KR20120136460A - A pharmaceutical comprising the extract of ixeris dentata nakai for treating or preventing skin disease - Google Patents

Abstract

PURPOSE: A composition containing Ixeris dentata Nakai extract for preventing and treating dermatitis is provided to prevent skin barrier damage and to suppress hypersensitivity of IL-1 beta. CONSTITUTION: A pharmaceutical composition for preventing and treating dermatitis contains Ixeris dentata Nakai extract as an active ingredient. The extract reduces IgE and IL-1beta amount in blood. An agent for preventing and treating dermatitis contains the extract as an active ingredient. The agent is manufactured in the form of powder, granules, tablets, capsules, suspension, emulsion, syrup, aerosol, suppository, or sterilized injection solution by adding pharmaceutically acceptable carriers, excipients, or diluents. A health functional food for preventing and treating dermatitis contains the extract as an active ingredient and sitologically acceptable food additives.

Description

A composition comprising the extract of Ixeris dentata Nakai for treating or preventing skin disease}

The present invention, in the skin diseases including atopic dermatitis and contact dermatitis, not only impairs the barrier function of the skin, but also inhibits the hypersensitivity of immunoglobulin E (IgE), and is an inflammatory cytokine interleukin- The present invention relates to a composition for preventing, ameliorating and treating skin diseases by inhibiting excessive secretion of 1β.

The composition for the prevention, improvement and treatment of the skin disease of the present invention has a technical feature of including the extract as an active ingredient.

In general, the range of skin diseases includes atopic dermatitis, contact dermatitis, seborrheic dermatitis, molar eczema, tachycardia, congestive dermatitis, heterogeneous eczema, sebaceous eczema, and self-sensitizing eczema. Etc. are included.

The cause of the development of such a skin disease is not yet clearly known, and because the daily symptoms also appear variously, such as dry skin, eczema, the cause of the disease can not be explained by any one.

In other words, environmental factors, genetic predisposition, immunological reactions, and skin barrier abnormalities can be considered as major causes.

First, as an exogenous stimulant, environmental pollution such as smoke caused by industrialization, carpets, beds and sofas caused by Western-style dwellings, and substances causing allergies such as house dust and ticks due to an increase in room temperature (allergens) I can.

In other words, with the progress of industrialization and the increase of environmental pollution, exogenous stimulus increases, causing various skin diseases.

In the case of endogenous secretions, skin diseases, in particular, atopic dermatitis, etc., may occur due to various substances generated by autoimmune hypersensitivity.

However, it is important to note that even in the case of a skin disease caused by either an exogenous stimulus or an endogenous secretion, scratching of the itchy skin destroys the barrier function of the skin and easily invades various irritants, which further exacerbates the skin disease.

In other words, immunoglobulin E (IgE) acts on proteins secreted from keratinocytes, causing autoimmune hypersensitivity reactions and exacerbating skin diseases.

Typically, patients with skin diseases such as atopic dermatitis and contact dermatitis tend to feel itching more easily than the general population, and have a very sensitive response to minor irritation.

When the disease is worsened, Langerhans cells present in the skin, when IgE and the receptor FcRI bind together to the externally invading antigen, monocyte chemotactic protein 1 (MCP-1) and interleukin Secretes -16 (interleukin-16).

Langerhans cells also deliver antigens to T-cells to induce Th 2 (helper T cell 2) proliferation.

By Th 2, monocytes gather into the skin, which differentiates them into inflammatory dendritic cells (IDECs), which are tumor necrosis factor (TNF-) inflammatory cytokines. Excess secretion of α), interleukin-1 (IL-1) and interleukin-6 (IL-6) leads to a process of exacerbating skin diseases.

Herein, the interleukin-1 (IL-1) family includes IL-1α, IL-1β, and IL-1RA, and IL-1α is known to be bioactive to precursors, but IL-1β is bioactive only to mature bodies. have.

In addition, the skin as geuleum process of skin disease worse is there is described also as Staphylococcus aureus, most of the atopic skin of dermatitis There are crowded very much Staphylococcus approximately 10 ⁷ as CFU / cm ² 200 times higher than normal It is known that levels of staphylococci exist.

That is, because of these bacteria, immunoglobulin E (IgE) is continuously produced, and the ceramidase secreted by these bacteria induces itching by breaking down ceramide, which maintains the subcutaneous moisturizing ability. It will continue to exacerbate skin diseases.

Here, in the case of skin diseases such as atopic dermatitis, it is accompanied by an increase in blood IgE and eosinophils, and conventionally, IgE has been accepted to the extent of forming dimples (urticaria) on the skin in a broad sense. .

That is, it is thought that dung margin does not change into an eczema reaction even if it is strongly scratched, and an eczema reaction is easily formed by scratching in case of skin with a deficit disorder.

However, recent studies have clearly confirmed that the eczema reaction can occur directly by the action of IgE.

In summary, the process of exacerbating skin diseases including atopic dermatitis and contact dermatitis is that scratching the itchy skin causes the barrier function of the skin to be destroyed and various stimulants are easily invaded.

In this process, inflammatory cytokines, tumor necrosis factor (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6), are excessively secreted, and immunoglobulin E ( Hypersensitivity to IgE) may exacerbate skin diseases.

On the other hand, in the past, research has been conducted toward developing immunosuppressive agents and bioreactive substances as a treatment for skin diseases such as atopic dermatitis.

There are steroids as immunosuppressive agents, and IFN-γ and antihistamine are typical bioregulators.

However, they have a rapid anti-inflammatory effect, but the symptoms worsen when they stop using and block the skin's immune system. Therefore, they increase the risk of bacterial infection and therefore cannot be used for a long time.

In the meantime, we conducted a study to prevent, ameliorate and treat skin diseases by using extracts from the skin, and to apply the extract to the DNFB-induced skin disease animal model to observe changes in IgE and IL-1β. The survival rate was observed by applying to the human keratinocytes, and the following description will be made in relation to the DNFB-induced skin disease model and crust.

First, 2,4-dinitrofluorobenzene (DNFB) is known to cause atopic dermatitis symptoms when applied to experimental mice.

However, this skin disease model is generally regarded as T cell mediated antigen specific dermatitis.

Therefore, DNFB-induced skin diseases can be regarded as skin diseases caused by autoimmune hypersensitivity reactions including atopic dermatitis or contact dermatitis.

Ixeris dentata Nakai) is an annual or biennial herb belonging to the compositae, distributed mainly in Korea, Japan, and China, and grows in mountains, fields, and fields.

In oriental medicine, it is also called chaemin (황 菜), yellow and green (黄瓜 彩). In spring, all parts of the plant, including roots, are used for edible, medicinal and ornamental purposes.

On the other hand, among the articles published in relation to the moths, the related to the present invention, “Analysis of the roots of the moths and the cell survival rate and DPPH radical scavenging activity of the extract” (Hong Seul-ki et al., 3, 2010, Vol. 43 No. 2) discloses the results of examining the survival rate and the antioxidant activity of renal cell lines (vero cells) and hepatic cell lines (chang cells).

In addition, "Physiological activity of fresh moth extract" (Myung-Jo Kim et al., Korean Society of Food and Nutrition, Vol. 31, No. 5, 2002.10, page (s): 924-930), showed that moth powders had antimutagenic and cancer cell growth inhibitory effects. Has been disclosed.

In summary, the study of the present invention was applied to DNFB-induced skin disease animal model to observe the change of IgE and IL-1β, and also to observe the change in survival rate by applying the extract to keratinocytes of human skin. Through, there has been no attempt to prevent, ameliorate and treat skin diseases, particularly skin diseases caused by autoimmune hypersensitivity reactions.

An object of the present invention is to provide a composition for preventing, ameliorating and treating skin diseases by continuously taking without causing side effects.

An object of the present invention, in the skin diseases including atopic dermatitis and contact dermatitis, not only impairs the barrier function of the skin, but also inhibits the hypersensitivity of immunoglobulin E (IgE), inflammatory cytokines By inhibiting excessive secretion of interleukin-1β, to provide a composition for preventing, ameliorating and treating skin diseases.

The present invention, by adding a pharmaceutically acceptable carrier, excipient or diluent, etc. to the active ingredient containing the moth extract, to provide a preventive and therapeutic agent for skin diseases formulated in pharmaceutical unit dosage form, to solve the technical problem do.

The carrier, excipient, and diluent may include tods, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, undetermined. Vaginal cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

In addition, the pharmaceutical dosage form may be used in the form of a pharmaceutically acceptable salt, and may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.

In addition, when formulating the active ingredient containing the moth extract may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. commonly used.

In addition, each of the pharmaceutical dosage forms may be formulated in the form of powders, granules, tablets, capsules, oral preparations such as suspensions, emulsions, syrups, aerosols, suppositories, and sterilized injection solutions according to conventional methods .

The solid preparation for oral administration may be prepared by mixing at least one excipient, for example starch, with calcium carbonate, sucrose or lactose, gelatin, and the like in the extract. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.

Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories.

As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like may be used.

Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The preferred dosage of the active ingredient according to the present invention may be appropriately selected by those skilled in the art depending on the condition and the weight of the patient, the degree of disease, age, sex, drug form, administration route and period.

The extract of the present invention can be administered to mammals such as mice, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous injection.

The present invention is to solve the technical problem by providing a dietary supplement composition for the prevention and improvement of skin diseases by adding a food supplement additive to the active ingredient containing the moth extract.

Examples of the food to which the extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.

It can also be added to foods or beverages for the purpose of preventing and improving skin aging.

At this time, the amount of the extract in the food or beverage may be 0.01 to 20% by weight of the total food, and the health beverage composition may be added in a proportion of 0.02 to 5 g, preferably 0.3 to 1 g, have.

The health functional beverage composition of the present invention is not particularly limited to other ingredients containing the extract, and may contain various flavors or natural carbohydrates, etc. as additional ingredients, as in general drinks.

Examples of the aforementioned natural carbohydrates include monosaccharides such as glucose, fructose; Disaccharides such as maltose, sucrose and the like and polysaccharides such as dextrins, cyclodextrins and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. In addition to the above, 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 to the above, the active ingredient of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, Preservatives, colloidal thickeners, pH adjusting agents, stabilizers, antiseptics, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like.

In addition, the active ingredient of the present invention may contain flesh for the production of natural fruit juice and fruit juice drinks and vegetable drinks.

These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.

The composition containing the present invention moth extract as an active ingredient, by taking continuously without bringing side effects, the effect of preventing, improving and treating skin diseases is remarkable.

The composition containing the present invention extract as an active ingredient is remarkable effect of improving the manifestation of skin diseases including atopic dermatitis and contact dermatitis.

The composition containing the present invention extract as an active ingredient, the skin disease including atopic dermatitis and contact dermatitis, the effect of suppressing the amount of serum IgE is remarkable.

The composition containing the present invention extract as an active ingredient, the skin disease including atopic dermatitis and contact dermatitis, the effect of inhibiting serum IL-1β is remarkable.

The composition containing the present invention extract as an active ingredient, even in the group treated with hydrogen peroxide (H ₂ O ₂ ), the effect of increasing the survival rate of human keratinocytes is remarkable.

The composition containing the present invention moth extract as an active ingredient, in the skin diseases including atopic dermatitis and contact dermatitis, not only impairs the barrier function of the skin, but also the hypersensitivity of immunoglobulin E (IgE) By inhibiting and inhibiting excessive secretion of the inflammatory cytokine interleukin-1β, the effect of preventing, improving and treating skin diseases is remarkable.

1 is a view showing the effect of improving the expression of skin disease in the extract of DNFB-derived skin disease animal model.
Figure 2 is a view showing the effect of inhibiting the serum IgE extract in the DNFB-induced skin disease animal model.
3 is a diagram showing the effect of inhibiting serum IL-1β in the extract of DNFB-derived skin disease animal model.
FIG. 4 is a diagram showing the effect of crust extract on increasing cell viability of human keratinocytes.

The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms and the inventor may properly define the concept of the term in order to best describe its invention It should be construed as meaning and concept consistent with the technical idea of the present invention.

Therefore, the embodiments described in the present specification and the configurations shown in the drawings are merely the most preferred embodiments of the present invention and are not intended to represent all of the technical ideas of the present invention. Therefore, various equivalents It should be understood that water and variations may be present.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings.

Example  1. Preparation of nirvana extract

In order to prepare the extract extract to be used in this example, 100 g of extract was heated in 1 L of water for 3 hours to obtain an extract.

The extract was filtered and then lyophilized to prepare an extract powder.

Here, the filtration process of the extract was used gauze and / or filter paper (filter paper), it was lyophilized by adding water to the concentrated.

By repeating the above process, to obtain the extract extract, was used while storing the sample in the freezer.

Experimental Example  1.Spirit extract extracts skin disease in skin disease animal model. Improve Effect

1-1. Experimental animal

Four-week old BALB / c mouse females were purchased from Mulmul Science and were acclimated for one week in an animal kennel with automatic contrast control with a 12 hour cycle (09: 00-21: 00) under constant temperature and humidity.

These animals did not show any general symptoms at the time of acquisition and during adaptation.

During the adaptation period, the feed was fed free of mouse feed and the free distilled water (DW).

1-2. DNFB Induced Skin Disease Animal Models

After depilation of experimental animals, skin with acetone: irritant dissolved 0.15% 2,4-dinitro-1-fluorobenzene (DNFB) in olive oil (1: 3) solution 100 μl twice a week for 4 weeks.

1-3. Test group  Configuration and active ingredient processing

The test group consisted of five groups, which consisted of three groups: the normal control group, the DNFB-induced skin disease group (DNFB), and the oral sample group (DNFB + ID). .

In the normal control group (ACE), acetone: olive oil (1: 3) solution was applied to the epithelium, such as epilation.

DNFB-induced skin disease group (DNFB) hair removal irritant with 0.15% 2,4-dinitro-1-fluorobenzene (DNFB) dissolved in acetone: olive oil (1: 3) solution 100 μl (2 times / week) was applied to the dorsal epithelium.

The sample oral administration group (DNFB + ID) induced oral dermatitis in the same manner as the DNFB-induced skin disease group, and orally administered the extract.

After the test, serum and skin tissue of each group of test animals were obtained.

1-4. Its effect is to improve skin disease.

1 is a diagram showing the effect of improving the expression of skin disease after treatment of the extract in the DNFB-induced skin disease animal model, it is compared with the photograph taken to improve the degree of skin disease.

The sample oral administration group (DNFB + ID) continuously induces skin diseases in the same manner as the DNFB-induced skin disease group, and the oral extract was orally administered for 4 weeks from 4 weeks to 8 weeks.

As shown in FIG. 1, it can be seen that in the fourth week, the DNFB-induced skin disease group (DNFB) and the sample oral administration group (DNFB + ID) are completely expressed in the skin disease state.

However, comparing the expression of skin disease in DNFB-induced skin disease group (DNFB) and oral administration group (DNFB + ID) at week 8, it can be seen that moth extract significantly improved the expression of skin disease.

Experimental Example  2. Serpentine Extracts Serum in Skin Disease Animal Model IgE Suppressing effect

2-1. Preparation for experiment

In the same manner as in Experiment 1, after forming the test group and treating the active ingredient, serum of the test animal was obtained at 8 weeks.

2-2. Immunoglobulin  E ( IgE ) Measure

Serum IgE of each test group was measured using the ELISA method.

Specifically, the mouse monoclonal anti-IgE is diluted in 1% BSA coating buffer and coated on a 96-well plate (96-well plate) for about 8 hours.

Standard IgE and blood samples (50 μL) were reacted in a coated 96-well plate vessel, washed with phosphate buffer saline with 5% tween20, and then biotinylated IgE.

After reacting with avidin peroxidase (avidin peroxidase) was washed with a buffer solution, the ABTS solution was added and the absorbance was measured by an ELISA reader at 405nm wavelength.

2-3. Statistical processing

The experimental results were obtained by using the ANOVA test ( p -value), and was determined to be significant when p <0.05.

2-4. Serpent Extract Serum IgE Suppressing effect

Figure 2 is a view showing the effect of inhibiting the serum IgE extract in the DNFB-induced skin disease animal model.

As shown in Figure 2, in the DNFB-induced skin disease group (DNFB) it can be seen that the amount of serum IgE was measured high.

In comparison, the amount of serum IgE was significantly decreased in the oral administration group (DNFB + ID) administered orally with moth extract, indicating that the moth extract had a serum IgE inhibitory effect.

Experimental Example  3. Serpentine Extracts Serum in Skin Disease Animal Model IL -1β inhibitory effect

3-1. Preparation for experiment

In the same manner as in Experiment 1, after forming the test group and treating the active ingredient, serum of the test animal was obtained at 8 weeks.

Statistical treatment was applied in the same manner as in Experiment 2.

3-2. Interleukin 1-beta IL -1β) measurement

In the same manner as in Experiment 2, serum IL-1β of each test group was measured using an ELISA method.

3-3. Serpent Extract Serum IL -1β inhibitory effect

3 is a diagram showing the effect of inhibiting serum IL-1β in the extract of DNFB-derived skin disease animal model.

As shown in FIG. 3, in the DNFB-induced skin disease group (DNFB), the amount of interleukin 1-beta (IL-1β), which is known as an inflammatory cytokine, was measured to be high.

In comparison, the amount of serum IL-1β was significantly decreased in the oral administration group (DNFB + ID) with oral administration of cranberry extract. Can be.

Experimental Example  4. Crow Extract is a person Keratinocyte  cell Survival rate  Increasing effect

4-1. Preparation for experiment

The skin protection effect of moth on peroxide was measured by the cell survival rate against apoptosis.

MTT assay for measuring cell viability was performed as follows.

First, the cells to be used for the experiment (HaCaT cells) were dispensed in a 24-well cell culture plate at 1 × 10 ⁵ cells / ml for 3 hours, and the stabilized cells were treated with concentrations of the moth extract of the present invention. After a certain time, H ₂ O ₂ was treated and then reacted with MTT (0.5 mg / mL) for 3 hours.

Purple insoluble formazan produced from MTT by living cells was dissolved in DMSO, and absorbance was measured by an ELISA reader at a wavelength of 540 nm. The measured formazan production was expressed as absorbance.

Statistical treatment was applied in the same manner as in Experiment 2.

4-2. Crow Extract Cells Survival rate  Increasing effect

FIG. 4 is a diagram showing the effect of crust extract on increasing cell viability of human keratinocytes.

As shown in FIG. 4, in the group treated with hydrogen peroxide (H ₂ O ₂ ) only, the keratinocytes were damaged as compared to the normal control group, and the cell survival rate was remarkably decreased.

In comparison, it was found that the survival rate of the cells increased in concentration-dependent groups in the group treated with the extract.

However, when the concentration of cranberry extract is very high, the possibility of damaging the cells was also confirmed.

Comprehensively Experimental Examples 1 to 4, when comparing the expression status of the skin diseases of the DNFB-induced skin disease group (DNFB) and the sample oral administration group (DNFB + ID) with the naked eye, the moth extract extracts the skin disease expression The effect to improve is remarkable.

In addition, the amount of serum IgE was significantly decreased in the DNFB-induced skin disease group (DNFB), whereas in the oral administration group (DNFB + ID) with oral administration of the extract, the amount of serum IgE was significantly reduced. The effect of inhibiting serum IgE is remarkable.

In addition, in the DNFB-induced skin disease group (DNFB), the amount of interleukin 1-beta (IL-1β), which is known as an inflammatory cytokine, was measured to be high. In serum, the amount of serum IL-1β was significantly reduced, and therefore, the effect of crust extract on serum IL-1β was remarkable.

In addition, compared to the group treated only with hydrogen peroxide (H ₂ O ₂ ), the group treated with the extract moth extract is remarkably effective in increasing the survival rate of human keratinocytes.

Therefore, moth extract extracts not only impairs the barrier function of the skin in skin diseases including atopic dermatitis and contact dermatitis, but also inhibits the hypersensitivity of immunoglobulin E (IgE) and the inflammatory cytokine interleukin- By suppressing excessive secretion of 1β, it can be said that the effect of preventing, improving and treating skin diseases is remarkable.

Claims (9)

Ixeris dentata Nakai) pharmaceutical composition for the prevention and treatment of skin diseases containing the extract as an active ingredient.
The method of claim 1,
The moth extract extract pharmaceutical composition, characterized in that the amount of immunoglobulin E (Immunoglobulin E, IgE) and the amount of interleukin-1β (Interleukin-1β, IL-1β) in the blood is reduced.
The method of claim 1,
The moth extract is a pharmaceutical composition, characterized in that to increase the survival rate of human keratinocytes.
The method of claim 1,
The skin disease is a pharmaceutical composition comprising atopic dermatitis and contact dermatitis.
Ixeris dentata Nakai) A prophylactic and therapeutic agent for skin diseases containing the extract as an active ingredient, formulated in a pharmaceutical unit dosage form by adding a pharmaceutically acceptable carrier, excipient or diluent.
The method of claim 5, wherein
The pharmaceutical unit dosage form is selected from the group consisting of powders, granules, tablets, capsules, suspensions, emulsions, syrups, oral formulations of aerosols, suppositories, and sterile injectable solutions.
Ixeris dentata Nakai) A health functional food for the prevention and improvement of skin diseases by using the extract as an active ingredient, but adding a food acceptable food additive.
The method of claim 7, wherein
The food is a health functional food, characterized in that the powder, granules, tablets, capsules or beverages.
Ixeris dentata Nakai) Skin disease prevention and improvement agent for skin application containing extract as an active ingredient.

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