Topical preparations

Abstract

Crystallization of tranexamic acid can be inhibited by preparing an external preparation containing (A) one or more selected from tranexamic acid, tranexamic acid derivatives, and salts thereof, and (B) one or more selected from arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, derivatives thereof, and salts of these and their derivatives.

Description

Technical Field

[0001] The present invention relates to an external preparation containing tranexamic acid.

Background Art

[0002] Tranexamic acid has a hemostatic effect and an anti-inflammatory effect and is widely used in dentifrices, pharmaceuticals, etc. It also has an effect of improving rough skin and a whitening effect and is used as an external preparation for skin or hair such as cosmetics.

[0003] However, while tranexamic acid is water-soluble, it is highly crystalline, and there is a problem that crystals are easily precipitated due to evaporation of moisture. As a method for suppressing crystallization of such tranexamic acid, a method of using phytic acid (Patent Document 1: JP-A-2018-48097), polyhydroxy acid (Patent Document 2: JP-A-2013-121955), etc. in combination has been proposed. However, a method having a more excellent effect of suppressing crystallization of tranexamic acid has been desired.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] The present invention has been made in view of the above circumstances, and an object thereof is to provide an external preparation having an effect of suppressing crystallization of tranexamic acid.

Means for Solving the Problems

[0006] As a result of diligent research to achieve the above objective, the inventors discovered that a remarkable effect in inhibiting the crystallization of tranexamic acid can be obtained by using a specific amino acid in combination, and thus the present invention was conceived.

[0007] Accordingly, the present invention provides the following topical preparation. Hereinafter, cosmetic ingredient names may be used as ingredient names. 1. (A) One or more selected from tranexamic acid, tranexamic acid derivatives and salts thereof, and (B) One or more selected from arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, derivatives thereof, and salts thereof and their derivatives. A topical preparation containing [ingredient]. 2. The topical preparation according to claim 1, wherein component (B) is one or more selected from arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, theanine, pyrrolidone carboxylic acid, and salts thereof. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide a topical preparation that has a remarkable effect in inhibiting the crystallization of tranexamic acid. As a result, the effects of tranexamic acid can be fully exerted, and the appearance of the topical preparation is also good, as is the user experience. [Brief explanation of the drawing]

[0009] [Figure 1] These are photographs taken after 24 hours of storage at room temperature in a crystallization inhibition test of tranexamic acid with 0.5% by mass, 0.25% by mass, 0.125% by mass, 0.16% by mass of phytic acid, and a blank. [Modes for carrying out the invention]

[0010] The present invention will be described in detail below. [(A) component] Component (A) is one or more selected from tranexamic acid, tranexamic acid derivatives, and salts thereof, and can be used alone or in appropriate combinations of two or more. Tranexamic acid is trans-4-aminomethylcyclohexane-1-carboxylic acid. Examples of tranexamic acid derivatives include ester derivatives such as tranexamic acid cetyl ester and amide derivatives such as tranexamic acid methylamide. Salts are not particularly limited and include, for example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, metal salts such as aluminum, iron, and zinc, and organic amine salts such as ammonium, monoethanolamine, diethanolamine, triethanolamine, and stearylamine.

[0011] (A) The content of component is not particularly limited, but is preferably 1 to 5% by mass in the topical preparation, and more preferably 1 to 2% by mass.

[0012] [(B) Component] (B) Component is one or more selected from arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, derivatives thereof, and salts thereof and their derivatives, and can be used alone or in appropriate combinations of two or more.

[0013] The above-mentioned arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, and γ-aminobutyric acid (GABA) are amino acids, and may be D-isomers, L-isomers, or DL-isomers. Examples of derivatives of these include ester derivatives in which the hydrogen atoms in the amino acid are substituted with alkyl groups, alkenyl groups, aryl groups, etc.; ester derivatives in which the hydrogen atoms of the hydroxyl group are substituted with acyl groups; ether derivatives in which the hydrogen atoms of the hydroxyl group are substituted with alkyl groups, alkenyl groups, aryl groups, etc.; amide derivatives in which the hydrogen atoms of the amino group are substituted with acyl groups; and amine derivatives in which the hydrogen atoms of the amino group are substituted with alkyl groups, alkenyl groups, aryl groups, etc. Specifically, examples include theanine and pyrrolidone carboxylic acid, which are derivatives of glutamic acid.

[0014] The salts of the above amino acid salts and amino acid derivatives are not particularly limited, and examples thereof include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, metal salts such as aluminum, iron, and zinc, and organic amine salts such as ammonium, monoethanolamine, diethanolamine, triethanolamine, and stearylamine.

[0015] As the component (B), arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, theanine, pyrrolidone carboxylic acid, and salts thereof are preferable from the viewpoint of the crystallization inhibitory effect of tranexamic acid.

[0016] Combinations of glutamic acid or its salt and γ-aminobutyric acid or its salt, and combinations of γ-aminobutyric acid or its salt and theanine are preferable because a synergistic effect of the crystallization inhibitory effect of tranexamic acid can be obtained.

[0017] The content of the component (B) is not particularly limited, but is preferably 0.05 to 5% by mass, more preferably 0.125 to 2% by mass, and still more preferably 0.25 to 1% by mass in the external preparation. By setting it within this range, the crystallization inhibitory effect of tranexamic acid is further improved.

[0018] Particularly in the case of the following components or their salts, the following ranges are particularly preferable. Arginine or its salt: 0.5 to 2% by mass Aspartic acid: 0.125 to 1% by mass Glutamic acid: 0.125 to 1% by mass Glycine: 0.75 to 1.25% by mass Proline: 1 to 2% by mass Serine: 0.25 to 1% by mass [[ID=3!]] Threonine: 0.5 to 1% by mass Theanine: 0.125 to 0.25% by mass γ-Aminobutyric acid: 0.125 to 0.25% by mass Pyrrolidone carboxylic acid: 0.25 to 0.5% by mass

[0019] The mass ratio of component (A) to component (B), represented as (A):(B), is preferably 20:1 to 0.5:1, more preferably 16:1 to 1:1, and even more preferably 8:1 to 2:1. This range further enhances the crystallization inhibitory effect of tranexamic acid.

[0020] [Optional ingredients] The topical preparation of the present invention may contain appropriate amounts of ingredients commonly used in topical preparations, as long as they do not impair the effects of the present invention. Examples of such ingredients include functional ingredients such as whitening agents, anti-aging agents, moisturizers, preservatives, antibacterial agents, enzymes, and plant extracts, as well as oils, surfactants, fragrances, pigments, pH adjusters, and purified water. These can be used individually or in appropriate combinations of two or more ingredients in appropriate amounts.

[0021] In particular, it is preferable to incorporate a polyhydric alcohol into the topical preparation of the present invention. The polyhydric alcohol can be used alone or in appropriate combinations of two or more types. Examples of polyhydric alcohols include isopentyl diol, ethyl hexanediol, caprylyl glycol, glycol, (C15-18) glycol, (C20-30) glycol, glycerin, diethylene glycol, diglycerin, dithiaoctanediol, dipropylene glycol, thioglycerin, 1,10-decanediol, decylene glycol, triethylene glycol, trimethylhydroxymethylcyclohexanol, phytantriol, phenoxypropanediol, 1,2-butanediol, 2,3-butanediol, butylethylpropanediol, 1,3-butylene glycol, BG, PG, 1,2-hexanediol, hexylene glycol, pentylene glycol, methylpropanediol, mentanediol, lauryl glycol, and the like.

[0022] When polyhydric alcohols are included, their content is preferably 1.0 to 30.0% by mass in the topical preparation, and more preferably 2.0 to 30.0% by mass.

[0023] The topical preparation is not particularly limited to pharmaceuticals, quasi-drugs, cosmetics, etc. It is especially suitable for topical preparations for the skin and hair. The skin is not particularly limited to the face, scalp, arms, and other parts of the body, but does not include the oral cavity. The form of the topical preparation is not particularly limited and can be a liquid, suspension, emulsion, cream, ointment, gel, lotion, aerosol, etc. Forms that are expected to have an inhibitory effect on the crystallization of tranexamic acid include liquids and lotions.

[0024] When used as an external preparation, particularly as an external preparation for quasi-drugs or cosmetics, examples of applications include basic cosmetics such as lotions, emulsions, creams, gels, serums, sunscreens, packs, masks, hand creams, body lotions, and body creams; skin cleansers such as facial cleansers, makeup removers, and body shampoos; scalp and hair cosmetics such as shampoos, conditioners, and treatments; and makeup cosmetics such as foundations, lipsticks, and mascaras.

[0025] The pH of the topical preparation is not particularly limited, but is preferably 3 to 8 at 25°C, and more preferably 5.0 to 7.0.

[0026] [Method for inhibiting the crystallization of tranexamic acid] The present invention provides a method for inhibiting the crystallization of tranexamic acid, comprising (A) a topical preparation containing one or more selected from tranexamic acid, tranexamic acid derivatives, and salts thereof, and (B) one or more selected from arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, γ-aminobutyric acid, derivatives thereof, and salts thereof and their derivatives. Alternatively, a tranexamic acid crystallization inhibitor containing the above components (A) and (B) can also be used. The preferred components, amounts, etc., are the same as described above. [Examples]

[0027] The present invention will be specifically described below with reference to examples and comparative examples, but the present invention is not limited to the following examples. In the following examples, unless otherwise specified, "%" in the composition indicates mass%, and ratios indicate mass ratios. The amounts of each component in the table are the amounts converted to pure content.

[0028] Crystallization inhibition tests were conducted on the following components at the concentrations indicated in the table. The results are also shown in the table. [Example of test: Inhibition of tranexamic acid crystallization] (1) Test sample (pH 3-8) A composition with the following composition was prepared. Tranexamic acid 2% 1,3-Butylene glycol 30% Sample Table: Concentration Purified water remainder Total 100%

[0029] (2) Test method The above composition was added to the following plate at a rate of 3.0 g / well, stored at room temperature for 24 hours, and then image analysis was performed using the method described in (3) below. plate Manufactured by STEM Co., Ltd. Material: PS (Polystyrene) Plate size: 128 x 86 x 20 mm Model number: 6 holes (flat bottom) Well diameter × height (mm): φ33.5 × 16.7

[0030] (3) Image analysis Image analysis Scanner: Docu Center-IV C5575 (manufactured by Fuji Xerox) Image capture resolution: 300dpi Image analysis software: ImageJ (ver. 1.50i) The area inside the image well was selected in a circular shape using the Oval tool, and the Mean gray value was measured using Analyze / Measure.

[0031] (4) Based on the Mean gray value results, the crystallization inhibitory effect of tranexamic acid is shown according to the following criteria. A lower value indicates a higher crystallization inhibitory effect of tranexamic acid. +++: Less than 20 ++: 20 or more, less than 40 +: 40 or more, less than 60 -: 60 or more

[0032] The following are abbreviations. Ala:L-alanine Arg: L-arginine Asp: L-aspartic acid Cys:DL-Cysteine Glu: L-glutamic acid Gly: L-glycine His: L-histidine Ile:L-isoleucine Pro:L-Proline Ser: L-serine Thr:DL-Threonine Tyr:L-tyrosine Poly-Lys: Poly-L-Lysine Poly-PA: Sodium Polyphosphate Theanine: L-theanine GABA: γ-aminobutyric acid PCA: DL-pyrrolidone carboxylic acid

[0033] [Table 1]

[0034] Figure 1 shows photographs of the crystallization inhibition tests of tranexamic acid with the following concentrations: Aspartic acid 0.5%, 0.25%, 0.125%, phytic acid 0.16%, and a blank, after 24 hours of storage at room temperature. It was confirmed that aspartic acid has a higher crystallization inhibition effect on tranexamic acid than phytic acid.

[0035] [Table 2]

[0036] From the above results, it was confirmed that arginine, aspartic acid, glutamic acid, glycine, proline, serine, threonine, theanine, γ-aminobutyric acid, and pyrrolidone carboxylic acid have an inhibitory effect on the crystallization of tranexamic acid.

[0037] [Table 3]

[0038] Based on the above results, no crystallization inhibitory effect of tranexamic acid was observed for alanine, cysteine, histidine, isoleucine, tyrosine, polylysine, and sodium polyphosphate.

[0039] [Table 4]

[0040] [Table 5]

[0041] The results in Table 3 show that the combined use of Glu:L-glutamic acid and GABA:γ-aminobutyric acid has a synergistic effect in inhibiting the crystallization of tranexamic acid. From the results in Table 4, since the total amount was adjusted to 0.125%, if GABA and Theanine had an additive effect, it would be "+", but since it is "++", it was confirmed that the combined use of GABA (γ-aminobutyric acid) and Theanine (L-theanine) had a synergistic effect in inhibiting the crystallization of tranexamic acid.

[0042] [Examples, Comparative Examples] A lotion with the composition shown in Table 4 was prepared by mixing and dissolving ingredients other than purified water in purified water. The cosmetic product name is used. The crystallization inhibitory effect of tranexamic acid was evaluated using the same method as above. The results are also shown in the table.

[0043] Table 6

Claims

1. (A) A tranexamic acid crystallization inhibitor to be incorporated into a scalp or skin topical preparation containing 1 to 2% by mass of tranexamic acid, which is a liquid or lotion preparation. (B) A crystallization inhibitor for tranexamic acid, containing aspartic acid, proline, threonine, theanine, and one or more selected from alkali metal salts, alkaline earth metal salts, or metal salts thereof as active ingredients.

2. A method for inhibiting the crystallization of tranexamic acid, comprising: (A) a scalp or skin external preparation containing 1 to 2% by mass of tranexamic acid, which is a liquid or lotion preparation; and (B) one or more selected from aspartic acid, proline, threonine, theanine, and their alkali metal salts, alkaline earth metal salts, or metal salts.

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