KR20130052243A - Agent for reducing skin irritation comprising carnosic acid or derivatives thereof - Google Patents

Abstract

PURPOSE: A skin irritation relieving agent containing carnosic acid or a derivative thereof is provided to suppress release of IL-8(interleukin-8), MCP-1(monocyte chemotactic protein-1), and IL-6(interleukin-6), and to relieves skin irritation due to retinoid or surfactant. CONSTITUTION: A skin irritation relieving agent contains carnosic acid denoted by chemical formula 1, a derivative thereof, or pharmaceutically acceptable salt thereof as an active ingredient. The skin irritation relieving agent relieves inflammation, skin dryness, erythema, horny substance, itching, or burning sensation. The skin irritation is caused by retinoid or surfactant of an external use skin formulation. The retinoid is selected from the group consisting of retinol, retinal, and retinoic acid.

Description

Agent for reducing skin irritation comprising carnosic acid or derivatives

The present invention relates to a skin irritation reducing agent comprising carnosic acid, derivatives thereof or pharmaceutically acceptable salts thereof.

Skin, which is directly exposed to the external environment and plays an important role in protecting the body from it, is directly exposed to various harmful environments such as synthetic compounds, ultraviolet rays, and microorganisms, and thus, skin is easily exposed to adverse reactions such as erythema, edema, itching, and inflammation. This adverse reaction is not only aesthetic problem, but it is known that the substances produced during the inflammatory reaction cause pigmentation of the skin and promote the collapse of skin elastic fibers to increase skin wrinkles.

In general, given stimulation from the outside, keratinocytes (Keratinocoyte) or Langerhan's cells (Langerhan's cells) make and release a variety of cytokines (Cytokine). These cytokines are essentially released during skin irritation and local inflammatory processes. In the case of irritant contact dermatitis, interleukin-6 (IL-6) and interleukin-8 (IL-8) ), MCP-1 (Monocyte chemotatic protein-1) is known to increase.

On the other hand, sensitive skin reacts more sensitively than normal skin to cosmetics used to protect the skin or various transdermal absorbents applied to the skin, such as dry skin, inflammation, erythema, keratin abnormalities, itching or burning, etc. Highly prone to symptoms For example, retinoids, which are used as the main active ingredients in cosmetics for improving wrinkles, promote the recovery of collagen and elastin to give elasticity to the skin and improve wrinkles. There are many side effects that cause local inflammatory reactions due to redness and peeling of the stratum corneum, making it difficult for those with sensitive skin to use. In addition, SLS (Sodium lauryl sulfate), an anionic surfactant mainly included in cosmetics, such as soaps, toothpastes, and shampoos, is added to cosmetic ingredients to inhibit cell metabolism and destroy cell membranes. It is known as a substance causing skin reactions. In addition, ingredients such as emulsifiers, chemical preservatives for long-term preservation of the product, backings, matrix reservoirs or adhesives, solubilizers, plasticizers, permeation enhancers, crosslinkers, which are commonly included in transdermal absorbents, It can act as the main causative agent of adverse reactions.

In order to prevent contact or allergic dermatitis caused by the above ingredients, only cosmetic products are manufactured in which the active ingredient that is likely to cause irritation is removed or the concentration is lowered. It can be said that it is not exhibited. Thus, if the cosmetics include a substance to relieve irritation may include more active ingredients, the effect may also be increased.

Carnos acid rosemary ( Rosmarinus officinalis ) or Salvia officinalis is a major potency component that is known to have excellent antioxidant effects. In addition, carnosic acid and its derivatives are known to promote the synthesis of nerve growth factor (Nve growth factor), which is also effective in improving neurodegenerative diseases. However, there are no known uses for stimulating carnosic acid.

United States Patent Application Publication No. 2001/0034370 (Published October 25, 2001)

One aspect of the present invention is to provide a skin irritant.

Another aspect of the present invention is to provide a cosmetic composition that does not irritate the skin.

One aspect of the present invention includes carnoic acid, a derivative thereof or a pharmaceutically acceptable salt thereof represented by the following Chemical Formula 1 as an active ingredient,

R in Formula 1 provides a skin irritant selected from the group consisting of -COOH, -COO-C ₁ to C ₅ alkyl, -C ₁ to C ₅ alcohol and -C ₂ to C ₁₀ alkoxyalkyl. .

Another aspect of the present invention provides a cosmetic composition comprising the skin irritant.

The skin irritation reducing agent according to the present invention may include carnoic acid, its derivatives or pharmaceutically acceptable salts thereof as an active ingredient, thereby alleviating inflammation, skin drying, erythema, keratin abnormality, itching or burning due to skin irritation. have. In particular, by inhibiting the release of IL-8 (Interleukin-8), MCP-1 (Monocyte Chemotactic Protein-1) and IL-6 (Interleukin-6), skin irritation by retinoids or surfactants can be alleviated. In addition, the cosmetic composition according to the present invention by including the skin irritation mitigator, even those with sensitive skin can be used freely.

As used herein, the term "skin" refers to a tissue covering the body surface of an animal, and is a concept of the broadest notion including a scalp and hair as well as a tissue covering a body surface such as a face or a body. In addition, in the present specification, "sensitive skin" may be defined as skin that is prone to adverse reactions such as stinging, itching, burning, burning, redness, dryness, and inflammation due to low resistance to external stimuli. The causes of such sensitive skin include congenital skin characteristics, family history, medical history, misuse of cosmetics, living environment or stress. As used herein, the term "extract" is a broad concept including all materials obtained by extracting the components of natural products, regardless of the extraction method, extraction solvent, extracted components or the form of the extract.

"Alkyl" as used herein means a monovalent saturated aliphatic hydrocarbon group. Hydrocarbon groups can be straight or branched. In one aspect of the invention “alkyl” may have 1 to 5 carbon atoms (“C ₁ to C ₅ alkyl”), specifically 1 to 3 carbon atoms (“C ₁ to C ₃ alkyl”) And more specifically 1 to 2 carbon atoms (“C ₁ to C ₂ alkyl”).

As used herein, "alkoxy" refers to an -OR group, where R refers to an alkyl group as defined above. Specifically "alkoxy" refers to methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy or 1,2-dimethylbutoxy and the like. Including but not limited to.

As used herein, “alcohol” means a —ROH group, where R means an alkyl group as defined above. Specifically, "alcohol" includes, but is not limited to, methanol, ethanol, propanol, isopropanol, butanol or amyl alcohol.

As used herein, "alkoxyalkyl" refers to the group -ROR 'wherein R and R' mean an alkyl group as defined above and may be the same or different from one another.

As used herein, "pharmaceutically acceptable" means the approval of a government or equivalent regulatory body to use in animals, more specifically in humans, by avoiding significant toxic effects when used in conventional medicinal dosages. It can be received or approved, or listed in a pharmacopoeia or recognized as another general pharmacopeia.

As used herein, "pharmaceutically acceptable salts" means salts according to one aspect of the invention that are pharmaceutically acceptable and have the desired pharmacological activity of the parent compound. The salt is formed from (1) an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, or the like; Or acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3- (4-hydroxybenzoyl) Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo [2,2,2] -oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert Acid addition salts formed with organic acids such as butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; Or (2) salts formed when the acidic protons present in the parent compound are substituted.

Hereinafter, the present invention will be described in detail.

One aspect of the present invention comprises a carnosic acid of Formula 1, a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient, R is -COOH, -COO-C ₁ to C ₅ Alkyl, -C ₁ to It provides a skin irritation-reducing agent selected from the group consisting of C ₅ alcohols and -C ₂ to C ₁₀ alkoxyalkyls.

Another aspect of the present invention includes carnoic acid of Formula 1, a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient, wherein R is -COOH, -COO-C ₁ to C ₃ alkyl and -C ₁ To provide a skin irritation reducing agent selected from the group consisting of to C ₃ alcohol.

Another aspect of the present invention provides a skin irritation-releasing agent comprising as an active ingredient carnoic acid (Formula 2), carnoic acid methyl ester (Formula 3), carnoic acid methyl alcohol (Formula 4), or pharmaceutically acceptable salts thereof. to provide.

In one aspect of the invention, carnosic acid, derivatives thereof or pharmaceutically acceptable salts thereof are selected from rosemary ( Rosmarinus). officinalis ) or sage ( Salvia officinalis ) can be obtained by extraction and extraction by conventional extraction methods in the art. In another aspect of the invention, carnosic acid, derivatives thereof or pharmaceutically acceptable salts thereof include hydrothermal or solvent extracts of rosemary or sage. The solvent includes at least one organic solvent, in particular one selected from the group consisting of alcohol, hexane, acetone, ethyl acetate, diethyl ether, ethyl methyl ketone, and chloroform, and more specifically includes C ₁ to C ₅ alcohols. .

In another aspect of the present invention, carnosic acid, derivatives thereof or pharmaceutically acceptable salts thereof may be obtained by synthesis by conventional methods in the art.

In one aspect of the invention, carnosic acid, its derivatives, or pharmaceutically acceptable salts thereof, include IL-8 (Interleukin-8), which is an inflammatory mediator that is released during the inflammatory response caused by retinoid stimulation to the skin and By inhibiting the release of MCP-1 (Monocyte Chemotactic Protein-1), skin irritation caused by retinoids can be alleviated. In another aspect of the invention, carnosic acid, derivatives thereof or pharmaceutically acceptable salts thereof inhibit the release of IL-6 (Interleukin-6), an inflammatory mediator that is released when the surfactant irritates the skin. The skin irritation caused by the surfactant can be alleviated. Thus, preparations comprising carnosic acid, derivatives thereof or pharmaceutically acceptable salts thereof can alleviate skin irritation.

Skin irritation relief agent according to an aspect of the present invention may relieve skin irritation, dry skin, erythema, keratin abnormalities, itching or burning. In another aspect of the present invention, skin irritation includes skin irritation by an external preparation for skin, specifically skin irritation by a retinoid or surfactant in the external preparation for skin. Skin irritation relief agent according to one aspect of the present invention may exhibit a particularly excellent effect in relieving skin irritation for sensitive skin.

In one aspect of the invention, retinoid refers to vitamin A and its derivatives generically, including but not limited to one or more selected from the group consisting of retinol, retinal and retinoic acid. In one aspect of the invention, the surfactant includes an anionic surfactant, and specifically, but not limited to Sodium Lauryl Sulfate (SLS).

The skin irritation relief agent according to one aspect of the present invention is 0.01% to 20% by weight, specifically 0.1% to 10% by weight, more specifically 0.5% to 5% by weight, based on the total weight of the skin irritant. Acid, derivatives thereof, or pharmaceutically acceptable salts thereof. When included in the above range is not only suitable for showing the intended effect of the present invention, it can satisfy both the stability and safety of the composition, it may be appropriate to include in the above range in terms of cost-effectiveness. Specifically, when the carnos acid, its derivatives, or pharmaceutically acceptable salts thereof is less than 0.01% by weight, sufficient skin irritation-reducing effects may not be obtained, and when it exceeds 20% by weight, safety and formulation stability may be lowered.

One aspect of the present invention provides a topical skin composition comprising the skin irritant. The external preparation composition for the skin includes a cosmetic composition, and the cosmetic composition includes a cosmetic composition for inhibiting skin aging, skin whitening, skin wrinkle improvement, skin exfoliation, acne improvement, psoriasis improvement or hair loss improvement. . Specifically, the cosmetic composition may be a composition including a retinoid or a surfactant, and may improve symptoms such as inflammation, skin drying, erythema, keratin abnormality, itching or burning due to the retinoid or the surfactant. In addition, the cosmetic composition does not deteriorate functions such as washing power, emulsifying power, dispersing power, osmotic power and bubble power of the surfactant. Sensitive skins, on the other hand, readily respond to irritation and therefore respond better to ingredients contained in cosmetic compositions such as retinoids or surfactants. The cosmetic composition according to one aspect of the present invention may be used by a person having sensitive skin by including a skin irritation reducing agent comprising carnosic acid, a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient.

The cosmetic composition according to the present invention may be provided in all formulations suitable for topical application. For example, it may be provided as a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an oil phase in water, a suspension, a solid, a gel, a powder, a paste, a foam or an aerosol composition. Compositions of such formulations may be prepared according to conventional methods in the art.

The cosmetic composition according to the present invention may include other ingredients in addition to the above-mentioned substances within the range not impairing the main effect, preferably giving a synergistic effect to the main effect. In addition, the cosmetic composition according to the present invention may further include a moisturizer, an emulsifier, an ultraviolet absorber, a preservative, a fungicide, an antioxidant, a pH adjuster, organic and inorganic pigments, flavors, coolants, or limiting agents. The blending amount of the above components can be easily selected by those skilled in the art within the range that does not impair the object and effect of the present invention, the blending amount may be 0.01 to 5% by weight, specifically 0.01 to 3% by weight based on the total weight of the composition. have.

One aspect of the present invention provides a pharmaceutical composition comprising the skin irritant as an active ingredient. The pharmaceutical composition may include a pharmaceutical composition for inhibiting skin aging, skin whitening, skin wrinkle improvement, skin exfoliation, acne improvement, psoriasis improvement, or hair loss improvement, and specifically, a retinoid or a surfactant. Can be. In addition, the pharmaceutical composition may include a skin irritation-releasing agent comprising carnosic acid, a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient, so that those with sensitive skin may use it without hesitation.

The formulation of the pharmaceutical composition according to an aspect of the present invention may be a solution, suspension, emulsion, gel, drop, suppository, patch or spray, but is not limited thereto. The formulations can be readily prepared according to conventional methods in the art, and include excipients, hydrating agents, emulsifying accelerators, suspending agents, salts or buffers for controlling osmotic pressure, colorants, spices, stabilizers, preservatives, preservatives or other compatible agents. Adjuvants may be used as appropriate.

The active ingredient of the pharmaceutical composition according to one aspect of the present invention will vary depending on the age, sex, weight, pathology and severity of the subject to be administered, the route of administration or the judgment of the prescriber. Dosage determination based on these factors is within the level of one skilled in the art and its daily dosage may be, for example, from 0.1 mg / kg / day to 100 mg / kg / day, more specifically from 5 mg / kg / day to 50 mg / kg. May be, but is not limited to.

Hereinafter, the configuration and effects of the present invention will be described in more detail with reference to Examples and Test Examples. However, the following examples and test examples are provided only for the purpose of illustration in order to help the understanding of the present invention, but the scope and scope of the present invention is not limited thereto.

Example 1 Obtaining Carnosic Acid

Rosemary ( Rosmarinus officinalis) or sage (Salvia officinalis) can be obtained Carnot seusan in a conventional extraction methods in the art from. Specifically, the leaves of rosemary or sage are heated and extracted with 70% (v / v) to 100% (v / v) ethanol for 2 days in an extractor equipped with a reflux condenser at 50 ° C. Water is then added within a range of no more than 50% of the total volume of ethanol to induce precipitation formation including carnosic acid from the extract. At this time, the precipitation formation temperature is maintained not to exceed 20 ℃. Three times or more in the same manner as described above to induce the formation of precipitates with ethanol and water to obtain carnosic acid.

Example 2 Preparation of Carnoic Acid Methyl Ester

1 g of carnosic acid obtained in Example 1 is dissolved in 30 ml of a mixed solvent of benzene and chloroform, and then 1.5 ml of TMS-diazomethane is slowly added dropwise. After the reaction temperature is maintained at 0 ℃ stirred for 30 minutes. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and then purified by column chromatography (hexane: ethyl acetate = 7: 1) to obtain 680 mg of carnoic acid methyl ester. NMR data of the carnoic acid methyl ester obtained by the above method is as follows.

¹ H NMR (300 MHz, CDCl ₃ ) 7.47 (s, 1H), 6.54 (s, 1H), 5.78 (s, 1H), 3.7 (s, 3H), 3.31 (1H, dt), 3.20 (1H, m ), 2.82-2.70 (2H, m), 2.29 (1H, m), 1.86 (m, 1H), 1.68 (m, 1H), 1.61 (m, 1H), 1.56 (dd, 1H), 1.46 (dt, 1H), 1.31 (m, 1H), 1.24 (m, 1H), 1.22 (d, 3H), 1.20 (d, 3H), 1.00 (s, 3H), 0.80 (s, 3H).

Example 3 Preparation of Carnosic Acid Methyl Alcohol

100 mg of carnoic acid obtained in Example 1 was dissolved in 5 ml of THF solvent, and 1.5 ml of LAH was slowly added dropwise. Then, the reaction temperature is maintained at 80 ℃ and stirred for 5 hours. After the reaction, the mixture was extracted with 5% aqueous hydrochloric acid solution and ethyl acetate, concentrated under reduced pressure, and then purified and separated by column chromatography (hexane: ethyl acetate = 10: 1) to give 32 mg of methyl carnosate methyl alcohol. The NMR data of carnoic acid methyl alcohol obtained by this method is as follows.

¹ H NMR (300 MHz, CDCl ₃ ) ¹ H NMR (300 MHz, CDCl ₃ ) 8.6 (s, 1H), 6.53 (s, 1H), 4.51 (d, 1H), 3.98 (d, 1H), 3.21 ( m, 2H), 2.86 (m, 2H), 1.86 (m, 1H), 1.68 (m, 1H), 1.61 (m, 1H), 1.56 (dd, 1H), 1.46 (dt, 1H), 1.31 (m) , 1H), 1.24 (m, 1H), 1.22 (d, 3H), 1.20 (d, 3H), 1.00 (s, 3H), 0.80 (s, 3H).

Test Example 1 Confirmation of IL-8 and MCP-1 Free Inhibitory Efficacy

Test cells, keratinocytes (HaCaT, obtained from Dr. NE Fusenig, Deutsches Krebsforschungszentrum, Heidelberg, Germany) and 10% fetal bovine serum (Fetal bovine sereum, FBS, obtained from Gibco, USA) and 1 Using a DMEM (Dulbecco's Modified Eagle Medium, Lonza, USA) medium containing% Penicillin-Streptomycin (Gibco, USA), the drug was applied to a 96-well plate (48 well plate). After dispensing at a density of 2 × 10 ⁴ cells / well, the cells were incubated for 24 hours under 37 ° C. and 5% CO ₂ conditions. After the culture solution was removed, the cells were washed once with 200 μl of phosphate buffered saline (PBS), and 200 μl of DMEM medium containing fetal bovine serum was added and incubated for 24 hours. Then treated with Examples 1 to 3 and the positive control (hydrocortisone) for 10 minutes with DMEM containing 1% fetal calf serum, the retinoic acid of 100 ppm concentration: Sigma-Aldrich, USA) and incubated for 24 hours. 50 μl of the culture solution was taken, and the free inhibitory effect of these inflammatory mediators was evaluated by ELISA using IL-8, MCP-1 ELISA kit (available from BD pharmigen, USA). Specifically, a standard curve is calculated based on the absorbances of the reference materials rh IL-8 and rh MCP-1 (obtained by BD pharmigen, USA), and then the absorbances of the treated materials are substituted by applying the absorbances of the treated materials. The amount of inflammation mediators was obtained. Thereafter, the free inhibition rate (%) of IL-8 and MCP-1 was obtained according to the following formula, and the results are shown in the following table.

% Inhibition = 100 x [1- (Inflammation mediator secretion in substance treatment group / Inflammation mediator secretion in retinoic acid alone treatment group)]

Test substance Concentration (ppm) IL-8 MCP-1 Inhibition rate
(%) % Inhibition compared to hydrocortisone % Inhibition % Inhibition compared to hydrocortisone Retinoic acid 100 - - - - Carnos acid
(Example 1) One 20.4 22.0 79.6 96.6 5 45.4 49.0 92.5 112.1 10 84.9 91.6 93.4 113.3 Carnosic Acid Methyl Ester
(Example 2) One 30.1 32.5 85.1 103.1 5 51.8 55.9 102 124 10 92.4 99.7 105 127.7 Carnosic Acid Methyl Alcohol
(Example 3) One 25.8 27.9 82.1 99.5 5 53.1 57.3 98.7 119.6 10 93.4 100.8 102.3 124 Positive control group
(Hydrocortisone) One 92.6 - 82.5 -

As shown in Table 1, in the group treated with carnosic acid or derivatives thereof, the release of IL-8 and MCP-1 by retinoic acid was inhibited in a concentration-dependent manner. Especially with regard to MCP-1 free inhibition, it showed almost the same inhibition rate as hydrocortisone, a steroid known to cause side effects such as skin atrophy and vasodilation. As such, carnosic acid and its derivatives have excellent effects in relieving skin inflammation and skin irritation caused by retinoic acid. It may be an alternative skin irritant.

Test Example 2 Confirmation of IL-6 Free Inhibitory Effect

Except that 100 ppm of sodium lauryl sulfate was used as keratinocytes, the keratinocytes were treated in the same manner as in Test Example 1, and the cytokines IL- of the positive controls (hydrocortisone) of Examples 1 to 3 were used. The glass inhibitory effect of 6 was evaluated. Specifically, a standard curve was drawn based on the absorbance of rh IL-6 (obtained by BD pharmigen, USA) to obtain the reaction formula between the absorbance and the reference material, and then the absorbances of the treated materials were substituted to obtain the amounts of these cytokines. Thereafter, IL-6 free inhibition was calculated using the same formula as in Test Example 1, and the results are shown in the following table.

Test substance Concentration (ppm) IL-6 Inhibition rate
(%) % Inhibition compared to hydrocortisone Sodium lauryl sulfate 100 - - Carnos acid
(Example 1) One 70.4 86.5 5 78.6 96.6 10 84.7 104.1 Methyl carnosate
Ester
(Example 2) One 81.2 99.6 5 89.7 110.1 10 95.4 117.2 Methyl carnosate
Alcohol
(Example 3) One 74.0 90.9 5 81.2 99.7 10 87.9 107.9 Positive control group
(Hydrocortisone) One 81.4 -

As can be seen from Table 2, in the group treated with carnosic acid or derivatives thereof, the release of IL-6 by the surfactant was inhibited in a concentration-dependent manner. It is estimated to have almost the same inhibitory activity as the steroid hydrocortisone. As such, carnoic acid and its derivatives have excellent effects in relieving skin irritation and skin irritation caused by surfactants, and therefore, steroids, which have been widely used because of their side effects, are effective in relieving skin inflammation and skin irritation. It may be an alternative skin irritant.

Test Example 3 Evaluation of Efficacy in Human Skin Erythema

Safety Evaluation of CTFA (The Cosmetic Toiletry and Fragrance Association) to evaluate the inhibitory effects of retinol on skin erythema induced by the retinol of Examples 1 to 3 in healthy volunteers who had never taken steroid preparations and nonsteroidal anti-inflammatory drugs within one month before the start of the test Evaluation was conducted according to the Safety Testing Guideline (1981). Specifically, the composition formulated as Table 3 below was applied twice a day (50 μl / 1.5 × 1.5 cm 2) inside the forearm of 15 subjects, and wrapped for 3 hours in a wrap to assist absorption. . The test period was adjusted in consideration of the response level and skin condition of the subject, and was up to 3 weeks. The test was carried out daily before morning application, and the last test was carried out until 8 days after the application. Evaluation was continued after application to reflect the recovery of irritation, and no score was given when erythema completely disappeared and only pigmentation remained. At each test point, the degree of stimulation was evaluated according to the determination method shown in Table 4 below, and the results of calculating the stimulation inhibition rate (%) of Examples 1 to 3 based on the degree of stimulation of the comparative example are shown in Table 5 below.

ingredient Content (% by weight) Comparative example Examples 1 to 3 Test substance - 1.0 Retinol 3000 IU 3000 IU Wax 4.00 4.00 Polysorbate 1.50 1.50 Sorbitan sesquioleate 0.70 0.70 Liquid paraffin 5.00 5.00 Caprylic / Caprictriglycerides 5.00 5.00 glycerin 3.00 3.00 Butylene glycol 3.00 3.00 Propylene glycol 3.00 3.00 Carboxyvinyl polymer 0.10 0.10 Triethanolamine 0.20 0.20 antiseptic Suitable amount Suitable amount Pigment Suitable amount Suitable amount Spices Suitable amount Suitable amount Purified water to 100 to 100

Skin irritation grade Mild erythema One Severe erythema 2 Severe erythema with edema 3 Severe erythema with edema and blisters
(intense erythema with edema and vesicle) 4

Stimulation Relief (%) Comparative Example 1 - Example 1 42.3 Example 2 39.8 Example 3 33.5

As can be seen from the above results, carnoic acid or derivatives thereof of Examples 1 to 3 have an effect of inhibiting erythema induced by retinol in human skin. That is, it can be seen that carnoic acid or a derivative thereof has an excellent effect of alleviating skin irritation clinically.

Formulation examples of compositions according to one aspect of the present invention are described below, but may be applied to various other formulations, which are not intended to be limiting but merely illustrative of the invention.

Formulation Example 1 Flexible Lotion

According to the composition described in the table below to prepare a flexible lotion in a conventional manner.

Compounding ingredient Content (% by weight) Carnos acid 0.1 glycerin 3.0 Butylene glycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 Phage-12 nonylphenyl ether 0.2 Polysorbate 80 0.4 ethanol 10.0 Triethanolamine 0.1 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 2] nutrition lotion

To prepare a nourishing lotion according to the composition described in the table below.

 Compounding ingredient Content (% by weight) Carnosic Acid Methyl Ester 0.5 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxyvinyl polymer 0.1 Wax 4.0 Polysorbate 60 1.5 Caprylic / Capric Triglycerides 5.0 Squalane 5.0 Sorbitassquioleate 1.5 Liquid paraffin 0.5 Cetearyl Alcohol 1.0 Triethanolamine 0.2 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 3] Nourishing cream

Nutritional creams are prepared by conventional methods according to the compositions set forth in the table below.

Compounding ingredient Content (% by weight) Carnosic Acid Methyl Alcohol 1.0 glycerin 3.0 Butylene glycol 3.0 Liquid paraffin 7.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / Capric Triglycerides 3.0 Squalane 5.0 Cetearyl Glucoside 1.5 Sorbitan stearate 0.4 Polysorbate 60 1.2 Triethanolamine 0.1 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 4] Massage cream

Massage cream is prepared in a conventional manner according to the composition described in the table below.

Compounding ingredient Content (% by weight) Carnos acid 1.5 glycerin 8.0 Butylene glycol 4.0 Liquid paraffin 45.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / Capric Triglycerides 3.0 Wax 4.0 Cetearyl Glucoside 1.5 Sesqui oleic acid sorbitan 0.9 Vaseline 3.0 paraffin 1.5 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 5] Pack

Packs are prepared by conventional methods according to the compositions described in the table below.

Compounding ingredient Content (% by weight) Carnosic Acid Methyl Ester 0.1 glycerin 4.0 Polyvinyl alcohol 15.0 Hyaluronic acid extract 5.0 Beta Glucan 7.0 Allantoin 0.1 Nonyl Phenyl Ether 0.4 Polysorbate 60 1.2 ethanol 6.0 Preservative, coloring, fragrance Suitable amount Purified water Balance

[Formulation Example 6] ointment

Ointment is prepared by a conventional method according to the composition shown in the following table.

Compounding ingredient Content (% by weight) Carnosic Acid Methyl Alcohol 0.1 glycerin 8.0 Butylene glycol 4.0 Liquid paraffin 15.0 Beta Glucan 7.0 Carbomer 0.1 Caprylic / Capric Triglycerides 3.0 Squalane 1.0 Cetearyl Glucoside 1.5 Sorbitan stearate 0.4 Cetearyl Alcohol 1.0 Wax 4.0 Preservative, coloring, fragrance Suitable amount Purified water Balance

Claims (11)

Skin irritation reducing agent comprising as an active ingredient carnos acid, a derivative thereof or a pharmaceutically acceptable salt thereof represented by Formula 1 below:
[Formula 1]

In Formula 1, R is selected from the group consisting of -COOH, -COO-C ₁ to C ₅ alkyl, -C ₁ to C ₅ alcohol and -C ₂ to C ₁₀ alkoxyalkyl.
The method of claim 1,
R is selected from the group consisting of -COOH, -COO-C ₁ to C ₃ alkyl, and -C ₁ to C ₃ alcohol.
The method of claim 1,
Skin irritation relievers are skin irritants that relieve skin irritation, dry skin, erythema, keratin abnormalities, itching or burning.
The method of claim 1,
Skin irritation includes skin irritation including skin irritation by external skin preparations.
The method of claim 4, wherein
Skin irritation by skin external preparations includes skin irritation agents comprising skin irritation by retinoids or surfactants in the skin external preparations.
The method of claim 5, wherein
Retinoids are skin irritants, including at least one selected from the group consisting of retinol, retinal and retinoic acid.
The method of claim 1,
Carnosic acid, its derivatives or pharmaceutically acceptable salts thereof is an extract for skin irritation, which is an extract of one or more selected from rosemary and sage.
The method of claim 1,
A skin irritation relaxing agent comprising carnosic acid, a derivative thereof or a pharmaceutically acceptable salt thereof in an amount of 0.01 to 20% by weight based on the total weight of the skin irritation relaxing agent.
Cosmetic composition containing a skin irritation reducing agent according to any one of claims 1 to 8.
The method of claim 9,
Cosmetic composition for skin aging inhibition, skin whitening, skin wrinkle improvement, skin keratin improvement, acne improvement, psoriasis improvement or hair loss improvement.
The method of claim 9,
Cosmetic composition is a cosmetic composition comprising a sensitive skin.