KR20140000627A - Medicinal herb composition for improvement, treatment and prevention of gastrointestinal motility disorders - Google Patents

Abstract

The present invention relates to a medicinal herb composition for curing, treating, preventing gastrointestinal motility disorders with reduced toxicity by adjusting the extraction condition and composition of medicinal herbs. In the composition which contains extracts of Chinese pepper and poncirus, a Chinese pepper extract is obtained by using water or less than 30% of ethanol aqueous solution, and a mixture ratio of the Chinese pepper and poncirus is greater than 1:8. The composition remarkably treats the gastrointestinal motility disorders especially intestinal obstruction after surgery compare to a case where the Chinese pepper or poncirus is used alone, shows excellent effects on curing, treating, and preventing the gastrointestinal motility disorders, and reduces toxicity and generation of side effects from the Chinese pepper and poncirus while maintaining a remedial effect of the herbs for a long time.

Description

MEDICINAL HERB COMPOSITION FOR IMPROVEMENT, TREATMENT AND PREVENTION OF GASTROINTESTINAL MOTILITY DISORDERS}

The present invention relates to a herbal composition for improving, treating, and preventing diseases of the gastrointestinal motility disorder, and more particularly, to a composition in which toxicity is reduced by adjusting extraction conditions and composition ratios of the herbal medicine.

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 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.

It is an unripe fruit of Citrus aurantium L or Poncirus trifoliata Rafin or Citrus trifoliata. Fruits are alkaloids such as poncirin, hesperidin, rhoifolin, narifin, naringin, and neohesperidin, flavonoid glycosides, and skimmianine, and pinene. It is known to contain essential oils such as myrcene (myrcene), limonene (limonene), camphene (camphene), and has an anti-allergic effect. Korean Patent No. 10-635658 discloses an example in which ileus extract or mixed with dermis is used for post-operative intestinal obstruction, but the amount administered for the actual treatment is 500 mg / 5 ml / kg to 1 g /. With a large capacity of 5 ml / kg (Experimental Examples 6 and 7), there are aspects that are difficult to be utilized in actual clinical.

Sancho is a deciduous broad-leaved deciduous tree, Zanthoxylum piperitum, or its equivalent plant, Zanthoxylum bungeanum or Zanthoxylum schinifolium. As a vinegar, a flower, a candle, a seaweed, a weed, etc. are called. The acid component contains acid sulfol I-IV of acid amide, and essential oils include citronellal, 1,8-cineol, dipentane, α-terpineol, etc. (xanthoxylol) has been reported separately, and it is known for its sanitary, antibacterial and insecticidal effects. It is also used as an antidote for intestinal parasite control and carp poison.

Although Jisil and Sancho have been used as herbal medicines in the past, they have been described in herbal medicines and the like. However, none of the prior arts has been taught or disclosed that synergistic improvement of gastrointestinal function has been shown by combining Jisil and Sancho.

The present inventors conducted a test for confirming the effect on the gastrointestinal motility for various combinations of herbal medicines to develop a herbal composition showing the effect of treating and improving gastrointestinal dysfunction. It was confirmed through animal experiments that can be effectively used for gastrointestinal motility disorders. In addition, changes in toxicity according to the extraction conditions and combinations of the herbal extracts were studied through animal experiments. By combining these results, the extraction conditions and composition ratios of the herbal medicines were adjusted to reduce the toxicity while securing the efficacy of the herbal compositions. To complete.

The present invention is to reduce the toxicity by adjusting the extraction conditions and the composition of the components of the herbal medicine while securing the medicinal effect in the herbal composition without excellent gastrointestinal function improving effect and side effects that can be used for the prevention, improvement or treatment of gastrointestinal dyskinesia disorders The purpose is to provide.

In order to achieve the above object, in the present invention, in the herbal composition for improving, treating, or preventing gastrointestinal motility disorders, which contains an extract of Sancho and fruit juice as an active ingredient, the extract of Sancho is extracted with water or an aqueous ethanol solution of 30% or less. It provides a composition characterized by.

Here, it is preferable that the mixing ratio of the sancho and fruit fruit extract is 1: 8 or more, and the range of 1: 8-1: 12 is especially preferable.

In the present invention, as a result of research for the development of a good herbal composition with no side effects to promote the gastrointestinal motility, the gastrointestinal motility promoting effect is used when used in combination with the herbaceous acid and liquor which is widely known and rarely used as a side effect It turned out to be very good. That is, even if a small amount of Sancho and Jisil used in combination or in combination with each other, each showed a synergistic gastrointestinal function improvement effect compared to the use alone. In addition, the change in toxicity according to the extraction ratio and the extraction solvent of the acid and fruit room was studied through animal experiments, and as a result, it was found that the extraction solvent and the composition ratio to reduce the toxicity while securing the efficacy of the herbal composition.

The composition comprising the extract of Sancho and fruit juice according to the present invention in a specific composition ratio can be used as an oral preparation for improving, treating or preventing gastrointestinal motility disorders, and as a food, health supplement or health functional food for improving functional gastrointestinal motility disorders. .

Hereinafter, the composition comprising the herb and fruit extract according to the present invention is referred to as a herbal composition.

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 of the same herbal medicine that can be used for the same or similar purposes as the preventive and therapeutic purposes of the present invention.

Specifically, the present invention (Zanthoxyli Fructus) is a vinegar (Zanthoxylum piperitum), its flowering plant (Zanthoxylum bungeanum), vinegar (Zanthoxylum schinifolium), zelkova (Zanthoxylum armatum var subtrifoliatum) or bark Zanthoxylum coreanum).

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

In the herbal composition of the present invention, the herbaceous and fruit extracts can be obtained by extracting each herbal with water or an aqueous ethanol solution of 30% or less as a mixed solvent of water and ethanol. In the case of extracting the acid and the fruit compartment separately, the fruit compartment extraction solvent is not limited to water or 30% or less ethanol aqueous solution, water, C ₁ to C ₄ alcohol, or a mixed solvent thereof may be used. Examples of the C ₁ to C ₄ alcohols include methanol, ethanol, propanol and butanol, with ethanol being most preferred. The extraction 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 extracts of Sancho and Jissil can be prepared by any extraction method known to those skilled in the art of herbal medicine extraction, for example, 5 to 100 ℃, preferably 10 to 80 ℃, more preferably about 1 to about room temperature It may be prepared by stirring extraction, boiling water extraction, cold extraction, reflux cooling extraction or ultrasonic extraction for 100 hours, preferably 8 to 72 hours, preferably by cold extraction. The obtained extract can be filtered, concentrated under reduced pressure or dried to obtain the final extract.

The herbal compositions comprising the extracts of the herbaceous acid and fruiting fruit of the present invention are effective in improving, treating or preventing gastrointestinal motility disorders, and in particular, exhibit an excellent effect on the recovery of postoperative gastrointestinal function, including postoperative intestinal obstruction.

In addition, the herbal composition consisting of a combination of acid and fruit extract of the present invention exhibits a significantly superior intestinal transfer rate compared to the case of administering each of the main component of the extract and the main fruit extract, the combination of these two herbs is a gastrointestinal motility disorder disease Has been shown to exhibit synergistic effects in the improvement, treatment and prevention of

In the present invention, Sancho and fruit extracts are effective on 5-HT ₄ receptor, on dopamine D2 receptor, on muscarinic receptors, on motilin receptors, on adrenergic α2A receptors, 5- It was confirmed to exhibit an effect on the HT _1A receptor. As described above, the herbal composition comprising an extract of Sancho and Ji-sil according to the present invention regulates the action of various receptors affecting gastrointestinal motility, such as 5-HT _4, and is very effective in gastrointestinal motility disorders such as functional dyspepsia by a complex mechanism. Excellent therapeutic effect. In particular, the herbal compositions comprising a combination of Sancho and fruiting extracts of the present invention exhibit excellent synergistic post-operative gastrointestinal function improvement above their normal group in the postoperative gastrointestinal function recovery experiments by their synergistic action. Therefore, when the herbal composition of the present invention is administered, the gastrointestinal function, which has been degraded due to the surgery, is quickly restored, thereby enabling rapid discharge.

As used herein, “gastrointestinal motility disorder” refers to a disease 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 dysfunction, gastrointestinal dyskinesia due to chemotherapy, intestinal obstruction due to gastrointestinal dyskinesia, and postoperative intestinal obstruction. Postoperative gastrointestinal function impairment and degradation, gastrointestinal dyskinesia or constipation due to myotonic dystrophy, and preferably, gastroesophageal reflux disease, functional dyspepsia, irritable colitis, postoperative gastrointestinal function impairment and degradation, and Although constipation can be illustrated, it is not limited only to these. For example, it can be ameliorated or treated by modulating the action of various receptors that affect gastrointestinal motility, namely 5-HT ₄ receptor, dopamine D2 receptor, muscarinic receptor, motilin receptor, adrenergic α2A receptor and 5-HT _1A receptor. Pathological conditions that are included are included in the gastrointestinal motility disorders defined herein.

As defined herein, “postoperative gastrointestinal dysfunction” refers to a condition in which gastrointestinal function is temporarily impaired or degraded due to surgery, and includes postoperative ileus. Postoperatively, intestinal obstruction is clinically a state of inhibition of gastrointestinal motor function that occurs after laparotomy, and a rapid recovery of postoperative gastrointestinal function is a crucial factor in accelerating the time of discharge. In general, the gastrointestinal motility function normally recovers within 2 to 3 days after open surgery, and often progresses to paralytic ileus that does not heal naturally and continues for more than 3 days. Surgery is meant to include laparoscopic or arthroscopy and other robotic surgeries, as well as surgery for uterine and other organs, as well as surgery for small bowel disease.

The herbal medicine used in the present invention can be seen that there is almost no toxicity or side effects since it is secured by using it for a long time in the past, but it is toxic according to the extraction solvent and composition combination ratio when extracted using an organic solvent rather than the traditional method of preparing a powder. And the likelihood of side effects occurring. Accordingly, in the present invention, the extraction conditions and the combination ratio are reduced to the extent that toxicity and side effects are reduced to the extent possible to develop the drug while showing a certain drug efficacy. According to the present invention, as a composition comprising an extract of Sancho and fruiting filaments, the composition having a limited combination ratio with the extraction solvent has little toxicity and side effects, and thus can be used safely even for long-term administration for the purpose of improving, treating and preventing gastrointestinal motility disorders.

Oral preparations for ameliorating, treating or preventing gastrointestinal motility disorders comprising the extracts of Sancho and perilla according to one aspect of the present invention may include pharmaceutically acceptable carriers, excipients and / or diluents. It can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like according to the method of. The dosage of the oral preparation of the present invention may be administered by dividing the herbicidal and fruiting extract active ingredients into doses of 0.1 to 100 mg / kg body weight per day.

Functional gastrointestinal motility disorders foods, health supplements or functional foods comprising the extract of Sancho and fruit juice according to another aspect of the present invention in a specific composition ratio may include a food acceptable carrier and / or additives, usually It may be formulated into a food according to the method of. Foods of the present invention can be appropriately added or reduced the content of the herbal composition within the range expected to improve functional gastrointestinal motility disorders, and 0.1 to 99% by weight, based on the total weight of the food extract of the active ingredient of the herbaceous and fruiting, preferably 1 To 90% by weight.

The herbal composition according to the present invention includes a combination of fruit and pepper extracts, which significantly improves gastrointestinal motility, especially postoperative intestinal obstruction, compared with the case of administering fruit or pepper extract alone to improve, treat or treat gastrointestinal motility disorders. Excellent effect on prevention. In addition, it is traditionally used for a long time and is composed of herbal drugs that ensure the stability, and adjusted the ratio of the extraction solvent and the combination to reduce the toxicity and side effects while maintaining the efficacy, there is little concern of side effects or toxicity even in long-term use.

Hereinafter, the present invention will be described in more detail through Examples and Experimental Examples. However, the following Examples are only examples of the present invention, and the scope of the present invention is not limited to these.

Manufacturing Example  1: Preparation of Herbs and Herbs Extract of Herbal Medicine

1-1. Preparation of Fruity Fruit Extract

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

menstruum Yield (g) yield(%) 70% Ethanol (P70E) 22 22 80% Ethanol (P80E) 11.2 11.2 95% ethanol (P90E) 3 3

1-2 Preparation of single extract

Dried pickles from Kyungdong market (Seoul) were purchased and used for experiments. 1750 mL of 30%, 50%, 70%, and 90% ethanol aqueous solution was added to 250 g of dried acid, and the extract was extracted at room temperature for 24 hours. The extract was concentrated under reduced pressure at 55 to 65 ° C. and dried to give an acid extract of each solvent. Ie, 30%, 50%, 70%, and 90% ethanol soluble acidic extracts (hereinafter referred to as Z30E, Z50E, Z70E and Z90E) were obtained. In addition, 1750 mL of distilled water was added to 250 g of dry acid, extracted with boiling water at 100 ° C. for 1 hour, and the extract was concentrated under reduced pressure at 55 to 65 ° C., followed by drying. Refer to). Table 2 shows the yield of each extract.

menstruum Yield (g) yield(%) Hot water (ZWE) 12.5 5.0 30% Ethanol (Z30E) 26.5 10.6 50% Ethanol (Z50E) 37.3 14.9 70% Ethanol (Z70E) 32.3 12.9 90% Ethanol (Z90E) 16.9 6.76

Manufacturing Example  2: Combination Preparation of Sancho and Fruit Extracts

2-1. Sancho and Fructus Extract Combination 1

For the fruit extract obtained by extracting with 70% ethanol in Preparation Example 1-1 and the extract of the extract obtained with 70% ethanol in Preparation Example 1-2, the fruit extract based on the weight of the extract of 1 Mixtures at the weight ratios of: 3 and 1: 2.3 were used to prepare the combined fruit and pepper extract of the present invention (hereinafter referred to as PZ713 and PZ7123) having a mixing ratio of 1: 3 and 1: 2.3, and used in the following experimental examples.

2-2. Herb and Fruit Extract Combination 2

For the fruit extract obtained by extracting with 70% ethanol in Preparation Example 1-1 and the extract of the extract obtained with 50% ethanol in Preparation Example 1-2, the fruit extract based on the weight of the extract of 1 Mixing ratios of 1: 1, 1: 1.5, 1: 2.3, 1: 3, 1: 4, 1: 9, and 1:12 in a weight ratio of 1: 1, 1: 1.5, 1: 2.3, 1: 3, 1 Fruit and pepper extract extracts of the present invention (hereinafter referred to as PZ511, PZ5115, PZ5123, PZ513, PZ514, PZ519 and PZ5112) of 4: 4, 1: 9 and 1:12 were prepared and used in the following experimental examples.

In addition, the following experimental example was administered to the group administered the only extract obtained by extracting with 70% ethanol in Preparation Example 1-1 and the extract of Sancho alone obtained by extracting with 50% ethanol in Preparation Example 1-2 It was used as a comparative group of 1.

2-3. Herb and Fruit Extract Combination 3

For the fruit extract obtained by extracting with 70% ethanol in Preparation Example 1-1 and the extract obtained with 30% ethanol in Preparation Example 1-2, the fruit extract based on the weight of the extract of 1 A combination of fruit and acid extracts with mixed ratios of 1: 1, 1: 4, 1: 9 and 1:12 in a weight ratio of 1: 1, 1: 4, 1: 9 and 1:12 (hereinafter, referred to as PZ311, PZ314, and PZ319). And PZ3112) were obtained and used in the following experimental examples.

2-4. Herb and Fruit Extract Combination 4

For the fruit extract obtained by extracting with 70% ethanol in Preparation Example 1-1 and the extract obtained by boiling water extraction in Preparation Example 1-2, the fruit extract was 1: 3 based on the weight of the extract. Mixing by weight ratio yielded a combined extract of Ji-sil and Sancho (hereinafter referred to as PZW13) having a mixing ratio of 1: 3, which was used in the following experimental example.

Experimental Example  One: After surgery  Gastrointestinal function recovery effect experiment

In order to determine the effect of the herbal compositions obtained in the above examples 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).

This experimental example is a method for measuring the intestinal transport rate in the rats induced postoperative ileus, to evaluate the effect of the herbal extract according to the present invention on postoperative gastrointestinal function recovery.

200-240 g of male SD rats (Orient, Republic of Korea) were bred for 1 week while maintaining a light / dark cycle at a temperature of 22-24 ° C. and a humidity of 50-70%. Standard diets and negative water were freely consumed. The animals were fasted for 24 hours, and surgery was performed on the rats except the normal group to induce postoperative ileus. Surgery was anesthetized with isofluorane (ASJ9AC. Abbott Lab) and an incision about 2 cm in the abdomen was made. The intestines and appendix were carefully taken out of the body and stimulated by finger massage from the appendix to the duodenum for about 10 minutes. After the massage, the intestines and cecum were carefully inserted again through the incision in the abdomen. The incision site was sutured. At 3 hours and 30 minutes after the operation, the extracts of the combined fruit and pepper extracts prepared in the above examples, the extracts of the fruit and pepper extracts were orally administered at 5 ml / kg doses as test drugs. The test drug was suspended in 5% Pluronic F-68 (P1300, SIGMA), and the negative control group was orally administered the same dose of 5% Pluronic F-68 without the test drug. The normal group underwent the operation of anesthesia as a rat without surgery, and then orally administered 5% Fluronic F-68 at the same dose as the test drug-treated group without the test drug.

30 minutes after the administration, Evans Blue (E2129, SIGMA, 50 mg / ml) was orally administered 0.2 mL. All rats were euthanized by cervical dislocation 20 minutes after Evansblue 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 transfer rate (ITR) according to the following equation. The results are shown in Table 3 below.

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

Statistical treatment was analyzed by the Unpaired t-test using Prism4 (GraphPad), the effectiveness of the pharmacological effect of the combination treatment group of Sancho and fruit extract of the present invention compared with the negative control group ( ^* P <0.05, ^** P <0.01, ^*** P <0.001).

Experimental group Capacity (ml / kg) Intestinal transfer rate (%) Normal group - 59.5 Negative control group - 31.8
Acid extract (Z30E) alone administration group 7 31.9 21 36.8 42 44.0
Acid extract (Z50E) alone administration group 10 35.0 30 39.1 60 41.9 120 37.6 Sancho and
Basement
extract
Combination (PZ)
Administered group Sancho: Knowledge room = 1: 1 (PZ311) 84 52.7 Sancho: Gile = 1: 4 (PZ314) 105 55.4 Sancho: Gile = 1: 9 (PZ319) 70 52.0 Sancho: Knowledge Room = 1:12 (PZ3112) 91 59.7 Sancho: Knowledge Room = 1:12 (PZ3112) 182 63.5 Sancho: Knowledge room = 1: 1 (PZ511) 120 64.3 Sancho: Gate = 1: 1.5 (PZ5115) 150 65.9 Sancho: Gate = 1: 3 (PZ513) 120 59.6 Sancho: Gate = 1: 4 (PZ514) 150 69.2 Sancho: Gloss = 1: 9 (PZ519) 100 58.8 Sancho: Knowledge room = 1:12 (PZ5112) 130 60.0
Fruit extract (P70E) alone administration group 40 41.9 60 40.2 90 41.3 120 44.9 500 41.8

As can be seen from the table, the negative control group significantly reduced the gastrointestinal transport rate compared to the normal group. As a result of the combination of the extracts of the fruiting and sancho extract according to the present invention, it showed an excellent gastrointestinal transport rate close to or above the normal group, and showed a significantly superior synergistic effect compared to the individual administration group of the sancho and the fruiting.

Experimental Example  2: In the rat One time  Dose Toxicity Test

In order to determine the toxicity of the herbal composition obtained in the above Example in a single dose to the rat, the experiment was performed according to the following method.

Seven-week-old male SD rats (Orient, South 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 negative water were freely consumed. Animals were fasted for 24 hours, and then the oral herb extracts prepared in Example were administered orally at a dose of 10 ml / kg, respectively. The test drug was used suspended in 5% Pluronic F-68 (P1300, SIGMA). The negative control group was orally administered 5% Pluronic F-68 at the same dose as the test group without the test drug.

After a single oral administration of the test drug, mortality and side effects were observed for one week, and Table 4 shows the results.

Experimental group Volume
(Ml / kg) Death Side Effect Negative control group - 0 none
Sancho
And
Basement
extract
Combination (PZ)
Administered group Sancho: Basement = 1: 3 (PZW13) 2000 0/3 none Sancho: Basement = 1: 3 (PZ313) 2000 0/3 none Sancho: Basement = 1:12 (PZ3112) 2000 0/10 none Sancho: Knowledge room = 1: 2.3 (PZ5123) 2000 1/4 Abdominal stomach, cramps, eye and nasal bleeding Sancho: Basement = 1: 3 (PZ514) 1000 0/4 Abdominal stomach, cramps, eye and nasal bleeding Sancho: Basement = 1: 4 (PZ514) 1000 0/10 Abdominal stomach, cramps, eye and nasal bleeding Sancho: Basement = 1: 4 (PZ514) 1500 1/10 Abdominal stomach, cramps, eye and nasal bleeding Sancho: Basement = 1: 4 (PZ514) 2000 1/10 Abdominal stomach, cramps, eye and nasal bleeding Sancho: Knowledge room = 1: 2.3 (PZ7123) 2000 2/3 Caused by secretions around the eyes and nose
Coat hair pollution Sancho: Basement = 1: 3 (PZ713) 2000 3/4 Caused by secretions around the eyes and nose
Coat hair pollution

As can be seen from the table, no death and no side effects were observed in the Sancho hot water extract and 30% ethanol extract, but death and side effects were observed in the 70% ethanol extract and 50% ethanol extract. In other words, it was found that the lower the ethanol content of the extract was reduced toxicity.

The herbal composition has the advantage of using a high-safety natural product, and considering the ongoing toxicity test for safety evaluation, it is determined that at least a single dose toxicity test should not be observed deaths and side effects. Therefore, the herbal extract of the herbal extracts should be used to extract the toxic hot water or less than 30% ethanol aqueous solution.

Experimental Example  3: Oral Dose Toxicity in Dogs

In order to determine the toxicity of the herbal compositions obtained in the above examples in single and two doses to dogs, experiments were carried out according to the following method.

Male Beagle dogs (Orient, Republic of Korea) of 10-12 kg were bred for more than a month while maintaining a light / dark cycle at a temperature of 22-24 ° C and a humidity of 50-70%. Standard diets and negative water were freely consumed. After fasting the test animals for 24 hours, the combination of the herbaceous acid and fruit extract prepared in Example was filled into the capsule as a test drug and administered orally. The control group was orally administered a capsule not filled with the test drug.

After oral administration of the test substance once or twice, mortality and adverse events were observed for 24 hours. Adverse events were observed by selecting herbal compositions and doses containing 30% ethanol acid extract that would not show death, referring to mortality and toxicity symptoms in single-dose rats. Table 5 shows the results.

Experimental group Dose (mg / kg / day) Number of doses Side Effect Sancho and
Lychee extract
Combination (PZ)
Administered group Sancho: Gile = 1: 4 (PZ314) 200 One Vomiting and diarrhea Sancho: Gloss = 1: 8 (PZ318) 200 One none Sancho: Gloss = 1: 8 (PZ318) 200 2 Vomiting and diarrhea Sancho: Knowledge Room = 1:12 (PZ3112) 200 One none Sancho: Knowledge Room = 1:12 (PZ3112) 400 One Yanbian Sancho: Knowledge Room = 1:12 (PZ3112) 600 One throw up

As shown in the table, it was observed that the higher the composition of the acidic: fruit chamber, the lower the toxicity. That is, in the herbal composition containing 30% ethanol extract of Sancho, when the composition ratio of Sancho: jiji was 1: 8, if the dose was 200 mg / kg, vomiting and diarrhea were observed when administered twice, but the composition ratio of Sancho: jiji was In case of 1:12, vomiting was observed at the dose of 600 mg / kg, but no adverse effect was observed at 200 mg / kg. Therefore, in consideration of the advantages of using a high-safety herbal medicine and toxicological tests conducted in the safety evaluation, the herbal composition of the present invention should use a hot water or a ethanol solution of 30% or less ethanol solution reduced toxicity, The composition ratio is 1: 8 or more, preferably in the range of 1: 8 to 1:12 product development is judged to be most preferred.

Claims (10)

A composition for improving, treating, or preventing gastrointestinal motility disorders, which contains an extract of the herbaceous acid and fruiting fruit as an active ingredient, wherein the herbal extract is extracted with water or an aqueous ethanol solution of 30% or less. The composition according to claim 1, wherein the mixing ratio of the extract of Sancho and fruit fruit is 1: 8 or more. The composition according to claim 2, wherein the mixing ratio of the herbaceous and fruiting extract is 1: 8 to 1:12. The method of claim 1, wherein the pepper is a bark of Zanthoxylum piperitum, Zanthoxylum bungeanum, Zanthoxylum schinifolium, Zanthoxylum armatum var subtrifoliatum or Zanthoxylum coreanum Characterized by a composition. The composition of claim 1, wherein the fruit is an immature fruit of Korean fruit (Poncirus trifoliate), Chinese fruit (Citrus aurantium) or Citrus grandis. The composition of claim 1, wherein the fruit extract is extracted with water, C ₁ to C ₄ alcohols, 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 dysfunction, gastrointestinal dyskinesia due to chemotherapy, bowel obstruction due to gastrointestinal dyskinesia, Postoperative intestinal obstruction, postoperative gastrointestinal dysfunction, gastrointestinal dyskinesia due to myotonic dystrophy or constipation. 8. The composition of claim 7, wherein the gastrointestinal motility disorder is postoperative ileus or postoperative gastrointestinal dysfunction. An oral preparation for improving, treating or preventing gastrointestinal motility disorders comprising the composition according to claim 1. Functional gastrointestinal motility disorders food, health supplement or health functional food comprising the composition according to claim 1.