Topical skin components

Abstract

[Problem] To provide a skin care composition that effectively inhibits tyrosinase activity. [Solution] A skin care composition comprising (A) a cyclic carboxamide derivative having a specific structure or a salt of the derivative, and (B) an organic acid having a specific structure or a salt of the acid.

Description

[Technical Field]

[0001] The present invention relates to a topical skin composition comprising a cyclic carboxamide derivative having a specific structure or a salt thereof, and an organic acid having a specific structure or a salt thereof. [Background technology]

[0002] It is known that cyclic carboxamide derivatives having a specific structure have the effect of inhibiting heparanase activity. It has been proposed to incorporate them into cosmetics, for example, as wrinkle-improving agents or as whitening agents effective in preventing or suppressing pigmentation such as age spots (Patent Document 1).

[0003] A composition containing a combination of 1-piperidinepropionic acid and pyridinecarboxamide has been proposed for use as a skin whitening agent (Patent Document 2). [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] International release 2011 / 040496 [Patent Document 2] International release 2019 / 029922

[0005] Pigmentation in the epidermis of the skin is caused by melanin accumulation, and it is believed that tyrosinase activity in melanocytes plays a significant role in this. Surprisingly, the inventors' research has revealed that compositions comprising a combination of a cyclic carboxamide derivative having a specific structure and an organic acid or a salt thereof having a specific structure effectively inhibit tyrosinase activity. The present invention is based on these findings.

[0006] The present invention provides the following: [1](A) A cyclic carboxamide derivative represented by formula (a) or a salt thereof [ka] (In the formula, R 1 This is a hydrocarbon group having 1 to 6 carbon atoms, which may be substituted with a hydroxyl group, or a hydrogen atom. X is -CH2- or -N(R 2 )- and here, R 2 is a hydrocarbon group having 1 to 6 carbon atoms, which may be substituted with a hydroxyl group, or a hydrogen atom, and na is an integer between 1 and 3), and (B) Organic acids or salts represented by formula (b) [ka] (In the formula, nb is an integer between 2 and 5.) A topical skin composition comprising [the specified ingredient]. [2] In formula (a) of component (A), R 1 However, it is a hydroxyalkyl group having 1 to 3 carbon atoms. X is -CH2- or -NH-, and The composition according to [1], wherein na is 1. [3] The composition according to [1] or [2], wherein component (A) is 1-(2-hydroxyethyl)-2-imidazolidinone. [4] The composition according to any one of [1] to [3], wherein the amount of component (A) is 10 to 50 mg / mL. [5] The composition according to any one of [1] to [4], wherein component (B) is 1-piperidinepropionic acid. [6] The composition according to any one of [1] to [5], wherein the amount of component (B) is 5 to 40 mg / mL. [7] A whitening cosmetic composition as described in any of [1] to [6]. [8] A composition according to any one of [1] to [7] that has tyrosinase inhibitory activity.

[0007] According to the present invention, a topical skin composition that effectively inhibits tyrosinase activity can be provided. Specific description of the invention

[0008] The present invention relates to a topical skin composition (hereinafter sometimes referred to as the composition) comprising (A) a cyclic carboxamide derivative having a specific structure or a salt thereof, and (B) an organic acid having a specific structure or a salt thereof. Pigmentation such as freckles, chloasma, and dullness is generally often caused by melanin accumulation, and it is considered that the tyrosinase activity in melanocytes greatly affects the accumulation of melanin in the epidermis. The composition according to the present invention has tyrosinase inhibitory activity and can effectively inhibit tyrosinase activity. As a result, the production of melanin can be suppressed, and pigmentation can be prevented and suppressed. Therefore, the composition according to the present invention is preferably a whitening cosmetic. In this specification, "whitening" mainly means suppressing the production of melanin and preventing freckles, chloasma, dullness, etc. In a preferred embodiment, the composition according to the present invention is a tyrosinase inhibitor.

[0009] (A) Cyclic carboxamide derivative or a salt thereof The composition according to the present invention comprises a cyclic carboxamide derivative represented by the formula (a) or a salt thereof (hereinafter sometimes referred to as component (A). The same applies to other components). [Chemical formula] In the formula, R 1 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom, X is -CH2- or -N(R 2 )-, where R 2 is a hydrocarbon group having 1 to 6 carbon atoms which may be substituted with a hydroxyl group, or a hydrogen atom, and na is an integer of 1 to 3. The above hydrocarbon group is not particularly limited and may be, for example, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, a cycloalkylalkyl group, a haloalkyl group, an alkoxyalkyl group, an alkoxycarbonylalkyl group, and is preferably an alkyl group.

[0010] In a preferred form, in formula (a) of component (A), R 1 is a hydroxyalkyl group having 1 to 3 carbon atoms, X is -CH2- or -NH-, and na is 1. Specific examples of the cyclic carboxamide derivative represented by formula (a) include, for example, the following.

Chemical formula

[0011] Component (A) may be a salt of the cyclic carboxamide derivative represented by formula (a). The type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt. Examples of inorganic salts include hydrochloride, sulfate, phosphate, hydrobromide, sodium salt, potassium salt, magnesium salt, calcium salt, magnesium salt, ammonium salt, etc. Examples of organic salts include acetate, lactate, maleate, fumarate, tartrate, methanesulfonate, p-toluenesulfonate, triethanolamine salt, amino acid salt, etc.

[0012] One or more kinds of component (A) can be blended. The blending amount of component (A) is preferably 10 to 50 mg / mL, more preferably 15 to 40 mg / mL, and even more preferably 25 to 35 mg / mL with respect to the total amount of the composition.

[0013] (B) Organic acid or its salt The composition according to the present invention comprises an organic acid represented by formula (b) or a salt thereof. [ka] In the formula, nb is an integer between 2 and 5. This organic acid is classified into 1-piperidinepropionic acid (n=2), 4-(1-piperidinyl)butanoic acid (n=3), 5-(1-piperidinyl)pentanoic acid (n=4), and 6-(1-piperidinyl)hexanoic acid (n=5) depending on the number of n, but of these, 1-piperidinepropionic acid is preferred.

[0014] Component (B) may be a salt of an organic acid represented by formula (b). The type of salt is not particularly limited as long as it is a pharmacologically acceptable salt, and may be an inorganic salt or an organic salt. Examples of inorganic salts include hydrochloride, sulfate, phosphate, hydrobromide, sodium salt, potassium salt, magnesium salt, calcium salt, and ammonium salt. Examples of organic salts include acetate, lactate, maleate, fumarate, tartrate, citrate, methanesulfonate, p-toluenesulfonate, triethanolamine salt, diethanolamine salt, and amino acid salt.

[0015] (B) One or more components may be included. The amount of component (B) is preferably 5 to 40 mg / mL, more preferably 10 to 30 mg / mL, and even more preferably 15 to 25 mg / mL, relative to the total amount of the composition.

[0016] The ratio of component (A) to component (B) ((A) / (B)) is preferably 0.25 to 10, and more preferably 0.5 to 5, in terms of mass ratio.

[0017] (C)Water The cosmetic composition according to the present invention may contain (C) water. As the water, water used in cosmetics, quasi-drugs, etc., can be used, for example, purified water, ultrapure water, ion-exchanged water, tap water, etc.

[0018] In addition to the above-mentioned components, the cosmetic composition according to the present invention may contain any other components commonly used in cosmetics and pharmaceuticals. Examples of optional components include humectants, lower alcohols, thickeners, surfactants, metal ion chelating agents, neutralizing agents, pH adjusters, antioxidants, preservatives, pharmaceuticals, UV absorbers, powder components, oily components, fragrances, etc., and one or more of these may be included as long as they achieve the effects of the present invention.

[0019] The dosage form of the composition according to the present invention is not particularly limited, and can take any form such as a solution system, solubilized system, emulsified system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, ointment, gel, aerosol, etc. Furthermore, the form of use is not particularly limited, and can take any form such as a lotion, emulsion, cream, essence, jelly, gel, ointment, pack, mask, foundation, etc. The composition according to the present invention can be manufactured according to conventional methods. [Examples]

[0020] The present invention will be specifically described based on the following examples, but the present invention is not limited to these examples.

[0021] [Preparation of composition] To ultrapure water, 1-(2-hydroxyethyl)-2-imidazolidinone as component (A) and 1-piperidinepropionic acid as component (B) were added in the amounts shown in Table 1, and the mixture was stirred to prepare the compositions of Example 101, Comparative Examples 101 and 102.

[0022] [Evaluation of tyrosinase inhibitory activity] The effects of the compositions of Example 101 and Comparative Examples 101 and 102 on tyrosinase activity using dihydroxyphenylalanine (DOPA) as a substrate were evaluated using the following procedure. 20 μL of each example and comparative example composition or control (ultrapure water was used for the control), 40 μL of a 40 units / mL tyrosinase (CAS No. 9002-10-2, Sigma-Aldrich) solution, and 100 μL of a 100 mM phosphate buffer (pH 6.8) were added to a 96-well plate (Corning) and incubated at 23 °C for 3 minutes. For the blank, 100 mM phosphate buffer was used instead of the tyrosinase solution. Three wells were used for each treatment group. After 3 minutes, 50 μL of a 2.5 mM 3,4-L-dihydroxyphenylalanine (L-DOPA, CAS No. 59-92-7, Wako) solution was added, the 96-well plate was shaken at 270 rpm for 10 seconds, and the absorbance at 490 nm (OD 490 ) was measured using a microplate reader (SPARK 10M, TECAN). The measured plate was incubated at 23 °C for 10 minutes, and after 10 minutes, the absorbance at 490 nm (OD 490 ) was measured. The tyrosinase inhibition activity rates of the examples and comparative examples were calculated by the following formula. Tyrosinase inhibition activity rate (%) = 100 - [{(As10 - Ab10) - (As0 - Ab0)} / (Ac10 - Ac0) × 100] In the formula, Ab0: OD of the blank before incubation 490 Ab10: OD of the blank after incubation 490 Ac0: OD of the control before incubation 490 Ac10: OD of the control after incubation 490 As0: OD of each example and comparative example composition before incubation 490 As10: OD of each example and comparative example composition after incubation 490 That is. The obtained results were described in Table 1.

[0023] [Significance test] For each evaluation, significance testing was performed using an unpaired t-test against the control and each example and comparative composition. All tests were two-sided, with a significance level of less than 5%. The p-values ​​are shown in Table 1. [Table 1]

[0024] [Prescription Examples 1-14] The following table shows examples of formulations of compositions according to the present invention. The values ​​in the table represent mass percent. [Table 2] [Table 3] [Table 4] [Table 5] [Table 6] [Table 7] [Table 8]

Claims

1. (A) 1-(2-hydroxyethyl)-2-imidazolidinone or a salt thereof, and (B) 1-Piperidinepropionic acid or its salt It includes, A skin whitening cosmetic, a composition for external use on the skin.

2. The composition according to claim 1, wherein the amount of component (A) is 10 to 50 mg / mL.

3. The composition according to claim 1 or 2, wherein the amount of component (B) is 5 to 40 mg / mL.

4. The composition according to claim 1 or 2, having tyrosinase inhibitory activity.

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