KR20090011796A - Anti-atopy or allergic dermatitis relieving composition containing natural herbal extracts - Google Patents

Abstract

A safe and useful composition for skin external application is provided to suppress isolation of histamine, to relieve vascular permeability and to improve atopic dermatitis symptom by comprising one or more extracts of oriental drug. A composition for skin external application comprises extract of oriental drug selected from Aloe, Violae Herba, pomegranate and Dendrobii Herba extracts as active ingredient. In the composition for skin external application for suppression of atopy, the active ingredient suppresses isolation of histamine and vascular permeability which is allergy symptom. The composition for skin external application is used as spray, gel, lotion, cream, essence.

Description

  Anti-atopy or allergic dermatitis relieving composition containing natural herbal extracts}

 The present invention is to suppress the release of histamine, a major cause of skin allergy, and to inhibit or relieve atopic diseases by inhibiting vascular permeability, which is atopic symptoms, herbal medicines such as presbyopia, magnetization, pomegranate, and grains It relates to an external preparation for skin containing at least one or more of the extract as an active ingredient.

Recently, the number of children diagnosed with atopic dermatitis is increasing, recurring recurrence, and not fully cured even as an adult, threatening even the social life of people involved in the disease, attracting social attention. It is estimated that 10 to 20% of the world's population suffers from this dermatitis, and the prevalence rate continues to increase due to the increase of substances that cause airborne allergies due to environmental pollution and the increase of environmental conditions that form dry skin. Is rising. However, as the etymology of the word atopy means 'weird' or 'inappropriate', it is true that the cause or the definite solution are not yet known.

   Clinically, atopic dermatitis has a relatively characteristic skin lesion and distribution according to the patient's age, and most of the symptoms occur at 2 to 6 months of age. This is divided into three periods, such as infancy, childhood, and puberty / adult. First of all, in infants from 2 to 3 months of age when atopic dermatitis begins, the symptoms of atopic dermatitis tend to develop red spots around the face, especially the cheeks, and gradually spread toward the ears and the neck. This period tends to be accompanied by a lot of oozes, sometimes with diaper rash or severe sweating on the neck. In the early years of 3-7 years of age, unlike infancy, a lot of rash does not occur, but the appearance of redness of the face may appear. In general, during this time, the child's skin is very rough, dry, and severely itchy than other children of the same age. It is especially pronounced in folding areas such as around the neck and behind the elbow or knee. There are some differences between the ages of 12 and 12. In most children, many of the symptoms of early childhood and early childhood disappear, but some of them become thicker and more pigmented. After puberty, atopic dermatitis usually improves with age, but may continue to be severe until adulthood. These symptoms may vary slightly from person to person, but atopy's most common symptom is severe itching.

In general, allergy in the human body appears in the form of atopic dermatitis, urticaria, bronchial asthma, allergic rhinitis, allergic keratitis in the skin, mast cells play a primary role, and histamine released from mast cells promotes vascular permeability. Induces inflammatory cells to infiltrate tissue. Therefore, sodium chromoline (Na-cromolyn) or ketotifen used in the treatment of allergic diseases is known as an effective histamine free inhibitor. The mechanisms of allergens induced by skin can be divided into early and late phases. In the early stages, T-helper cells are activated by foreign antigens in macrophages in tissues and B When IgE is generated in the cell, polyvalent antigens such as ticks and pollen bind to a plurality of IgE antibodies bound to the high-affinity IgE receptor (FcRIα) of the mast cell membrane to form a cross-linked receptor. And the aggregation of activated mast cells to increase the concentration of calcium ions (Ca ++) in the cytoplasm, degranulation, and secretion of histamine stored in mast cells. In addition, phospholipid A2 ( phospholipase A2), phospholipase D, and phospholipase A2 is arachidone in phosphatidylcholine. (Arachidonic acid) Phospholipase D produces phosphatidine from phosphatidylcholine, which is a chemical transfer material previously stored in mast cells such as histamine during degranulation. In addition to the release of preformed mediator, newly synthesized prostaglandin and leukotriene are secreted together, resulting in vasodilation, vascular permeability, and broncho smooth muscle contraction or hypersecretion. Causes a type allergic reaction. In the late phase, inflammatory reactions are predominant and primary inducers are released, followed by histamine, serotonin, and leukotrienes, as well as NCF, ECF, and PAF, which act as chemotactic factors for inflammatory cells such as eosinophils and neutrophils. Infiltration occurs and inflammatory reactions progress, causing histological changes in the allergic area. Stimulation of mast cells may include non-immune stimulation such as lectin or anaphylatoxin in addition to the stimulation by IgE mentioned above. Other medicines such as calcium ionophore A23187, histamine glass accelerators such as compound 48/80, codeine, morphine, substance P, etc. are known to release histamine by degranulating mast cells. When secreted histamine binds to vascular endothelial cells, vascular cells contract, causing extravasation of plasma in the blood into tissues. Endothelial cells also release prostacyclin and nitric oxide, which relax vascular muscle cells. It induces vasodilata by inducing the synthesis of substances such as nitric oxide. By the above mechanism, histamine secretion causes edema, flare, and itching, which is typical of type 1 immediate hypersensitivity reactions.

Therefore, it could be seen that a substance capable of inhibiting histamine secreted from mast cells and mitigating vascular permeability may provide a more suitable effect for the treatment and prevention of atopic dermatitis than a general immunosuppressive substance. However, the conventional techniques for preventing and alleviating skin allergies and itching have been to take antihistamines or apply steroids for external use. These drugs can lead to central nervous system disorders, digestive disorders, or confusion. Efforts have been made to find natural materials that can be made, but there are currently no clear materials for natural products. However, as the society becomes more advanced, allergic diseases are increasing rapidly, and the importance of preventive measures is more important than the treatment of diseases.

The present inventors used in oriental medicine in the concept of inhibiting histamine glass, inhibiting vascular permeability, and effectively alleviating or preventing skin inflammatory reactions associated with allergic symptoms in order to discover allergic dermatitis and skin itching material. As a result of exploring the efficacy of various herbal medicines, presbytery, magnetization, pomegranate, and grain extracts are excellent in histamine release and vascular permeability. It confirmed and completed this invention.

Therefore, it is an object of the present invention to provide a safe and useful skin external preparation composition which can improve the symptoms of atopic dermatitis by inhibiting histamine glass and reducing vascular permeability by containing at least one of the herbal extracts as an active ingredient.

 In order to achieve the above object, the composition for external application for skin according to the present invention comprises one or more herbal extracts of rosacea, magnetization, pomegranate, and grains as an active ingredient, and comprises 0.0001 to 10% by weight of the total composition.

 The present invention can improve the symptoms of skin diseases caused by histamine release and increased vascular permeability, specifically atopic dermatitis and the like, and can be used for the purpose of treating and preventing these skin diseases. To this end, the external preparation composition for skin of the present invention may be provided as a pharmaceutical and cosmetic composition for the purpose of treating and preventing the above skin diseases.

 <General Properties and Pharmacological Effects of Herbal Naturals Used in the Present Invention>

General properties and pharmacological actions of natural products used as features of the present invention are as follows. Aloe ferox Miller) refers to the entire plant belonging to the genus Aloe or one species. It is native to Africa and is a houseplant that is grown in greenhouses or raised at home for medicine. Aloe leaf juice contains aloe, aloe-emodin, nataloi, lavaberon (isoemodine), resin, etc. There is such an effect.

Viola mandshurica W. Becker is an outpost of the family of violets. It is distributed in Korea, China, Japan, and East Siberia, and grows in the fields. It is about 10cm high and has no stems and leaves with long sacks in the roots grow laterally. Ingredients include leaves and flowers, essential oils, flavonoids, saponins, vitamin C. salicylic acid, and pigments. The main component of the essential oil is methyl salicylate. The pigment component is beta carotene, violatin, flavoxanthin and the like. It is effective in clearing detoxification and hematopoiesis, and is used to treat single, target pain, sore throat, jaundice hepatitis, enteritis, and serous bite. In motion therapy, dexterity, inflammatory drugs, painkillers, and antidote are used to make decoctions for severe wounds, nausea, septic inflammation, malignant tumors and spontaneous dermatitis.

Pomegranate ( Punica) granatum Linne) is a deciduous shrub of the pomegranate family. Pomegranate is 5-7m long, has 75mm bright green lanceolate leaves, and has reddish orange flowers of lobe growing at the end of branches. Fruits are similar to the size of large oranges and are soft, have skin-like skins, and vary in color from tan to red. The main components of the juice are sugars (13.9% as invert sugar) and organic acids (1.5% as citric acid). Vitamins are rare except about 10mg% of vitamin C. The bark of stems and roots contains volatile alkaloids such as pellitierene and pseudo-pelletierene, the fruit bark contains tannins, mucus, chyme, and flowers with punicin and seeds. Contains glycerides of punicic acid. Pericarp is called pomegranate (石榴皮) in oriental medicine and is used for the treatment of diarrhea, bloody stool, redness, and intestinal parasites. Take 3-5g monthly, and wash it with decoction for skin itching.

Seokgok ( Dendrobium nonile Lindley) is an evergreen perennial plant of the family Orchidaceae, about 20cm high, and lives on the surface of rock or tree. It grows wild on the southern coast of Jeju Island. Root stems have a lot of thick roots, several stems come out to grow straight, old ones have no leaves, only nodes. The outpost is called Seokgok, and when it blooms in summer, the outpost is cut and dried in the sun. The main ingredient is 0.03% alkaloids, dendrorobin, nobilironine, and dendroxin. It is used as a medicinal herb in Gwansangcho, oriental medicine, and civilian. It is effective for constipation, strengthening immunity and cataracts.

As mentioned above, presbytery, magnetization, pomegranate, and grains have been used as therapeutic agents for various diseases in oriental medicine, but there has been no research on the treatment or prevention of atopic diseases through histamine release and vascular permeability inhibitory effects.

Therefore, the inventors of the present invention, while trying to develop a useful herbal medicine for skin allergy, confirmed that the presbyopia, magnetization, pomegranate, and Seokgok extract were useful for inhibiting the release of histamine and vascular permeability, which are allergic symptoms, in laboratory and animal experiments. In addition, the extract was found to be useful in the inflammatory reactions accompanying allergic symptoms to complete the present invention.

Hereinafter, the present invention will be described in detail with reference to Examples. However, embodiments according to the present invention may be modified in many different forms, the scope of the present invention should not be construed as limited to the embodiments described below.

Experimental Example 1. Preparation of Natural Extracts

Natural products were extracted in two ways using water and organic solvents. In the case of solvent extraction, after drying it was pulverized into particles of about 50 mesh with a pulverizer, and then cooled for 3-7 days with a solvent such as ethanol, concentrated under reduced pressure, and then lyophilized or spray dried to obtain a dry extract. In the case of water extraction, 50 g of herbal medicines were placed in 5 L of water, heated at 80 to 100 ° C. and boiled for 5 minutes, and then cooled five times to obtain 3.82 to 4.91 g of natural extract. The production method of the natural extract is not limited to the method described above. Extraction solvents in preparation using organic solvents include one or two or more selected from the group consisting of purified water, methanol, ethanol, propanol, butanol, ethylene glycol, propylene glycol, 1,3-butylene glycol, ethyl acetate, acetone Mixed solvents can be used.

Experimental Example 2 Experiment for Evaluating Histamine Free Inhibition in Rat Mast Cells

To evaluate histamine release inhibition in rat mast cells, male Sprague Dawley rats (SD rats) over 8 weeks old were used. SD rats over 8 weeks of age were not fed for two days before the experiment to reduce the volume of the intestinal tract to facilitate ascites harvesting. The epidermis was grasped with tweezers, the epidermis was cut with scissors, the buffer was placed in a 30 ml abdominal cavity and massaged for 30 seconds, and the ascites was collected using a pasteur pipette. 1 ml of the collected ascites was placed on the 2ml layer of 22.5% metrizamide solution so that the layers were not mixed, and then centrifuged by specific gravity to separate only mast cells in the ascites. Histamine was released by treatment of isolated mast cells with compound 48/80 (hereinafter referred to as Co48 / 80), and the extract was dissolved in dimethyl sulfoxide (DMSO) and treated in a volume of 1/100 of the cell culture medium to give a final concentration of 0.01%, After treating the mast cells for 30 minutes in advance to 0.001% and 0.0001%, Co48 / 80 was treated with 50 µg / ml for 15 minutes to release histamine. In order to quantify free histamine, histamine was extracted / purified from the supernatant using butanol and heptane and o-phthaldialdehyde was combined with separated histamine to determine the amount of free histamine by measuring fluorescence at excitation 360 nm and emission 440 nm. It was. The histamine release rate in mast cells was calculated by the following equation.

% Inhibition = (A-B) / A * 100

A: Histamine release rate when treated with Co48 / 80 alone

B: Histamine release rate in sample processing

Experimental results by the above inhibition rate calculation method are shown in Table 1 below.

     Table 1.Histine free inhibition rate of herbal extracts (%)

Extract concentration (%) 0.0001 0.001 0.01 Ketotifen 23.1 25.5 37.1 craftiness 11.9 18.2 23.9 Self-designation 15.8 21.7 23.4 Pomegranate 9.2 13.2 15.2 Seokgok 11.7 14.0 25.4

  As shown in Table 1, the herbal extract showed a histamine free inhibitory effect in rat mast cells, but was lower than the positive control group ketotifen, but showed a superior concentration-dependent inhibitory effect.

Experimental Example 3. Evaluation of Inhibitory Effect of Vascular Permeability Induced by Co48 / 80 upon Topical Administration>

  6-week old male Sprague-Dawley rat (SD rat) was used as an experimental animal model and compound 48/80 (Co 48/80) was used as an allergen. Four sites were selected for injection into the back skin of the experimental animals, and then injected with a solvent dissolved in an extract sample. After 30 minutes, compound 48/80 was injected. The extract sample was used after distilling under reduced pressure and concentration of ethanol extract in phosphate buffered saline (PBS). The final concentration of each extract was 0.05 mg per injection site. After intravenous injection of the drug substance, 500 μl of 1% Evans blue was injected intravenously into the tail of the experimental animal and left for 1 hour. After that, the injection site was cut and the Evans blue solution was cut into the tissue. The exuded part was cut out with scissors. The cut tissue was immersed in 1 ml of 1N KOH solution, reacted overnight at 37 ° C, and completely dissolved. Then, 9 ml of 0.6 N phosphoric acid + acetone (5:13) was added thereto, followed by centrifugation, and the supernatant was spectrophotometer at 620 nm. It was measured with a spectrophoto meter.

% Inhibition = [(A-B) / A] × 100

A: The amount of Evans blue extracted from the site where Co48 / 80 was injected after the solvent injection of the sample.

B: amount of Evans blue extracted from the site injected with Co48 / 80 after sample injection

Experimental results by the above inhibition rate calculation method are shown in Table 2 below.

    Table 2. Inhibitory Rate of Vascular Permeability of Herbal Extracts (%)

Extract concentration (mg / part) 0.05 Ketotifen (positive control) 90.8 Presbytery 69.2 Self-designation 82.9 Pomegranate 59.9 Stone grain 63.8

As a result of the local administration of each natural extract into the skin tissue, the degree of allergic inhibition by Co48 / 80 was evaluated.

Experimental Example 4. Anti-inflammatory Effect Evaluation

  (A) Evaluation of Inhibitory Effect on Rat Macrophage

   Raw 264.7 cells, macrophages, were cultured in a Dulbecco's modified Eagle's medium (DMEM). Lipopolysaccharide (LPS) was treated for macrophage activity. Macrophages are important immune cells that mediate allergic inflammatory reactions. Nitric oxide (NO) induces inflammatory responses upon stimulation of external antigens such as LPS and interleukin-6 (IL-6) and interleukin-1 beta. It is well known that expression of inflammatory mediator cytokine genes such as (IL-1β), TNF-α, and the like is significantly increased. Nitric oxide production was measured by the Griess method to investigate the effects of Chinese herbal extracts on the production of nitric oxide, an inflammatory mediator in macrophages. That is, after adding 10ug / ml and 100ug / ml of herbal extracts to macrophages cultured aseptically in the laboratory, LPS was added. NO production was inhibited. In particular, the 100 ppm treated group of preskins and grains showed almost 100% inhibition of NO production by LPS.

    Figure 1. Inhibitory effect of herbal extracts on NO production.

  (B) Effect of herbal extracts on TNF alpha production by LPS

   The effect of herbal extracts on the production of TNF-α, an inflammatory cytokine, was confirmed by enzyme-linked immunosorbent assay (ELISA). The presbyopia inhibited TNF alpha increase by LPS by 50% at 100 ppm concentration, but had little effect on TNF alpha inhibition at 10 ppm concentration. Pomegranate, grain, magnetization and mixed extracts also inhibited TNF alpha production by about 30-40% at 100 ppm (Figure 2).

   Figure 2. Inhibitory effect of herbal extracts on TNF alpha production in macrophages.

   (C) Effect of herbal extracts on cytokine gene expression by LPS

The effects of Chinese herbal extracts on the gene expression of inflammatory mediated cytokines were investigated by reverse transcriptase (RT-PCR). Pomegranate, pomegranate, and presbyopia inhibited the expression of IL-6 and IL-1 beta in a concentration-dependent manner. (Figure 3).

        Figure 3. Effect of herbal extracts on inflammatory cytokine gene expression.

The inventors of the present invention confirming the effectiveness of the presbyopia, magnetization, pomegranate, and grain extract by the above method was included in the compositions of the herbal extracts, such as essences were evaluated as excellent atopic symptoms relief effect was completed the present invention.

  According to the present invention, the composition for atopic dermatitis containing presbyopia, magnetization, pomegranate and grain extract is effective in improving atopic disease by inhibiting histamine release and relieving vascular permeability. It can also be used safely because it does not show any side effects in the skin.

  When the present invention is described in more detail, the present invention relates to atopic dermatitis composition containing the presbyopia, magnetization, pomegranate, grains extract obtained by the above method, each composition is based on the base of each product in general The composition of atopic dermatitis, characterized in that it comprises 0.01 ~ 10% by weight of dry, resid of the presbytery, magnetization designation, pomegranate and grain extract as a dry residue, and confirmed its efficacy through clinical experiments.

<Examples 1-5 and Comparative Examples>

Essence of the present invention is easily prepared by a conventional manufacturing method, but is not limited only to the following examples, various atopy inhibitor formulations, such as spray, lotion, cream, gel, cosmetics, hair cleaner, for the purpose of suppressing itching, It turns out that it can be applied to face washes, body washes and soaps.

Hereinafter, the present invention will be described based on Examples and Comparative Examples.

Examples 1-5

Essence was prepared by mixing well in the mixer at the composition ratios shown in Table 4.

Comparative Example 1

  Essence was prepared in the same manner as in Examples 1 to 5, except that the herbal extracts were not mixed.

TABLE 3

Raw material name (% by weight) Comparative Example 1 Example 1 Example 2 Example 3 Example 4 Example 5 Propylene glycol 10.0 10.0 10.0 10.0 10.0 10.0 glycerin 10.0 10.0 10.0 10.0 10.0 10.0 Sodium hyaluronate solution (1%) 5.0 5.0 5.0 5.0 5.0 5.0 Presbytery Extract - 0.1 - - - - Magnetized extract - - 0.1 - - - Pomegranate Extract - - - 0.1 - - Seokgok Extract - - - - 0.1 - Mixed Extract (Pomegranate: Stone Grain; Presbytery: Magnetization = 1: 1: 1: 1) - - - - 0.4 ethanol 5.0 5.0 5.0 5.0 5.0 5.0 Polyoxyethylene Cured Castor Oil 1.0 1.0 1.0 1.0 1.0 1.0 Spices Quantity Quantity Quantity Quantity Quantity Quantity Purified water To 100 To 100 To 100 To 100 To 100 To 100

Experimental Example 5. Evaluation of atopic dermatitis alleviation effect

In order to evaluate the atopic dermatitis alleviation effect of the prepared Examples 1 and 2, and Comparative Example 1, the effect evaluation was performed on 30 children and 1-10 years old infants with atopic dermatitis. The application method was applied to the whole body by dividing the test sample into the right and the left by double-blinded test, respectively, and prohibiting the use of other moisturizers that could affect the effect of the test sample. Two or four weeks after application of the test sample, SCORAD (SCORAD: SCORing Atopic Dermatitis) was used to evaluate the effect of the test sample. The results are shown in Table 7.

<Judge criteria>

Extent criteria: Area = damage area / 100

Intensity criteria:-erythema (1/2/3)

                           -Edema (1/2/3)

                           -Exudate (1/2/3)

                           -Skin peeling (1/2/3)

                           Taekwondo degree (1/2/3)

                           -Drying degree (1/2/3)

Subjective criteria:-itching (1-10)

                Insomnia (1-10)

Score calculation = (degree of criterion / 5) + (7 / strength) + subjective

TABLE 4

Classification Week 0 2 weeks 4 Weeks Example 1 SCORAD 59.4 29.8 22.5 Improvement - 50% 62% Example 5 SCORAD 61.7 20.8 82% Improvement - 66% 79% Comparative Example 1 SCORAD 60.8 48.2 46.6 Improvement 0- 21% 23%

From the above evaluation result, which is a comprehensive evaluation of atopic dermatitis, which is an allergic disease, Examples 1 and 5 to which herbal extracts were added are superior to Comparative Example 1, and from 2 weeks after applying to the skin, the degree of atopic dermatitis relief is excellent. I could confirm it. In particular, after 4 weeks, in Example 5, an excellent improvement effect of 82% was found, which can improve atopic dermatitis in general.

  As described above, according to the present invention, the composition for atopic dermatitis containing presbytery, magnetization, pomegranate and grain extract is effective in improving atopic disease by inhibiting histamine release and relieving vascular permeability. It can also be used safely because it does not show any side effects in the skin.

Claims (5)

 A composition for external application for skin containing at least one herbal extract selected from presbytery, designated magnetization, pomegranate, and pomegranate extract as an active ingredient.  According to claim 1, wherein the active ingredient inhibits the release of histamine (histamine) and the external topical composition for inhibiting atopic dermatitis, characterized in that the vascular permeability (allergic symptoms) inhibition.   The composition of claim 1, wherein the herbal extract content is 0.0001 to 10% by weight based on the total weight of the composition. According to claim 2, wherein the composition means atopy inhibiting composition, characterized in that consisting of any one selected from the group of sprays, gels, lotions, creams, essences, etc., cosmetics, scalp cleaning composition, systemic cleansing agent, face wash Anti-itch composition, characterized in that consisting of any one of the formulations selected from the group such as skin protectants from soap, UV, etc.  According to claim 3, the herbal extract is at room temperature using at least one mixed solvent selected from purified water, methanol, ethanol, propanol, butanol, glycerol, propylene glycol, 1,3-butylene glycol, n-hexane, chloroform Itching and depressurizing concentration method, the content is 0.0001 to 010% by weight based on the total weight of the composition, characterized in that itching and / or atopic relief composition.