KR20240006777A - Pharmaceutical composition for preventing or treating inflammatory skin diseases comprising extracts of Sasa borealis - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating inflammatory skin diseases containing Sasa borealis extract as an active ingredient, wherein the Sasa borealis extract does not exhibit cytotoxicity and inhibits TARC (thymus and activation-regulated chemokine) and MDC (macrophage) -derived chemokine), it can be used as a composition for preventing, treating, or improving inflammatory skin diseases, and is useful as a reagent composition for inhibiting TARC or MDC release and as a method for inhibiting release. It can be.

Description

Pharmaceutical composition for preventing or treating inflammatory skin diseases comprising extracts of Sasa borealis}

The present invention relates to a pharmaceutical composition for preventing or treating inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

Skin is an organ that constitutes the exterior of the body and is an important physical barrier that protects the body from various external physical and chemical stimuli while maintaining internal homeostasis. The skin not only prevents external outflow of moisture and electrolytes, regulates body temperature, maintains temperature homeostasis, responds to stimuli such as touch, pressure, pain, and heat, but also performs immune functions, vitamin D synthesis, etc. performs the function of

Problems that occur that prevent the skin from performing its function are called skin diseases. Among them, inflammatory skin diseases in which the skin becomes inflamed are diseases that cause symptoms such as redness, swelling, heat, and pain. The types are contact dermatitis and irritation. It is classified into contact dermatitis, allergic contact dermatitis, phototoxic and photoallergic contact dermatitis, contact urticaria syndrome, atopic dermatitis, seborrheic dermatitis, bullous eczema, coin-shaped eczema, autosensitizing dermatitis, housewives' eczema, and stasis dermatitis.

Inflammatory skin diseases involve several cells such as T lymphocytes, Langerhans cells, eosinophils, and dermal keratinocytes, and are caused by several factors such as cytokines, chemokines, and immunoglobulin molecules. Among them, keratinocytes are components that make up most of the epidermis of the skin and act as inducers and targets of immune responses occurring in the skin.

Recently, as the incidence of hypersensitivity or inflammatory skin diseases has increased due to changes in living environments such as industrialization and Western eating habits, the market for inflammatory skin diseases is also increasing, and various folk remedies, biological agents, etc. are being used, and medically Corticosteroids are widely used for oral use, topical ointment, and nasal spray, but in the case of inflammatory skin diseases, long-term treatment is often required, which not only causes time and cost problems, but also has side effects. , the development of treatments for inflammatory skin diseases that overcome the above problems is actively underway.

Meanwhile, Sasa borealis is an evergreen, broad-leafed small bamboo from the Poaceae family that grows very thin and straight to a height of 1 to 2 m and a diameter of 3 to 6 mm. Among the types of bamboo, it belongs to the Sasa genus. The stem is very thin and short, and the leaf sheath is still attached. It is reported that bamboo shoots are very effective in treating diabetes, fire disease, high fever, heat exhaustion, liver disease, high blood pressure, stroke, stomach ulcers, and hemorrhoids, and was recently added to the list of raw materials that can be used in food by the Ministry of Food and Drug Safety. It can also be used as food. However, there has been no report yet on the effect of Siberia extract on suppressing skin inflammation.

1. Republic of Korea Patent No. 10-2007728 (registered on July 31, 2019)

The purpose of the present invention is to provide a pharmaceutical composition for preventing or treating inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

Another object of the present invention is to provide a health functional food composition for preventing or improving inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

Another object of the present invention is to provide a cosmetic composition for preventing or improving inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

To achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

In addition, the present invention provides a health functional food composition for preventing or improving inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

In addition, the present invention provides a cosmetic composition for preventing or improving inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

According to the present invention, it was confirmed that the Sasa borealis extract does not exhibit cytotoxicity and exhibits an anti-inflammatory effect, such as suppressing the release of TARC (thymus and activation-regulated chemokine) and MDC (macrophage-derived chemokine). It can be used as a composition for preventing, treating or improving skin diseases, and can be usefully used as a reagent composition and method for inhibiting the release of TARC or MDC.

Figure 1 shows the results of confirming the cytotoxicity of the bamboo extract.
Figure 2 shows the results of confirming the inhibitory effect of TARC (thymus and activation-regulated chemokine) and MDC (macrophage-derived chemokine) release of the bamboo extract.

Hereinafter, the present invention will be described in more detail.

The present invention provides a pharmaceutical composition for preventing or treating inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

The extract may be extracted with a solvent selected from the group consisting of water, (C1-C4) alcohol, and mixtures thereof, but is not limited thereto.

Additionally, the extract can inhibit the release of thymus and activation-regulated chemokine (TARC) or macrophage-derived chemokine (MDC).

The inflammatory skin diseases include contact dermatitis, irritant contact dermatitis, allergic contact dermatitis, phototoxic and photoallergic contact dermatitis, contact urticaria syndrome, autosensitization dermatitis, stasis dermatitis, acne, atopic dermatitis, allergic dermatitis, seborrheic dermatitis, papular urticaria, It may be one or more selected from the group consisting of eczema and psoriasis, but is not limited thereto.

The pharmaceutical composition of the present invention is prepared in unit dose form or in a multi-dose container by formulating it using a pharmaceutically acceptable carrier according to a method that can be easily performed by a person skilled in the art. It can be manufactured by internalizing it.

The pharmaceutically acceptable carriers are those commonly used in preparation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Includes, but is not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc. In addition to the above components, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc.

In the present invention, the content of additives included in the pharmaceutical composition is not particularly limited and can be appropriately adjusted within the content range used in conventional formulations.

The pharmaceutical compositions include injectable formulations such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, tablets, creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, paste agents, and cataplasmase agents. It may be formulated in the form of one or more external skin preparations selected from the group consisting of, but is not limited to this.

The pharmaceutical composition of the present invention may additionally contain pharmaceutically acceptable carriers and diluents for formulation. The pharmaceutically acceptable carriers and diluents include excipients such as starch, sugar and mannitol, fillers and extenders such as calcium phosphate, cellulose derivatives such as carboxymethylcellulose, hydroxypropylcellulose, gelatin, alginate, polyvinyl pyrrolidone. It includes, but is not limited to, binders such as talc, calcium stearate, lubricants such as hydrogenated castor oil and polyethylene glycol, disintegrants such as povidone and crospovidone, and surfactants such as polysorbate, cetyl alcohol, glycerol, etc. The pharmaceutically acceptable carrier and diluent may be biologically and physiologically friendly to the subject. Examples of diluents include, but are not limited to, saline, aqueous buffers, solvents, and/or dispersion media.

The pharmaceutical composition of the present invention can be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally, or topically) depending on the desired method. For oral administration, it can be formulated as tablets, troches, lozenges, aqueous suspensions, oily suspensions, powders, granules, emulsions, hard capsules, soft capsules, syrups, elixirs, etc. In the case of parenteral administration, it can be formulated as an injection, suppository, powder for respiratory inhalation, aerosol for spray, ointment, powder for application, oil, cream, etc.

The dosage of the pharmaceutical composition of the present invention is determined by the patient's condition, weight, age, gender, health, dietary constitution specificity, nature of the preparation, degree of disease, administration time of the composition, administration method, administration period or interval, excretion rate, and The range may vary depending on the drug form and can be appropriately selected by a person skilled in the art. For example, it may range from about 0.1 to 10,000 mg/kg, but is not limited and may be administered once to several times a day.

The pharmaceutical composition may be administered orally or parenterally (eg, intravenously, subcutaneously, intraperitoneally, or topically applied) depending on the desired method. The pharmaceutically effective amount and effective dosage of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time, administration route, etc. of the pharmaceutical composition, and those skilled in the art will know that it is effective for the desired treatment. Dosage can be easily determined and prescribed. The pharmaceutical composition of the present invention may be administered once a day, or may be administered in several divided doses.

In addition, the present invention provides a health functional food composition for preventing or improving inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

The present invention can be generally used with commonly used foods.

The food composition of the present invention can be used as a health functional food. The term “health functional food” refers to food manufactured and processed using raw materials or ingredients with functionality useful to the human body in accordance with the Health Functional Food Act, and “functionality” refers to food that is related to the structure and function of the human body. It means ingestion for the purpose of controlling nutrients or obtaining useful health effects such as physiological effects.

The health functional food composition may contain common food additives, and its suitability as a “food additive” is determined in accordance with the general provisions and general test methods of the food additive code approved by the Ministry of Food and Drug Safety, unless otherwise specified. The decision is made based on the specifications and standards for the item.

Items listed in the “Food Additives Code” include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid; natural additives such as subchromic pigment, licorice extract, crystalline cellulose, high-liquid pigment, and guar gum; Examples include mixed preparations such as sodium L-glutamate preparations, noodle additive alkaline preparations, preservative preparations, and tar coloring preparations.

The food composition of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. For example, among health functional foods in the form of capsules, hard capsules can be manufactured by mixing and filling the composition according to the present invention with additives such as excipients in a regular hard capsule, and soft capsules can be manufactured by mixing and filling the composition according to the present invention. It can be manufactured by mixing with additives such as excipients and filling it with a capsule base such as gelatin. The soft capsule may contain plasticizers such as glycerin or sorbitol, colorants, preservatives, etc., if necessary.

Definitions of terms such as excipients, binders, disintegrants, lubricants, coagulants, flavoring agents, etc. are described in literature known in the art and include those with the same or similar functions. There is no particular limitation on the type of food, and it includes all health functional foods in the conventional sense.

In the present invention, the term “prevention” refers to all actions that suppress or delay a disease by administering the composition according to the present invention. In the present invention, the term “treatment” refers to any action that improves or beneficially changes the symptoms of a disease by administering the composition according to the present invention. In the present invention, “improvement” means any action that improves the bad condition of a disease by administering or ingesting the composition of the present invention to an individual.

In addition, the present invention provides a cosmetic composition for preventing or improving inflammatory skin diseases containing Sasa borealis extract as an active ingredient.

The cosmetic composition includes skin lotion, skin softener, skin toner, astringent, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, foundation, essence, nutritional essence, pack, soap, cleansing foam, It may be formulated with one or more selected from the group consisting of cleansing lotion, cleansing cream, body lotion, and body cleanser, but is not limited thereto.

Specifically, the cosmetic composition can be prepared in a general emulsification formulation and solubilization formulation. For example, lotion such as softening lotion or nourishing lotion; Emulsions such as facial lotion and body lotion; Creams such as nutritional cream, moisture cream, eye cream, etc.; essence; cosmetic ointment; spray; gel; pack; sunscreen; makeup base; Foundation, such as liquid type, solid type, or spray type; powder; Make-up removers such as cleansing creams, cleansing lotions, and cleansing oils; Alternatively, it may be formulated as a cleansing agent such as cleansing foam, soap, or body wash, but is not limited to this. Additionally, the skin external preparation may be formulated as an ointment, patch, gel, cream, or spray, but is not limited thereto.

In addition to the essential ingredients, in each formulation, other ingredients may be appropriately mixed in the cosmetic composition, depending on the type of formulation or purpose of use, within the range that does not impair the purpose of the present invention.

The cosmetic composition may contain a generally acceptable carrier and may be appropriately mixed with, for example, oil, water, surfactant, moisturizer, lower alcohol, thickener, chelating agent, colorant, preservative, fragrance, etc., but is not limited thereto. no.

The acceptable carrier may vary depending on the formulation. For example, when formulated into ointments, pastes, creams or gels, animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or these are used as carrier ingredients. Extracts may be used.

When the cosmetic composition is formulated as a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silcate, polyamide powder, or extracts thereof may be used as carrier ingredients, and in the case of a spray, chlorofluorohydride may be used. It may further include propellants such as carbon, propane, butane or dimethyl ether.

When the cosmetic composition is formulated as a solution or emulsion, a solvent, solubilizing agent, or emulsifying agent may be used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl benzoate, propylene glycol, 1,3-Butylglycol oil may be used, in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan.

When the cosmetic composition is formulated as a suspension, the carrier component includes water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used.

When the cosmetic composition is formulated into soap, alkali metal salts of fatty acids, fatty acid hemiester salts, fatty acid protein hydrolyzates, isethionates, lanolin derivatives, fatty alcohols, vegetable oils, glycerol, sugars, etc. are used as carrier ingredients. can be used

The cosmetic composition may contain fatty substances, organic solvents, solubilizers, thickeners, gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, and fragrances commonly used in the industry depending on the quality or function of the final product. , surfactants, water, ionic or non-ionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic activators, commonly used in cosmetics. It may additionally contain auxiliaries commonly used in the fields of cosmetology or dermatology, such as any other ingredients.

However, the auxiliaries and their mixing ratio may be appropriately selected so as not to affect the desirable properties of the cosmetic composition according to the present invention.

In addition, the present invention provides a reagent composition for inhibiting the release of TARC (thymus and activation-regulated chemokine) or MDC (macrophage-derived chemokine) containing Sasa borealis extract as an active ingredient.

Additionally, the present invention provides a method for inhibiting thymus and activation-regulated chemokine (TARC) or macrophage-derived chemokine (MDC) release comprising treating a Sasa borealis extract.

Hereinafter, the present invention will be described in detail through examples to aid understanding. However, the following examples only illustrate the content of the present invention and the scope of the present invention is not limited to the following examples. Examples of the present invention are provided to more completely explain the present invention to those skilled in the art.

[Experimental Example 1] Preparation of bamboo leaf extract

Sasa borealis leaves dried with hot air were extracted using 70% ethanol at 80°C for 6 hours. The bamboo leaf extract was filtered through filter paper (Advantec, No. 5A, ToKyo, JAPAN), then lyophilized using a freeze dryer (FDU-2100, EYELA, JAPAN) and recovered in powder form. The recovered extract was stored at -20°C and used.

[Experimental Example 2] Cell culture

rttemberg, Germany)에서 분양 받아 사용하였으며, HaCaT 피부각질세포는 10% 소태아혈청(fetal bovine serum; FBS, Welgene, Daegu, Korea)과 1% 페니실린-스트렙토마이신(penicillin-streptomycin, Welgene, Daegu, Korea)이 포함된 DMEM(Welgene, Daegu, Korea)을 사용하여 37℃ 및 5% CO₂ 조건의 인큐베이터(incubator)에서 배양하였다. Skin keratinocytes (HaCaT keratinocytes) used in the present invention are obtained from Cell Lines Service (CLS, Eppelheim, Baden-W)

rttemberg, Germany), and HaCaT skin keratinocytes were treated with 10% fetal bovine serum (FBS, Welgene, Daegu, Korea) and 1% penicillin-streptomycin (Welgene, Daegu, Korea). ) was used and cultured in an incubator under 37°C and 5% CO ₂ conditions using DMEM (Welgene, Daegu, Korea) containing .

[Experimental Example 3] Measurement of cell viability for bamboo leaf extract

To measure cell viability, HaCaT skin ^{keratinocytes} were seeded in a 96-well cell culture plate at 1 250 and 500 μg/ml) and cultured for 24 hours. After incubation, MTT solution (5 μg/ml) was treated in each well and reacted for 4 hours at 37°C and 5% CO ₂ , and then the eluted formazan crystals were dissolved using DMSO. Absorbance was measured at 550 nm using a microplate reader (Spectramax Plus 384, Molecular devices, San Jose, California, USA). The cell survival rate according to the treatment concentration of the bamboo extract was expressed as a percentage relative to the control group.

[Experimental Example 4] Measurement of emission of TARC and MDC

To confirm the release of TARC (thymus and activation-regulated chemokine) and MDC (macrophage-derived chemokine) following treatment with bamboo leaf extract, ELISA technique was used. First, HaCaT skin keratinocytes (5 × 10 ⁶ cells/well) were seeded in a 6-well cell culture plate and cultured at 37°C and 5% CO ₂ for 24 hours. After 24 hours, the bamboo leaf extract was treated in each well at different concentrations (50, 100, 250, and 500 μg/ml) and cultured for 2 hours, and then treated with TNF-α and INF-γ (10 ng/ml) for 24 hours. processed over time. After treatment with a stimulator, the supernatant of the cultured cells was collected and centrifuged (13,000 rpm, 4°C, 10 minutes) to remove impurities. Using the collected supernatant, the release amount of TARC and MDC was measured using the TARC/MDC ELISA kit (R&D systems, Minneapolis, MN, USA). Silymarin (50 and 100 μg/ml) was used as a positive control.

[Experimental Example 5] Statistical analysis

All results obtained in the above experimental examples were expressed as the mean ± standard deviation of the measured values of three or more repeated experiments, and statistical analysis of the experimental results was performed using Student's t-test, with a p value of 0.05. If it is below, it was judged to be significant.

[ Example One] HaCaT Measurement of cell viability of bamboo leaf extract on skin keratinocytes

According to Experimental Example 3, after treatment of HaCaT skin keratinocytes with bamboo leaf extract, cell viability was analyzed using MTT assay.

As a result, it was confirmed that cell death of HaCaT skin keratinocytes did not occur at all concentrations when treated with bamboo leaf extract (Figure 1).

[ Example 2] TNF -α and IFN Skin inflammation induced by -γ HaCaT Analysis of the inhibitory effect of TARC and MDC release of bamboo leaf extract on skin keratinocytes

TARC and MDC are known as chemokines that appear when skin inflammation occurs due to the reaction of cytokines inside the skin. In order to confirm the skin inflammation suppressing effect of the bamboo leaf extract, according to Experimental Example 4, HaCaT skin The inhibitory effect of TARC and MDC release from keratinocytes of bamboo leaf extract was analyzed.

As a result, it was confirmed that skin inflammation was induced by treatment with TNF-α and INF-γ in HaCaT skin keratinocytes by increasing the release amount of TARC and MDC by 11.8-fold and 10.1-fold, respectively. TARC (The half maximum inhibition concentration, IC ₅₀ , 398.94 μg/ml) and MDC (IC ₅₀ , 302.33 μg/ml) were confirmed to decrease in a concentration-dependent manner as the treatment concentration of bamboo leaf extract increased (Figure 2).

This means that by suppressing TARC and MDC secreted by skin keratinocytes, the migration of immune cells to skin keratinocytes is suppressed and factors that can cause hypersensitivity reactions are removed, thereby improving atopic dermatitis and enhancing skin immunity.

As the specific parts of the present invention have been described in detail above, it is clear to those skilled in the art that these specific techniques are merely preferred embodiments and do not limit the scope of the present invention. do. That is, the practical scope of the present invention is defined by the appended claims and their equivalents.

Claims (3)

A pharmaceutical composition for preventing or treating inflammatory skin diseases containing Sasa borealis extract as an active ingredient. A health functional food composition for preventing or improving inflammatory skin diseases containing Sasa borealis extract as an active ingredient. A cosmetic composition for preventing or improving inflammatory skin diseases containing Sasa borealis extract as an active ingredient.