KR20050008949A - The fraction extracted from herbal medicine and improving gastrointestinal motor function - Google Patents

Abstract

PURPOSE: Provided is a fraction extracted from the herbal medicine including Ponciruc trifoliata rafin, Fraxinus rhynchophylla Hance or their mixture using one of water, alcohol and alcohol solution. Therefore, it improves gastrointestinal motor function. CONSTITUTION: The fraction for improving gastrointestinal motor function is characterized by extracting Ponciruc trifoliata rafin, Fraxinus rhynchophylla Hance or their mixture with one solvent selected from the group consisting of water, alcohol and alcohol solution, wherein the alcohol is methanol or ethanol; the weight ratio of Ponciruc trifoliata rafin to Fraxinus rhynchophylla Hance is 1:0.5-4. A pharmaceutical preparation for improving gastrointestinal motor function is characterized by containing the fraction.

Description

Herbal extract for improving gastrointestinal motility function {THE FRACTION EXTRACTED FROM HERBAL MEDICINE AND IMPROVING GASTROINTESTINAL MOTOR FUNCTION}

The present invention relates to a herbal extract for improving gastrointestinal motility function.

Gastrointestinal motor dysfunction, such as gastroesophageal reflux disease, gastrointestinal palsy, vomiting, postoperative intestinal obstruction and constipation, is one of the most common diseases in industrialized countries.

Drugs that promote attenuated gastrointestinal motility include cisapride, metoclopramide, domperidone, erythromycin, ondansetron, tropisetron, and mosapride (mosapride) and the like have been developed and used. However, these drugs have a relatively small effect on the movement of the small intestine and the large intestine while the improvement of the gastric exercise is the main action. In particular, cisapride, which is known to be excellent in promoting gastrointestinal motility, has been found to have serious side effects causing cardiac arrhythmias.

Therefore, in view of the therapeutic efficacy and side effects of these existing drugs developed as a gastrointestinal motility improver, the development of safe drugs that act more selectively on the small or large intestine is urgently needed.

Among the above-described inhibition patterns of gastrointestinal motility, postoperative ileus refers to the inhibition of gastrointestinal motility after clinically open surgery, and the typical symptom of postoperative ileus is the excretion of flatus and stool. Impotence, bowel sound reduction and abdominal distension. Normally, gastrointestinal motility is restored to normal within 2 to 3 days after open surgery, often progressing to paralytic ileus, which does not heal naturally and continues for more than 3 days. When postoperative ileus occurs in a patient who has undergone open surgery, the patient's physical pain as well as length of stay and cost are greatly increased. The pathogenesis of intestinal obstruction after surgery has been suggested to reduce the secretion of acetylcholine due to excessive stimulation of adrenergic nerves following laparotomy and inflammatory reactions induced in the surgical procedure. Situation. There have been no treatments developed for the treatment of intestinal obstruction after nasal gastric suction. However, cisapride has been frequently used to treat intestinal obstruction. In situations where the efficacy has not been clearly verified, use is limited due to the above side effects.

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 causing chronic constipation. Chronic constipation caused by morphine administration is one of the major causes of poor quality of life of cancer patients. However, there is not much research to treat morphine-induced constipation compared to pain given to patients.

On the other hand, Pociliri Fructus refers to the unripe fruit of the Poncirus trifoliata Rafinesque. Fruits are indigestible due to indigestion, food is not in the appetite or constipation due to constipation is not effective. In addition, the chambers are known to inhibit the movement of the intestinal tract and have an antiallergic effect.

In addition, the dermis (Aurantii Nobilis Pericapium) refers to the mature skin of the tangerine ( Citrus unshiu Markovich) or its related plant. Dermis is swelling in the stomach when you can not eat a lot, or vomiting and diarrhea when you can not digest well to lighten the inside. The dermis is also a sweat and expectorant used for colds. Dermal immersion fluids are known to excite the cardiovascular and intestinal tract of rabbits and rats, and to have blood pressure elevation and vasoconstrictive action.

The present invention is designed to meet the above demands, an object of the present invention is to have the effect of improving the gastrointestinal motility function, the fractions dissolved after adding methanol or ethanol to the fruit alone or mixed extract of the dermis and fruit and the extract It turns out that there is no side effect is to use the extract for improving the gastrointestinal motility function.

Figure 1 shows the effect of the extract according to the invention on the trend of the concentration of ranitidine in serum over time,

Figure 2 shows the effect of the extract according to the present invention on the gastrointestinal motility function in a steady state,

Figure 3 shows the effect of the extract according to the invention on the inhibition of gastrointestinal motor function by atropine,

Figure 4 shows the effect of the extract according to the present invention on gastrointestinal motility inhibition by morphine,

Figure 5 shows the effect of the extract according to the present invention on intestinal obstruction after surgery,

Figure 6 shows the efficacy of postoperative intestinal obstruction of the extract according to the present invention in comparison with cisapride.

The present invention provides a herbal extract for improving gastrointestinal motility function.

Hereinafter, the present invention will be described in detail.

(1) First aspect of the invention

The present invention provides an extract for improving gastrointestinal motility function by extracting the fruiting chamber using any one solvent selected from the group consisting of water, alcohol and aqueous alcohol solution.

The extract according to the present invention can be extracted by conventional methods using any one solvent selected from the group consisting of water, alcohol and aqueous alcohol solution. For example, after putting the fruit into a boiling water extractor and adding 5 to 20 times of solvent, boil it for 30 minutes to 2 hours at 90 to 110 ° C, leave it at room temperature for 1 to 3 hours, and then filter the extract in liquid form. You can get it. Alternatively, the obtained liquid extract may be dried to obtain an extract in the form of a powder extract.

(2) a second aspect of the invention

In another aspect, the present invention provides an extract for improving gastrointestinal motility function, which comprises only the fraction dissolved in alcohol after dissolving the fruit extract obtained using water in the first aspect of the present invention.

The extract according to the present invention can be obtained by adding only 10-50 times the solvent weight of the extract to the fruit extract obtained using water in the first aspect of the present invention and taking only the fraction dissolved in alcohol. The extract according to the present invention can be obtained in liquid form or powder extract form.

The alcohol may be an alcohol which is usually used for extraction, preferably methanol or ethanol.

(3) a third aspect of the invention

The present invention provides an extract for improving gastrointestinal motility function by extracting the dermis and the fruit chamber using any one solvent selected from the group consisting of water, alcohol and aqueous alcohol solution.

The extract according to the present invention can be extracted by a conventional method using any one solvent selected from the group consisting of water, alcohol and aqueous alcohol solution of the dermis and fat. For example, put the dermis and the fruit in a boiling water extractor, add 5 to 20 times the solvent of the mixed weight of the dermis and the fruit and boil at 90-110 ° C. for 30 minutes to 2 hours, and leave it at room temperature for 1 to 3 hours. And then filtered to obtain an extract in liquid form. Alternatively, the obtained liquid extract may be dried to obtain an extract in the form of a powder extract.

In the preparation of the extract, it is preferable to extract the dermis and the fruit juice by mixing in a ratio of 1: 0.5 to 4. Most preferably, when the extract is prepared, the dermis and the fruit juice are mixed in a weight ratio of 1: 2.

The extracts according to the present invention can improve gastrointestinal motility by significantly increasing steady-state gastrointestinal transport rate compared to cisapride and metoclopramide, and dose-dependent when gastrointestinal motility is inhibited by administration of atropine. Increasing gastrointestinal transport rate has the effect of improving gastrointestinal motility.

In addition, the extracts according to the present invention can treat morphine-induced constipation by restoring gastrointestinal motility by dose-dependently increasing the gastrointestinal tract transfer rate in a situation where gastrointestinal motility is inhibited due to morphine administration. In addition, the extract according to the present invention has an effect of improving the gastrointestinal motility function even in the postoperative ileus, and its efficacy and safety is superior to that of cisapride that has been prescribed for patients with ileus after the operation.

In addition, the extracts according to the present invention do not have acute toxicity and behavioral toxicity, and because they are natural extracts of herbal medicines, there is no concern about side effects when compared to synthetic pharmaceuticals.

Therefore, extracts according to the present invention can be used as an active ingredient of gastrointestinal motility function, postoperative ileus treatment or morphine-induced constipation treatment.

The present invention also provides a pharmaceutical formulation containing the extract as an active ingredient. Specifically, the present invention provides a pharmaceutical formulation containing the extract as an active ingredient and prepared by a pharmaceutically acceptable method by mixing a pharmaceutically acceptable excipient and adjuvant. In general, in medicine, the effective dose of the extract according to the present invention is 10 g / day for adults and may be administered 1 to 3 times a day. However, the dosage can be varied, in particular, taking into account the constitution specificity and weight of the subject to be treated, the type and depth of the disease, the nature of the formulation, the nature of the drug administration and the duration or interval of administration.

The extracts can be administered orally or parenterally during clinical administration and can be used in the form of general pharmaceutical formulations. Specifically, the extract according to the present invention may be administered in various oral and parenteral dosage forms in actual clinical administration, and when formulated, diluents such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants that are commonly used, or It is prepared using excipients.

Solid formulations for oral administration include tablets, pills, powders, granules and capsules, and the like, which include at least one excipient such as potato starch, calcium carbonate, sucrose, colloidal silicic acid, lactose in non-aqueous extracts. And gelatin etc. are mixed and prepared. In addition to simple excipients, glidants such as magnesium stearate, talc and talc are also used.

Liquid preparations for oral administration include suspensions, solvents, emulsions, and syrups. These liquid preparations include water and liquid paraffin, which are simple diluents, as well as various excipients such as wetting agents, sweeteners, fragrances, and preservatives. Can be.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used. As the base of the suppository, uthepsol, macrogol, tween 61, cacao butter, laurin butter, glycerol, gelatin and the like can be used.

Hereinafter, the present invention will be described in detail by way of examples. However, the present invention is not limited by the following examples.

<Example 1>

1 kg of well-dried cellar, dried well, was washed with running water to remove impurities. The basement was placed in a boiling water extractor with 5 L of distilled water, boiled at 90 to 110 ° C. for 1 hour, and left at room temperature for 2 hours. The extract obtained through this process was filtered under reduced pressure, the same amount of distilled water was added to the residue again, and the same process was repeated two more times. 15 liters of distilled water was added to the filtrate, and the filtrate was concentrated under reduced pressure and freeze-dried. As a result, 244 g of dry powder extract was obtained.

<Example 2>

200 g of the dry powder extract obtained in Example 1 was placed in a Erlenmeyer flask with 1 L of methanol and stirred to be sufficiently mixed. The mixture was left for 10 hours or more to be separated into a layer dissolved in methanol and a sinking layer. Only the layer dissolved in methanol was taken, and then 1 L of methanol was added again, and the same procedure was repeated nine more times to obtain 10 L of a layer finally dissolved in methanol. The solution thus obtained was concentrated under reduced pressure, and then freeze-dried. As a result, 90 g of dry powder extract was finally obtained.

<Example 3>

The dry and dried dermis and cellar were gently washed with running water to remove contaminants. The dermis and the fruit room were mixed at a weight ratio of 1: 2 (total 1 kg) and placed in a boiling water extractor with 5 L of distilled water, then boiled at 90 to 110 ° C. for 1 hour, and left at room temperature for 2 hours. The extract obtained through this process was filtered under reduced pressure, and then the same amount of distilled water was added to the residue again, and the same process was repeated two more times. 15 liters of distilled water was added to the filtrate, and the filtrate was concentrated under reduced pressure and freeze-dried. Finally, 251 g of dry powder extract was obtained.

Experimental Example 1

Effect of the extract of the present invention on the gastrointestinal motility function of human

In order to determine the effect of improving the gastrointestinal motility of the extract according to the present invention was carried out the following experiment. In this experiment, ranitidine was used as an indicator. Since ranitidine is mainly absorbed in the small intestine, the effect of the extract according to the present invention on the gastrointestinal motility function is measured by measuring the area under the concentration curve (AUC) in the serum of ranitidine. That is, when there is no change in the small intestinal membrane permeability of ranitidine itself, the lower the AUC of ranitidine, the faster the ranitidine penetrates the small intestine.

The experimental method is as follows.

(1) Oral doses of ranitidine 300 mg were administered to 6 healthy adult males, and blood was collected after 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours. (Term 1 in FIG. 1, control).

After 7 days, 10 g of the extract prepared in Example 3 was orally administered, and then 30 minutes later, oral administration and blood collection of ranitidine were performed in the same manner as in step 1 above (called step 2 in FIG. 1, Example 3). .

Serum was separated from the blood collected from the first and second stages, and ranitidine concentration in each serum was determined by HPLC analysis. Specifically, the serum sample was acetonitrile and then protein-resolved and centrifuged to obtain a sample capable of HPLC analysis. Specific HPLC analysis conditions were Gilson HPLC system (Villiers-le-Bel, France) and reverse phase C18 column. (250 × 0.6 mm, particle size 5 μm) was used, and the mobile phase was prepared by mixing 0.05 M phosphate buffer solution (pH 6.9) and acetonitrile at 81:18 (v / v). Flow rate was 0.8 ml, and the detector detected ranitidine at 313 nm using a UV detector.

The results are shown in FIG.

As shown in FIG. 1, it can be seen that stage 2 ranitidine AUC decreased to half the level of stage 1 AUC.

(2) Effect of Ranitidine on Small Intestinal Membrane Permeability

About 2 cm of jejunum sites of rats fasted for 20 hours were taken, cut out and extended to the mesenteric border and attached to the Ussing Chamber. Inject the Hans' balanced salt solution (HBSS) buffer into each of the earthing chambers, namely the small intestinal membrane mucosa and blood layers, and leave for about 30 minutes with the flow of carbogen gas (95% O ₂ /5% CO ₂ ). It was. 1 mM of ranitidine was added to the mucosal layer, and after 30, 60, 90, and 120 minutes, 500 µl of the buffer of the blood layer was taken, and the buffer was immediately added. The ranitidine content in the buffer taken over time was quantified by the above HPLC analysis (control).

30 minutes before the addition of ranitidine, 1 mg / ml of the extract prepared in Example 3 was added to the mucosal layer, and after the ranitidine was added, the ranitidine content in the buffer taken over time was quantified (experimental group).

There was no significant difference in the content of ranitidine in the buffer of the control group and the experimental group obtained at the same time, and the calculated small intestinal membrane permeability coefficient of ranitidine was not significantly different between the control group and the experimental group. Thus, it was shown that Example 3 had no effect on the small intestinal membrane permeability of ranitidine.

Through this, it can be seen that the extract according to the present invention has an effect of promoting gastrointestinal motility.

Experimental Example 2

Effect of Extracts According to the Invention on Gastrointestinal Transport Rate in Steady State

In order to determine the effect of the extract according to the present invention on the gastrointestinal transport rate was performed as follows. The gastrointestinal tract transfer rate (%) can be calculated by multiplying the distance (cm) in the small intestine moving distance of the indicator material by the total length of the small intestine (pyloric to inlet entrance; cm) and multiplying by 100. The band used an activated carbon suspension (Charcoal meal) as an indicator material.

The experimental method is as follows.

Before the experiment, male SD rats weighing 250-300 g were fasted for about 20 hours and water was allowed to drink freely. The herbal extract administration group was orally administered to the rat 1g / 5ml / kg extract prepared in Example 1 or Example 3. After 30 minutes, 1 ml of activated carbon suspension was orally administered. After another 30 minutes, the rats were killed and opened immediately. The distance of travel (cm) and the total length of the small intestine (cm) of the activated carbon suspension were measured, and the gastrointestinal tract transfer rate (%) was calculated by the method described above.

The control group was subjected to the same method as above except for oral administration of 5 ml / kg of distilled water instead of the extract according to the present invention. In addition, the comparative drug administration group was orally administered 3 mg / 5 ml / kg of cisapride or metoclopramide, which is widely known as a conventional gastrointestinal motility promoter, instead of the extract according to the present invention. It was.

The results are shown in FIG.

As shown in FIG. 2, the gastrointestinal transfer rate when orally administered with cisapride or metoclopramide showed a value similar to that of the control group. Thus, cisapride and metoclopramide did not affect the gastrointestinal transfer rate of normal rats. However, when oral administration of the extracts prepared in Examples 1 and 3 according to the present invention, the gastrointestinal transport rate significantly increased. In particular, in the extract prepared in Example 1 according to the present invention, the gastrointestinal tract transfer rate was significantly higher than that of Example 3. Therefore, the extract according to the present invention can be used as an active ingredient of the gastrointestinal motility function promoter.

Experimental Example 3

Effect of the extract of the present invention on the inhibition of gastrointestinal motor function by atropine

In order to determine the effect of the extract according to the present invention on the inhibition of gastrointestinal motility by atropine, the following experiment was performed. Atropine inhibits gastrointestinal motility. In this experiment, Evans blue solution, which is colored blue, was used as an indicator, and the moving distance (cm) of the small intestine of the Evans blue solution was divided by the total length of the small intestine (pyloric to inlet; cm). The gastrointestinal tract transfer rate (%) was calculated by multiplying by 100. And, this was used as an index for evaluating the effect on the inhibition of gastrointestinal motor function.

The experimental method is as follows.

Before the experiment, male ICR mice weighing 25-30 g were fasted for about 18 hours and water was allowed to drink freely. After dissolving the extract prepared in Example 1 according to the present invention in 0.5% methyl cellulose, depending on the administration group, respectively, 10mg / 10ml / kg, 30mg / 10ml / kg, 100mg / 10ml / kg, 300mg / 10ml / kg, and 1 g / 10 ml / kg orally administered to the mice. After 30 minutes, mice were subcutaneously injected with 30 mg / 10 ml / kg of atropine dissolved in saline. After another 30 minutes, 0.1 ml of 50 mg / ml Evans Blue solution dissolved in physiological saline was orally administered to the mice. Twenty minutes after the oral administration of Evans Blue solution, mice were lethal and opened immediately, the entire small intestine was quickly aligned, and the gastrointestinal transfer rate was calculated by the method described above.

In the case of the comparative drug administration group, the gastrointestinal transport rate was determined by the same method as above except that orally administered cisapride at a concentration of 10 mg / 10ml / kg instead of the extract according to the present invention.

In the case of the control group, the gastrointestinal transport rate was determined by the same method as above except that 10 ml / kg of 0.5% methyl cellulose was orally administered instead of the extract according to the present invention.

The results are shown in FIG.

As shown in Figure 3, it can be seen that the extract prepared in Example 1 according to the present invention dose-dependently increased the gastrointestinal transport rate of the mice inhibited gastrointestinal motility due to the administration of atropine. Therefore, the extract according to the present invention can restore the gastrointestinal motility function inhibited by atropine administration.

Experimental Example 4

Effect of the extract of the present invention on the inhibition of gastrointestinal motor function by morphine

In order to determine the effect of the extract according to the present invention on the inhibition of gastrointestinal motility by morphine, the following experiment was performed. Morphine is widely used as an analgesic to alleviate pain caused by cancer, and has a side effect of strongly inhibiting the gastrointestinal motility of the patient after administration. In this experimental example was evaluated the effect on the inhibition of gastrointestinal motor function by morphine in the same manner as in Experiment 3.

The experimental method is as follows.

Subcutaneous injection of morphine 1mg / 10ml / kg instead of atropine in Experimental Example 3, 100mg / 10ml / kg, 300mg / 10ml / kg, and 1g / 10ml the extract prepared in Example 1 according to the present invention The gastrointestinal transport rate was measured by the same method as Experimental Example 3, except that three doses of / kg were administered.

The results are shown in FIG.

As shown in Figure 4, it can be seen that the extract prepared in Example 1 according to the present invention dose-dependently increased the gastrointestinal transport rate of the mice inhibited gastrointestinal motility due to morphine administration. Therefore, the extract according to the present invention can restore the gastrointestinal motility function inhibited by morphine administration.

Experimental Example 5

Effect of the extract of the present invention on intestinal obstruction after surgery (1)

In order to determine the effect of the extract according to the invention on the postoperative ileus was performed the following experiment. In this experimental example, the effect of the extract according to the present invention on the intestinal obstruction after surgery as a method of measuring the gastrointestinal transport rate of the rat that caused the postoperative intestinal obstruction.

The experimental method is as follows.

Prior to the experiment, male SD rats weighing 150-200 g were fasted for about 48 hours and water was allowed to drink freely. The extract prepared in Examples 1 or 2 according to the present invention was dissolved in distilled water, and then orally administered to rats at a dose of 500 mg / 5 ml / kg, respectively.

In the case of the comparative drug administration group, the layer which was not dissolved in methanol was concentrated under reduced pressure in Example 2, lyophilized to prepare an extract, and then orally administered to the rat at the same dose of 500 mg / 5 ml / kg.

The normal group and the control group were orally administered 5 ml / kg of distilled water instead of the extract according to the present invention.

At 25 minutes after the administration of the extract according to the present invention, rats were anesthetized with ether, the abdominal hair was removed, placed on the surgical plate, and sterilized with 70% ethanol. After 30 minutes from the time of extract administration, 1cm below the sternum was incised 2cm downward from the sternal using a scalpel. The catheter from the cecum to the duodenum was carefully removed using a ring tweezers, and then gently massaged from the cecum to the pyloric region. This process was repeated three times for about 5 minutes. The surgery was completed by carefully placing the removed gastrointestinal tract back into the abdominal cavity and then suturing the incision with a surgical suture. After 1 hour of opening, 0.1 ml of 50 mg / ml Evans Blue solution dissolved in physiological saline was orally administered to rats.

Since the process up to the gastrointestinal transport rate was measured in the same manner as in Experimental Example 3.

In the normal group, an open surgery procedure was omitted after anesthesia induction.

The results are shown in FIG.

As shown in FIG. 5, the control group significantly reduced the gastrointestinal transport rate compared to the normal group, and the rats to which the extract according to the present invention was significantly increased compared to the control group. Can be. Therefore, the extract according to the present invention can be used as an active ingredient in the treatment of intestinal obstruction after surgery. On the other hand, in the case of the comparative drug administration group, the gastrointestinal transport rate did not show a significant difference from the control group, which means that a substance having a function of improving gastrointestinal motility during the postoperative intestinal obstruction in the extract according to the present invention was prepared by the method of Example 2 More concentrated.

Experimental Example 6

Effect of the extract of the present invention on intestinal obstruction after surgery (2)

The extract prepared in Example 2 according to the present invention was compared with the efficacy of cisapride to restore the gastrointestinal motor function in the postoperative ileus.

The experimental method is as follows.

Prior to the experiment, male SD rats weighing 150-200 g were fasted for about 48 hours and water was allowed to drink freely. 30 minutes before opening, the extract administration group according to the present invention, after dissolving the extract prepared in Example 2 in distilled water, 10mg / 5ml / kg, 100mg / 5ml / kg, and 1g / 5ml / Rats were orally administered at a dose of kg. The cisapride administration group was orally administered 5 ml / kg of distilled water instead of the extract according to the present invention.

Five minutes before opening, 1 ml / kg of 0.57M ascorbic acid was administered intravenously through the tail vein of the rat to the extract administration group according to the present invention. In the cisapride-treated group, cisapride dissolved in 0.57M ascorbic acid was dosed through the tail vein of the rat at doses of 0.1 mg / 1 ml / kg, 1 mg / 1 ml / kg, and 10 mg / 1 ml / kg, respectively. Intravenously.

Immediately after intravenous administration, rats were anesthetized with ether, and then laparotomy was performed in the same manner as in Experimental Example 5, and the gastrointestinal transport rate was also measured by the same time schedule and method.

In the control group, 0.57M ascorbic acid 1ml / kg was administered intravenously after 5ml / kg oral distilled water instead of the extract and cisapride according to the present invention, and all other schedules were performed in the same manner as the extract administration group. It was.

The normal group performed the same procedures as the control group except for omitting the laparotomy after anesthesia induction.

The results are shown in FIG.

As shown in Figure 6, the extract or cisapride prepared in Example 2 according to the present invention was found to increase the gastrointestinal transfer rate in a dose-dependent manner in the postoperative ileus. However, in the 10 mg / kg administration group of cisapride, 5 out of 10 died and apparent abnormal symptoms were observed in 5 surviving behaviors, but no abnormal symptoms were found in the extract administration group according to the present invention. Therefore, the extract according to the present invention has a function of improving gastrointestinal motility in the postoperative ileus, and even when administered in doses that have a similar effect to cisapride, no serious toxicity is found in the cisapride group. It can be seen that it is a safe drug.

Experimental Example 7

Acute Toxicity of Extracts According to the Invention

example In order to determine the acute toxicity of the extract according to the invention was carried out the following experiment.

The experimental method is as follows.

After dissolving the extracts prepared in Examples 1 and 3 according to the present invention in distilled water, respectively, 250 mg / 10 ml / kg, 500 mg / 10 ml / kg, 1 g / 10 ml / kg, 2 g / 10 ml / kg and 5 g / ICR mice were orally administered at a dose of 10 ml / kg and observed for 14 days of mortality and changes in various behavioral patterns.

In the control group, 10 ml / kg of distilled water was orally administered instead of the extract according to the present invention.

As a result, none of the mice to which the extract according to the present invention was administered died and no abnormalities were found in other anatomical findings compared to the control.

Experimental Example 8

Effect of Extracts According to the Invention on General Behavior of Mice

In order to determine the effect of the extract according to the invention on the general behavior of the mouse was carried out the following experiment.

The experimental method is as follows.

After dissolving the extracts prepared in Examples 1 and 3 according to the present invention in distilled water, respectively, 0, 500mg / 10ml / kg, 1g / 10ml / kg, 2g / 10ml / kg and 5g / 10ml / kg Abnormal behavior was not observed at all doses of ICR mice orally after Irwin's test.

Preparation Example 1 Preparation of Injection Liquid

Injection solutions containing 10 mg of the active ingredient were prepared by the following method. 10 g of the extract of Example 1, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. The solution was bottled and sterilized by heating at 20 ° C. for 30 minutes.

The components of the injection liquid are as follows.

Extract of Example 1. . . . . . . . . . . . . . . . . . . . . 10 g

Sodium chloride. . . . . . . . . . . . . . . . . . . . . . . . 0.6g

Ascorbic acid. . . . . . . . . . . . . . . . . . . . . . . .0.1 g

Distilled water . . . . . . . . . . . . . . . . . . . . . . . . . Quantitative

Preparation Example 2 Preparation of Tablet

Tablets containing 15 mg of active ingredient were prepared by the following method.

10 g of the extract of Example 2 was mixed with 175.9 g lactose, 180 g potato starch and 32 g colloidal silicic acid. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 160 g potato starch, 50 g talc and 5 g magnesium stearate to this was made into a tablet.

The components of the tablet are as follows.

Extract of Example 2. . . . . . . . . . . . . . . . . . . . 10 g

Lactose. . . . . . . . . . . . . . . . . . . . . . . .175.9 g

Potato starch. . . . . . . . . . . . . . . . . . . . . . . . .340 g

Colloidal silicic acid. . . . . . . . . . . . . . . . . . . . . .32 g

10% gelatin solution. . . . . . . . . . . . . . . . . . . Quantitative

Talc. . . . . . . . . . . . . . . . . . . . . . . . . . .50 g

Magnesium Stearate. . . . . . . . . . . . . . . . . . . 5 g

Preparation Example 3 Preparation of Tablet

Tablets were prepared in the same manner as in Formulation Example 2, except that 10g extract of Example 3 was used instead of 10g extract of Example 2 in Formulation Example 2.

As described above, the extract according to the present invention has the effect of improving the gastrointestinal motility function. Specifically, the extract according to the present invention may exhibit an effect of promoting gastrointestinal motility in a steady state. In addition, the extract according to the present invention can restore the state in which the gastrointestinal motility is inhibited due to atropine administration. In addition, the extract according to the present invention can restore a state in which gastrointestinal motility is inhibited due to morphine administration. In addition, the extract according to the present invention can improve the gastrointestinal motility function in the intestinal obstruction situation after surgery, and has a wider safety range than the cisapride known as a conventional gastrointestinal motility promoter. In addition, the extract according to the present invention is free of acute toxicity and behavioral toxicity.

Therefore, the extract according to the present invention can be used as an active ingredient of gastrointestinal motility improving agent, postoperative ileus treatment, or morphine-induced constipation treatment.

Claims (9)

The extract for improving the gastrointestinal motility function extracted from the fruit room using any one solvent selected from the group consisting of water, alcohol and aqueous alcohol solution. An extract for improving the gastrointestinal motility function, which comprises only the fraction dissolved in alcohol after dissolving the fruit extract obtained using water. The extract for improving the gastrointestinal motility function of the dermis and the fruit compartment extracted by using any one solvent selected from the group consisting of water, alcohol and aqueous alcohol solution. The extract for improving gastrointestinal motility function according to any one of claims 1 to 3, wherein the alcohol is methanol or ethanol. 4. The extract for improving gastrointestinal motility, according to claim 3, wherein the dermis and the perilla are extracted by mixing at a weight ratio of 1: 0.5 to 4. A gastrointestinal motility function improving agent containing the extract of any one of claims 1 to 4. A postoperative ileus treatment comprising the extract of any one of claims 1 to 4. A therapeutic agent for morphine-induced constipation containing the extract of any one of claims 1 to 4. A pharmaceutical preparation for improving gastrointestinal motility function comprising the extract of any one of claims 1 to 4.