KR20070069625A - Cosmetic composition containing mentha piperita extract for reducing irritation in skin irritated by retinoid - Google Patents

Abstract

A cosmetic composition containing the extract of Mentha Piperita for reducing skin irritation caused by retinoid is provided to inhibit expression of inflammation-causing materials such as ICAM-1 (intercellular adhesion molecule-1) and IL-1alpha(interleukin-1 alpha) factor. The cosmetic composition for reducing skin irritation and inflammation caused by retinoid contains 0.1-1 wt.% of the extract of Mentha Piperita which inhibits expression of IL-1alpha factor, and erythema and edema formation responses irritated by retinoid, wherein the retinoid is retinol, retinal or retinoic acid; and the Mentha Piperita extract contains 0.9-1.8 g/l of polyphenols having antioxidizing effects.

Description

Cosmetic composition containing peppermint extract to alleviate skin irritation caused by retinoids {Cosmetic composition containing Mentha Piperita extract for reducing irritation in skin irritated by retinoid}

The present invention relates to a cosmetic composition having an effect of alleviating skin irritation caused by retinoids, and more particularly, by containing peppermint extracts to suppress the expression of inflammatory mediators and to have the effect of relieving skin irritation and inflammation caused by retinoids. It relates to a cosmetic composition.

Retinoids act on keratinocytes to promote cell differentiation, increase the production of collagen and elastin to form thick mucus layers, and inhibit keratinization to increase skin elasticity and inhibit wrinkle formation. It is used as an active ingredient in wrinkle improvement cosmetics and is used to treat skin diseases such as acne, psoriasis and keratinous abnormalities.

However, retinoids can cause side effects when applied to the skin, which is known to cause symptoms such as dry skin, erythema, keratin, itching, burning (Textbook of Contact Dermatitis, 323). This is a characteristic symptom of retinoid-specific irritant contact dermatitis called reinoid dermatitis. Many receptors are involved in the action of retinoids in the skin, and stimuli such as scaling and peeling are partially related to pharmacological action. Therefore, in retinoid application treatments, softening creams may be added to the carrier to reduce irritation, or an entrapped microsponge gel formulation may be used, or polyprepolymers may be used to reduce penetration. (Exog Dermatol 2002; 1: 68-73).

Despite the skin side effects of these retinoids, retinoids have been used continuously because of their excellent wrinkle reduction and other pharmacological effects, and researches to develop retinoid derivatives with different structures or new formulations are actively conducted to reduce these skin side effects. It's going on.

As such, various studies have been attempted to minimize the skin side effects of retinoids having a beneficial effect on the skin, which is particularly urgently required in the cosmetic industry.

Until now, hypoallergenic skin cosmetics have been developed so as not to cause contact dermatitis, allergic dermatitis, etc. by removing the active ingredients that may cause irritation. However, environmental and psychological factors require the use of active ingredients in cosmetics for sensitive skin owners. Therefore, in the conventional retinoid-containing cosmetics industry, there have been attempts to alleviate adverse reactions by controlling cytokines and inflammatory mediators, and to relieve skin irritation caused by retinoids through skin barrier strengthening and skin protection functions. Specific examples include the bradykinin antagonist (see USP 5,849,312) for the control of inflammatory mediators and the adverse reaction of sensitive skin, and the application of a cytokine TNF-α inhibitor as a sensitive skin agent (USP 5,851,556). .

In general, looking at the mechanism of stimulation or inflammatory response, human keratinocytes or Langerhans cells can be produced and released from various cytokines by external substances. These cytokines are essential for promoting immune system activation in the human body and are essential for skin irritation and local inflammatory reactions (J Appl Toxicol 16: 65-70, 1996). Indeed, increased irleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) in irritant contact dermatitis It has been reported (Contact Dermatitis 35: 355-60, 1996, Dec). Intracellular Adhesion Molecule-1 (ICAM-1) is also an essential molecule in the adhesion between keratinocytes and lymphocytes. Protein and gene levels in skin irritation and local inflammatory processes Increased expression of ICAM-1 was observed (Free Rad Biol Med, 28: 219-227, 2000). The expression of ICAM-1 molecules on the surface of keratinocytes is induced by the interferon-γ (IFN-γ), an inflammatory cytokine. It can be expected to act as a component.

Accordingly, the present inventors have studied to effectively use retinoids, which are useful as cosmetics due to skin aging prevention and wrinkle improvement, but have been difficult to use due to side effects such as skin irritation and inflammation, and thus, ICAM as a surface molecule related to the inflammatory response pathway. -1 and inflammatory cytokines, particularly IL-1α, are involved in the formation of skin irritation by retinoids, and by reversing the reaction by regulating the expression of these inflammatory mediators, mitigates skin irritation of retinoids to the skin. It has been found that the effect can be achieved. For its development, while conducting research on herbal extracts and natural-derived substances that have already been used in cosmetics, medicines, etc. and proven safe, mediated inflammatory mediators against retinoid-induced skin irritation in human cells cultured with peppermint extracts. It has excellent ability to suppress the expression of the molecule and can be used as an excellent irritant component of the retinoid-containing cosmetics, finally found to inhibit the skin side effects of the retinoids used as an active ingredient of the functional cosmetics to complete the present invention.

Accordingly, it is an object of the present invention to provide a functional cosmetic composition for relieving skin irritation and inflammation caused by retinoids.

In order to achieve the above object, the present invention provides a cosmetic composition for skin irritation and inflammation relief by retinoids, characterized in that it contains peppermint extract.

The present invention contains the peppermint extract 0.1 to 1% by weight based on the total weight of the composition, the peppermint extract is characterized by inhibiting the expression of IL-1α by retinoid stimulation, inhibiting erythema and edema.

In addition, the retinoid of the present invention is characterized in that at least one selected from the group consisting of retinol, retinal and retinoic acid.

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

Peppermint (Mentha Piperita) extract, an active ingredient of the composition of the present invention, contains 0.9 to 1.8 g / L of polyphenol, which is known to have an antioxidant effect in an aqueous solution having a distinctive flavor and amber color of mint leaves.

In one embodiment of the present invention was used as a peppermint extract calmiskin manufactured by Silab.

In addition, the cosmetic composition according to the invention is characterized in that it contains a peppermint extract in an amount of 0.1 to 1% by weight based on the total weight of the composition. This is because if the content of peppermint extract is less than 0.1% by weight has little effect, if the content of more than 1% by weight may cause problems in skin safety is not preferable.

Retinoid of the present invention is a generic term for a compound related to vitamin A, and includes retinol, retinal, retinoic acid, and the like. In particular, retinol is a precursor of retinic acid, which is absorbed into the skin, and then gradually changes to retinic acid, so the effect is somewhat lower, but the side effects are relatively low, and are used as a cosmetic composition for anti-aging or wrinkle improvement. The retinoid of the cosmetic composition of the present invention may contain one or more selected from the group consisting of retinol, retinal and retinolic acid.

Hereinafter, the present invention will be described in detail based on the test examples, but the scope of the present invention is not limited thereto.

In the present invention, in order to determine whether the cosmetic composition containing peppermint extract has an inflammation-releasing function for a common inflammation-causing agent, the degree of expression control of inflammatory mediators in cells was tested (Test Example 1). However, it was not possible to confirm the anti-inflammatory function expected for the general provoking agents, so the expression level of the inflammatory mediators in the cells stimulated with the active form of retinoic acid to confirm whether the retinoid-specific stimulating function The degree of control was tested (Test Example 2). In addition, cumulative stimulation evaluation through rabbits was performed to evaluate the efficacy in the living body (Test Example 3), and further human cumulative stimulation evaluation (Test Example 4) to alleviate the stimulation for retinoids in human skin Final effect was confirmed.

In the following test example, the unit of retinol, IU (international unit), is a unit representing the activity or amount of an enzyme or vitamin, and 1 IU is given to vitamin A deficient young rats to increase their weight by 3 g per day. Refers to the amount of vitamin A.

Experimental Example 1 Evaluation of Inhibitory Effect of ICAM-1 Molecule on Induction Expression by IFN-γ as an Inflammatory Mediator

Human keratinocyte cell line HaCaT was cultured with DMEM (Dulbecco's Modified Eagle's Media, BioWhittaker) containing 10% fetal bovine serum (FBS) in 2 x 10 ⁴ cells in each well of a 96-well test plate. After incubation for 12 hours, and diluted with DMEM culture to an appropriate concentration, put the sample to be evaluated for efficacy and further incubated for 12 hours. After washing with PBS, ICAM-1 expression was induced on the surface of HaCaT cell line by further incubation for 24 hours in DMEM medium containing 20 unit / mL of IFN-γ.

After diluting the human T lymphocyte cell line Jurkat to 1 × 10 ⁷ / mL with PBS, a fluorescent dye calcein-AM (Fluka 17783), which is selectively stained only in living cells, was added to a final concentration of 5 mM for 30 minutes. Incubated. The excess dye stained on the cells and washed with PBS was repeated three times to prepare a culture solution RPMI-1640 (BioWhittaker) to 3 × 10 ⁶ / mL. After the induction of ICAM-1 molecules on the surface of the HaCaT cell line was completed, the culture medium was removed, washed thoroughly, and 3 × 10 ⁵ Jurkat cell lines stained with calcein-AM were added to each well and incubated for 1 hour. It was. The procedure of removing excess Jurkat cells that did not adhere to the HaCaT cell line with PBS was repeated four times, and fluorescence was measured at a wavelength of 480/530 nm using a fluorescence microplate reader. The degree of adhesion between the HaCaT cell line and the Jurkat cell line means the expression level of the ICAM-1 molecule, the value of which is proportional to the intensity of the measured fluorescence, and the expression inhibition rate is calculated by Equation 1 below and the results are shown in Table 1 below. It was.

Expression Inhibition Rate (%) = [(Fluorescence measurement when stimulus and peppermint extract were given together-Fluorescence measurement when only stimulus was given) ÷ (Fluorescence measurement when only stimulus was given)] × 100

Composition Extract concentration Fluorescence measurement Expression inhibition rate Irritation source (20 unit / mL IFN-γ) - 10,241 - Irritation Source + Peppermint Extract 10 PPM 10,243 -0.02% Irritation Source + Peppermint Extract 100 PPM 10,228 0.13%

 From the results of Table 1, peppermint extract was found to have a very low level of inhibitory effect on the expression of ICAM-1 molecules by IFN-γ, which is a common inflammation-causing factor in skin keratinocytes.

[Test Example 2] Evaluation of IL-1α Biosynthesis Inhibitory Effect of Peppermint Extract by Retinoic Acid Stimulation in the Corneous Cell Line HaCaT

Human keratinocyte cell line HaCaT was added to each well of a 96-well test plate in Dwell (Dulbecco's Modified Eagle's Media, GIBCO BRL, Life Technologues) medium containing 10% fetal bovine serum (FBS). 10 ⁴ cells were attached and incubated for 24 hours. After the medium was removed, it was washed once with 200 μl of phosphate buffered saline (PBS), and 200 μl of DMEM medium containing no FBS was added thereto, followed by incubation for 24 hours. Thereafter, the extracts to be evaluated by DMEM containing 1% fetal calf serum were treated by the concentrations shown in Table 2 below and incubated for 24 hours. 50 μl of the culture solution was taken to measure the inhibitory effect of retinoic acid on IL-1α release through IL-1α ELISA (Pharmingen, Inc.), and the results are shown in Table 2 below.

ingredient Extract concentration (ppm) IL-1α (pg / ml) % Inhibition ¹⁾ Voice contrast - 8.93 - Retinoic acid (100 μM) - 30.75 - Retinoic Acid (100μM) + Peppermint Extract 100 18.34 56.9 ¹⁾ Calculation is based on the difference between IL-1α production of HaCaT cells not treated with retinoic acid and cells treated with retinoic acid.

From the results of Table 2, peppermint extract was found to have the effect of inhibiting the biosynthesis of IL-1α, an inflammation mediator by retinoic acid stimulation in human keratinocyte line HaCaT.

[Test Example 3] Retinol erythema stimulation efficacy evaluation of peppermint extract through animal testing

On the back skin of the New Zealand white rabbit, the composition shown in Table 4 was repeatedly applied twice a total of eight times for four days at intervals of two times a day. After application of the substance, the cumulative erythema and the skin formation score and the edema formation score were accumulated to determine the cumulative skin irritation index. Skin cumulative stimulation index was evaluated according to the criteria shown in Table 3, the results are shown in Table 4 below. The stimulus index shown in the results is based on the commonly used method of calculating the Primary Irritation Index (Draize, J.H., Appraisal of the safety of chemical in foods, drugs and cosmetics). Stimulation relaxation rate was calculated using the following equation 1, the results are shown in Table 4.

Stimulus relaxation rate (%) = 100 × (1- {sum of example index} / {sum of comparative index})

Degree of skin irritation grade 1) No erythema and no erythema formation. Very mild erythema (only visible to the naked eye) Clear erythema Strong to moderate erythema Deep erythema Strong erythema and crust formation  0 1 2 3 4 2) No edema formation Edema Very mild edema (only visible to the naked eye) Clear edema (distinct from clear) Moderate edema (if swollen up to 1 mm) Strong edema (swelling more than 1 mm and exposed area) Extended out)  0 1 2 3 4 Primary irritation index (P.I.I.) = (average of sum of erythema rating and edema rating) / 4

Composition Extract concentration (%) Stimulation Relief (%) ²⁾ Comparative Example: (+) Retinol 3000 IU + Vehicle - - Example: (+) Retinol 3000 IU + Peppermint Extract 1.0% 28.13 ²⁾ Calculation of stimulation relaxation rate based on the difference between the cumulative stimulation index between the group not coated with retinol and the group coated

 From the results of Table 4, it was found that the peppermint extract has an effect of alleviating skin irritation caused by retinol.

Test Example 4 Evaluation of Efficacy of Skin Erythema by Retinol in Peppermint Extract-Containing Formulations by Human Test

A guideline for evaluating the safety of the Peppermint Extract's retinol-induced skin erythema-induced effects in healthy volunteers who had never taken nonsteroidal anti-inflammatory drugs and other steroid preparations for a month before entering the study. (Safety Testing Guideline, 1981, p3). That is, the composition formulated as shown in Table 5 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. Put it. 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 up to 8 days after the patch application. Evaluation was continued even after the end of the patch to reflect the degree of recovery of stimulation, and no score was given when erythema completely disappeared and only pigmentation remained. At each test time point, the degree of stimulation was evaluated according to the determination method of Table 6 below, and the stimulation relaxation rate was calculated by the above equation 1 from the sum and the results are shown in Table 7 below.

ingredient Content (% by weight) Comparative Example 1 Example 1 Peppermint Extract - 1.0 Retinol 3000 IU 3000 IU Beeswax 4.00 4.00 Polysorbate 1.50 1.50 Sorbitan sesquioleate 0.70 0.70 Liquid paraffin 5.00 5.00 Caprylic / Capric Triglycerides 5.00 5.00 glycerin 3.00 3.00 Butylene glycol 3.00 3.00 Propylene glycol 3.00 3.00 Carboxy Vinyl Polymer 0.10 0.10 Triethanolamine 0.20 0.20 antiseptic Quantity Quantity Pigment Quantity Quantity Spices Quantity Quantity Purified water to 100 to 100

Degree of irritation of skin grade Mild erythema with intense erythema edema with intense erythema edema Severe erythema with edema and blisters 1 2 3 4

Composition Stimulation Relief (%) Comparative Example 1 - Example 1 26.7

 From Table 7, it was confirmed that the formulation containing the peppermint extract of the present invention has an effect of inhibiting erythema induced by retinol in human skin.

The external preparation composition of the present invention prevents or alleviates skin irritation and inflammation production by retinoids, and is not particularly limited in the formulation thereof, for example, softening longevity, nourishing longevity, massage cream, nourishing cream, pack, gel or It may have a formulation of a skin-adhesive cosmetic, and may also be a cosmetic composition having a transdermal dosage form such as lotion, ointment, gel, cream, patch or spray.

In addition, in each formulation, other components can be appropriately selected and blended by those skilled in the art without difficulty depending on the kind of the external preparation or the purpose of use.

As described above, the cosmetic composition containing the peppermint extract, which is a natural extract provided by the present invention, protects the skin from retinoid irritation and regulates the expression of inflammatory mediators to relieve skin irritation by retinoids.

Claims (6)

Cosmetic composition for skin irritation and inflammation relief by retinoids, characterized in that it contains peppermint extract. The cosmetic composition according to claim 1, wherein the peppermint extract contains 0.1 to 1% by weight based on the total weight of the composition. The cosmetic composition according to claim 1, wherein the peppermint extract inhibits the expression of IL-1α by retinoid stimulation. The cosmetic composition according to claim 1, wherein the peppermint extract inhibits erythema and edema formation reaction due to retinoid stimulation. The cosmetic composition according to claim 1, wherein the retinoid is at least one selected from the group consisting of retinol, retinal and retinoic acid. Skin irritation and inflammation relieving method by retinoids using peppermint extract.