KR20200132286A - Methods for the manufacture of health food for improving gastrointestinal disorders by using bokbunja extract - Google Patents

Abstract

The present invention relates to health food and a pharmaceutical composition for preventing or alleviating gastrointestinal motility disorders containing an extract of Rubus coreanus as an active component. The extract of Rubus coreanus of the present invention is harmless since the extract of Rubus coreanus is derived from a natural product, and exhibits an excellent contraction exercise of the stomach, thereby being able to be usefully used for an agent for treating gastrointestinal motility disorders.

Description

Methods for the manufacture of health food for improving gastrointestinal disorders by using bokbunja extract}

Gastrointestinal dyskinesia is not a histopathological and biochemical lesion of the gastrointestinal tract, but functional related to gastrointestinal peristalsis.

Symptoms include gastroesophageal reflux disease, functional indigestion, irritable bowel disease, gastrointestinal paralysis, vomiting, postoperative intestinal obstruction and constipation.

It appears in various aspects, such as, and is a disease with a fairly high prevalence in Korea as well as in developed countries.

[0003] These gastrointestinal motility disorders are often difficult to know the exact pathogenesis, but the recent serotonin (5-HT) receptors

In the intestine, especially in the intestinal endocrine cells in the small intestine, focusing on the central role in the peristalsis of the gastrointestinal tract,

The development of new gastrointestinal motility promoters is being made, centering on drugs that regulate rotonin. However, most 5-HT3 can

Solution antagonists improve the symptoms of delayed gastrointestinal fasting in rats, but the improvement is not clear in humans and other species.

Some 5-HT receptor antagonists were discontinued because they were pointed out as having significant side effects to pregnant women or people with cerebrovascular disease. One

On the other hand, in case of decreased gastrointestinal motor function after surgery, especially in the case of intestinal obstruction after surgery, secretions in the gastrointestinal tract are removed by nasal aspiration.

Treatment of symptom relief to eliminate symptoms is known, and cisapride has been frequently used as a drug, but its use is limited due to the side effects. Albimopan, a synthetic drug, for the recovery of gastrointestinal function after recent surgery

(alvimopan, Entereg) has been approved by the US FDA. However, toxicity and side effects to be used for gastrointestinal dysfunction

There is an urgent need to develop safe drugs derived from these reduced natural products.

[0004] On the other hand, bokbunja (Rubus coreanus Miquel) is a deciduous shrub belonging to the Rosaceae family, and is known as a country of origin in China.

In Korea, Jeju Island and southern regions are major production areas, and dark red fruits are harvested and edible in early summer. Example

In oriental medicine, it has been known as a valuable medicinal herb as a summary of tonic, gangjeong, and interpolation.

It has been used in the back. In addition, bokbunja has antioxidant effect, inhibitory effect on growth of Helicobacter pylori, hypothalamus-pituitary gland

-Improve the symptoms caused by incompatibility of reproductive secretion in female rats with ovarian removal by enhancing the function of the gonadotropin.

It is known that there is a fruit.

[0005] Accordingly, the present inventors have a composition for preventing or treating gastrointestinal motility disorders from bokbunja having various effects

I tried to develop water.

[0006] Korean Patent No. 0532703 discloses a composition for the prevention and treatment of gastrointestinal dyskinesia including a herbal compound

And Korean Patent Publication No. 2012-0090003 discloses a composition for improving, treating and preventing gastrointestinal dyskinesia.

Although disclosed, for preventing or improving gastrointestinal motility disorders containing the bokbunja extract of the present invention as an active ingredient

There is no description of health food and pharmaceutical compositions.

The present invention is derived from the above requirements, the present invention is the survival rate of cells treated with bokbunja extract and

Sex rats' pyloric motor ability was measured, and as a result, the extract was not cytotoxic and improved pyloric motor ability.

By confirming that there is an effect, the present invention was completed.

In the present invention, it was confirmed the effect of improving the pyloric motor ability of male rats using bokbunja extract. Bokbun of the present invention

Since purple extract is derived from natural products, it is harmless to the human body and exhibits excellent gastrointestinal contractile exercise effect.

It is expected to be usefully used for the treatment of disorders and diseases.

In order to achieve the object of the present invention, the present invention is a gastrointestinal tract containing an extract of Rubus coreanus as an active ingredient

Provides health food for preventing or improving movement disorders.

[0015] In a health food for preventing or improving gastrointestinal motility disorders disease according to an embodiment of the present invention, the bokbunja extract is

It may be a molecular hot water extract, but is not limited thereto. In a health food for preventing or improving gastrointestinal motility disorders disease according to an embodiment of the present invention, the bokbunja hot water extract

May be extracted by mixing water with bokbunja and cultivating it at 60~80℃, preferably at 70℃ with constant temperature shaking

After extracting the amount, it may be prepared by filtering, but is not limited thereto.

[0017] In the health food according to an embodiment of the present invention, the gastrointestinal motility disorder is functional indigestion, ulcerative indigestion,

Non-ulcer indigestion, gastroesophageal reflux disease, reflux esophagitis, gastric asthenia, false bowel obstruction, gastric motor paralysis, constipation, irritable bowel

Syndrome, irritable colitis, diabetic gastrointestinal dyskinesia, gastrointestinal dyskinesia due to chemotherapy, gastrointestinal dyskinesia

A word selected from the group consisting of intestinal obstruction, gastrointestinal dyskinesia due to myotonic dystrophy and non-cardiac chest pain.

It may be one, but is not limited thereto.

[0018] In addition, for the purpose of preventing or improving gastrointestinal motility disorders, the bokbunja extract of the present invention in food or beverage

Can be added. The amount of the extract in the food or beverage can be added in 001 to 15% by weight of the total food weight.

And, the health beverage composition can be added in a ratio of 002 to 5 g, preferably 03 to 1 g, based on 100 ml.

have.

[0019] The health functional beverage composition of the present invention has other properties other than containing the extract as an essential ingredient in the indicated ratio

There are no special restrictions on the powder, and as an additional ingredient, various flavoring agents or natural carbohydrates, etc.

It may contain. Examples of the above-described natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides, eg

For example, maltose, sucrose, etc.; And polysaccharides such as dextrin, cyclodextrin, etc.

Sugar and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin,

Stevia extract, e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.)

It can be used conveniently. The ratio of the natural carbohydrate is generally about 1 to 20 g per 100 ml of the composition of the present invention,

It is preferably about 5 to 12 g.

[0020] In addition to the above, the extract of the present invention is a variety of nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, etc.

Miscellaneous agents, coloring agents and heavy agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloids

It may contain thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like.

In addition, the extract of the present invention contains flesh for the production of natural fruit juice and fruit juice beverage and vegetable beverage.

can do. These ingredients can be used independently or in combination, and the proportion of these additives is so important.

Although not, it is generally selected from 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

[0021] In a health food for preventing or improving gastrointestinal motility disorders disease according to an embodiment of the present invention, the food is dairy products, feet

Soybean milk, drink, meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soup,

It may be selected from the group consisting of beverages, alcoholic beverages, and vitamin complexes, but is not limited thereto.

Does not.

[0022] In addition, the present invention prevents or prevents gastrointestinal motility disorders containing an extract of bokbunja (Rubus coreanus) as an active ingredient

It provides a pharmaceutical composition for treatment.

[0023] In a pharmaceutical composition for preventing or treating gastrointestinal motility disorders disease according to an embodiment of the present invention, the gastrointestinal exercise field

Ae's diseases include functional indigestion, ulcerative indigestion, non-ulcer indigestion, gastroesophageal reflux disease, reflux esophagitis,

Gastric asthenia, false bowel obstruction, gastric motor paralysis, constipation, irritable bowel syndrome, irritable colitis, diabetic gastrointestinal dyskinesia, harmony

Gastrointestinal dyskinesia due to therapy, intestinal obstruction due to dyskinesia of the digestive tract, gastrointestinal dystrophy due to muscular dystrophy

And it may be any one selected from the group consisting of non-psychic chest pain, but is not limited thereto.

[0024] The pharmaceutical composition for preventing or treating gastrointestinal motility disorders diseases of the present invention comprises the extract based on the total weight of the composition

002 to 80% by weight, preferably 002 to 50% by weight.

[0025] The composition containing the extract of the present invention is a suitable carrier, excipient, ordinarily used in the preparation of a pharmaceutical composition.

And it may further include a diluent.

[0026] The pharmaceutical dosage form of the extract of the present invention may be used in the form of a pharmaceutically acceptable salt thereof, and

It can be used alone or in combination with other pharmaceutically active compounds as well as in an appropriate set.

[0027] The composition containing the extract according to the present invention is a powder, granule, tablet, capsule, suspension according to a conventional method, respectively

It can be formulated and used in the form of oral dosage forms such as liquids, emulsions, syrups, and aerosols, external preparations, suppositories, and sterile injectable solutions.

have. Carriers, excipients and diluents that may be included in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphine.

Acid, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzo

A variety of compounds including ate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, or

Mixtures are mentioned. When formulated, usually used fillers, extenders, binders, wetting agents, disintegrants, surfactants

It is prepared using a diluent or excipient such as. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules.

Agents, etc., and such solid preparations include at least one excipient, such as starch, calcium calcium, in the strain extract.

Prepared by mixing bonate (calcium carbonate), oligosaccharide, sucrose or lactose, gelatin, etc.

do. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid for oral use

Formulations include suspensions, liquid solutions, emulsions, syrups, etc., but water and liquid paraffin, which are commonly used simple diluents, are used.

In addition, various excipients, for example, wetting agents, sweetening agents, fragrances, preservatives, and the like may be included. For parenteral administration

Formulations include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. Non-aqueous solvents and suspensions

Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, ethyl oleate

Injectable esters and the like can be used. Suppository bases include witepsol, macrogol, tween 61, car

Kaoji, laurin paper, glycerogelatin, and the like may be used.

The preferred dosage of the extract of the present invention is the patient's condition and weight, the degree of disease, the drug form, the route and duration of administration.

Depends on, but may be appropriately selected by those skilled in the art. However, for a desirable effect, the weight of the present invention

The output is preferably administered at 00001 to 100 mg/kg per day, preferably 0001 to 100 mg/kg. Administration is

It can be administered once a day, or it can be divided several times. The above dosage is in any way the scope of the present invention

Is not limited to.

[0029] The extract of the present invention may be administered to mammals such as mice, mice, livestock, and humans by various routes. Administration of all

Mode can be expected, for example, oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dura mater or cerebrovascular

(intracerebroventricular) can be administered by injection.

In addition, the present invention provides a constipation treatment containing the extract of bokbunja (Rubus coreanus) as an active ingredient.

In addition, the present invention provides a feed additive containing bokbunja (Rubus coreanus) extract as an active ingredient.

When the feed additive of the present invention is administered to livestock showing symptoms of decreased gastric movement, the effect of improving gastric movement can be seen.

When the feed additive of the present invention is mixed with water of livestock, it can be mixed and used in a conventional manner.

[0033] Hereinafter, the present invention will be described in detail by examples. However, the following examples are only to illustrate the present invention,

The contents are not limited to the following examples.

[0034] Materials and methods

1 bokbunja hot water extract manufacturing

Distilled water was added to the bokbunja sample and then cultured with constant temperature shaking for 3 hours at 60 to 80°C. Filter paper for the obtained extract

(Whatman filter paper, No2) was filtered to remove impurities and then freeze-dried. Solubility of hot water extract

As a result, it was confirmed that it was dissolved in sterile water, and to prevent oxidation of the sample, it was used while frozen at -80°C. This thread

Bokbunja hot water extract obtained from the test was expressed as JBMI-RW.

[0037] 2 Cytotoxicity test

[0038] Cytotoxicity was tested for cytotoxicity of a sample against normal cells using 293T cells, which is a human kidney epithelial cell line.

293T cells were purchased from Korea Cell Line Bank (KCLB21573) and contain 10% fetal bovine serum (FBS).

It was cultured using one DMEM medium. The health status and life or death of the cells are always 80-90% after observation with a phase contrast microscope.

The cells were subcultured while maintaining the condition above, and the cells were incubated at 37℃ in a constant temperature cell incubator in which 5% CO2 was injected.

Cultured.

[0039] MTS(3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) in 293T, which is a human kidney epithelial cell line, which is a normal cell line, to check the stability of the sample) -2H-tetrazolium) test method to measure cell viability

I did. 15×10 cells in a 96-well plate

4

After dispensing each cell/well, sample by concentration (1, 10, 25, 50, 100 ㎍/㎖)

Treated and cultured for 24 hours under conditions of 37°C and 5% CO2. After incubation, add MTS solution and incubate again for 4 hours

After that, the absorbance was measured at 490 nm with a microplate reader. Cell viability was calculated according to the following equation.

All.

Cell viability (%) = (absorbance of the sample addition group / absorbance of the control group) × 100

[0041] 3 Evaluation of the efficacy of improving gastrointestinal pyloric motor ability

[0042] Male rats (Dawiey, 6 weeks old, 200-250g) were bred in a breeding device maintained at 24±05℃, and water and feed were freely

Were allowed to ingest. After separating the stomach of the rat sacrificed with cervical dislocation, it was placed in a wide vitreous container containing Krebs solution.

After removing the mucous membrane of the pyloric sinus area, a section is made in size of 2×5㎜. One side of the section is in a 10 ml tracheal tank.

Fix it to the tissue fixing device, and make a ring on the other side and connect it to an isometric muscle contraction transducer (Grass, FT-03).

A basic tension of 05 g was applied. Drug administration or full-length stimulation is carried out after a stabilization period of 1 hour has passed, and stabilization

During the period, the Creves solution was replaced at about 15 minute intervals. Data recording and storage is performed by a data integration device (Powerlab

4/25, Adinstruments) and the software Chart 702 were used. Mix gas (95% O2 and 5% CO2) during the experiment.

It was put in, and the temperature in the water bath was kept constant at 37±05°C.

Nutrients are NaCl 120mM, KCl 46mM, CaCl2 25mM, MgCl2 12mM, NaHCO3 22mM, NaH2PO4 12mM and 95% of O2 and 5% CO2

Krebs hydrogen carbonate buffer (pH74) containing glucose oxidized to 115 mM was used. Extract liquid in sterile water

It was melted and used.

[0044] 4 statistical processing

[0045] The significance test between groups of the experimental results is significant when p<005 by performing a post-test comparison with Duncan's one-way analysis of variance

(SPSS V12, New York, NY, USA)

[0046] Example 1 Cytotoxicity test of hot water extract of bokbunja

Cytotoxicity test was performed on the extract. Using normal cells, 293T cells, the stability of Bokbunja hot water extract

As a result of confirmation, it was confirmed that little cytotoxicity appeared up to the highest concentration of treatment, 100 ㎍/㎖.

It was shown that the stability of the treatment was high (Fig. 1)

[0048] Example 2 gastrointestinal pyloric motor ability improvement measurement result

[0049] To check the gastrointestinal motility of JMBI-RW, the gastrointestinal pylorus was separated to measure the contraction tension (FIG. 2) The contraction tension is a sample

The shrinkage tension of each sample concentration was reflected based on 100% of the group not treated with.

JMBI-RW group was observed to increase to 1176 ± 147% when 30 ㎍ / ㎖ treatment, 1473 ± 100 ㎍ / ㎖ treatment

The contraction tension was significantly increased to 284% (Fig. 3). These results show that the extract of bokbunja promotes the contraction of the stomach

It is believed that it can help improve constipation.

Claims (1)

A health food for preventing or improving gastrointestinal motility disorders, containing extracts of Rubus coreanus as an active ingredient.

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