JP2007070268A - External preparation for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means for improving stability of a preparation using a nonionic surfactant, particularly stability in high-temperature storage, in an external preparation for skin. <P>SOLUTION: The external preparation for skin excellent in stability in high-temperature storage is obtained by including one or more kinds of materials selected from a group consisting of a peptide having lysyl-glutamine as a partial structure or salts thereof into an external preparation base material. Especially, the effect of the external preparation for skin is remarkable in a preparation system using a surfactant having a polyoxyethylene chain. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an external preparation for skin such as cosmetics.

  In external preparations for skin, surfactants are used in various ways by taking advantage of their emulsifying action, solubilizing action, and touch improving action. In particular, since emulsions and creams can be administered with an aqueous component and an oily component at the same time and have a good feel when used, they are widely applied to cosmetics and skin external medicines. These surfactant compounds include anionic surfactants such as fatty acid soaps and alkyl sulfates, and nonionic surfactants such as polyoxyethylene fatty acid esters, polyglycerin fatty acid esters, and sucrose fatty acid esters. Various synthetic polymers having surface active ability such as alkyl-modified carboxyvinyl polymer, viscosity minerals such as laponite and bentonite are known. In particular, nonionic surfactants are used in many cosmetics because of their mild irritation to the skin. Among them, surfactants having a polyoxyethylene chain are frequently used because of their low skin irritation and high surface activity. The polyoxyethylene chain in the surfactant having the polyoxyethylene chain is stabilized by spreading the polyoxyethylene chain into water by coordination of the water molecule with the hydrogen bond to the oxygen atom in the ether bond in the chain. . The surfactant having a polyoxyethylene chain utilizes the surface active action formed by spreading of the polyoxyethylene chain into water and a lipophilic alkyl chain. The hydration ability of the polyoxyethylene chain stabilized in water by such a hydrogen bond is easily affected by an increase in temperature and the presence of a salt, and sometimes the stability and the like are impaired. Therefore, it is desired to develop a technology for improving the stability of a pharmaceutical system using a nonionic surfactant, particularly a nonionic surfactant having a polyoxyethylene chain. As a result of various studies, Developed technologies that use emulsifiers that have salt tolerance (see, for example, Patent Document 1), technologies that use nonionic surfactants and polyhydric alcohol polyhydric fatty acid esters that are liquid at room temperature (see, for example, Patent Document 2), etc. Has been. However, such technology does not always improve stabilization, and it can be said that development of a stabilization method not based on these is desired.

  In addition, as cosmetics containing peptides, a technique of incorporating a dipeptide having glutamine as a structural unit and glycogen and SOD into cosmetics (see, for example, Patent Document 3), ε-N- (γ-glutamyl) lysine For cosmetics for the purpose of moisturizing (see, for example, Patent Document 4), and technology for incorporating a dipeptide having an arginine residue at the N-terminus as a skin softening agent (for example, Patent Document 5) See) is known.

  Here, a skin external preparation containing a peptide having lysyl-glutamine as a partial structure is not known, and a skin external preparation containing a peptide having lysyl-glutamine as a partial structure uses a nonionic surfactant. It has not been known at all to have an effect of improving the stability of the prepared preparation.

Japanese Patent Laid-Open No. 01-210029 Japanese Patent Laid-Open No. 11-035447 JP 2003-306420 A Japanese Patent Laid-Open No. 05-301814 JP 07-330572 A

  The present invention has been made under such circumstances, and an object of the present invention is to provide means for improving the stability of a preparation using a nonionic surfactant.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that a topical skin preparation containing a peptide having lysyl-glutamine as a partial structure is stable in a preparation using a nonionic surfactant. As a result, the present invention has been completed. That is, the present invention is as follows.

(1) A skin external preparation characterized by containing one or more selected from the group consisting of peptides having lysyl-glutamine as a partial structure or salts thereof.
(2) The external preparation for skin according to (1), wherein the peptide is a dipeptide or a tripeptide.
(3) The external preparation for skin according to (1) or (2), wherein the peptide is a compound represented by the following structural formula (I).

構造式（Ｉ）

Structural formula (I)

(4) The skin external preparation according to any one of (1) to (3), wherein the content of the peptide in the external preparation for skin is 0.01 to 10% by mass.
(5) The skin external preparation according to any one of (1) to (4), further comprising a nonionic surfactant.
(6) The external preparation for skin according to (5), wherein the nonionic surfactant is a surfactant having a polyoxyethylene chain.
(7) Further, 0.01 to 1% by mass of one or more selected from alkyl glycyrrhetinate, glycyrrhizic acid or a salt thereof, characterized in that any one of (1) to (6) Item 1. An external preparation for skin according to item 1.
(8) The external preparation for skin according to (7), wherein the glycyrrhizic acid or a salt thereof is dipotassium glycyrrhizinate and the alkyl glycyrrhetinate is stearyl glycyrrhetinate.
(9) The external preparation for skin according to any one of (1) to (8), which is a cosmetic.
(10) The external preparation for skin according to any one of (1) to (9), which is a quasi-drug.

  ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation useful for the skin external preparation excellent in stability of a formulation system can be provided by making the skin external preparation contain the peptide which has lysine-glutamine as a partial structure.

(1) Peptide having lysyl-glutamine, which is an essential component of the external preparation for skin of the present invention, or a salt thereof The external skin preparation of the present invention contains a peptide having lysyl-glutamine as a partial structure, or a salt thereof It is characterized by that. The compound represented by the structural formula (I) is lysyl-glutamine, which is a dipeptide compound in which the α-position carboxyl group of lysine is amide-bonded between the α-position amino groups of glutamine. Such a dipeptide compound can be prepared by a conventional method. For example, di-BOC-lysine commercially available from Tokyo Kasei Kogyo Co., Ltd. is converted into an acid chloride form with thionyl chloride, and reacted with glutamine. The compound of structural formula (I) can be obtained by deprotection with. Here, it is also possible to synthesize a tripeptide form by reacting another amino acid as an acid chloride form without deprotecting the BOC group during the synthesis reaction of these dipeptide forms.

Production Example 1 Production of Compound of Structural Formula (I) 10 g of thionyl chloride was added to 2.46 g of di-BOC-lysine and stirred at room temperature for 30 minutes, and then excess thionyl chloride was distilled off. This was dissolved in dichloromethane, and dropped into a solution obtained by adding 2.60 g of glutamine and triethylamine to dichloromethane with vigorous stirring, and further stirred at room temperature for 24 hours. After the precipitate was filtered off, the filtrate was concentrated and fractionated and purified on a silica gel column (eluted with chloroform / methanol = 100/0 to 95/5). The fraction was concentrated and treated with trifluoroacetic acid to deprotect the protecting group. After concentration, the mixture was passed through Diaion HP-20 and eluted with water / ethanol = 100/0 to 80/20 to obtain 2.02 g of the compound of structural formula (I).

<Production Example 2> Production of (lysyl-glutaminyl) -alanine 10 g of thionyl chloride was added to 2.46 g of di-BOC-lysine and stirred at room temperature for 30 minutes, and then excess thionyl chloride was distilled off. This was dissolved in dichloromethane, and dropped into a solution obtained by adding 2.60 g of glutamine and triethylamine to dichloromethane with vigorous stirring, and further stirred at room temperature for 24 hours. After the precipitate was filtered off, the filtrate was concentrated and fractionated and purified on a silica gel column (eluted with chloroform / methanol = 100/0 to 95/5). After concentration of the fraction, 10 g of thionyl chloride was added and stirred at room temperature for 30 minutes, and then excess thionyl chloride was distilled off. This was dissolved in dichloromethane, and dropped into a solution obtained by adding 2.4 g of alanine and triethylamine to dichloromethane with vigorous stirring, and further stirred at room temperature for 24 hours. After the precipitate was filtered off, the filtrate was concentrated and fractionated and purified on a silica gel column (chloroform / methanol = 100/0 to 92/8). The fraction was concentrated and treated with trifluoroacetic acid to deprotect the protecting group. After concentration, it was passed through Diaion HP-20 and eluted with water / ethanol = 100/0 to 80/20 to obtain 2.62 g of (lysyl-glutaminyl) -alanine.

  A peptide having lysyl-glutamine as a partial structure may be used in the form of a salt. The types of bases to be used in the form of salts include hydrochloric acid, bromic acid mineral acids, acetic acid, citric acid, oxalic acid, ascorbic acid and other organic acids, glutamic acid, aspartic acid and other acidic amino acids, ammonia, sodium Examples thereof include alkali metals such as potassium, alkaline earth metals such as calcium and magnesium, and amines such as monoethanolamine, diethanolamine and triethanolamine, but hydrochlorides can be advantageously used in consideration of solubility and the like.

  The peptide having lysyl-glutamine as a partial structure or a salt thereof thus obtained is an odorless white powder and hardly soluble or insoluble in various organic solvents such as ethanol, acetone, etc., but in alkaline water or acidic water. It dissolves, especially dissolves well in acidic to weakly acidic water, and can be blended in various cosmetic bases.

  In the present invention, the content of the peptide having lysyl-glutamine as a partial structure or a salt thereof is generally 0.01 to 10% by mass, preferably 0.05 to 5% by mass, based on the total amount of the cosmetic. It is. If the amount is less than 0.01% by mass, the effect of the present invention cannot be sufficiently obtained, and even if the amount exceeds 10% by mass, the effect is not enhanced, which is uneconomical.

(2) External preparation for skin of the present invention The present invention uses a nonionic surfactant by containing a peptide having 0.01 to 10% by mass of lysyl-glutamine as a partial structure or a salt thereof. The present invention relates to an external preparation for skin with improved stability of the preparation. In the present invention, since the inclusion of the peptide is useful for improving the stability of a preparation using a nonionic surfactant, the present invention contains a nonionic surfactant. Preferably it is. Examples of such nonionic surfactants include surfactants having a polyoxyethylene chain, surfactants having a polyglycerin chain, and saccharide surfactants. Particularly preferred are surfactants having a polyoxyethylene chain. This is because the effect of the present invention is remarkable.

  Examples of the surfactant having a polyoxyethylene chain include polyoxyethylene (10EO) monolaurate, polyoxyethylene monostearate (10EO), polyoxyethylene (25EO) monostearate, polyoxyethylene (40EO). Polystearic acid ester, polyoxyethylene fatty acid ester such as polyoxyethylene (10EO) monooleate, polyoxyethylene (9EO) lauryl ether, polyoxyethylene (20EO) stearyl ether, polyoxyethylene (20EO) oleyl ether, etc. Polyoxyethylene alkyl ether, polyoxyethylene (20EO) sorbitan monopalmitate, polyoxyethylene (20EO) sorbitan monostearate Polyoxyethylene sorbitan fatty acid ester such as ter, polyoxyethylene (6EO) sorbitan monooleate, polyoxyethylene sorbite fatty acid ester such as polyoxyethylene (60EO) sorbit tetrastearic acid, polyoxyethylene (6EO) monolauric acid, Polyoxyethylene (5EO) glyceryl monostearate, polyoxyethylene (15EO) glyceryl monostearate, polyoxyethylene (5EO) glyceryl monooleate, polyoxyethylene (15EO) glyceryl monooleate, etc. Polyoxyls such as oxyethylene glyceryl fatty acid ester, polyoxyethylene (20EO) hydrogenated castor oil, polyoxyethylene (50EO) hydrogenated castor oil Ethylene castor oil can be exemplified. Examples of the surfactant having a polyglycerol chain include polyglycerol fatty acid esters such as hexaglycerol monooleate, decaglycerol monolaurate, and decaglycerol monostearate. In addition, saccharide surfactants include sorbitan fatty acid esters such as sorbitan monolaurin chain ester, sorbitan monopalmitic acid ester, sucrose fatty acid ester such as sucrose monolauric acid ester, sucrose monomyristic acid ester, octyl glucoside, etc. Examples thereof include alkyl glycosides. Among these nonionic surfactants, in the present invention, it is particularly preferable to contain a surfactant having a polyoxyethylene chain. This is because the effect of the present invention is most easily obtained when a surfactant having a polyoxyethylene chain is used. Moreover, as a compounding quantity of these nonionic surfactant, 0.1 to 10 weight% is preferable.

  Moreover, since the external preparation for skin of the present invention has an effect of improving the stability of a preparation using a nonionic surfactant, a nonionic surfactant such as glycyrrhizinate is used. It is also preferred to apply to a formulation system containing a compound that may affect the stability of the formulation system. That is, in order to make use of the effects of the present invention, it is also a preferred form that the external preparation for skin of the present invention contains an anti-inflammatory component such as glycyrrhizinate. Such components are known as active ingredients of quasi drugs, and as salts of glycyrrhizic acid, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, monoethanolamine Examples thereof include amine salts such as diethanolamine and triethanolamine, basic amino acid salts such as lysine and arginine, ammonium salts and the like, but alkali metal salts can be advantageously used in consideration of solubility and the like. Of these, dipotassium salts are commercially available and can be purchased and used, which is preferable. The content of one or more selected from alkyl glycyrrhetinate, glycyrrhizic acid or a salt thereof in the external preparation for skin of the present invention is preferably 0.01% by mass to 1.0% by mass, 0.05 -0.5 mass% is more preferable. Use as a quasi-drug in combination with such an anti-inflammatory component is also an effective method of use of the present invention.

  In the external preparation for skin of the present invention, in addition to the above-mentioned components, optional components that are usually used in cosmetics and external preparations for skin can be contained. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil Oils such as hardened oil, mole, hardened castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, waxes, liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum , Hydrocarbons such as microcrystalline wax, higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid, cetyl alcohol, stearyl alcohol, isostearyl Alcohol, behenyl alcohol, octyldodecanol, higher alcohol such as myristyl alcohol, cetostearyl alcohol, cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, malic acid Diisostearyl, di-2-ethylhexanoic acid ethylene glycol, dicaprate neopentyl glycol, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, tri Synthetic ester oils such as trimethylolpropane isostearate and pentane erythritol tetra-2-ethylhexanoate, dimethylpolysiloxane, methylphenylpoly Loxane, linear polysiloxane such as diphenylpolysiloxane, cyclic polysiloxane such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane, amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, Oil agents such as silicone oil such as modified polysiloxane such as fluorine-modified polysiloxane, anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether of alkyl sulfate, chloride Cationic surfactants such as stearyltrimethylammonium, benzalkonium chloride, laurylamine oxide, imidazoline-based amphoteric surfactants (2-cocoyl-2-imida Zolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), amphoteric surfactants such as acylmethyltaurine, propylene glycol fatty acid esters ( Propylene glycol monostearate), hardened castor oil derivatives, glycerin alkyl ether, POE alkylphenyl ethers (POE nonylphenyl ether, etc.), pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.) ), Nonionic surfactants such as tetronics, glycerin, 1,3-butanediol, isoprene glycol, 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1, -Octanediol, polyethylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, 2,4-hexylene glycol and other polyhydric alcohols, sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, etc. Moisturizing ingredients, guar gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, heparan Sulfuric acid, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, mu Itine sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, keratosulfate, locust bean gum, succinoglucan, carolinic acid, chitin, chitosan, carboxymethyl chitin, agar, polyvinyl alcohol, polyvinyl pyrrolidone, carboxyvinyl polymer, polyacrylic acid Thickeners such as sodium, polyethylene glycol, bentonite, surface may be treated, mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic anhydride (silica), aluminum oxide, barium sulfate, etc. Powders, surface may be treated, bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments, surface may be treated, mica Titanium, fish phosphorus foil, oki Pearl agents such as bismuth chloride, red 202, red 228, red 226, yellow 4, blue 404, yellow 5, red 505, red 230, red 223 which may be raked No., Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204 and other organic pigments, polyethylene powder, polymethyl methacrylate, nylon powder, Organic powders such as organopolysiloxane elastomers, paraaminobenzoic acid UV absorbers, anthranilic acid UV absorbers, salicylic acid UV absorbers, cinnamic acid UV absorbers, benzophenone UV absorbers, sugar UV absorbers 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole, 4-methoxy-4′-t-butyldibenzo UV absorbers such as ilmethane, lower alcohols such as ethanol and isopropanol, vitamin A or a derivative thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B12, vitamin B15 or Vitamin B such as derivatives thereof, vitamin E such as α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetate, vitamin D, vitamin H, vitamin H, pantothenic acid, panthetin, pyrroloquinoline quinone, etc. Preferred examples can be given. The skin external preparation of this invention can be manufactured by processing these according to a conventional method.

  The topical skin preparation of the present invention contains an active ingredient of one or more quasi-drugs selected from anti-inflammatory agents such as alkyl glycyrrhetinate, glycyrrhizic acid or a salt thereof, and the quasi-drug. It is also possible and preferable. In the case of taking such a quasi-drug form, in the indication that it is a quasi-drug, an indication that it is a quasi-drug that appealed to reduce inflammation, and how to use it, Take an appropriate amount and include it in cut cotton etc. in a lightly inflamed area, lightly rubbing it, applying it by pressing operation, indication that the inflammation is reduced by the application, and the operation Therefore, it is preferable that a display indicating that the use is immediately stopped is given when a feeling of burning or burning is felt.

  The external preparation for skin of the present invention can be obtained by treating these components according to a conventional method. The dosage form of the external preparation for skin of the present invention is not particularly limited, and specific examples include creams, emulsions, milk lotions, packs and the like.

  Hereinafter, the present invention will be described in more detail with reference to examples, but it is needless to say that the present invention is not limited to such examples.

A skin external preparation 1 of the present invention was prepared according to the formulation shown below. That is, weigh each component of a), b) and c), heat i), b) and c) to 80 ° C. and stir b) to b) and then add c) to the topical skin preparation. 1 was obtained. In Example 1, Comparative Example 1 was obtained by replacing lysyl-glutamine (Production Example 1) with water.
I)
Glycerin 5.0% by mass
1,3-butanediol 5.0% by mass
Polyoxyethylene (50EO) hydrogenated castor oil 1.0% by mass
α-tocopherol 0.1% by mass
B)
Water 40.0% by mass
Carboxyvinyl polymer 0.2% by mass
(Goodrich)
Dipotassium glycyrrhizinate 0.1 mass c)
Lysyl-glutamine (Production Example 1) 2.0% by mass
Water 46.6% by mass

According to the formulation shown below, the skin external preparation 2 of the present invention was prepared in the same manner as in Example 1. In Example 2, Comparative Example 2 was obtained by replacing lysyl-glutamine (Production Example 1) with water.
I)
Glycerin 5.0% by mass
1,3-butanediol 5.0% by mass
Sucrose monolaurate 0.5% by mass
Decaglycerin monolaurate 0.5 mass%
α-tocopherol 0.1% by mass
B)
Water 40.0% by mass
Carboxyvinyl polymer 0.2% by mass
(Goodrich)
Dipotassium glycyrrhizinate 0.1 mass c)
Lysyl-glutamine (Production Example 1) 2.0% by mass
Water 46.6% by mass

<Test Example 1> Formulation stability test 1
After the skin external preparations produced in Example 1 and Example 2 were allowed to stand at 20 ° C. for 1 day, the viscosity (mPs) was measured with a rotary viscometer. Thereafter, the mixture was allowed to stand at 50 ° C. for 1 week, returned to 20 ° C. for 1 day, and the viscosity was measured again. The results are shown in Table 1.

  From the results shown in Table 1, it was found that the external preparation for skin 1 of Example 1 was suppressed from decreasing in viscosity after high-temperature storage as compared with the sample of Comparative Example 1. Also in the skin external preparation of Example 2, it turned out that the fall of the viscosity at the time of high temperature storage is suppressed compared with the sample of the comparative example 2. However, the skin external preparation 1 using a polyoxyethylene-based surfactant has less decrease in viscosity than the skin external preparation 2 using a polyglycerin or a saccharide-based surfactant, and the effect of the present invention. Appears more clearly.

A skin external preparation 3 of the present invention was prepared according to the formulation shown below. That is, the components (a) were mixed and heated to 80 ° C. On the other hand, each component of (b) was mixed and heated to 80 ° C. To the mixture of (I), the mixture of (B) was added and stirred to emulsify, and then cooled to 35 ° C. to obtain a skin external preparation 3 of the present invention. In Example 3, lysyl-glutamine (Production Example 1) was replaced with water as Comparative Example 3.
I)
Polyoxyethylene (20EO) stearate 2.0% by mass
Polyoxyethylene (5EO) glyceryl monostearate 1.0% by mass
Squalane 10.0% by mass
Cetyl isooctanoate 4.0% by mass
Cetanol 5.0% by mass
Methylparaben 0.2 mass%
Glycerin 10.0% by mass
1,3-butanediol 5.0% by mass
(B)
Dipotassium glycyrrhizinate 0.01% by mass
Lysyl-glutamine (Production Example 1) 1.0% by mass
Water 61.79% by mass

<Test Example 2> Formulation stability test 2
The hardness of the external preparation for skin prepared in Example 3 was measured. Each sample was filled in a glass container having a diameter of 5 cm and a height of 3 cm, covered, and stored at 20 ° C. for 1 day. Then, using a hardness meter (Curdmeter MAX ME-303), using a contact surface of 8 mmφ and a load of 100 g Hardness was measured. Next, each sample was stored in a thermostatic chamber at 50 ° C. for one week. After storage for 1 week, the sample was returned to the room at 20 ° C., and the hardness was measured after 1 hour. The results are shown in Table 2.

  From the results shown in Table 2, it was found that the external preparation for skin 3 of the present invention suppressed the decrease in hardness after high-temperature storage as compared with the sample of Comparative Example 3.

A skin external preparation 4 of the present invention was prepared according to the formulation shown below. That is, the components (a) were mixed and heated to 70 ° C. On the other hand, each component of (b) was mixed and heated to 70 ° C. Preliminarily emulsified by adding the mixture of (i) to the mixture of (b), and further emulsified uniformly with a homomixer, and cooled to 30 ° C. with stirring after emulsification to obtain the skin external preparation 4 of the present invention. It was. In Example 4, Comparative Example 4 was obtained by replacing lysyl-glutamine (Production Example 1) with water.
I)
Behenyl alcohol 1.0 mass%
Cetyl isooctanoate 2.0% by mass
Squalane 8.0 mass%
Stearic acid 0.5% by mass
Polyoxyethylene (40EO) monostearate ester 1.0% by mass
Glycerol monostearate 0.5% by mass
α-tocopherol 0.1% by mass
Methylparaben 0.1% by mass
B)
1,2-octanediol 2.0% by mass
Glycerin 5.0% by mass
Carboxyvinyl polymer 0.2% by mass
Dipotassium glycyrrhizinate 0.05% by mass
C)
Lysyl-glutamine (Production Example 1) 0.2% by mass
Water 79.35% by mass

According to the formulation shown below, the skin external preparation 5 of the present invention was produced in the same manner as in Example 4. In Example 5, the tripeptide prepared in Production Example 2 was replaced with water and used as Comparative Example 5.
I)
Behenyl alcohol 1.0 mass%
Cetyl isooctanoate 2.0% by mass
Squalane 8.0 mass%
Stearic acid 0.5% by mass
Polyoxyethylene (20EO) monostearate ester 1.0% by mass
Polyoxyethylene (6EO) sorbitan monooleate 0.5% by mass
Glycerin monolaurate 0.5% by mass
Stearyl glycyrrhetinate 0.1% by mass
Methylparaben 0.1% by mass
B)
1,2-pentanediol 2.0% by mass
1.2-butanediol 5.0% by mass
Carboxyvinyl polymer 0.1% by mass
Dipotassium glycyrrhizinate 0.1% by mass
C)
Tripeptide (Production Example 2) 4.0% by mass
75.1% by mass of water

<Test Example 3> Formulation stability test 3
Each sample produced in Example 4 and Example 5 was allowed to stand at 20 ° C. for 1 day, and then the viscosity was measured with a rotary viscometer. Thereafter, the mixture was allowed to stand at 50 ° C. for 1 week, returned to 20 ° C. for 1 day, and the viscosity was measured again. The results are shown in Table 3.

  From the results of Table 3, the skin external preparation 4 of Example 4 and the skin external preparation 5 of Example 5 have a higher viscosity maintaining effect after high-temperature storage than the samples of Comparative Example 4 and Comparative Example 5, respectively. It was found that the structure of the formulation system was stabilized.

  The present invention can be applied to skin external preparations such as quasi drugs and cosmetics.

Claims (10)

A skin external preparation characterized by containing one or more selected from the group consisting of peptides or salts thereof having lysyl-glutamine as a partial structure. The skin external preparation according to claim 1, wherein the peptide is a dipeptide or a tripeptide. The skin external preparation according to claim 1 or 2, wherein the peptide is a compound represented by the following structural formula (I).

Structural formula (I) Content in the skin external preparation of the said peptide is 0.01-10 mass%, The skin external preparation in any one of Claims 1-3 characterized by the above-mentioned. Furthermore, the non-ionic surfactant is contained, The skin external preparation in any one of Claims 1-4 characterized by the above-mentioned. The skin external preparation according to claim 5, wherein the nonionic surfactant is a surfactant having a polyoxyethylene chain. Furthermore, 0.01-1 mass% of 1 type or 2 types or more selected from alkyl glycyrrhetic acid, glycyrrhizic acid, or its salt is contained, The any one of Claims 1-6 characterized by the above-mentioned. Skin external preparation. The external preparation for skin according to claim 7, wherein glycyrrhizic acid or a salt thereof is dipotassium glycyrrhizinate and alkyl glycyrrhetinate is stearyl glycyrrhetinate. It is a cosmetic, The skin external preparation in any one of Claims 1-8 characterized by the above-mentioned. The external preparation for skin according to any one of claims 1 to 9, which is a quasi-drug.