KR20120090003A - Composition for improvement, treatment and prevention of gastrointestinal motility disorders - Google Patents

Abstract

PURPOSE: A medicinal composition containing Zanthoxylum piperitum DC and Citrus aurantium extract is provided to promote gastrointestinal motility and to prevent and treat gastrointestinal motility disorder. CONSTITUTION: A composition for preventing or treating gastrointestinal motility disorders contains Zanthoxylum piperitum DC and Citrus aurantium extract as an active ingredient. The composition is a pharmaceutical or food composition. The extract is prepared using water, C1-C4 alcohol, or a mixture solvent thereof. A food, health supplementary food, or health functional food for treating functional gastrointestinal motility disorders contains the extract as an active ingredient. An oral formulation for preventing or treating gastrointestinal motility disorder contains the crude drug extract of Zanthoxylum piperitum DC and Citrus aurantium extract as an active ingredient.

Description

Composition for improvement, treatment and prevention of gastrointestinal motility disorders}

The present invention relates to herbal compositions for improving, treating and preventing diseases of the gastrointestinal motility disorders.

Gastrointestinal motility disorders include surgery including gastroesophageal reflux disease, functional dyspepsia, irritable colitis, gastrointestinal palsy, vomiting, diabetic gastrointestinal disorder, gastrointestinal motility due to chemotherapy, bowel obstruction due to gastrointestinal motility disorder, postoperative ileus It refers to a pathological condition in which normal gastrointestinal motility is impaired, inhibited or impaired, such as gastrointestinal dysfunction, gastrointestinal dyskinesia due to myotonic dystrophy and constipation.

Gastrointestinal motility disorder is a disease with a high prevalence in developed countries as well as in Korea. Gastroesophageal reflux disease, functional dyspepsia, irritable bowel disease, gastrointestinal palsy, vomiting, postoperative intestinal obstruction and constipation. And functional symptoms related to gastrointestinal peristalsis rather than biochemical lesions.

Functional dyspepsia is confined to the upper abdomen and presents symptoms such as pain and discomfort consistently and repeatedly. Irritable bowel disease can cause constipation or diarrhea, with constipation in the lower abdomen, or alternating constipation and diarrhea every few days. These diseases are not easy to treat because they are diagnosed by various gastrointestinal symptoms without obvious organic lesions, and most of the symptoms are repeatedly improved and worsened and are affected by food and stress. Postoperative intestinal obstruction is a condition that inhibits the gastrointestinal motility that occurs clinically after open surgery. Representative symptoms include bloating, stool, incapacitation, decreased intestinal tract, and abdominal distension. In general, gastrointestinal motility is restored normally within 2-3 days after open surgery, often leading to paralytic ileus, which does not heal naturally and continues for more than 3 days. The pathogenesis of intestinal obstruction has been suggested to reduce acetylcholine secretion due to excessive stimulation of adrenaline nerve following laparotomy and inflammatory reactions induced during surgery, but the exact pathogenesis is unknown. In addition, morphine, which has been widely used as an analgesic agent to alleviate pain caused by cancer, has a high frequency of strongly inhibiting gastrointestinal motility of patients after administration and has side effects of inducing chronic constipation. Chronic constipation due to morphine administration is one of the major factors that reduce the quality of life of patients.

These gastrointestinal motility disorders are often difficult to know the exact pathogenesis, but the recent serotonin (5-HT) receptors are distributed in the gastrointestinal tract, especially intestinal endocrine cells, focusing on the central role in peristalsis of the gastrointestinal tract, The development of new gastrointestinal motility promoters is centered around serotonin-modulating drugs. In particular, 5-HT ₃ antagonists, such as granitone and ondansetron, are anti-nausea agents and treatments to reduce visceral hypersensitivity. 5-HT ₄ agonists promote gastrointestinal peristalsis by increasing gastric contractility and propulsion pressure. It is being developed as a treatment for constipation including functional dyspepsia, and the 5-HT _1P agonist has been developed as a functional dyspepsia treatment because it has a relaxation effect at the bottom of the crisis. However, most 5-HT ₃ receptor antagonists, such as ondansetron, ameliorate the symptoms of delayed gastrointestinal fasting in rats, but are not evident in other species, including humans. Cisapride, a 5-HT ₄ agonist and a 5-HT ₃ receptor antagonist, was one of the gastrointestinal motility promoters that was effectively used to treat functional dyspepsia, but was discontinued due to the high side effects of pregnant women and those with cardiovascular disease. . Meanwhile, as other 5-HT ₄ receptor agonists, tegaserod, prucalopride, and the like are in clinical trials, and target lower digestive system abnormalities. On the other hand, for the postoperative gastrointestinal dysfunction, especially postoperative ileus, there is a known treatment for symptomatic relief to remove gastrointestinal secretions by nasal guards when it occurs, and cisapride has been frequently used as a drug. It is true. Recently, a synthetic drug, alvimopan (Entereg ^® ), was approved by the US FDA in relation to postoperative gastrointestinal function recovery (2008). However, there is an urgent need to develop safe drugs derived from natural products with reduced toxicity and side effects for use in gastrointestinal dysfunction.

Fruits are unripe fruits of Citrus aurantium L or Poncirus trifoliata Rafin or Citrus trifoliata. Fruits include alkaloids such as flavonoid glycosides such as poncirin, hesperidin, rhoifolin, narifin, neohesperidin, neohesperidin, and skimmianine, and pinene, It is known to contain essential oils such as myrcene (myrcene), limonene (limonene), camphene (camphene), etc., and has an anti-allergic effect. Although it may be used for postoperative ileus treatment (Korean Patent No. 10-635658), the amount used for post operative ileus treatment as described in Experimental Example 6 and Experimental Example 7 above is 500mg / 5ml / kg and 1g / With a large capacity of 5ml / kg, there are some aspects that are difficult to be utilized in actual clinical practice.

Sancho is a bark of the deciduous broad-leaved tree, Zanthoxylum piperitum, or its similar plant, Zanthoxylum bungeanum and Zanthoxylum schinifolium, belonging to the genus Rutanacea. It is called flower, candle, seaweed, weed and the like. The acid component contains acid amides Sansul I-IV and essential oils include citronellal, 1, 8-cineol, dipentane, α-terpineol, etc. (xanthoxylol) has been reported separately, and it is known for its sanitation, antibacterial and insecticidal effects. It is used as an antidote for intestinal parasite control and carp poison.

However, none of the prior art teaches or discloses synergistic gastrointestinal function synergistic effects of the combination of the fruiting and sancho.

The present inventors conducted a test for confirming the effect on the receptors related to gastrointestinal motility for various combinations of herbal medicines to develop a herbal composition exhibiting the effect of treating and improving gastrointestinal dysfunction. The present invention has been completed by confirming that it can be effectively used for diseases of the gastrointestinal motility disorder by showing selective and excellent effects on receptors related to.

Korean Patent No. 10-635658

It is an object of the present invention to provide an herbal composition that is free of excellent gastrointestinal function-improving effects and side effects that can be used for the prevention, improvement or treatment of gastrointestinal motility disorders.

In order to achieve the above object, the present invention provides a composition for improving, treating or preventing diseases of the gastrointestinal motility disorders containing the extract of Sancho and fruit as active ingredients.

Meanwhile, the composition of the present invention is a pharmaceutical composition or a food composition.

In another aspect, the present invention provides a functional gastrointestinal motility disorders food, health supplements or health functional foods containing an extract of Sancho and fruit fruit as an active ingredient.

The present invention also provides oral preparations for the improvement, treatment or prevention of gastrointestinal motility disorders, which contains an extract of Sancho and perilla as active ingredients.

The present invention also provides the use of Sancho and perilla extract for the preparation of a medicament for the amelioration or treatment of gastrointestinal motility disorders.

The present invention also provides a method for ameliorating or treating gastrointestinal motility disorders, comprising administering to the mammal, including a human body, a therapeutically effective amount of acid and fruit extracts.

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

The present invention has been studied for the development of a good herbal composition with no side effects for promoting gastrointestinal motility, the results show that the gastrointestinal motility promoting effect is very excellent when using a combination of sancho and fruit fat which is known to have little side effects and is widely known as a herbal medicine Revealed. Therefore, the combination of the herb and the fruit can be used as an active ingredient of the pharmaceutical composition for preventing or treating gastrointestinal motility disorders and the food, dietary supplement or functional food composition for improving functional gastrointestinal motility disorders.

Hereinafter, the pharmaceutical composition and the food composition according to the present invention are collectively referred to as a herbal composition.

In the herbal composition, the acid and fruit are not particularly limited in combination ratio, but preferably, the acid: fruit may be included in a weight ratio of 1: 0.001 to 100, more preferably 1: 0.01 to 70. Sancho and lychee, even in small amounts, when used in combination or in combination with one another, show a synergistic effect on gastrointestinal tract function as compared to the case where they are used alone.

On the other hand, the herbal medicine constituting the herbal composition of the present invention obviously corresponds to the same in the art and includes all the herbal medicines, which are considered to be used for the same or similar purposes as the preventive and therapeutic purposes of the present invention.

Specifically, in the present invention, Zanthoxyli fructus is Zanthoxylum piperitum, its plant is Zanthoxylum bungeanum, Zanthoxylum schinifolium, Zanthoxylum armatum var subtrifoliatum or Royal Bark (Zanthoxylum coreanum) refers to the skin.

In the present invention, the fruit room (Ponciri Fructus) refers to the immature of the domestic fruit room (Poncirus trifoliate), Chinese fruit room (Citrus aurantium), or the same plant as the citrus grandis (Citrus grandis).

The herbal and fruit extracts of the herbal composition of the present invention can be obtained by extracting each herbal medicine separately or together with water, C ₁ to C ₄ alcohol, or a mixed solvent thereof. C ₁ to C ₄ alcohols can be exemplified by methanol, ethanol, propanol and butanol, with ethanol being most preferred. The solvent may be used in an amount of 1 to 50 times, preferably about 3 to 30 times the weight of the herbal medicine.

The acid and fruit solvent extract may be prepared by any extraction method known to those skilled in the art of herbal extraction, but from about 5 to 100 ℃, preferably from 10 to 80 ℃, more preferably from about 1 to 100 at room temperature It may be prepared by stirring extraction, boiling water extraction, cold extraction, reflux cooling extraction or ultrasonic extraction, preferably cold extraction for a period of time, preferably 8 to 72 hours. The obtained extract can be filtered, concentrated under reduced pressure or dried to obtain the final extract.

The herbal composition comprising a combination of the herbaceous acid and the fat chamber of the present invention is effective in preventing, ameliorating or treating gastrointestinal motility disorders, and in particular, exhibits an excellent effect on recovery of postoperative lowered gastrointestinal function including postoperative ileus.

In addition, the herbal composition comprising a combination of acid and fruit of the present invention shows a significantly superior intestinal transfer rate compared to the case of administering the main component of the herb and fruit, respectively, these two herbs prevent and treat gastrointestinal dyskinesia It has been shown to exhibit synergy in.

In addition, in the present invention, the herbaceous and fruit extracts have effects on 5-HT ₄ receptors, effects on dopamine D2 receptors, effects on muscarinic receptors, effects on motilin receptors, effects on adrenergic α2A receptors, It was shown to show an effect on the 5-HT _1A receptor. As described above, the herbal composition comprising the sancho and the fruit chamber of the present invention modulates the action of various receptors affecting gastrointestinal motility, such as 5-HT _4, and is very excellent in treating gastrointestinal motility disorders such as functional dyspepsia by a complex mechanism. Effect. In particular, the herbal composition comprising the sancho and the fruit chamber of the present invention exhibited an excellent postoperative gastrointestinal function improvement over the normal group without surgery by this synergistic effect. Therefore, by quickly administering the herbal composition of the present invention, the gastrointestinal function, which has been degraded due to surgery, can be quickly restored, thereby enabling a quick discharge.

As used herein, “gastrointestinal motility disorder” refers to a disorder caused by a condition in which normal gastrointestinal motility is impaired, inhibited or impaired. These gastrointestinal motility disorders include gastroesophageal reflux disease, functional dyspepsia, irritable colitis, gastrointestinal palsy, vomiting, diabetic gastrointestinal motility, gastrointestinal motility due to chemotherapy, bowel obstruction due to gastrointestinal motility, and postoperative ileus Gastrointestinal dysfunction and impairment after surgery, gastrointestinal dyskinesia or constipation due to myotonic dystrophy, preferably gastroesophageal reflux disease, functional dyspepsia, irritable colitis, postoperative gastrointestinal dysfunction and constipation, but It is not limited. For example, it can be improved or treated by modulating the action of various receptors that affect gastrointestinal motility: 5-HT ₄ receptor, dopamine D2 receptor, muscarinic receptor, motilin receptor, adrenergic α2A receptor and 5-HT _1A receptor. Morbidity is included in the gastrointestinal motility disorders defined herein.

As defined herein, “postoperative gastrointestinal dysfunction” refers to a condition in which gastrointestinal function is impaired or degraded temporarily due to surgery, and includes postoperative ileus. Postoperative intestinal obstruction is clinically impaired in the gastrointestinal motility function after laparotomy. The rapid recovery of gastrointestinal function after surgery is a decisive factor in the early discharge period. In general, gastrointestinal motility is restored normally within 2-3 days after open surgery, often leading to paralytic ileus, which does not heal naturally and continues for more than 3 days. Surgery includes laparoscopic or arthroscopy and other robotic operations, as well as open surgery, and includes surgery of the uterus and other organs, as well as surgery for small bowel disease.

The herbal composition according to the present invention contains herbal medicines which have been proven to be safe while being used for a very long time, and thus have little toxicity and side effects, so that they can be used for a long time for the purpose of preventing gastrointestinal motility disorders, or when used for long-term treatment.

Pharmaceutical compositions according to one aspect of the invention may contain a pharmaceutically acceptable carrier, excipient and / or diluent.

The pharmaceutical composition may appropriately reduce the mixing ratio of the constituent herbs within the range that effectively maintains the therapeutic or prophylactic effect of gastrointestinal motility disorder disease, 0.1 to the total weight of the composition of the herbal components constituting the composition according to the present invention To 99 wt%.

Carriers, excipients and diluents that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.

The pharmaceutical compositions of the present invention may also be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, external preparations, suppositories, and sterile injectable solutions according to conventional methods. . More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid form forms at least one excipient such as starch, calcium carbonate, sucrose or lactose. (lactose), gelatin can be prepared by mixing. In addition to simple excipients, lubricants such as magnesium stearate talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

In a preferred embodiment of the present invention, in particular, it shows a good dissolution rate in the gastrointestinal tract can significantly increase the bioavailability, can block the odor peculiar to the herbal medicine can eliminate the discomfort when taking, and the size is reduced to facilitate the patient Preferred formulations are to be taken. For example, when formulated into tablets and capsules, magnesium metasilicate, calcium phosphate, microcrystalline cellulose, povidone, crospovidone, magnesium stearate, etc. may be included as inert ingredients, thereby increasing bioavailability and reducing the size of the preparation. have. Tablets and capsules use microcrystalline cellulose, lactose, magnesium metasilicate, calcium phosphate, povidone as binder, crospovidone as disintegrant, and magnesium stearate as lubricant, to block the unique flavor of natural products, It disintegrates rapidly and can be formulated for high bioavailability, small final tablets and capsules for ease of taking. When formulated as a suspension, it is possible to mask the bitterness peculiar to herbal medicines by additionally using a sweetener such as licorice flour or taumartin or an adsorbent such as bentonite or kaolin. In addition, by coating the tablet with a coating such as Eudragit E100, Opadry ^® , Acryl-EZE ^® can further mask the bitter taste peculiar to herbal medicines.

The pharmaceutical composition of the present invention can be administered to various mammals by various routes, for example, orally, parenterally, such as subcutaneous injection, intravenous injection, intramuscular injection, intrasternal injection or infusion, or rectally. Can be.

In order to obtain a prophylactic or therapeutic effect of gastrointestinal motility disorders, the pharmaceutical composition of the present invention may be administered in an amount of 0.1 mg to 100 mg per 1 kg of body weight per day based on the dry powder of the solvent extract. It can be divided into several doses. Dosage may vary depending on the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, severity of disease, and the like.

In addition, a food composition according to another aspect of the present invention may include a food acceptable carrier and / or additives. The food composition of the present invention may be formulated as a conventional functional gastrointestinal motility disorder foods, dietary supplements or dietary supplements known in the art.

In the present invention, the health supplement or health functional food is a powder, granules, tablets, pills, capsules, suspensions, emulsions, syrups, emulsifiers, liquids, extracts, gums, using raw materials or ingredients having useful functions for the human body. It may be prepared in the form of tea, jelly or a beverage.

The food composition can be appropriately added to or lowered the mixing ratio of the constituent herbs within the range that effectively maintains the improvement and / or prophylactic effect of the gastrointestinal motility disorder disease, the herbal components constituting the composition according to the present invention to the total weight of the composition 0.1 to 99% by weight, preferably 1 to 90% by weight.

The herbal composition according to the present invention may be to be administered at the same time as the herbal and fruit fat contained as an active ingredient, a predetermined interval within a range that can exhibit the effect of preventing, improving or treating the gastrointestinal dyskinesia of the composition It may be administered sequentially. If the herbal and fruit compartment combinations are to be administered at predetermined intervals, each active ingredient may be formulated in a separate, separate formulation. When it is desired to simultaneously administer a combination of Sancho and Ji-sil, they may be formulated in a uniformly mixed form in one formulation, or may be formulated in separate formulations and then simultaneously administered.

The composition according to the present invention comprises a combination of fat chamber and sancho, thereby significantly improving gastrointestinal motility, in particular postoperative ileus. Accordingly, the composition exhibits a superior effect on the prevention, improvement or treatment of diseases of the gastrointestinal motility disorder, and is composed of herbal medicines that have been used for a long time, and thus there is little concern about side effects or toxicity.

Hereinafter, the present invention will be described in more detail through Examples and Experimental Examples. However, the present invention is not limited by the following examples.

< Comparative example  1> Preparation of Single Herb Extract of Fruits and Sancho

1-1 Preparation of Fruits and Vegetables Extract

The dried fruit room was purchased at Gyeongdong Market (Seoul) to remove impurities and used for experiments. To 100 g of dried cellars, 800 ml of 70%, 80%, and 90% ethanol aqueous solution was added and extracted at room temperature for 24 hours, and the resultant was concentrated under reduced pressure at 55-65 ° C. and dried, followed by drying for each solvent, namely 70%, 80 %, And 90% ethanol soluble fate extracts (hereinafter referred to as P70E, P80E and P90E) were obtained (see Table 1).

Preparation of 1-2 Sancho Extract

The dried Sancho was purchased from Gyeongdong Market (Seoul) and the impurities were removed and used for the experiment. 1750ml of 30%, 50%, 70%, 90% ethanol aqueous solution was added to 250 g of dried acidic acid, extracted at room temperature for 24 hours, and concentrated under reduced pressure at 55-65 ° C, followed by drying. %, 50%, 70%, and 90% ethanol soluble acid herb extracts (hereinafter referred to as Z30E, Z50E, Z70E and Z90E) were obtained (see Table 2).

<Example 1> Preparation of herbal extracts of the fruit and sancho combination of the present invention

1-1. Preparation of Acid and Fruit Extracts of the Present Invention

The fruit extract obtained by extracting with 70% ethanol in Comparative Example 1-1 and the extract extracted with 50% ethanol in Comparative Example 1-2, based on the weight of the extract, 1: 1, 1 Mix with weight ratios of 1: 1.5, 1: 3, 1: 4, 1: 9 and 1:12, and the mixture ratio is 1: 1, 1: 1.5, 1: 3, 1: 4, 1: 9 and 1:12 The fruit extract and the herb extract of the present invention (hereinafter referred to as PZ511, PZ5115, PZ513, PZ514, PZ519, and PZ5112) were prepared and used in the following experimental examples. In addition, the extract was extracted with 70% ethanol in Comparative Example 1-1. The group to which the only fruit extract obtained and the extract obtained by extracting with 50% ethanol in Comparative Example 1-2 was used as a comparative group of Experimental Example 1 below.

1-2 Preparation of Acid and Fruit Extracts of the Present Invention

The fruit extract obtained by extracting with 70% ethanol in Comparative Example 1-1 and the extract extracted with 30% ethanol in Comparative Example 1-2, based on the weight of the extract, 1: 1, 1 Mixtures of 1: 4, 1: 9, 1:12 by weight, and the blending ratio of 1: 1, 1: 4, 1: 9, 1:12, and fruit extracts (hereinafter referred to as PZ311, PZ314, PZ319, PZ3112) Was obtained and used in the following experimental example.

Experimental Example 1 Postoperative Gastrointestinal Function Recovery Effect

In order to determine the effect of the herbal composition obtained in the above example on postoperative ileus, an experiment was performed according to the method disclosed in the literature as follows (Yohei Tokita et al. J Pharmacol Sci . 2007).

In this experimental example, the effect of the extract according to the present invention on the postoperative gastrointestinal function recovery as a method of measuring the intestinal transport rate of the rats that induced postoperative ileus.

200-240g male SD rats (Orient, Republic of Korea) were bred for 1 week while maintaining a light / dark cycle with a temperature of 22-24 ° C and a humidity of 50-70%. Standard diets and drinking water were allowed to be consumed freely. The animals were fasted for 24 hours, and then surgery was performed on the rats except the normal group to induce postoperative ileus. The surgery was anesthesia with isofluorane (ASJ9AC.Abbott Lab) and an incision about 2 cm in the abdomen was made. The small intestine and the cecum were carefully taken out of the body and massaged with a finger for 10 minutes from the cecum to the duodenum to stimulate. After the massage, the small intestine and cecum were carefully inserted again through the incision in the abdomen. The incision site was closed. After 3 hours and 30 minutes of operation, the fruit extract of the present invention prepared in Example 1 and the extract of each of the fruit extracts and the fruit extract were separately orally administered at a dose of 5 ml / kg as test drugs. The test drug was suspended in 5% Pluronic F-68 (P1300, SIGMA), and the negative control group was orally administered with the same dose of 5% Pluronic F-68 without the test drug. The normal group underwent the operation of anesthesia as the rat without any surgery, and then orally administered 5% Fluronic F-68 at the same dose as the test drug group without the test drug.

After 30 minutes of administration, Evans Blue (E2129, SIGMA, 50 mg / ml) dissolved in physiological saline was added to the normal group, the negative control group, and the control group of each of the fruiting and sancho groups as the normal group, the negative control group, and the combination of the fruiting and sancho combination administration groups of the present invention. 0.2 ml oral administration. All rats were euthanized by cervical distal bone 20 minutes after Evans Blue administration and small intestine was extracted. The collected small intestine was measured by measuring the total length and the moving distance of Evans Blue and calculating the intestinal transfer rate (ITR) according to Equation 2 below, and the results are shown in Table 3 below.

[Equation 2]

ITR (%) = Evans Blue Travel Distance / Total Collection Length

Statistical analysis was performed using Prism4 (GraphPad) to analyze the significance by Unpaired t-test, and the efficacy of pharmacological effects of the group treated with the herbicidal and ventricular combinations of the present invention was compared with that of the negative control group ( ^* P <0.05, ^** P < 0.01, ^*** P <0.001).

As can be seen in the above table, the negative control group significantly reduced the gastrointestinal transport rate compared to the normal group, and when the combination of the fruiting and sancho in accordance with the present invention was administered, a significantly superior gastrointestinal tract near or above the normal group was found. The feed rate is shown. In addition, it showed a significantly superior synergistic effect compared to the single administration group of the sancho and fruit chambers.

<Experimental Example 2>

Effect of Morphine Administration on Gastrointestinal Function Improvement in Gastrointestinal Movement Inhibition Model

In order to investigate the effects of the herbal compositions obtained in the above examples on the gastrointestinal motility improvement in the gastrointestinal motility inhibition model induced by morphine administration, experiments were performed according to the method disclosed in the literature as follows (Hiroyuki F et al. Brain research . 2006).

200-240g male Sprague-Dawley rats (Orient, Republic of Korea) temperature 22-24 ℃, humidity was 50-70% to maintain a light and dark cycle to breed for 1 week. Standard diets and drinking water were allowed to be consumed freely. After fasting the animals for 24 hours, 3 mg / kg of morphine (morphine sulfate hydrate (Lot No: N008001, BCWorld Pharm.) Was subcutaneously administered to rats other than the normal group to induce gastrointestinal motility inhibition. After 30 minutes, the acid and fruit extract of the present invention prepared in Example 1-1 (mixing ratio 1: 4) and the acid and fruit extract of the present invention prepared in Example 1-2 (mixing ratio 1:12) The single extracts of each of the larvae and the fruit were orally administered at a dose of 5 ml / kg, respectively, as the test drug, which was suspended in 5% Pluronic F-68 and used in the negative control group without the test drug. Oral administration of 5% Pluronic F-68 of the normal group was not administered morphine, the normal group was orally administered 5% Fluronic F-68 of the same dose as the test drug administration group without the test drug.

After 30 minutes of administration, 0.2 ml (50 mg / ml) of Evans Blue dissolved in physiological saline was orally administered to the normal group, the negative control group, the fruit extract alone group, the acid extract extract group, and the acid and extract extract groups of the present invention, respectively. . All rats were euthanized by cervical distal bone 20 minutes after Evans Blue administration and small intestine was extracted. The collected small intestine was measured by measuring the total length and the moving distance of Evans blue, and then statistically processed after calculating the intestinal transport rate (ITR) according to Equation 3 below, and the results are shown in Table 4 below.

&Quot; (3) &quot;

ITR (%) = Evans Blue Travel / Total Collection Length

Statistical analysis was performed using the Unpaired t-test using Prism4 (GraphPad), and the efficacy of the medicinal effects of the Sancho and fruit extracts of the present invention was compared with that of the negative control group ( ^* P <0.05, ^** P < 0.01, ^*** P <0.001).

As can be seen in the above table, the negative control group significantly reduced the gastrointestinal transport rate compared to the normal group, and when the combination of the fruiting and sancho in accordance with the present invention was administered, a significantly superior gastrointestinal tract near or above the normal group was found. The feed rate is shown. In addition, it showed a significantly superior synergistic effect compared to the single administration group of the sancho and fruit chambers.

<Experimental Example 3>

Glycokinetic Movement Receptors of the Herbal Medicine Composition of the Present Invention In vitro  Bonding test

A study was conducted to find out which mechanism of action of the chambers of the present invention and the herbaceous acid has an effect on the gastrointestinal motility. Specifically, the herbaceous acid and chile extracts prepared in Example 1-2 were mixed in a weight ratio of 1:12 weight of acetic acid: fruiting; PZ3112) containing the herbal composition at a concentration of 0.1, 1, 10, 100, 1,000 μg / ml In preparation, radioligand binding assays were performed on receptors such as 5-HT4, Dopamine D2, Muscarinic M1, M2, M3, Motilin, Adrenergic α2A, 5-HT1A, which affect gastrointestinal motility. Commissioned to Ricerca Biosciences in Taipei, Taiwan).

IC50 and inhibition constants (Ki) values for each target receptor were measured and shown in Table 5 below. IC50 values were derived using a non-linear, least squares regression analysis method using MathIQ ^™ (ID Business Solutions Ltd., UK). The inhibitory constant (Ki) values were derived using the Cheng Prusoff equation method. (Cheng, Y., Prusoff, WH, Biochem. Pharmacol. 22: 3099-3108, 1973).

As can be seen from the results below, the fruit extract of the fruit and the herb combination of the present invention is 5-HT4, dopamine D2, muscarinic M1, M2, M3, motilin, adrenergic α2A, 5-HT1A, etc. that affect the gastrointestinal motility It has been shown to work in combination with various receptors. Specifically, the binding affinity of the 5-HT4 receptor, the dopamine D2 receptor, the muscarinic receptors, the motilin receptor, the adrenergic α2A receptor, and the 5-HT1A receptor was shown in Table 5.

Hereinafter, an example of the preparation of the composition containing the mixed herbal extract of the present invention will be described, but the present invention is not intended to be limited thereto, but is intended to be described in detail.

Formulation example  1. Tablets prepared by dry granulation method

30 g of solid fat extract and 120 g of solid acetic acid extract are mixed with 180 g of microcrystalline cellulose type 12, 40 g of lactose, and then again mixed with 10 g of silicon dioxide, 5 g of copovidone, and 2.5 g of magnesium stearate, followed by granulation using a slugging method. I was overlooked by hope. The sieved granules were mixed with 10 g of crospovidone and 2.5 g of magnesium stearate, and then compressed into tablets.

Formulation example  2. Tablets prepared by the wet granulation method (fluid granulation drying)

30 g of solid fat extract and 120 g of solid acetic acid extract were mixed with 200 g of microcrystalline cellulose type 12 and 25 g of low-substituted hydroxypropyl cellulose, and 10 g of povidone was dissolved in purified water and spray-dried to the above mixture using a fluidized bed granulator. 10 g of crospovidone and 5 g of magnesium stearate were mixed with the dried mixture, and then compressed into tablets.

Formulation example  3. Tablets prepared by wet granulation method using solution

30 g of solid fat extract, 120 g of solid acid extract, and 20 g of povidone were dispersed in 50% ethanol, and then wet granules were made by adsorbing the solution to a mixture of 74 g of microcrystalline cellulose, 140 g of lactose, 10 g of pregelatinized starch, and 80 g of silicon dioxide. The granules were dried, sieved through No. 18, mixed with 20 g of crospovidone and 6 g of magnesium stearate, and then compressed into tablets.

Formulation example  4. Fruit room  Sancho extract Soft X  Tablets prepared by the wet granulation method using a solution containing

After dispersing 120 g of dried fruit extract extract, 30 g of acid extract extract extract, and 14 g of povidone in ethanol, wet granules were prepared by adsorbing the solution to a mixture of 47 g of microcrystalline cellulose, 17 g of lactose, 46 g of pregelatinized starch, and 100 g of silicon dioxide. The granules were dried, sieved through No. 18, mixed with 20 g of crospovidone and 6 g of magnesium stearate, and then compressed into tablets.

Formulation example  5. Fruit room  Sancho extract Soft X  Containing solution Magnesium silicate and aluminate  Tablets prepared by wet granulation method by adsorption on calcium phosphate

120 g of fruit extract extract soft extract extract, 30 g of acid extract extract extract, and 14 g of hydroxypropyl cellulose were dispersed in ethanol, and the solution was adsorbed to a mixture of 20 g of microcrystalline cellulose, 60 g of magnesium aluminate silicate, and 30 g of calcium phosphate to make wet granules. . The granules were dried, sieved through No. 18, mixed with 20 g of crospovidone and 6 g of magnesium stearate, and then compressed into tablets.

Formulation example  6. Fruit room  Sancho extract Soft X In Magnesium Aluminate  Tablets prepared by adsorption by wet granulation

After dispersing 120 g of fruit extract soft extract extract, 10 g of acid extract extract soft extract extract, and 9 g of povidone, 10 g of microcrystalline cellulose and 40 g of magnesium aluminate silicate were adsorbed to prepare a wet granule. The granules were dried, sieved through No. 18, and then mixed with 8 g of crospovidone and 3 g of magnesium stearate, and then compressed into tablets.

Claims (11)

A composition for improving, treating, or preventing gastrointestinal motility disorders, which contains an extract of Sancho and fruit juice as an active ingredient. The composition of claim 1, wherein the composition is a pharmaceutical composition or a food composition. The composition of claim 1, wherein the vinegar is a bark of Zanthoxylum piperitum, Zanthoxylum bungeanum, Zanthoxylum schinifolium, Zanthoxylum armatum var subtrifoliatum, or Zanthoxylum coreanum. . According to claim 1, wherein the acid and fruit extract is extracted with water, C ₁ to C ₄ alcohol or a mixed solvent thereof. According to claim 1, wherein the acid and fruit extract is extracted with water, C ₁ to C ₄ alcohol or a mixed solvent thereof. According to claim 1, wherein the gastrointestinal dyskinesia is gastroesophageal reflux disease, functional dyspepsia, irritable colitis, gastrointestinal palsy, vomiting, diabetic gastrointestinal dyskinesia, gastrointestinal dyskinesia due to chemotherapy, bowel obstruction due to gastrointestinal dyskinesia, A composition selected from the group consisting of postoperative intestinal obstruction, postoperative gastrointestinal dysfunction, gastrointestinal dyskinesia due to myotonic dystrophy and constipation. The composition of claim 6, wherein the gastrointestinal dyskinesia is postoperative ileus or postoperative gastrointestinal dysfunction. Food, dietary supplement or functional food for the improvement of functional gastrointestinal motility, containing the herb and fruit extract as an active ingredient. An oral preparation for the improvement, treatment or prevention of gastrointestinal motility disorders, comprising the herbal extracts of the extracts of the herbaceous and fruiting according to any one of claims 1 to 5 as an active ingredient. 10. The oral preparation of claim 9, which is a tablet comprising fruit and acid extract and magnesium aluminate silicate. The oral preparation according to claim 10, wherein the fruit and the extract of the acetic acid extract are prepared by a wet granulation method by adsorbing magnesium metasilicate aluminate on magnesium metasilicate.