KR20110069917A - A composition for treatment of atopic dermatitis containing gyungokgo - Google Patents

Abstract

PURPOSE: A composition and health food using a small amount of Gyungokgo is provided to relieve itchness, inflammation, and skin edema and to treat or prevent atopic dermatitis. CONSTITUTION: A composition for preventing or treating atopic dermatitis contains 0.0001-1000 mg/kg of Gyungokgo as an active ingredient. Gyungokgo contains Rehmanniae Radix crudus, Wolfiporia cocos, ginseng, and honey. A cosmetic composition and health food are used for treating atopic dermatitis.

Description

Composition for the treatment or prevention of atopic dermatitis containing jadeite {A composition for treatment of Atopic dermatitis containing Gyungokgo}

The present invention relates to a composition for preventing or treating atopic dermatitis, and more particularly, to atopic dermatitis prevention or treatment composition and health functional food containing jadeite as an active ingredient.

Atopic dermatitis is a chronic skin disease characterized by dry skin as well as overgrowth of the epidermis, erythema, edema, severe pruritus, exudation and scab. The cause of atopic dermatitis is not clear yet, but genetic factors, imbalances of immune function, and environmental factors are known to be related.

To date, it has been reported that immunologically, T lymphocyte activation, cytokine system abnormalities, decreased cellular mediated immunity, and increased IgE play an important role in the pathology of atopic dermatitis.

Atopic dermatitis is growing more and more in countries where industrialization is underway and is likely to accelerate without proper prevention and treatment.

The main symptoms of atopic dermatitis are severe itching, dry skin, rashes, rashes, crusts and scaly skin scales.

There is no clear treatment to cure atopic dermatitis, and atopic dermatitis requires long-term treatment and treatment to avoid causing factors and change atopic constitution, rather than to cure the target.

      To date, prescriptions for atopic dermatitis have been dominated by chemical medications such as steroids, antihistamines and antibiotics. Steroids (adrenal corticosteroids) have anti-inflammatory and immunosuppressive effects and have excellent effects, but when used for a long time, various and severe side effects such as skin pigmentation, skin keratinization, abdominal pain and fever may occur. Antihistamines reduce the symptoms of itching by preventing histamine from being released from mast cells, but are used as a temporary measure, not as a fundamental treatment, and may have side effects such as insomnia, anxiety, and loss of appetite when taken for a long time.

Accordingly, there are many attempts to find a therapeutic agent with a high therapeutic effect and fewer side effects from natural products or herbal medicines, and active research is currently in progress.

The present inventors have tried to find a composition effective for improving atopic dermatitis without side effects, and as a result, it is effective in relieving atopic dermatitis even with a small amount of jadeite, and itching, inflammation and other symptoms caused by atopic dermatitis, skin edema, serum IgE and obesity It has been confirmed that the cell number can be reduced to complete the present invention.

Accordingly, an object of the present invention is to provide a composition and health functional food for preventing or treating atopic dermatitis.

In order to achieve the above object, the present invention provides a composition for preventing or treating atopic dermatitis and health functional food containing jadeite as an active ingredient.

Gyeongokgo of the present invention can be produced according to the traditional method using the four herbs, such as Saengjihwang, Bokryeong, ginseng, honey.

In one embodiment of the present invention, the amount of the medicinal herb was to be composed of ginseng 6.2g, ginseng 6.2g, Bokryeong 12.4g, fresh green juice 39.9g and 41.5g honey.

A jadeite is a kind of drowning medication that helps life and improve blood, and according to consent, it is very effective in maintaining and activating the functions of all organs in the human body. In addition, jadeite is not only effective as a blood and blood stimulant, but in particular, those who feel fatigue due to weak intestine, those who have a weak stomach, have indigestion, enteritis, intestinal cramps frequently, severe abdominal pain, and the weather changes only a little. When cold or cold, it is effective for people who catch colds, breathe with bronchial asthma and have severe sea cough. Especially, when the weak and weak old man wears, gray hair is black and teeth are newly raised and life is extended. It is listed in the book.

On the other hand, according to the results of modern research on jadeite, jadeite has an antioxidant effect, thereby contributing to cell physiological activity. In addition, jadeite is known to be effective in alleviating the skin aging phenomenon, improve skin wrinkles and have a skin whitening effect.

Atopic dermatitis, which is the main therapeutic object of the present invention, is a chronic and recurrent inflammatory skin disease that begins mainly in infancy or childhood and is accompanied by pruritus (itch), dry skin and characteristic eczema. In infancy, it begins with eczema on the stretched side of the face and limbs, but as it grows, it is characteristic of eczema in the flexion of the arms and behind the knee, and in many cases it tends to improve naturally as it grows. . In adults, the skin of the folds thickens lichenification (lichenification), and eczema on the face is often compared to infants. Atopic dermatitis is on the rise worldwide, with a prevalence rate of 20% of the population.

According to an embodiment of the present invention, in NC / Nga mice induced with atopy with DNCB, when jadeite is administered at a low concentration (12.5 mg / kg) and at a high concentration (25.0 mg / kg), the atopy of the jadeite administration group is higher than that of the atopy group. It was confirmed that the symptoms were significantly suppressed (see Example 4).

The above-mentioned atopy group refers to a group coated only with DNCB, an atopy-inducing reagent.

According to one embodiment of the present invention, it was confirmed that jadeite can reduce skin inflammation and ear edema in the atopic group due to DNCB administration (see Examples 5 and 6).

In general, serum total IgE is increased in mouse models that induce atopy, and many cytokines associated with inflammation are produced in immune-related organs. Based on this fact, the weight of the spleen, a representative organ involved in immunity, was measured after the end of the experiment. The spleen plays an important role in inducing an immune response to antigens in the bloodstream and is a place to respond to systemic infections. In atopic dermatitis that occurs when DNCB is applied, immune-related organs actively collect antigens, generate T cells and B cells, and generate an immune response, thereby increasing the weight of the spleen.

In the experiments of the present invention, the spleen weight of the atopy group was increased three times than that of the normal group, and the weight of the spleen was decreased when the jadeite was administered, indicating that the composition containing the jadeite significantly reduced atopic dermatitis. (See Examples 7, 8).

In addition, when jadeite was administered to atopic dermatitis-induced mice, it was confirmed that jadeite significantly inhibited increased mast cell infiltration and degranulation due to repeated application of DNCB (see Example 9).

In conclusion, in the present invention, it was found that the composition containing jadeite has the effect of improving atopic dermatitis.

The composition for preventing or treating atopic dermatitis of the present invention may be used in a pharmaceutical unit dosage form by adding a pharmaceutically acceptable excipient or diluent to the jadeite.

The composition of the pharmaceutical unit dosage form of the present invention is a formulation for oral administration such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, sterile injectables, suppositories and transdermal administrations according to conventional methods. Can be formulated and used. Excipients and diluents that may be included in the composition include lactose, glucose, white sugar, sorbitol, mannitol, xylitol, corn starch, potato starch, gum arabic, gelatin, methylcellulose, polyvinylpyrrolidone, purified water, methyl paraoxybenzoate, para Propyl oxybenzoate, talc, magnesium stearate. If necessary, it is formulated with diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants and the like.

As an example of one form, the composition containing the jadeite of the present invention may be formulated as a solid preparation for oral administration. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which are formulated by mixing at least one excipient such as starch, sugar or lactose, gelatin and the like with the extract. Become In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.

As another example, the composition containing the jadeite of the present invention may be formulated into a liquid preparation for oral administration. Liquid preparations for oral administration include suspensions, solvents, emulsions, syrups, and the like. In addition to the commonly used inert diluents (e.g., purified water, ethanol, liquid paraffin), various excipients may be used. Wetting agents, sweetening agents, fragrances, preservatives and the like can be included.

As another example, the composition containing the jadeite of the present invention may be formulated into a parenteral preparation. Parenteral preparations containing jadeite include sterilized aqueous solutions, non-aqueous solvents, suspension injections, emulsion type injections, and lyophilized injections.

As another example, the present invention provides a sanitary article comprising a composition containing jadeite.

Sanitary ware containing jadeite of the present invention can be used as sanitary napkins, soaps, shampoos, bath booms, etc., and vegetable oils such as propylene glycol, polyethylene glycol, olive oil, and, if necessary, preservatives, stabilizers, wetting agents, or emulsifiers, osmotic pressure. Salts or buffers for the control may also be used.

Preferably, in order to improve atopic dermatitis, the composition containing jadeite can be applied to the skin simultaneously with oral administration.

As used herein, an "effective amount" refers to an amount exhibiting a prophylactic or therapeutic effect when administered to a patient. The dosage of the composition according to the present invention may be appropriately selected depending on the route of administration, subject, age, sex, weight, individual difference and disease state. Preferably, the composition of the present invention can vary the content of the active ingredient according to the degree of disease, preferably can be contained in jadeite 0.0001 to 10000mg / kg. More preferably, it is administered in an amount of 0.0001 to 1000 mg / kg.

In another aspect, the present invention provides a dietary supplement for improving atopic dermatitis, including jadeite as an active ingredient.

The health functional food means a food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients having useful functions for the human body. Functionality refers to obtaining useful effects on health use such as nutrient control or physiological action on the structure and function of the human body. The active ingredient of jadeite is added to food materials such as beverages, teas, spices, gums, confectionery, etc., or manufactured in various forms of formulations. There are no side effects and the like, and excellent portability, the health functional food of the present invention can be taken as a supplement for improving atopic dermatitis.

The health functional food may be prepared including jadeite and food acceptable food supplements.

The health functional beverage composition of the health functional food of the present invention is not particularly limited to other components except for containing the jadeite, and may contain various flavors or natural carbohydrates, etc. as additional components, as in general beverages. Examples of the aforementioned natural carbohydrates include monosaccharides such as glucose, fructose; Disaccharides such as maltose, sucrose and the like and conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and sugar alcohols such as xylitol, sorbitol, erythritol. In addition to the foregoing, natural flavors (tauumatin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavors (saccharin, aspartame, etc.) may be advantageously used as flavoring agents. . The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition, the composition containing the jadeite of the present invention as an active ingredient can be used as a cosmetic composition for improving atopic dermatitis.

The components included in the cosmetic composition of the present invention include components conventionally used in cosmetic compositions in addition to jadeite as an active ingredient, for example, conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavors, and excipients It includes. In addition, the cosmetic composition may further include a skin absorption promoting substance to enhance the effect.

 Cosmetic compositions of the invention can also be prepared in all formulations commonly prepared in the art, including, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing, It may be formulated with hair cosmetics, oils, and the like, but is not limited thereto. More specifically, the cosmetic composition of the present invention skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutrition cream, moisture cream, hand cream, foundation, Sunscreens, essences, nutritional essences, packs, soaps, cleansing foams, cleansing lotions, cleansing creams, body lotions and body cleansers, emulsions, press powders, loose powders and eye shadows.

When the formulation of the present invention is a paste, cream or gel, an excipient component may be animal oil, vegetable oil, wax, paraffin, starch, cellulose derivative, polyethylene glycol, bentonite, talc or zinc oxide.

Lactose, talc, aluminum hydroxide, calcium silicate or polyamide powder may be used as excipient components when the formulation of the present invention is a powder or a spray, and especially in the case of a spray additionally includes a propellant such as propane / butane or dimethyl ether can do.

 When the formulation of the invention is a solution or emulsion, solvents, solubilizers or emulsions are used as excipient components, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethyleneglycol or sorbitan.

 When the formulation of the present invention is a suspension, excipient components include water, liquid diluents such as ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, and microcrystals. Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing, an excipient component is aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide ether Sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

Hereinafter, the Examples are only for illustrating the present invention in more detail, the following Examples and Experimental Examples are merely to illustrate the present invention is not limited to the contents of the present invention by these examples, It will be apparent to those of ordinary skill in the art that modifications, substitutions, insertions, and the like, which are commonly known, may be included in the scope of the present invention.

Example 1 Experimental Animal Preparation and Sample Preparation

1-1. Experimental animals

The experimental animals used in this experiment were 8-week-old SPF female NC / Nga mice (23 ± 3g), which were supplied from the central experimental animal, and were used in the experiment after being adapted for one week at the experimental animal breeding ground. During the experiment, solid feed and water were ingested freely, and the room temperature (22 ± 2 ℃), relative humidity (60 ± 5%) and contrast were maintained for 12 hours. One day before the start of the experiment, the hair was removed from the lower part of the ear of the test animal to the upper part of the tail using a mouse hair removal clipper, and then the hair was completely removed by applying a cream hair removal agent. This animal experiment was conducted in accordance with the regulations of the Animal Experiment Ethics Committee with prior review by Wonkwang University Animal Experiment Ethics Committee.

1-2. Sample Preparation

It was prepared by dissolving DNCB (Junsei Chemical Co., Ltd), an atopy-inducing reagent used in the experiment, in a solvent (acetone: olive oil = 4: 1 mixed) so as to have a concentration of 1% and 0.5%. The jadeite used in this experiment was prepared by using four kinds of herbs such as Saenghwanghwang, Bokryeong, Ginseng, and Honey in the laboratory according to the traditional method. Each medicinal constituent of the jadeite is in the ratio shown in Table 1 per 100g.

[Table 1] Composition and ratio of jadeite

Herbaceous  Herbal medicine  Volume  Ginseng  Ginseng Radix Alba, KP  6.2 g  Ghost  Hoelen, KP 12.4 g Green juice  Rehmannia Juice  39.9 g  Seal Honey, KP  41.5 g  Total  100 g

Example 2 Atopic Dermatitis Induction and Sample Treatment in NC / Nga Mice That Are Atopic Animals

All animals were provided with free diet and drinking water. A total of 12 animals were used, and each group was assigned to 3 animals divided into 4 groups. 3 normal groups orally administered 100 μl of purified water without DNCB, 3 μl orally administered purified water and 3 atopy groups with hydrophilic petroleum jelly on the back, and DNCB applied. Three low-dose sample administration groups with oral administration (12.5 mg / kg) and skin application (0.5 mg / mouse), oral administration with high-concentration extracts (25.0 mg / kg) and skin application (1.0 mg / mouse) Three high concentration sample dose groups were used.

 The back of the 8-week-old female NC / Nga mouse was epilated and left for 24 hours to heal fine wounds of the skin that may occur during the epilation process. After 24 hours, 100 μl of 1% DNCB per mouse was applied to the back and both ears for 4 consecutive days to induce atopic dermatitis. After 3 days of stopping DNCB application, 100 μl of 0.5% DNCB was evenly applied to the same site three times a week to maintain atopic dermatitis. Samples were administered daily from the start of the experiment (FIG. 1).

Example 3 Statistical Processing

All experimental results were expressed as mean ± standard deviation, and statistical significance test was performed by Student's t- test.

<Example 4> Effect of jadeite on the symptoms of atopic dermatitis in NC / Nga mice, atopy experimental animals

At the beginning of the experiment, changes in skin tissue such as mice (erythema, itching, dry skin, edema, sores, and lichen) were observed for 3 weeks.

Simultaneous application of the DNCB solution and oral administration of the sample was performed to observe atopic symptoms on the back skin of the mouse applied to the skin. The skin of the normal group was clean, and the atopic group showed various symptoms of atopic dermatitis such as erythema, edema, tear, skin, and thyroiditis, and the atopic group in the low concentration (12.5 mg / kg) and high concentration (25.0 mg / kg) groups. In comparison, atopic symptoms were significantly suppressed (FIG. 2).

Example 5 Effect of jadeite on body weight change in NC / Nga mice, experimental animals

At the beginning of the experiment, body weight was measured while observing external changes in skin tissue such as mice (erythema, itching, dry skin, edema, soreness, and lichen). The average body weight of the animals confirmed at the start of the experiment was 22-23 g, which was not different between the groups. During the experiment, the atopy group showed a significant fluctuation in weight change significantly compared to the normal group, and at the end of the experiment, the weight was decreased compared to the start of the experiment. There was a slight increase or decrease in the sample administration group, but the weight gain was increased compared to the atopy group. Body weight change was significant between each experimental group (FIG. 3).

Example 6 Effect of jadeite on ear edema in NC / Nga mice, experimental atopy animals

At the beginning of the experiment, ear thickness changes were measured while observing changes in skin tissue such as mice (erythema, itching, dry skin, edema, sores, and lichen). Ear swelling was used with vernier calipers (Mitutoyo, Japan).

Ear thickness of the mouse was measured once every two days from the start of the experiment to the end of the experiment. In the atopy group, ear thickness was the highest on 4th and 8th day, and the thickness of ear was slightly decreased, but increased compared to normal group or sample administration group, and high concentration group (25.0 mg / kg) and low concentration group. Ear edema was suppressed in both groups (12.5 mg / kg), especially in the high concentration group, compared to the normal group. (FIG. 4).

Example 7 Effect of jadeite on spleen weight in NC / Nga mice, atopy experimental animals

To examine the immune response of mice to DNCB, tissues and blood were collected at the end of the experiment, and the spleens were extracted and weighed (Table 2). The spleen weight of the atopy group increased about 3 times compared to the normal group, and the sample-administered group suppressed 49.6% and 44.8%, respectively, compared to the atopic group.

TABLE 2

group Spleen weight (g) Normal 0.0867 ± 0.0065 Atopy   0.2874 ± 0.0823 * Jadeite administration group (12.5mg / kg)    0.1921 ± 0.0177 ** Jadeite administration group (25.0mg / kg) 0.1985 ± 0.2017

(* p <0.05, ** p <0.01 versus normal group)

<Example 8> Effect of jadeite on the serum IgE concentration in NC / Nga mice as atopic experimental animals

At the end of the experiment, the blood was drawn from the heart with a syringe, and then serum was separated by centrifugation at 5,000 rpm for 3 minutes at 4 ° C. Store at -75 ° C. freezer until use in experiments. IgE concentration in serum of NC / Nga mice was measured using an ELISA (enzyme-linked immunosorbent assay kit (Shibayagi)). Into each 96 well plates, 5 μl of serum taken from the mouse and 45 μl of dilution buffer were mixed, 50 μl were dispensed into each well, and placed on a shaker at room temperature for 2 hours. After standing, the mixture was washed three times for 5 minutes with a washing buffer solution.

 Biotin-conjugated anti-IgE antibody was added thereto, and the resultant was left at room temperature for 2 hours and washed again three times. 50 μl of HRP-conjugated avidin was added thereto, placed on a shaker at room temperature for 1 hour, and washed again. 50 μl of chromogenic substrate reagent (TMB) was added thereto, and the resultant was allowed to stand for 5 minutes. Then, 50 μl of stop solution was added thereto, and the absorbance was measured by an ELISA reader (450 nm).

The concentration of IgE in the normal group was 465.33 ± 86.43 ng / ml, and in the atopy group, it was 1082.4 ± 170.93 ng / ml, which was 2.3 times higher than that of the normal group. In the low dose group (12.5 mg / kg), 763.0 ± 57.98 ng / ml in the sample dose group, and 632.5 ± 3.54 ng / ml in the high concentration group (25.0 mg / kg) were significantly inhibited compared to the atopy group (Table 3). .

[Table 3]

group IgE (ng / ml) Normal 465.33 ± 86.43 Atopy    1082.4 ± 170.93 * Jadeite administration group (12.5mg / kg)     763.0 ± 57.98 ** Jadeite administration group (25mg / kg)     632.5 ± 3.54 ***

Each value is mean ± S.D. (n = 3). * p <0.001, ** p <0.05, *** p <0.005 versus atopy

<Example 9> Effect of jadeite on mast cell number in NC / Nga mouse, an atopy experimental animal

In order to observe the infiltration of mast cells in the atopic skin induced by DNCB, the back skin tissue was stained with Alcian blue to observe mast cells.

At the end of the experiment mice were sacrificed and the back and ear tissues were removed and fixed in 10% neutral formalin for 24 hours. The tissue was embedded with paraffin and cut to 5 μm thickness. Mast cells in tissues were observed by staining with alcian blue. Malignant blue-positive mast cells were expressed in cell number / mm ² by counting cells in one graticule at 100-fold magnification.

The number of mast cells was 7.5 ± 0.58 in the normal group and 59.75 ± 2.75 in the atopy group, which was about 8 times higher than the normal group. The number of mast cells in the low dose oral and ointment samples was 40 ± 5.35 and the high concentration was 42.75 ± 2.75, higher than that of the normal group but significantly lower than the atopy group (Table 4). 5, 6).

[Table 4]

group Mast cell count Normal 19.038 ± 10.75 Atopy 167.2 ± 42.36 # Jadeite administration group (12.5mg / kg) 90 ± 8.48 ## Jadeite administration group (25mg / kg) 50.667 ± 17.32 ###

(#p <0.001 versus normal group, ## p <0.01 ### p <0.005 versus atopy group.)

1 shows a schematic diagram of the experimental protocol. 100 μl of 1% DNCB per mouse was applied to the dorsal region for 4 consecutive days, and 100 μl of 0.5% DNCB was evenly applied on the 8th, 10th and 12th days.

Figure 2 shows the atopic improvement effect of jadeite in mice with atopic dermatitis induced by DNCB. Normal (n = 3) is the no-treated group, Atopy (n = 3) is the atopy group treated with DNCB only, and the 3rd and 4th jadeite are 12.5mg / kg and 25mg / kg, respectively. It's a group.

Figure 3 shows the weight change of the mouse to which DNCB is applied. Each value is mean ± S.D. Represented by. * p <0.05, ** p <0.01 range showed a significant change compared to the normal group, and compared to the atopy group in the range of #p <0.05 means a significant change.

Figure 4 shows the effect of jadeite on ear edema in mice to which DNCB was applied. Each value is mean ± S.D. Represented by. There was a significant change in the normal group in the range of * p <0.05, ** p <0.01, and the atopy group in the range of #p <0.05, ## p <0.005.

5 shows the results of observing infiltration of mast cells in mice to which DNCB was applied.

6 shows the results of pathological examination of skin lesions in mice to which DNCB was applied. Skin tests were stained with hematocillin and eosin (magnification x100).

Claims (8)

A composition for the prevention or treatment of atopic dermatitis, containing jadeite as an active ingredient. The composition of claim 1, wherein the jadeite is made of raw sulfur, bokyeong, ginseng and honey. The composition according to claim 1 or 2, wherein the jadeite is contained in an amount of 0.0001 to 1000 mg / kg. The composition of claim 1, wherein the jadeite relieves edema in atopic dermatitis lesions. 2. The composition of claim 1, wherein the jadeite reduces serum total IgE concentration by inhibiting T lymphocyte activity by atopy. Cosmetic composition for improving atopic dermatitis containing jadeite as an active ingredient. Health functional food for improving atopic dermatitis containing jadeite as an active ingredient. Hygiene products for atopic dermatitis improvement comprising a composition containing jadeite as an active ingredient.

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