KR101689826B1 - Composition comprising butanol fraction of Ecklonia cava for prevention and treatment of gastroesophageal reflux disease - Google Patents

Abstract

The present invention relates to a composition containing a fractionated butanol fraction, wherein the composition containing the fractionated butanol fraction or the health functional food is excellent in improving the symptoms of reflux esophagitis, and a pharmaceutical composition for treating, preventing and improving these diseases , And can be easily used as a health functional food.

Description

[0001] The present invention relates to a composition for preventing or treating reflux esophagitis, which comprises a fractionated butanol fraction of Ecklonia cava, and a composition for prevention or treatment of gastroesophageal reflux disease

The present invention relates to a composition for preventing or treating reflux esophagitis containing a butanol fraction.

Reflux esophagitis is a disease in which the stomach contents (mainly acid and pepsin) are refluxed into the esophagus and cause various clinical symptoms and mucosal changes such as heartburn and upper abdominal pain. The longer the time of exposure to acid, the more severe the lesion is and the chronic progression. Excess esophageal acid and pepsin are the main cause of esophageal reflux esophagitis, whereas non-erosive reflux disease is normal and the esophageal sensation is abnormally sensitized to acid and pepsin. have.

Histamine receptor antagonist (H ₂ RA, H ₂ receptor antagonist), which is an inhibitor of acid secretion, was used in the past as an initial treatment for reflux esophagitis. However, severe esophagitis is not satisfactory for treatment and is highly resistant to acid secretion Proton pump inhibitor (PPI) has been widely used because it has proven its cost-effectiveness superiority.

However, even when the proton pump inhibitor is used, the recurrence rate is high and there is a problem that it must be taken for a long time. In fact, taking 8 weeks of treatment, reflux esophagitis is treated, but 50 to 80% of patients are reported to recur within 1 year after discontinuation of the drug. It has been reported that long-term use of proton pump inhibitors for the treatment of reflux esophagitis causes neuroendocrine cell tumors. In 2010, the US FDA recommended that PPI drugs be taken for a long period of time or longer The risk of fracture may be increased. Therefore, there is a desperate need to develop a therapeutic agent for reflux esophagitis, which is excellent in the therapeutic effect of reflux esophagitis and safe for the human body even for a long time.

Ecklonia cava is a 1 to 2 meter long arboreal vegetation distributed in the southern coast of Korea, Jeju Island, Japan, etc. It lives in deep sea (lunch zone: gradually), and is the main raw material for making alginic acid, iodine and potassium. And is mainly edible. Seaweeds such as mosses are rich in phlorotannines such as polyphenols, which are composed of only a fluoroglucinol monomer. In recent years, such a phlorotannin compound has been used as a physiologically active substance capable of treating various diseases It is in the limelight.

The inventors of the present invention have been interested in the various physiological activities of the fractionated butanol fraction of the menthol, while studying the therapeutic effect of the brain disease of the fractionated butanol fraction disclosed in Korean Patent Registration No. 1244828, The present inventors have completed the present invention by confirming that the fraction has an excellent effect of inhibiting reflux esophagitis besides the effect of treating brain diseases.

Korean Patent Registration No. 1244828 (registered as a pharmaceutical composition or functional food composition for inhibiting the production of beta-amyloid oligomers and fibrils containing the fraction of butanol as an active ingredient, 2013.03.12.) Japanese Unexamined Patent Publication No. 2006-219376 (UREASE INHIBITOR, published on Aug. 24, 2006) Korean Patent Publication No. 2004-0057103 (Degenerative arthritis composition containing seaweed extract, disclosed on July 02, 2004) Korean Patent Publication No. 2010-0131809 (Anti-inflammatory Composition, Dec. 16, 2010) Korean Patent Publication No. 2011-0035127 (Composition for inhibiting inflammation, which comprises phlorotannin derived from Momopsis and Ganoderma lucidum extract as an active ingredient, published on Apr. 4, 2011)

It is an object of the present invention to provide a composition for preventing or treating reflux esophagitis containing a butanol fraction.

The present invention relates to a method for the prevention or treatment of reflux esophagitis, comprising the step of fractionating a C1-C4 alcohol extract of Ecklonia cava or an aqueous solution extract of C1-C4 alcohol with hexane, dichloromethane, ethyl acetate and butanol, ≪ / RTI >

The mentha butanol fraction is prepared by adding water of 1 to 200 times the weight of the extract to the aqueous extract of C1-C4 alcohol extract or C1-C4 alcohol extract of the menthol, adding hexane thereto, Dichloromethane was added to the hexane-free water layer to remove the dichloromethane layer to obtain a dichloromethane-free water layer. Ethyl acetate was added to the dichloromethane-free water layer, and then an ethyl acetate layer was added thereto. To obtain an ethyl acetate-free product layer, butanol is added to the ethyl acetate-unavailable product layer to obtain only a butanol layer, and the butanol layer is concentrated and dried to obtain a butane fraction.

The composition may further comprise one or more pharmaceutically acceptable excipients such as cimetidine, ranitidine, nizatidine, famotidine, lapthidine, omeprazole, s omeprazole, rabeprazole, pantoprazole, lansoprazole, dexranoprazole, anaprazole, tenatoprazole, At least one drug selected from the group consisting of losartan, losartan, losartan, losartan, soporozan, soporozan, simaflid citrate and sodium alginate may be added.

The present invention also provides a health functional food for preventing or improving reflux esophagitis containing the above-mentioned butanol fraction.

The health functional food may be selected from the group consisting of various foods, beverages, gums, tea, vitamin complex, and health functional foods.

Hereinafter, the present invention will be described in detail.

The present invention relates to a composition for preventing or treating reflux esophagitis, which comprises a sensory butanol fraction obtained by successively fractionating a citrus extract of C1-C4 alcohol or an aqueous solution of C1-C4 alcohol with hexane, dichloromethane, ethyl acetate and butanol . The C1 to C4 alcohols may be selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol and isobutanol. The aqueous solution of the C1 to C4 alcohol is preferably an aqueous solution of 30 to 95% (v / v), more preferably an aqueous solution of 50 to 95% (v / v), most preferably 70 to 95% Aqueous solution.

The aqueous solution of the C1-C4 alcohol or the C1-C4 alcohol used in the preparation of the aqueous extract of the C1-C4 alcohol extract or the C1-C4 alcohol of the menthol may be 1 to 40 times the volume (1 to 40 liters per kg) And preferably 5 to 40 times. The extraction conditions of the menthol C1-C4 alcohol extract may be 1 to 48 hours at 20 to 100 < 0 > C.

The C1-C4 alcohol extract or the C1-C4 alcohol aqueous extract solution of the menthol may be a concentrate of the filtrate obtained by adding C1-C4 alcohol extract or C1-C4 alcohol to the citron and then heating. The extract of C1 to C4 alcohol or the aqueous solution of C1 to C4 alcohol of the above menthol is preferably in the form of a dried product.

 The butanol fraction of the menthol may be sequentially fractionated with hexane, dichloromethane, ethyl acetate and butanol after dissolving the extract of C1-C4 alcohol or the aqueous solution of C1-C4 alcohol in water.

More specifically, a suspension is prepared by adding 1 to 200 times the volume of water to the aqueous extract of the C1-C4 alcohol extract or the C1-C4 alcohol of the above menthol, by weight of the extract, adding hexane, and then removing the hexane layer The dichloromethane layer was removed by adding dichloromethane to the hexane-free water layer, and the dichloromethane-free water layer was obtained. Ethyl acetate was added to the dichloromethane-free water layer, and the ethyl acetate layer was removed After obtaining an ethyl acetate-unusable water layer, butanol is added to the ethyl acetate-unavailable solvent layer to obtain only a butanol layer, and the butanol layer is concentrated and dried to obtain a filtered butanol fraction.

Hexane, dichloromethane, and ethyl acetate were added to the water layer, the hexane layer, the dichloromethane layer, and the ethyl acetate layer were further added to the water layer, and the process of removing the hexane layer, the dichloromethane layer and the ethyl acetate layer was repeated 2-4 times Additional can be done. Likewise, the process of collecting the butanol layer by adding butanol to the ethyl acetate-unavailable product layer may be repeatedly performed two to four times.

In the production of the sensory fraction, hexane, dichloromethane, ethyl acetate or butanol is added at a rate of 0.5 to 5 times the volume of the non-soluble water layer or a suspension of the aqueous extract of the C1-C4 alcohol extract or the C1-C4 alcohol, . The composition in the mixed state in which the solvent for each fraction is added may be strongly shaken or mixed so that the active ingredient or physiologically active ingredient in the gentle extract may be eluted into the solvent.

During the sequential fractionation, the fraction may be prepared at a temperature of 20 to 50 ° C, but is not limited thereto. The fractionation time for adding each solvent is not particularly limited, but it is preferably fractionated within 10 minutes to 1 day. The thus-prepared sensory butanol fraction can be removed by hot air drying, vacuum drying or freeze-drying.

The sensory butanol fraction may be isolated or isolated by known methods used for the isolation and extraction of plant components, such as extraction with an organic solvent (alcohol, ether, acetone, etc.), partition with hexane and water, And may be further fractionated or purified by a suitable combination method.

The chromatography can be carried out using silica gel column chromatography, LH-20 column chromatography, ion exchange resin chromatography, medium pressure liquid chromatography chromatography, thin layer chromatography (TLC), silica gel vacuum liquid chromatography, and high performance liquid chromatography.

H ₂ receptor antagonists in the compositions of the present invention, in addition to Ecklonia cava butanol fraction used as the acid reflux treatment in current clinical (H ₂ RA, H ₂ receptor antagonist) drug, cimetidine, ranitidine, nizatidine, famotidine, La petite Dean and (P-CAB), a potent opioid analgesic inhibitor (P-CAB), and a proton pump inhibitor (PPI), Omeprazole, S-omeprazole, rabeprazole, pantoprazole, lansoprazole, dexranprazole, anaprazole, Potassium Competitive Acid Blocker), such as inlavaprazan, sonaprazan, mosapride citrate, which is a digestive tract movement improver, sodium alginate, a mucosal protective agent, or the like.

The present invention also provides a pharmaceutical composition for the prevention or treatment of reflux esophagitis, which comprises a fractionated butanol fraction and a pharmaceutical excipient. The menthol butanol fraction may be added to the pharmaceutical composition of the present invention in an amount of preferably 0.001 to 99.0% by weight, more preferably 0.001 to 30% by weight.

The pharmaceutical compositions may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to conventional methods. The pharmaceutical excipients that may be included in the pharmaceutical composition are as follows. Preferably, the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, such as starch, calcium carbonate, sucrose, Lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The dosage of the pharmaceutical composition of the present invention will depend on the age, sex, body weight of the subject to be treated, the particular disease or condition to be treated, the severity of the disease or condition, the route of administration and the judgment of the prescriber. Dosage determinations based on these factors are within the level of ordinary skill in the art and generally the dosage ranges from 0.01 mg / kg / day to approximately 2000 mg / kg / day. A more preferable dosage is 1 mg / kg / day to 500 mg / kg / day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection. Since the sensory butanol fraction of the present invention has little toxicity and side effects, it can be safely used for prolonged use for preventive purposes.

In addition, the present invention provides a health functional food for prevention and improvement of reflux esophagitis, comprising a fractionated butanol fraction and a pharmaceutically acceptable food-aid additive. The mentha butanol fraction may be added to the health functional food of the present invention in an amount of preferably 0.001 to 99.0% by weight, more preferably 0.001 to 30% by weight. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamins , And health functional foods.

The present invention relates to a composition containing a fractionated butanol fraction, wherein the composition containing the fractionated butanol fraction or the health functional food is excellent in improving the symptoms of reflux esophagitis, and a pharmaceutical composition for treating, preventing and improving these diseases , And can be easily used as a health functional food.

On the other hand, Japanese Patent Laid-Open Publication No. 2006-219376 discloses a technology related to a therapeutic agent for an inflammatory disease containing an algae extract containing a menthol as an effective treatment for gastritis due to inhibition of Helicobacter pylori, 0057103, the anti-inflammatory effect is disclosed in Korean Patent Publication No. 2010-0131809. Korean Patent Publication No. 2011-0035127 discloses an anti-inflammatory effect of phlorotannin derived from Momopsis and Rhizoma extract. However, it has not been disclosed at all in the prior art that the butanol fraction of menthol has a therapeutic effect of reflux esophagitis.

FIG. 1 is a graph showing the results of examining the therapeutic effect of reflux esophagitis on the phlegm extract or fractions of Examples 1-1 and 1-2 and Comparative Examples 1 to 3 of the present invention using an animal model of reflux esophagitis.

Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, the intention is to provide an exhaustive, complete, and complete disclosure of the principles of the invention to those skilled in the art.

≪ Example 1: Preparation of ganoderma butanol fraction >

Example 1-1. Ganoderma lucidum butanol fraction

1 liter of ethanol (purity: 99.9%) was added to 100 g of dried persimmon, and the mixture was extracted at 65 DEG C for 3 hours. Then, the extract was filtered to obtain an extract, and then the extraction procedure was repeated three times. The extracts thus obtained were collected, concentrated under reduced pressure at 40 ° C or lower, and then lyophilized to obtain 15 g of a chewy ethanol extract. To the menthol ethanol extract, 1.5 L of distilled water was added to suspend the suspension, the same volume of hexane was added thereto, and the mixture was separated into a hexane layer and a hexane layer. The process of adding hexane again to the hexane-free water layer was repeated three times to collect only the hexane layer and then dried under reduced pressure to obtain 3.1 g of hexane fraction. To the remaining hexane-free water layer was added dichloromethane of the same volume as the hexane-free water layer (dichloromethane was added three more times as in the case of adding hexane) to obtain 0.7 g of a dichloromethane fraction. Using the same method, 4.1 g of the ethyl acetate fraction and 2.1 g of the butanol fraction were obtained. Finally, the remaining water layer was collected separately and vacuum-dried to obtain 4.5 g of the water-soluble fraction.

Examples 1-2. Chimeric butanol fraction (2)

The same procedure as in Example 1-1 was used to prepare a menthol butanol fraction, which was prepared by adding a 70% (v / v) aqueous ethanol solution instead of ethanol (purity: 99.9%), Dichloromethane, ethyl acetate and butanol were sequentially added to prepare a butanol fraction.

≪ Comparative Example 1 > Preparation of Ganoderma lucidum ethanol extract &

In the method described in Example 1-1, a sparing ethanol extract was obtained.

< Comparative Example  2. Moth Hexane Fraction  Manufacturing>

By the method described in Example 1-1, a fractionated hexane fraction was obtained.

&Lt; Comparative Example 3: Preparation of Ethyl Acetate Fractions &

By the method described in Example 1-1, a citrate ethyl acetate fraction was obtained.

EXPERIMENTAL EXAMPLE 1 Test for Effectiveness of Refractory Esophagus on Gastric Extract or Fraction

In order to confirm the therapeutic effect of reflux esophagitis on the phlegm extract or fractions of Examples 1-1 and 1-2 and Comparative Examples 1 to 3 of the present invention, an animal model of reflux esophagitis was derived. Seven weeks old Sprague-Dawley (SD) male rats were fasted for 24 hours (7 rats per group) and a sufficient amount of water was supplied. After 24-hour fasting, the body weight of each rat was measured, and the control drug omeprazole (Sigma-Aldrich) and the test substance extract or fraction were suspended in 0.5% CMC (carboxymethyl celluse) Orally. To induce reflux, the abdomen was opened to ligate the pylorus, which is the border of the stomach and duodenum, and the upper gastro-esophageal sphincter, which forms the boundary between the esophagus and the stomach, was given a 1 cm longitudinal wound, causing sphincter relaxation abnormally, . In addition, the transition zone between the forestomach and the glandular stomach was ligated to the spleen and the abdomen was closed with cotton yarn. The esophageal lesion size and degree of esophagitis were observed after inhalation anesthesia 6 hours after the end of the operation, and esophageal lesion inhibition rate (%) of the test substance-administered group of the present invention was compared to that of the control (untreated group: CMC solvent) 1, which are numerically represented in FIG.

division Dose
(Mg / kg) Esophageal lesion inhibition rate compared to control
(%) Control group (untreated group) - - Example 1-1
(Butanol fraction of ethanol extract of chewing gum) 50 80 Examples 1-2
(Butanol fraction of 70% ethanol aqueous solution extract) 50 75 Comparative Example 1
(Phytotoxic ethanol extract) 50 20 Comparative Example 2
(Hexane fraction of ethanol extract of chewing gum) 50 35 Comparative Example 3
(Ethylacetate fraction of the ethanol extract of cuttlefish) 50 40 Omeprazole 10 90

Referring to Table 1 and FIG. 1, it can be confirmed that the sensory butanol fraction of Examples 1-1 and 1-2 of the present invention significantly suppresses esophageal injury as compared with the control group (no treatment after reflux esophagitis) . These effects are superior to those obtained by oral administration of chewing ethanol extract, hexane fraction and ethyl acetate fraction.

<Experimental Example 2 Effect of Protective Extracts or Fractions on Esophageal Mucosa>

The gut extracts or fractions of Examples 1-1 and 1-2 and Comparative Examples 1 to 3 of the present invention in which the therapeutic effect was confirmed in the rat reflux esophagitis disease model were compared with those of the esophageal mucosa component hexosamine ) And the amount of sialic acid were measured.

Experimental Example 2-1. Measurement of Hexosamine Content in Esophageal Tissue

The esophageal tissues of all the test groups obtained in Experimental Example 1 were immersed in ethanol (purity: 99.9%), respectively, and then left in acetone for 2 days and in ether for 1 day, followed by degreasing and drying. After weighing the sample, 5 ml of 4N HCl solution was added and heated at 100 ° C for 9 hours to hydrolyze. After cooling at room temperature, the filtrate was collected. To 0.5 ml of the filtrate, 0.5 ml of 4N NaOH solution was added to neutralize, and 1 ml of acetylacetone solution was added. After shaking, the mixture was heated at 100 ° C for 20 minutes, cooled, added with 5 ml of isoamylalcohol, shaken for 2 minutes Respectively. Next, the supernatant was centrifuged at 3,000 rpm for 10 minutes to take 2 ml of the supernatant, and then 0.5 ml of the chromogenic solution was added thereto, and the mixture was allowed to stand for 15 minutes. Then, the absorbance was measured at 530 nm and the absorbance of the supernatant was measured using glucosamine The content of sosamine was converted.

Experimental Example 2-2. Measurement of the amount of sialic acid in esophageal tissue

The esophagus tissues of all the test groups obtained in Experimental Example 1 were immersed in ethanol (purity 99.9%), respectively, and then left in acetone for 2 days and in ether for 1 day, followed by degreasing and drying. After weighing the specimen, 5 ml of 0.1 N H ₂ SO ₄ solution was added and heated at 80 ° C for 1 hour to hydrolyze. After cooling at room temperature, the filtrate was collected by filtration. 0.2 ml of periodate solution and 0.1 ml of periodate solution were added to 0.2 ml of the filtrate, and the mixture was allowed to stand at room temperature for 20 minutes. Then, 1 ml of 10% (w / v) arsenite solution was added thereto until the tan color disappears . Then, 3 ml of 0.6% (w / v) thiobarbituric acid (TBA) solution was added to the flask, the flask was closed, the flask was heated at 100 ° C for 15 minutes, cooled, left in a cold bath for 5 minutes and centrifuged at 3,000 rpm for 10 minutes The supernatant was taken and absorbance was measured at 549 nm. The content of sialic acid was converted from the calibration curve prepared using N-acetylneuraminic acid.

The results of confirming the content of hexosamine and sialic acid are shown in Table 2 below. As shown in Table 2, the group of the reflux esophagitis induction group (control group) showed a higher concentration of hexosamine and sialic acid than the normal group not inducing reflux esophagitis And the content of hexosamine and sialic acid was significantly increased at the time of administration of the fractionated butanol fraction of Examples 1-1 and 1-2, The content of hexosamine and sialic acid is higher than that of the other groups. These results suggest that the esophageal tissue was normalized as the components of the esophageal mucosa reduced by the reflux esophagitis were healed by the sensory butanol fractions of Examples 1-1 and 1-2 and that the sensory butanol fraction This suggests that the recurrence rate of reflux esophagitis can be lowered by creating esophageal tissue under protective conditions.

group Dose
(Mg / kg) Unit: ㎍ / 100㎎ dry tissue Sialic acid Hexosamin Normal group - 130.1 1105.2 Control group (untreated group) - 93.2 919.9 Example 1-1
(Butanol fraction of ethanol extract of chewing gum) 50 146.7 1323.2 Examples 1-2
(Butanol fraction of 70% ethanol aqueous solution extract) 50 135.3 1226.1 Comparative Example 1
(Phytotoxic ethanol extract) 50 110.3 1081.3 Comparative Example 2
(Hexane fraction of ethanol extract of chewing gum) 50 115.2 1051.2 Comparative Example 3
(Ethylacetate fraction of the ethanol extract of cuttlefish) 50 116.3 1052.2 Omeprazole 10 132.4 1153.2

< Experimental Example  3. Toxicity test>

Experimental Example 3-1. Acute toxicity

This experiment was conducted to investigate the toxicity of the fractionated butanol fraction of Example 1-1 of the present invention to the animal body in an acute (within 24 hours) when an excessive amount of the fractionated butanol fraction of the present invention was consumed in a short period and determine the mortality rate. Twenty ICR mice were injected into each of the control and experimental groups. In the control group, only the PEG-400: tween-80: ethanol (8: 1: 1, v: v: 80: ethanol (8: 1: 1, v: v: v). After 24 hours of administration, the respective mortality rates were examined. As a result, it was confirmed that the mice survived in the control group and in the experimental group administered with the manganese butanol fraction of Example 1-1 at a concentration of 2 g / kg / day.

Experimental Example 3-2. Organ organs toxicity test in experimental group and control group

In the long-term toxicity test, the fractionated butanol fraction of Example 1-1 of the present invention was administered to C57BL / 6J mice (10 rats per group) for 8 weeks at each concentration. In order to investigate the effects on the organs (tissues) of animals, an experimental group in which the fractionated butanol fraction of Example 1-1 was administered and PEG-400: tween-80: ethanol (8: 1: 1, v: v : v). After 8 weeks, the blood was collected from the animals of the control group and the concentration of GPT (glutamate-pyruvate transferase) and BUN (blood urea nitrogen) was measured using a Select E (Vital Scientific NV, Netherland) Respectively. As a result, GPT, which is known to be related to hepatotoxicity, and BUN, which is known to be related to renal toxicity, showed no significant difference compared to the control group. In addition, liver and kidney were cut from each animal, followed by a general tissue section preparation, histological observation with an optical microscope, and no abnormalities were observed in all tissues.

&Lt; Formulation Example 1 >

Formulation Example 1-1. Manufacture of tablets

200 g of the sensory butanol fraction of Example 1-1 of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. To this mixture was added a 10% gelatin solution, which was pulverized and passed through a 14-mesh sieve. This was dried, and a mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into tablets.

Formulation Example 1-2. Injection preparation

1 g of the fractionated butanol fraction of Example 1-1 of the present invention, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was placed in a bottle and sterilized by heating at 20 DEG C for 30 minutes.

<Formulation Example 2: Food Preparation>

Formulation Example 2-1. Manufacture of cooking seasonings

The safflower butanol fraction of Example 1-1 of the present invention was added to the cooking seasoning at 1 wt% to prepare a cooking sauce for health promotion.

Formulation Example 2-2. Manufacture of flour food products

The fragrant butanol fraction of Example 1-1 of the present invention was added to wheat flour at 0.1 wt%, and bread, cake, cookies, crackers and noodles were prepared using this mixture to prepare health promotion foods.

Preparation Example 2-3. Manufacture of soups and gravies

The fragrant butanol fraction of Example 1-1 of the present invention was added to soup and juice at 0.1 wt% to prepare soup for health promotion and juice.

Formulation Example 2-4. Manufacture of dairy products

The sensory butanol fraction of Example 1-1 of the present invention was added to milk in an amount of 0.1 wt%, and various dairy products such as butter and ice cream were prepared using the milk.

Formulation Example 2-5. Vegetable juice manufacturing

0.5 g of the fractionated butanol fraction of Example 1-1 of the present invention was added to 1,000 ml of tomato juice or carrot juice to prepare vegetable juice for health promotion.

Formulation Example 2-6. Manufacture of fruit juice

0.1 g of the fractionated butanol fraction of Example 1-1 of the present invention was added to 1,000 ml of apple juice or grape juice to prepare fruit juice for health promotion.

Claims (2)

The concentrate of C1-C4 alcohol extract or C1-C4 alcohol aqueous solution extract of Ecklonia cava was suspended in water and then fractionated with hexane, dichloromethane, ethyl acetate and butanol in order to obtain a sensory butanol fraction Wherein the pharmaceutical composition is for preventing or treating reflux esophagitis. The concentrate of C1-C4 alcohol extract or C1-C4 alcohol aqueous solution extract of Ecklonia cava was suspended in water and then fractionated with hexane, dichloromethane, ethyl acetate and butanol in order to obtain a sensory butanol fraction Characterized by a health functional food for preventing or improving reflux esophagitis.

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