KR100881445B1 - Composition for protection of skin and improvement of skin diseases and process for preparation thereof - Google Patents

Abstract

The present invention as an active ingredient, Angelica, Cheonggung, Saenghwang, Sewao, Astragalus, Licorice, Gilgyeong, Pogongyoung, Baekjak, Baekchul, Brown root, Peppermint, Sine, Dermis, Yulmu and dry ratio, and then extracted with water or extracted with water and then mixed The present invention relates to a composition for protecting skin and improving skin diseases containing a water extract or a dry powder thereof, and a method for producing the same.

Description

Composition for protection and skin disease improvement and method for manufacturing the same {Composition for protection of skin and improvement of skin diseases and process for preparation

1 is a graph showing the interferon-γ production effect of the composition according to the present invention.

The present invention relates to a herbal composition for skin protection and skin disease improvement, and more specifically, as an active ingredient, Angelica, Cheongung, Saengjihwang, Shou, Astragalus, Licorice, Giltyeong, Pogongyoung, Baekjak, Baekchul, Brown root, Mint, Sign Allergic skin diseases, such as atopic dermatitis, containing water extracts or dried powders thereof, which are mixed with water, dermis, silk radish and dry rate (dried balm) and then extracted with water or mixed with water, and psoriasis, eczema, acne The present invention relates to a composition for improving skin wrinkles and the like caused by aging and the like, as well as to dermatitis diseases.

The skin of the human body is an indispensable organ for the maintenance of life, which physically and chemically protects the body from extraterrestrial and performs the biochemical functions necessary for metabolism of the whole body. All abnormalities that appear on the skin, including human hair, hands and toenails, are called skin diseases, or skin diseases. Since the skin covers the surface of the body, there are many opportunities for direct contact with stimuli or various pathogens from the outside, and are greatly affected by the body. In addition, even minor changes of the skin can be seen by eye and touched by hand, and it is easy to perform pathological histological examination and examination of microorganisms by taking a part of the lesion, and to easily diagnose the diagnosis of individual diseases. The type is considerably larger than that of other organs, and the disease name is complicated. 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.

Inner skin diseases include gastrointestinal disorders, liver disease, kidney disease, metabolic disorders, blood diseases, visceral tumors, and endocrine disorders.Inners such as friction, pressure, and bruises act on the skin directly from the outside world. In addition to stimulation, animal, vegetable, mineral poisons, other drugs, radiation, heat, cold, microorganisms such as bacteria, filamentous fungi, protozoa, virus, and skin parasites. In addition, hereditary skin diseases and birthmarks and birthmarks are caused by genes and are included in endogenous skin diseases.

Among skin diseases, especially atopic dermatitis is a disease caused by an allergic reaction. The allergic reaction is divided into early specific immune response and late inflammatory response. Most 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 the 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 to mediate the initial stages of the reaction. Chemical transporters, including histamines, are the causative agents of various clinical symptoms seen early in the allergic reaction, with histamines accounting for the largest amount. Therefore, the action by histamine in the allergic reaction is important, the symptoms include vasodilation, edema. Prostaglandin and platelet-activating factor are also known chemical transporters for allergic reactions. Symptoms resulting from the action of a chemical delivery agent may include skin symptoms such as dimples, pruritis, and skin redness.

Currently, the number of patients with skin problems and skin diseases continues to increase due to environmental pollution, dietary habits and genetic causes. In the United States, 5-12% of the population suffers from skin diseases, and in Korea, there are about 2 to 3 million skin disease patients. Nevertheless, most of the steroids that have serious side effects are presently used as therapeutic agents or ameliorators. Recently, immunosuppressive agents have been developed, but there are no special therapeutic agents or ameliorators that have cured effects without concern for side effects. . Although the global market for these skin disease treatments is worth US $ 1.3 billion, it is accompanied by side effects such as decreased immune function, skin atrophy, disruption of children, expansion of capillaries, acne and adrenal cortex, Can not be done. In addition, there are known examples of the development of anti-inflammatory or skin disease, such as the active ingredient extracted from the known herbal medicines for the treatment of skin diseases, but mostly to relieve itching and inflammation, but does not cure the disease.

On the other hand, due to aging of the cells, physiological natural phenomena, skin cells, which are the basic units that make up the skin, are not normally divided, and the regeneration period is gradually longer, and the skin loses its elasticity. It starts to occur. Currently, surgery or ointment and vitamin C therapy are used to repair skin wrinkles due to aging, but it is not enough to maintain a firm and elastic skin, which is a long-time desire of human beings. In addition, skin anti-aging and skin improver using natural products such as fruit acid or kimchi extract have been developed for many years, but it only functions as skin improver by inhibiting androgen, a male hormone, and increasing sebum secretion. There is no effect as a therapeutic agent for skin diseases.

In recent years, so-called "medical skin care", which combines medical treatment and skin care, has been greatly developed for skin treatment not only in Korea, but also in the United States, Europe and Japan. However, it only improves the appearance of acne, blemishes, freckles, etc. It is unclear for allergic skin diseases, diseases caused by reduced immune function and aging.

Meanwhile, interferon-γ secreted by immune cells plays an important role in increasing immunomodulatory capacity through antigen-specific and nonspecific immune responses in monocytes and macrophages. Decreased interferon-γ secretion exacerbates atopic symptoms due to increased IgE production or reduced antigenic clearance. Interferon-γ 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.

Therefore, there is an urgent need for the development of a product that can maintain the young skin through the improvement of immune function by the production of interferon-γ in the human body and fundamentally improve skin diseases such as allergy by regulating histamine production.

The present inventors conducted a continuous study to solve the problems of conventional skin diseases, including skin problems, and at the same time to develop a composition that does not have side effects such as decreased immune function, renal function, abnormal hormone secretion. As a result, it was confirmed that there is an effect to improve the skin disease as well as to regulate the immune function when used by mixing a single substance excellent in the conventional allergic reaction and completed the present invention.

Accordingly, an object of the present invention is to provide a composition and a method for producing the same that fundamentally treat the cause of skin problems by regulating human immune function, rather than simply improving or temporarily treating the skin.

The present invention as an active ingredient, Angelica, Cheonggung, Saenghwang, Sewao, Astragalus, Licorice, Gilgyeong, Pogongyoung, Baekjak, Baekchul, Brown root, Peppermint, Sine, Dermis, Yulmu and dry ratio, and then extracted with water or extracted with water and then mixed The present invention relates to a composition for skin protection and skin disease improvement, comprising a water extract or dried powder thereof.

Angelica used as a raw material herbal in the present invention is blood donation blood, landscaping pain, yunjangcheong; Celestial arches are vigorous; Saengjihwang is blue fever, lively; Sewage is interpolated, bleeding, stool, sea swelling; Astragalus has boil, turbid poison, drainage, and aching pain; Licorice has antitussive, expectorant, detoxifying, alveolar, anti-inflammatory, analgesic and anti-hypersensitive effects; Gil-Gyeong is an expectorant with a fermented stomach; Pogongyoung has the ability to detoxify, lysate, antibacterial, antiviral, antifungal, diuretic; Other ingredients have some of the efficacy of high-label, natural shallow sea, vitality, dissipative wind heat, mid-season, mid-heavy branch, clear heat drainage, and dihydrogen species.

In the present invention, each of the herbal medicines are extracted by the conventional method, the active ingredients, or after mixing the herbal medicines at once, and if necessary, concentrated to dry it to powder. In the present invention, preferably, each herbal medicine is mixed in a prescribed weight ratio and then extracted with water.

The composition according to the invention preferably further contains a pharmaceutically or food or cosmetically acceptable carrier. Pharmaceutically acceptable carriers that can be used in the compositions of the present invention are conventional in the pharmaceutical art, for example, in the case of oral preparations, binders, lubricants, disintegrants, excipients, solubilizers, stabilizers, etc. In the case of formulations for topical administration, there are bases, excipients, lubricants, preservatives and the like. If necessary, it may be prepared in the form of pills, granules, tablets or capsules, and, if necessary, may be used in a different dosage form when used.                     

The raw materials for the preparation of the composition according to the present invention are Angelica, Cheonggung, Saengjihwang, Sewao, Astragalus, Licorice, Gilgyeong, Pogongyoung, Baekjak, Baekchul, Brown Root, Peppermint, Sinus, Dermis, Yulmu and Dried Rate. 8: 2-8: 1-6: 3-12: 1-6: 2-8: 8-16: 2-8: 2-8: 1-8: 1-8: 0.5-4: 0.5-4: It is contained in the weight ratio of 1-16: 0.5-20.

The composition ratio of the herbal medicines is obtained on the basis of repeated experimental results, and if lower than the lower limit, the physiological activity effect of the component may be reduced, and if higher than the upper limit, the physiological activity effect of the other components may be reduced. There is a fear that cooperation will be reduced.

The composition of the present invention can be used as a skin protection and skin disease improving agent, this effect is confirmed from Experimental Examples 1 to 4 below. The composition according to the present invention is believed to enhance skin protection and skin disease improvement by regulating the production of cytokines and chemical mediators from immune-related cells.

The composition of the present invention, for example, Angelica 2-8 g, Cheongung 2-8 g, Saengjihwang 2-8 g, Sewage 1-6 g, Astragalus 3-12 g, Licorice 1-6 g, Gil length 2-8 g, Pogongyoung 8-16 g, Baekjak 2-8 g, Baekchul 2-8 g, Brown root 1-8 g, Mint 1-8 g, Sine 0.5-4 g, Dermis 0.5-4 g, Young radish 1-16 g, and dry rate 0.5 800 ml of water are poured into a mixture of -20 g, decocted for about 2 hours, concentrated to about 150 ml and made into a tan.

A typical single dose of the composition is 1.5 to 2.5 ml per kg of body weight based on the type of tanning and is taken three times a day. For example, for an adult weighing 60 kg, take 90-150 ml once three times a day. When the solution of this capacity is used as a lyophilized powder, it is 0.5 to 1 g / 1 times. However, the dosage of the composition may be increased or decreased depending on the patient's weight, age, sex, severity of the condition and digestion. 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 1 Preparation of Liquid

Angelica 4g, 4 g of Cheongung, 4 g of raw jihwang, 4 g of sewage, 3 g of astragalus, 6 g of licorice, 3 g of licorice, 4 g of pogongyoung, ginseng 4 g, white extract 4 g, black root 4 g, mint 4 g, signature 2 To a mixture of g, 2 g of dermis, 8 g of barley radish and 10 g of dryness was poured 800 ml of water, decocted for about 2 hours and concentrated to about 150 ml to form a liquid.

Example 2: Preparation of Other Formulations

Pills, granules, tablets and capsules were prepared from the extract of Example 1 according to a conventional method.

Example 3: Preparation of Food

After freeze-drying the extract of Example 1, the powder was mixed with chocolate to prepare a food according to a conventional method.

Experimental Example 1 Measurement of the Histamine Release Inhibitory Effect of the Composition According to the Present Invention

In order to measure the histamine release inhibitory effect of the composition according to the present invention, the following experiment was performed.

Inject the rat abdominal cavity with about 30 ml of Tyrode buffer B (137 mM NaCl, 5.3 mM glucose, 12 mM NaHCO ₃ , 2.7 mM KCl, 0.3 mM NaH ₂ PO ₄ ) and inhale the abdomen for 90 seconds. Massage about. Then, the peritoneum was carefully opened to collect Tyrod buffer B containing intraperitoneal cells with a Pasteur pipette. The cell-containing solution was then centrifuged at 150 x g for 10 minutes to precipitate the cells. Tirod buffer B was added to the precipitated cells, followed by pipetting, followed by slightly stacking on 22.5% metrizamide solution and centrifugation at 400 × g for 15 minutes to obtain only precipitated cells. Α-MEM (minimum essential medium) / 50% FBS (fetal bovine serum) was added to the precipitated cells and pipetted to mast cells by 95% or more by toluidine blue staining method and viability by trypan blue staining. It was confirmed that more than 97%, it was used in the experiment.

Α-MEM / 50% FBS was added to the purified mast cells and carefully pipetted, and then divided into 2 × 10 ⁵ cells. Incubate at 37 ° C. for 10 minutes prior to treatment of the composition of Example 1 to stabilize the cells, and the aqueous solution of Example 1 was 0.01, 0.1, 1.0 mg / ml (the composition of Example 1 per ml of distilled water, respectively). 0.01, 0.1, 1 mg dissolved) and treated at 37 ° C. for 30 minutes. Shortly thereafter, 5.0 μg / ml (amount of reagent per volume) was added for 10 minutes for each compound 48/80 (Baltzly et al, 1949. A family of long acting depressors. Journal of American Chemical Society 71, 1301-1305). Treated. After completion of the reaction, the supernatant and the cells were separated by centrifugation at 400 × g.

Histamine quantitation was measured at 438 nm by OPA-phthaldialdehyde spectrofluorometry, and the inhibition rate of histamine secretion was calculated using the following formula:

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

 A: amount of histamine when no drug is added

 B: amount of histamine when drug is added

The results are shown in Table 1.

Effect of the composition according to the invention on compound 48/80 inducible histamine release Composition of Example 1 (mg / ml) % Inhibition No treatment (saline) - 0.01 20.54 ± 3

As shown in Table 1, it was confirmed that the secretion of histamine from the peritoneal mast cells induced by 'Compound 48/80' was suppressed by about 20% at the concentration of 0.01 mg / ml of the composition of the present invention.

Experimental Example 2: Determination of the effect on the skin allergic reaction of the composition according to the present invention

In order to investigate the effect on the passive skin allergic reaction of the composition according to the present invention, a passive cutaneous anaphylaxis (PCA) reaction was caused by the following method.

As an experimental animal, five ICR rats weighing 5 to 35 g at 4 to 6 weeks of age 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.

The skin was sensitized by injecting anti-DNP (dinitrophenyl) IgE into the skin of the rats, and then 48 hours later, the antigen DNP-HSA (dinitrophenyl-human serum albumin) was injected intravenously into the tail to induce an IgE dependent skin response. At this time, DNP-HSA was diluted with PBS (phosphate buffered saline). 100 ng of anti-DNP IgE was injected into the rat's back, and 48 hours later, a mixture of 4% Evans blue and DNP-HSA 1: 1 was injected into the tail vein of the rat. One hour before administration of the antigen (DNP-HSA), 0.01, 0.1 and 1 g / kg body weight of the extract of Example 1 were orally administered to the rats, respectively.

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. The results are shown in Table 2.                     

Effect of the composition according to the invention on passive skin allergic reaction (* P <0.05) Composition (g / kg) of Example 1 Dyeing amount (μg / site) % Inhibition No treatment (saline) 1.373 ± 0.131 - 0.01 0.627 ± 0.075 54.31 ± 4 * 0.1 1.0097 ± 0.071  26.49 ± 2 * One 1.001 ± 0.074 27.11 ± 2

As shown in Table 2, it was found that the most inhibiting passive skin allergic reaction in the composition of 0.01 g / kg concentration. This result means that the oral administration of the composition according to the present invention can significantly suppress local, that is, skin allergic reactions.

Experimental Example 3: Determination of the effect of the composition according to the invention on the edema reaction

As experimental animals, four ICR rats weighing 25 to 35 g at 4 to 6 weeks of age 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.

First, the composition of Example 1 was orally administered by concentration (0.01, 0.1, and 1 g / kg), and then reacted for 1 hour. Compound 48/80 (20 g / L) was then injected subcutaneously inside the rat ear using a micro syringe and the ear thickness of the site where the edema reaction occurred after 40 minutes was measured. The results are shown in Table 3.                     

Effect of the composition according to the invention on compound 48/80 induced induction edema reaction (* P = 0.004 , ** P = 0.001) Composition (g / kg) of Example 1 Ear thickness (mm) % Inhibition No treatment (saline) 0.253 ± 0.016 - 0.01 0.177 ± 0.015 30.42 ± 1.4 0.1 0.133 ± 0.004  47.231 ± 1.84 * One 0.117 ± 0.012  56.71 ± 4.7 **

As shown in Table 3, the composition according to the present invention did not have a significant effect at low concentrations, it was found that the most suppress the edema reaction at a concentration of 1 g / ㎏, P <0.005 significant results Got it.

Experimental Example 4: Determination of interferon-γ production effect of the composition according to the present invention

Whether the composition according to the invention induces the production of interferon-γ responsible for the immune enhancing function was investigated as follows.

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. Incubate at 37 ° C. for 10 minutes prior to treatment of the composition of Example 1 to stabilize the cells, and the aqueous solution of Example 1 was 0.01, 0.1, 1.0 mg / ml (the composition of Example 1 per ml of distilled water, respectively). 0.01, 0.1, 1 mg dissolved), and reacted for 24 hours. After completion of the reaction, the supernatant and the cells were separated by centrifugation at 400 × g. In order to investigate the protein level of interferon-γ in the separated supernatant, an enzyme linked immunosorbent assay (ELISA) was performed as follows.

Anti-human interferon-γ (1 μg / ml), a monoclonal antibody against interferon-γ, was diluted with PBS (pH 7.4) and coated in 100 μl each in a 96-well plate, followed by 12 h at 4 ° C. It was left. The plate was 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 recombinant interferon-γ to be used as a standard curve were added and then left at 37 ° C. for 2 hours. Each well was then washed again and added to secondary antibody biotin-bound interferon-γ (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-ethylbenzthiazoline-6-6-sulfonic acid)) substrate was added, and color development was measured at 405 nm using an ELISA reader.

The results are shown in FIG. As shown in FIG. 1, it was found that the production of interferon-γ was most increased in 0.01 mg / ml of the composition according to the present invention (B, no treatment; * P = 0.014).

As described above, the composition of the present invention can be used as a therapeutic agent for allergic skin diseases, such as atopic dermatitis, by inhibiting histamine secretion, inhibiting allergic reactions such as passive skin allergic reaction and edema edema. By increasing interferon- [gamma] production, which is important for regulation, it can be effectively used as an adjuvant for the treatment of wrinkles, psoriasis, dry skin, itching, chronic eczema and acne due to aging due to deterioration or degradation of immune function. In addition, since the skin of the human body is very soft when taken, it can be used as an effective oral cosmetic for skin care.

Claims (11)

As an active ingredient, the water obtained by mixing Angelica, Cheongung, Saengjihwang, Sewao, Astragalus, Licorice, Gilkyung, Pogongyoung, Baekjak, Baekchul, Brown root, Mint, Sine, Dermis, Yulmu and Dried Rate and then extracting with water or after extracting with water Containing an extract or a dry powder thereof, the composition for the treatment or allergy to allergy. The weight ratio of Dongguk, Cheonggung, Saengjihwang, Shouo, Astragalus, Licorice, Gilgyeong, Pogongyoung, Baekjak, Baekchul, Brown root, Peppermint, Sinus, Dermis, Yulmu and dry rate is 2-8: 2-8. 8: 1-6: 3-12: 1-6: 2-8: 8-16: 2-8: 2-8: 1-8: 1-8: 0.5-4: 0.5-4: 1-16: 0.5-20 allergy treatment or immunopotent composition. Allergic treatment or immunostimulating composition of claim 1 or 2 for use as a medicament. According to claim 3, Allergy or immuno-enhancing composition formulated as a liquid formulation. Water extract obtained by mixing Angelica, Cheongung, Saengjihwang, Sewao, Astragalus, Licorice, Gilgyeong, Pogongyoung, Baekjak, Baekchul, Brown root, Peppermint, Sine, Dermis, Yulmu and Dried Rate and extracting with water or after extracting with water A method for preparing a composition according to claim 1 or 2, wherein the powder obtained by drying the water extract is mixed with a pharmaceutically acceptable carrier. An allergic skin disease or inflammatory skin disease improving agent containing the composition according to claim 1 or 2. The agent for improving allergic skin diseases or inflammatory skin diseases according to claim 6 for oral or dermal application. As an active ingredient, the water obtained by mixing Angelica, Cheongung, Saengjihwang, Sewao, Astragalus, Licorice, Gilkyung, Pogongyoung, Baekjak, Baekchul, Brown root, Mint, Sine, Dermis, Yulmu and Dried Rate and then extracting with water or after extracting with water Allergy symptom improvement or immune enhancing food containing extract or its dry powder. delete The weight ratio of Dongguk, Cheongung, Saengjihwang, Shouo, Astragalus, Licorice, Gilgyeong, Pogongyoung, Baekjak, Baekchul, Brown Root, Mint, Sinus, Dermis, Yulmu and Dried Rate are from 2 to 8: 2 to 8: 8: 1-6: 3-12: 1-6: 2-8: 8-16: 2-8: 2-8: 1-8: 1-8: 0.5-4: 0.5-4: 1-16: Allergy symptom improvement or immune boosting food for 0.5 to 20 people. delete

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