JP5069965B2 - Topical skin preparation - Google Patents

Description

  The present invention relates to a skin external preparation in the form of an emulsifier or a solubilizer containing 4-alkylresorcinol.

In external preparations for skin, such as cosmetics, micelle formation technology such as emulsification technology or solubilization technology is one key technology. This is because there is an advantage that the lipophilic component and the hydrophilic component can be simultaneously administered to the skin by taking the emulsifier form or the solubilizer form.
On the other hand, 4-alkylresorcinol is already known to be an active ingredient of an external preparation for skin having excellent melanin production inhibitory action (see, for example, Patent Document 1, Patent Document 2, and Patent Document 3). When emulsified or solubilized in skin external preparations, the formed emulsion particles (dispersed phase particles of emulsion) and micelles are affected by various environments to cause coalescence and association. There exists a problem that these particle diameters are easy to increase. Such an increase in particle size eventually causes separation / separation of the preparation and precipitation of insoluble substances such as crystals in the preparation. Furthermore, it is said that such an increase in particle diameter not only affects the stability of the external preparation for skin, but also affects the transdermal absorbability of the active ingredient contained in the external preparation for skin. In particular, 4-alkylresorcinol is a component that exerts its action by densely passing through a tissue in which stratum corneum cells are layered and building a barrier, and reaches the target site. In order to fully exhibit the above, it is necessary to control the particle size of the emulsion particles and micelles to an appropriate size and maintain it for a long period of time. The appropriate size is said to be as small as several μm or less (see, for example, Non-Patent Document 1).

On the other hand, protein hydrolyzate such as silk, acylated by introducing an acyl group having 10 to 30 carbon atoms, is already known as a cosmetic raw material and is used for the purpose of moisturizing hair (for example, , Patent Literature 4, Patent Literature 5, Patent Literature 6, and Patent Literature 7). However, the effect of such components on micelles is not known at all. In addition, a technique for combining a non-acylated protein hydrolyzate and a resorcinol into a skin external preparation is known (see, for example, Patent Document 8 and Patent Document 9). The coalescence / association of micelles of the external preparation for skin containing emulsifier or solubilizer containing resorcinols could not be suppressed.
That is, it is not known that the acylated protein hydrolyzate has an action of suppressing the coalescence / association of micelles of an external preparation for emulsifier or solubilizer containing 4-alkylresorcinol. Also, an emulsifier-type or solubilizer-type skin external preparation containing acylated protein hydrolyzate and 4-alkylresorcinol has not been known.

JP 2006-282554 A JP 2006-124358 A JP 2006-124357 A JP 2004-196733 A JP 07-304653 A Japanese Patent Laid-Open No. 04-308515 Japanese Patent Laid-Open No. 03-020208 Special Table 2007-502326 JP 2000-44460 A Luppi B., et.al., Drug Deliv. 2002; 9 (3): 147-52

  The present invention has been made under such circumstances. In the skin external preparation in the form of an emulsifier or solubilizer containing 4-alkylresorcinol and / or a salt thereof, the emulsion particles or micelles are combined. 1. To provide a means to suppress the meeting.

  In view of such a situation, the present inventors suppressed the integration / association of micelles in an emulsifier-type or solubilizer-type skin external preparation containing 4-alkylresorcinol and / or a salt thereof. As a result of earnest research efforts, the protein hydrolyzate acylated with an acyl group having 10 to 30 carbon atoms has the effect of suppressing the coalescence / association of emulsion particles and micelles. I found out and came to complete the invention. That is, the present invention is as follows.

(1) 1) 4-alkylresorcinol and / or salt thereof, 2) protein hydrolyzate and / or salt thereof acylated with an acyl group having 10 to 30 carbon atoms , and 3) surfactant (carbon number 10) A skin external preparation in the form of an emulsifier or a solubilizer, comprising a protein hydrolyzate and / or a salt thereof acylated with ˜30 acyl groups) .
(2) The average particle size of emulsion particles or micelles after storage at 40 ° C. for 1 month after production is 1.0 to 2.0 times the average particle size of emulsion particles or micelles immediately after production, The external preparation for skin according to (1).
(3) It is an emulsifier type, and the average particle size of emulsion particles immediately after production and the average particle size of emulsion particles after storage for 1 month at 40 ° C. after production are both 10 μm or less, The external preparation for skin according to (1) or (2).
(4) It is a solubilizer form, and the average particle size of micelles immediately after production and the average particle size of micelles after storage at 40 ° C. for 1 month are both 1.0 μm or less. The external preparation for skin according to (1) or (2).
(5) The skin external preparation according to any one of (1) to (4), wherein the protein hydrolyzate is a silk protein hydrolyzate.
(6) The acyl group is at least one of a lauroyl group, a myristoyl group, a palmitoyl group, a stearoyl group, an isostearoyl group and an oleoyl group, according to any one of (1) to (5) The skin external preparation as described.
(7) The 4-alkylresorcinol is 4-n-butylresorcinol, 4-cyclopentylresorcinol, 4-cyclohexylresorcinol, 4- (1-phenyl) ethylresorcinol, 4- (2-phenyl) ethylresorcinol, 4-iso Octyl resorcinol, 4-amyl resorcinol, 4-isoamyl resorcinol, 4-isobutyl resorcinol, 4-tertiary butyl resorcinol, 4- (1-methylpropyl) resorcinol, 4- (1-methylbutyl) resorcinol, 4- (1-ethyl Propyl) resorcinol, 4- (1-ethyl-2-methylpropyl) resorcinol, 4- (1-isopropyl-2-methylpropyl) resorcinol, 4- (1-dimethyl-3-methylbutyl) resorcinol 4- (1-butylpentyl) resorcinol, 4- (1-isobutyl-3-methylbutyl) resorcinol and 4-isostearylresorcinol, any one of (1) to (6) An external preparation for skin according to crab.
(8) The skin external preparation according to any one of (1) to (7), further comprising at least one of the following components.
(component)
Ascorbic acid, triterpenic acid, salicylic acid, phytosterol, ceramide, tranexamic acid, hydroquinone, and derivatives thereof.

  ADVANTAGE OF THE INVENTION According to this invention, in the emulsifier form or the solubilizer form external preparation for skin containing 4-alkyl resorcinol, the means which suppresses coalescence and association of an emulsion particle or a micelle can be provided. Thereby, it becomes possible to fully exhibit the effect | action represented by the whitening effect | action of 4-alkyl resorcinol.

<1> 4-Alkylresorcinol and / or its salt which is an essential component of the skin external preparation of this invention contains 4-alkylresorcinol and / or its salt as an essential component. The alkyl group in 4-alkylresorcinol may be linear, branched or cyclic, and preferably has 2 to 20 carbon atoms, more preferably 3 to 18 carbon atoms. . Specifically, the alkyl group includes a propyl group, an n-butyl group, an i-butyl group, a tert-butyl group, an amyl group, an isoamyl group, a cyclopentyl group, a cyclohexyl group, an isooctyl group, a 1-methylpropyl group, 1 -Methylbutyl group, 1-ethylpropyl group, 1-ethyl-2-methylpropyl group, 1-isopropyl-2-methylpropyl group, 1-dimethyl-3-methylbutyl group, 1-butylpentyl group, 1-isobutyl-3 Preferred examples include -methylbutyl group, 1-phenylethyl group, 2-phenylethyl group, and 4-isostearyl group. Of these, an n-butyl group is preferable.
4-alkylresorcinol is a method of condensing resorcin and a carboxylic acid corresponding to the above alkyl group in the presence of zinc chloride and reducing with zinc amalgam / hydrochloric acid, or resorcin and an alcohol corresponding to the above alkyl group. It can be produced by a known method such as a method of condensation at a high temperature of ˜400 ° C. (for example, Lille. J. Bitter, LA. Peiner. V, Tr. Nauch-Iasled. Inst. Slantsev (1969), No. 18, 127, Japanese Patent Laid-Open No. 2006-124358, Japanese Patent Laid-Open No. 2006-124357). Moreover, you may use a commercial item.

  Moreover, the salt of 4-alkylresorcinol should just be a physiologically acceptable salt normally used for a skin external preparation. For example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, organic amine salts such as ammonium salt, triethylamine and triethanolamine, and basic amino acid salts such as lysine and arginine are preferably exemplified. The

In the skin external preparation of this invention, 1 type may be contained among 4-alkyl resorcinol and its salt, and 2 or more types may be contained.
The content of 4-alkylresorcinol and / or a salt thereof in the external preparation for skin of the present invention can be determined according to the use etc. of the external preparation for skin, but is preferably 0.1 with respect to the total amount of external preparation for skin. -1 mass%, more preferably 0.2-0.5 mass%.

<2> Acylated protein hydrolyzate and / or salt thereof, which is an essential component of the skin external preparation of the present invention. The skin external preparation of the present invention is a protein hydrolyzed by an acyl group having 10 to 30 carbon atoms. Products and / or salts thereof. The acylated protein hydrolyzate is a product obtained by acylating the amino group of a polypeptide obtained by hydrolyzing a protein.
The protein may be a protein used in a skin external preparation such as cosmetics, and is not particularly limited. Preferred examples include collagens such as collagen derived from fish and collagen derived from pigs, and shellfish proteins such as conchiolin. Among these proteins, silk protein is preferably used. The molecular weight of the protein hydrolyzate is preferably about 200 to 1,000.
The acyl group may be linear or branched, and may be saturated or unsaturated. Carbon number is 10-30, and the thing of 10-24 is more preferable. Specifically, lauroyl group, myristoyl group, palmitoyl group, stearoyl group, behenoyl group, isostearoyl group, isopalmitoyl group, oleoyl group, linoloyl group and the like can be preferably exemplified, lauroyl group, myristoyl group, palmitoyl group, Those selected from stearoyl groups, isostearoyl groups and oleoyl groups are more preferred, and lauroyl groups are particularly preferred.
The acylated protein hydrolyzate may have one kind or two or more kinds among these acyl groups. For example, the protein hydrolyzate may be acylated using a natural oil-derived fatty acid containing a plurality of fatty acids such as coconut oil. In addition, the protein hydrolyzate acylated with the fatty acid derived from coconut oil is also called a cocoyl protein hydrolyzate.

  The acylated protein hydrolyzate can be produced, for example, as follows. The protein is hydrolyzed using an acid such as hydrochloric acid or sulfuric acid, an alkali such as sodium hydroxide or potassium hydroxide, or a protease such as pepsin, trypsin or papain. When using an acid or an alkali, reaction time can be shortened by heating to about 40-100 degreeC as needed. When protease is used, reaction conditions can be set according to the optimum pH and temperature of the enzyme. The hydrolyzate thus obtained is preferably purified through gel filtration, ultrafiltration, dialysis, an ion exchange column or the like after neutralization treatment as necessary.

  Subsequently, the protein hydrolyzate is acylated. The acylation can be performed using an acylating agent. As the acylating agent, acid chloride or the like can be used. Specifically, the acylated protein hydrolyzate used in the present invention can be obtained by reacting the fatty acid corresponding to the acyl group with an acid chloride and reacting with the polypeptide in the presence of an alkali.

  Further, the acylated protein hydrolyzate can be used as it is, but it is also a preferable form to form a salt with an alkali or the like. The salt of the acylated protein hydrolyzate may be a physiologically acceptable salt usually used in cosmetics and the like. For example, alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, organic amine salts such as ammonium salt, triethylamine and triethanolamine, and basic amino acid salts such as lysine and arginine are preferably exemplified. However, a sodium salt is preferable in terms of usability.

  The acylated protein hydrolyzate is commercially available, and it is also preferable to purchase and use such a commercial product. Commercially available products include “Promois ECP-C” (coconut oil fatty acid hydrolyzed collagen potassium salt; manufactured by Seiwa Kasei Co., Ltd.), “Promois EFLS” (Lauroyl silk protein hydrolyzate sodium salt; manufactured by Seiwa Kasei Co., Ltd.) And “Promois EF-118 (IS)” (isostearoyl silk protein hydrolyzate; manufactured by Seiwa Kasei Co., Ltd.).

The skin external preparation of the present invention may contain one of the acylated protein hydrolyzate and its salt, or may contain two or more.
The content of the acylated protein hydrolyzate and / or salt thereof in the external preparation for skin of the present invention is preferably 0.05 to 5% by mass, more preferably 0.1%, based on the total external preparation for skin. Contains 1% by mass. Further, the content of the acylated protein hydrolyzate and / or salt thereof is preferably 0.5 to 10 times by mass, more preferably 1 to 5 times by mass with respect to 4-alkylresorcinol and the like. .
The acylated protein hydrolyzate and / or salt thereof may be used as an emulsifier-type or solubilizer-type skin external preparation that is stored in a significant environmental change, for example, in a high temperature range or stored in a very low temperature range and frozen. Due to such environmental changes, the emulsion particles or micelles coalesce and associate with each other and have an action of suppressing an increase in the particle size.

<3> External preparation for skin of the present invention The external preparation for skin of the present invention contains the essential components and is in the form of an emulsifier or a solubilizer.
In the external preparation for skin of the present invention, the average particle diameter of emulsion particles or micelles after storage for 1 month at 40 ° C. is preferably 1.0 to 2.0 of the average particle diameter of emulsion particles or micelles immediately after manufacture. Times, more preferably 1.0 to 1.5 times. In addition, the average particle size of the emulsion particles or micelles after storage for 1 month at 5 ° C. after production is preferably 1.0 to 1.5 times the average particle size of the emulsion particles or micelles immediately after production, more preferably 1.0 to 1.1 times. In this case, the method for measuring the average particle size of emulsion particles or micelles after storage at 40 ° C. and 5 ° C. for one month after production and the method for measuring the average particle size of emulsion particles or micelles immediately after production are the same.
In the case of the emulsifier form, both the average particle size of the emulsion particles immediately after production and the average particle size of the emulsion particles after storage at 40 ° C. for 1 month are preferably 10 μm or less, more preferably 8 μm or less. It is. In addition, the average particle size of the emulsion particles after being stored at 5 ° C. for 1 month after production is preferably 10 μm or less, more preferably 8 μm or less.
In the case of the solubilizing agent form, the average particle size of micelles immediately after production and the average particle size of micelles after storage for 1 month at 40 ° C. after production are both preferably 1.0 μm or less, more preferably It is 0.8 μm or less, more preferably 0.2 μm or less. In addition, the average particle diameter of micelles after storage for 1 month at 5 ° C. is preferably 0.8 μm or less, more preferably 0.3 μm or less, and even more preferably 0.1 μm or less.
The measurement method of the average particle diameter in these cases is as follows.
That is, 1% of 1% osmic acid was added to about 1 g of the composition, scooped with a spatula, poured into liquid nitrogen, made into a frozen mass, and this was used as an autocrytome using a 10 mass% carboxymethylcellulose aqueous solution. The sample is frozen and fixed on the sample stage, cut into a thickness of 5 μm by an auto cryotome, and a section is prepared. This is fixed to an adhesive tape, freeze-dried, gold-deposited, and used as a sample. The sample is magnified 15000 times with a scanning electron microscope, the structure of the round convex portion corresponding to the micelle in 20 fields of view is extracted, actually measured on the enlarged photograph, and the average is obtained.

  When the external preparation for skin of the present invention is in the form of an emulsifier, the effect of suppressing a decrease in the action of 4-alkylresorcinol due to coalescence and association of emulsion particles can be remarkably enjoyed.

Moreover, it is preferable that the skin external preparation of this invention contains surfactant as an emulsifier or solubilizer for forming emulsion particle | grains or a micelle. In this case, the surfactant is not particularly limited as long as it is usually used for an external preparation for skin, and examples thereof include the following.
Natural surfactants such as lecithin, anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether alkyl sulfate; stearyltrimethylammonium chloride, benzalkonium chloride, lauryl Cationic surfactants such as amine oxides; imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine-based surfactants (alkylbetaines, amides) Amphoteric surfactants such as betaine, sulfobetaine), acylmethyltaurine, etc .; sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquistearate, sorbitan sesquioleate, etc.), glycerin fat Acids (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hydrogenated castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene monostearate) Sorbitan, etc.), POE sorbite fatty acid esters (POE-sorbitol monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerol monoisostearate, etc.), POE fatty acid esters (POE monooleate, POE distearate, etc.), POE alkyl Ethers (POE behenyl ether, POE2-octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluro Type, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), sucrose fatty acid Nonionic surfactants such as esters and alkyl glucosides.
Among these, POE alkyl ethers, sucrose fatty acid esters, and sorbitan fatty acid esters are preferably used.

  In addition, acrylic acid / alkyl methacrylate copolymers and / or salts thereof, carboxyvinyl polymers and / or salts thereof, alkyl-modified carboxyvinyl polymers and / or alginates, polyhydric alcohol esters of alginic acid, xanthan gum, hydroxypropyl cellulose, casein, Thickeners such as pectin are also preferably used.

Moreover, it is preferable that the skin external preparation of this invention further contains the component which becomes easy to occur coalescence and an association by setting it as the component of an emulsifier form or a solubilizer form. This is because such a component can also enjoy the same effects as those received by 4-alkylresorcinol. Such a component is not particularly limited as long as it is used in a skin external preparation such as a cosmetic or a skin external medicine.
For example, in the case of a cosmetic, ascorbic acid and / or a salt thereof, an ester such as ascorbic acid phosphate and / or a salt thereof or a salt thereof, an ascorbic acid-2-glucoside and / or a salt thereof ascorbic acid glycoside Ascorbic acid or derivatives thereof such as ursolic acid and / or salt thereof; tersolic acid and / or salt thereof; triterpenic acid and / or salt thereof such as betulinic acid and / or salt thereof; ursolic acid benzyl ester; Triterpenic acid such as triterpenic acid esters such as acid methyl ester, ursolic acid lauryl ester, ursolic acid phosphoric acid ester, ursolic acid sulfuric acid ester; campesterol, sitosterol, stigmasterol and other phytosterols, campesterol glucoside, Phytosterols such as tosterol glucoside, stigmasterol glucoside, stigmasterol maltoside or derivatives thereof; salicylic acid and / or salts thereof, salicylic acid esters such as methyl salicylate and ethyl salicylate, 3-methoxysalicylic acid, 3-ethoxysalicylic acid, 4-methoxy Salicylic acid such as salicylic acid, 4-ethoxysalicylic acid, 4-propoxysalicylic acid, 4-isopropoxysalicylic acid, 4-butoxysalicylic acid, 5-methoxysalicylic acid, 5-ethoxysalicylic acid, 5-propoxysalicylic acid and / or its salt salicylic acid or the like Derivatives; Ceramides such as Ceramide Type 1, Ceramide Type 2, Ceramide Type 3, Ceramide Type 4, Ceramide Type 5, Ceramide Type 6, Ceramide Type 7, etc .; Tranexamic acid or its derivatives, such as tramicamic acid esters such as tramicamic acid esters such as ethyl tranexamic acid, propyl tranexamic acid, tranexamic acid methylamide, tranexamic acid alkylamide; hydroquinone and / or salt thereof, hydroquinone glucoside Hydroquinone glycosides such as hydroquinone maltoside, hydroquinone or derivatives thereof, vitamin A or derivatives thereof, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ or derivatives thereof, vitamins Vitamin B such as B ₁₂ , Vitamin B ₁₅ or derivatives thereof, α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetate such as vitamin E acetate, vitamin D, vitamin Vitamins such as Min H, pantothenic acid, panthetin, pyrroloquinoline quinone and the like can be suitably exemplified, and if they are drugs for external use on skin, antifungal agents such as bifonazole, terbinafine, butenafine, ciclopirox, estrogens such as estradiol, estriol, Anti-inflammatory agents such as indomethacin, ketoprofen, ketotifen and tiaramid hydrochloride, bactericides such as chlorohexidine gluconate, benzalkonium chloride and popidone iodine, steroids such as dexamethasone and prednisolone, antibiotics such as gentamicin sulfate, bacitracin, minomycin and paromycin Etc. can be suitably exemplified. Although preferable content of this active ingredient changes also with the kind of component, it is 0.01-10 mass%, respectively, More preferably, it is 0.05-5 mass%.

  In the external preparation for skin of the present invention, in addition to the above components, optional components that are usually used in external preparations for skin can be contained.

  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, hydrogenated oil, molasses, hydrogenated castor oil, Oils and waxes such as beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax; hydrocarbons such as liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, microcrystalline wax; Higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, isopalmitic acid, stearic acid, behenic acid, undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl alcohol, Higher alcohols such as nyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol, etc .; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, diacid malate Isostearyl, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, tri-2-ethylhexanoate trimethylolpropane, triisostearin Synthetic ester oils such as acid trimethylolpropane and tetra-2-ethylhexanoic acid pentane erythritol; dimethylpolysiloxane, methylphenylpolysiloxane, diphth Chain polysiloxanes such as nylpolysiloxane, cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane, amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, fluorine-modified Oil agents such as silicone oil such as modified polysiloxane such as polysiloxane; polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, Polyhydric alcohols such as 1,2-pentanediol; moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid, sodium lactate; surface treated Mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic acid (silica), aluminum oxide, barium sulfate, etc .; surface may be treated, bengara, yellow oxidation Iron, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments; surface treated pearlescent agents such as titanium mica, fish phosphorus foil, bismuth oxychloride; rake Red 202, Red 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow Organic dyes such as No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204; polyethylene powder, polymethyl methacrylate, nylon powder, orange Organic powders such as ganopolysiloxane elastomer; paraaminobenzoic acid UV absorber, anthranilic acid UV absorber, salicylic acid UV absorber, cinnamic acid UV absorber, benzophenone UV absorber, sugar UV absorber UV absorbers such as 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole and 4-methoxy-4′-t-butyldibenzoylmethane; lower alcohols such as ethanol and isopropanol Preferred examples can be given.

The skin external preparation of the present invention is suitable for, for example, a skin external pharmaceutical composition, cosmetics including quasi-drugs, and skin external goods. Particularly preferred is a quasi-pharmaceutical product among external pharmaceutical compositions or cosmetics for skin. Further, the dosage form is not particularly limited as long as it is an emulsifier form or a solubilizer form, and for example, a lotion, emulsion, essence, cream, powder cosmetic, and the like are preferably exemplified.

  The external preparation for skin of the present invention can be used for the purpose of treatment, prevention and improvement of specific skin diseases and symptoms according to various actions possessed by 4-alkylresorcinol and the like, for example, melanin production It is preferably used as a skin external preparation for suppression, anti-inflammatory, antibacterial, acne care, antioxidant, whitening, and cosmetics (including quasi-drugs) for preventing or improving pigmentation. Specifically, cosmetics such as sun care lotion and sun care milk, basic cosmetics for UV protection, under makeup, control colors, and foundations are preferable.

  The skin external preparation of this invention can be manufactured by processing the said essential component and arbitrary components in accordance with a conventional method.

  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 solubilizer-type lotion (quasi-drug) was prepared according to the formulation shown below. That is, the components of (a) and (b) were heated to 80 ° C., respectively, and gradually added to (a) with stirring to solubilize and then cooled by stirring to obtain a solubilizer-type lotion 1. In the same manner, “Promois EFLS” (lauroyl silk protein hydrolyzate sodium salt; manufactured by Seiwa Kasei Co., Ltd.) was replaced with water, Comparative Example 1, and POE (80) hydrogenated castor oil was replaced with Comparative Example 2, Acyl Comparative Example 3 was also prepared in the same manner by substituting “Promois Silk-1000 (manufactured by Seiwa Kasei Co., Ltd.)” which is a hydrolyzed silk protein hydrolyzate.

<Test Example 1>
Frozen sections of Lotion 1, Comparative Example 1, Comparative Example 2 and Comparative Example 3 were prepared, and from the enlarged photo 15000 times, the particle diameters of the convex portions corresponding to micelles were measured, and the average was obtained. The particle size was taken. The specific measurement method is as described above. Similarly, the average particle size was determined for those stored at 40 ° C. for 1 month and those stored at 5 ° C. for 1 month. The results are shown in Table 2. From this, it can be seen that in the lotion of the present invention, the coalescence and association of micelles is remarkably suppressed.

<Test Example 2>
The whitening effect of the lotion 1, comparative example 1, comparative example 2 and comparative example 3 stored at 5 ° C. for 1 month was examined. That is, six 2 cm × 4 cm sites were prepared on the inner side of the forearm, one of which was the untreated control site, and the remaining 5 sites were irradiated with 1.5 MED UV irradiation (SE light) once a day for 5 consecutive days. The tanned part was prepared, and application of the specimen was started on each part from the third day after the tanned part was prepared. One site was used as a sunburn control site, and no sample was administered. The application amount was 20 μl / site, and the number of administrations was 60 times. Twenty-four hours after the last administration, the color difference (ΔE) relative to the untreated control site was measured with a “color difference meter CR-400” (manufactured by Konica Minolta). The results are shown in Table 3. As a result, the whitening effect of Lotion 1 in which the micelle particle size was kept fine was the most excellent. From this, it was found that the action of 4-alkylresorcinol can be increased by suppressing the coalescence / association of the emulsifier form.

By the same operation as in Example 1, an oil-in-water emulsifier type emulsion 1 (quasi-drug), which is an external preparation for skin of the present invention, was prepared. Comparative Example 4 in which “Promois EFLS” was replaced with water, Comparative Example 5 in which POE (80) hydrogenated castor oil was replaced, and Comparative Example 6 in which “Promois Silk-1000” was replaced were also prepared. Emulsion 1, Comparative Example 4, Comparative Example 5, and Comparative Example 6 were evaluated in the same manner as Test Example 1 and Test Example 2. The results are shown in Tables 5 and 6. It can be seen that, in the emulsifier form as well as the solubilizer form, “Promois EFLS”, an acylated protein hydrolyzate, suppresses the coalescence and association of micelles. Further, the whitening effect of the emulsion 1 was remarkable as compared with Comparative Example 4 , Comparative Example 5 and Comparative Example 6 .

  The same investigation as in Example 2 was performed by replacing 4-n-butylresorcinol in Emulsion 1 with another 4-alkylresorcinol. However, the stability was evaluated only at 40 ° C. for 1 month, where the change was severe in Example 2. The results are shown in Table 8. From this, it was found that also in a skin external preparation containing 4-alkylresorcinol other than 4-n-butylresorcinol, the acylated protein hydrolyzate suppresses coalescence / association of emulsion particles.

  “Promois EFLS” of Latex 1 was replaced with “Promois ECP-C” (coconut oil fatty acid hydrolyzed collagen potassium salt; manufactured by Seiwa Kasei Co., Ltd.), “Promois EF-118”, which is another acylated protein hydrolyzate. (IS) ”(isostearoyl silk protein hydrolyzate; manufactured by Seiwa Kasei Co., Ltd.), the same examination as in Example 3 was performed. The results are shown in Table 10.

  According to the prescription shown below, it operated similarly to Example 2 and Example 4, and compared the joint action of the micelle in acylated hydrolyzed protein. The results are shown in Table 12. The particularly superior effect of lauroyl silk protein hydrolyzate was demonstrated in the same experiment.

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

Claims (8)

1) 4-alkylresorcinol and / or salt thereof, 2) protein hydrolyzate and / or salt thereof acylated with an acyl group having 10 to 30 carbon atoms , and 3) surfactant (having 10 to 30 carbon atoms) A skin external preparation in the form of an emulsifier or a solubilizer, characterized by containing a protein hydrolyzate and / or a salt thereof acylated with an acyl group . The average particle size of emulsion particles or micelles after storage at 40 ° C. for 1 month after production is 1.0 to 2.0 times the average particle size of emulsion particles or micelles immediately after production, Item 1. An external preparation for skin according to Item 1. 2. The emulsifier type, and the average particle size of the emulsion particles immediately after production and the average particle size of the emulsion particles after storage at 40 ° C. for 1 month are both 10 μm or less. Or the external preparation for skin of 2. It is a solubilizer form, and the average particle size of micelles immediately after production and the average particle size of micelles after storage at 40 ° C. for one month after production are both 1.0 μm or less, Item 3. The topical skin preparation according to Item 1 or 2. The skin external preparation according to any one of claims 1 to 4, wherein the protein hydrolyzate is a silk protein hydrolyzate. The skin according to any one of claims 1 to 5, wherein the acyl group is at least one of a lauroyl group, a myristoyl group, a palmitoyl group, a stearoyl group, an isostearoyl group and an oleoyl group. Topical agent. The 4-alkylresorcinol is 4-n-butylresorcinol, 4-cyclopentylresorcinol, 4-cyclohexylresorcinol, 4- (1-phenyl) ethylresorcinol, 4- (2-phenyl) ethylresorcinol, 4-isooctylresorcinol, 4-amylresorcinol, 4-isoamylresorcinol, 4-isobutylresorcinol, 4-tertiarybutylresorcinol, 4- (1-methylpropyl) resorcinol, 4- (1-methylbutyl) resorcinol, 4- (1-ethylpropyl) resorcinol 4- (1-ethyl-2-methylpropyl) resorcinol, 4- (1-isopropyl-2-methylpropyl) resorcinol, 4- (1-dimethyl-3-methylbutyl) resorcinol, 4 It is at least one of (1-butylpentyl) resorcinol, 4- (1-isobutyl-3-methylbutyl) resorcinol and 4-isostearylresorcinol, according to any one of claims 1-6. Topical skin preparation. Furthermore, the skin external preparation as described in any one of Claims 1-7 containing at least one of the following components.
(component)
Ascorbic acid, triterpenic acid, salicylic acid, phytosterol, ceramide, tranexamic acid, hydroquinone, and derivatives thereof.