which is thinner, more than 10% of the general population. It is usually caused by chronic Helicobacter infection, by chemical agents such as alcohol, tobacco, and NASIDs. Depending on the degree of gastritis, it is classified as severe gastritis (gastritis) from severe gastritis (gastritis suspicion), severe gastritis with severe degree. Chronic gastritis is classified as surface gastritis and atrophic gastritis. The surface gastritis is an early stage and only changes in the mucous membrane are present in the endoscopic findings. Atrophic gastritis progresses more here, and the mucosa becomes thinner and thinner. It says. Gastritis may also progress to stomach cancer. The progression of gastric cancer in gastritis can be seen as chronic gastritis> atrophic gastritis> intestinal epithelium burn> stomach cancer.

Gastric ulcer is caused by gastric acid or pepsin, which causes erosion to the mucosal layer and damage and destruction of the gastric mucosa. It can cause complications such as hemorrhage. It feels burning in the upper abdomen or lower part of the sternum, It should be taken every six months.

Duodenitis is inflammation of the duodenal mucosa. The duodenal mucosa is damaged by stomach acid or pepsin, and it is caused by the excessive use of stomach acid, the use of helicobacter, smoking, analgesic anti-inflammatory drug. Coffee, alcohol and other irritating foods avoid, vomiting, nervousness, abdominal bloating, anorexia, indigestion, heartburn, upper abdominal pain, fever and other symptoms appear.

Gastro-esophageal reflux disease refers to a disease in which gastric acid or stomach contents reflux into the esophagus, causing uncomfortable symptoms such as burning of the inside of the chest, thighs, or complications. This condition is called reflux esophagitis or erosive esophagitis because of the morphological changes such as ulcers or erosions in the esophagus. Gastroesophageal reflux disease (GERD) is a category of gastroesophageal reflux disease, but endoscopy does not reveal mucosal damage or Barrett's esophagus (gastric acid reflux and esophageal perforation) It is called reflux disease.

The cause of gastroesophageal reflux disease is that the stomach contents can be refluxed into the esophagus even in normal people, but if reflux is frequent and prolonged, it can cause reflux symptoms and esophagitis. The most important pathway of gastroesophageal reflux disease is believed to be caused by temporary relaxation of the lower esophageal sphincter (LES), and anatomical deficits such as esophageal hiatal hernia, low pressure of the lower esophageal sphincter This can be the cause.

If there are characteristic symptoms of heartburn or acid reflux, gastric acid reflux disease may be suspected. These symptoms can be diagnosed by endoscopy and esophageal damage caused by gastric acid reflux can be identified.

Gastroesophageal reflux disease is a chronic disease and requires continuous treatment. In gastroesophageal reflux disease, the goal of treatment is to effectively eliminate uncomfortable symptoms caused by reflux and to prevent complications. The most effective treatment for gastroesophageal reflux disease is to reduce gastric acid secretion with histamine H2 receptor antagonists or proton pump inhibitors. The dosage of the drug is determined by the severity of the disease and its symptoms, and the goal of the drug administration is to raise the acidity of the stomach above pH 4 during the daytime during which frequent reflux occurs.

Rubus crataegifolius ) is a plant belonging to the genus Rubus (Rosaceae), which has a large number of thorns, a reddish brown stem, and a leaf that is out of alignment. Wild raspberries are delicious, temperate and poisonous. The outposts of raspberries contain flavonoids and the roots contain triterpene saponins as the main component. In addition, it contains organic acids, malic acid, and vitamin C. In general, plants of the genus Lubus have been used for medicinal purposes (fruits), roots and leaves, and fruits of the genus Lubus have been used in the private sector for the treatment of tonic, soft tissue, fungal and diabetes. Leaves are effective for asthma, and their roots are known to be effective for hemostasis, hematopoiesis, infertility, and menstrual irregularities.

The king elm ( Ulmus macrocarpa Hance) is a deciduous broad-leaved arboreous tree with origins in Korea, Russia, and Mongolia, and is known to grow near valleys and valleys in the middle northern part of Korea. The skin of the elm elk is called 楡 皮 or milky white bark, and the root bark is called 楡 根 皮.

According to Dongyubogam, the elm tree is good for swelling or swelling of a part of the body due to inflammation or tumor, and it is also a very good medicine for nausea. Especially, gastritis, gastric ulcer, duodenal ulcer, small intestine ulcer, colonic ulcer, rectal ulcer, and ulcer ulcer are excellent in all diseases of gastric ulcer.

Gardenia jasminodes are the number of evergreen shrubs in Korea, China, and Japan, and they are about 2m high. It is a small shrub that grows in Jeonnam and southern part of Jeju island and grows about 2m to 3m. It is used as ornamental water, flowers are used as spices, fruits are used as medicine for fever and analgesics. According to Donguibogam, antiphlogistic, microbial inhibition, stomach protection, diuretic and cerebral hemorrhage are said to have side effects if taken for a long time.

While trying to find an effective substance for gastrointestinal diseases, the present inventors have found that a mixture of Raspberry Mizukami, an extract and a dandruff extract of King Ranmatum exhibits an antibacterial effect against Helicobacter pylori . To this mixture, a mixture of a gardenia extract or a lactobacillus It was confirmed that the above-mentioned restorative effect was excellent in an animal model of gastric injuries induced by Helicobacter pylori infection, alcoholic, stressful or NASIDs, and that the above mixture could be useful for the prevention or treatment of gastrointestinal diseases Thereby completing the present invention.

An object of the present invention is raspberries (Rubus crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus macrocarpa ) of the present invention to prevent or treat gastrointestinal diseases.

Another object of the present invention is to provide a method for treating rubella Crataegifolius Rubi Fructus Extract and Ulmus Ulmus macrocarpa ) of the present invention to prevent or treat gastric mucosal damage by using a mixture of the mucus extract of the present invention.

Another object of the present invention is to provide a method for treating rubella Crataegifolius Rubi Fructus Extract and Ulmus Ulmus macrocarpa ) of the present invention to prevent or ameliorate gastrointestinal diseases.

Another object of the present invention is to provide a method for treating rubella Crataegifolius Rubi Fructus Extract and Ulmus Ulmus macrocarpa ) of the present invention to prevent or ameliorate gastric mucosal damage.

In order to achieve the above object, the present invention raspberries (Rubus Crataegifolius Rubi Fructus Extract and Ulmus Ulmus The present invention also provides a pharmaceutical composition for preventing or treating a gastrointestinal disorder, which comprises a mixture of Echinochloa crus-galli extract and macrocarpa .

The invention also raspberries (Rubus crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus The present invention also provides a pharmaceutical composition for preventing or treating gastric mucosal injury comprising a mixture of an extract of Echinochloa crus- galli and a macrocarpa extract as an active ingredient.

The present invention also relates to a method for producing a plant extract comprising a mixed extract of two or more plants selected from the group consisting of a rubid plant including wild strawberry, an elm including King elm, and a gruel including a gardenia, A pharmaceutical composition for the prevention or treatment of gastrointestinal diseases, wherein the raspberries are Rubus crataegifolius , Rubus coreanus , Rubus occidentalis , or Rubus ideaus ), and the elm elm is Ulmus macrocarpa hans macrocarpa Hans ) or ulmus davidiana japonica ( Ulmus davidiana var.japonica), and the gardenia is Gardenia jasminoides Ellis or Gardenia jasminoides < RTI ID = 0.0 > there is. wherein the lactic acid bacteria are selected from the group consisting of Lactobacillus acidophilus , L. gasseri , L. fermentum , L. plantarum , Lactobacillus sp. L. reuteri , L. rhamnosus , B. bifidum , B. breve or Bifidobacterium longbum ( B ), Bifidobacterium longbum The present invention also provides a pharmaceutical composition for the prevention or treatment of gastrointestinal diseases.

The invention also raspberries (Rubus The present invention provides a health functional food for preventing or ameliorating a gastrointestinal disorder comprising a mixture of Crataegifolius Rubi Fructus extract and Ulmus macrocarpa whey protein extract as an active ingredient.

The invention also raspberries (Rubus The present invention provides a health functional food for preventing or ameliorating gastric mucosal damage comprising a mixture of Crataegifolius Rubi Fructus extract and Ulmus macrocarpa whey protein extract as an active ingredient.

The invention also raspberries (Rubus crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus a method for preventing, ameliorating or treating a gastrointestinal disorder, comprising administering to a subject a mixture of a bacteriostatic extract of Bacillus macrocarpa .

The invention also raspberries (Rubus for use in the preparation of a medicament for the prevention, improvement or treatment of gastrointestinal disorders crataegifolius) and immature (Rubi Fructus ) extract and a mixture of Ehrlichia bark extract of Ulmus macrocarpa .

The invention also raspberries (Rubus crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus a method for preventing, ameliorating or treating gastric mucosal injury comprising administering to a subject a mixture of a mucilage extract of macrocarpa .

Furthermore, the present invention raspberries (Rubus for use in the preparation of a medicament for the prevention, improvement or treatment of gastric mucosal damage crataegifolius) and immature (Rubi Fructus ) extract and a mixture of Ehrlichia bark extract of Ulmus macrocarpa .

The mixture of the raspberry microsomes and the extract of the present invention and the extract of Eurasia japonica extract of the Royal Alnus exhibits an antibacterial effect against Helicobacter pylori and further comprises a mixture of a gardenia extract or a lactobacillus strain to the Helicobacter pylori infection, By increasing the recovery of damaged tissue in stressed or non-steroid gastric injured animal models, it can be usefully used for the prevention, treatment or amelioration of gastrointestinal disorders.

1 is Helicobacter pylori (H. pylori) 5 jong milky of raspberry and crude extract, Ulmus macrocarpa for the (26695, 95-113, 92-82-1, 95-45, 92-331 strain) the extract, gardenia Extract or a mixture thereof.

Figure 2 illustrates the Lactobacillus bacteria (Lactobacillus) antimicrobial activity of Helicobacter pylori (H. pylori) 3 jong (PDEF444-12-1, 26695 and the 92-20 strain) according to the treatment concentration.

3 is Helicobacter pylori (H. pylori) and Immature milky of raspberry extract, Ulmus macrocarpa for five species (26695, 95-113, 92-82-1, 95-45, and 92-331 strain) the extract, or their (Probiotics) was added to the mixture.

FIG. 4 is a time-series representation of the production of an animal model infected with Helicobacter pylori ( H. pylori ) and the processing of the extract.

Figure 5 shows the inflammation index in the case of extract and mixture treatment of infected animal models with Helicobacter pylori ( H. pylori ).

Figure 6 shows the appearance of H & E stained tissues upon treatment of extracts and mixtures in infected animal models with H. pylori .

FIG. 7a shows the results of restoration of raspberry immature and extract (RF), milky white almond extract (UL) and gardenia extract (GJ), respectively, on an animal model of gastrointestinal injury.

FIG. 7b shows a mixture of raspberry art and extracts and a mixture of the extracts of Ehrlichia cylindrica and the elicitor (RF + UL); Mixture of raspberry art, extract and gardenia extract (RF + GJ); And a mixture of royal bark extract and gardenia extract of royal elm (UL + GJ); The result of recovery is shown.

FIG. 7c shows a mixture of raspberry art and extracts, a mixture of Echinochloa crus-galli extract and gardenia extract (RF + UL + GJ); (RF + UL + GJ) and probiotics (RF + UL + GJ + Pro) treated with a mixture of wild strawberry extract,

Hereinafter, the present invention will be described in detail.

The present invention relates to a process for the production of Rubus crataegifolius) and immature (Rubi The present invention also provides a pharmaceutical composition for preventing or treating a gastrointestinal disorder, which comprises a mixture of an extract of Fructus and an extract of Ulmus macrocarpa .

It is preferably obtained from April to September, more preferably from May to August, and more preferably from May to July, and more preferably, from May to July. Most preferred, but not limited thereto.

The raspberry immature and extract can be prepared by a manufacturing method comprising the following steps.

1) Extracting the undiluted raspberry with an extraction solvent;

2) filtering the extract of step 1); And

3) Concentrating the filtered extract of step 2) under reduced pressure and drying.

In this method, the extraction solvent of step 1) may be water, alcohol or a mixture thereof. The alcohol may be a C ₁ to C ₂ lower alcohol, and specifically, the alcohol may be methanol or ethanol.

The extraction method of step 1) may be shaking extraction, Soxhlet extraction or reflux extraction. At this time, the extraction temperature is preferably 40 to 80 ° C, more preferably 50 to 70 ° C, but is not limited thereto. In addition, the extraction solvent is preferably added in an amount of 2 to 20 times the weight of the undiluted starch used in the extraction, more preferably 5 to 15 times, but not limited thereto. Further, the extraction time is preferably 2 to 20 hours, more preferably 5 to 15 hours, but is not limited thereto. In addition, the number of extraction times is preferably 1 to 5 times, more preferably 1 to 3 times, but is not limited thereto. Extraction is not sufficiently carried out within the range of the extraction temperature, the extraction time or the extraction frequency, so that the content of the active ingredient in the raw strawberry and the extract may be insignificant. Or the efficiency of the extraction operation may be lowered because the extraction yield is not increased any more.

The vacuum concentration in the step 3) may be performed using a vacuum decompression concentrator or a vacuum rotary evaporator. The drying may be vacuum drying, vacuum drying, boiling drying, spray drying or freeze-drying.

The milky white bark of the elm elseworth refers to the husk of the elm elk. The elongate white elm extract of the elm elm can be produced by a manufacturing method comprising the following steps.

1) Extracting the extract from the wheat bran of elm elm;

2) filtering the extract of step 1); And

3) Concentrating the filtered extract of step 2) under reduced pressure and drying.

In this method, the extraction solvent of step 1) may be water, alcohol or a mixture thereof. The alcohol may be a C ₁ to C ₂ lower alcohol, and specifically, the alcohol may be methanol or ethanol.

The extraction method of step 1) may be shaking extraction, Soxhlet extraction or reflux extraction. At this time, the extraction temperature is preferably 10 to 40 ° C, more preferably 15 to 35 ° C, but is not limited thereto. In addition, the extraction solvent is preferably added in an amount of 2 to 20 times the weight of the undiluted starch used in the extraction, more preferably 5 to 15 times, but not limited thereto. Further, the extraction time is preferably 2 to 20 hours, more preferably 5 to 15 hours, but is not limited thereto. In addition, the number of extraction times is preferably 1 to 5 times, more preferably 1 to 3 times, but is not limited thereto. Extraction is not sufficiently performed within the range beyond the conditions of the extraction temperature, extraction time, or extraction frequency, so that the content of the active ingredient in the extract of Eucalyptus species of the elm elm may be insignificant. Or the efficiency of the extraction operation may be lowered because the extraction yield is not increased any more.

The vacuum concentration in the step 3) may be performed using a vacuum decompression concentrator or a vacuum rotary evaporator. The drying may be vacuum drying, vacuum drying, boiling drying, spray drying or freeze-drying.

The gastrointestinal disorder may be any one selected from the group consisting of Helicobacter pylori gastritis, non Helicobacter pylori gastritis, gastric ulcer, duodenal ulcer, Kollinger-Ellison syndrome, reflux esophagitis, erosion of the ulcer or gastric mucosa, bleeding, have.

In the composition of the present invention, water or alcohol is added to the dry matter of each of the raspberry unripe and the king elm, and the mixture of the extract of the raspberry, In the above-mentioned weight ratio.

It is preferable that the raspberry immature extract, the extract and the milky lotus extract of royal elm are mixed in a weight ratio of 1: 0.01 ~ 100. According to a specific embodiment of the present invention, it is most preferable to mix at a weight ratio of 1: 3 to 3: 1. The above mixture may also include a mixture of the crude raspberry and the milky white dry matter of the royal elm at the above weight ratio and extracting the same with the composite composition.

In a specific example of the present invention, the present inventors confirmed that each of the raspberry unripe, the extract (RF) and the milky white extract (UL) of the royal elm inhibited the growth of Helicobacter pylori , when treated with than was confirmed that the wild strawberry and crude extract and the mixture of blood milky extract of Ulmus macrocarpa (RF + UL) is inhibiting the growth of Helicobacter pylori (Helicobacter pylori) more effectively (see Fig. 1).

In addition, the present inventors have found that, when an animal model infected with Helicobacter pylori is treated with each of raspberry smooth muscle, extract (RF) and whey elm extract (UL), the growth of Helicobacter pylori is inhibited from the animal model (RF + UL), which is a mixture of Raspberry undiladense and extracts and the extract of Eurasia japonica, was more effective in inhibiting the growth of Helicobacter pylori than that of each extract alone 4).

In addition, the present inventors have found that when an animal model infected with Helicobacter pylori infected with raspberry, raspberry (RF), wheat bran extract (UL) and gardenia extract (GJ) (RF + UL), which is a mixture of Raspberry undiluted extract and extract of Ehrlichia cylindrica and Ehrlichia cylindrica extract of Echinochloa eucalyptus, more effectively reduced inflammation than that of each extract alone (see FIG. 5).

In addition, the present inventors confirmed that the damaged stomach tissue of the animal model was restored when the raspberry microorganism and the extract (RF) and the wheat bran extract (UL) of the royal elm were respectively treated with the Helicobacter pylori infection animal model, (RF + UL) of raspberry microsomes and extracts and Ehrlichia toronifera extracts of the elm trees more effectively restored damaged gastric tissues (see FIG. 6).

In addition, the present inventors confirmed that the injured stomach tissue of the animal model was restored when the animal model of alcoholic stomach injured was treated with each of the raspberry unripe, the extract (RF) and the wheat bran extract (UL) (RF + UL) of the extracts of raspberry and the extract of Ehrlichia japonica and the extract of Echinochloa crus-galli was more effectively restored the damaged stomach tissues (see Table 5, Figs. 7A to 7C).

In addition, the present inventors confirmed that the damaged stomach tissue of the animal model was restored when the raspberry immature, the extract (RF), and the wheat bran extract (UL) (RF + UL), a mixture of raspberry smooth muscle extracts and extracts of Ehrlichia cylindrica and Eurasia japonica extract, was more effective in restoring injured stomach tissues (see Table 6).

In addition, the present inventors confirmed that the damaged gastric tissues of the animal model were restored when the non-steroidal gastric injured animal model was treated with each of raspberry smooth muscle, extract (RF), and milky white almond extract (UL) (RF + UL), a mixture of raspberry microsomes and extracts of Echinochloa crus-galli and Echinochloa crus-galli extracts, showed more effective restoration of damaged stomach tissues than that of each extract alone (see Table 7).

Therefore, inhibiting the raspberry immature and extract, and mixtures milky blood extract of Ulmus macrocarpa the growth of Helicobacter pylori (Helicobacter pylori), reduce inflammation of Helicobacter pylori infection in animal models, H. pylori infections, alcoholic, or bis Tero And effectively restores the stomach tissue in an injured animal model. Therefore, it can be usefully used in pharmaceutical compositions for the prevention or treatment of gastrointestinal diseases.

The pharmaceutical composition for preventing or treating gastrointestinal diseases may further comprise Gardenia jasmoides extract.

The gardenia extract may be produced by a manufacturing method comprising the following steps.

1) extracting a gardenia with an extraction solvent;

2) filtering the extract of step 1); And

3) Concentrating the filtered extract of step 2) under reduced pressure and drying.

In the above method, the gardenia may include all parts such as the leaves, stem, root, and fruit of the gardenia, and may be at least one selected from the group consisting of leaves, stem, roots and fruit. According to a specific embodiment of the present invention, it is most preferable to use the fruit of gardenia as a gardenia.

In this method, the extraction solvent of step 1) may be water, alcohol or a mixture thereof. The alcohol may be a C ₁ to C ₂ lower alcohol, and specifically, the alcohol may be methanol or ethanol.

The extraction method of step 1) may be shaking extraction, Soxhlet extraction or reflux extraction. At this time, the extraction temperature is preferably 40 to 80 ° C, more preferably 50 to 70 ° C, but is not limited thereto. In addition, the extraction solvent is preferably added in an amount of 2 to 20 times the weight of the undiluted starch used in the extraction, more preferably 5 to 15 times, but not limited thereto. Further, the extraction time is preferably 2 to 20 hours, more preferably 4 to 10 hours, but is not limited thereto. In addition, the number of extraction times is preferably 1 to 5 times, more preferably 1 to 3 times, but is not limited thereto. Extraction is not sufficiently carried out within the range of the extraction temperature, the extraction time or the extraction frequency, so that the content of the active ingredient in the raw strawberry and the extract may be insignificant. Or the efficiency of the extraction operation may be lowered because the extraction yield is not increased any more.

The vacuum concentration in the step 3) may be performed using a vacuum decompression concentrator or a vacuum rotary evaporator. The drying may be vacuum drying, vacuum drying, boiling drying, spray drying or freeze-drying.

In the composition of the present invention, water or an alcohol is added to the dry matter of the raspberries immature, white elm, and the gardenia of the royal elm to obtain a single extract, And may be prepared by mixing a sole extract with the above weight ratio.

It is preferable that the raspberry microsomal extract, the extract of Eucalyptus tritaeniorhynchus, the Eucalyptus japonica extract and the gardenia extract of royal elm are mixed at a weight ratio of 1: 0.01-100: 0.01-100. According to a specific embodiment of the present invention, mixing is most preferred in a weight ratio of 1: 1. The above mixture may also include a mixture of the crude raspberry and the milky white dry matter of the royal elm at the above weight ratio and extracting the same with the composite composition.

In a specific embodiment of the present invention, the inventors have shown that mixing a gardenia extract (RF + UL + GJ) with a mixture of raspberry innoculation and a mixture of extracts and a milky white extract of royal elm (RF + UL) (See Fig. 5).

In addition, the present inventors have successfully restored damaged gastric tissues by mixing (RF + UL + GJ) a mixture of gardenia extract and a mixture of extracts of wheat bran and extracts of hyperlipidemia (RF + UL) in a Helicobacter pylori infected animal model (See Fig. 6).

In addition, the present inventors have successfully restored damaged gastric tissues by mixing (RF + UL + GJ) a mixture of the extract of raspberry and the mixture of extracts and the hyperlipidemic extract of royal elm (RF + UL) (See Table 5 and Figures 7a to 7c).

In addition, the present inventors have also found that by mixing the gardenia extract (RF + UL + GJ) with a mixture of the raspberry microsomes and the extract of the extract of the elm and the mixture of the milky white extract of the elm (RF + UL) (See Table 6).

In addition, the present inventors further examined the effect of the mixture of the gardenia extract (RF + UL + GJ) and the mixture of the extract of the raspberry and the mixture of the extract of Eurasia japonica (RF + UL) (See Table 7).

Thus, the mixture of the raspberry inflorescences and the extract, the Ehrsia bark extract of the Royal Elm tree and the Gardenia Extract reduces the inflammation of the Helicobacter pylori infected animal model and inhibits the gastric tissue in Helicobacter pylori infection, alcoholic, And thus can be usefully used in pharmaceutical compositions for the prevention or treatment of gastrointestinal diseases.

The pharmaceutical composition for the prevention or treatment of gastrointestinal diseases may further comprise a strain of Lactobacillus or a culture thereof.

In a particular embodiment of the invention, the inventors confirmed that suppressing the growth of Lactobacillus bacteria (Lactobacillus), Helicobacter pylori strains (Helicobacter pylori) (see Fig. 2).

The present inventors also mixed a lactobacillus strain with a mixture (RF + UL) of extract of raspberry (R), extract (RF), extract of Milkweed (UL), extract of Raspberry and extract of Milkworm and extract of Milkweed , It was confirmed that the effect of inhibiting the growth of Helicobacter pylori was enhanced (see FIG. 3 and Table 3).

In addition, the present inventors have found that Helicobacter pylori ( Helicobacter pylori ) from the top of an animal model when treated with a mixture of extracts of Rubus amyloliquefaciens, extracts of Eurasia japonica and extracts of gardenia (RF + UL + GJ) (RF + UL + GJ + Pro) was mixed with a mixture (RF + UL + GJ) of the raspberry-like immature fruit and the extract, the Eurasia bark extract of royal elm and the gardenia extract (RF + UL + GJ) It was found that more effectively inhibit the growth of Helicobacter pylori (Helicobacter pylori) (see Table 4).

In addition, the present inventors have found that when a mixture of an infantile rubella and an extract, a mixture of Echinochloa crus-galli extract and a gardenia extract (RF + UL + GJ) is reduced in an animal model infected with Helicobacter pylori, (RF + UL + GJ + Pro) mixture of the lactobacillus strain (RF + UL + GJ) and the mixture of the extract of Rubus coreanus L., (See FIG. 5).

In addition, the present inventors have also found that when an animal model of alcoholic damage is treated with a mixture of extract of raspberry, a mixture of Echinosophora koreensis extract and Gardenia extract (RF + UL + GJ) (RF + UL + GJ + Pro) was added to the mixture (RF + UL + GJ) of the raspberry microsomes and extracts, the Ehrsia bark extract of king elm and the gardenia extract (See Table 5 and Figs. 7A to 7C).

In addition, the present inventors have found that, when an animal model of stress-induced gastric injuries is treated with a mixture of extract of raspberry, extract of Ehrlichia cylindrica and extract of gardenia (RF + UL + GJ) (RF + UL + GJ + Pro) was added to the mixture (RF + UL + GJ) of the raspberry microsomes and extracts, (See Table 6).

In addition, the present inventors have found that when an animal model of non-steroidal gastric injured animal is treated with a mixture of extract of raspberry, extract of Eurasia japonica and extract of gardenia (RF + UL + GJ) (RF + UL + GJ + Pro) was mixed with a mixture (RF + UL + GJ) of the above-mentioned Raspberry, (See Table 7).

Thus, a mixture of the raspberry inflorescence and the extract and the Eurasia bark extract of royal elm; Or the Rubus immature and extract, the composition further comprising a milky blood extract, and gardenia culture of Lactobacillus bacteria to the mixture of the extract of Ulmus macrocarpa, the H. pylori inhibited the growth of (Helicobacter pylori) and H. pylori inflammation of the infected animal model And effectively restores stomach tissue in an animal model of Helicobacter pylori infection, alcoholic, or bisteroid infected animals, and thus can be usefully used in pharmaceutical compositions for the prevention or treatment of gastrointestinal diseases.

In addition, the present invention relates to a method of treating Rubus The present invention also provides a composition for preventing or treating gastric mucosal injury comprising a mixture of a crataegifolius extract and a milky white extract of Ulmus macrocarpa as an active ingredient.

The gastric mucosal injury may be due to Helicobacter pylori infection, alcohol or drug.

In a specific example of the present invention, the present inventors have found that when an animal model infected with Helicobacter pylori is treated with each of raspberry immature and extract (RF) and whey elm (UL) extracts, (RF + UL), a mixture of Raspberry undiluted extract and extracts of Echinochloa crus-galli and Echinochloa crus-galli extracts, showed a more effective restoration of damaged gastric tissues (see FIG. 6) than when each extract was treated alone.

In addition, the present inventors confirmed that the injured stomach tissue of the animal model was restored when the animal model of alcoholic stomach injured was treated with each of the raspberry unripe, the extract (RF) and the wheat bran extract (UL) (RF + UL) of raspberry innoculation and the extract and the Eurusia elaphicus extract of the elm elongate more effectively restored the damaged stomach tissue (see Table 5 and Figs. 7a to 7c).

In addition, the present inventors confirmed that the damaged stomach tissue of the animal model was restored when the raspberry immature, the extract (RF), and the wheat bran extract (UL) (RF + UL), a mixture of raspberry smooth muscle extracts and extracts of Ehrlichia cylindrica and Eurasia japonica extract, was more effective in restoring injured stomach tissues (see Table 6).

In addition, the present inventors confirmed that the damaged gastric tissues of the animal model were restored when the non-steroidal gastric injured animal model was treated with each of raspberry smooth muscle, extract (RF), and milky white almond extract (UL) (RF + UL), a mixture of raspberry microsomes and extracts of Echinochloa crus-galli and Echinochloa crus-galli extracts, showed more effective restoration of damaged stomach tissues than that of each extract alone (see Table 7).

Thus, the mixture of the Raspberry infestant, the extract, and the Ehrsia bark extract of the royal elm effectively restores the stomach tissue in Helicobacter pylori infection, alcoholic, or nysterically impaired animal models, Can be usefully used in compositions.

The present invention also relates to a method for producing a plant extract comprising a mixed extract of two or more plants selected from the group consisting of a rubid plant including wild strawberry, an elm including King elm, and a gruel including a gardenia, A pharmaceutical composition for preventing or treating a gastrointestinal disorder,

The raspberries are classified into Rubus crataegifolius , Rubus coreanus , Rubus occidentalis ) or Rubus ( Rubus ideaus); and the king of elm moose wool mark Carpathian Hans (Ulmus macrocarpa Hans) or wool moose Dhabi Diana japonica (Ulmus davidiana japonica), and the gardenia is Gardenia jasminoides Ellis or Gardenia jasminoides var. ovariflia, and the lactic acid bacterium is Lactobacillus acidophilus ( L. Lactobacillus acidophilus , L. gasseri , L. fermentum , L. plantarum , L. reuteri , L. lactobacillus, L. the present invention provides a pharmaceutical composition for the prevention or treatment of gastrointestinal diseases such as rhamnosus , B. bifidum , B. breve or B. longum . do.

The pharmaceutical composition according to the present invention may contain 10 to 95% by weight of the mixed extract and the lactic acid bacterium culture, which are effective ingredients, based on the total weight of the composition. In addition, the pharmaceutical composition of the present invention may further comprise at least one active ingredient which exhibits the same or similar functions in addition to the above-mentioned effective ingredients.

The pharmaceutical compositions of the present invention may comprise carriers, diluents, excipients or mixtures thereof conventionally used in biological preparations. Pharmaceutically acceptable carriers can be used as long as they are suitable for delivering the composition in vivo. Specifically, the carrier is selected from Merck Index, 13th ed., Merck & Sterile water, Ringer's solution, dextrose solution, maltodextrin solution, glycerol, ethanol, or a mixture thereof. If necessary, conventional additives such as an antioxidant, a buffer, a bacteriostatic agent and the like may be added.

When the composition is formulated, a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient may be added.

The compositions of the present invention may be formulated into oral or parenteral formulations. Oral preparations may include solid preparations and liquid preparations. The solid preparation may be a tablet, a pill, a powder, a granule, a capsule, or a troche. The solid preparation may be prepared by adding at least one excipient to the composition. The excipient may be starch, calcium carbonate, sucrose, lactose, gelatin or a mixture thereof. In addition, the solid preparation may comprise a lubricant, examples of which include magnesium stearate, talc, and the like. On the other hand, the liquid preparation may be a suspension, a solution, an emulsion or a syrup. At this time, the liquid preparation may contain an excipient such as a wetting agent, a sweetener, a fragrance, a preservative, and the like.

The parenteral preparation may contain injections, suppositories, respiratory inhalation powders, aerosol formulations for spraying, powders and creams. The injection may include a sterilized aqueous solution, a non-aqueous solvent, a suspending agent, an emulsion, and the like. As the non-aqueous solvent or suspension, vegetable oils such as propylene glycol, polyethylene glycol and olive oil, and injectable esters such as ethyl oleate may be used.

The invention also raspberries (Rubus crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus The present invention provides a health functional food for preventing or ameliorating a gastrointestinal disorder which comprises a mixture of an extract of Echinochloa crus-galli ( Macrocarpa ) as an active ingredient.

The above-mentioned Raspberry unripe, extract and royal elm extract are as described above.

In the health functional food of the present invention, water or alcohol is added to the dry matter of the raspberry microsomes and the milky white elm, respectively, to prepare a sole extract, May be prepared by mixing the extracts alone in the above-mentioned ratio by weight.

It is preferable that the raspberry immature extract, the extract and the milky lotus extract of royal elm are mixed in a weight ratio of 1: 0.01 ~ 100. According to a specific embodiment of the present invention, it is most preferable to mix at a weight ratio of 1: 3 to 3: 1. The above mixture may also include a mixture of the crude raspberry and the milky white dry matter of the royal elm at the above weight ratio and extracting the same with the composite composition.

The health functional food for preventing or ameliorating the gastrointestinal diseases may further comprise Gardenia jasminoides extract. In addition, the health functional food for preventing or ameliorating the gastrointestinal disorder may further comprise a strain of Lactobacillus or a culture thereof.

The above gardenia extract and Lactobacillus strain or a culture solution thereof are as described above.

The gastrointestinal disorder may be any one selected from the group consisting of Helicobacter pylori gastritis, non Helicobacter pylori gastritis, gastric ulcer, duodenal ulcer, Kollinger-Ellison syndrome, reflux esophagitis, erosion of the ulcer or gastric mucosa, bleeding, have.

In a particular embodiment of the invention, the present inventors and inhibit the growth of (Helicobacter pylori) mixture pylori Helicobacter milky blood extract of Rubus immature and extract and Ulmus macrocarpa, reduce inflammation of Helicobacter pylori infection in animal models, Since it has been confirmed that the gastric tissue is effectively restored in an animal model of Helicobacter pylori infection, alcoholic, or bisteriodestructural damage, it can be usefully used for a health functional food for prevention or improvement of gastrointestinal diseases.

In addition, the present inventors have found that the mixture of the above-mentioned Raspberry infestation with the extract, the wheat bran extract of royal elm and the gardenia extract reduces the inflammation of the Helicobacter pylori infection animal model and is effective against Helicobacter pylori infection, alcoholic, Since it has been confirmed that the gastric tissue is effectively restored, it can be effectively used for a health functional food for prevention or improvement of gastrointestinal diseases.

Further, the present inventors have also found that a mixture of the above-mentioned raspberry infestation and extract and a milky white extract of royal elm; Or reduce inflammation of the Rubus immature and extract, Royal composition to milky blood mixture of the extract and gardenia extract of Elm further comprising a Lactobacillus culture medium inhibits the growth of Helicobacter pylori (Helicobacter pylori) and H. pylori infection in animal models And has been found to effectively restore stomach tissue in an animal model of Helicobacter pylori infection, alcoholic, or bisteriform damage, and thus can be usefully used in health functional foods for the prevention or amelioration of gastrointestinal diseases.

The invention also raspberries (Rubus crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus The present invention provides a health functional food for preventing or ameliorating gastric mucosal damage comprising a mixture of an extract of Echinochloa crus-galli extract and macrocarpa as an active ingredient.

The gastric mucosal injury may be due to Helicobacter pylori infection, alcohol or drug.

In a specific embodiment of the present invention, the present inventors have found that the mixture of the Raspberry infestation with the extract and the extract of Eurusia barkiflora extract effectively restores the stomach tissue in an animal model of Helicobacter pylori infection, alcoholic, or nysteriostatic injury , It can be usefully used for a health functional food for preventing or ameliorating gastric mucosal injury.

The raspberry microsomes and extracts of the present invention may be added directly to food or may be used in combination with other food or food ingredients. At this time, the content of the active ingredient to be added may be determined depending on the purpose, and may generally be 0.01 to 90 parts by weight of the total food weight.

The form and kind of the health functional food are not particularly limited. Specifically, the health functional food may be in the form of a tablet, a capsule, a powder, a granule, a liquid and a ring. The health functional food may contain various flavors, sweeteners or natural carbohydrates as an additional ingredient. The sweeteners may be natural or synthetic sweeteners, examples of natural sweeteners include tau martin and stevia extract. On the other hand, examples of synthetic sweeteners include saccharin and aspartame. The natural carbohydrates may be monosaccharides, disaccharides, polysaccharides, oligosaccharides, sugar alcohols, and the like.

The health functional food of the present invention may contain, in addition to the above-described additional ingredients, a nutrient, a vitamin, an electrolyte, a flavoring agent, a colorant, a pectin and a salt thereof, an alginic acid and its salt, an organic acid, a protective colloid thickening agent, , Glycerin, alcohol, and the like. These components may be used independently or in combination. The proportion of the additive may be selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

The invention also raspberries (Rubus crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus a method for preventing, ameliorating or treating a gastrointestinal disorder, comprising administering to a subject a mixture of a bacteriostatic extract of Bacillus macrocarpa .

The extract of Rubus juncea, Extract, and Royal Elm tree of the present invention may have the above-described characteristics. The mixture of the above-mentioned extracts of the wild strawberry and the extract and the extract of royal alm tree may further comprise Gardenia jasmoides extract, and may further comprise a Lactobacillus strain or a culture thereof.

The subject may be a mammal, particularly a human.

The composition of the present invention can be administered orally or parenterally according to the desired method. Parenteral administration may include intraperitoneal, rectal, subcutaneous, intravenous, intramuscular or intrathecal injection.

The composition may be administered in a pharmaceutically effective amount. This may vary depending on the type of disease, severity, activity of the drug, sensitivity of the patient to the drug, administration time, route of administration, duration of treatment, However, for the desired effect, the amount of the active ingredient contained in the pharmaceutical composition according to the present invention may be 0.0001 to 1,000 mg / kg, specifically 0.001 to 500 mg / kg. The administration may be once a day, and may be several times.

The composition of the present invention may be administered alone or in combination with other therapeutic agents. When administered concomitantly, the administration can be sequential or simultaneous.

The invention also raspberries (Rubus for use in the preparation of a medicament for the prevention, improvement or treatment of gastrointestinal disorders crataegifolius) and immature (Rubi Fructus ) extract and a mixture of Ehrlichia bark extract of Ulmus macrocarpa .

The extract of Rubus juncea, Extract, and Royal Elm tree of the present invention may have the above-described characteristics. The mixture of the above-mentioned extracts of the wild strawberry and the extract and the extract of royal alm tree may further comprise Gardenia jasmoides extract, and may further comprise a Lactobacillus strain or a culture thereof.

The invention also raspberries (Rubus crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus a method for preventing, ameliorating or treating gastric mucosal injury comprising administering to a subject a mixture of a mucilage extract of macrocarpa .

The extract of Rubus juncea, Extract, and Royal Elm tree of the present invention may have the above-described characteristics. The mixture of the above-mentioned extracts of the wild strawberry and the extract and the extract of royal alm tree may further comprise Gardenia jasmoides extract, and may further comprise a Lactobacillus strain or a culture thereof.

The subject may be a mammal, particularly a human.

The composition of the present invention can be administered orally or parenterally according to the desired method. Parenteral administration may include intraperitoneal, rectal, subcutaneous, intravenous, intramuscular or intrathecal injection.

The composition may be administered in a pharmaceutically effective amount. This may vary depending on the type of disease, severity, activity of the drug, sensitivity of the patient to the drug, administration time, route of administration, duration of treatment, However, for the desired effect, the amount of the active ingredient contained in the pharmaceutical composition according to the present invention may be 0.0001 to 1,000 mg / kg, specifically 0.001 to 500 mg / kg. The administration may be once a day, and may be several times.

The composition of the present invention may be administered alone or in combination with other therapeutic agents. When administered concomitantly, the administration can be sequential or simultaneous.

Furthermore, the present invention raspberries (Rubus for use in the preparation of a medicament for the prevention, improvement or treatment of gastric mucosal damage crataegifolius) and immature (Rubi Fructus ) extract and the Royal elm ( Ulmus macrocarpa ). < / RTI >

The extract of Rubus juncea, Extract, and Royal Elm tree of the present invention may have the above-described characteristics. The mixture of the above-mentioned extracts of the wild strawberry and the extract and the extract of royal alm tree may further comprise Gardenia jasmoides extract, and may further comprise a Lactobacillus strain or a culture thereof.

Hereinafter, the present invention will be described in detail with reference to examples.

However, the following examples are illustrative of the present invention, but the present invention is not limited thereto.

<Example 1> raspberry and immature (Rubus crataegifolius , Rubi Fructus )

Raspberry inflorescence and fruit were lyophilized and powdered using a grinder. Ethanol was added to 100 g of the powdered sample 10 times, and the mixture was extracted at 60 DEG C for 10 hours. The extract was filtered using a filter paper, the filtrate was concentrated under reduced pressure, and then lyophilized to obtain an extract of the final raspberry (hereinafter referred to as RF).

&Lt; Example 2 > Ulmus macrocarpa ) &Lt; / RTI &gt;

The elm bark (milky white) was lyophilized and pulverized using a pulverizer. Ethanol was added to 100 g of the powdered sample 10 times, and the mixture was extracted at room temperature for 8 hours. The extract was filtered using a filter paper, the filtrate was concentrated under reduced pressure, and then lyophilized to obtain a milky white extract (hereinafter referred to as UL) of the final elm.

&Lt; Example 3 > Gardenia jasminoides ) Preparation of extract

Gardenia fruit was pulverized using a pulverizer. 10 g of distilled water was added to 100 g of the powdered sample, and the mixture was extracted at 60 DEG C for 6 hours. The extract was filtered using a filter paper, and the filtrate was concentrated under reduced pressure, followed by lyophilization to give a final gardenia extract (hereinafter referred to as GJ).

<Example 4> Probiotics culture

Lactobacillus plantarum obtained from KNRRC was inoculated into MRS medium and cultured at 37 DEG C for 24 hours to obtain a culture broth of probiotics.

< Experimental Example  1> extract and Probiotics  Helicobacter according to treatment Filial  Evaluation of antimicrobial activity

The Helicobacter pylori 26695, 95-113, 92-82-1, 95-45 and 92-331 strains, which were distributed on the MRS agar plate at KNRRC, As shown in Table 1, the extract (100 占 퐂 / mL) prepared in Examples 1 to 4, the culture medium of probiotics and a mixture thereof were loaded onto agar plates. After incubation at 37 ° C for 24 hours, the diameter of the inhibition zone where growth of Helicobacter pylori was inhibited was measured. Clarithromycin, an antibiotic, was used as a control.

	Extract and mixture treatment conditions
Experiment 1	RF (10 [mu] g)
Experiment 2	UL (10 [mu] g)
Experiment group 3	GJ (10 [mu] g)
Experiment group 4	RF + UL (1: 1) (5 μg + 5 μg)
Experiment group 5	RF + UL (1: 3) (2.5 占 퐂 + 7.5 占 퐂)
Experiment group 6	RF + UL (3: 1) (7.5 占 퐂 + 2.5 占 퐂)
Experiment group 7	Clarithromycin
Experiment group 8	Pro (probiotics) (10 8 CFU)

Fig. 1 shows the extracts prepared in Examples 1 to 4 for Helicobacter pylori (26695, 95-113, 92-82-1, 95-45 and 92-331 strains) Milky skin extract, and gardenia extract), and a mixture of probiotics and a mixture thereof. Extracts (RF) and extracts of Ulmus bark (UL) from Raspberry (R), showed the antimicrobial activity against five species of Helicobacter pylori, but did not exhibit antibacterial activity. The antimicrobial effect of Helicobacter pylori was increased when 1: 1 mixture of raspberry (R), extract (RF) and wheat elm extract (UL)

< Experimental Example  2> Lactobacillus  Helicobacter according to treatment concentration Filial  Evaluation of antimicrobial activity

The Helicobacter pylori PDEF444-12-1, 26695 and 92-20 strains, which were distributed on the agar plate at KNRRC of Gyeongsang National University Medical School, were plated on the agar plate, and the lactose Bacillus cultures were loaded onto agar plates at 10 ⁷ , 10 ⁶ , 10 ⁵ and 10 ⁴ CFU (colony forming unit). After incubation at 37 ° C for 24 hours, the diameter of the inhibition zone where growth of Helicobacter pylori was inhibited was measured.

Fig. 2 shows antibacterial activities of three Helicobacter pylori (PDEF444-12-1, 26695 and 92-20 strains) according to Lactobacillus treatment concentration. All of the three Helicobacter pylori strains were found to have increased antimicrobial activity with increasing concentrations of Lactobacillus.

< Experimental Example  3> Probiotics  Helicobacter according to the contained extract treatment Filial  Evaluation of antimicrobial activity

Helicobacter pylori 26695, 95-113, 92-82-1, 95-45, and 92-331 strains were purchased from the KNRRC of Gyeongsang National University Hospital on agar plate. As shown in Table 2, the extract (1000 占 퐂 / mL) prepared in Examples 1 to 4, the probiotic culture solution and the mixture thereof were loaded onto agar plates. After incubation at 37 ° C for 24 hours, the diameter of the inhibition zone where growth of Helicobacter pylori was inhibited was measured.

	Extract and mixture treatment conditions
Experiment 1	RF (10 [mu] g)
Experiment 2	UL (10 [mu] g)
Experiment group 3	RF + Pro (10 [mu] g + 10 < 4 > CFU)
Experiment group 4	UL + Pro (10 μg + 10 4 CFU)
Experiment group 5	RF + UL + Pro (5 + + 5 + + 10 4 CFU)

Fig. 3 is a graph showing the effects of probiotics (bacteriophage) on the immature raspberry and the extracts, Eurasia bark extract of royal elm or mixtures thereof against five species of Helicobacter pylori (26695, 95-113, 92-82-1, 95-45 and 92-331 strains) Probiotics) was added. The antimicrobial effect against Helicobacter pylori was significantly increased when mixed with probiotic broth (Pro), compared with single treatment of raspberry unmilled, extract (RF) and wheat elm (UL) appear. Especially, the antimicrobial effect against Helicobacter pylori was the most excellent when mixed with raspberry unripe and extract (RF), wheat elm extract (UL) and probiotic broth (Pro).

< Experimental Example  4> Helicobacter according to extract and mixture treatment Filial  Determination of minimum inhibitory concentration

Helicobacter pylori strains shown in Table 3 were cultured at a concentration of 10 ⁸ CFU, and the extracts, probiotic cultures and mixtures thereof prepared in Examples 1 to 4 as shown in Table 3 were each mixed in Helicobacter pylori culture broth . After culturing the cells at 37 ° C for 24 hours after plating on the agar plate, the concentration (MIC ₇₀ ) of each extract or mixture in which the growth of Helicobacter pylori was inhibited by 70% or more was determined.

	MIC 70 ([mu] g / mL)
Helicobacter pylori strain name	RF	UL	GA	RF + UL (1: 1)	RF + Pro (10 5 CFU)	UL + Pro (10 5 CFU)	RF + UL + Pro (RF: UL = 1: 1, Pro: 10 5 CFU)	Clarithromycin
51	150	300	> 500	75	100	250	75	<1
52	150	350	> 500	75	100	250	50	<1
26695	200	350	> 500	100	100	250	75	<1
SS1	150	300	> 500	75	100	200	50	<1
92-20	150	300	> 500	75	75	200	50	<1
92-30	150	300	> 500	75	75	250	50	<1
92-33-1	200	350	> 500	100	100	250	75	<1
92-82-1	200	350	> 500	100	100	300	75	<1
95-113	200	300	> 500	150	100	250	75	<1
95-45	150	300	> 500	100	100	200	50	<1
PDEF444-12-1	150	300	> 500	100	100	150	75	<1

MIC ₇₀ of 150 mg / mL of MIC ₇₀ was 150 ~ 200 mg / mL for 11 species of Helicobacter pylori, and MIC ₇₀ of 300 mg / mL of UL extract of wild elm GJ) showed almost no antibacterial effect.

The antimicrobial effect of Helicobacter pylori was increased when the mixture of Rice Strawberry (R), Extract (RF) and Eelgrass (Ul) extracts (UL) The antibacterial activity against Helicobacter pylori was also increased when the probiotic broth (Pro) was added to the extracts of raspberry (R), extract (RF) and wheat elm (UL). (RF + UL + Pro) showed the highest antimicrobial effect in all strains of Helicobacter pylori except 51 strains of Helicobacter pylori. Therefore, the extracts of Rubus corea mushroom and Astragalus membranaceus have antimicrobial activity against Helicobacter pylori. When the extracts are treated by mixing them with each other or by mixing the probiotics culture solution, the antibacterial effect is increased appear.

< Experimental Example  5> Helicobacter Filly ( H. pylori ) Antimicrobial Effect of Extracts and Mixtures in Infected Animal Models

After Balb / c mice were stabilized, Helicobacter pylori was administered at 2 x 10 ⁸ CFU three times at intervals of two days as shown in Fig. Four weeks after the administration, the Helicobacter pylori infection was examined by culturing Helicobacter pylori and histological examination on a mouse part of the experimental group. After 4 weeks, the extract and its mixture were orally administered as shown in Table 4 . After the treatment of the extracts and the mixture for 4 weeks was completed, the stomach of Helicobacter pylori was counted by removing the mouse stomach.

The test group of Helicobacter pylori infection (8 weeks) in control group 2 was conducted for 8 weeks instead of 4 weeks for inducing Helicobacter infection in FIG. 4, and amoxicillin, clarithromycin and omeprazole of control group 3 were treated instead of the extract.

Experimental group		Treatment condition	The number of bacteria detected above Log 10 CFU
Control 1	Helicobacter pylori infection (4 weeks)	2.0 × 10 8 CFU	2.1 × 10 5
Control group 2	Helicobacter pylori infection (8 weeks)	2.0 × 10 8 CFU	7.7 × 10 7
Control group 3	Amoxicillin (AMX) + clarithromycin (CLM) + omeprazole (OMP)	138 + 30 + 30 mg / kg	8.2 × 10 2
Experiment 1	RF	150 mg / kg	7.5 x 10 3
Experiment 2	UL	150 mg / kg	4.3 × 10 4
Experiment group 3	GJ	150 mg / kg	3.2 × 10 5
Experiment group 4	RF + UL	75 + 75 mg / kg	4.8 x 10 3
Experiment group 5	RF + GJ	75 + 75 mg / kg	7.6 × 10 3
Experiment group 6	RF + UL + GJ	50 + 50 + 50 mg / kg	5.7 x 10 3
Experiment group 7	RF + UL + GJ + Pro	50 + 50 + 50 mg / kg + 10 5 CFU	2.3 x 10 3

Antibacterial effects of extracts and mixtures in Helicobacter pylori infected animal model were the highest in antimicrobial effect of raspberry microsomes and extracts (RF), and antimicrobial effect of ginger extract (GJ) .

The antimicrobial effect of Helicobacter pylori was the highest when mixed with raspberry (R) and extract (R) and milky (R) UL (UL +). The extracts were found to increase the antimicrobial effect when they were mixed with each other. Experimental group 7 (RF + UL + GJ + Pro) supplemented with probiotic broth (Pro) showed increased antimicrobial activity against Helicobacter pylori by adding probiotics.

Therefore, antimicrobial effect of raspberry microsomal, extract (RF) and milky white elderberry (UL) extracts on Helicobacter pylori infected animal models was confirmed. The extracts were mixed or treated with probiotics When treated, the antibacterial effect was increased.

< Experimental Example  6> Helicobacter Filly  Anti-inflammatory effects of extracts and mixtures in infected animal models

Balb / c mice were infected with Helicobacter pylori in the same manner as in Experimental Example 5, and the stomachs of the same control group and the experimental group in Experimental Example 5 were extracted to measure the inflammatory score of stomach tissue. Inflammation index was determined by measuring the WBC, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), tumor necrosis factor receptor 1 (TNFR1) and tumor necrosis factor receptor 2 (TNFR2) The regulations.

Figure 5 shows the inflammatory index of the stomach when treated with extracts and mixtures in an animal model of Helicobacter pylori infection. (RF + UL + GJ) and the experimental group 7 (RF + UL + GJ), which were treated with the mixture of the extracts, showed that the inflammation index was lower than that of the control group in all the experimental groups + Pro) was similar to that of control group 3, which is a positive control group. Experimental group 3, Gardenia extract (GJ), was shown to be effective in lowering the inflammation caused by Helicobacter pylori infection than the antimicrobial effect against Helicobacter pylori.

< Experimental Example  7> Helicobacter Filly  Recovery effects of extracts and mixtures on infected animal models

Balb / c mice were infected with Helicobacter pylori in the same manner as in Experimental Example 5, and stomachs of the same control group and experimental group in Experimental Example 5 were excised to stain H & E stomach tissues. Based on the results of the staining, the histology score was derived. The tissue index was determined by counting the fibrous structure of the cells, the roundness of the nucleus and the number of cells.

Figure 6 shows the appearance of H & E stained stomach tissue when treated with extracts and mixtures in an animal model of Helicobacter pylori infection. FIG. 6 shows that the experimental group 6 (RF + UL + GJ) and the experimental group 6 (RF + UL + GJ + Pro) were almost similar to normal tissues. (GJ), an experimental group, was superior to the antimicrobial effect of Helicobacter pylori on the recovery of gastric tissue damaged by Helicobacter pylori infection.

< Experimental Example  8> Recovery effect of extracts and mixtures on gastric damage in animal models with alcoholic gastric injuries

A 4 week old SPF male mouse was purchased and subjected to a purifying period for one week, and then a healthy mouse having a body weight of 30 to 40 g was used in the experiment. Seven mice were used in each experimental group. The extracts prepared in Examples 1 to 4 and the mixture thereof were orally administered under the conditions shown in Table 5 after being fasted for 24 hours in a state in which water could be freely taken. After 30 minutes of oral administration, 65% ethanol was prepared in 150 mM HCl solution and oral administration of 1.0 mL of 65% ethanol per animal was induced for 1 hour. After 1 hour, the mouse stomach was removed and fixed in 2% formalin solution. The fixed stomach was incised along the stomach of Taiwan and then the stomach was visually observed and the length of stomach ulcer was measured to calculate the gastric ulcer index and gastric ulcer inhibition rate. The control group administered water instead of the extract.

group	Name of sample	Dosing substance	Dose (mg / kg)	Gastric ulcer index (mm)	(%)
A	Aa	Control group	-	133.26 + - 16.94	-
	Ab	Cimetidine	100	20.33 + - 23.73	84.75
	Ac	RF	150	94.97 8.05	29.29
	Name	UL	150	108.48 ± 11.51	19.23
	Ae	GJ	150	91.77 + - 6.77	31.11
B	Ba	Control group	-	110.38 ± 15.10	-
	Bb	Cimetidine	100	22.64 ± 11.06	79.51
	Bc	RF + UL	75 + 75	48.73 + - 6.46	55.27
	Bd	RF + GJ	75 + 75	25.13 + - 4.37	77.23
	Be	UL + GJ	75 + 75	53.23 + - 2.69	53.23
C	Ca	Control group	-	105.37 ± 6.77	-
	Cb	Cimetidine	150	18.88 ± 19.88	82.08
	Cc	RF + UL + GJ	50 + 50 + 50	23.34 ± 9.11	78.04
	CD	RF + UL + GJ + Pro	50 + 50 + 50 + 10 5 CFU / mL	16.53 + - 5.79	84.76

Table 5 and Figures 7a to 7c show recovery results in the treatment of extracts and mixtures for alcohol-damaged stomach tissue. Referring to Table 5 and FIG. 7A to FIG. 7C, it was found that the gastric-protective effect was enhanced when the extract was mixed with the extract, rather than the extract alone. These results showed that the combination of two extracts resulted in an increased gastric protective effect when the three extracts were mixed, and the inhibition rate of cimetidine, a positive control, was almost the same when the three extracts were mixed. When three kinds of extracts were mixed with the probiotics culture solution than the three kinds of extracts, the protective effect was higher. Therefore, it is effective to prevent the alcoholic stomach damage by the raspberry microsomes, the wheat blooms and the gardenia extracts of the elm elderberry. When the extract is mixed with the extracts or the probiotics are mixed with the extracts, The effect can be further increased.

< Experimental Example  9> Effect of extracts and mixtures on gastric damage in animal models of stress-induced gastric damage

A 4 week old SPF male mouse was purchased and subjected to a purifying period for one week, and then a healthy mouse having a body weight of 30 to 40 g was used in the experiment. Seven mice were used in each experimental group. After fasting for 24 hours, the extracts prepared in Examples 1 to 4 and their mixtures were orally administered under the conditions shown in Table 6. After 40 minutes, the mice were placed in a cage and allowed to stand in the air for 6 hours. Mouse stomachs were excised and fixed in 1% formalin solution. The fixed stomach was incised along the stomach of Taiwan and then the stomach was visually observed and the length of stomach ulcer was measured to calculate the gastric ulcer index and gastric ulcer inhibition rate. The control group administered water instead of the extract.

group	Dosing substance	Dose (mg / kg)	Gastric ulcer index (mm)	(%)
A	Control group	-	120.22 + - 8.27	-
	Stillen	20	21.32 ± 4.56	82.26
	RF	150	78.14 + - 7.23	35.00
	UL	150	97.82 ± 3.21	18.63
	GJ	150	81.67 + - 8.71	32.12
B	Control group	-	131.37 + - 6.23	-
	Stillen	20	27.78 ± 5.14	75.86
	RF + UL	75 + 75	59.11 + - 4.91	55.46
	RF + GJ	75 + 75	29.37 + - 2.58	77.64
C	Control group	-	127.18 + - 4.23	-
	Stillen	100	30.37 ± 3.23	76.12
	RF + UL + GJ	50 + 50 + 50	28.17 + - 7.37	77.85
	RF + UL + GJ + Pro	50 + 50 + 50 + 10 5 CFU / mL	20.37 + - 6.51	84.25

Table 6 shows the recovery results of treatment of extracts and mixtures for stressed damaged tissues. Table 6 shows that the gastric juice protection effect was increased when the extract was mixed with the extracts alone (RF + GJ) (RF + UL + GJ), the stomach protective effect was significantly elevated, and stomach ulcer suppression was similar to that of the positive control styrene. In addition, when three kinds of extracts were mixed with probiotics culture medium (RF + UL + GJ + Pro), the highest gastric protective effect was obtained. Therefore, it is effective to prevent the stressful stomach damage by the raspberry microsomes, the wheat bloom, and the gardenia extract of the elm elderberry. When the extract is mixed with the extract or the probiotic is mixed with the extract, The protection effect can be increased.

< Experimental Example  10> Recovery effect of extracts and mixtures on gastric damage in nonsteroidal gastric injured animal model

A 4 week old SPF male mouse was purchased and subjected to a purifying period for one week, and then a healthy mouse having a body weight of 30 to 40 g was used in the experiment. Seven mice were used in each experimental group. After fasting for 24 hours, the extracts prepared in Examples 1 to 4 and their mixtures were orally administered under the conditions shown in Table 7. After 1 hour, indomethacin (70 mg / kg) was orally administered and allowed to stand for 1 hour to induce stomach injury. Mouse stomachs were excised and fixed in 1% formalin solution. The fixed stomach was incised along the stomach of Taiwan and then the stomach was visually observed and the length of stomach ulcer was measured to calculate the gastric ulcer index and gastric ulcer inhibition rate. The control group administered water instead of the extract.

group	Dosing substance	Dose (mg / kg)	Gastric ulcer index (mm)	(%)
A	Control group	-	124.26 ± 7.97	-
	Cimetidine	100	21.58 ± 3.92	82.63
	RF	150	76.69 + - 2.37	38.28
	UL	150	102.35 ± 2.16	17.63
	GJ	150	64.36 + - 7.73	51.8
B	Control group	-	108.78 + - 6.45	-
	Cimetidine	100	13.89 ± 7.23	87.23
	RF + UL	75 + 75	62.79 + - 4.23	42.27
	RF + GJ	75 + 75	39.91 + - 2.73	68.79
C	Control group	-	117.23 + - 4.92	-
	Cimetidine	100	16.14 + - 2.23	86.23
	RF + UL + GJ	50 + 50 + 50	19.09 + - 7.23	83.71
	RF + UL + GJ + Pro	50 + 50 + 50 + 10 5 CFU / mL	8.94 ± 2.73	92.37

Table 7 shows the recovery of extracts and mixtures treated with non-steroidal anti-inflammatory agents (NSAIDs) on stomach tissues damaged. As shown in Table 7, when the extract was mixed with the extracts, the gastric-protective effect was increased. In particular, when the extracts were mixed with the wild-type raspberry extract, UL) and three extracts (RF + UL + GJ), the gastric protective effect was greatly elevated, showing a similar inhibition rate of cimetidine as the positive control group. In addition, the combination of probiotics (RF + UL + GJ + Pro) showed the highest gastric efficacy compared with the conventional treatment, cimetidine. Therefore, it is effective to prevent the nonsteroidal stomach damage by the raspberry microsomes, the wheat blooms and the gardenia extracts of the elm elderberry. When the extract is mixed with the extract or the probiotics are mixed with the extract, The damage protection effect can be increased.

Claims (17)

1. Rubus crataegifolius) and immature (Rubi A pharmaceutical composition for preventing or treating a gastrointestinal disorder, comprising a mixture of an extract of Fructus and an extract of Ulmus macrocarpa .
2. The pharmaceutical composition according to claim 1, wherein the composition further comprises Gardenia jasminoides extract.
3. The pharmaceutical composition according to claim 1 or 2, wherein the composition further comprises a strain of Lactobacillus or a culture thereof.
4. The pharmaceutical composition according to claim 1, wherein the extract is extracted using water, a C ₁ to C ₂ lower alcohol or a mixture thereof as a solvent.
5. [Claim 3] The method according to claim 2, wherein the mixture of the extracts is prepared by mixing the extract of Rubus amyloliquefaciens with the extract of Eurasia japonica and the extract of Gardeniaceae and the gardenia extract at a weight ratio of 1: 0.01 ~ 100: 0.01 ~ 100 A pharmaceutical composition.
6. The method according to claim 1 or 2, wherein the gastrointestinal disorder is selected from the group consisting of Helicobacter pylori gastritis, non Helicobacter pylori gastritis, gastric ulcer, duodenal ulcer, Sollinger-Ellison syndrome, reflux esophagitis, erosion of the ulcer or gastric mucosa, Wherein the composition is any one selected from the group consisting of oral, rectal, and edema.
7. Claim 1 or 2, wherein the mixture of the extract of H. pylori (H. pylori) is gastrointestinal disease prevention or treatment a pharmaceutical composition for inhibiting the growth of the.
8. Rubus crataegifolius) and immature (Rubi A composition for preventing or treating gastric mucosal injury comprising a mixture of an extract of Fructus and an extract of Ulmus macrocarpa .
9. A mixed extract of two or more plants selected from the group consisting of Rubus plants including wild strawberry, Elmia including king elm, and Japanese gardenia including gardenia, and a method for preventing or treating gastrointestinal diseases comprising, as an active ingredient, As therapeutic pharmaceutical compositions,

   The raspberries are classified into Rubus Cratagiflous), Lou Correa booth Augustine (Rubus coreanus), Lou Booth Occidental lease (Rubus occidentalis or Rubus ideaus ,

   The elms of the elms are Ulmus macrocarpa &lt; RTI ID = 0.0 &gt; macrocarpa Hans ) or Ulmus davidiana var.japonica,

   The Gardenia jasminoides ( Gardenia jasminoides) Ellis or Gardenia jasminoides &lt; RTI ID = 0.0 &gt; there is. ovariflia)

   The lactic acid bacteria may be selected from the group consisting of Lactobacillus acidophilus , L. gasseri , L. fermentum , L. plantarum , Lactobacillus luterium L. reuteri , L. rhamnosus , B. bifidum , B. breve or Bifidobacterium longum . A pharmaceutical composition for preventing or treating gastrointestinal diseases.
10. Rubus crataegifolius) and immature (Rubi Fructus ) extract and a mixture of Echinochloa crus- galli extract of Ulmus macrocarpa as an active ingredient.
11. [Claim 11] The health functional food according to claim 10, wherein the health functional food further comprises Gardenia jasminoides extract.
12. 12. The health functional food according to claim 10 or 11, wherein the health functional food further comprises a strain of Lactobacillus or a culture thereof.
13. Rubus crataegifolius) and immature (Rubi Fructus ) extract and a mixture of Echinochloa crus- galli extract of Ulmus macrocarpa as an active ingredient.
14. Rubus crataegifolius) and immature (Rubi A method for the prevention, amelioration or treatment of gastrointestinal diseases, comprising administering to a subject a mixture of an extract of Escherichia coli Fructus and an extract of Ulmus macrocarpa .
15. Rubus for use in the preparation of a medicament for the prevention, improvement or treatment of gastrointestinal diseases (Rubus crataegifolius) and immature (Rubi Fructus ) extract and a mixture of an extract of a milky white of Ulmus macrocarpa .
16. Rubus crataegifolius) and immature (Rubi A method for preventing, ameliorating or treating gastric mucosal injury comprising administering to a subject a mixture of an extract of Fructus and an extract of Ulmus macrocarpa .
17. Rubus for use in the preparation of a medicament for the prevention, improvement or treatment of gastric mucosal damage (Rubus crataegifolius) and immature (Rubi Fructus ) extract and a mixture of an extract of a milky white of Ulmus macrocarpa .

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