KR100892180B1 - Composition comprising powder of tangerine peel or the extract thereof for treating and preventing gastrointestinal disease - Google Patents

Abstract

The present invention relates to a composition containing a tangerine peel powder or an extract thereof as an active ingredient, and in detail, the tangerine peel powder or extract thereof exhibits a gastric ulcer inhibiting effect, and thus a pharmaceutical composition and health functional food for preventing and treating gastrointestinal diseases. It can be used as.

Tangerine peel, extract, stomach ulcer, pharmaceutical composition, dietary supplement

Description

Composition comprising powder of tangerine peel or the extract describes for treating and preventing gastrointestinal disease}

The present invention relates to a pharmaceutical composition and health functional food for the prevention and treatment of gastrointestinal diseases containing tangerine peel powder or extracts thereof as an active ingredient.

Gastric ulcer is one of chronic digestive diseases caused by the digestion of gastric mucosa due to the stronger digestion of gastric acid, pepsin and other attack factors than the resistance of mucosa, local mucosal blood flow, humoral and gastric secretion inhibitors. Gastric acid has been recognized as the leading cause of gastric mucosal damage and gastric ulcers. In the case of double gastritis, it means damage to the gastric mucosa and gastric ulcer to the submucosa.

Prolonged exposure to oxidative stress in various gastrointestinal disorders, such as gastritis resulting from gastric mucosa and microvascular damage to the gastric mucosa, can damage DNA by reactive oxygen and provide various gastrointestinal causes. In addition, free radicals have been reported to be one of the causes of gastric mucosal injury caused by NSAID and Helicobactor pylori (Halter F., Pathology of peptic ulcer disease ., Pp1-13, 1995). In particular, Helicobacter pylori has been identified as a causative agent of gastritis and gastroduodenal ulcers since it was separated by Warren and Marshall in 1983 (Lancet, 1 , pp1273-1275, 1983) ( J. infect. Dis ., 161 , pp626-633, 1990; Am. J. Med ., 91, pp566-572, 1991), and are currently recognized as one of the factors for the development of gastric cancer, which has been the subject of worldwide interest and research. Helicobacter pylori is a Gram-negative bacillus inhabiting the junctions of gastric mucosal epithelial cells. Its optimum pH is 7.0-7.4 and grows in aerobic conditions at 30-37 ° C. A change to the (Coccoid) form is observed. Previously, gastrointestinal disorders such as gastritis and gastric ulcers were primarily known to be caused by excessive gastric acid secretion, ie, excessive gastric acid secretion, and caused by stress, food, and genetic factors, but recently, when infected by Helicobacter It is hypothesized that inflammation occurs. When inflammation spreads to the submucosa of the stomach, it develops gastric ulcers and does not progress directly to gastric cancer, but when helicobacter is infected, it is known that 3-5 times more likely to develop gastric cancer. Several years ago, antacids, histamine receptor antagonists, and ulcer drugs have been used for the treatment of such gastrointestinal diseases. In addition, it is known that activating a substance with antioxidant capacity or an enzyme with an active oxygen binding ability can prevent gastrointestinal diseases caused by oxidative damage (Park KH, Cha Sm, Choi Js, Ki ND., Evaluation of neutralizing capacities). of antacid products, Yakhak Heoeji ., 27, pp 13-22, 1983).

To date, the prevention and treatment of digestive diseases caused by H. pylori rely on various antibiotics represented by triple chemotherapy, but there is still a risk of emergence of resistant bacteria or recurrence due to continuous use. It has been pointed out as a limitation, and drugs such as cimetidine and omeprazole, which are widely used as treatments for gastric ulcers, have serious side effects such as decreased sexual function and digestive function. There is an urgent need to develop alternative drugs to treat the disease.

On the other hand, the tangerines contain essential oils and various flavonoid derivatives, and about 150 mg of vitamin C and 76 µg of vitamin B1. As a function of the blood vessels of the heart, a small amount of dermis premise increases the contractile force and increases the blood volume of the toad's extracted heart, but does not affect the heart rate. In high doses, the heart was inhibited. Hwangjinpi, dermis inhibits the growth of Staphylococcus aureus, Katarrhococcus, Hemolytic Hemophilus, and Influenza. They also found that it contains a lot of B vitamins. In the former, 100g of herbal medicine contains 100µg of vitamin B1, and the latter contains about 50µg (Information and Shin Mingyo, Doha Hyangje Metabolism , Yeonglimsa, p784, 1998)

Recently, efforts have been made to find active ingredients capable of inhibiting Helicobacter pylori from various natural materials. The development status of domestic and foreign gastric disease treatment agents and preventive agents is a composition for the treatment of gastric diseases using mugwort (Korean Patent Publication No. 2002-0046488), a composition for the prevention and treatment of gastric ulcer containing leaflet extract and berberine (Korean publication). Patent No. 2001-0100198), Fucoidan contained in red algae or brown algae as an active ingredient, which inhibits the settling of Helicobacter pylori on the gastric mucosa and is useful for the prevention and treatment of ulcers and tumors. 1995-0007868) and an antacid (Korea Patent Publication No. 2005-0088816) made of polysaccharide, shell of crab or shrimp, squid bone, chitin, chitosan, and chitosan, but the effect of gastrointestinal diseases through the experiment of tangerine peel alone Is not disclosed or taught anywhere else.

Therefore, the present inventors conducted an experiment to confirm the effect of inhibiting gastric ulceration in mice that caused gastric injury using tangerine peel powder or extracts thereof in order to derive other effective substances other than cimetidine and opulazole, which are widely used as a therapeutic agent for gastric diseases. As a result, the present invention was completed by confirming that the tangerine peel powder or extract thereof is effective against gastrointestinal diseases.

An object of the present invention to provide a pharmaceutical composition and health functional food for the prevention and treatment of gastrointestinal diseases containing tangerine peel powder or extract thereof as an active ingredient.

In accordance with the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of gastrointestinal diseases containing tangerine peel powder or extract thereof as an active ingredient.

The extract comprises water, including purified water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof, preferably water, ethanol or a mixed solvent thereof, more preferably water or an extract available in a 95% ethanol solvent. do.

The gastrointestinal disorders include gastric ulcer, acute gastric ulcer, chronic gastric ulcer, duodenal ulcer, peptic ulcer, acute gastritis, chronic gastritis, gastric hyperplasia, gastric neurosis, gastric hydration, gastric dilatation, acidosis (paraxia), stomach cramps, pyloric stenosis, atrophic torsion, Gastric polyp (or), gastric stone or gastric cancer, preferably gastric ulcer, acute gastric ulcer, chronic gastric ulcer, duodenal ulcer, peptic ulcer, acute gastritis, chronic gastritis or hyperacidity, more preferably gastric ulcer, acute gastric ulcer, chronic gastric ulcer, duodenal ulcer Or peptic ulcer disease.

Hereinafter, the present invention will be described in detail.

Tangerine peel powder or extract thereof of the present invention can be obtained as follows.

Tangerine peel powder or extract thereof of the present invention, the peeled citrus peeled only after collecting water and dried for about 10 to 40 hours at about 10 to 50 ℃ after washing with water, to obtain a dried tangerine peel powder of the present invention, Water, lower alcohols having 1 to 4 carbon atoms or mixed solvents thereof, including purified water of about 1 to 30 times, preferably about 5 to 20 times, more preferably 8 to 15 times of the obtained tangerine peel powder, preferably Preferably about 1 to 5 days at 20 ° C. to 100 ° C., preferably 50 ° C. to 100 ° C. extraction temperature, preferably in water, ethanol or a mixed solvent thereof, more preferably in water or 95% ethanol solvent. The extraction method of stirring extraction, cold extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction for about 1 to 3 days, preferably extracted by stirring extraction method, and then filtered and concentrated the filtrate under reduced pressure and freeze It can be obtained orange peel extract of the present invention to crude.

The pharmaceutical composition for preventing and treating gastrointestinal diseases of the present invention comprises 0.1 to 50% by weight of the tangerine peel powder or extract thereof based on the total weight of the composition.

The pharmaceutical composition containing the tangerine peel powder or extract thereof as an active ingredient may further include appropriate carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.

The pharmaceutical composition containing the tangerine peel powder or extract thereof according to the present invention may be formulated in the form of external preparations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, and sterile injectable solutions according to conventional methods, respectively. It can be used in combination, preferably provides a pharmaceutical composition in the form of an external preparation for the ointment, warning, lotion, lining, pasta or cataplasm. Carriers, excipients and diluents which may be included in the composition containing tangerine peel powder or extracts thereof include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, Gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules or capsules, and the like form at least one excipient such as starch, calcium carbonate, sucrose ( Sucrose) or lactose (Lactose), gelatin, etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspensions, liquid solutions, emulsions, or syrups, and may include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water or liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As the non-aqueous solvent and suspending agent, vegetable oils such as propylene glycol, polyethylene glycol and olive oil, injectable esters such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter and glycerogelatin may be used.

Preferred dosages of the tangerine peel powder or extracts thereof of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention may be administered in 0.0001 ~ 100 mg / kg, preferably in an amount of 0.001 ~ 100 mg / kg divided once or several times a day.

The pharmaceutical composition of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural and intracerebroventricular injections.

In addition, the present invention provides a health functional food for preventing and improving gastrointestinal diseases containing tangerine peel powder or extracts thereof as an active ingredient.

       Tangerine peel powder or extract thereof of the present invention can be used in a variety of drugs, food and beverages for the prevention and treatment of gastrointestinal diseases. Foods to which the tangerine peel powder or extract thereof may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, and health supplements, and the like, which are granules, tablets, capsules, or beverages. Can be used as

Tangerine peel powder or extract thereof of the present invention is a drug that can be used with confidence even for long-term administration for the purpose of prevention because there is little toxicity and side effects.

In addition, the tangerine peel powder or extract thereof of the present invention may be added to food or beverage for the purpose of preventing and improving gastrointestinal diseases. At this time, the amount of the tangerine peel powder or extract thereof in the food or beverage is generally added to 0.01 to 15% by weight of the total food weight of the health food composition of the present invention, the health beverage composition is 0.02 to based on 100 ml 30 g, preferably 0.3 to 10 g.

The health beverage composition of the present invention contains the tangerine peel powder or extracts thereof as essential ingredients in the indicated ratios, and there is no particular limitation on the liquid component, and various flavors or natural carbohydrates as additional ingredients may be used as additional ingredients. It may contain. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose, for example polysaccharides such as maltose and sucrose, and conventional sugars such as dextrin and cyclodextrin. Sugar alcohols such as xylitol, sorbitol and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above, the tangerine peel powder of the present invention or extract thereof may be used in various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, such as flavoring agents, coloring and neutralizing agents (cheese, chocolate, etc.), pectic acid and its Salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. In addition, the tangerine peel powder or extracts thereof of the present invention may contain a pulp for producing natural fruit juice and fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, the present invention will be described in detail by Examples and Experimental Examples.

However, the following Examples and Experimental Examples are only illustrative of the present invention, and the content of the present invention is not limited to the following Examples and Experimental Examples.

Example  One. Tangerine peel Manufacture of powder

Gather only the peeled Jeju citrus fruits from the store and wash them with water, then dry them at about 35 ℃ for about 20 hours, and use 100g of dried tangerine peeler (FM-909T (c), Shinhanil Electronics Co., Ltd., Korea). First milled to 50 mesh (Mesh), and then second milled using a turbo mill (CYCLOTEC 1093, FOSS, USA) to obtain a dried orange peel powder 900 (g) of 200 mesh or less, Experimental Example Used as a sample of 1.

Example 2. Preparation of Tangerine Peel Extract

2-1. Tangerine peel  Preparation of 95% Ethanol Soluble Extract

10 L of 95% ethanol was added to 1 kg of the tangerine peel powder of Example 1-1 and stirred at 25 ° C. for 24 hours. The filtered solution was filtered through a filter paper, and the filtrate was concentrated under reduced pressure (Evaporator, JP / NN, EYELA) to remove alcohol, and freeze dry system (Freeze dry system, LABCONCO, USA) to obtain 137 g of orange peel 95% ethanol soluble extract. Was obtained and used as a sample of Experimental Example 1 below.

2-2. Tangerine peel  Preparation of Water Soluble Extracts

10 times of water was added to the alcohol extraction residue of Example 1-2, followed by filtration to remove water, and then the precipitate was dried at 40 ° C. for 24 hours to obtain 234 g of tangerine soluble water extract. Experimental Example 1 Was used as a sample.

Reference Example  1. Preparation for experiment

1-1. Laboratory Animal Preparation

Experimental animals received Sprague-Dawley male rats with an average body weight of about 150-250 g from BioLink and published 5 animals per experiment. Mice were separated and bred one by one in the metal cage (Cage), and the solid feed and water was supplied sufficiently, the environment in the breeding room was maintained at 22 ± 2 ℃, relative humidity 60 ~ 70%, photoperiod 12 hours. At this time, all the experimental animals were used for experiments after breeding for at least two weeks.

1-2. Statistical processing

The ulcer index measured in this experiment was expressed as mean ± standard deviation, and the significance of the difference between each mean was Duncan's multiple range test at P <0.05.

Experimental Example  1. Inhibitory effect of stomach ulcer

Mizui et al. (Mizui T, Doteuchi M., Effect of polyamines on acidified ethanol-) were used to examine the gastrointestinal ulcer inhibition effect of tangerine peel powder or its extracts. induced gastic lesions in rats, Jpn J Pharmacol . , 33, pp 939-943, 1983) .

First, in order to artificially damage the gastrointestinal tract of the mouse, the test material was orally administered to the mouse of Reference Example 1, which was fasted for 24 hours, and after 30 minutes, 1 ml of ethanol hydrochloride (60% Ethanol + 0.3M HCl) was again orally administered. After 1 hour of fasting and water saving, the mouse was anesthetized by inhaling ethyl ether, followed by cervical slaughtering and lethal to remove the stomach. 10 ml of 2% formalin (10%) in the extracted stomach was fixed for 10 minutes, and the incidence of incision was measured by measuring the length of the injured part (mm). At this time, each treatment group used 100ml of distilled water as an excipient, the negative control group was conducted by a blank test, the positive control group 100mg / kg cimetidine (Cimetidine, sigma, USA) and 100mg / Omeprazole (Omeprazole, sigma, USA) kg was used. In addition, the same method as the gastric injury experiment of hydrochloric acid-ethanol (HCl-Ethanol) except that it was changed to indomethacin instead of the hydrochloric acid-ethanol to artificially damage the mouse stomach, and left for 5 hours after fasting and saving water. The experiment was performed using the following, the efficacy is expressed as a ratio using the following equation 1, all the experimental results are shown in Table 1 below.

Gastric ulcer inhibition effect (ratio) = (negative control-test sample) / (negative control-positive control) * 100

As shown in Table 1, the gastrointestinal ulceration index of the tangerine peel powder was 7.3 and 13.8%, respectively, as compared to cimetidine and oxazole, the positive control groups of each mouse model. The gastrointestinal ulceration index of the tangerine peel extract showed a significant effect of up to 79.1 and 81.0% compared to the positive control group of cimetidine and oxazole.

Therefore, it was confirmed that the tangerine peel extract has an effect of suppressing gastrointestinal ulcer induction, and the gastrointestinal ulcer has a lower effect of inhibiting gastrointestinal disorders than cimetidine or ozolazole but has less harmful factors to the human body when considering side effects on the existing drugs. Confirmed that it can.

Hereinafter, an example of the pharmaceutical composition and the health functional food comprising the tangerine peel powder or an extract thereof of the present invention will be described, but the present invention is not intended to limit the present invention but only to be described in detail.

Formulation example  One. Powder  Produce

      20 mg of tangerine peel powder of Example 1

Lactose 100 mg

Talc 10 mg

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Formulation example  2. Preparation of Tablets

      10 mg of tangerine peel extract of Example 2-1

      Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation example  3. Manufacture of capsule

      10 mg of tangerine peel extract of Example 2-1

      3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.

Formulation example  4. Preparation of Injectables

      10 mg of tangerine peel extract of Example 2-2

Mannitol 180 mg

Sterile distilled water for injection 2974 mg

Na ₂ HPO ₄ 12H ₂ O 26 mg

According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).

Formulation example  5. Liquid  Produce

20 mg of tangerine peel extract of Example 2-2

10 g of isomerized sugar

5 g of mannitol

Purified water

According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added to the mixture, and then the above ingredients are mixed, purified water is added to adjust the total amount to 100 ml, and then filled in a brown bottle. The solution is prepared by sterilization.

Formulation example  6. Manufacture of healthy food

1000 mg of tangerine peel powder of Example 1

Vitamin Mixture

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing the nutraceutical composition according to a conventional method.

Formulation example  7. Manufacture of health drinks

1000 mg of tangerine peel extract of Example 2-2

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

After mixing the above components in accordance with a conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.

Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

As described above, the tangerine peel powder or extract thereof of the present invention has excellent gastric ulcer inhibitory effect and may be used as a pharmaceutical composition and health functional food useful for preventing and treating gastrointestinal diseases.

Claims (6)

A pharmaceutical composition for the prevention and treatment of gastric ulcer, acute gastritis or chronic gastritis containing 95% ethanol extract of tangerine peel as an active ingredient. delete delete delete Health functional food for the prevention and improvement of gastric ulcer, acute gastritis or chronic gastritis containing 95% ethanol extract of tangerine peel as an active ingredient. delete