JP6721310B2 - Anti-staining agent and anti-staining cosmetic or anti-skin external preparation containing the same - Google Patents

Description

TECHNICAL FIELD The present invention relates to a stain-preventing agent containing pantothenic acid and its derivative as an active ingredient, and a stain-preventing cosmetic or a stain-preventing external skin preparation containing the stain-preventing agent.

Air pollution consists of various types of chemical substances and/or xenobiotics and particles, and the main substances are smoke emitted from automobiles, thermal power plants, incinerators, fireplaces, volcanic eruptions, soil particles, etc. Emissions of carbon monoxide, sulfur oxides (sulfur dioxide, etc.), nitrogen oxides (nitrogen dioxide, etc.), hydrocarbons and nitrogen oxides, etc. Photochemical oxidants such as ozone (O3) and polycyclic aromatic hydrocarbons (PAHs) generated by the photochemical reaction of volatile organic compounds (VOC) (aldehydes such as formaldehyde) derived from combustion and volatilization from petroleum products. , PAH, dioxins, etc.), and fine particles such as asbestos derived from minerals and industrial products are widely known.

In fact, many of them are subject to regulation by the Air Pollution Control Law in Japan, and measures such as emission standards are set. However, with regard to particulate matter (PM), cross-border transportation from neighboring countries is becoming a very serious problem around Japan these days. The Air Pollution Control Law specifies "particulate matter in automobile exhaust gas" as a particulate matter that is subject to legal regulations. It is used only as a substance.

As for the effects of various types of chemical substances and/or xenobiotics and particles that cause the air pollution on the human body, the effects on the respiratory system have been widely discussed because they may be directly inhaled. On the other hand, since the skin is the outermost organ in the living body and is constantly exposed to the outside world, it has the potential to come into direct contact with air pollutants as in the respiratory system.

By the way, it has been reported that air pollutants such as tobacco smoke are associated with the formation of wrinkles on the skin, a decrease in transparency, or psoriasis through the generation of nitrogen oxides or reactive oxygen species. Further, it is known that ozone induces dysfunction of the stratum corneum through the production of lipid peroxide, or induces cyclooxygenase-2 (COX-2) which is an inflammatory marker (Non-patent Document 1). Moreover, while heavy metals are required for vital maintenance as essential nutrients, toxic effects can occur when they are not in physiological concentrations, ie when exposed to excessive amounts of metals in the environment. The amount of metals present in the atmosphere is increasing, resulting in increased levels of heavy metals in the body through ingestion of contaminated food and exposure to metals in the atmosphere, resulting in damage to the tertiary and quaternary structure of proteins. May give. As a result, the catalytic activity is reduced, and the damaged protein may serve as an antigen to cause an immune reaction. Furthermore, some heavy metals have been shown to penetrate and accumulate in the skin (Non-Patent Document 2). Moreover, many organic compounds, especially many PAHs, are adsorbed on the surface of the particulate matter. These polycyclic aromatic hydrocarbons adsorbed on the surface of the particles and the dust carried by the urban air can penetrate the skin tissue, where they can be biologically transformed. Metabolism in these livers is well described in the literature, leading to the formation of monohydroxylated metabolites (detoxification pathway), epoxides and diol epoxides (toxication pathway). Similar phenomena can be observed in the skin, and it has been reported that CYP over-induction by PAHs triggers skin troubles, and these compounds have carcinogenic and immunogenic effects on the skin. It is known (Non-Patent Document 3).

Furthermore, metabolites of CYP1 of PAHs in epidermal cells are known to excessively induce CD86 expression in immune cells (THP-1) (Non-Patent Document 4). The expression of CD86 in THP-1 is generally used as a marker for the h-CLAT (human Cell Line Activation Test) method, which is an alternative method for the skin sensitization test, and a chemical substance that induces CD86 expression to 150% or more is sensitizing. Since it is judged to be present, it can be said that overinduction of CD86 expression is an undesirable situation in the skin.

Valacchi G, Ann NY Acad Sci. 2012 Oct;1271:75-81. Lansdown AB. Crit Rev Toxicol. 1995;25(5):397-462. Review Wu Z. Exp Dermatol. 2014 Apr;23(4):260-5. Hennen J. Toxicol Sci. 2011 Oct;123(2):501-10.

The present invention provides a pollution preventive agent for preventing a pollutant that causes air pollution from causing a skin disorder, and a pollution preventive cosmetic or a skin prevention external preparation containing the pollution preventive agent. It is an issue.

The present inventors have an effect of alleviating cytotoxicity caused by contaminants in epidermal cells and an effect of suppressing CYP1 excessive induction, and further suppress excessive induction of immune cells induced by CYP1 metabolites in epidermal cells. As a result of diligent research on the antifouling agent characterized by the above, it was found that pantothenic acid and its derivatives show remarkable usefulness, and the present invention has been completed.

The conventional anti-pollution agents are mainly anti-adhesion and permeation agents for the skin that pollute pollutants that cause air pollution, or detergents, but have no effect on the pollutants that have penetrated into the skin. The present inventors have paid attention to the mechanism by which contaminants penetrating the inside of the skin cause skin troubles in epidermal cells, and the remarkable effects of pantothenic acid and its derivatives against the cytotoxicity-relieving effect and the suppression of CYP1 over-induction effect. From the finding of usefulness, it is possible to provide a cosmetic composition for preventing contamination and an external preparation for skin which are effective against skin troubles caused by contaminants.

The antifouling agent according to the present invention contains pantothenic acid and its derivative as an active ingredient, and when applied to the skin surface as a cosmetic and a skin external preparation containing the same, an effect of preventing skin damage due to contaminants. Is expressed.

As pantothenic acid and its derivative used in the present invention, pantothenic acid and its salt, pantothenol, ethyl dicarboethoxy pantothenate, pantheteine sulfonic acid and its salt, pantolactone, panthenyl ethyl ether, panthenyl ethyl ether acetate, Panthenyl triacetate, pantethine, pantothenic acid polypeptide, panthenyl hydroxypropyl steardimonium chloride, dimethiconol pantethenol and the like can be used alone or in combination.

The amount of the anti-staining agent to be added to the anti-staining cosmetic and anti-staining external preparation for skin is different depending on the use, the dosage form, the purpose of addition and the like, and is not particularly limited, but in general, pantothenic acid The amount of the derivative and its derivative in the external preparation is preferably 0.001 to 10.0% by mass, more preferably 0.01 to 5.0% by mass.

An existing anti-inflammatory agent, rough skin preventive/ameliorating agent, and pigmentation preventive/improving agent can be blended with the anti-contaminating cosmetics and anti-staining external preparations containing the anti-staining agent. The combined use of these components brings about a synergistic effect of the present effect and does not impair the present effect.

The cosmetics and skin external preparations containing the present air pollution inhibitor include hydrocarbons such as liquid paraffin, vegetable oils and fats, and waxes as components to be added to cosmetics, quasi-drugs, etc. within a range that does not impair the effects of the present invention. , Synthetic ester oils, silicone oil phase components, fluorine oil phase components, higher alcohols, fatty acids, thickeners, UV absorbers, powders, pigments, coloring materials, anionic surfactants, Cationic surfactant, nonionic surfactant, amphoteric surfactant, polyhydric alcohol, sugar, polymer compound, physiologically active ingredient, transdermal absorption enhancer, solvent, antioxidant, perfume, preservative, etc. Can be blended.

The dosage form of the anti-staining cosmetics and the anti-staining external preparations containing the anti-staining agent is arbitrary, such as lotions, lotions, emulsions, creams, packs, ointments, dispersions, solids and mousses. It can take any dosage form. In addition to cosmetics, it can be preferably used for external skin preparations, pharmaceutical ointments and the like.

The present invention will be specifically described below with reference to examples, but the technical scope of the present invention is not limited thereto.

The evaluation was carried out using Standard Reference Materials (SRM) 1975 obtained from National Institute of Standards and Technology (NIST) as a model compound of the pollutant. Details of SRM1975 are available from the NIST website.

<Example 1>
Mitigating action on epidermal cell cytotoxicity caused by contaminants 1. Outline of test The mitigating action of various pantothenic acids and their derivatives on epidermal cell cytotoxicity caused by contaminant exposure was evaluated.
2. Experimental method The samples shown in Table 1 and SRM1975 were added to the epidermal cells and cultured for 24 hours. Then, the survival rate of the epidermal cells was detected by the MTT method, and the relaxation effect of each sample was evaluated by the survival rate with respect to the sample and SRM1975 untreated cells.

3. Results The results are shown in Table 1. The survival rate of epidermal cells treated with a mixture of various pantothenic acid and its derivative 0.06-0.50 mmol/L and SRM1975 was compared with that of SRM1975 only (various pantothenic acid And the derivative thereof was treated with 0.00 mmol/L), the cell survival rate was significantly improved as compared with the survival rate of the epidermal cells. In other words, all pantothenic acid and its derivatives were found to have a palliative effect on cell damage due to SRM1975 treatment. Among the pantothenic acid and its derivatives, ethyl dicarboethoxy pantothenate exhibited a remarkable effect.

<Example 2>
Inhibitory effect on CYP1 excess induction of epidermal cells by contaminants 1. Outline of test The inhibitory effects of various pantothenic acids and their derivatives on CYP1 excess induction of epidermal cells by exposure to contaminants were evaluated.
2. Experimental method The samples shown in Table 2 and SRM1975 were added to the epidermal cells and cultured for 24 hours. Then, the gene expression of CYP1 was evaluated by the Realtime RT-PCR method (Applied Biosystem). Cyclophilin was used as an internal standard substance, and analysis was carried out by the ΔΔCT method (Experimental Medicine, Separate Volume, Real-Time PCR Experiment Guide, Well-known from Principles, Yodosha Co., Ltd., p.34-38). The CYP1 induction inhibitory effect of each sample was evaluated by the expression ratio with respect to the sample and SRM1975 untreated cells.
3. Results The results are shown in Table 2. In all of the pantothenic acid and its derivatives, an inhibitory action against CYP1 by SRM1975 treatment was observed.

<Example 3>
Inhibition of immune hyper-response in immune cells by metabolites of contaminants in epidermal cells 1. Outline of test Dicarboethoxypantothenic acid against immune hyper-response in immune cells by CYP1 metabolites of epidermal cells by exposure to contaminants The inhibitory effect of ethyl was evaluated.

2. Experimental Method The samples shown in Tables 3 and 4 and SRM1975 were added to the three-dimensional cultured epidermal model, and the cells were cultured for 48 hours. Then, the survival rate of the three-dimensional cultured epidermis model was detected by the Alamar Blue method (Invitrogen), and the cytotoxicity-reducing effect of each sample in the three-dimensional cultured epidermis model was evaluated by the survival rate of the sample and the SRM1975 untreated model. ..
Further, at this time, the sample and SRM1975 were added, and the culture supernatant obtained by culturing the three-dimensional culture epidermis model for 48 hours was collected, and the immune cells (THP-1) were dispersed in the culture supernatant and cultured for 24 hours. The number of CD86-positive cells in the cultured immune cells was measured by the flow cytometry method. At the same time, Mouse IgG was used as an internal standard, and the survival rate of immune cells was measured by the PI method.

3. Results The results of the survival rate of the three-dimensional cultured epidermis model are shown in Table 3. The survival rate of the three-dimensional cultured epidermal model treated with a mixture of ethyl dicarboethoxy pantothenate 2% and SRM1975 was compared with that of SRM1975 only (dicarbethoxypantothene). The cell viability was improved as compared with the viability of the three-dimensional cultured epidermis model treated with ethyl acetate (0%). That is, also in the three-dimensional cultured epidermis model, similar to the epidermal cells, the relaxing effect of ethyl dicarboethoxypantothenate on the cell damage caused by SRM1975 treatment was observed.

Further, Table 4 shows the results of the inhibitory action against CD86 over-induction by CYP1 metabolites. Culture supernatant of a three-dimensional cultured epidermal model treated with a mixture of ethyl dicarboethoxypantothenoate 2% and SRM1975 for comparison with CD86 of immune cells treated with a culture supernatant of a three-dimensional cultured epidermal model without SRM1975 CD86 of immune cells treated with S. cerevisiae was significantly reduced in CD86 induced excessively in the three-dimensional cultured epidermal model treated with SRM1975 only (0% ethyl dicarboethoxypantothenate). That is, in immune cells, the inhibitory effect of ethyl dicarboethoxypantothenate on the induction of CD86 excess by SRM1975 treatment was observed.

The application examples of the anti-staining cosmetic and anti-staining external preparations containing the anti-staining agent of the present invention are shown below. The blending amount is% by mass. In all of Examples 4 to 10, the effect of suppressing epidermal cell damage due to exposure to pollutants was confirmed by the evaluation method described in Examples 1 to 3.

<Example 4>
Antifouling lotion Ethyl dicarboethoxy pantothenate 0.01 (mass%)
Squalane 0.20
Decaglyceryl monolaurate 2.00
Sodium hyaluronate 0.20
1,3-butylene glycol 3.00
Ethyl alcohol 10.00
Preservative Suitable amount Perfume Suitable amount Purified water Balance (preparation method) Mix at 50°C until uniform, cool to room temperature, and then complete the preparation.

<Example 5>
Emulsion oil phase for pollution prevention Ethyl dicarboethoxy pantothenate 0.3 (mass%)
Pantothenol 0.3
d-δ-tocopherol 0.1
Squalane 5.0
Cetyl 2-ethylhexanoate 5.0
Dimethyl polysiloxane (100 mPa·s) 0.5
Cetyl palmitate 0.5
Behenyl alcohol 1.5
Stearic acid 0.5
Lipophilic glyceryl monostearate 1.0
Monostearic acid POE (20) sorbitan 1.0
Teoroleic acid POE (40) sorbitan 1.5
Water phase Propylene glycol 7.0
Xanthan gum 0.1
Preservative Appropriate amount Purified water Balance (preparation method) Dissolve oil phase and water phase uniformly at 80°C. The aqueous phase is added while stirring the oil phase, and the mixture is stirred until it becomes uniform and then cooled to room temperature to complete the preparation.

<Example 6>
Antifouling cream oil phase Ethyl dicarboethoxy pantothenate 0.5 (mass%)
Squalane 3.0
Behenyl alcohol 4.0
Vaseline 3.0
Liquid paraffin 15.0
Water phase POE(20) sorbitan monostearate 3.0
1,3-butylene glycol 3.0
Preservative Suitable amount Perfume Suitable amount Purified water Balance (preparation method) Dissolve the oil phase and the water phase uniformly at 80°C. The aqueous phase is added while stirring the oil phase, and the mixture is stirred until it becomes uniform, and then cooled to room temperature to complete the preparation.

<Example 7>
Antifouling beauty liquid oil phase Pantothenol 0.1 (mass%)
Squalane 1.0
Behenyl alcohol 4.0
Vaseline 3.0
Liquid paraffin 15.0
Water phase POE(20) sorbitan monostearate 3.0
Decaglyceryl monolaurate 1.0
Xanthan gum 0.1
1,3-butylene glycol 10.0
Preservative Suitable amount Perfume Suitable amount Purified water Remainder (preparation method) An oil-in-water emulsion composition was prepared by a conventional method.

<Example 8>
Beauty oil for prevention of pollution Ethyl dicarboethoxy pantothenate 3.0 (mass%)
Isocetyl myristate 10.0
Jojoba oil 5.0
Natural vitamin E 0.1
Squalane Remainder (preparation method) All components were heated and mixed until uniform, to prepare.

<Example 9>
Anti-contamination sunscreen cream oil phase Ethyl dicarboethoxy pantothenate 0.5 (mass %)
Pantothenol 0.5
Liquid paraffin 7.0
Decamethylcyclopentasiloxane 3.0
Cetyl alcohol 4.0
Condensed hexaglyceryl ricinoleate 0.5
POE (20) cetyl ether 1.0
Octyl paramethoxycinnamate 7.0
Powder phase Titanium oxide 3.0
Water phase Sodium cetyl sulfate 1.0
Stearoylmethyl taurine sodium 0.3
1,3-butylene glycol 5.0
Xanthan gum 0.3
Preservative Appropriate amount Purified water Balance (preparation method) Dissolve oil phase and water phase uniformly at 80°C. After the powder phase is added to the oil phase, the aqueous phase is added while stirring the oil phase, and the mixture is stirred until it becomes uniform and then cooled to room temperature to complete the preparation.

<Example 10>
Scalp beauty essence oil phase for prevention of pollution Ethyl dicarboethoxy pantothenate 0.5 (mass%)
Pantothenol 0.5
Cetyl phosphate 0.7
Cetanol 0.5
Jojoba seed oil 3.5
Methylheptyl laurate 2.0
Water phase Arginine 0.55
1,3-butylene glycol 5.0
Phenoxyethanol 0.4
Carbomer 0.2
Preservative Appropriate amount Purified water Balance (preparation method) Dissolve the oil phase and water phase uniformly at 80°C. Add the aqueous phase while stirring the oil phase, stir until uniform, and then cool to room temperature to complete the preparation.

Claims (5)

An agent for preventing skin contamination by polycyclic aromatic hydrocarbons, which contains ethyl dicarboethoxy pantothenate as an active ingredient. The anti-fouling agent according to claim 1, wherein ethyl dicarboethoxypantothenate exhibits a cytotoxicity-reducing effect of polycyclic aromatic hydrocarbons on epidermal cells. The antifouling agent according to claim 1, wherein ethyl dicarboethoxypantothenate suppresses excessive induction of CYP1 in epidermal cells. The antifouling agent according to claim 1, wherein ethyl dicarboethoxypantothenate suppresses an excessive immune response caused by metabolites of polycyclic aromatic hydrocarbons in epidermal cells. A stain-preventing cosmetic or a stain-preventing skin external preparation, which comprises the stain-preventing agent according to any one of claims 1 to 4.