KR20220047436A - Korean Medicinal Compounds for Improving Gastroesophageal Reflux Disease Comprising Herbal Mixture - Google Patents

Abstract

The present invention relates to a health functional food composition for improving gastroesophageal reflux disease, and a Korean medicinal compound for preventing or treating the gastrointestinal disease, comprising a herbal mixture. The compounding ratio of the extract of the present invention is derived through a process of oriental medicine dialectic. The present invention has an excellent symptom improvement effect in patients with gastroesophageal reflux disease.

Description

Korean Medicinal Compounds for Improving Gastroesophageal Reflux Disease Comprising Herbal Mixture comprising mixed herbal medicines

The present invention relates to a health functional food composition for improving gastroesophageal reflux disease, and a herbal composition for preventing or treating gastrointestinal diseases, comprising a mixed herbal medicine as an active ingredient.

Gastroesophageal reflux disease (GERD) is a disease caused by the reflux of gastric or duodenal contents into the esophagus. do. The most important path of pathogenesis of gastroesophageal reflux disease is considered to be due to the temporary relaxation of the lower esophageal sphincter (LES). etc. may be the cause. The typical symptoms of gastroesophageal reflux disease are heartburn and acid reflux, which usually occur easily after eating a large amount of food or in a supine position. Gastroesophageal reflux disease (GERD) is one of the most common diseases affecting millions of people worldwide (Nasi, de Moraes-Filho et al., Arq Gastroenterol. 2001), and its clinical importance is growing among various gastrointestinal diseases. In addition, modern lifestyle habits such as obesity, high-fat diet, and physical inactivity further increase the incidence of gastroesophageal reflux disease, and there is an urgent need for a treatment for this. In particular, gastroesophageal reflux disease (GERD) is a chronic disease and requires continuous treatment because symptoms often recur when treatment is stopped or the dose of the drug is reduced.

The most effective known treatment for gastroesophageal reflux disease is to decrease gastric acid secretion with histamine H ₂ -receptor antagonists or proton pump inhibitors (PPIs). The dose of the drug is determined according to the severity of the disease and symptoms, and the goal of drug administration is to raise the acidity in the stomach to pH 4 or higher during the daytime when reflux occurs frequently. The greater the degree of pathological gastric acid exposure in the esophagus, the stronger the gastric acid suppression method is required.

As an example, as a prior art related to the prevention and treatment of gastroesophageal reflux disease, Korean Patent No. 10-1841662 is disclosed, which is a solid dispersion of esomeprazole prepared by spray-drying and improved acid instability. is about In detail, it relates to an optimal composition solid dispersion with improved acid instability, including esomeprazole alkali salt, an alkalizing agent and a hydrophilic polymer, and a pharmaceutical composition comprising the same.

However, although H ₂ -receptor blockers and gastrointestinal motility agonists are helpful in relieving symptoms, they have insignificant effects in severe and severe reflux esophagitis. In addition, antacids such as mylanta, Maalox, Tums, Rolaids, and Graviscon neutralize stomach acid, but antacids containing magnesium may cause diarrhea. Antacids containing aluminum may cause constipation, and inflammation of the esophagus cannot be cured. PPI, represented by omeprazole, blocks gastric acid secretion by inhibiting the pump of gastric acid-producing cells. causes In addition, despite the use of PPI, as more than 10% of patients currently experience the recurrence of gastroesophageal reflux disease, the need to develop substances for preventing and improving gastroesophageal reflux disease derived from natural products that are less toxic, have fewer side effects to the human body, and exhibit excellent effects is emerging. is becoming

In this situation, the present inventors have developed a health functional food composition and herbal medicine composition for improving gastroesophageal reflux disease containing mixed herbal ingredients as an active ingredient, and completed the present invention by establishing the blending ratio of herbal ingredients through the process of oriental medicine dialectical debate. .

One technical problem to be achieved by the present invention is 15 to 17 parts by weight of moryu powder, 3 to 5 parts by weight of porridge, 3 to 5 parts by weight of ground fruit, 3 to 5 parts by weight of gold, 3 to 5 parts by weight of new grain, and 2 to 5 parts by weight of licorice. It is to provide a functional health food composition for improving gastroesophageal reflux disease, comprising the extract provided by extracting the mixed herbal material containing 4 parts by weight as an active ingredient.

Another technical problem to be achieved by the present invention is 15 to 17 parts by weight of rice flour, 3 to 5 parts by weight, 3 to 5 parts by weight of ground fruit, 3 to 5 parts by weight of gold, 3 to 5 parts by weight of new grains and 2 parts by weight of licorice. It is to provide an herbal composition for the prevention or treatment of gastrointestinal diseases, comprising as an active ingredient the extract provided by extracting the mixed herbal medicine containing to 4 parts by weight.

The technical problems to be achieved by the present invention are not limited to the technical problems mentioned above, and other technical problems not mentioned can be clearly understood by those of ordinary skill in the art to which the present invention belongs from the description below. There will be.

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

As an aspect for solving the above-mentioned problems, the present invention provides 15 to 17 parts by weight of moss flour, 3 to 5 parts by weight of porridge, 3 to 5 parts by weight of ground fruit, 3 to 5 parts by weight of gold, 3 to 5 parts by weight of new grain. And it provides a health functional food composition for improving gastroesophageal reflux disease, comprising an extract provided by extracting a mixed herbal medicine containing 2 to 4 parts by weight of licorice as an active ingredient.

The functional health food composition for improving gastroesophageal reflux disease of the present application includes, as an active ingredient, an extract of a mixed herbal medicine extracted by mixing the herbal substances described below in a predetermined ratio. Unless otherwise specified, herbal medicine refers to a cut of a specific part of a medicinal plant described herein, or a processed product thereof, unless otherwise specified, and the described medicinal plant is mainly expressed by scientific name, but includes varieties and subspecies.

moryeobun

Moryeobun (牡蠣粉) is a powder made by burning the shells of oysters. It is usually used as an oral remedy in oriental medicine, or as an oral medicine for fever, mongseol (夢泄), lobster fever (帶下), and thirst. To paraphrase, moryeo is a washed and dried oyster shell, and the names used in oriental medicine are Yeohap (蠣蛤) and Mohap (牡蛤). It is a conch of Ostrea gigas Thunb., Ostrea rivuralis Gould., and Ostrea rivuralis Gould. Oyster shellfish are found in the East, West, and South Seas of our country. Catch the conch at any time except spawning season and wash and dry it. The taste is salty and the nature is flat.

The moryeo flour acts on the nerves and liver, and strengthens and nourishes the tone (陰精), removes phlegm, softens the hardened, and stops sweating. It also cures oil wells (遺精), stops diarrhea, and treats boils. It has been shown through several experiments that it lowers the acidity of the stomach. Eumheo (陰虛) is used for chest pain, palpitations, dizziness, pain, and cold sweats. Take 10~30g per day in the form of soup, powder, or pills.

kill

Phyllostachyos Caulis in Taeniam is a shade-dried middle layer of Phyllostachys nigra var. Membrane-shaped or long wooden rod-shaped. Although the width and thickness are uneven, there are also pieces with a thickness of 1 to 3 mm. The outer surface is light green to yellowish green or grayish white, and there are some in powder form. The vagina is light, elastic and fibrous. This medicine has a slight odor and a mild taste. In Bonchogangmok (本草綱目), the efficacy was divided into Damjuknyeo (淡竹茹), Gojukryeo (苦竹茹), and Geunjuknyeo. It was said to be effective when vomiting blood, uterine bleeding, and nosebleeds, and when blood is mixed in urine with damjuk-ryo, it was said to be effective for fever caused by overwork.

branch

It refers to the unripe fruit of Poncirus trifoliata Rafinesque, a deciduous broad-leaved tubercle belonging to the Rutaceae family. It has a round shape with a diameter of 3 cm. The flowering period of the dandelion is March-May, the fruiting period is September-November, and the harvesting period is September-October. It is known to grow wild on islands such as Jeju-do and Gadeok-do in the southern part of Korea, and is cultivated and harvested in Gyeongju and the central and southern regions of Korea. In <Donguibogam>, it is described that Jisil removes the walls of the chest and sides, and the crust removes the walls and disperses the carriers of the chest. Yes (Hong Ik-jae, Tea Life Culture Exhibition, July 10, 2012). The ripe fruit is called crust, and the fruit and crust have different efficacy and are used for different purposes. In addition, according to the Food and Drug Administration, licorice is known to exhibit anti-inflammatory efficacy, efficacy against gastritis and gastric ulcer, efficacy related to metabolic osteoporosis disease, and anticancer activity (Food and Drug Administration Herbal Medicine Information System). In the present invention, the fruit may be purchased commercially sold, or harvested or grown in nature.

Gold

Gold means gold ( Scutellaria baicalensis Georgi), a perennial herb in the family Lamiaceae. The root is used medicinally, and in oriental medicine, it is used as an ingredient in Gagam Yijintang, Galgeunhaegitang, Ganghwalchangchultang, Geumgweedangguisan, etc. Stearic acid, Neobaicalein, Indole, Benzoic acid acid), etc. It is known in Oriental medicine that “sexuality is good and non-existent, and 味 is 苦”. In Dongui Bogam, “Gold is stable for the fetus and has hemostatic effect. ) and yeolgyeol (熱結) are released while detoxifying.” The efficacy is explained.

new song

Singok (Massa Medicata Fermentata) is a yeast that is fermented with yeast bacteria by kneading powder or bran with ingredients such as red bean powder, mashed apricot seeds, ragweed mugwort juice, sagebrush juice, and willow juice. It is an irregular yellow-brown to brown mass. It is easy to powder, light, coarse and brittle. The composition is brown, and there is a mixture of brownish fibrous substances. The drug has a hoarse odor and a slightly bitter taste. It strengthens the function of the digestive system and has the effect of comforting the stomach along with the action of helping digestion. It is effective when you feel tired, when your chest is stuffy and full, when you have vomiting and diarrhea, and when you have a stomach ache due to eohyeol after childbirth. As a result of pharmacological experiments, it was reported that there was a gastric effect.

licorice

Licorice (Glycyrrhizae Radix et Rhizoma) is used as it is as the root and rhizome of Glycyrrhiza uralensis Fischer, Glycyrrhiza glabra Linne, or Glycyrrhiza inflata Batal, or the epidermis is removed. It is one of the medicines being used. The medicinal part is a root and a rhizome, and the root is cylindrical, 25-100 cm long, and 5-35 mm in diameter. The outer surface is reddish-brown or yellowish-brown, and the vertical folds, dents, and shell eyes are distinct, and there are sparsely fine root marks, and the quality is firm. The cut cotton is fibrous, yellowish-white, powdery, and the cambium has distinct rings, and the waterline is radial and sometimes with gaps. The rhizome is cylindrical, and there are bud marks on the outer surface, and there are numbers in the middle of the cut surface. When the cross section of this drug is viewed under a microscope, the peeled licorice has several layers of yellowish-brown cork, and one to three layers of cork cortex on the inside. In the skin, there are bundles of bast fibers, which are thickened and less cotton, and these bundles are mainly composed of crystalline cell rows. The ducts are well visible, but in old ones, they are not close to the cambium and are generally degenerated and invisible. The repair is radial and penetrates the cambium to reach the skin, and the repair cells are full of starch granules. The conduits are large, singly or in groups, arranged radially between the waterlines. Bundles of xylem fibers surrounded by rows of crystal cells are scattered between conduits and conduits. There are numbers in the rhizome, and there are calcium oxalate single crystals and starch granules in the flow cells of the skin and neck. Peeled licorice lacks the bark and parts of the phloem.

The mixed herbal material used in the extract of the present application is 15 to 17 parts by weight of mulberry flour, 3 to 5 parts by weight, 3 to 5 parts by weight of ground fruit, 3 to 5 parts by weight of gold, 3 to 5 parts by weight of new grain, and 2 to 4 parts by weight of licorice. includes wealth. The above compounding ratio of the extract of the present invention was derived through the process of dialectical debate by administering and receiving feedback from the present inventors in the course of treating numerous patients in oriental medicine hospitals for several decades. When the extract of the above combination ratio is administered to a patient with gastroesophageal reflux disease, a significant improvement effect is exhibited. According to an experimental example of the present application, it was found that a significant difference in effect was observed compared to the comparative example in which a drug having a lower ratio of moryeo was administered. The above result is only an exemplary experimental result, and the experimental result that the compounding ratio is superior to other compounding ratios has been proven in the course of research.

According to one embodiment of the present application, the mixed herbal material may further include any one or more herbal materials selected from the group consisting of cine, cloves, ginger and jujube. In this case, the efficacy can be maximized, and the taste and aroma of the entire composition can be enhanced. Specifically, the mixed herbal material may further include 2 to 4 parts by weight of cine, 1 to 2 parts by weight of cloves, 5 to 7 parts by weight of ginger, and 5 to 7 parts by weight of jujube.

The extract of the present application is obtained by extracting after mixing the above-mentioned herbal materials. As used herein, the term "extract" refers to a preparation obtained by squeezing a herbal medicine with an appropriate leachate and evaporating the leachate, but is not limited thereto. It may be a dried product obtained by drying, a crude product thereof, or a purified product. The extract of the mixed herbal medicine can be prepared using a general extraction method, separation and purification method known in the art. The extraction method is not limited thereto, but preferably methods such as hot water extraction, hot water extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction may be used.

According to one embodiment of the present application, the extract can be prepared by extracting with an extraction solvent or fractionation by adding a fractionation solvent to an extract prepared by extraction with an extraction solvent. The extraction solvent is not limited thereto, but a solvent such as water, an organic solvent or a mixture thereof may be used, and the organic solvent is an alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, hexane or A non-polar solvent of dichloromethane or a mixed solvent thereof may be used. In addition, preferably water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof may be used, and more preferably water may be used. In an embodiment of the present invention, an extract using water as the solvent was prepared. In the present application, the extract is also referred to as an herbal extract.

According to one embodiment of the present application, the extract may be an extract extracted by putting the mixed herbal medicine in a water heater together with the extraction solvent and shaking at a high temperature. Specifically, the extract may be agitated by adding the mixed herbal material to 10 to 1,000 parts by weight of water. More preferably, 200 to 300 parts by weight of the solvent may be heated and extracted by adding the mixed herbal material. In addition, according to one embodiment of the present application, the extract may be extracted for 6 to 10 hours, specifically 7 to 9 hours at a temperature of 80 to 110 ℃. When extracted at a temperature higher than this, the active ingredients may be denatured, and when extracted at a temperature lower than this, the active ingredients may not be extracted to the desired degree.

According to one embodiment of the present application, the extract extracted by heating of the present invention may be one that is further shaken after removing the solute of the mixed herbal material. Specifically, it may be agitated until 1/5 to 1/4 of the added solvent remains.

In addition, the extract may be filtered. For the filtration, filtration methods used in the art, such as atmospheric filtration, reduced pressure filtration, pressure filtration, ultrafiltration, microfiltration, and reverse osmosis filtration, may be used. The pore size of the filter used for filtration may be 20 to 40 μm, and if the pores of the filtration filter are larger than this, the feeling of foreign matter may increase, and if the pores of the filtration filter are smaller than this, the main active ingredient may be excluded.

In addition, the extract may be concentrated. The concentration may include methods such as concentration under reduced pressure heating, concentration under atmospheric pressure, spray drying, drum drying, freeze drying, and the like, and among them, concentration under reduced pressure may be used. Specifically, the concentrate may be concentrated to contain up to 40 to 50% by weight of solids. The concentration of solids in the extract can be measured through the weight of the solids remaining when evaporated.

The extract of the present invention has a use for improving gastroesophageal reflux disease. As used herein, the term "gastroesophageal reflux disease" refers to a disease caused by reflux of gastric or duodenal contents into the esophagus, and includes reflux esophagitis, which is damage and inflammation of the esophageal mucosa caused by reflux. In addition, the composition of the present invention can prevent or treat gastroesophageal reflux disease, and chest pain such as burning sensation caused by reflux esophagitis, nausea, sore throat, sore throat, esophagitis, cough, expectoration, asthma, aspiration pneumonia, etc. can be treated According to an experimental example of the present application, the extract is administered to patients with gastroesophageal reflux disease to improve gastroesophageal reflux symptoms such as heartburn, acid reflux, sleep disturbance, additional drug use without a doctor's prescription, and epigastric pain and nausea It has been confirmed that this can be done. More specifically, it was confirmed that there was a significant improvement for reflux esophagitis and the resulting heartburn or acid reflux. Accordingly, in the present invention, there may be provided a health functional food composition for improving reflux esophagitis and heartburn or acid reflux symptoms resulting therefrom, including the extract.

"Health functional food" as defined herein means a food manufactured and processed using raw materials or ingredients useful for the human body according to Health Functional Food Act No. 6727, and "functionality" means the human body's It refers to intake for the purpose of obtaining useful effects for health purposes such as regulating nutrients with respect to structure and function or physiological effects.

Foods to which the extract of the present invention can be added include, for example, various foods, beverages, gum, tea, vitamin complexes, health functional foods, and the like.

According to one embodiment of the present application, the extract may be formulated in an amount of 200 to 300 mg at a time based on the extract concentrate (concentrate having 40 to 50% by weight of solid content) provided by the above-described extraction method. In addition, the dosage of the extract may be increased or decreased depending on the route of administration, the degree of disease, sex, weight, age, and the like. In general, it is preferable to be formulated with the above content based on adults, but the dosage is not intended to limit the scope of the present invention in any way. Administration 1 to 3 times a day is preferred, and more preferably, administration twice a day maximizes the effect of improving gastroesophageal reflux symptoms. The health functional food composition of the present application is preferably administered for 2 weeks or more, and more specifically, administration for 4 weeks or more is suitable for improving gastroesophageal reflux symptoms.

Carriers, excipients and diluents that may be included in the health functional food composition comprising the extract of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The extract of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., oral dosage forms, external preparations, suppositories, and sterile injection solutions according to conventional methods, respectively. According to an embodiment of the present application, it is formulated into a capsule, but is not limited thereto. For the formulation, the extract of the present invention may be powdered. Specifically, the concentrated extract and excipients such as dextrin may be powdered through a spray drying method.

In the case of formulation, it is prepared using commonly used diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient, for example, starch, calcium carbonate, sucrose, or It is prepared by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. may be included. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like can be used.

As used herein, the term “ameliorate” or “improvement” includes preventing further gastrointestinal disease or symptoms from appearing when a gastrointestinal disease or symptom has already developed, and eliminating gastrointestinal disease or symptoms when it has not yet developed include

As another aspect for solving the above-described problems, the present invention provides 15 to 17 parts by weight of moringa powder, 3 to 5 parts by weight of porridge, 3 to 5 parts by weight of ground fruit, 3 to 5 parts by weight of gold, 3 to 5 parts by weight of new grain. It provides an herbal composition for the prevention or treatment of gastrointestinal diseases, comprising as an active ingredient the extract provided by extracting the mixed herbal material containing 2 to 4 parts by weight of licorice and licorice.

The terms used herein are the same as described above.

As used herein, “oriental medicine” refers to medicines formulated according to the principles of oriental medicine. Generally, in Korea, it refers to a preparation classified as an herbal medicine according to the Pharmaceutical Affairs Act.

As used herein, “gastrointestinal disease” refers to a disease associated with a dysfunction of the gastrointestinal tract. Any disease causing the above-mentioned gastroesophageal reflux symptoms is included without limitation. When the above gastroesophageal reflux symptoms appear more chronically, it is considered a gastrointestinal disease as used herein. In other words, gastrointestinal diseases include epigastric pain, epigastric discomfort, epigastric pain, heartburn, epigastric cramps, chest pain, early satiety, acid reflux, postprandial satiety, epigastric pressure, epigastric bloating, nausea, belching, vomiting, and difficulty breathing. It has been confirmed that symptoms can be improved. More specifically, it includes dysfunction of the gastrointestinal tract causing heartburn or acid reflux, epigastric pain and nausea, and the like.

As used herein, the term “prevent” or “prevention” refers to the absence of a gastrointestinal disease or symptom if it has not yet developed, or to prevent further gastrointestinal disease or symptoms from appearing if the gastrointestinal disease or symptom has already developed. it means.

As used herein, the term “treat” or “treatment” refers to any treatment for a disease or gastroesophageal reflux disease associated with a gastrointestinal disease, and who has a predisposition to the disease or disease but has not yet been diagnosed with the disease or disease. preventing the development of a disease or disorder in a non-human mammal; inhibiting a disease or disorder, eg, by preventing its progression; alleviating a disease or condition, eg, by causing regression of the disease or condition; or alleviating the symptoms caused by the disease or condition, for example, by stopping the disease or condition.

On the other hand, each description and embodiment disclosed herein may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed herein are within the scope of the present invention. In addition, it cannot be said that the scope of the present invention is limited by the specific descriptions described below.

In addition, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Also, such equivalents are intended to be encompassed by the present invention.

The herbal extract of the present invention is derived from the formulation ratio through the process of oriental medicine apologetics, and shows an excellent symptom improvement effect in patients with gastroesophageal reflux disease. Accordingly, the extract of the blending ratio may be provided as a health functional food and herbal composition.

It should be understood that the effects of the present invention are not limited to the above-described effects, and include all effects that can be inferred from the configuration of the invention described in the detailed description or claims of the present invention.

1 is a schematic diagram of a process for preparing an herbal composition according to the present invention.

Hereinafter, the present invention will be described in more detail by way of Examples. However, the following examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

Preparation Example 1. Preparation method of Example 1 and Comparative Example 1

Example 1

1,600 g of porridge flour, 400 g of porridge, 400 g of ground fruit, 400 g of gold, 400 g of new grain, and 300 g of licorice. Add 5.0 L of purified water based on 1 ingredient (20 cheaps) to a boiling pot for 8 hours at a temperature of 100 ° C at 1 atmosphere. It was extracted by shaking to 1.2L. The extract was filtered through a micro filter (30 μm), and concentrated until the solid content was 40% or more. 500ml of the obtained herbal extract concentrate and dextrin were powdered in a ratio of 5:5 through a spray-drying method to obtain 500g. 450 mg of powder was placed in the capsule so that one serving was 225 mg based on the extract concentrate.

placebo

In Example 1, using 500 mL of purified water instead of the herbal extract in Example 1, a dextrin powder was prepared by a spray dryer method to prepare a capsule.

Comparative Example 1

Capsules were prepared in the same manner as in Example 1, except that 400 g of mulberry flour was added.

Test Example 1. Clinical evaluation

test design

GERD-Q (Korean version of the Gastroesophageal reflux disease Questionnaire) is a questionnaire for evaluating the severity of symptoms of gastroesophageal reflux disease. It is a simple six-item self-management tool rated as 2010;59:714-721.). The questionnaire was developed for the case of receiving first treatment at a primary medical institution for upper gastrointestinal symptoms without prior treatment experience. In the West, it is known to be helpful in determining the degree of diagnosis and treatment of gastroesophageal reflux disease. In this study, the researchers used the Korean version of GERD-Q, which was translated and reverse-translated with approval from the original author (EJ Gong, KW Jung, YW Min, KS Hong, HK Jung, et al. Journal of Neurogastroenterology and Motility 2019; 25 (1): 91-99.).

The composition of the GERD-Q consists of 4 symptoms (heartburn, acid reflux, sleep disturbance, use of additional drugs without a doctor's prescription) to increase the positive predictive value of gastroesophageal reflux disease (GERD) and 2 symptoms (epithelial pain) to increase the negative predictive value of gastroesophageal reflux disease. , nausea). That is, the former four symptoms are findings suggesting gastroesophageal reflux disease, and the latter two symptoms are findings suggesting the possibility of other diseases than gastroesophageal reflux disease. For each item, the presence or absence of symptoms in the past week is indicated in 4 stages. Each stage consists of days 0 (asymptomatic), 1 day, 2-3 days, and 4-7 days of symptom onset, respectively. Positive predictiveness items are increased from 0 to 3 points, and negative predictive rating items are decreased from 3 to 0 points, so that all items are summed and scored (range 0-18 points). The GERD-Q score was calculated as the sum of these scores and ranges from 0 to 18. In the GERD-Q questionnaire, the standard for dividing normal and abnormal scores was 8 points.

The clinical trial was designed as a patient blind, assessor blind intervention test.

Selection of test subjects

The present inventors recruited patients to Gangnam Widam Oriental Medicine Hospital as test subjects. Forty-five adult males and females between the ages of 20 and 65 with a prior GERD-Q score of 8 or higher were selected. Patients with chronic diseases such as hypertension, diabetes, and hyperlipidemia were excluded, and those taking drugs for chronic diseases were also excluded.

45 patients were divided into 3 groups of 15 patients each. Group 1 is a control group administered with a placebo, group 2 is a group administered with Example 1, and group 3 is a group administered with Comparative Example 1. The capsules administered to groups 1 to 3 all had the same properties, so that the patient could not know what kind of drug was being administered. Table 1 shows the sex and age of 45 subjects.

Subject identification code army castle age One One One 57 2 One One 24 3 One One 55 4 One 2 46 5 One 2 41 6 One One 48 7 One One 51 8 One One 36 9 One 2 48 10 One 2 21 31 One One 25 32 One 2 34 33 One One 38 34 One 2 41 35 One One 51 11 2 One 43 12 2 One 34 13 2 2 41 14 2 One 51 15 2 One 61 16 2 2 58 17 2 One 31 18 2 2 28 19 2 2 31 20 2 One 37 36 2 2 21 37 2 One 51 38 2 2 37 39 2 One 45 40 2 2 58 21 3 2 50 22 3 One 41 23 3 One 20 24 3 One 48 25 3 2 45 26 3 2 41 27 3 One 41 28 3 2 50 29 3 2 32 30 3 2 37 41 3 One 21 42 3 2 31 43 3 One 41 44 3 2 52 45 3 One 54

Clinical characterization of test subjects

Table 2 shows the results of GERD-Q analysis of 45 subjects before intervention.

District 1 District 2 District 3 One 11 10 13 2 17 11 15 3 10 9 13 4 9 15 15 5 13 17 15 6 15 14 9 7 10 9 12 8 12 14 19 9 13 15 12 10 15 12 11 11 11 14 10 12 14 11 10 13 14 12 15 14 12 10 10 15 13 13 13

Before the intervention, normality was tested to determine whether there was any difference in clinical characteristics between the three groups through a one-way ANOVA, and the KS test (Kolmogorov-Smirnova) and Shapiro-Wilk test were used. The assay results are shown in Table 3.

army Kolmogorov-Smirnov Shapiro-Wilk statistic degrees of freedom Significance Probability statistic degrees of freedom Significance Probability before arbitration District 1 .106 15 .200 .976 15 .930 District 2 .146 15 .200 .952 15 .564 District 3 .139 15 .200 .930 15 .271

Since the significance values of Kolmogorov-Smirnov and Shapiro-Wilk of all groups were greater than 0.05, it could be seen that the GERD-Q values of all groups were normally distributed. Accordingly, it was determined that the normality of the distribution between each group, an important assumption condition of the one-way analysis of variance (ANOVA), was satisfied.

Meanwhile, descriptive statistical values for the mean and standard deviation of the result values are summarized in Table 4 below.

number of test subjects Average Standard Deviation standard error 95% on average
confidence interval minimum maximum lower limit upper limit District 1 15 12.60 2.197 .567 11.38 13.82 9 17 District 2 15 12.40 2.414 .623 11.06 13.74 9 17 District 3 15 12.80 2.678 .691 11.32 14.28 9 19 Sum 45 12.60 2.387 .356 11.88 13.32 9 19

In the above results, the homogeneity of variance based on Levine's test is shown in Table 5. Since the significance probability was 0.05 or more, it was judged that there was no problem with the assumption of equal variance.

Levene statistics df1 df2 Significance Probability .242 2 42 .786

On the other hand, one-way ANOVA was performed on the premise that normality and homogeneity between each group were satisfied according to the above results. Since the significance probability was 0.904, it could be concluded that there was no difference in the GERD-Q result values between each group before the intervention.

sum of squares df mean square F Significance Probability military-to-military 1.200 2 .600 .101 .904 military-my 249.600 42 5.943 Sum 250.800 44

Arbitration method

Among 45 test subjects, group 1 was orally mediated with placebo, group 2 with Example 1, and group 3 with Comparative Example 1 twice a day (morning and evening) for 4 weeks.

Post-intervention clinical characterization

Table 7 shows the results of GERD-Q on 45 test subjects after 4 weeks of intervention.

District 1 District 2 District 3 One 10 8 10 2 15 10 14 3 8 11 12 4 11 16 15 5 14 9 13 6 13 13 8 7 12 5 12 8 12 8 18 9 14 12 13 10 13 11 10 11 10 7 15 12 15 6 9 13 11 11 14 14 12 9 10 15 11 12 12

In order to analyze whether the analysis results for the clinical characteristics follow a normal distribution, the KS test (Kolmogorov-Smirnov) and the Shapiro-Wilk test were used. The assay results are shown in Table 8.

army Kolmogorov-Smirnov Shapiro-Wilk statistic degrees of freedom Significance Probability statistic degrees of freedom Significance Probability after arbitration District 1 .113 15 .200 .961 15 .712 District 2 .120 15 .200 .980 15 .966 District 3 .143 15 .200 .968 15 .825

Since the significance probability values of Kolmogorov-Sminov and Shapiro-Wilk of all groups were greater than 0.05, it could be seen that the GERD-Q values of all groups were normally distributed. Accordingly, it was determined that the normality of the distribution between each group, an important assumption condition of the one-way analysis of variance (ANOVA), was satisfied.

On the other hand, the descriptive statistical values for the mean and standard deviation of the results are shown in Table 9 below.

number of test subjects Average Standard Deviation standard error 95% on average
confidence interval minimum maximum lower limit upper limit One 15 12.07 1.981 .511 10.97 13.16 8 15 2 15 9.87 2.875 .742 8.27 11.46 5 16 3 15 12.33 2.664 .688 10.86 13.81 8 18 Sum 45 11.42 2.718 .405 10.61 12.24 5 18

In the above results, the homogeneity of variance based on Levine's test is shown in Table 10. Since the significance probability was about 0.05 or more, it was judged that there was no problem with the assumption of equal variance.

Levene statistics df1 df2 Significance Probability .993 2 42 .379

On the other hand, one-way ANOVA was performed on the premise that normality and homogeneity between each group were satisfied according to the above results. Since the significance probability was 0.020, it could be judged that there was a difference in the mean value between each group.

sum of squares df mean square lie Significance Probability military-to-military 54.978 2 27.489 4.276 .020 military-my 270.000 42 6.429 Sum 324.978 44

Post hoc test (multiple comparisons)

For the difference in the mean value between each group, it was specifically attempted to confirm the difference in the mean value between the groups through a post-hoc test. It was analyzed using Turkey HSD, Bonferroni, and Dunnett T3 test, and the results of the mean value difference between groups are shown in Table 12 below.

　
　 (I) military (J) military average difference
(IJ) standard error Significance Probability 95% confidence interval lower limit upper limit Tukey HSD District 1 Army 2 2.200 .926 .056 -.05 4.45 3 Army -.267 .926 .955 -2.52 1.98 District 2 Army 1 -2.200 .926 .056 -4.45 .05 3 Army -2.467 .926 .029 -4.72 -.22 District 3 Army 1 .267 .926 .955 -1.98 2.52 Army 2 2.467 .926 .029 .22 4.72 Bonferroni Army 1 Army 2 2.200 .926 .066 -.11 4.51 3 Army -.267 .926 1.000 -2.58 2.04 Army 2 Army 1 -2.200 .926 .066 -4.51 .11 3 Army -2.467 .926 .033 -4.78 -.16 3 Army Army 1 .267 .926 1.000 -2.04 2.58 Army 2 2.467 .926 .033 .16 4.78 Dunnett T3 Army 1 Army 2 2.200 .901 .064 -.10 4.50 3 Army -.267 .857 .985 -2.45 1.91 Army 2 Army 1 -2.200 .901 .064 -4.50 .10 3 Army -2.467 1.012 .062 -5.03 .10 3 Army Army 1 .267 .857 .985 -1.91 2.45 Army 2 2.467 1.012 .062 -.10 5.03

As described above, group 2 mediated by Example 1 showed a significant difference in mean values compared with group 1 (control group) mediated by placebo and group 3 mediated by comparative example 1. Accordingly, it can be seen that excellent results are obtained according to the administration of the herbal composition of the present invention, which is significant depending on the setting of the compounding ratio.

Comparative analysis of statistical values before and after intervention by group

Statistical values before and after intervention for each group were analyzed using a non-parametric Wilcoxon signed rank test. Tables 13 to 18 show the statistical value comparison analysis results for groups 1 to 3.

District 1 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 8 8 64 positive rank 5 5.4 27 tie 2 Sum 15

District 1 Post-arbitration_score - Pre-arbitration_score Z -1.324 Approximate significance (two-tailed) .186

District 2 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 13 8.27 107.50 positive rank 2 6.25 12.50 tie 0 Sum 15

District 2 Post-arbitration_score - Pre-arbitration_score Z -2.729 Approximate significance (two-tailed) .006

District 3 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 10 6.10 61.00 positive rank 2 8.50 17.00 tie 3 Sum 15

District 3 Post-arbitration_score - Pre-arbitration_score Z -1.811 Approximate significance (two-tailed) .070

As described above, there was no significant difference before and after the intervention in group 1 mediated with placebo and group 3 mediated by Comparative Example 1, whereas group 2 mediated by Example 1 showed statistically significant results before and after the intervention. showed Therefore, it can be seen that, in the intervention of Example 1, there was a significant improvement in the symptomatic function of gastroesophageal reflux disease compared to the case where the placebo and Comparative Example 1 were mediated.

Heartburn and acid reflux scores before and after intervention

As a result of checking the most improved areas of the GERD-Q symptom score table before and after the intervention, it was confirmed that the items of heartburn and acid reflux improved the most. Only heartburn and acid reflux scores are shown in Tables 19 and 20 below.

Heartburn score before intervention Heartburn score after intervention District 1 District 2 District 3 District 1 District 2 District 3 One 3 2 2 2 0 One 2 One One One One One One 3 2 One 2 2 0 One 4 One One 3 2 2 2 5 2 2 3 2 0 2 6 One One One One 0 One 7 3 0 2 3 0 3 8 2 2 3 2 0 2 9 3 2 One 3 One One 10 One One 2 One 0 2 11 3 One One 2 0 3 12 One 2 One 2 0 One 13 2 3 3 One One 2 14 One One One One 0 One 15 One 3 3 0 2 2 Average 1.8 1.5 1.9 1.7 0.5 1.7

Acid reflux score before intervention Acid reflux score after intervention District 1 District 2 District 3 District 1 District 2 District 3 One 2 2 2 2 One 2 2 3 3 3 3 2 3 3 2 2 3 One One 3 4 One 3 3 2 3 3 5 2 3 3 3 0 2 6 3 2 2 2 One 2 7 3 One 3 3 0 3 8 3 3 2 3 One 2 9 2 3 3 2 One 2 10 3 3 2 2 One 2 11 One 3 3 0 0 3 12 2 2 One 2 One One 13 2 3 2 One One 2 14 3 2 2 2 0 2 15 3 3 3 2 2 2 Average 2.3 2.5 2.5 2.0 1.0 2.3

The heartburn item was comparatively analyzed through Wilcoxon signed rank test and shown in Tables 21 to 26 below, and the acid reflux item was comparatively analyzed through Wilcoxon signed rank test. Thus, it is shown in Tables 27 to 32 below.

District 1 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 4 3.50 14.00 positive rank 2 3.50 7.00 tie 9 Sum 15

District 1 Post-arbitration_score - Pre-arbitration_score Z -.816 Approximate significance (two-tailed) .414

District 2 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 12 7.21 86.50 positive rank One 4.50 4.50 tie 2 Sum 15

District 2 Post-arbitration_score - Pre-arbitration_score Z -2.961 Approximate significance (two-tailed) .003

District 3 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 7 4.50 31.50 positive rank 2 6.75 13.50 tie 6 Sum 15

District 3 Post-arbitration_score - Pre-arbitration_score Z -1.155 Approximate significance (two-tailed) .248

When the Wilcoxon signed-rank test was conducted to confirm the change in the mean value before and after the intervention in each group in relation to heartburn, the average score in group 1 changed from 1.8 to 1.7 before and after the intervention, and the approximation There was no significant difference with a significance probability p=0.414, and in group 2, the average score changed from 1.5 to 0.5 before and after the intervention, and statistically significant improvement was shown with an approximate significance probability p=0.003. In group 3, the average score changed from 1.9 to 1.7 before and after the intervention, and there was no significant difference with an approximate significance probability p=0.248.

District 1 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 7 5.00 35.00 positive rank 2 5.00 10.00 tie 6 Sum 15

District 1 Post-arbitration_score - Pre-arbitration_score Z -1.667 Approximate significance (two-tailed) .096

District 2 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 14 7.50 105.00 positive rank 0 .00 .00 tie One Sum 15

District 2 Post-arbitration_score - Pre-arbitration_score Z -3.360 Approximate significance (two-tailed) .001

District 3 N average rank rank sum Post-arbitration_score - Pre-arbitration_score negative rank 3 2.00 6.00 positive rank 0 .00 .00 tie 12 Sum 15

District 3 Post-arbitration_score - Pre-arbitration_score Z -1.732 Approximate significance (two-tailed) .083

When the Wilcoxon signed-rank test was conducted to confirm the change in the mean value before and after the intervention in each group in relation to acid reflux, the average score before and after the intervention in group 1 changed from 2.3 to 2.0. There was no significant difference with a significance probability p=0.096, and in group 2, the average score changed from 2.5 to 1.0 before and after the intervention, and statistically significant improvement was shown with an approximate significance probability p=0.001. In group 3, the average score changed from 2.5 to 2.3 before and after the intervention, and there was no significant difference with an approximate significance probability p=0.083.

In group 2, the overall GERD-Q average score improved by 2.53 points, from 12.4 points to 9.87 points. . From this, it was found that the herbal composition of the present invention has a particularly improving effect on heartburn and acid reflux among gastroesophageal reflux symptoms.

The description of the present invention described above is for illustration, and those of ordinary skill in the art to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. For example, each component described as a single type may be implemented in a dispersed form, and likewise components described as distributed may also be implemented in a combined form.

The scope of the present invention is indicated by the following claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included in the scope of the present invention.

Claims (8)

Provided by extracting mixed herbal materials containing 15 to 17 parts by weight of mulberry flour, 3 to 5 parts by weight of porridge, 3 to 5 parts by weight of licorice, 3 to 5 parts by weight of gold, 3 to 5 parts by weight of new grain, and 2 to 4 parts by weight of licorice. A health functional food composition for improving gastroesophageal reflux disease, comprising an extract as an active ingredient.
The method of claim 1, wherein the mixed herbal medicine further comprises 2 to 4 parts by weight of cloves, 1 to 2 parts by weight of cloves, 5 to 7 parts by weight of ginger, and 5 to 7 parts by weight of jujubes, for improving gastroesophageal reflux disease A health functional food composition.
The health functional food composition for improving gastroesophageal reflux disease according to claim 1, wherein the extract is extracted by immersing the mixed herbal drug in 10 to 1,000 parts by weight of a solvent.
The health functional food composition for improving gastroesophageal reflux disease according to claim 1, wherein the extract is concentrated to 40 to 50% by weight of solids.
The health functional food composition for improving gastroesophageal reflux disease according to claim 4, wherein the extract is formulated in an amount of 200 to 300 mg at a time.
The health functional food composition for improving gastroesophageal reflux disease according to claim 1, wherein the extract is extracted for 6 to 10 hours at 80 to 110°C.
The health functional food composition for improving gastroesophageal reflux disease according to claim 1, wherein the gastroesophageal reflux disease is gastroesophageal reflux disease and heartburn or acid reflux caused thereby.
Provided by extracting mixed herbal materials containing 15 to 17 parts by weight of mulberry flour, 3 to 5 parts by weight of porridge, 3 to 5 parts by weight of licorice, 3 to 5 parts by weight of gold, 3 to 5 parts by weight of new grain, and 2 to 4 parts by weight of licorice. An herbal composition for the prevention or treatment of gastrointestinal diseases, comprising the extract as an active ingredient.

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