KR102538076B1 - Cosmetics composition containing N-Propylphosphate phytosphingosine compound - Google Patents

Abstract

The present invention relates to a cosmetic composition containing an N-propylphosphate phytosphingosine compound that has an effect of relieving skin inflammation or relieving skin irritation, which is inducible with nitrogen monoxide, IL-6, which mediates skin inflammatory response and irritation in cell experiments. , IL-8, PGE ₂ , and has excellent effects in inhibiting histamine secretion. Therefore, the present invention has a very excellent advantage of providing a cosmetic composition having an anti-inflammatory and anti-irritation effect on irritation caused by the use of cosmetics, characterized in that it contains N-propylphosphate phytosphingosine as an active ingredient.

Description

Cosmetic composition containing N-Propylphosphate phytosphingosine compound {Cosmetics composition containing N-Propylphosphate phytosphingosine compound}

The present invention relates to a cosmetic composition containing an N-propylphosphate phytosphingosine compound, and more particularly, to a cosmetic composition having an effect of relieving skin inflammation or relieving skin irritation.

The skin is a part directly exposed to the external environment, and acts to protect the human body from rapid environmental changes, ultraviolet rays or toxic chemicals, microorganisms, and the like.

In recent years, the intensity of ultraviolet rays has increased due to the destruction of the ozone layer due to industrialization, climate change has occurred frequently due to global warming, living environments by interiors containing toxic chemicals, eating habits favoring instant food due to busy daily life, and misused Human skin is also becoming sensitive due to external stimuli such as cosmetics and detergents.

As the number of people with sensitive skin increases, the demand for hypoallergenic cosmetics is also increasing. Harmful ingredients unrelated to the purpose of skin protection, such as preservatives, surfactants, fragrances, and colorants, are used in cosmetics used for skin protection and beautification and cleanliness.

Recently, as functionality is emphasized rather than safety of raw materials, the raw materials used may cause trouble such as irritation or inflammation on sensitive skin.

Looking specifically at skin troubles that may occur due to the use of cosmetics, there are irritations such as itching, stinging, and burning sensations, and inflammatory troubles such as erythema and edema.

Although the cause of skin side effects caused by cosmetics has not been precisely identified, it can be said that irritation and inflammatory reactions occur by activating the immune system by interacting with epidermal or dermal cells by infiltration of irritants into the skin due to an abnormality in the skin barrier. can

Such inflammation is a defense action of biological tissues against external substances, and includes physiological reactions such as activation of inflammatory mediators and immune cells present in local blood vessels or body fluids, secretion of inflammatory mediators, and tissue destruction, as well as erythema, edema, fever, and pain. appearing as external symptoms.

Regarding external stimuli, major substances that mediate the inflammatory response include nitric oxide (NO), histamine and prostaglandins secreted from mast cells. Several cytokines are involved in generating these inflammatory mediators.

Meanwhile, interleukin-6 and 8 (interleukin-6, interleukin-8: IL-6, IL-8) are inflammatory cytokines in monocytes, fibroblasts, endothelial cells and keratinocytes, and also induce histamine release in mast cells. .

In order to suppress or reduce side effects that cause skin problems such as irritation or inflammation from the use of cosmetics, many studies using natural extracts have been conducted, and numerous patents have been published.

However, natural extracts are difficult to commercialize because the indicator substance that shows the effect is unclear, so the durability of the efficacy is questionable, and even if the indicator substance is confirmed, the amount is very small and the cost required for separation and purification is excessive. .

In order to overcome these disadvantages of natural extracts, the present inventors have synthesized novel substances from natural compounds with guaranteed safety, do not cause irritation to the skin, and suppress the secretion of the above-mentioned inflammatory mediators to relieve skin inflammation and irritation. During research to develop an effective cosmetic, it was confirmed that the N-Propylphosphate phytosphingosine compound has excellent skin inflammation and irritation relief effects, and the present invention was completed.

Patent Document 1: Republic of Korea Patent Registration No. 101471818 (2014.12.11)

Accordingly, in the present invention, the N-Propylphosphate phytosphingosine compound inhibits the secretion of inducible nitric oxide, IL-6, IL-8, PGE ₂ and histamine that mediate skin irritation and inflammatory response in cell experiments. It was effectively suppressed, and through a skin patch clinical trial, irritation relief and soothing effects on sensitive skin were confirmed, and it was proven that it was safe for human skin.

Accordingly, the present invention relates to a cosmetic composition having an anti-inflammatory and anti-irritant effect on irritation caused by use of cosmetics, comprising an N-Propylphosphate phytosphingosine compound as an active ingredient.

A cosmetic composition according to one embodiment of the present invention is N-propylphosphate phytosphingosine compound (I) or compound (II) represented by Formula 1:

[Formula 1]

X = H: compound (I)

X = OH: Compound (II)

Characterized in that it contains.

In the cosmetic composition according to one embodiment of the present invention, the cosmetic composition is characterized in that it has a skin inflammation relief or skin irritation relief effect.

In the cosmetic composition according to one embodiment of the present invention, the cosmetic composition is any one selected from the group consisting of emulsion, cream, essence, gel, lipstick, foundation, gel, shampoo, rinse, treatment, body cleanser, and sunscreen It is characterized in that it consists of one dosage form.

The N-propylphosphate phytosphingosine and the cosmetic composition containing the same according to the present invention inhibit the secretion of inducible nitric oxide, IL-6, IL-8, PGE ₂ and histamine that mediate skin inflammatory response and stimulation in cell experiments. It has an excellent effect on skin patching, and the effect was confirmed through clinical trials of skin patch, and it was proved that it is safe for human skin. Therefore, the present invention has a very excellent advantage of providing a cosmetic composition having an anti-inflammatory and anti-irritation effect on irritation caused by the use of cosmetics, characterized in that it contains N-propylphosphate phytosphingosine as an active ingredient.

1 is a diagram showing the chemical structure of the N-propylphosphate phytosphingosine compound contained in the cosmetic composition according to the present invention.

Before describing the present invention in more detail, the terms or words used in this specification and claims should not be limited to their usual or dictionary meanings, and the concept of terms is appropriately used to describe the invention in the best way. It should be interpreted as a meaning and concept consistent with the technical spirit of the present invention based on the principle that it can be defined in the following way. Therefore, the configuration of the embodiments described in this specification is only one preferred example of the present invention, and does not represent all of the technical spirit of the present invention, so various equivalents and modifications that can replace them at the time of the present application It should be understood that there may be

Hereinafter, preferred embodiments of the present invention will be described in detail so that those skilled in the art can easily practice the present invention.

In order to develop cosmetics effective in relieving skin inflammation and irritation caused by the use of cosmetics, the inventors of the present invention synthesized new substances from natural compounds with guaranteed safety and conducted research. N-Propylphospate phytosphingosine compound (Formula 1) was synthesized, and this compound mediates skin inflammatory response and stimulation, inducible nitric oxide (NO), IL-6, IL-8, PGE ₂ and histamine secretion, it was found that there is an excellent effect, and based on this, the present invention was completed.

[Formula 1]

X = H: compound (I)

X = OH: Compound (II)

Therefore, an object of the present invention is to provide a cosmetic composition having an alleviating effect on skin inflammation and irritation caused by cosmetic use, and more specifically, containing N-Propylphosphate phytosphingosine compound as an active ingredient It is to provide a cosmetic composition having a skin inflammation relief and irritation relief effect, characterized in that.

In the present invention, N-Propylphosphate phytosphingosine compound was synthesized from natural substance Phytosphingosine, and the present invention contains it as an active ingredient to relieve inflammation and irritation. To provide a cosmetic composition having.

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

The present inventors referred to many literatures to synthesize and develop ingredients that can alleviate skin irritation and inflammation caused by external stimuli or cosmetic use by synthesizing and developing natural products or compounds using natural materials with guaranteed safety, and laboratory tests was carried out.

During intensive research, N-Propylphosphate phytosphingosine compound synthesized from natural substance phytosphingosine was found to be inducible nitric oxide (N-monoxide) that mediates skin inflammation and irritation response through cell experiments. NO), IL-6, IL-8, PGE ₂ and histamine secretion was found to have excellent effects, and based on this finding, the present invention was completed.

Phytosphingosin is also one of the sphingo lipid precursors constituting ceramide, an important component that protects the skin in the stratum corneum, and is known to play a role in protecting the skin from microorganisms while being present in small amounts in skin cells.

Sphingo lipids such as ceramide-1-phosphate, sphingosylphosphorylcholine and sphingosine-1-phosphate act on keratinocytes and immune cells of the skin, It is known as a biological control agent for inflammatory skin diseases such as psoriasis vulgaris and atopy.

1. Burkhard Kleuser, Lukasz Japtok. Sphingolipids and inflammatory disease of the skin.

Review Handb Exp Pharmacol. 2013;(216):355-72.

On the other hand, ceramide has various derivatives having sphingosine, phytosphigosine, and sphinganine as a basic skeleton, but currently only phytosphingosine can be mass-produced from microorganisms.

For this reason, many studies have been conducted on the development of skin protection products using phytosphingosin in cosmetic compositions, and recently, studies on skin protection using derivatives of phytosphingosin have been published. there is.

2. Byung-Hak Kim, Ji Min Lee. Et al: Phytosphingosine derivatives ameriolate skin inflammation by inhibiting NF-kB and JAK/STAT signaling in keratinocyte and mice: J Invest Dermatol. 2014 Apr;134(4):1023-1032

3. Woo Jin Lee, Seunghyun Bang, et al: Inhibitory effects of N,N,N-Trimethyl phytosphingosine Iodide on melanogenesis via ERK activation mediated MITE degradation: Biosci Biotechnol Biochem. 2016;80(1):121-7

While conducting research using phytosphingosine derivatives, the present researchers also synthesized N-Propylphosphate phytosphingosine compounds, and experimented with mouse macrophages to investigate skin inflammation and irritation relief effects In addition, we tried to prove its efficacy through human fibroblast and skin patch clinical trials.

The method for synthesizing the N-propylpphosphate phytosphingosine compound used in the present invention can be briefly explained through Formula 2 below.

[Formula 2]

(X = H or OH)

Phytosphingosine used in the present invention was purchased and used commercially available phytosphingosine produced by microbial fermentation, and the IUPAC name is (2S,3S,4R)-2-Aminooctadecane-1,3,4-triol . The synthesis method will be described in more detail in the experimental example.

Since the N-Propylphosphate phytosphingosine compound synthesized according to the present invention exhibits amphiphilicity, it is not only soluble in water-soluble solvents and non-aqueous solvents, but also has surface active properties, and also has 90 It shows stability even at a high temperature of ~120 ℃ and shows stability regardless of pH. Such characteristics are very advantageous when the compound of the present invention is formulated into a cosmetic composition or a pharmaceutical composition, and particularly facilitates formulation as an external skin preparation.

The N-Propylphosphate phytosphingosine compound synthesized according to the present invention has a cytotoxicity mitigating effect by lactic acid, a skin irritant material commonly used in skin irritation relieving studies, and skin irritation in cell experiments. It showed excellent effects in suppressing the secretion of inducible nitric oxide, IL-6, IL-8, PGE ₂ and histamine that mediate the inflammatory response. In the results of the human skin patch test, the skin irritation relief effect was excellent.

Based on the above studies, a cosmetic composition containing N-propylphosphate phytosphingosine as an active ingredient and having an anti-inflammatory and anti-irritation effect on irritation caused by cosmetic use was completed. In addition to the N-Propylphosphate phytosphingosine compound, which is an active ingredient, the cosmetic composition of the present invention includes ingredients commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, conventional adjuvants such as vitamins, pigments and flavors, and carriers.

The cosmetic composition according to the present invention is not particularly limited in its formulation, and is prepared in formulations such as emulsion, cream, essence, serum, gel, lipstick, foundation, gel, shampoo, rinse, treatment, body cleanser, sunscreen, etc. It can be.

Hereinafter, the present invention will be described in more detail through experimental examples and formulation examples, but the scope of the present invention is not limited to the following experimental examples and formulation examples.

Experimental Example 1. Synthesis of N-Propylphosphate Phytosphingosine Compound (I)

Dissolve phytosphingosine (2g, 6.3mM) and 3-oxopropyl dihydrogen phosphate (3-oxopropyl dihydrogen phosphate: 1g, 6.5mM) in a mixed solvent of tetrahydrofuran (10ml)/methylenchloride (10ml) Then, a catalytic amount of magnesium sulfate (MgSO ₄ ) was added and the mixture was stirred at room temperature.

After stirring at room temperature for 1 hour, it was confirmed by TLC that the reaction was complete, and the organic solvent was blown off using a vacuum to obtain a residue.

20 ml of methanol was added to the above residue and dissolved, sodium borohydride: 0.5 g, 13.2 mM) was added and the mixture was stirred at room temperature for 1 hour.

30 ml of ethyl acetate and 10 ml of distilled water were added and shaken, and the organic layer was separated, and then the organic solvent was blown off using a vacuum to obtain 2.5 g of a residue.

The above residue was separated and purified using flash column chromatography (CHCl ₃ /MeOH/H ₂ O 70:25:5) to obtain a pure N-Propylphosphate phytosphingosine compound. (I) (2.45 g, yield: 85%) was obtained. mp: 125 ^o C.

1H NMR (300 MHz, DMSO-d6) ;5.52 (s, 1H), 5.40 (s, 1H), 5.37 (s, 1H), 4.49 (s, 1H), 4.20 (s, 2H), 4.04-4.51 ( m, 2H), 3.32-3.45 (m, 4H), 2.50-2.55 (m, 3H), 1.72-1.84 (m, 2H), 1.37-1.43 (m, 2H), 1.24-1.26 (m, 24H), 0.79-0.92 (m, 3H)

Component analysis result: C21H46NO7P (455.56); Calcd: C, 55.37; H, 10.18; N, 3.07; P ,6.80.

found: C, 55.35; H, 10.12; N, 3.12; P, 6.73

Experimental Example 2. Synthesis of N-Hydroxypropylphosphate phytosphingo sine compound (II)

Phytosphingosine (2g, 6.3mM) and glyceraldehyde-3-phosphate (Glyceraldehyde-3-phosphate: 1.1g, 6.5mM) were dissolved in a mixed solvent of tetrahydrofuran (10ml)/methylenchloride (10ml) , Magnesium sulfate (MgSO ₄ ) was added in a catalytic amount and stirred at room temperature.

After stirring at room temperature for 1 hour, confirming that the reaction was complete by TLC, the organic solvent was blown off using a vacuum to obtain a residue. 20 ml of methanol was added to the above residue and dissolved, sodium borohydride: 0.5 g, 13.2 mM) was added and the mixture was stirred at room temperature for 1 hour.

30 ml of ethyl acetate and 10 ml of distilled water were added and shaken, and the organic layer was separated, and then the organic solvent was blown off using a vacuum to obtain 2.5 g of a residue.

The above residue was separated and purified using flash column chromatography (CHCl ₃ /MeOH/H ₂ O 70:25:5) to obtain pure N-hydroxypropylphosphate phytosphingosine ) Compound (II) (2.5 g, yield: 84%) was obtained. mp: 108 ^o C

1 H NMR (300 MHz, DMSO-d6); 7.72 (s, 1H), 5.37-5.40 (m, 3H), 4.49 (s, 1H), 4.23-4.35 (m, 1H), 4.20 (s, 2H), 3.98-4.11 (m, 1H), 3.50- 3.58 (m, 1H), 3.32-3.45 (m, 4H), 3.05-3.15 (m, 2H), 2.50-2.55 (m, 1H), 1.37-1.43 (m, 2H), 1.24-1.26 (m, 24H) ), 0.79-0.92 (m, 3H)

Component analysis result: C21H46NO8P (471.56); Calcd: C, 53.49; H, 9.83; N, 2.97; P ,6.57.

found: C, 53.51; H, 9.80; N, 3.02; P, 6.53

Experimental Example 3. Soothing effect from skin cell stimulation by lactic acid

In order to confirm whether the N-Propylphosphate phytosphingosine compound of the present invention has a soothing effect on skin irritation, a skin cell stimulation mitigation experiment using lactic acid was performed.

Fibroblast, a human skin cell, was cultured in a T-75 flask (Falcon, USA) containing DMEM (sigma) until it reached 80% growth, and then in a 96-well plate (Falcon, USA) containing DMEM. It was cultured for 12 hours until 1×10 ⁵ cells/well.

After cell culture, it was confirmed whether the cells were completely adhered and formed well through a microscope, and the experiment was conducted as follows using 0.2% lactic acid as a skin cell stimulator. At the concentration of lactic acid, normal skin cells are generally all killed. 200 μl of DMEM containing 0.2% lactic acid was added to each of 96 wells of the plate in which fibroblasts were cultured, and N-Propylphosphate phytosphingosine compounds (I and II) were added at 50 and 100 μl, respectively. , 200, 500 and 1,000 μg/ml.

As a control, N-Propylphosphate phytosphingosine (N-Propylphosphate phytosphingosine) compound and lactic acid were not added, and as a control group, only lactic acid was added. 10 μg of MTT ([3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reagent was added to each well to compare cell viability after 12 hours elapsed after the test substance was added. After each was added and allowed to stand for 4 hours, the absorbance of each well was measured using an ELISA reader (Molecular Devices), and the cell viability was measured by Equation 1 below. The results are shown in Table 1 below.

<Equation 1>

Cell viability (%) = [(control absorbance - test substance absorbance) / control absorbance] × 100

Concentration of N-propylphosphate phytosphingosine compound (μg/ml) Cell viability (%) Compound (I) Compound (II) Compound (I)+
lactic acid Compound (II)+
lactic acid lactic acid 50 99 99 50 55 0 100 98 99 65 85 0 200 97 98 90 95 0 500 98 98 92 97 0 1000 97 97 95 97 0

As shown in Table 1, the N-Propylphosphate phytosphingosine compound of the present invention showed little cell stimulation with increasing concentration and did not affect cell survival. In addition, since all cells are killed by lactic acid, the survival rate of the cells increased as the treatment concentration of the N-Propylphosphate phytosphingosine compound increased.

Therefore, it can be seen that the N-Propylphosphate phytosphingosine compound of the present invention has an effect of inhibiting skin cell death by alleviating stimulation of skin cells by lactic acid.

Experimental Example 4. Inhibition of PGE ₂ and IL-6, IL-8 production

Human fibroblasts were inoculated in a 6-well culture plate at a concentration of 1 x 10 ⁵ cells and cultured in a 37 °C 5% CO ₂ incubator for 24 hours. After treating the well with 500 μm of H ₂ O ₂ and stimulating for 24 hours, N-nicotinoyl phytosphingosine of the present invention was treated by concentration and reacted for 48 hours, and the culture medium was collected and subjected to ELISA analysis.

A kit from AssayDesign was used for PGE ₂ , and a kit from Endogen was used for IL-6 and IL-8. The experiment was conducted according to the manual of each company. The measurement of the inhibitory effect of this experimental example was calculated by Equation 2 below. The results are shown in Table 2 below. The control group is a group treated only with N-nicotinoyl phytosphingosine.

<Equation 2>

Inhibition effect = [1-(test sample - control)/( H ₂ O ₂ - control)] × 100

Example PGE ₂ pg/ml
(inhibiting effect) IL-6 pg/ml
(inhibiting effect) IL-8 pg/ml
(inhibiting effect) control group 74.5 25.4 32.3 H ₂ O _{2 (} 500 μm) 316.2 175.7 320.5 H ₂ O ₂ 500 μm + compound (I) ( 50 μg) 187.3 (53.3%) 104.8 (47.2%) 175.2 (50.4%) H ₂ O ₂ 500 μm + compound (I) ( 100 μg) 150.4 (68.6%) 84.4 (60.7%) 112.6 (72.1%) H ₂ O ₂ 500 μm + compound (I) (150 μg) 91.6 (92.9%) 38.6 (91.2%) 54.4 (92.3%) H ₂ O ₂ 500 μm + Compound (II) ( 50 μg) 185.7 (54%) 102.0 (49%) 170.9 (51.9%) H ₂ O ₂ 500 μm + compound (II) ( 100 μg) 146.5 (70.2%) 82.7 (61.9%) 109.4 (73.2%) H ₂ O ₂ 500 μm + compound (II) (150 μg) 90.5 (93.4%) 36.8 (92.4%) 53.6 (92.6%)

As a result of the experiment, it was confirmed that the production of PGE2, IL-6, and IL-8, which are inflammatory mediators, was remarkably reduced by the addition of N-Propylphosphate phytosphingosine compound, showing a high inhibitory effect. In particular, when treated with a concentration of 150 μg / ml, it was confirmed that more than 90% of the inhibitory effect was shown in PGE2, IL-6 and IL-8.

Experimental Example 5. Confirmation of NO secretion inhibitory effect

In order to evaluate the skin inflammation relieving effect of the N-propylphosphate phytosphingosine compound according to the present invention, the change in secretion of nitric oxide (NO) was measured.

Raw 264.7 cells, which are mouse macrophages, were added to DMEM (Dulbecco's Modified Eagle's Medium) medium with 10% FBS (fetal bovine serum), 100 units/mL penicillin, and 100 μg/mL streptomycin, and then cultured in an incubator ( 37 °C, 5% CO2).

When the cells grew to about 80% of the bottom of the 100 mm dish, lipopolysaccharide was added at a concentration of 100 ng/mL to the DMEM culture medium containing 1% FBS to induce an inflammatory response of the cells.

After adding N-Propylphosphate phytosphingosine compounds to Raw 264.7 cells by concentration and incubating for 24 hours, the culture medium was collected and NO secretion was measured with a Griess reagent system (Kim JK et al., Biochem Biophys Res Commun., 345, pp1215-1223, 2006), and the obtained results are shown in Table 3 below.

N-propylphosphate phytosphingosine concentration (μg/mL) control group 10 50 100 150 NO secretion amount
(% compared to control group) Compound (I) 100 65 48 25 10 Compound (II) 100 62 41 17 10

As shown in Table 3, when the N-propylphosphate phytosphingosine compound of the present invention was treated, NO production induced by lipopolysaccharide was reduced in a concentration-dependent manner. Through these results, when using the N-propylphosphate phytosphingosine compound of the present invention, skin inflammation can be effectively alleviated.

Experimental Example 6. Evaluation of inhibition of histamine secretion by N-propylphosphate phytosphingosine (N-Propylphosphate phytosphingosine) compound

Beta-hexosaminidase (β-hexosaminidase) is a substance constituting granules of mast cells, and histamine secretion by degranulation of mast cells is proportional to the amount of beta-hexosaminidase released. Therefore, the histamine secretion inhibitory effect of the N-Propylphosphate phytosphingosine compound was confirmed by measuring the amount of beta-hexosaminidase released in RBL-2H3 cells, a rat mast cell line.

After suspending RBL-2H3 cells in DMEM containing 10% FBS, 2×10 ⁵ cells per well were dispensed into a 24-well plate, and then sensitized with 0.5 μg/ml DNP-IgE per well and 5% CO2 Incubated overnight in an incubator. Afterwards, the cells in each well were washed twice with Siraganian buffer (119 mM NaCl, 5 mM KCl, 5.6 mM glucose, 0.4 mM MgCl2, 25 mM HEPES, 40 mM NaOH, 1 mM CaCl2, 0.1% BSA, pH 7.2) and then 37 It was pre-reacted with Siraganian buffer for 10 minutes at ° C., and after adding N-Propylphosphate phytosphingosine compound by concentration, it was reacted again for 10 minutes. Thereafter, the cells were treated with antigen (DNP-BSA, 10 μg/ml) for 30 minutes at 37°C to degranulate the cells, put them on ice for 10 minutes to terminate the reaction, and take 20 μl of the supernatant and transfer it to a 96-well plate. 1 mM p-nitrophenyl-N-acetyl- β-D-glucosaminide was added, incubated for 1 hour, stop solution (0.1 M Na2CO3/NaHCO3) was added, and absorbance was measured at 405 nm by ELISA and quantified.

As shown in Table 4 below, when the N-Propylphosphate phytosphingosine compound of the present invention is treated, β-hexosaminidase is reduced in a concentration-dependent manner, and at a concentration of 150 μg / mL, about 80% is released This suppression could be observed.

N-Propylphosphate Phytosphingosine
Concentration (μg/mL) control group 10 50 100 150 beta-hexosaminidase
Secretion amount (% compared to the control group) Compound (I) 100 75 60 35 22 Compound (II) 100 70 58 32 20

Experimental Example 7. Confirmation of skin irritation relief effect through skin patch clinical test

In order to evaluate the skin irritation relief effect of the N-propylphosphate phytosphingosine compound according to the present invention, cosmetics containing sodium dodecyl sulfate (SDS), a surfactant known as a skin irritation inducing substance, are listed in Table 5 below. It was prepared as described above, and the irritation induction and skin reactivity thereto were measured through a skin patch experiment, and the skin irritation mitigation effect by the surfactant was compared and measured.

Furtherance Formulation Example 1 (% by weight) Comparative Formulation Example 1 (% by weight) Control Example (% by weight) Compound (II) One One sodium dodecyl sulfate 2.0 2.0 sodium hyaluronate 0.5 0.5 0.5 beta glucan One One One Butylene Glycol 3 3 3 carbomer 0.3 0.3 0.3 glycerin 3 3 3 Tocopheryl Acetate 1.5 1.5 1.5 lecithin 2 2 2 MCTs 5 5 5 beeswax One One One shea butter 3 3 3 stearic acid 3 3 3 camellia oil 3 3 3 Distilled water To 100 To 100 To 100

Twenty women in their 20s and 30s who had no past history of hypersensitivity to skin irritation and no current skin disease or skin allergy symptoms were targeted.

First, the test site was wiped with 70% ethanol and then dried. 15 μg of the prepared test substance was dropped into a fin chamber (Finn chamber, 100 × 10, EPITEST, Finland), and then sealed patched on the inside of the forearm of the test subject.

The patch was applied for 24 hours, and after removing the patch, the test site was marked with a marker pen. After 1 hour and 24 hours, respectively (1 hour, 2 hours after patch removal = 24 hours, 48 hours including patch attachment), use a magnifying glass (8MC-150, DAZOR, USA) to observe the presence or absence of erythema and edema at the test site did

The skin reaction was determined according to the rules of the International Contact Dermatitis Research Group (ICDRG) (Table 6 below), and the average skin reactivity was calculated by Equation 3 below, and the results are shown in Table 7.

sign score Evaluation standard - 0.0 unresponsive ± 0.5 faint or mild erythema + 1.0 Well-defined but mild erythema, edema and papules ++ 2.0 Marked erythema, papules and vesicles +++ 3.0 Severe erythema, bulla, scab formation

<Equation 3>

Average skin reactivity = (score × number of responding subjects x 100 x 1/2) / (maximum score × total number of subjects)

division
24 hours 48 hours average skin reactivity
(n=20) ± ₊ ++ +++ ± + ++ +++ control example One One 0.83 Comparative Formulation Example 1 9 2 3 One 7.50 Formulation Example 1 6 One 2.92

As can be seen in Table 7, in the skin patch clinical trial, the control example in which only the N-propylphosphate phytosphingosine compound (II) of the present invention was added showed almost no skin irritation, and comparative formulation example 1 containing sodium dodecyl sulfate showed strong skin irritation, and Formulation Example 1 containing N-propylphosphate phytospingosine compound (II) of the present invention showed excellent irritation relief effect.

Experimental Example 8. Skin soothing effect through clinical trials

After dividing the volunteers with severe skin troubles into 30 people per evaluation group, each group used the nutritional cream of Formulation Example 2 and Comparative Formulation Example 2 in Table 8 below twice a day for 2 weeks, and the scores shown in Table 9 below Based on this, skin trouble relief and soothing effects were evaluated.

Furtherance Formulation Example 2 (% by weight) Comparative Formulation Example 2 (% by weight) Compound (II) One sodium hyaluronate 5 5 beta glucan One One butylene glycol 3 3 beta glucan 2 2 carbomer 0.3 0.3 Tocopheryl Acetate 1.5 1.5 lecithin 2 2 Aracel 165 1.5 1.5 beeswax One One shea butter 3 3 stearic acid 3 3 camellia oil 3 3 Distilled water To 100 To 100

Skin Condition Evaluation Criteria grade 1. Skin trouble relieving effect
Skin troubles such as acne, pimples, and atopy are very aggravated One Slightly aggravated skin problems such as acne, pimples, and atopy 2 Skin troubles such as acne, pimples, and atopy are the same as before use 3 Slightly improved skin troubles such as acne, pimples, and atopy 4 Skin troubles such as acne, pimples, and atopy are greatly improved 5 2. Skin soothing effect
Skin conditions such as erythema, dryness, itching, foreign body sensation, etc. are very sensitive One Slightly sensitive skin conditions such as erythema, dryness, itching, foreign body sensation 2 Skin conditions such as erythema, dryness, itchiness, and foreign body sensation are the same as before use 3 Skin conditions such as erythema, dryness, itchiness, and foreign body sensation are slightly calmed 4 Skin conditions such as erythema, dryness, itchiness, and foreign body sensation are very calmed 5

division Skin trouble relieving effect skin soothing effect Formulation Example 2 4.5 4.4 Comparative Formulation Example 2 3.2 3.1

As shown in Table 10, it can be seen that the cosmetics containing N-propylphosphate phytosphingosine are superior in skin soothing and trouble relieving effects compared to cosmetics containing nothing simple.

As described above, the N-propylphosphate phytosphingosine of the present invention inhibits the secretion of inducible nitric oxide, IL-6, IL-8, PGE ₂ and histamine that mediate skin inflammatory response and stimulation in cell experiments. It was discovered that there was an excellent effect, and the effect was confirmed through a skin patch clinical experiment, and it was proven that it was safe for human skin.

Therefore, the effect of the present invention is to provide a cosmetic composition having an anti-inflammatory and anti-irritation effect on irritation caused by cosmetic use, characterized in that it contains N-propylphosphate phytosphingosine as an active ingredient.

Having described specific parts of the present invention in detail above, it is clear that these specific techniques are merely preferred embodiments for those skilled in the art, and the scope of the present invention is not limited thereto. Accordingly, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

Claims (3)

N-Propylphosphate phytosphingosine Compound (I) or Compound (II) represented by Formula 1 below:
[Formula 1]

X = H: Compound (I)
X = OH: Compound (II)
A cosmetic composition characterized in that it contains. The method of claim 1,
The cosmetic composition is a cosmetic composition characterized in that it has a skin inflammation relief or skin irritation relief effect. The method of claim 1,
The cosmetic composition is characterized in that composed of any one formulation selected from the group consisting of emulsion, cream, essence, gel, lipstick, foundation, gel, shampoo, rinse, treatment, body cleanser, and sunscreen. Cosmetic composition.

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