KR102671714B1 - Composition for improving gastrointestinal function comprising mulberry fruit as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for improving gastrointestinal function containing a mulberry extract as an active ingredient, which can show improvement in gastrointestinal function through gastrointestinal peristalsis activity by including mulberry extract, and improves gastrointestinal function and eliminates the problem of side effects by including it. It is possible to provide compositions, food compositions, health functional foods, and pharmaceutical compositions that are excellent in functionality and preference without the need for food.

Description

Composition for improving gastrointestinal function containing mulberries as an active ingredient {COMPOSITION FOR IMPROVING GASTROINTESTINAL FUNCTION COMPRISING MULBERRY FRUIT AS AN ACTIVE INGREDIENT}

The present invention relates to a composition for improving gastrointestinal function containing mulberries as an active ingredient. By including mulberries as an active ingredient, the composition improves gastrointestinal tract function by improving gastrointestinal motility, and has an excellent effect of improving gastrointestinal function, but also eliminates the problem of side effects by containing a natural product as an active ingredient. It relates to a composition that has excellent palatability and functionality.

Acetylcholine (ACh) receptors [Muscarinic receptor (mAChR), nicotinic receptor (nAChR)] have an important function in regulating physiological movements of the gastrointestinal tract. The subtypes of mAChR (Muscarinic receptor) mainly distributed in the gastrointestinal tract of mammals are M2 and M3, and it is known that the control of gastrointestinal motility is mainly achieved by the action of these mAChR subtypes. In addition, nAChRs (Nicotinic receptors) distributed in the gastrointestinal tract are also involved in the regulation of intestinal motility. These receptors are known to act on the excitatory motor neurons of the nerve plexus connected to the intestinal longitudinal smooth muscle at the anterior nerve junction of the gastrointestinal tract. there is. The activity of the M3 receptor, a mAChR receptor subtype mainly distributed in the gastrointestinal tract, hydrolyzes PIP2 (Phosphatidyl inositol 4,5-bisphosphate) in the cell membrane, causing an increase in intracellular Ca ²⁺ ions, thereby increasing intestinal motility and preneural synapse. nAChRs distributed in the subterminals contract longitudinal muscles by causing the release of ACh.

Meanwhile, gastrointestinal motility disorders include gastric and esophageal reflux, functional dyspepsia, irritable colitis, gastrointestinal paralysis, vomiting, diabetic gastrointestinal motility disorder, gastrointestinal motility disorder due to chemotherapy, ileus due to digestive tract motility disorder, and postoperative ileus. It refers to a condition in which normal gastrointestinal motility is impaired, inhibited, or damaged, such as gastrointestinal dysfunction after surgery or gastrointestinal motility disorder due to myotonic dystrophy.

Gastrointestinal motility disorders occur quite frequently in developed countries as well as in Korea, and show a variety of symptoms, especially gastrointestinal paralysis, which causes pain and discomfort in daily life. These gastrointestinal motility disorders are functional symptoms related to gastrointestinal peristalsis rather than histopathological or biochemical lesions of the gastrointestinal tract.

Currently, gastrointestinal motility disorders are diagnosed through the diagnosis of various symptoms without obvious organic lesions, so treatment is not simple, and most symptoms repeatedly improve and worsen and are greatly changed by food, stress, etc.

Currently, representative gastrointestinal motility stimulants include drugs such as Domperidone, metoclopramide, levosulpiride, mosapride, and itopride.

Among them, gastrointestinal motility stimulants such as metoclopramide, domperidone, cisapride, levosulpride, and erythromycin are known to be effective in several studies. , Metoclopramide is the most commonly used anti-dopamine drug. It inhibits dopamine receptors in the central nervous system and gastrointestinal tract, and dopamine plays a role in inhibiting gastrointestinal motility. Metoclopramide enhances gastroduodenal motility, improves gastric emptying function, and has an analgesic effect, so it improves the symptoms of patients suffering from diseases caused by gastrointestinal motility disorders such as functional dyspepsia. However, when used for a long period of time, the symptom improvement effect is not effective. It decreases and acts on dopamine receptors in the central nervous system, which can cause side effects in the nervous system in up to 24% of patients.

In particular, gastrointestinal motility disorders often require long-term use because they repeatedly improve and worsen, and there is an urgent need for the development of natural product-derived gastrointestinal motility stimulants that are safe for the human body even when taken for a long period of time.

In the present invention, the present invention was completed to provide a composition that contains mulberry extract as an active ingredient and shows an effect of improving gastrointestinal function without causing side effects.

KR 10-0607705 B1 KR 10-2022-0074353 A

The purpose of the present invention is to provide a composition that exhibits gastrointestinal function improvement activity, including a mulberry extract.

In addition, another object of the present invention is to provide a food composition, health functional food, or pharmaceutical composition containing a composition for improving gastrointestinal function containing a mulberry extract.

In order to achieve the above object, a composition for improving gastrointestinal function according to an embodiment of the present invention contains mulberry extract as an active ingredient.

The improvement in gastrointestinal function occurs through activation of gastric motility.

The composition is used for gastroesophageal reflux disease, functional dyspepsia, irritable colitis, gastrointestinal paralysis, vomiting, diabetic gastrointestinal motility disorder, gastrointestinal motility disorder due to chemotherapy, intestinal obstruction due to digestive tract motility disorder, postoperative ileus, and postoperative gastrointestinal dysfunction. , is selected from the group consisting of gastrointestinal motility disorder, infantile colic, and constipation due to myotonic dystrophy, and shows the effect of improving one or more symptoms.

The extract is extracted using an extraction solvent selected from the group consisting of water, C1 to C6 lower alcohols, and mixtures thereof.

A food composition for improving gastrointestinal function according to another embodiment of the present invention includes a composition for improving gastrointestinal function containing mulberry extract as an active ingredient.

A health functional food for improving gastrointestinal function according to another embodiment of the present invention includes a composition for improving gastrointestinal function containing the mulberry extract as an active ingredient.

A pharmaceutical composition for preventing or treating symptoms caused by decreased gastrointestinal function according to another embodiment of the present invention includes a composition for improving gastrointestinal function containing the mulberry extract as an active ingredient.

Hereinafter, the present invention will be described in more detail.

In the present invention, 'prevention' refers to any action that suppresses or delays the progression of the disease or disease to which the term applies, or one or more symptoms of the disease or disease, by administering the composition of the present invention.

In the present invention, 'improvement' means any action in which the disease or disease to which the term applies, or one or more symptoms of the disease or disease, is improved or beneficially changed by administration of the composition of the present invention.

In the present invention, unless otherwise stated, 'treatment' refers to reversing, alleviating, inhibiting the progression of, or preventing the disease or disease to which the term applies, or one or more symptoms of the disease or disease. The term 'treatment' used herein refers to the act of treating when 'treating' is defined as above.

As used herein, the term 'active ingredient' refers to an ingredient that can exhibit the desired activity alone or in combination with a carrier that is not active on its own.

The term 'extract' used in this specification has the meaning commonly used in the art as a crude extract, as described above, but in a broad sense also includes fractions obtained by additional fractionation of the extract. In other words, plant extracts include not only those obtained using the above-described extraction solvent, but also those obtained by additionally applying a purification process. For example, fractions obtained by passing the extract through an ultrafiltration membrane with a certain molecular weight cut-off value, separation by various chromatographs (designed for separation according to size, charge, hydrophobicity, or affinity), etc. Fractions obtained through purification methods are also included in the plant extract of the present invention.

The terminology used herein is for describing embodiments and is therefore not intended to limit the invention. As used herein, singular forms also include plural forms, unless specifically stated otherwise in the context. As used in the specification, 'comprise' and/or 'comprising' refers to the presence of one or more other components, steps, operations and/or elements. or does not rule out addition.

A composition for improving gastrointestinal function according to an embodiment of the present invention contains mulberry extract as an active ingredient.

The gastrointestinal tract is a long tube from the oral cavity to the anus, including the mouth, esophagus, stomach, and intestines. The gastrointestinal tract supplies energy for human survival and ingredients necessary for body tissue composition, and controls the intake and movement of food and the ingested food. Through functions such as decomposition, secretion of enzymes, hormones and electrolytes that can break down food, absorption and excretion of digested food, intake of food and absorption of nutrients from it and excretion of remaining substances It can absorb the ingredients necessary for energy and body tissue composition in the human body.

As gastrointestinal function is important for the human body to absorb nutrients and energy from food, we attempted to demonstrate the effect of improving gastrointestinal function by the mulberry extract of the present invention.

The mulberry (Morus alba L.) is the fruit of the mulberry tree or mountain mulberry tree, and is also called mourning heart or mourning fruit. It is a black-purple drupe with a diameter of 2cm and an appearance similar to a grape. It grows from light green to red at first, then changes to dark red mixed with red when fully ripe. Depending on the variety, it begins to ripen around late May and mostly ripens over 2 to 3 weeks until around mid-June, and can be harvested for a short period from early summer in June to July. Its origin is East Asia, and it is widely distributed from tropical to temperate regions. Most mulberry varieties are imported from Asia, and in Korea, it is mainly cultivated in Boeun, North Chungcheong Province, Wonju, Gangwon Province, Sangju, North Gyeongsang Province, Wanju, Jeonbuk Province, and Jeongeup.

It began to be used as medicine during the Tang Dynasty. It has mild medicinal properties and a sweet and sour taste. It contains many types of sugar, organic acids, mucilage, vitamin B1, vitamin B2, and vitamin C. Its pharmacological effects are known to have diuretic, antitussive, and tonic effects. It is used when you feel dizzy due to anemia, there is a sound in your ears, and your face is pale. It is also effective when your hair suddenly turns gray due to functional weakness of the whole body, you have difficulty hearing, and you feel very tired and dizzy in your eyes. In addition, if diabetic patients take it when they feel very thirsty, it will quench their thirst. It is also effective for people who are oversensitive due to nervous breakdown, and it is also taken when the head is heavy and dizzy due to arteriosclerosis or high blood pressure. Additionally, it detoxifies alcoholism and has a diuretic effect. If a person takes it for a long time, the lower body becomes healthy, the eyes become clear, gray hair turns black, and it also has a beneficial effect on the tonic function. However, it is best not to use it when you have diarrhea.

By using the mulberries, the present invention can improve gastrointestinal motor activity and prevent, treat or improve symptoms caused by decreased gastrointestinal function.

The improvement in gastrointestinal function occurs through activation of gastric motility.

The peristalsis of the gastrointestinal tract is a muscle movement that forms propagating contraction waves in the digestive tract, etc., and its basic purpose is to move food toward the esophagus, stomach, intestines, and anus. It is caused by the independent or automatic activity of the neuromuscular system, which consists of the smooth muscle system in which longitudinal muscles and circular muscles oppose each other, and the longitudinal nervous system that mutually dominates both. In more detail, it is mainly caused by the longitudinal muscles (mainly longitudinal muscles) in tubular organs. Longitudinal muscles can contract and move food, and at this time, transverse muscles (circular muscles) are also involved.

The peristalsis disorder of the gastrointestinal tract may be caused by abnormal contraction of the smooth muscles of the gastrointestinal tract, which may cause constipation, diarrhea, abdominal distension, etc., and may also be accompanied by abdominal pain.

Accordingly, in the present invention, by including mulberry extract as an active ingredient, the effect of improving gastrointestinal tract function can be shown by promoting peristalsis of the gastrointestinal tract.

The composition is suitable for gastroesophageal reflux disease, functional dyspepsia, irritable colitis, gastrointestinal paralysis, vomiting, diabetic gastrointestinal motility disorder, chemotherapy-induced gastrointestinal motility disorder, intestinal obstruction due to digestive tract motility disorder, postoperative ileus, and postoperative gastrointestinal dysfunction. , is selected from the group consisting of gastrointestinal motility disorder, infantile colic, and constipation due to myotonic dystrophy, and shows the effect of improving one or more symptoms.

The composition may further include additional natural extracts in addition to the mulberry extract.

Preferably, the composition may further include Jeju wild rose extract, Dalgae extract, and Sanbijang extract.

The Jeju starling (Rosa luciae) is a deciduous broad-leaved shrub of the dicotyledonous Rosaceae family, growing in sunny areas at the foot of mountains or in moist river areas. It is 1 to 2 m high. The ends of the branches droop down and form a vine shape. There are thorns all over the pot. The leaves are alternate and pinnately compound. There are 5 to 9 small leaves, shaped like an oval or an upside-down egg, and are 2 to 3 cm long. Both ends of the leaves are narrow and the edges of the stipules are almost smooth. Flowers bloom in white or light pink from May to June and hang in panicles at the ends of new branches. The peduncle is hairless or has glandular hairs. The calyx pieces are lanceolate and bent backwards. The petals are shaped like an upside-down egg, have concave ends, and are fragrant. Hair grows on the style. The fruit is round in shape and ripens red in September. The fruit contains several achenes about 3 mm in diameter, which are white and hairy. The young leaves are eaten as a vegetable and the fruits are used as medicine for edema, arthritis, and swelling in oriental medicine and folk medicine. Distributed in Korea, Japan, etc.

Commelina communis is an annual herb of the monocotyledonous endospermia family, and is also called moongae or chicken's bottom wash. It commonly grows on roadsides, grasslands, and wetlands near streams. The lower part of the stem grows obliquely to the side, crawls on the ground, roots from the nodes, and has many branches. The upper part of the stem stands upright and is 15 to 50 cm high. The leaves are alternate, egg-shaped, lanceolate, 5 to 7 cm long and 1 to 2.5 cm wide. The tips of the leaves become increasingly pointed, and the lower part becomes a membranous sheath (translucent like thin paper). The flowers bloom in light blue from July to August and are wrapped in bracts at the ends of flower stems emerging from the leaf axils and hang in cyme inflorescences. The bracts are wide heart-shaped, folded inward, have sharp ends, and are about 2cm long. There are three calyx pieces, oval-shaped, and 4 mm long. There are three petals, two of which are large, round, and light blue, and the other is lanceolate, white, and small. There are three stamens and three useless stamens without anthers, and one pistil. The fruit is an oval-shaped capsule and splits into three when dried. Young leaves are eaten in spring. In oriental medicine, the leaves are used as a medicine called Apcheokcho (鴨). It has a great fever-reducing effect, has a diuretic effect, and is also used for diabetes. The juice of the fresh leaves is used for burns. Distributed in Korea, Japan, China, the Ussuri River basin, Sakhalin, and North America.

The Serratula coronata subsp. insularis is a perennial plant of the dicotyledonous plant Campanula Asteraceae and grows in mountainous areas. It is 30 to 140 cm in height. There are vertical lines, the rhizome is hard like a tree, and the stem stands straight. The leaves attached to the roots are egg-shaped, long oval shaped, have sharp ends, and are completely split like feathers. The forked pieces are oval-shaped, have irregular sawtooth edges, and the petioles are 11 to 30 cm long. The leaves on the stem are similar to the leaves on the roots, but become smaller as they go up. Flowers bloom in light red-purple colors from July to October, and the head flowers are 3 to 4 cm in diameter, with one each at the end of the branch and stem. The involucre is bell-shaped and yellowish green. The bract pieces are arranged in six rows, and the outer and middle pieces have sharp ends and have some spiderweb-like hairs on the outside. The fruit is an achene, cylindrical, and about 6 mm long. The hairs are 11 to 14 mm long, brown, and have no feather-like hair. Young shoots are eaten as vegetables. Distributed in Korea and Japan.

Even more preferably, the composition may contain 30 to 50 parts by weight of Jeju wild rose extract, 30 to 50 parts by weight of Dalgae extract, and 10 to 30 parts by weight of Sanbijang extract, based on 100 parts by weight of mulberry extract.

According to the above weight range, the functionality of the composition can be maintained or slightly improved by Jeju starling, wild rose, and mountain birch, while palatability can be improved. Accordingly, if the above range is used, the effect of improving gastrointestinal function is increased by mixing each extract. It can exhibit the highest activity, there is no cytotoxicity problem due to the use of natural extracts, and it can be provided as a food composition, health functional food, or pharmaceutical composition that can be taken for a long period of time and has improved palatability.

The extract is extracted using an extraction solvent selected from the group consisting of water, C ₁ to C ₆ lower alcohols, and mixtures thereof.

The method of preparing the extract may be a conventional extraction method in the art, such as ultrasonic extraction, leaching, and reflux extraction. Specifically, it may be an extract obtained by extracting a natural product from which foreign substances have been removed by washing and drying with water, alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof, and may be an extract obtained by sequentially applying the solvents to the sample.

The ultrasonic extraction method proceeds at 30 to 50°C for 0.5 to 2.5 hours, and the extraction solvent is water or 50 to 100% alcohol with 1 to 6 carbon atoms. Specifically, extraction is performed at 40 to 50°C for 1 to 2.5 hours, and the extraction solvent is water or 70 to 80% alcohol with 1 to 6 carbon atoms.

The leaching method is carried out at 15 to 30°C for 24 to 72 hours, and water or 50 to 100% alcohol with 1 to 6 carbon atoms is used as the extraction solvent. More specifically, it is carried out at 20 to 25°C for 30 to 54 hours, and the extraction solvent is water or 70 to 80% alcohol with 1 to 6 carbon atoms.

The reflux extraction method is based on 100 mL of water and alcohol with 1 to 6 carbon atoms, 10 to 30 g of pulverized natural product, reflux time of 1 to 3 hours, and 50 to 100% of alcohol or water with 1 to 6 carbon atoms. More specifically, based on 100 mL of alcohol with 1 to 6 carbon atoms or 100 mL of water, 10 to 20 g of pulverized natural product, 1 to 2 hours of reflux time, and 70 to 90% of alcohol or water with 1 to 4 carbon atoms.

The extraction solvent can be used in an amount of 2 to 50 times, more specifically, 2 to 20 times the weight of the sample. For extraction, the sample may be left for 1 to 72 hours, more specifically, 24 to 48 hours for leaching in the extraction solvent.

After extraction, the extract can be fractionated by sequentially applying a new fractionation solvent. The fractionating solvent used during fractionation is at least one selected from the group consisting of water, hexane, butanol, ethyl acetic acid, ethyl acetate, methylene chloride, and mixtures thereof, and is preferably ethyl acetate or methylene chloride.

After obtaining the extract or fraction, additional methods such as concentration or freeze-drying can be used.

A food composition for improving gastrointestinal function according to another embodiment of the present invention includes a composition for improving gastrointestinal function containing mulberry extract as an active ingredient.

At this time, the amount of the composition in the food or beverage can be about 0.01 to 15% by weight of the total weight of the food, and the health drink composition can be added at a rate of about 0.01 to 10g based on 100 ml, but is not limited thereto. .

When the food composition of the present invention is a beverage composition, other than containing the extract as an essential ingredient in the ratio indicated, there are no particular restrictions on other ingredients, and various flavoring agents or natural carbohydrates may be contained as additional ingredients like ordinary beverages. You can. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose, etc.; Disaccharides such as maltose, sucrose, etc.; and polysaccharides, such as common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (thaumatin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used, but are not limited to these. The ratio of the natural carbohydrate may generally range from about 1 to 20 g per 100 ml of the composition of the present invention, but may not be limited thereto.

In addition to the above, the composition of the present invention contains various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its It may contain salt, organic acid, protective colloidal thickener, Ph adjuster, stabilizer, preservative, glycerin, alcohol, carbonating agent used in carbonated beverages, etc., but may not be limited thereto.

In addition, the composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks, and these ingredients can be used independently or in combination. The proportion of these additives is not critical, but may be selected in the range of about 0.1 to about 20 parts by weight per 100 parts by weight of the composition of the present invention, but is not limited thereto.

A health functional food for improving gastrointestinal function according to another embodiment of the present invention includes a composition for improving gastrointestinal function containing the mulberry extract as an active ingredient.

It is possible to provide a functional food composition including the composition for improving gastrointestinal function, and by including it, a health functional food can be provided. In the present invention, a "health functional food" refers to a composition that uses specific ingredients as raw materials for the purpose of health supplementation. It includes health supplements as foods manufactured and processed by methods such as extraction, concentration, purification, and mixing of specific ingredients contained in food ingredients. Other food ingredients provide biological defense, regulation of biological rhythm, and prevention of disease. It is a food that has been designed and processed to fully exert bioregulatory functions such as health and recovery on the living body, and includes all foods that also have functions related to disease prevention and disease recovery.

A pharmaceutical composition for preventing or treating symptoms caused by decreased gastrointestinal function according to another embodiment of the present invention includes a composition for improving gastrointestinal function containing the mulberry extract as an active ingredient.

Specifically, the pharmaceutical composition is prepared as a powder, granule, or powder according to a conventional method, respectively.

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

In the present invention, carriers, excipients, and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, and calcium phosphate. , calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations include the extract and its fractions with at least one excipient such as starch, calcium carbonate, It is prepared by mixing sucrose, lactose, and gelatin. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, and syrups, and may contain various excipients such as wetting agents, sweeteners, fragrances, and preservatives in addition to the commonly used simple diluents such as water and liquid paraffin. there is.

Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurin, glycerogenatin, etc. can be used.

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount, and the term "pharmaceutically effective amount" in the present invention refers to the amount used to treat or prevent a disease with a reasonable benefit/risk ratio applicable to medical treatment or prevention. It refers to a sufficient amount, and the effective dose level is determined by the severity of the disease, the activity of the drug, the patient's age, weight, health, gender, the patient's sensitivity to the drug, the administration time, route of administration, and excretion rate of the composition of the present invention used. Factors including the duration of time, drugs used in combination or concurrently with the compositions of the present invention used, and other factors well known in the medical field. The pharmaceutical composition of the present invention can be administered alone or in combination with a known immunotherapeutic agent. It is important to consider all of the above factors and administer the amount that will achieve the maximum effect with the minimum amount without side effects.

The present invention can provide a composition for improving gastrointestinal function containing mulberry extract as an active ingredient.

The present invention can provide food compositions, health functional foods, and pharmaceutical compositions with excellent functionality and high preference by including a composition for improving gastrointestinal function containing mulberry extract as an active ingredient.

Figure 1 shows the cytotoxicity evaluation results of the mulberry extract of the present invention.

Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily implement it. However, the present invention may be implemented in many different forms and is not limited to the embodiments described herein.

[Preparation Example 1: Preparation of mulberry extract]

1. Preparation of mulberry extract (ME)

The mulberries were washed in water and then freeze-dried. Afterwards, the freeze-dried mulberries were pulverized in a blender, leached at room temperature for 48 hours using 80% ethanol, and the sample was filtered to prepare mulberry extract (ME).

[Preparation Example 2: Composition for improving gastrointestinal function containing complex extract]

1. Preparation of composition

Preparation of natural extracts

Jeju starlings were washed in water and then freeze-dried. Afterwards, the freeze-dried Jeju starling was pulverized in a blender, leached at room temperature for 48 hours using 80% ethanol, and the sample was filtered to prepare Jeju starling extract (JE).

Preparation of other natural extracts

Dalgae extract (DE) and wild birch extract (SE) were prepared by replacing only the natural products with dalgae and sanbijang in the same manner as the Jeju wild rose extract (JE).

Preparation of complex extract

The mulberry extract (ME), Jeju wild rose extract (JE), Dalgae extract (DE), and Sanbigiga extract (SE) were mixed within the weight range of Table 1 below to prepare composite extracts (MX 1 to MX8).

MX1 MX2 MX3 MX4 MX5 MX6 MX7 MX8 MX9 M.E. 100 100 100 100 100 100 100 100 100 J.E. - 40 - - 20 30 40 50 60 DE - - 40 - 20 30 40 50 60 S.E. - - - 40 20 30 40 50 60

(Unit: parts by weight)

[Experimental Example 1: Evaluation of cytotoxicity of natural extracts]

1. Measurement of cell viability

cell culture

RAW 264.7 cells, a mouse macrophage cell line, were purchased from the Korea Cell Line Bank (KCLB) and used. The RAW 264.7 cells were cultured in an incubator controlled at 37°C and 5% CO ₂ using DMEM medium containing 10% FBS and 1% penicillinstreptomycin.

Cell viability measurements

RAW 264.7 cells were distributed in a 96-well plate at a concentration of ¹ As a positive control group, 1 ug/mL of lipopolysaccharide (LPS) was treated. After culturing for 24 hours, CCK-8 solution (10 mL/well) was added to each well and treated at 37°C for 2 hours to produce 450 mL. Absorbance was measured using an ELISA reader (TECAN, Mnnedorf, Switzerland) at nm wavelength.

The results are shown in Figure 1 below. As shown in Figure 1, the mulberry extract prepared in Preparation Example 1 showed a survival rate of more than 90% at all concentrations compared to the positive control, confirming that there was no cytotoxicity.

In the same manner as the cytotoxicity evaluation of the mulberry extract (ME), the cytotoxicity evaluation of Jeju wild rose extract (JE), dalgae extract (DE), and wild birch extract (SE) was conducted, and the results of the experiment showed that at all concentrations, the cytotoxicity was higher than 90%. As the survival rate is shown, it can be confirmed that there is no problem of cytotoxicity due to the use of the natural extract.

[Experimental Example 2: Effect of mulberry extract (ME) on improving gastrointestinal function]

To determine the effect of the mulberry extract (ME) on gastrointestinal motility, the following experiment was conducted.

2-1. Confirmed effect of promoting intestinal movement and secretion of intestinal motility hormones

1) Check the effect of promoting bowel movement

Gastrointestinal transit was analyzed to confirm the intestinal motility promoting function of mulberry extract (ME). First, SD rats were classified into three groups (Control group: Vehicle group, low-concentration mulberry extract administration group (MELo group, 200 mg), high-concentration mulberry extract administration group (MEHi group, 400 mg), and normal control group (No). Then, each experimental group Loperamide was administered to rats to reduce gastrointestinal motility, and charcoal (3% activated charcoal suspended in 0.5% aqueous methylcellulose) (Sigma-Aldrich Co.) was administered to rats. After oral administration of 3ml, the intestines of the euthanized rats were collected 30 minutes later, the total intestinal length and the movement distance of activated carbon were measured, and the movement rate of food in the intestines was calculated as follows. The results are in the table below. It is shown in 2.

[Equation 1]

Movement rate of food in the intestines (%) = [(Total small intestine length - Movement distance of activated carbon)/Total small intestine length)] ×100

Length of small intestine (cm) Activated carbon movement rate (%) No 132.5 82.7 Vehicle 110.2 40.0 MELo 120.7 67.8 MEHi 131.8 75.2

(Unit: cm, %)

Referring to Table 2, it can be seen that the movement of activated carbon in the group administered mulberry extract increased more than in the vehicle group with reduced gastrointestinal motility, and that the movement rate also increased as the concentration increased.

2) Confirmation of the effect of promoting intestinal motility hormone secretion

The effect of the mulberry extract (ME) according to the present invention on the expression of intestinal motility hormones secreted in the large intestine was confirmed. An ELISA kit (Cusabio Biotech Co., Ltd., Wuhan, China) was used to measure the expression of the intestinal motility hormones cholecystokinin (CCK), gastrin, and somatostatin (SS). 100 mg of colon tissue was weighed, pulverized by adding 1 ml of phosphate buffered saline (PBS, pH 7.2-7.4) stored on ice, centrifuged at 4°C for 5 minutes at a speed of 1,000 x g, and the supernatant was centrifuged. Obtained. Accordingly, after adding the three types of hormone antibodies (separately to each well) and incubating at 37°C for 1 hour, HRP-Streptavidin solution was added and further cultured at 37°C for 1 hour. did. Then, TMP One-Step Substrate Reagent was added and reacted at 37°C for 30 minutes, and then a stop solution was added to stop the reaction. Afterwards, the absorbance was measured at 450 nm using a Molecular Devices VERSA max Plate reader (Sunnyvale, CA, USA). The results are shown in Table 3 below.

CCK Gastrin SS No 1.0 1.0 1.0 Vehicle 0.4 0.2 0.5 MELo 0.7 0.4 0.7 MEHi 0.9 0.5 0.9

(Unit: cm, %)

As a result, as shown in Table 3 above, the concentration of three types of intestinal hormones decreased in the Vehicle group with impaired gastrointestinal motility, while it increased in a concentration-dependent manner in the MELo and MEHi groups administered the mulberry extract according to the present invention. Therefore, it was confirmed that the mulberry extract according to the present invention has the effect of restoring the decreased concentration of intestinal motility hormones due to decreased gastrointestinal motility.

2-2. Delayed gastric emptying effect induced by confinement stress

1) Delayed gastric emptying effect

To measure the effect of the mulberry extract (ME) of the present invention on inhibiting gastric emptying delay, an experiment was conducted using a rat model as follows.

The efficacy of the mulberry extract (ME) of the present invention on gastric emptying rate was compared using the test group. Water was administered as a control group (No), and Mosapride was administered as a positive control group.

7-week-old male Sprague-Dawley rats were purchased from Central Laboratory Animals, and after an acclimatization period of 1 week, healthy rats weighing 250 to 270 g were used in the experiment. The mulberry extracts MELo (200 mg/kg) and MEHi (400 mg/kg) prepared above and Mosapride 10 mg/kg as a positive control were orally administered once to rats that were fasted for 24 hours and water-deprived for 3 hours, and then administered for 60 days. Minutes later, 2 mL of semisolid test meal (30 g of feed mixed with 90 mL of 0.5% methyl cellulose) was forcibly orally administered using a disposable sonde. 30 minutes after forced ingestion of the semi-solid diet, the animal was anesthetized using CO ₂ and the stomach was removed through laparotomy. The cardia and pyloric regions of the extracted stomach were sutured and their weight was measured. After measuring the weight, an incision was made in the upper part of the stomach, all stomach contents were washed with distilled water, and the weight of the dried empty stomach was measured.

The results of repeating the same test three times were analyzed, and the average gastric emptying rate (GER) was calculated using Equation 2 below using the measured weight of the remaining semi-solid diet. The results are shown in the table below. It is shown in 4.

[Equation 2]

Gastric emptying, %) = [1 - (Weight of semi-solid food remaining in the stomach after drug administration / Weight of semi-solid food remaining in the stomach at 0 hours)] x 100

Above discharge rate (%, mean ± standard error) No water 13.28±3.16 Positive control group Mosapride (10mg/kg) 50.66±4.99 MELo ME (200mg/kg) 38.16±1.84 MEHi ME (400mg/kg) 46.25±3.52

(unit : %)

Referring to Table 4 above, it can be seen that the effect of inhibiting gastric emptying delay by the mulberry extract of the present invention is improved in a concentration-dependent manner.

Therefore, it was confirmed that the mulberry extract of the present invention can exhibit an effect of suppressing delayed gastric emptying by improving gastrointestinal function.

2) Recovery effect on appetite suppression induced by confinement stress

To measure the effect of mulberry extract on gastrointestinal transport capacity, an experiment was conducted as follows using a rat model.

7-week-old male Sprague-Dawley rats were purchased from Central Laboratory Animals, and after an acclimatization period of 1 week, healthy rats weighing 250 to 270 g were used in the experiment. To evaluate the effect on the ability to recover from appetite suppression, rats that had fasted for 20 hours and were water-deprived for 3 hours were confined in a rat correction frame for 6 hours to induce stress. Afterwards, 10 mg/kg, 200 mg/kg, and 400 mg/kg of mulberry extract and 3 mg/kg of the control substance Mosapride were administered orally once, and detention stress was additionally applied for 60 minutes. Vehicle was orally administered to normal rats and stress was not induced. After drug administration, pre-measured feed was given and feed intake was measured for 30 minutes. The experimental results are shown in Table 5 below. A 0.5% methylcellulose aqueous solution was used as the vehicle.

Feed intake (g) Normal group (No) 0.5% methylcellulose aqueous solution 4.50±0.85 control group 0.5% methylcellulose aqueous solution (stress induction) 1.90±0.95 Positive control group Mosapride (10mg/kg) 2.00 ±1.03 M.E. ME (10mg/kg) 2.10±1.09 MELo ME (200mg/kg) 2.88±0.99 MEHi ME (400mg/kg) 3.50±0.89

(Unit: g)

Referring to Table 5 above, it can be seen that the mulberry extract of the present invention has a superior improvement effect on reducing feed intake compared to Mosapride added to the positive control group, and that the effect is further improved as the mulberry extract concentration increases. there is.

3) Effect on delayed gastric emptying induced by detention stress

7-week-old male Sprague-Dawley rats were purchased from Central Laboratory Animals, and after an acclimatization period of 1 week, healthy rats weighing 250 to 270 g were used in the experiment. To evaluate the effect on gastric emptying rate, 30, 200, and 400 mg/kg of mulberry extract and 30 mg/kg of itopride as a positive control were administered to rats that had been water-deprived 3 hours before drug administration after fasting for 24 hours. 60 minutes after drug administration, free intake of 1.5 g of pre-measured feed was induced for 10 minutes, and then feed intake was measured. After free intake, they were detained in a correction frame for 90 minutes to induce stress. Stress-induced rats were killed using CO ₂ gas, the stomach was removed, the stomach contents were collected, and dried to calculate the gastric emptying rate. The experimental results are shown in Table 6 below.

Gastric emptying rate (%) Normal group (No) Vehicle 82.2±10.8 control group Vehicle (stress induction) 60.8±11.2 Positive control group Itopride (30mg/kg) 65.4±13.7 M.E. ME (30mg/kg) 66.2±10.1 MELo ME (200mg/kg) 72.6±11.5 MEHi ME (400mg/kg) 78.1±12.7

(unit : %)

Referring to Table 6 above, it can be seen that the gastric emptying rate is improved by the mulberry extract of the present invention. In other words, compared to the case of administering itopride, which is a positive control group, a more excellent effect of improving gastric emptying delay can be confirmed by administering the mulberry extract of the present invention.

[Experimental Example 3: Experiment on the effect of the composition of the present invention (MX1 to 9) on improving gastrointestinal function]

In order to demonstrate the effect of the composition of the present invention on improving gastrointestinal function, the same experiment as Experimental Example 2 was conducted, and only the extract was replaced with the composition of the present invention.

In addition, the above results show the comparative results for mulberry extract (MEHi) fixed at an index of 3, and the index was evaluated as a number between 1 and 10. The higher the number, the better the effect of improving gastrointestinal function, and the results are comprehensively shown in Table 7 below.

MX1 MX2 MX3 MX4 MX5 MX6 MX7 MX8 MX9 Effect of promoting bowel movement 3 3 4 4 6 7 9 9 8 intestinal motility
Hormone secretion promoting effect 3 4 3 4 6 8 9 9 7 Delayed gastric emptying effect 3 4 4 3 5 7 8 9 5 Effects of detention stress on delayed gastric emptying 3 4 3 4 6 8 9 9 7

(Unit: index)

Referring to Table 7 above, in the case of MX2 to 4, which contain Jeju briar extract (JE), Dalgae extract (DE), and Sanbigiga extract (SE) in addition to the mulberry extract (ME), which is a single extract, the mulberry extract (ME) It can be seen that it has a slightly improved effect of promoting intestinal motility, promoting secretion of intestinal motility hormones, and inhibiting delayed gastric emptying compared to the case containing only .

In addition, in the case of MX5 to MX9, which contain all the natural products of mulberry, Jeju wild rose, wild rose, and mountain birch, the effect was further improved. In particular, based on 100 parts by weight of mulberry extract, 30 to 50 parts by weight of Jeju wild rose extract, wild rose, It can be confirmed that MX6 to MX8 containing 30 to 50 parts by weight of the extract and 30 to 50 parts by weight of the spleen extract exhibit a better effect of improving gastrointestinal function.

[Experimental Example 4: Effect of improving palatability of the composition of the present invention]

Tea drinks containing each of the above composite compositions (MX1 to MX9) were prepared, and 40 adult men and women in their 20s to 50s were tasted and then evaluated for flavor and taste to evaluate preference with an index of 1 to 10. did. For relative evaluation, the MX1 (ME) of the present invention, extracted by immersion in water, was fixed to an index of 3 and evaluated as a relative index value. The results were synthesized and averaged, and then rounded to two decimal places to obtain a comprehensive result in Table 8 below. It is expressed as

MX1 MX2 MX3 MX4 MX5 MX6 MX7 MX8 MX9 taste 3.0 3.5 4.0 3.5 7.0 8.5 9.0 9.0 8.0 incense 3.0 4.0 4.0 4.0 7.5 8.5 9.0 9.0 7.5 Synthesis
preference 3.0 3.8 4.0 3.8 7.3 8.5 9.0 9.0 7.8

(Unit: index)

Referring to Table 8, compared to MX1 containing only the mulberry extract (ME) of the present invention, MX2 to MX4 each additionally contain Jeju wild rose extract (JE), Dalgae extract (DE), and Sanbigi extract (SE). In this case, you can see that preference increases.

In the case of MX5 to MX9, which are contained in the form of a complex extract rather than as a single extract, the effect is further improved. This is because the unique aroma of a single natural product is alleviated by using a mixture of natural extracts, and the effect is improved through the harmony of taste and aroma. This means that it can show excellent preference.

In particular, for 100 parts by weight of mulberry extract (ME), which is the preferred weight part, 30 to 50 parts by weight of Jeju starberry extract (JE), 30 to 50 parts by weight of Dalgae extract (DE), and 30 to 50 parts by weight of Sanbigiani extract (SE) It can be seen that when mixed by volume, the overall preference for taste and aroma is the best, making it possible to provide a composition with high preference.

Therefore, the composition containing the mixed composition has no problem of side effects by containing natural extracts, has an effect of improving gastrointestinal tract function, and has excellent taste and aroma evaluation, so it can be used as a food composition, health functional food, or pharmaceutical composition with high functionality and preference. It was confirmed that provision of was possible.

Although the preferred embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements made by those skilled in the art using the basic concept of the present invention defined in the following claims are also possible. falls within the scope of rights.

Claims (7)

Contains mulberry extract, Jeju briar extract, Dalgae extract, and wild birch extract as active ingredients.
Composition for improving gastrointestinal function. According to clause 1,
The improvement in gastrointestinal function occurs through activation of gastric motility.
Composition for improving gastrointestinal function. According to clause 1,
The composition is suitable for treating gastroesophageal reflux disease, functional dyspepsia, A group consisting of gastrointestinal paralysis, vomiting, diabetic gastrointestinal motility disorder, chemotherapy-induced gastrointestinal motility disorder, ileus due to digestive tract motility disorder, postoperative ileus, gastrointestinal dysfunction, gastrointestinal motility disorder due to myotonic dystrophy, infantile colic, and constipation. Showing an improvement effect on one or more symptoms selected from
Composition for improving gastrointestinal function. According to clause 1,
The extract is extracted using an extraction solvent selected from the group consisting of water, C ₁ to C ₆ lower alcohols, and mixtures thereof.
Composition for improving gastrointestinal function. Comprising a composition according to any one of claims 1 to 4
Food composition for improving gastrointestinal function. Comprising a composition according to any one of claims 1 to 4
Health functional food for improving gastrointestinal function. Comprising a composition according to any one of claims 1 to 4
It is a pharmaceutical composition for preventing or treating symptoms caused by decreased gastrointestinal function,
Symptoms due to the above-mentioned decline in gastrointestinal function include gastroesophageal reflux disease, functional dyspepsia, gastrointestinal paralysis, vomiting, diabetic gastrointestinal motility disorder, gastrointestinal motility disorder due to chemotherapy, ileus due to digestive tract motility disorder, postoperative ileus, and gastrointestinal dysfunction. , one or more symptoms selected from the group consisting of gastrointestinal motility disorder due to myotonic dystrophy, infantile colic, and constipation.
Pharmaceutical composition for preventing or treating symptoms caused by decreased gastrointestinal function.