TW201141529A - Improvement medicament for chromatosis - Google Patents

Abstract

The subject of present invention is to provide an improvement medicament for chromatosis having novel main nucleus, and a skin external agent comprising the said improvement medicament for chromatosis. The improvement medicament for chromatosis composed of the compound represented by following general formula (1) and/or pharmacologically acceptable salts thereof has excellent improvement to chromatosis, and a skin external agent for skin whitening can be provided by preparing the skin external agent comprising the said improvement medicament for chromatosis, [wherein R1 represents liner or branched alkyl of 1 to 6 carbon atoms; R2 represents hydrogen atom, or liner or branched alkyl of 1 to 4 carbon atoms].

Description

[Technical Field] The present invention relates to a novel pigment precipitation improving agent and a skin external preparation suitable for a cosmetic. In detail, the present invention relates to a compound represented by the following general formula (1) And/or a pigment precipitation improving agent which is a pharmacologically acceptable salt, and a skin external preparation containing the pigment precipitation improving agent. Further, in the description of the present invention, the term "cosmetic material" is defined as including a medical external product. Ο

(wherein R represents a linear or branched alkyl group having a carbon number of 1 to 6; and r2 represents a hydrogen atom or a linear or branched alkyl group having a carbon number of 1 to 4). [Prior Art] Pigmentation, freckles, chloasma, and pigmentation spots in the skin after sun exposure are caused by the activation of melanocytes present in the skin, and melanin production is remarkable and hyperactive. status. As a component having an effect of preventing or improving the occurrence and deterioration of such skin pigmentation problems, ascorbic acid, hydrogen peroxide, colloidal sulfur, glutathione, hydroquinone, catechol, etc. have a whitening effect. A compound (whitening agent) is widely known (for example, refer to Non-Patent Document 1 and Non-Patent Document 2), and an external preparation for skin containing the above-mentioned component as an active ingredient is widely used. Now, in terms of the action sequence of compounds known as whitening agents, tyrosinase inhibitory inhibition, tyrosinase-associated protein 201141529 decomposition, due to dendrite elongation in melanocytes have been reported. Inhibition and inhibition of various mechanisms of action such as melanin transfer, and there are target molecules for individual action mechanisms. In order to function properly for the target molecule and to exhibit a high whitening effect, it is useful for organic low molecules in which the target molecules interact appropriately. Moreover, due to the difference in the target molecules, the structural characteristics of the organic low molecules that interact appropriately with the respective target molecules and the chemical structure for maximizing the pharmacological action shown by the organic low molecules are also optimized. For the prevailing. Further, the present whitening agent is a compound which has a molecular function of a plurality of whitening targets in addition to a compound having high availability and selectivity, and a compound having a new action sequence. A general term for an organic compound having an amino group and a carboxyl group in an amino acid-based molecule, in particular, an α-amino acid is widely studied as a constituent unit of a protein which exhibits various functions in a living body. Alpha-amino acids such as cysteine, arginine, valine, threonine, serine, glycine, etc. present in living organisms, and α-amino acids are included in the constituent elements Peptide derivatives have been reported for a wide variety of physiological activities. With respect to the biological activity of α-amino acid and its derivatives, anti-aging effects are known only in the field of cosmetics (for example, refer to Patent Document 1) 'moisturizing action (for example, 'refer to Patent Document 2), The effects of whitening action (for example, refer to Patent Document 3) and interface activation are combined with cosmetics and the like for the purpose of the effects. Further, in general, such amino acids and derivatives thereof are excellent in solubility, dispersibility, and water solubility, and 201141529 is expected to have high safety, and blending with cosmetics and the like is widely studied. However, the aforementioned (X-amino acid and its derivatives have antibacterial, moisturizing or whitening effects and the like, and it is difficult to say that it is sufficiently practicable, and the α-amino acid and its derivative for improving biological activity. The research on glycine acid, which is a kind of α-amino acid, is known to have betaine-type amphoteric interfacial activity in Ν-mercapto and Ν-long-chain alkyl glycine derivatives. The interfacial activation action such as action or semi-polar interfacial activity (for example, refer to Patent Document 4 and Patent Document 5) is blended into a surfactant such as a cosmetic, a detergent, a sputum, or a toothpaste. Glycine and its thiol derivatives have been reported to have a whitening effect (for example, refer to Patent Document 6) 'but with regard to Ν-alkylglycine derivatives, especially regarding hydrazine; gibberellic acid (creatinine) Acid (sarcosine), only known to have a grain-improving effect (for example, refer to Patent Document 7), and the whitening effect is completely unknown. [Prior Art Document] Patent Document: 2004-Special Open 2002-Special Kaiping 05-Spec Open 2002-Special Open 2001-Special Open 2004-W02007/0 1 [ [Patent Document 2] [Patent Document 3] [Patent Document 4] [Patent Document 5] [Patent Document 6] [Patent Document 7] Non-Patent Document No. 115438, No. 087928, No. 3 0 1 8 1 Bulletin 322491, pp. 261531, 3 1 5 3 8 4, 3, 6 6 2 booklet 201141529 [Non-Patent Document 1] Inspector of Takeda K., "The usefulness of cosmetics, evaluation technology, and future prospects", Pharmacy Daily Publication (2001) [Non-Patent Document 2] Osaki Kenno, FRAGRANCE JOURNAL' Temporary Supplement, No. 14, 1995, 118-126 [Summary of the Invention] [Problems to be Solved by the Invention] The present invention is based on In this case, a pigment precipitating agent having a novel mother nucleus having excellent pigmentation improving effect and a skin external preparation containing the pigment precipitating agent are provided as a problem. [Means for solving the problem] In the case of the present inventors, the inventors of the present invention have found that the compound represented by the general formula (1) and/or the pharmacologically acceptable ones can be found as a result of continuous efforts to concentrate on a pigmentation improving agent suitable for a cosmetic (including a medical external product). The present invention has been completed in view of the fact that the salt is improved in the effect of improving the pigmentation. The present invention is as follows. <1> A pigment precipitation improver which is a compound represented by the following formula (1) and/or Or such pharmacologically acceptable salts.

N (1) or 2 (wherein Ri represents a linear or branched alkyl group having a carbon number of 1 to 6; R 2 represents a hydrogen atom, and the carbon number is a linear or branched base) ° &lt; 2 &gt;&lt;1&gt; The pigment precipitation improving agent described in the above formula (1) 201141529 is a compound represented by the following formula (2) and/or a pharmacologically acceptable salt thereof,

(wherein R3 represents a linear or branched alkyl group having a carbon number of 1 to 6). The pigment precipitation improving agent of the above formula (2) is N-methylglycine and/or a pharmacologically acceptable salt thereof. &lt;4&gt; The skin external preparation according to any one of <1> to <3>, wherein the skin external preparation according to any one of &lt;1&gt; The pigment precipitating agent is contained in an amount of from 0.0001% by mass to 20% by mass based on the total amount of the external preparation of the skin. &lt;6&gt; The skin external preparation described in <4> or <5>, which is a cosmetic (including a medical external product). The skin external preparation according to any one of <4>, which is an oil emulsifier type in oil. (8) The skin external preparation according to any one of <4>, which is whitening. &lt;9&gt; A method for improving pigmentation of skin, which is characterized in that a compound represented by the following formula (1) and/or a pharmacologically acceptable salt thereof are administered to a pigmentation Improvement to the necessary parts, 201141529

(wherein R! represents a direct bond or a branch of a branch having a carbon number of 1 to 6; Rz represents a hydrogen atom, and the carbon number is i~4: a chain or a branch of a branch) ° [Embodiment] [Formation for Carrying Out the Invention] &lt;Pigment Precipitating Improver of the Present Invention&gt; The dye precipitation improving agent of the present invention is characterized by the compound represented by the above formula (1) and/or pharmacologically acceptable thereof Permissible salt composition. The pigmentation-improving agent of the present invention has an effect of preventing pigmentation precipitation in addition to a pigmentation-preventing effect of lightening or removing a pigment precipitate which has already been formed, and a compound having a function of preventing pigmentation is also included in the present invention. Pigmentation improver. In other words, the pigment precipitation improving agent of the present invention contains the above-mentioned general formula (1) and has a function of preventing or improving pigmentation. The effect of improving the pigmentation in the present invention can be judged by, for example, whether or not the pigmentation inhibiting action is evaluated in the "Evaluation of the pigmentation inhibition by ultraviolet irradiation using colored guinea pigs" described in the examples below. In the evaluation of the pigmentation inhibition of the examples described later, the effect of the pigmentation-preventing effect means that it is considered to have a pigmentation-preventing effect in the evaluation substance administration group as compared with the control group (vehicle control group). The pigment precipitation inhibitor of the present invention is preferably compared with the control group. The evaluation of the pigmentation inhibition of the substance administration group is considered to be statistically significant. Further, the compound represented by the above formula (1) and/or the pharmacologically acceptable salt of the formula 201141529, in addition to having an excellent pigmentation prevention or improvement effect, is excellent in solubility in a hydrophilic or lipophilic medium, and on the skin. Formulation of an external preparation or the like is easy. Further, the stability in the preparation and the skin retention property are excellent, and the excellent effect of preventing or improving pigmentation is exhibited. Further, the preventive or ameliorating action of the pigment precipitation of the compound means tyrosinase inhibitor inhibition, tyrosinase gene expression inhibition, tyrosinase protein expression inhibition, tyrosinase-related protein decomposition, etc. In addition to the inhibitory action of the aminase activity and the melanin production inhibitory action such as inhibition of dendritic elongation in melanocytes and melanin transfer inhibition, it is estimated that the melanin producer is inhibited by a new action sequence. Therefore, glycine or thioglycine improves the performance of the unimproved pigmentation. In the compound represented by the above formula (1), R represents a straight or branched alkyl group having a carbon number of 1 to 6; and R2 represents a hydrogen atom or a linear or branched alkane having a carbon number of 1 to 4. base. The above 1 is preferably a linear or branched alkyl group having 1 to 4 carbon atoms, more preferably a methyl group or an ethyl group. Specific examples of R1 include methyl, ethyl, η-propyl, isopropyl, η-butyl, isobutyl, tert-butyl, pentyl, hexyl and the like. The above R2 is preferably a hydrogen atom or a methyl group. Specific examples of R2 include a hydrogen atom, a methyl group, an ethyl group, a propyl group, a butyl group and the like. Among the compounds represented by the above formula (1), a compound represented by the following formula (2) and/or a pharmacologically acceptable salt thereof can be preferably used. More preferably, N-methylglycine and/or such pharmacologically acceptable salts are preferred. •10- 201141529 ο

(wherein 'R3 represents a straight or branched alkyl group having a carbon number). In the compound represented by the formula (2), r3 represents a linear or branched alkyl group having a carbon number of 6 . The above R3 is preferably a linear or branched alkyl group having 1 to 4 carbon atoms, more preferably a methyl group or an ethyl group. Specific examples of R3 include a methyl group, an ethyl group, an η-propyl group, an isopropyl group, an η-butyl group, an isobutyl group, a tertiary butyl group, a pentyl group, a hexyl group and the like. Specific examples of the compound represented by the above formula (2) and/or such pharmacologically acceptable salts can be exemplified by N-methylglycine, N-ethylglycine, and N-(η- Propyl)glycine, N-(isopropyl)glycine, Ν-(η-butyl)glycine, Ν-(isobutyl)glycine, Ν-(tri-butyl)glycine Amino acids 'Ν-(n-pentylglycine), Ν-(η-hexylglycine), and the pharmacologically acceptable salts thereof. More preferably, Ν-methylglycine, Ν-ethylglycine and such pharmacologically acceptable salts are exemplified. The compound represented by the above formula (2) and/or the pharmacologically acceptable salt thereof have particularly excellent pigmentation prevention or improvement effects. Further, it is excellent in solubility in a hydrophilic or lipophilic medium, and it is easy to prepare a preparation for external use such as skin. Further, the preparation has excellent stability and skin storage properties, and exhibits an excellent effect of prevention or improvement of pigmentation. Further, among the compounds represented by the above formula (1), specific examples of the compound not belonging to the compound represented by the above formula (2) are exemplified by methyl methacrylate and hydrazine-methyl group. Ethyl glycinate, Ν-methylglycine propyl ester, Ν-methylglycine butyl ester, Ν-ethylglycine methyl ester, -11 - 201141529 N-ethylglycolamine Acid ethyl ester, N-ethylglycine propyl ester, N-ethylglycine butyl ester, N-propylglycine methyl ester, N-propylglycine ethyl ester, N -propyl propyl glycinate, N-propylglycine butyl ester, N-butylglycine methyl ester, N-butylglycine ethyl ester, N-butylglycine Propyl ester, N-butyl glycinate butyl ester. The compound represented by the above formula (1) or formula (2) can be produced by using a glycine derivative having a protective group such as a commercially available tertiary butoxycarbonyl group (Boc group) as a starting material. For example, in an anhydrous N,N-dimethylformamide solvent, an alkyl group reaction using sodium hydride and a corresponding halogenated alkyl group is carried out, and then a protective group is removed by a deprotection reaction to produce. Further, a commercially available product may be used, and it may be purchased from a reagent manufacturer such as Tokyo Chemical Industry Co., Ltd. This compound can also be used as a pigment precipitation improving agent as it is, but it can also be converted into a salt form by treatment with a pharmacologically acceptable acid or base, and used as a salt. For example, preferred are inorganic acid salts of hydrochlorides, sulfates, nitrates, phosphates, carbonates, and the like; maleic acid salts, fumarates, oxalates, citrates, lactic acid An organic acid salt of a salt, a tartrate, a methanesulfonate, a p-toluenesulfonate or a besylate; an alkali metal salt such as a sodium salt or a potassium salt; an alkaline earth metal salt such as a calcium salt or a magnesium salt; An organic amine salt such as an ethylamine salt, a triethanolamine salt, an ammonium salt or a monoethanolamine salt 'piperidine salt; or a basic amino acid salt such as an amine salt or a arginine salt. The pigment precipitation improving agent of the present invention thus obtained has an effect of preventing or improving the coloration of the pigment, and is effective as an external preparation for skin -12-201141529. Although the action sequence of the pigment precipitation improving agent of the present invention is not clear, the tyrosinase activity such as inhibition of tyrosinase activity and inhibition of tyrosinase gene expression, tyrosinase-related protein decomposition, etc. Inhibition, melanin production inhibition by melanin transfer inhibition by dendritic elongation in melanocytes, and inhibition of melanin production by a new action sequence. In the case where the pigment precipitation improving agent of the present invention is used as an active ingredient of a skin external preparation, the pigment precipitation improving agent is contained in an amount of 0.0001% by mass to 2% by mass, more preferably 0.001% by mass based on the total amount of the external preparation for skin. The mass % ' is more preferably 0.005 to 5 mass%. When the total amount of the external preparation for skin is less than 0.0001% by mass, the effect of preventing or improving the pigmentation tends to be lowered, and even if the amount is more than 20% by mass, the effect tends to reach the highest point, so that it is lowered. The freedom of prescription. Further, the pigmentation-preventing agent of the present invention and the external preparation for skin containing the pigmentation-improving agent are used for prevention or improvement of pigmentation prevention or improvement, and are intended to prevent or improve by pigmentation. As a main use, for example, "including "whitening" and "freckle improvement" are used. &lt;External preparation for skin of the present invention&gt; The external preparation for skin of the present invention contains the pigment precipitation improving agent of the present invention. The skin external preparation of the present invention may contain only one kind of the pigment precipitation improving agent of the present invention, or may be used in combination of two or more kinds. The external preparation for skin of the present invention is related to pigment-related abnormalities such as "preparation for pigmentation prevention or improvement", "for whitening", and "for freckle improvement" by the use of the pigment-precipitating agent of the present invention in the combination of the present invention. The effect of prevention or improvement. In addition to the pigment precipitation improving agent which is an essential component, the external preparation for skin of the present invention may contain any component which is usually used for the external preparation for skin. As such an optional component, a hydrocarbon such as squalane, petrolatum or microcrystalline wax; an ester of jojoba oil, carnaubawax, octyldodecyl oleate or the like: olive oil, tallow, or the like may be contained. a triglyceride such as coconut oil; a fatty acid such as stearic acid, oleic acid or retinoic acid; a higher alcohol such as oleyl alcohol, stearyl alcohol or octyldodecanol; thiosuccinate Or an anionic surfactant such as sodium polyoxyethylene alkyl sulfate: an amphoteric surfactant such as an alkylbetaine salt; a cationic surfactant such as a dialkylammonium salt; a sorbitan fatty acid ester; a fatty acid monoglyceride, such a polyoxyethylene adduct; a nonionic surfactant such as a polyoxyethylene alkyl ether or a polyoxyethylene fatty acid ester; polyethylene glycol, glycerin, 1,3 - butyl Polyols such as alcohols; viscosity-increasing gelling agents, antioxidants, UV absorbers, colorants, preservatives, powders, etc. Manufacturing is done without any difficulty by processing these ingredients in accordance with the usual practice. The pigment precipitation improver and the optional component of the present invention are treated according to a conventional method, and a lotion, an emulsion, an essence, a cream, a mask cosmetic, a washing material, and the like can be prepared. The external preparation for skin of the present invention may be any one of the dosage forms which can be adapted to the skin, but it is excellent in adaptability to the skin, such as lotion, lotion, cream, serum, etc., which are suitable for the skin to be infiltrated by the active ingredient. Formulation-14-201141529 is preferred. The invention is further illustrated by the following examples, but it should be understood that the invention is not limited to the examples. &lt;Example 1: Method for producing Compound 1 and Compound 2&gt;

N-methylglycine (compound!)

The compound 1 and the compound 2 can be synthesized, for example, according to the method described in "Basic and Experimental Synthesis of Peptide" (Kowloon Co., Ltd.). As a starting material, Boc-Gly (Korean Peptide Co., Ltd.) was used, dissolved in anhydrous N,N-dimethylformamide (Wako Pure Chemical Industries Co., Ltd.), using sodium hydride and equivalent alkane. After the alkylation reaction of the base halide (methyl iodide, ethyl iodide, and Wako Pure Chemical Industries Co., Ltd.), the acid is subjected to a deprotection reaction by an acid such as hydrochloric acid, and further, a free base is formed by ion exchange. Compound 1 or Compound 2 can be obtained as a target. Further, the compound can also be purchased as a commercially available reagent from a manufacturer of reagents such as Tokyo Chemical Industry Co., Ltd. In the examples of the present invention, compounds purchased from Tokyo Chemical Industry Co., Ltd. were used. &lt;Physical constant of Compound 1&gt; 4-Dragon 11 (d6-DMSO): δ 2.44 (2H, s), 3.09 (3H, S). &lt;Physical constant of Compound 2&gt; 1H-NMR (D20): δ 1.30 (3Η, t, J = 7·8Ηζ), 3.12 -15- 201141529 (2H, q, J=7.8Hz.), 3,61 (2H, s) · &lt;Test Example 1: By using colored Inhibition of chymidine precipitation&gt; The back skin of 8 colored guinea pigs was electrically shaved, and this part was covered with 2x2 cm of the left and right sides, and the FL20S-E30 lamp was used as a light source to illuminate the outer line. This operation was repeated on the first, third, fifth, and eighth days of the test to induce pigmentation. Next, Compound 1 was dissolved in 70% (v/v) 5% (w/v), and a 70% (v/v) aqueous solution of ethanol containing Compound 1 was prepared as a control. At the end of the ultraviolet irradiation at the first day of the test, the aqueous ethanol solution and the aqueous ethanol solution were applied. The application site was applied once a day, 30 μm each, and this was continued every day for 5 weeks. Coating start date (before the first irradiation and after 3 weeks (the 22nd day of the test) and after 5 weeks (using a color difference meter (CR-200, Konica Minolta measures the skin brightness (L*値) of each test site, refinement and L*値 on the 36th minus the L* 前 before UV irradiation, the higher the degree of L* lanthanide pigmentation, the lower the 偃 inhibits pigmentation. The results are shown in Table 1. UV-irradiated color shear and razor hair removal And the black cloth of 300mJ/cm2 of the irradiation window was carried out, and the aqueous solution of ethanol in two places became a solution. In addition, the ultraviolet test of the first test containing the compound 1 in the designated test room (to the test No. 35 1) was carried out.日), Co., Ltd., since the test of the 22nd AL*値.艮口, ,AL *値大可•16- 201141529 [Table i] Compound 1 concentration △L*値△L*値(w/ V ) (after 3 weeks) (after 5 weeks) Control group (aqueous ethanol solution) - -11.71 ± 0.45 - 10.11 ± 0.62 5% aqueous solution of compound 1 - 10.98 ± 0.81 - 7.30 ± 0.84 △ L * 値 indicates 8 Average ± standard error of the example. &lt;Example 2: Skin external preparation (lotion 1) of the present invention, comparison 1 and 2 &gt; 'The cosmetic (cosmetic) of the external preparation for skin of the present invention was prepared according to the description of Table 2. That is, the prescription component was heated to 80 ° C, stirred, dissolved, and stirred and cooled. A cosmetic (makeup 1) was obtained, and the obtained lotion 1 was a uniform composition and was a very stable preparation. Similarly, a comparative example in which "the pigment precipitation improving agent (compound 1) of the present invention" was replaced with water was prepared. The lotion 2 of 1 and the lotion 3 of Comparative Example 2 in which the pigment precipitation improving agent (compound Ο) of the present invention is substituted with arbutin. -17- 201141529 [Table 2]_

_Ingredients_ Compound 1_ POE (60) Hardened castor oil 1,3-Butanediol . Glycerin _ Polyethylene glycol 400 1,2-Pentanediol Xanthan gum _

Methylparaben water _P 卞 卞 Example 3: Skin external preparation (cream) of the present invention&gt; According to Table 3, an oil-based water cream was prepared. In other words, each of the components was heated to 80 ° C in 1 and slowly added to 2 ′ in 1 to be emulsified, and the particles were homogenized by a homogenizer, and the sample was cooled to obtain a cosmetic (cream 1 ). The resulting cream 1 did not separate and was a very stable preparation. -18- 201141529 [Table 3] Ingredient content (% by mass) 1 Sucrose fatty acid ester 0.5 Vaseline 1.0 Lanolin 3.0 Flow paraffin 8.0 Low viscosity polyoxyl 3 0.0 Stearyl alcohol 0.5 Stearic acid 0.55 Undecylenic acid monoglycerol Ester 2.0 Organically modified Bentonite 2.0 2 1,3-Butanediol 5.0 Glycerin 20.0 Compound 1 5.0 Methylparaben 0.2 Water 22.1 Potassium hydroxide 0.05 Polyglucosideoxyethyl methacrylate (molecular weight about 10 10,000) 0.1 Total 1 00.0 -19- 201141529 &lt;Example 4: Skin external preparation of the present invention (emulsion 1) &gt; A cosmetic preparation according to the formulation of Table 4, which is prepared as a skin external composition of the present invention (emulsion 1) ). That is, the components of 1, 2, and 3 are heated to 80 ° C, while 2 is slowly added to 3 while stirring and neutralized, and then slowly stirred. 1 is added, and the particles are homogenized to obtain uniformity of the particles. Cosmetics (lotion 1). The resulting emulsion 1 did not separate and was a very stable formulation. [Table 4] Ingredient content (% by mass) 1 Squalane 10.0 Sorbitan sesquistearate 2.0 Titanium dioxide 1.0 butyl p-hydroxybenzoate ~.. one-to-one.-" 0.1 2 ---- — &quot; ·Μ 1,3-butanediol 5.0 xanthan gum 0.1 Pemulen TR-1 0.2 (acrylic acid. Alkyl methacrylate) — methylparaben 0.1 compound 1 5.0 __________—water 50.0 3 ------—potassium hydroxide 0.1 ----------- Water 26.4 Total 100.0 -20- 201141529 &lt;Test Example 2: Ultraviolet irradiation in humans by lotion~3 Inhibition effect of pigmentation precipitation> The pigmentation inhibitory effect was examined using the skin external preparations of the lotion 1, the lotion 2 (Comparative Example 1) and the lotion 3 (Comparative Example 2). In the inner part of the wrist of the member who participated in the free will, the 1.5cmxl.5cm part is divided into two upper and lower sections, and each of the two places is 4 times in the ultraviolet irradiation part designed to be the least erythema (1 MED). Three exposures were made for three consecutive days. One 后 after the end of the irradiation, 50 μί of the sample was applied every 35 days for 35 consecutive days. One of the four sites was used as the untreated site. 24 hours after the end of the 35th application, the skin brightness (L*値) of each test site was measured by a color difference meter (CR-300, Konica Minolta Co., Ltd.), and the L of the treatment site relative to the untreated portion was calculated. *値 difference (AL*). The stronger the degree of L* lanthanide pigmentation and the lower the enthalpy. Therefore, the larger Δ L *値, the more the pigmentation can be suppressed. The results are shown in Table 5. From this, it is understood that the cosmetic (cosmetic lotion 1) of the external preparation for skin of the present invention has an excellent pigmentation inhibiting effect. It is considered to be a pigment precipitation inhibitory effect of the aforementioned Compound 1 contained in the lotion 1 - 21 - 201141529 [Table 5] Skin external preparation △ L* 値 lotion 1 0.93 lotion 2 (Comparative Example 1) 0.22 Makeup Water 3 (Comparative Example 2) 0.69 [Industrial Applicability] The present invention can be applied to a skin external preparation such as a cosmetic for whitening. [Simple description of the diagram] 〇 /\\\ [Description of main component symbols] 〇 w -22-

Claims (1)

201141529 VII. Patent application scope: 1. A pigment precipitation improving agent' is a compound represented by the following general formula (1) and/or a pharmacologically acceptable salt thereof. (wherein R represents a linear or branched alkyl group having a carbon number of 1 to 6; and R2 represents a hydrogen atom or a linear or branched alkyl group having 1 to 4 carbon atoms). 2. The pigment precipitation improving agent of the first aspect of the invention, wherein the compound represented by the formula (1) is a compound represented by the following formula (2) and/or a pharmacologically acceptable salt thereof, (wherein R3 represents a linear or branched alkyl group having a carbon number of 1 to 6). 3. The pigment precipitation improving agent according to claim 2, wherein the compound represented by the formula (2) is N-methylglycine and/or a pharmacologically acceptable salt thereof. A skin external preparation containing the pigmentation improving agent according to any one of claims 1 to 3. 5. The skin external preparation according to item 4 of the patent application, wherein the pigment deposition improving agent is contained in an amount of from 0.0001% by mass to 20% by mass based on the total amount of the external preparation for skin. 6. The skin external preparation according to claim 4 or 5, which is a cosmetic (including a medical external product). -23-201141529. The skin external preparation according to any one of claims 4 to 6, which is an oil emulsifier type in oil. 8. The external preparation for skin according to any one of claims 4 to 7, which is used for whitening. -24- 201141529 IV. Designated representative map: (1) The representative representative of the case is: None. (2) A brief description of the symbol of the representative figure: Μ 〇 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: