KR20090053055A - Composition for preventing and/or treating dermatitis or increasing immunnity comprising natural plants extract - Google Patents

Abstract

The present invention is for the prevention and treatment of allergic skin diseases and inflammatory skin diseases, including atopic dermatitis of Pyeongwisan and its Gagambang, including dermis, thick pepper, licorice and ginger and jujube as an active ingredient, or for enhancing immunity The present invention relates to a pharmaceutical composition, a dietary supplement, and a method of manufacturing the same.

Pyungwisan, Atopy, Skin Disease, Immune Enhancement

Description

Composition for preventing and / or treating Dermatitis or increasing immunnity comprising natural plants extract}

The present invention relates to a herbal composition that prevents and treats allergic skin diseases including atopic skin diseases and inflammatory skin diseases including psoriasis and eczema acne, and enhances immunity. For the prevention or treatment of allergic skin diseases including atopic dermatitis and psoriasis, eczema acne, including dermis, thick pepper, licorice and flat stomach acid including ginger and jujube Or it relates to a pharmaceutical composition and health functional food for immuno-enhancing, and a method for producing the same.

The skin of the human body is an indispensable organ for the maintenance of life, which physically and chemically protects the body from the outside world and performs the biochemical functions necessary for metabolism of the whole body. Relatively common skin diseases include atopic dermatitis, contact dermatitis, seborrheic dermatitis, urticaria, athlete's foot, psoriasis, psoriasis, herpes simplex / shingles, dry skin, housewives and acne.

Currently, the number of patients with skin problems and skin diseases continues to increase. In developed countries such as the United States, about 10% of the population suffers from skin diseases, and in Korea, the situation is similar.

Other causes of skin diseases include mechanical stimuli such as friction, compression, and bruises that act directly on the skin from the outside world, as well as animal, vegetable and mineral poisons, other drugs, radiation, heat, cold, or bacteria, filamentous fungi, protozoa, Microorganisms such as viruses and skin parasitic animals, and the like, and endogenous disorders include gastrointestinal disorders, liver disease, kidney disease, metabolic disorders, blood diseases, visceral tumors, and endocrine disorders. In addition, hereditary skin diseases, birthmarks and birthmarks are included in endogenous skin diseases because their cause is caused by genes.

Among skin diseases, in particular, atopic dermatitis is a representative skin disease that occurs in people with atopic allergies, and is one of chronic skin diseases commonly referred to as febrile fever, and is a recurrent chronic dermatitis with severe pruritus. In recent decades, the prevalence of atopic dermatitis continues to increase due to the increase in airborne allergens due to environmental pollution and the increase in conditions for forming dry skin, and 10 to 20 of the world's population It is known that% suffer from this dermatitis. The main symptoms are itching and dry skin, and the immunological characteristics may be accompanied by other allergic diseases such as urticaria, asthma, allergic rhinitis and allergic conjunctivitis.

Allergic reactions of atopic dermatitis can be divided into early specific immune response and late inflammatory response. Almost allergic reactions occur through mast cells and are activated through high-affinity IgE receptors (FcεRI) on the cell membrane. When the IgE antibody bound to the IgE receptor forms a bridge by antigen, histamine and chondroitin sulfate stored in the granules through the action of phospholipase C, protein kinase C, and calcium ions , Heparin, protease and the like are released, which mediate the early stages of the reaction. Electrochemical carriers, including histamine, are the causative agents of various clinical symptoms seen early in the allergic reaction, with the largest amount being histamine. Therefore, in the allergic reaction, the action by histamine is the main, the symptoms include vasodilation, edema. In addition, prostaglandin and platelet-activating factor are chemical transporters that are attracting attention in allergic reactions.Skin symptoms such as dimples, pruritus, and redness of the skin can be caused by the action of chemical transporters. There is this.

On the other hand, aging of the cells proceeds as the period of regeneration of the skin cells, which are the basic units constituting the skin, due to physiological natural phenomena, is not normal, and is gradually increased. As the cells age, the skin loses its elasticity and wrinkles develop as the aging keratin accumulates and dries. Currently, surgery or ointment and vitamin C therapy are used to restore the skin caused by aging, but it is not enough to maintain a tight and elastic skin.

Recently, anti-aging and skin improving agents using natural products have been developed. However, some of them have a function as a skin improver against androgen (androgen) inhibitory effect and sebum secretion increase inhibitory effect, but it does not provide a practical effect as a treatment for skin diseases. In recent years, medical skin care (medical skin care), a combination of medical treatment and skin care skin treatment has been developed not only in Korea, but also in the United States, Europe, Japan, etc. for the treatment of allergies skin diseases, etc. However, acne, blemishes, freckles, etc. to improve the situation still many skin diseases are not overcome.

Meanwhile, interferon-gamma secreted by immune cells plays an important role in increasing immunomodulatory capacity through antigen-specific and nonspecific immune responses in monocytes and macrophages. Decreased secretion of interferon-gamma exacerbates atopic symptoms due to increased IgE production or reduced antigenic ability. Interferon gamma also acts on T lymphocytes to enhance their differentiation and maturation. It also promotes the differentiation of Th1 lymphocytes in CD4 T lymphocytes and inhibits the proliferation of Th2 lymphocytes. This effect is mediated by activating monocytes to secrete IL-12 and activating T lymphocytes to express functional IL-12 receptors.

In the treatment of skin diseases including such atopic dermatitis, inflammatory dermatitis, steroids are usually widely used. However, steroids can cause various side effects such as decreased immune function, thinning or atrophy of the skin, and flushing. In long-term use, steroids may cause steroidal acne, steroidal skin (skin atrophy, capillary expansion, purpura), steroidal effects. Injections, perioral dermatitis, hair loss, pigment loss, ancestors, bullous dermatitis, skin bleeding may occur. Moreover, there exists a possibility that administration may be carried out with the cause intact, and drug dependence may arise.

In addition to steroids, there are many known examples of anti-inflammatory or dermatological agents that have been developed for the treatment of skin diseases by extracting the active ingredients known for their effects. However, most of them are effective in relieving itching and inflammation. It is not a level, so the application is actually limited. As described above, herbal preparations for the purpose of prevention or treatment that have excellent side effects while still having fewer side effects have not been developed, and most of the steroid preparations showing serious side effects are used.

In recent years, immunosuppressants have been developed and used as treatments for skin diseases. These preparations are clinically used due to side effects such as decreased immune function, skin atrophy, growth inhibition of children, capillary expansion, acne, and adrenal cortex. There is a problem that requires very careful use.

Therefore, the present inventors have the effects of preventing and treating allergic and inflammatory skin diseases while minimizing side effects such as decreased immune function, renal function, abnormal hormone secretion, etc., which have conventional skin disease treatment agents, and to develop a composition having an immune enhancing effect. As a result of this study, the results of the present invention confirmed that alleviated allergic skin diseases including atopic dermatitis and other inflammatory skin diseases, and immune enhancing effects, as a herbal prescription widely used in the treatment of gastrointestinal diseases, and completed the present invention. It became.

The present invention exhibits the effect of preventing and treating allergic and inflammatory skin diseases by suppressing allergic reactions, alleviating inflammation and improving immunity, and also comprising pharmaceutical compositions and health functional foods including Pyeongwisan and its additives having an immune enhancing effect. The purpose is to provide.

The present invention is to prevent or treat allergic skin diseases and inflammatory skin diseases, including atopic dermatitis of Pyeongwisan and its Gagambang as added as active ingredients, dermis, thick pepper, licorice as the main medicinal substances and added ginger and jujube The present invention relates to a pharmaceutical composition and a dietary supplement for use in immunotherapy or for immune enhancement.

The composition of the present invention has a prophylactic and therapeutic effect against allergic skin diseases such as atopic dermatitis and inflammatory skin diseases by inhibiting allergic reactions and inflammatory reactions such as histamine secretion inhibitory effect, passive skin suppression reaction and edema suppression reaction.

In addition, it enhances immune function by increasing the production of interferon gamma, which is important for the regulation of human immune function, and can be used as an adjuvant for the treatment of skin aging, psoriasis, dry skin, itching, chronic eczema and acne due to reduced immune function. This effect was confirmed from Experimental Examples 1 to 5 below.

Creation used as a raw medicine of the flat acid used in the present invention is a dry humidity, high humidity; The dermis is selfish, moist; Thick foil is a humid conductor; Licorice has the efficacy of bobby ripening, clear heat detoxification, rotation elimination, and harmony medicine.

In addition, jujube is Bobihwawi, ripe, and ginger has the efficacy of sweat sweating, warm earth, monetary harm.

The composition according to the present invention may be formulated by a method known in the pharmaceutical art, and may be mixed with the extract itself or a pharmaceutically acceptable carrier, excipient, etc., to prepare a conventional pharmaceutical preparation, for example, tablets, granules, capsules, powders. , Liquid or syrups; Alternatively, it may be formulated as an ointment, a warning agent, a pasta agent, a cataplasma agent, a cream agent, or an emulsion, and may be used in other formulations when used, and may be administered by various routes.

In addition, the composition according to the invention may further comprise a pharmaceutically acceptable carrier. Carriers that can be used in the composition of the present invention are conventional in the pharmaceutical field, for example, in the case of oral preparations, there are binders, lubricants, disintegrants, excipients, solubilizers, stabilizers, etc. In the case of formulations, there are bases, excipients, lubricants, preservatives and the like.

Referring to the present invention in more detail as follows.

In the composition according to the present invention, each herbal medicine such as creation, dermis, thick pepper, licorice, etc. may use commercially available herbal medicines, and may use the root, fruit peel, bark root portion of these herbs, These extracts may be used for (i) extracting each, or (ii) mixing and preparing the extracts, or (iii) powdering the herbal extracts by condensation drying.

In the composition according to the invention, each herbal medicine is preferably obtained by mixing with a constant weight ratio and then extracting with water.

The composition according to the present invention is preferably a mixture, dermis, thick, licorice 2 to 8: 1.25 to 5: 1 to 4: 0.5 to 2 by weight ratio.

In addition, the present invention may further include one or more herbal medicines selected from the group consisting of jujube and ginger and may be included in the weight ratio of 0.5 to 2 based on the creation, or ginger may be included in the weight ratio of 0.5 to 2 have.

More preferably, the composition according to the present invention is characterized in that the creation, the dermis, thick, licorice, jujube, ginger is included in the weight ratio of 8: 5: 4: 2: 2: 2, respectively.

When lower than the lower limit of the composition ratio of the above-mentioned herbal medicines, the physiological activity effect of the component may be reduced, and when higher than the upper limit, the physiological activity effect of the other components may be reduced, which may lower the synergy and cooperative action of the composition. have.

The composition of the present invention is, for example, but not limited to, 8g, dermis 5g, 4g thick, licorice 2g jujube 2, 1 to 3 mm of ginger, pour 600 mL of water and about 2 hours It can be decocted for half and concentrated to about 150 mL to form a probiotic.

A typical single dose of the composition is 1.5-2.5 mL per kg of body weight based on the single dose of flat stomach acid and is taken three times a day. When this amount of liquid is used as a lyophilized powder, it is 0.5 to 1 g / time. However, the composition of the present invention can be appropriately increased or decreased the dose depending on the weight, age, sex, severity of the patient and the digestive state. In other formulations, the appropriate amount calculated in consideration of the liquid dosage is administered orally.

Hereinafter, the present invention will be described in more detail with reference to the following Examples. The scope of the present invention is not limited in any way.

Example  One: Liquid  Produce

2 g of jujube (about 2 g), 3 g of ginger sliced in 1 to 3 mm (about 2 g) in 8 g, 5 g of dermis, 4 g of gourd, 2 g of licorice, pour 600 mL of water and decoction for about half an hour Concentrated and tanned.

Example  2: preparation of tablets

After lyophilizing and concentrated the concentrated solution prepared according to Example 1, 500 mg of the powder, 100 mg of lactose and 150 mg of starch were mixed, and the tablets were prepared by tableting according to a conventional method for preparing tablets.

Example  3: Preparation of Other Formulations

Pills, granules, capsules were prepared from the above extracts according to a conventionally known method.

Experimental Example  1: inhibitory effect of histamine release according to the present invention

By herbal extract The inhibitory effect of histamine release was investigated and the experiment was carried out as follows.

Inject 30 mL of Tyrode buffer B (137mM NaCl, 5.3mM Glucose, 12mM NaHCO ₃ , 2.7mM KCl, 0.3mM NaH ₂ PO ₄ ) into the abdominal cavity of the rat, and massage the abdomen for 90 seconds. Was carefully opened to collect Tirod buffer B containing intraperitoneal cells with a Pasteur pipette. Subsequently, the cell-containing solution was centrifuged at 150 × g for 10 minutes to precipitate the cells, pipetted with the addition of T-load buffer B to the precipitated cells, and then lightly stacked on 22.5% metrizamide solution and 400 Centrifugation at x g for 15 minutes gave only precipitated cells. Α-MEM (minimum essential medium) / 50% FBS (fetal bovine serum) was added to the electroprecipitated cells and pipetted to 95% or more mast cells by toluidine blue staining, and viability by trypan blue staining. This was confirmed to be more than 97% and used in the experiment.

Α-MEM / 50% FBS was added to the previously purified mast cells, pipetted carefully, and aliquoted to 2 × 10 5 cells. In order to stabilize the cells, the incubation was carried out at 37 ° C. for 10 minutes before treatment of the herbal extracts, and the aqueous solutions of the herbal extracts prepared in Example 1 were 0.01, 0.1, 1.0 mg / mL (the herbal extract 0.01, per mL of distilled water, respectively). 0.1, 1 mg dissolved) and treated at 37 ° C. for 30 minutes and immediately proceeded to Compound 48/80 (Baltzly et. al . , 1949. A family of long acting depressors. Journal of American Chemical Society 71, 1301-1305) was treated with 5.0 μg / mL (amount of reagent per volume) for 10 minutes. After completion of the reaction, the supernatant and the cells were separated by centrifugation at 400 × g.

The amount of histamine was measured at 438 nm by OPA (ο-phthaldialdehyde) spectrofluorometry, and the inhibition rate of histamine secretion was calculated using the following equation.

Inhibition Rate (%) = ((A-B) × 100] / A

 A: histamine when no drug is added

 B: Histamine amount when drug is added

As a result, it was confirmed that the secretion of histamine from the celiac mast cells induced by 'Compound 48/80' was concentration-dependently suppressed by the herbal extract. The highest effective concentration was 1 mg / mL and suppressed up to 9%, showing a significant result with P <0.05 for each concentration (FIG. 1).

Experimental Example  2: Effect of Herbal Extracts on Skin Allergic Reactions

The effects of herbal extracts on passive skin allergic reactions were investigated. First, a passive cutaneous anaphylaxis (PCA) reaction was caused in the following manner.

As an experimental animal, 5 rats of ICR varieties of 4-6 weeks old and weighing 25-35g were repeatedly used in each experimental group. First, the rats were fed 24 hours after sufficient feeding. The rats were obtained from the Korean Animal Center.

Skin sensitization by intradermal injection of anti-DNP (dinitrophenyl) IgE in the rats followed by intravenous injection of antigen DNP-HSA (dinitrophenyl-human serum albumin) into the tail 48 hours later to induce an IgE dependent skin reaction It was. At this time, DNP-HSA was diluted with PBS (phosphate buffered saline). After injecting 100ng of anti-DNP IgE into the rat's back, 48 hours later, 4% Evans blue and DNP-HSA mixed 1: 1 was injected into the tail vein of the rat. 1 g of the herbal extract of Example 1 (extract) / kg (body weight) was orally administered to rats 1 hour before the antigen (DNP-HSA).

After killing the rats, the reaction site was cut and 500 μl of 0.1 N potassium hydroxide was added. Then, 4.5 mL of acetone and phosphoric acid (5:13, w: w) mixed solution was added to extract pigments. The absorbance of the extract was measured at 620 nm and the amount of pigment was measured using the Evans Blue standard curve.

As a result, the passive skin allergic reaction was most suppressed at the 1 g / kg dose of the herbal extract. These results indicate that oral administration of herbal extracts can significantly inhibit local, ie, skin allergic reactions (Table 1-Effect of herbal medicine on passive skin allergic reactions * P <0.05).

Herbal Medicine Extract (g / kg) Dyeing amount (㎍ / site) Inhibition Rate (%) None (Saline) 8.94 ± 0.19 - 0.01 7.34 ± 0.21 17.9 ± 4 0.1 6.15 ± 0.22 31.2 ± 2 * One 5.31 ± 0.15 40.6 ± 2 *

Experimental Example  3: of herbal extract Ear  Effect on edema reaction

Experimental animals were repeated 4-6 weeks old and weighing 25-35g ICR mice (four mice) for each experimental group. First, the rats were fed 24 hours after sufficient feeding. The rats were obtained from the Korean Animal Center.

First, the herbal extract of Example 1 was orally administered at 0.01, 0.1, and 1 g / mL doses, and then reacted for 1 hour. Compound 48/80 (20 g / L) is then injected subcutaneously inside the rat ear using a micro syringe, and after 40 minutes the ear thickness at the site of the edema reaction has been measured. As shown in Table 2, it can be seen that there is no significant effect at low concentrations, it was found that the most suppressed the edema response at 1 g / kg and obtained a significant result with P <0.05 (Table 2-Compound Effect of extract on 48/80 induced edema response).

Herbal Medicine Extract (g / kg) Thickness of ear (mm) Inhibition Rate (%) None (Saline) 0.161 ± 0.003 - 0.01 0.153 ± 0.006 5 0.1 0.120 ± 0.010 25.5 ± 1 One 0.084 ± 0.004 47.8 ± 1 *

Experimental Example  4: of herbal extract Interferongamma  Produce effect

We investigated whether herbal extracts induce the production of interferon gamma, which is responsible for immune enhancing function.

T cell line Molt-4 was cultured in culture medium RPMI 1640 / FBS at 5% CO ₂ , 37 ° C. and then aliquoted to 3 × 10 5 cells. In order to stabilize the cells, the cells were pre-incubated at 37 ° C. for 10 minutes prior to treatment with the herbal extracts, and the aqueous solutions of the herbal extracts of Example 1 were 0.01, 0.1, and 1.0 mg / mL, respectively. Dissolved), and reacted for 24 hours, followed by incubation. After completion of the reaction, the supernatant and the cells were separated by centrifugation at 400 × g. Enzyme linked immunosorbent assay (ELISA) was performed to investigate the protein level of interferon gamma in the isolated supernatant.

Anti-human interferon gamma (1 μg / mL), a monoclonal antibody to interferon gamma, was diluted with PBS (pH 7.4) and coated 100 μl each in a 96-well plate, followed by 12 at 4 ° C. It was left for hours. The electrical plates were washed with PBS containing 0.05% Tween and then blocked for 1 hour with PBS containing 1% BSA, 5% sucrose, 0.05% NaN ₃ . After washing several times, the supernatant obtained by centrifugation and the recombinant interferon gamma to be used as a standard curve were added and left at 37 ° C. for 2 hours. Subsequently, each well was washed again and added to the secondary antibody biotin-bound interferon gamma (0.2 μg / mL) and left for another 2 hours at 37 ° C. The wells were washed and then avidin-linked peroxidase was added and left at 37 ° C. for 20 minutes. The wells were washed again, then ABTS (2,2′-Azino-bis (3-ethyl benzthiazol-ine-6-sulfonic acid) substrate was added and the color reaction was measured at 405 nm using an ELISA reader.

As a result, as shown in Figure 2, it was found that the herbal extracts increase the interferon gamma production concentration-dependently (* P <0.05).

Experimental Example  5: Herbal Extracts Improve Atopic Dermatitis

Recently, NC / Nga mice, which have been used as animal models of atopic diseases, do not cause atopic symptoms in SPF (specific pathogen free) breeding environment, but when they are raised under conventional conditions, erythema, edema and hematoma after 8 weeks Atopic symptoms such as edema and excoriation, erosion and scar, hair loss and skin dryness. In Experimental Example 5, the extent to which atopic symptoms naturally induced under conventional conditions was improved by oral administration of the herbal extract of Example 1 was observed. 29-week-old NC / Nga mice with atopic symptoms were orally administered daily with water and the herbal extract of Example 1 at 25 mg / kg and 250 mg / kg, respectively. As can be seen from the results of Figure 3, in the case of mice administered the herbal extract of the present invention, atopic symptoms were shown to improve.

Figure 1 shows the histamine inhibitory effect of the herbal extract of Example 1,

Figure 2 illustrates the interferon gamma production effect of the herbal extract of Example 1,

Figure 3 shows the results of atopic symptoms improved after oral administration of the herbal extract of Example 1.

Claims (14)

A pharmaceutical composition for the prevention or treatment of allergic skin diseases or inflammatory skin diseases, or for immuno-enhancing, comprising the extract, the dermis, the thick and licorice water extract or the dry powder of the water extract. The composition of claim 1, further comprising a water extract obtained by further mixing one or more selected from the group consisting of ginger and jujube, or a dry powder of the water extract. The composition according to claim 1, wherein the weight ratio of the creation, the dermis, the thick foil and the licorice is 2-8: 1.25-5: 1-4: 0.5-2. The composition of claim 2, wherein the jujube or ginger is a weight ratio of 0.5 to 2 and a weight ratio of 0.5 to 2, respectively, based on the total weight of the produce. Health functional food for allergic skin disease or inflammatory skin disease, which contains water extract of dermis, groin and licorice, or dry powder of water extract as an active ingredient, or for immune enhancement. The health functional food according to claim 5, comprising a water extract obtained by further mixing one or more selected from the group consisting of ginger and jujube, or a dry powder of water extract. A process for preparing the pharmaceutical composition according to claim 1 by mixing the creation, dermis, groceries and licorice mixture with water, and the water extract obtained from drying the powder obtained by drying with a pharmaceutically acceptable carrier. The method of claim 7, wherein the mixture obtained by further mixing one or more selected from the group consisting of jujube and ginger is extracted with water, and the powder obtained by drying the water extract obtained therefrom is mixed with a pharmaceutically acceptable carrier to obtain a pharmaceutical composition. Method of preparing the composition. A method for producing a dietary supplement according to claim 5, wherein the mixture of extract, dermis, groin and licorice is extracted with water, and the water extract obtained therefrom is dried with a carrier acceptable as a food. 10. The health functional food according to claim 9, wherein the mixture obtained by further mixing one or more selected from the group consisting of jujube and ginger is extracted with water, and the water extract obtained by drying the mixture is mixed with a food acceptable carrier. How to prepare. The oral composition according to claim 1 or 2, which has a formulation selected from tablets, granules, capsules, liquid preparations, or syrups. The skin coating composition according to claim 1 or 2, which has a formulation selected from ointment, warning agent, pasta agent, cataplasma agent, cream agent or emulsion. The pharmaceutical composition according to claim 1, wherein the allergic skin disease is atopic skin disease. The health functional food according to claim 5, wherein the allergic skin disease is atopic skin disease.

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