JP5165299B2 - Topical skin preparation - Google Patents

Description

  The present invention relates to an external preparation for skin in the form of an emulsifier or a solubilizer containing a whitening agent, an anti-inflammatory agent, or a dermal structure improving agent.

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, tranexamic acid, hydroquinone, ascorbic acid, triterpenic acid, etc., known as whitening agents (melanin production inhibitors), anti-inflammatory agents, and dermis structure improving agents, are tissues in which stratum corneum cells are densely layered to form a barrier In order to obtain a sufficient effect, it is necessary to sufficiently enhance the transdermal absorbability because it is a component that exhibits activity by passing through the skin and reaching the basal layer or dermis of the epidermis.
However, when these components are added to an emulsifier-type or solubilizer-type skin external preparation, the formed emulsion particles (dispersed phase particles of emulsion) and micelles are affected by various environmental effects. There is a problem in that the particle diameter increases and the transdermal absorbability tends to decrease. That is, in order to ensure sufficient transdermal absorbability of the above components, it is necessary to adjust 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). Further, the increase in particle diameter due to coalescence / association of micelles and emulsion particles eventually causes separation / separation and precipitation of insoluble matter such as crystals in the preparation. In particular, an external preparation for skin containing components having low solubility in oily components and low solubility in aqueous components, such as triterpenic acid derivatives and phytosterol derivatives, tends to cause precipitation of insoluble matters.

  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 1, Patent Literature 2, Patent Literature 3, and Patent Literature 4). However, the influence of such components on emulsion particles and micelles is not known at all.

JP 2004-196733 A JP 07-304653 A Japanese Patent Laid-Open No. 04-308515 Japanese Patent Laid-Open No. 03-020208 Luppi B., et.al., Drug Deliv. 2002; 9 (3): 147-52

  The present invention has been made under such circumstances, and is an emulsifier-type or solubilizer-type skin external preparation containing a whitening agent, an anti-inflammatory agent, or a dermis structure-improving agent. The objective is to provide a means to suppress unions and meetings.

In view of such a situation, the present inventors have combined emulsion particles and micelles in an emulsifier-type or solubilizer-type skin external preparation containing a whitening agent, an anti-inflammatory agent, or a dermis structure-improving agent.・ As a result of earnest research efforts to find a means to suppress association, protein hydrolyzate acylated with an acyl group having 10 to 30 carbon atoms has the effect of suppressing coalescence / association of emulsion particles and micelles. I found out that I have it and came to complete the invention. That is, the present invention is as follows.

(1) 1) Whitening agent, anti-inflammatory agent or dermis structure improving agent 0.01 to 10% by mass, 2) silk protein hydrolyzate and / or salt acylated with lauroyl group, and 3) surfactant (Excluding protein hydrolysates and / or salts thereof acylated with an acyl group having 10 to 30 carbon atoms),
Emulsifier, wherein the average particle size of emulsion particles or micelles after storage for 1 month at 40 ° C. after manufacture is 1.0 to 2.0 times the average particle size of emulsion particles or micelles immediately after manufacture A skin external preparation in the form of a solubilizer ,
The whitening agent is at least one selected from tranexamic acid or a derivative thereof, hydroquinone or a derivative thereof, triterpenic acid or a derivative thereof, ascorbic acid or a derivative thereof, and salicylic acid or a derivative thereof.
The anti-inflammatory agent is at least one selected from tranexamic acid or a derivative thereof, triterpenic acid or a derivative thereof, ascorbic acid or a derivative thereof, salicylic acid or a derivative thereof, and estradiol or a derivative thereof,
The dermatological structure improving agent is a skin external preparation, which is at least one selected from triterpenic acid or a derivative thereof, campesterol or a derivative thereof, and ascorbic acid or a derivative thereof.
(2) 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 skin external preparation as described in (1).
(3) 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).

  According to the present invention, a means for suppressing the coalescence / association of emulsion particles or micelles in an emulsifier-type or solubilizer-type skin external preparation containing a whitening agent, an anti-inflammatory agent or a dermis structure improving agent is provided. Can do. Thereby, it becomes possible to fully exhibit each effect | action of the said whitening agent, an anti-inflammatory agent, or a dermis structure improving agent.

<1> Whitening agent, anti-inflammatory agent or dermis structure improving agent which is an essential component of the skin external preparation of the present invention The skin external preparation of the present invention contains a whitening agent, anti-inflammatory agent or dermis structure improving agent. And
Examples of the whitening agent include tranexamic acid and / or salts thereof, tranexamic acid such as tranexamic acid ester such as ethyl tranexamic acid and propyl tranexamic acid, tranexamic acid methylamide, tranexamic acid alkylamide such as tranexamic acid ethylamide, and derivatives thereof;
Hydroquinone and / or derivatives thereof, such as hydroquinone glycosides such as hydroquinone and / or a salt thereof, hydroquinone glucoside, hydroquinone maltoside;
Ursolic acid and / or salt thereof, oleanolic acid and / or salt thereof, triterpenic acid and / or salt thereof such as betulinic acid and / or salt thereof, benzyl ursolate, methyl ursolate, lauryl laurate, ursolic acid phosphate ester , Triterpenic acid such as triterpenic acid esters such as ursolic acid sulfate or derivatives thereof;
Ascorbic acid and / or its salt, ascorbic acid ester or its salt such as ascorbic acid phosphate and / or its salt, ascorbic acid glycoside such as ascorbic acid 2-glucoside and / or its salt or its salt Acid or derivative thereof;
Salicylic acid and / or salt thereof, salicylic acid ester such as methyl salicylate, ethyl salicylate, 3-methoxysalicylic acid, 3-ethoxysalicylic acid, 4-methoxysalicylic acid, 4-ethoxysalicylic acid, 4-propoxysalicylic acid, 4-isopropoxysalicylic acid, 4- Salicylic acid such as butoxysalicylic acid, 5-methoxysalicylic acid, 5-ethoxysalicylic acid, 5-propoxysalicylic acid and / or salts thereof, or derivatives thereof;
Examples include ceramides such as ceramide type 1, ceramide type 2, ceramide type 3, ceramide type 4, ceramide type 5, ceramide type 6, and ceramide type 7.

Examples of the anti-inflammatory agent include tranexamic acid or derivatives thereof as described above; triterpenic acid or derivatives thereof; ascorbic acid or derivatives thereof; salicylic acid or derivatives thereof; ceramide; estrogen such as estradiol and estriol, indomethacin, ketoprofen, Vitamin Bs such as ketotifen, tiaramid hydrochloride, vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ or derivatives thereof, vitamin B ₁₂ , vitamin B ₁₅ or derivatives thereof; α-tocopherol, Vitamin E such as β-tocopherol, γ-tocopherol, and vitamin E acetate; vitamin H, pantothenic acid, panthetin, pyrroloquinoline quinone, and the like.

  Examples of the dermal structure-improving agent include triterpenic acid or derivatives thereof as described above; phytosterols such as campesterol, sitosterol, stigmasterol, campesterol glucoside, sitosterol glucoside, stigmasterol glucoside, stigmasterol maltoside, or the like Ascorbic acid or derivatives thereof as described above; ceramide; dexamethasone, prednisolone and the like.

  The preferred content of the whitening agent, anti-inflammatory agent or dermis structure improving agent is determined according to the type of the component, but is 0.01 to 10% by mass, more preferably 0.05 to 5% by mass. It is.

<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 is not particularly limited as long as it is a protein used in an external preparation for skin such as cosmetics, but is not limited, but is a grain protein such as soybean protein, wheat protein, rice protein, or a fiber-derived protein such as silk protein or sericin, 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, from the viewpoint of usability, a sodium salt is preferable.

  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 0.1 to 20 times by mass, more preferably relative to the whitening agent, anti-inflammatory agent or dermis structure improving agent. It is 0.2-2 mass times.
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 type, 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 after production are both preferably 10 μm or less, more preferably 9 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 9 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.
Add 1% of 1% osmic acid to about 1 g of the composition, scoop it with a spatula, put it into liquid nitrogen, make it into a frozen mass, and use this 10% by weight carboxymethylcellulose aqueous solution to make a sample of an auto cryotome Freeze and fix to a table, cut into 5 μm thickness with auto cryotome and create section. 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 skin external preparation of the present invention is in the form of an emulsifier, it can remarkably enjoy the effect of suppressing the decrease in the action of the whitening agent, anti-inflammatory agent or dermis structure improving agent, particularly due to coalescence and association of emulsion particles.

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 (PO
E behenyl ether, POE2-octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics Nonionic surfactants such as POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), sucrose fatty acid ester, alkyl glucoside and the like.
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, It is also preferable to use thickeners such as pectin.

  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; vitamins Preferred examples include epidermis structure improving agents such as A or derivatives thereof; antibiotics such as gentamicin sulfate, bacitracin, minomycin, paromycin, and antifungal agents such as bifonazole, terbinafine, butenafine, and ciclopirox.

  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 is used for the purpose of treatment, prevention and improvement of specific skin diseases and symptoms according to various actions possessed by the whitening agent, anti-inflammatory agent or dermis structure improving agent and the like. For example, melanin production inhibitor, anti-inflammatory, antibacterial, acne care, antioxidant, whitening skin preparation, cosmetics for preventing or improving pigmentation (including quasi-drugs) It is preferable to improve wrinkles and sag. Specifically, cosmetics such as sun care lotion and sun care milk, basic cosmetics for UV protection, cosmetics and anti-inflammatory drugs for anti-inflammation, basic cosmetics for wrinkle improvement, under-makeup and control Color and foundation 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.

  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, Comparative Example 1 in which “Promois EFLS” (lauroyl silk protein hydrolyzate sodium salt; manufactured by Seiwa Kasei Co., Ltd.) was replaced with water and Comparative Example 2 in which POE (80) hydrogenated castor oil was replaced were the same. It was prepared.

<Test Example 1>
Frozen sections of Lotion 1, Comparative Example 1 and Comparative Example 2 were prepared, and the particle diameter of the convex portion corresponding to the micelle was measured from an enlarged photograph of 15000 times this, and the average was obtained. . 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.

  In the same manner as in Example 1, an oil-in-water emulsifier type emulsion 1 (quasi-drug), which is a skin external preparation of the present invention, was prepared. Comparative Example 3 in which “Promois EFLS” was replaced with water and Comparative Example 4 in which POE (80) hydrogenated castor oil was replaced were also prepared. Emulsion 1, Comparative Example 3, and Comparative Example 4 were evaluated in the same manner as Test Example 1. The results are shown in Table 4. In the emulsifier form as well as the solubilizer form, it can be seen that “Promois EFLS”, which is an acylated protein hydrolyzate, suppresses the coalescence and association of micelles.

  Emulsions 2 to 10 were prepared by changing the ascorbic acid-2-glucoside of Emulsion 1 to the components shown in Table 6, and the same examination as in Example 2 was performed. However, the evaluation was limited to storage at 40 ° C. for one month, which had a significant change in Example 2. The results are shown in Table 6. From this, it was confirmed that the acylated protein hydrolyzate has an effect of suppressing coalescence / association of emulsion particles in an external preparation for skin containing various active ingredients.

In the same manner as in Example 3, emulsions 11 to 13 were prepared by examining the ascorbic acid-2-glucoside of emulsion 1 with the aqueous components shown in Table 8, and examined. The results are shown in Table 8. From this, it is understood that coalescence / association of emulsion particles is suppressed even in a skin external preparation containing an aqueous component.

  “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 (IS). ) "(Isostearoyl silk protein hydrolyzate; manufactured by Seiwa Kasei Co., Ltd.), emulsions 14 and 15 were prepared and examined in the same manner. The results are shown in Table 10. From this, it was found that any acylated protein hydrolyzate can be used, but lauroyl silk protein hydrolyzate is particularly excellent in suppressing coalescence and association of emulsion particles.

  According to the prescription shown below, it operated similarly to Example 2 and Example 5, 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 a skin external medicine and cosmetics.

Claims (3)

1) Whitening agent, anti-inflammatory agent or dermis structure improving agent 0.01 to 10% by mass, 2) silk protein hydrolyzate and / or salt thereof acylated with lauroyl group, and 3) surfactant (lauroyl group) Silk protein hydrolyzate and / or salt thereof acylated by
Emulsifier, wherein the average particle size of emulsion particles or micelles after storage for 1 month at 40 ° C. after manufacture is 1.0 to 2.0 times the average particle size of emulsion particles or micelles immediately after manufacture A skin external preparation in the form of a solubilizer ,
The whitening agent is at least one selected from tranexamic acid or a derivative thereof, hydroquinone or a derivative thereof, triterpenic acid or a derivative thereof, ascorbic acid or a derivative thereof, and salicylic acid or a derivative thereof.
The anti-inflammatory agent is at least one selected from tranexamic acid or a derivative thereof, triterpenic acid or a derivative thereof, ascorbic acid or a derivative thereof, salicylic acid or a derivative thereof, and estradiol or a derivative thereof,
The dermatological structure improving agent is a skin external preparation, which is at least one selected from triterpenic acid or a derivative thereof, campesterol or a derivative thereof, and ascorbic acid or a derivative thereof. 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. The skin external preparation described in 1. 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 1. An external preparation for skin according to Item 1.