KR101136285B1 - Herbal extract, pharmaceutical composition including the same and health functional food including the same - Google Patents

Abstract

PURPOSE: A mixture extract including Pharbitis nil seed extract and CorydalisTuber extract and a pharmaceutical composition containing the same are provided to improve gastrointestinal tract transition. CONSTITUTION: A mixture extract contains Pharbitis nil seed extract and CorydalisTuber extract in a weight ratio of 1:5. A pharmaceutical composition for preventing or treating gastrointestinal movement disorder contains the mixture extract. The disorder is caused by 5-HT3 receptor overactivation or 5-HT4 receptor antagonism. A health food contains the mixture extract and is manufactured in the form of powder, tablets, capsules, syrup, or drink.

Description

Herbal extract, pharmaceutical composition comprising the same and health functional food comprising the same {Herbal extract, pharmaceutical composition including the same and health functional food including the same}

The present invention relates to a herbal extract comprising a black shaft extract and corydalis extract, a pharmaceutical composition comprising the same and a health food comprising the same.

Pathological mechanisms of functional gastrointestinal disorders, such as gastrointestinal motility disorders, may act simultaneously and exhibit one symptom, but mainly occur in a combination of actions. According to symptoms, it is classified into ulcer-like dyspepsia, dysmotility-like dyspepsia, reflux-like dyspepsia, and nonspecific or unspecified functional dyspepsia.

The prevalence of these functional gastrointestinal diseases is 25 to 50% worldwide, and about 5% of all medical examinations require patients. In Western countries, the incidence rate is low, including 22% in the United Kingdom and 19% in the United States. In Korea, gastrointestinal disease is the second highest in all diseases, especially the incidence of gastrointestinal diseases is high, and 30-40% of the people are experiencing functional gastrointestinal diseases. As described above, functional gastrointestinal diseases are not only high in prevalence but also have severe symptoms, and therefore, patients need to be treated effectively because of poor quality of life and frequent medical treatment.

In the case of such a functional gastrointestinal disease, the cause causing the symptoms is obvious, but the cause is often not clear. As such, a functional gastrointestinal disease whose cause is not obvious is defined as a functional symptom rather than histopathological and biochemical organic lesions, and treatment is being performed in a direction of reducing the symptoms. Many symptoms of functional gastrointestinal disorders can be treated, primarily by promoting gastrointestinal motility.

Functional dyspepsia, one of the representative gastrointestinal motility disorders, is diagnosed by various various indigestion symptoms without any obvious organic lesions. Therefore, treatment is not simple and most symptoms are repeated and improved. The change is severe. These pathological mechanisms may work simultaneously and produce one symptom, but they usually occur in a combination of actions.

Representative functional dyspepsia agents include gastrointestinal motility promoters such as domperidone, metoclopramide, levosulpiride, mosapride, itopride and erythromycin. And other drugs. In addition, gastric acid secretion inhibitors and antacids are used because the typical symptoms of functional dyspepsia are heartburn and ulcers, but gastric acid secretion inhibitors and antacids, including H2 antagonists, often have a temporary effect (Vincenzo Stanghellini et al., Delayed). Gastric Emptying in Functional Dyspepsia, Current Treatment Options in Gastroenterology, 7, 259-264, 2004).

One of the recently used prokinetic drugs for the treatment of functional dyspepsia, 5-HT ₄ receptor agonists, improves symptoms without increasing tension at the bottom of the crisis. Cisapride, one of the 5-HT ₄ receptor agonists, has a gastric fasting effect and has a statistically significant effect compared to other drugs, but in association with the duodenum or intragastric pressure wavelength (> 6 cm), It raises the threshold for cognitive bloating in healthy people as well as in patients, and can have fatal side effects.

On the other hand, Korean Patent Application No. 10-2007-0019560 discloses that one or more herbal extracts selected from the group consisting of Baekja, Hyunho colors, black shaft and bodu are effective in preventing or treating gastrointestinal motility disorders. However, the Korean patent application does not disclose that the herbal extract comprising the black side extract and corydalis extract in a specific ratio has a particularly excellent effect on the gastrointestinal motility disorder disease.

The present invention provides a mixed extract comprising a black shaft extract and corydalis extract in a weight ratio of 1: 5.

The present invention provides a pharmaceutical composition for preventing or treating gastrointestinal motility disorder disease comprising a mixed extract comprising a black shaft extract and corydalis extract in a weight ratio of 1: 5.

The present invention provides a dietary supplement comprising a mixed extract comprising a black shaft extract and a corydalis extract in a weight ratio of 1: 5.

The present invention provides a preventive or therapeutic use of gastrointestinal motility disorder disease of the mixed extract comprising a black shaft extract and corydalis extract in a weight ratio of 1: 5.

The present invention provides a method of preventing or treating gastrointestinal motility disorder disease by administering to the subject a mixed extract comprising a black shaft extract and corydalis extract in a weight ratio of 1: 5.

The present invention is a heukchuk (Pharbitidis seed) extract of Corydalis and (CorydalisTuber) extract 1: extract provides a mixture comprising a weight ratio of 5.

Pharbitidis seed (Pharbitidis seed) is a seed of the morning glory (Pharbitis nil Choisy) of the Convolvulaceae and contains about 11% fat oil and 2% pharbitin, a resinous glycoside. Action is known (KP Part 2 pp651).

Corydalis Tuber is a tuber of the Poppyaceae family Corydalis ternata Nakai and other homologous plants.Berberine, 1-Canadine, Protopine, 1 Tetrahydrocoptisine (1-Tetrahydrocoptisine) contains, analgesic and sedation, jingyeong, jinjin, and ACTH secretion hyperactivity (KP Part 2 pp664).

The black shaft extract or corydalis extract exhibits a prophylactic or therapeutic effect on gastrointestinal motility disorders, and the mixed extract of the black shaft extract and corydalis extract exhibits better effects on gastrointestinal motility disorders than the respective extracts. .

Among the mixed extracts of the black shaft extract and corydalis extract, the mixed extract comprising the black shaft extract and corydalis extract in a weight ratio of 1: 5 compared to the composition comprising the black shaft extract and corydalis extract in different weight ratios against gastrointestinal motility disorder disease It shows a remarkably good effect. The mixed extract including the black shaft extract and the corydalis extract in a weight ratio of 1: 5 exhibits an excellent effect on the gastrointestinal motility disorder caused by 5-HT ₃ receptor hyperactivity and / or 5-HT ₄ receptor antagonistic activity. .

The cause of the gastrointestinal motility disorder disease is obvious in some cases, but the cause is often not clear. As such, the gastrointestinal motility disorder disease whose cause is not obvious is defined as a functional symptom rather than histopathological and biochemical organic lesions, and treatment is being made in a direction of reducing the symptoms.

Many symptoms of functional gastrointestinal disorders can be treated, primarily by promoting gastrointestinal motility.

The gastrointestinal motility disorder diseases include premature satiety, pain, epigastric discomfort, flatulence, heartburn, nausea, vomiting, functional dyspepsia, ulcer dyspepsia, non-ulcer dyspepsia, gastro-esophageal reflux disease, reflux esophagitis, gastrointestinal disorder Irritable bowel syndrome, diabetic gastrointestinal dysfunction, chemotherapy, gastrointestinal dysfunction, gastrointestinal dyskinesia, false bowel obstruction, gastric palsy, constipation, general irritable colitis, irritable colitis with constipation or diarrhea Gastrointestinal dyskinesia due to intestinal obstruction and myotonic dystrophy, and non-cardiac chest pain.

Among the disorders of the gastrointestinal tract disorders, the functional dyspepsia is a functional symptom that is not a histopathological and biochemical organic lesion but a symptom of persistent discomfort or pain in the upper abdomen, and is limited to the upper abdomen medically and repeatedly. Means all the symptoms associated with discomfort or pain. Specifically, functional dyspepsia includes gastrointestinal symptoms such as satiety, edema, abdominal bloating, premature satiety, belching, upper abdominal discomfort or pain, heartburn, nausea (nausea), vomiting, stomach acid reflux, and heart burn. do. About 30% of patients with functional dyspepsia are known to have gastrointestinal dyskinesia such as delayed gastric emptying time for food to reach the small intestine through the pylorus of the stomach. In addition, when food is ingested, the stomach is properly stretched to maintain gastrointestinal pressure.

Irritable bowel syndrome is a chronic condition that causes changes in abdominal pain and bowel habits, such as diarrhea, constipation, or repetition of diarrhea and constipation. The symptoms are intermittent but sometimes persistent and present for at least three months. Clinically, there are usually three aspects, which can be divided into two types: constipation, diarrhea, and alternating symptoms. In addition to changes in bowel habits and abdominal pain, patients with irritable bowel syndrome may have other symptoms such as bloating, indigestion, nausea, vomiting, headache, dysmenorrhea and frequent urination. The irritable bowel syndrome may include general colitis diseases including irritable colitis. Irritable bowel syndrome is regarded as a disorder caused by functional disorder because no structural, biochemical, or infectious cause can be found, and functional abnormality is associated with impaired intestinal sensation and motor function. For the treatment of diarrhea, anticholinergic or anticonvulsant drugs are used. If constipation appears, gastrointestinal motility accelerators are used.

Gastroesophageal reflux disease is a condition in which the contents of the stomach or duodenum are refluxed into the esophagus, causing symptoms or breakfast injuries, such as burning of the chest in the back of the sternum and reflux, that is, gastric fluid or stomach contents reflux into the pharynx, chest pain, swallowing Difficulty, swallowing pain, chronic laryngeal symptoms, sore throat, cough, hoarse. If the contractile force of the lower esophageal sphincter is weakened or the gastric or intraperitoneal pressure is increased to exceed the contractile force of the lower esophageal sphincter, gastric acid or gastric contents flow back into the esophagus, causing irritation of the lower esophagus and various related symptoms. Drug treatment for gastroesophageal reflux disease includes antacids, H ₂ receptor blockers, gastrointestinal motility inhibitors, and gastric acid secretion inhibitors. Antacids can help treat occasional mild reflux symptoms, while H ₂ receptor blockers do not relieve symptoms more than about one-third, and over half do not completely heal mucosa. Gastrointestinal motility promoters help to increase the lower esophageal sphincter muscle pressure, increase the esophageal peristalsis and promote gastric emptying time. It is also used to treat severe esophagitis patients with severe esophagitis and complications.

Gastric disability refers to a condition in which the muscular tension of the stomach wall is weakened. In general, peristalsis is also weakened at the same time. Independent neuropathy may occur when there is genital disease as a symptom of nervous breakdown or systemic neuropathy or as reflex neuropathy. Others, such as gastritis, chronic gastritis, indigestion, chronic appendicitis, etc. may occur as a result of various diseases, and subjective symptoms include bloating of the stomach. There is no abnormality in appetite, but because of fear of stomach bloating after meals, the weight is greatly reduced. I always feel trimmed and nauseous, and at the same time, the intestine is also in a state of disability, which is constipated and severe causes headaches and dizziness. In the treatment of gastrointestinal disability, gastrointestinal motility promoters are generally used.

Constipation can be divided into two types of laxative constipation, intestinal movement, but not constipated, constipated constipation that can not push the bowel movements, and rectal constipation that is normal, but does not cause bowel movements in the rectum. Use gastrointestinal stimulants to treat constipation.

The gastrointestinal motility disorders listed above may appear individually or together. For example, about one third of functional dyspepsia is accompanied by irritable subject syndrome, and other diseases such as gastroesophageal reflux disease, air swallowing, and cholelithiasis are often accompanied by functional dyspepsia. In addition, about 90% of patients with irritable bowel syndrome have functional dyspepsia.

The mixed extract comprising the black side extract and corydalis extract of the present invention in a weight ratio of 1: 5 may improve gastric emptying ability, gastric compliance and gastrointestinal metastasis of food, and may also activate gastrointestinal motility and hypersensitivity of the gastrointestinal tract. The reaction can be suppressed.

In other words, the mixed extract including the black shaft extract and Hyunho hyacinth extract of the present invention in a weight ratio of 1: 5 may promote the gastric emptying of the food much more smoothly than the composition comprising the Hyunho hyacinth extract and the black shaft extract in different weight ratios. It can prevent or treat gastrointestinal metastasis delay, can promote stomach swelling when ingesting food, and can effectively suppress visceral hypersensitivity reactions. Therefore, the mixed extract including the black shaft extract and the corydalis extract of the present invention in a weight ratio of 1: 5 is particularly gastric-esophageal reflux disease, non-cardiac chest pain, dyspepsia, gastrointestinal disorder, false bowel obstruction, constipation, irritable bowel syndrome and The same shows an excellent effect on diseases of the gastrointestinal motility disorders. In particular, a plurality of gastrointestinal motility disorders can show an excellent effect.

In addition, the mixed extract containing the black side extract and the corydalis extract of the present invention in a weight ratio of 1: 5 may improve gastric emptying ability, gastric compliance and gastrointestinal metastasis without adverse effects such as causing adverse effects on the heart. Can improve gastrointestinal motility.

The present invention may include both black shaft and sinusoidal co-existing herbal drugs that are obvious in the art and can be used for the same or similar purposes as the prophylactic or therapeutic purposes of the present invention.

The mixed extract including the black shaft extract and corydalis extract in a weight ratio of 1: 5 may be prepared by obtaining the black shaft extract and corydalis extract, respectively, and then mixing them in a weight ratio of 1: 5. In addition, after mixing the black side and the coarse color in a weight ratio of 1: 5, the mixed extract can be obtained from the mixture.

For example, the mixed extract pulverizes the black shaft and scallop color with a grinder, respectively, and mixes the pulverized black side and the pulverized scallop color in a weight ratio of 1: 5. About 1 to 25 times, preferably 5 to 15 times the amount of water, a lower alcohol such as ethanol or methanol, or a mixed solvent thereof, preferably a mixed solvent of water and ethanol, Extraction method such as hot water extraction, cold needle extraction, reflux cooling extraction or ultrasonic extraction for about 1 to 100 hours, preferably 65 to 80 hours at an extraction temperature of about 20 to 100 ℃, preferably 45 to 75 ℃ using Preferably, the extract may be extracted by hot water extraction to obtain a mixed extract including the black shaft extract and corydalis extract in a weight ratio of 1: 5.

The present invention provides a pharmaceutical composition for preventing or treating gastrointestinal motility disorder disease, including a mixed extract comprising the black shaft extract and corydalis extract in a weight ratio of 1: 5.

As described above, the mixed extract including the black axis extract and the corydalis extract in a weight ratio of 1: 5 may prevent or treat various symptoms of gastrointestinal motility disorders, and the composition comprising the same may effectively prevent or treat gastrointestinal motility disorders. It can be cured.

The pharmaceutical composition of the present invention comprises about 0.01 to about 80%, preferably about 1 to about 50% by weight of the mixed extract including the black axis extract and corydalis extract in a weight ratio of 1: 5.

The pharmaceutical composition of the present invention may further include an active ingredient having a therapeutic effect on gastrointestinal motility disorders, including functional dyspepsia, in addition to a mixed extract including a black extract and a corydalis extract in a weight ratio of 1: 5. For example, the pharmaceutical composition may include domperidone, metoclopramide, metoclopramide, levosulpiride, mosapride, itopride, erythromycin, and cisapride. cisapride) and the like.

The pharmaceutical composition of the present invention may further include other pharmaceutically active ingredients that have an effect on diseases other than the gastrointestinal motility disorder disease.

In addition, the pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, hormone therapy, drug treatment or biological response modifiers to treat the gastrointestinal motility disorders.

The pharmaceutical composition of the present invention may further include a suitable carrier, excipient, or diluent according to a conventional method, in addition to the mixed extract including the black side extract and the corydale extract in a weight ratio of 1: 5.

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

The pharmaceutical composition of the present invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally or topically) according to the desired method, and preferably orally.

The pharmaceutical composition of the present invention may be formulated in various preparations for administration. For example, the pharmaceutical composition of the present invention is a tablet, coated tablets, capsules, pills, granules, suppositories, solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, powders Or as a spray.

The pharmaceutical composition may be formulated into solid preparations such as tablets, pills, powders, granules or capsules or liquid preparations such as suspensions, solvents, emulsions or syrups for oral administration. Alternatively, the pharmaceutical composition may be formulated as a sterile aqueous solution, non-aqueous solvent, suspension, emulsion, lyophilized agent or suppository for parenteral administration.

When the pharmaceutical composition of the present invention is formulated with solids such as tablets, coated tablets, capsules, pills or granules, (a) fillers such as starch, lactose, sucrose, glucose, mannitol or silicic acid and Weight agent, (b) a binder such as carboxymethyl cellulose, alginate, gelatin, polyethylene glycol, microcrystalline cellulose, highly dispersible silica, natural gum, synthetic gum, povidone, copovidone, polyvinylpyrrolidone or gelatin, ( c) hygroscopic agents such as glycerol, (d) disintegrants such as agar, calcium carbonate or sodium carbonate, (e) dissolution retardants such as paraffin, (f) absorption accelerators such as quaternary ammonium compounds, (g) cetyl alcohol or glycerol Wetting agents such as monostearate, (h) adsorbents such as kaolin or bentonite, or (i) talc, calcium stearate, magnesium stearate, magnesium stearate, talc and high It may be formulated by adding a lubricant such as sieve polyethylene glycol or mixtures of the materials described in (a) to (i) above.

When the pharmaceutical composition is formulated with a liquid formulation such as suspension, solvent, emulsion or syrup, the pharmaceutical composition may contain various diluents such as water and liquid paraffin, wetting agents, sweeteners, fragrances, preservatives, preservatives, coloring agents, and the like. It can be formulated by adding branch additives. For example, the pharmaceutical composition may be formulated by further adding a sweetener such as peppermint oil, eucalyptus oil or saccharin.

When formulating the pharmaceutical compositions of the present invention into suppositories, fats such as polyethylene glycol, cacao fat, higher esters (e.g., C14-alcohols with C16-fatty acid), witepsol, macrogol, tween 61, can be formulated using water-soluble or insoluble excipients such as laurin paper and glycerol gelatin or mixtures thereof.

When the pharmaceutical composition of the present invention is formulated as a suspension for parenteral administration, liquid diluents such as water, ethyl alcohol, propylene glycol, polyethylene glycol, ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, fine Crystalline cellulose, aluminum metahydroxy, bentonite, agar, tragacanth, injectable esters such as ethyloleate, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil or sesame oil oil, or these Mixtures of these may be used.

When the pharmaceutical composition of the present invention is formulated into an ointment, paste, cream or gel, etc., animal and vegetable fats, wax paraffin, starch, targacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicic acid, talc, Zinc oxide or mixtures thereof and the like can be used.

When the pharmaceutical composition of the present invention is formulated as a powder or spray, it can be formulated using lactose, talc, silicic acid, aluminum hydroxide, calcium silicate, polyamide powder or mixtures thereof. In addition, when formulated with the spray agent, a conventional fossa such as chlorofluorohydrocarbon may be further used, and may be formulated as a nasal spray using Fiji-4000 and glycerin.

The pharmaceutical compositions according to the invention may be formulated into sustained or immediate release preparations using carriers, diluents, dispersants, surfactants, binders, lubricants and additives. For example, it may be formulated as a sustained release or immediate release preparation to release the active ingredient of the pharmaceutical composition according to the present invention to a specific site.

When the pharmaceutical composition according to the present invention is formulated into a sustained release formulation, it may be formulated in a sustained release form using a sealing agent composition such as a wax or a polymerizable material such as an enteric polymer, a water insoluble polymer, a hydrophobic compound or a hydrophilic polymer. . For example, when the pharmaceutical composition is formulated into tablets, capsules, pills, or granules, it may be formulated in a sustained release by forming a coating film on the outside.

In the formulation of the pharmaceutical composition of the present invention, the content of excipients and additives such as carriers, fillers, weighting agents, binders, wetting agents, disintegrating agents, dispersing agents, surfactants or diluents to be added is not particularly limited, and conventional formulations It may be appropriately adjusted within the content range used for the sake.

The dosage of the pharmaceutical composition of the present invention may vary depending on the weight, age, sex, health condition, diet, time of administration, method of administration, duration or interval of administration, excretion rate, constitution specificity, nature of the agent, severity of disease, etc. The range varies. For example, the pharmaceutical composition of the present invention may be administered in an amount of about 0.01 to about 10 g / kg, preferably about 1 to 5 g / Kg on the basis of the mixed ground before the mixed extract is extracted, the frequency of administration It may be administered once to several times daily.

The pharmaceutical composition of the present invention can be administered to various mammals such as rats, mice, livestock, humans, and the like. All modes of administration are not particularly limited and can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.

The herbal extract of the present invention has little toxicity and side effects, so it can be used with confidence even for prolonged administration for prophylactic purposes.

The present invention provides a health functional food comprising a mixed extract comprising black extract and corydalis extract in a weight ratio of 1: 5.

The health functional food defined in the present invention has been newly defined through the "2002 Act on Health Functional Food", and the health function defined in the Food and Drug Administration Notice 2004-12 is sufficiently established for the human body. Health foods listed in the Regulations List on the Recognition of Food Ingredients or Ingredients.

The health functional food of the present invention contains only herbal ingredients such as the black side extract and corydalis extract and is safe and can be taken for a long time in the form of food. In addition, the mixed extract containing the black axis extract and corydalis extract in a weight ratio of 1: 5 shows a remarkably excellent effect on gastrointestinal motility disorders, so when the intake of the mixed extract in food form for a long time is frequently expected in daily life It is possible to effectively prevent or ameliorate the symptoms of gastrointestinal dyskinesia, which is inevitable.

The mixed extract of the black shaft extract and corydalis extract is a health functional food may be a variety of foods, for example, beverages, gum, tea, vitamin complexes, health supplements and the like.

In addition, the health functional food comprising a mixed extract of the black shaft extract and corydalis extract may be in the form of pills, powder, granules, acupuncture, tablets, capsules or beverages.

The health functional food comprising a mixed extract of the black shaft extract and corydalis extract is about 0.01 to about 15% by weight of the mixed extract including the black shaft extract and corydalis extract in a weight ratio of 1: 5, based on the total weight of the total food, Preferably from about 0.2 to 10% by weight. When the health functional food is a beverage, the beverage may include about 0.1 to 30 g, preferably about 0.2 to 5 g, of a mixed extract including the black shaft extract and corydalis extract in a weight ratio of 1: 5 based on 100 mL. .

The health functional food may further comprise a food supplement acceptable food supplement additives in addition to the mixed extract of the black shaft extract and the corydalis extract.

When the health functional food is a beverage, the beverage may further include various liquid components in addition to the mixed extract of black side extract and corydalis extract. For example, the beverage may further include a flavourant or natural carbohydrates.

The content of the natural carbohydrate included in the beverage may be about 1 to 20 g, preferably about 5 to 12 g, based on 100 mL of negative.

The natural carbohydrates that may be included in the beverage are not particularly limited in kind, but may be, for example, disaccharides such as monosaccharides, glucose or fructose, polysaccharides such as maltose or sucrose, textine or cyclo Sugars such as dextrins, sugar alcohols such as xylitol, sorbitol or erythritol.

In addition, the flavoring agent that may be included in the beverage may include natural flavoring or synthetic flavoring. As the natural flavoring agent, stevia extracts such as tautin or rebaudioside A, glycyrgin, and the like may be used, such as saccharin or aspartame.

The beverage may further include an additive in addition to the natural carbohydrate or flavoring agent. For example, the beverage may be various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the health functional food of the present invention may contain a pulp for the production of natural fruit juice, fruit juice beverage or vegetable beverage. These components may be used alone or in combination.

The amount of the additive is not particularly limited and may be appropriately adjusted as necessary. For example, the additive may be included in an amount of about 20 parts by weight or less based on 100 parts by weight of the beverage.

The invention heukchuk (Pharbitidis seed) extract of Corydalis and (CorydalisTuber) an extract 1: provides a gastrointestinal motility disorder prevention or treatment of the mixed extract to use a weight ratio of 5.

The present invention is a heukchuk (Pharbitidis seed) extract of Corydalis and (CorydalisTuber) extract 1: by administering the mixed extract at a weight ratio of 5 to a subject provides a method for preventing or treating gastrointestinal motility disorders.

The mixed extract comprising the black side extract and corydalis extract of the present invention in a weight ratio of 1: 5 has a remarkably excellent effect on gastrointestinal motility disorder disease. Therefore, the pharmaceutical composition comprising the mixed extract can effectively prevent or treat the gastrointestinal motility disorder disease, and the food containing the mixed extract can effectively prevent or improve the gastrointestinal motility disorder disease.

1 is a diagram showing a therapeutic effect of the gastric accomodation disorder of the mixed extract comprising the black extract and corydalis extract of the present invention in a weight ratio of 1: 5.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.

In addition, the reagents and solvents mentioned below were purchased from Sigma unless otherwise noted. The experimental results of each experimental example were statistically processed using ANOVA (one way analysis of variance), and the significance test was performed at p <0.05 or p <0.01 level or less using the Student-Newman-Keuls Test. .

<Example>: Preparation of a mixed extract containing the black axis extract and corydalis extract in a weight ratio of 1: 5

The dried herbs of Corydalis Tuber and Pharbitis seed were purchased from Chinese herbal medicine in Kyungdong market and used after removing the contaminants. Dry corollas and black shafts were ground. 20 g of the pulverized black shaft and 100 g of crushed corydalis were mixed and 960 ml of an aqueous 50% ethanol solution was added thereto, stirred well at room temperature for 72 hours, extracted with hot water, and filtered. The filtrate was concentrated under reduced pressure at 55-65 ° C., and then lyophilized to obtain a soft extract xin mixed extract containing 1: 5 of black shaft extract and corydalis extract.

<Comparative Example 1>: Preparation of the mixed extract containing the black shaft extract and Hyunho red extract in a weight ratio of 1: 1

Except for using 20g of the ground black shaft and 20g of the pulverized cinnabar red, a mixed extract including the black shaft extract and cinnabar red extract in a weight ratio of 1: 1 was obtained using the same method as in Example.

<Comparative Example 2> Preparation of a mixed extract comprising a black shaft extract and a corydalis extract in a weight ratio of 1: 2

Using the same method as in the embodiment except for using the pulverized black shaft 20g and 40g of the pulverized cinnabar red to obtain a mixed extract comprising a black rake extract and coarse red extract in a weight ratio of 1: 2.

<Comparative Example 3> Preparation of a mixed extract containing the black shaft extract and Hyunho red extract in a weight ratio of 1: 3

Except for using 20g of the ground black shaft and 60g of the pulverized cinnabar red, a mixed extract including the black shaft extract and cinnabar red extract in a weight ratio of 1: 3 was obtained using the same method as in Example.

<Comparative Example 4> Preparation of the mixed extract containing the black shaft extract and corydalis extract in a weight ratio of 1: 4

Except for using 20g of the ground black shaft and 80g of the pulverized cinnabar red color, a mixed extract including the black shaft extract and cinnabar red color extract in a weight ratio of 1: 4 was obtained using the same method as in Example.

<Comparative Example 5> Preparation of the mixed extract containing the black shaft extract and Corydalis extract in a weight ratio of 1: 6

Except for using 20g of the ground black shaft and 120g of the pulverized cinnabar red color, a mixed extract including the black shaft extract and cinnabar red color extract in a weight ratio of 1: 6 was obtained using the same method as in Example.

Comparative Example 6 Preparation of a Mixed Extract Containing Black Axis Extract and Corydalis Extract in a Weight Ratio of 1: 7

Except for using 20g of the ground black shaft and 140g of the pulverized cinnabar red color, a mixed extract including the black shaft extract and cinnabar red color extract in a weight ratio of 1: 7 was obtained using the same method as in Example.

<Comparative Example 7> Preparation of the mixed extract containing the black shaft extract and Corydalis extract in a weight ratio of 1: 8

Except for using the pulverized black shaft 20g and 160g of the pulverized cinnabar red color using a substantially the same method as in Example to obtain a mixed extract comprising a black shaft extract and corydalis extract in a weight ratio of 1: 8.

<Comparative Example 8> Preparation of a mixed extract containing the black shaft extract and Corydalis extract in a weight ratio of 1: 9

Except for using 20g of the ground black shaft and 180g of the pulverized cinnabar red color, a mixed extract including the black shaft extract and cinnabar red extract in a 1: 9 manner was obtained using the same method as in the example.

<Comparative Example 9> Preparation of the mixed extract containing the black shaft extract and Corydalis extract in a weight ratio of 1: 10

Except for using 20g of the ground black shaft and 200g of the pulverized cinnabar red, a mixed extract including the black shaft extract and cinnabar red extract in a weight ratio of 1:10 was obtained using the same method as in Example.

Experimental Example 1 Gastric Emptying Effect

Experiments were performed using the gastric delay model described in the paper to determine the gastric emptying effect of the mixed extract comprising the black extract and the corydalis extract of the present invention in a weight ratio of 1: 5 (Calatayud S, Garcia Zaragoza E, Hernandez C, Quintana E, Felipo V, Esplugues JV, Barrachina MD.Downregulation of nNOS and synthesis of PGs associated with endotoxin-induced delay in gastric emptying.Am J Physiol Gastrointest Liver Physi2ol. 2002 Dec; 283 (6) : G1360-7))

250g male Sprague-Dawley rats were divided into groups based on their weight, and then purified and fed with standard diet and water at a temperature of 22-24 ° C and 60-80% humidity for a week. Fasted for hours. The drinking water was supplied during the fasting period, and the drinking water was also stopped 3 hours before the experiment. The mixed extract of Example or Comparative Example was suspended in 3% of hydroxy propyl methyl cellulose (hydroxy propyl methyl cellulose) at a concentration of 4 mg / mL and orally administered by 1 mL per horse.

After 45 minutes of oral administration, 2 mL of semisolid test meal per animal is orally administered by crushing the animal feed into water, and after 35 minutes, the stomach is sacrificed and the stomach is removed. The weight was measured. After the measurement, the stomach was washed with distilled water to remove the contents of the stomach and dried, and the weight of the stomach was measured again. Gastrointestinal discharge rate was calculated using the following formula 1, the results are shown in Table 1 below. The control group of Table 1 was orally administered only 1mL per horse physiological saline.

[Formula 1]

Gastric emptying (%) = [1- (the remaining semi-high form weight above / the half-high form weight at 0-hour)] x100

(0-hour semi-solid weight is a measure of semi-solid food remaining on the stomach at the expense of the semi-solid food immediately after administration)

[Table 1]

As can be seen in Table 1, when using the mixed extract of the embodiment including the black axis extract and corydalis extract in a weight ratio of 1: 5, the gastric emptying rate was 73.8% showed the highest value. In addition, compared to the mixed extract of Comparative Examples 1 to 9 containing the black shaft extract and corydalis extract in different ratios showed a high stomach discharge rate of about 50% to 200%.

Experimental Example 2 Confirmation of Gastrointestinal Transit (GIT) Treatment Effect Induced by Surgery

Experiments were carried out using a gastrointestinal metastasis delay model to determine the therapeutic effect of the mixed extract comprising the black extract and the corydalis extract of the present invention in a weight ratio of 1: 5. The gastrointestinal metastasis delay model suggests that fasting intestinal complex (MMC, Migartive motor complex) mainly affects gastric emptying and gastrointestinal movement, and focuses on the function of the gastrointestinal tract in functional dyspepsia. A model used for evaluation of efficacy (De Winter, BY, et al., Effects of mu- and kappa-opioid receptors on postoperative ileus in rats.Eur J Pharmacol, 1997. 339 (1): p. 63-7.) The experiment was carried out using.

250g SD rats (Sprague-Dawley rats) were separated by group based on their weight, and then purified and fed with standard diet and water at a temperature of 22 to 24 ° C and a humidity of 60-80% for a week. Fasted for hours. The drinking water was supplied during the fasting period, and the drinking water was also stopped 3 hours before the experiment. After the SD rats thus treated were anesthetized with ether, the surgical site was removed with a clipper, and then sterilized with povidone solution (Porvidone iodine). After a 5 cm incision of the skin, the abdominal wall and peritoneum were incised about 3 cm along the midline and massaged by hand to cause mild inflammation. Thereafter, the abdominal wall and peritoneal skin were closed using an auto clip, and then sterilized using a povidone solution (Porvidone iodine). After 4 hours of recovery time, the mixture of Examples or Comparative Examples was suspended in 3% hydroxypropylmethylcellulose at a concentration of 4 mg / mL and orally administered by 1 mL per horse.

After 1 hour from the administration of the mixture of the above embodiment or the mixture of Comparative Example, the fluorescent labeled dextran (Fluescein isocyanate-labeled dextran, FITC, 5 mM solution diluted 10-fold in physiological saline) was administered and autopsied after 15 minutes The small intestine from the duodenum to the cecum were extracted and divided into 10 equal parts. The equally divided tissues were placed in a 12 well plate and 1 mL of physiological saline was added and stored at 0-4 ° C. for 24 hours. Thereafter, fluorescence was measured for the supernatant of the well plate. From the fluorescence measurements, the distribution ratio of fluorescently labeled dextran to each part of the intestine evenly divided using Equations 2 and 3 was obtained, and gastrointestinal metastasis was expressed as a geometric center for the distribution of fluorescent dextran. (Miller, MS, JJ Galligan, and TF Burks, Accurate measurement of intestinal transit in the rat.J Pharmacol Methods, 1981. 6 (3): p. 211-7.). The results are shown in Table 2. In Table 2, the control group was administered 1mL per horse only saline after the operation.

[Equation 2]

Fluorescence distribution ratio (%) of each small intestine part = (fluorescence value / total fluorescence value of each part) × 100

[Equation 3]

Geometric center = {(sum of fluorescence ratio (%) × interval value of each small intestine)} ÷ 100

TABLE 2

As can be seen in Table 2, in the case of administering the mixed extract of the embodiment comprising a black shaft extract and corydalis extract in a weight ratio of 1: 5, Comparative Examples 1 to 9 of the black shaft extract and corydalis extract in different ratios of The geometric center value was about 2 times higher than the mixed extract. From this, it can be seen that the mixed extract of the present invention including the black shaft extract and the corydalis extract in a weight ratio of 1: 5 can more effectively treat the delay in gastrointestinal motility than the composition comprising the black shaft extract and the corydalis extract in different ratios. .

<Experiment 3> Confirmation of treatment effect for adaptive gastric accomodation disorder

The gastric compliance reaction is a normal reaction to food intake, and about 40% of functional dyspepsia patients have impaired gastric compliance, and are associated with premature satiety and reduced insecticidal symptoms in functional dyspepsia patients.

Tack, J., et al. Influence of tegaserod on proximal gastric tone and on the perception of gastric distension. Aliment Pharmacol Ther, 2003. 18 (10): p. 1031-7, Xu, J. and JDChen, Peripheral mechanisms of sibutramine involving proximal gastric motility in dogs. The experiment was performed as follows by referring to Obesity (Silver Spring), 2006.14 (8): p.1363-70.

Beagle dogs were housed in single cages for one week at 22-24 ° C. and 60-80% humidity for standard feeding and water supply.

Thirty minutes before surgery, 30 mg / Kg of cepharadine was administered as an antibiotic therapy. After anesthesia with zoletil intravenous injection, the posture was corrected to the supine position, and the surgical site was earned. A minimal incision of the exposed skin and muscle layer was made to open the abdominal cavity, expose the stomach, and support sutures at both ends. In order to minimize the bleeding area of the stomach, a small incision was made and the medial portion of the gastric fistula was inserted as short as possible. Absorb sutures were continuously sutured to the mucosa of the stomach and confirmed the fixation of the pistula, the stomach layer of the stomach was simply Lambert sutured and inserted the retaining ring and the stomach was repositioned. After confirming the position of the pistula, the peritoneum and the muscle layer were sutured with an absorbent suture to fix it firmly. Antibiotic (cephalexin 30mg / kg, BID) and anti-inflammatory drug (serratio peptidase 0.2mg / kg, BID) were administered for a week after surgery. The compliance test was performed after a recovery period of 2 weeks or more.

The beagle dog, fasted for 24 hours, was placed on a sling and fixed. Then open the gastric fistula cap, wash the inside of the stomach with water at the same temperature as the body temperature, insert a balloon connected to the Barostat (G & J Electronics) through the distal end and x-ray The location was confirmed by a photograph.

The balloon pressure was increased from 0mmHg to 1mmHg so that the excursion by breathing could be clearly observed.The pressure at which the volume of the balloon was 30cc or more was set as the minimum distending pressure (MDP) and the minimum expansion pressure + The experiment was carried out at a pressure of 2mmHg. After removing all the air from the balloon set to 0 mL to expand the folded balloon to 200 mL to confirm the normal operation. After 5 minutes of stabilization, either one of Examples or Comparative Examples 1 to 9 was suspended in 3% of hydroxypropylmethylcellulose at a concentration of 4 mg / mL, orally administered at a dose of 1 mL per kg, and then basal after 40 minutes. The acclimation volume (basal accommodation volume) was measured for 10 minutes and dissolved in a powder (ensure powder, 250kcal / 200cc) in 200 cc of water was supplied to eat as much as possible with a 50 mL syringe (syringe). Gastric acclimatization volume was measured at a pressure of minimum expansion pressure + 2 mmHg for 1 hour from the start of diet administration. Gastric compliance volume values according to time when the mixed extract of Example was administered are shown in FIG. 1.

In addition, as shown in the graph of FIG. 1 for the example, a graph is drawn with the X-side time and the Y-axis as the gastric compliance volume for the comparative examples, and the area value of the lower portion of the graph, that is, the gastric volume-time curve for 1 hour. The bottom area was calculated and shown in Table 3 below. In FIG. 1 and Table 3, the control group 1 is a group orally administered only 1 mL per kg of saline instead of the mixed extracts of Examples or Comparative Examples 1 to 9, and the control group 2 is sumatriptan instead of the mixed extracts of Examples or Comparative Examples 1 to 9 Is orally administered in an amount of 1 mL per kg body weight of the experimental animal.

[Table 3]

As can be seen in Table 3, when the mixed extract of the embodiment containing the black axis extract and corydalis extract in a weight ratio of 1: 5, Comparative X 1 which is a soft extract X containing the black axis extract and corydalis extract in different ratios. It showed an area value of about 20% to 60% higher than the mixed extract of 9 to 9. In addition, the area value was about 90% higher than that of the control group 1 administered with saline only, and about 40% higher than the control group 2 administered orally with sumatriptan. From this, the mixed extract containing the black shaft extract and the corydalis extract in a weight ratio of 1: 5 has a much higher adaptive gastric compliance disorder than the mixed extract containing the black shaft extract and the corydalis extract in different ratios and the conventionally used drug sumatriptan. It can be seen that more effective treatment.

Experimental Example 4 Analyzing Analgesic Effect on Visceral Hypersensitivity Reaction

Pain caused by visceral hypersensitivity is one of the common symptoms of gastrointestinal disorders (FGIDs), including functional dyspepsia. In order to confirm the analgesic effect on visceral hypersensitivity of the mixed extract including the black extract and the corydalis extract of the present invention in a weight ratio of 1: 5, Lin, C. and E.D. Al-Chaer, Long-term sensitization of primary afferents in adult rats exposed to neonatal colon pain. Brain Research, 2003. 971 (1): p. The experiment was performed according to the disclosed method of 73-82.

One week old SD rats were purchased with the mother and used for the experiments. Ten animals per cage were kept in a 12-hour day-night cycle and separated from the mother after 25 days of age. Twenty-four were given colorectal distension (CRD) during the day cycle, causing irritable rectum, and six were used as normal groups as they were. The experiment was conducted between 9 and 17 hours.

The irritable rectum was induced by rectal expansion according to the following method. Insert angioplasty balloon (Advanced Polymers Inc., length: 20.0mm; diameter: 3mm) into the descending rectum 3 cm through the anus and measure 60 mmHg (tensionometer) through the angioplasty balloon Pressure was applied to rats once daily at 8, 10 and 12 days of age for 1 minute to swell the rectum, causing irritable rectum.

Mixed extracts of any one of Examples or Comparative Examples 1 to 9 were suspended in 3% of hydroxypropylmethylcellulose at a concentration of 4 mg / mL in rats having an irritable rectal-induced hypersensitivity and weighing about 250 g, orally at 1 mL per horse. Administered. After about 40 minutes, the rats were anesthetized by intraperitoneal administration of pentobarbital sodium at a concentration of 50 mg / kg. The carotid artery was exposed by skin incision under anesthesia to fix and insert a P-50 tube connected to a blood pressure sensor to restore the skin and temporarily suture it. In order to apply a rectal swelling (CRD) to the balloon of the latex glove cut to 3cm length was prepared, the open part of the balloon was connected to the PE-tube and tied with a thread. After preparing for blood pressure measurement, the prepared balloon was inserted 4 cm deep through the anus and taped together with the tail to fix it so as not to be pushed out. The other end of the balloon connects a blood pressure monitor for pressure measurement. One hour after administration of the mixed extract of Example 1 or Comparative Examples 1 to 9, a stimulus was applied at a pressure of 20 to 90 mmHg and the change in blood pressure was recorded. At this time, rectal dilatation (CRD) stimulation was stopped when the blood pressure decreased after the stimulus was applied to reach a plateau and begin to increase again. When the pressure was restored to the basal blood pressure before applying the pressure at each stage, and the stable blood pressure was shown, the pressure was progressed to the next stage.

Blood pressure changes were recorded for the entire time of rectal dilatation (CRD) of 20-90 mmHg. The change in blood pressure was at least 5 cycles at the time of stable blood pressure at the level of basal blood pressure before applying CRD and at the minimum decrease after applying CRD. The difference between the mean blood pressure values was determined as the changed blood pressure value by analyzing blood pressure values of at least 5 cycles. The change in blood pressure of 15 mmHg or more was determined as the change in blood pressure when pain was detected as a criterion for the pain threshold.

The rectal swelling pressure value that causes 15mmHg blood pressure change was estimated using the quadratic equation (regression analysis method) between blood pressure and pressure, and the pressure value starting to cause blood pressure change of 15mmHg was calculated as the pain threshold. Shown in In Table 4, the control group 1 was administered only 1 mL per physiological saline instead of the mixed extract of the black extract and corydalis extract to the rats with irritable rectum, control 2 represents a normal group did not cause irritable rectum.

[Table 4]

As can be seen in Table 4, in the case of administering the mixed extract of the embodiment comprising a black shaft extract and corydalis extract in a weight ratio of 1: 5, Comparative Examples 1 to 9 of the black shaft extract and corydalis extract in different ratios Rectal swelling pressure, that is, the pain threshold, which causes the blood pressure change of 15 mmHg, was higher than the mixed extract, about 30% to 68% or more. In addition, the administration of the mixed extract of Example showed an increase in pain threshold of about 100% or more compared to the control.

From this, it can be seen that the mixed extract including the black shaft extract and the corydalis extract in a weight ratio of 1: 5 can more effectively treat the intestinal hypersensitivity than the mixed extract including the black extract and the corydalis extract in different ratios.

Claims (8)

Heukchuk (Pharbitidis seed) extract of Corydalis and (CorydalisTuber) an extract 1: extract mixed at a weight ratio of 5. The mixed extract of claim 1, wherein the mixed extract is obtained by mixing the black shaft and the corolla color, and then extracting the mixture. The mixed extract according to claim 1, wherein the mixed extract is a mixture of an extract of black shaft obtained from the black shaft and an extract of corydalis obtained from the corydalis. Heukchuk (Pharbitidis seed) extract of Corydalis and (CorydalisTuber) extract 1: Gastrointestinal motility disorder prevention or treatment a pharmaceutical composition comprising an extract mixture comprising a weight ratio of 5. According to claim 4, wherein the gastrointestinal motility disorder disease is functional dyspepsia, ulcer dyspepsia, non-ulcer dyspepsia, gastro-esophageal reflux disease, reflux esophagitis, gastric insufficiency, false bowel obstruction, gastric palsy, constipation, irritable bowel syndrome At least one selected from the group consisting of irritable colitis, diabetic gastrointestinal dysfunction, gastrointestinal dyskinesia due to chemotherapy, gastrointestinal obstruction due to digestive tract dysfunction, gastrointestinal dyskinesia due to myotonic dystrophy, and non-cardiac chest pain Phosphorus pharmaceutical composition. The method of claim 4, wherein the gastrointestinal motility disorder disease is 5-HT _3. Pharmaceutical compositions resulting from receptor hyperactivity or 5-HT ₄ receptor antagonism. Heukchuk (Pharbitidis seed) to extract and Corydalis (CorydalisTuber) Extract 1: dietary supplements containing the extract mixed at a weight ratio of 5. 8. The dietary supplement of claim 7, wherein the dietary supplement is a powder, tablet, capsule, syrup or beverage.

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