RU2428966C2 - Skin care preparation for external application in form of water-in-oil emulsion containing ceramides - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention is a cosmetic preparation for external application in form of a water-in-oil emulsion which contains ceramide in form of liposome, hectorite, modified quaternary ammonium salt, di(phytosteryl/octyldodecyl)N-lauroyl glutamate and phytosterol.

EFFECT: invention ensures adequate delivery of ceramide through the corneous layer.

2 cl, 4 ex, 8 tbl

Description

FIELD OF THE INVENTION

The present invention relates to preparations for external use for skin care, in particular to preparations for skin care for external use in the form of a water-in-oil emulsion.

State of the art

Today, one of the main problems in the field of dermatology is the exponential increase in cases of atopic dermatitis. The cause of atopic dermatitis is not clarified in detail, but it is believed that atopic dermatitis is caused by many factors, such as the reaction of skin hypersensitivity to many chemicals. Therefore, skin care products are needed to prevent chemicals from entering the living body. However, a component contained in an external skin care preparation administered for skin care may cause skin irritation. To prevent irritation, the effectiveness of this component is considered to improve the barrier function of the lower part of the stratum corneum by delivering ceramide or a similar substance to the dermis through the stratum corneum (Patent Documents 1 and 2). However, ceramides have low solubility in water and low solubility in oil, and there are many difficulties in obtaining compositions. Accordingly, improved methods for improving solubility for basic compositions using pseudoceramides (derivatives of ceramides) (patent document 3). Despite this, even if a skin preparation for external use produced by a similar technique is applied to the skin, it is very difficult to deliver ceramide directly to the dermis.

As means for delivering ceramide through the stratum corneum, agents have been developed for the formation of microspheres of a lipid bilayer membrane together with a phospholipid or similar substances (patent document 4). The technique facilitates the delivery of ceramide through the stratum corneum, but even when applying the technique, adequate delivery of ceramide through the stratum corneum is difficult, and the effects of ceramides in the skin care product for external use are not sufficiently manifested.

Organically modified clay minerals, such as organically modified bentonite and dimethyldystearylammonium chloride-modified hectorite, on the other hand, are used to stabilize the water-in-oil emulsion (Patent Documents 5 and 6). However, an external skin care preparation containing an organically modified clay mineral in conjunction with ceramide is not known.

Meanwhile, a skin-care preparation for external use in the form of a water-in-oil emulsion containing a diester of an N-acylated acidic amino acid is known (see Patent Documents 7, 8 and 9). However, an external preparation for skin care in the form of a water-in-oil emulsion containing a diester of an N-acylated acidic amino acid together with ceramide has not been fully studied.

Phytosterols are lipids that are found in plants and have a steroid skeleton, and typical examples include stigmasterol, sitosterol and campesterol. It is known that these components have an effect on the synchronization of the metabolic cycles of epidermal cells in the skin and the ability to increase the strength of the membrane, which has a two-layer structure in the liposome, etc. (Patent documents 10 and 11). However, an external skin care preparation in the form of a water-in-oil emulsion containing phytosterol together with ceramide is not known.

At the same time, crosslinked organosilicon compounds are generally used in an external skin care product such as a cosmetic, and the combined use of crosslinked organosilicon compounds and ceramide is known (for example, see Patent Document 12). However, an external skin care preparation in the form of a water-in-oil emulsion containing an organically modified clay mineral and crosslinked organosilicon compounds is not known.

[Patent Document 3] JP 2002-332208 A

[Patent Document 4] JP 2005-522463 A

[Patent Document 5] JP 11-246354 A

[Patent Document 6] WO 2003 / 041664A

[Patent Document 7] JP 5-279238 A

[Patent Document 8] JP 11-76799 A

[Patent Document 9] JP 8-20529 A

[Patent Document 10] JP 2004-230173 A

[Patent Document 11] JP 8-40823 A

[Patent Document 12] JP 2001-151628 A

Disclosure of invention

The purpose of the present invention is to provide a method for the delivery of ceramide through the stratum corneum for adequate manifestation of the effects of ceramide. In particular, it is an object of the present invention to provide an external skin care preparation containing ceramide that is capable of providing adequate delivery of ceramide in an external skin care preparation through the stratum corneum to the dermis when applying the external skin care preparation to the surface of the skin.

The authors of the present invention have carried out comprehensive studies to achieve the above objectives. As a result, they found that a skin-care product for external use in the form of a water-in-oil emulsion containing ceramide, an organically modified clay mineral, a diester of N-acylglutamic acid and phytosterol can sufficiently exhibit ceramide effects, therefore, consistent the present invention.

Thus, the present invention is as follows:

(1) a skin care preparation for external use in the form of a water-in-oil emulsion containing ceramide, an organically modified clay mineral, an N-acylglutamic acid diester and phytosterol;

(2) a skin preparation for external use according to (1), further comprising crosslinked dimethicone;

(3) a skin preparation for external use according to (1) or (2), wherein the ceramide is in the form of a liposome or niosome;

(4) a skin preparation for external use according to paragraphs. (1) to (3), wherein the organically modified clay mineral is a hectorite modified with a quaternary ammonium salt;

(5) a skin preparation for external use according to any one of paragraphs. (1) to (4), wherein the N-acylglutamic acid diester is di (phytosteryl / octyldodecyl) N-laurylglutamate;

(6) a skin preparation for external use according to any one of paragraphs. from (1) to (5), where the skin preparation for external use is a cosmetic product for protecting the skin from external chemical irritation; and

(7) a skin preparation for external use according to any one of paragraphs. from (1) to (6), in which the preparation for skin care for external use softens the course or prevents atopic dermatitis.

The best options for carrying out the invention

The skin care product for external use contains ceramide, an organically modified clay mineral, a diester of N-acylglutamic acid and phytosterol as mandatory components.

(1) Ceramide

A skin care product for external use contains ceramide as an essential component. In general, seven types of ceramides are known, ceramides of types 1-7, and all of them can be used. Of these, ceramides of types 2 and 3 are more preferred, and ceramide of type 2 is particularly preferred, and N-stearoyl-dihydroxy-sphignosin is particularly preferred. Ceramide products available for production are available and can be purchased and used. Preferred product examples include Ceramid I (manufactured by Cosmo Pharm) containing N- (27-octadecanoyloxy-heptacosanoyl) -phytosphingosine (type 1) as a component, Ceramid TIC-001 (manufactured by Takasogo International Corporation), containing N- stearoyl-dihydroxy-sphingosine (type 2) as a component, "Ceramid III" (manufactured by Cosmo Pharm) containing N-stearoyl-phytosphingosine (type 3) as a component, "Ceramid IIIA" (manufactured by Cosmo Pharm) containing N- linoleoyl-phytosphingosine (type 3) as a component, "Ceramid IIIB" (manufactured by Cosmo Pharm) containing N-oleoyl-phytosphingosine ( type 3) as a component, and Ceramid VI (manufactured by Cosmo Pharm) containing N-2-hydroxystearoyl-phytosphingosine (type 6) as a component.

These ceramides may be contained individually or in combination of 2 or more. The ceramide content of the external skin preparation of the present invention is preferably 0.02 to 5% by weight, more preferably 0.01 to 2% by weight.

Ceramides have an effect on strengthening the connection between the cells of the stratum corneum to improve the barrier function of the skin.

(2) Organically Modified Clay Mineral

The skin care product for external use contains an organically modified clay mineral as an essential component. The term “organically modified” as used herein means the attachment of an organic compound by strong or weak bond to a portion of a clay mineral through a covalent bond or ionic bond to impart a portion of the properties or all properties of the organic compound to the clay mineral. Examples of a method for organically modifying a clay mineral include: a method comprising preparing a quaternary ammonium salt of an organic compound and a clay mineral, and attaching an organic compound to bind to the anionic part of the clay mineral; and a method comprising preparing a carboxylic acid of an organic compound and a clay mineral and attaching an organic compound to a cationic part of a clay mineral, and a method comprising preparing a quaternary ammonium salt and a clay mineral and attaching an organic compound to the anionic part of the clay mineral is most preferred.

The quaternary ammonium salt used to organically modify the clay mineral is not limited to private salts, but examples thereof include a compound referred to as “quaternary”. Quaternary is a low molecular weight quaternary ammonium salt. In the present invention, it is preferable to use a compound registered in International Nomenclature Cosmetic Ingredients (INCI), or a compound included in a conventional quaternary skin preparation for external use. Among the quaternions, the quaternary ammonium salt represented by the following chemical formula (1) is preferably used, and particularly preferred examples thereof include stearyltrimethylammonium chloride, dimethyldystearylammonium chloride and benzyldimethylstearylammonium chloride. In particular, a clay mineral organically modified with stearyltrimethylammonium chloride, dimethyldistearylammonium chloride and the like is preferred, since it can form a stable water-in-oil emulsion.

In the chemical formula (1), R ₁ represents an alkyl group having from 10 to 22 carbon atoms, R ₂ represents an alkyl group having from 10 to 20 carbon atoms, a methyl group or benzyl group, R ₃ and R ₄ represent methyl group and X represents a halogen atom.

On the other hand, a clay mineral that is modified with a quaternary ammonium salt (unmodified clay mineral) is not particularly limited, as it is a clay mineral used in a conventional skin care preparation for external use. Examples of a clay mineral used in a conventional topical skin care preparation include: smectite, including hectorite, bentonite and montmorillonite; kaolinite; illite; marine clay mineral (marine clay); clay mineral of adenium; and pascalitis. Among them, hectorite, bentonite, montmorillonite and kaolinite are preferred, as they have excellent ability to stabilize a water-in-oil emulsion.

As a method for producing an organically modified clay mineral, as an embodiment of the invention, a method for modifying a clay mineral with a quaternary ammonium salt will be described. Unmodified clay mineral is dispersed in a dispersion medium. The dispersion medium is an aqueous solvent and may be water. The quaternary ammonium salt is additionally added to the dispersion medium containing unmodified clay mineral, and then mixed well. Quaternary ammonium salt can be added after dissolving in water. The amount of the quaternary ammonium salt is preferably from 0.1 to 20% by weight, more preferably from 0.5 to 15% by weight. the amount of dispersible unmodified clay mineral. A skin care product for external use containing such a composition can provide excellent skin health. After stirring, the dispersible substances are removed by filtration, then water is removed and dried, thereby obtaining an organically modified clay mineral that is used in the present invention. Alternatively, the organically modified clay mineral used in the present invention can be obtained by performing concentration under vacuum to remove the dispersion medium without removing dispersible substances by filtration, followed by drying. The final organically modified clay mineral is ground to the required size. Particle size is preferred from 1 to 1000 microns.

The organically modified clay mineral used in the present invention may be prepared as described above, or may be a commercially available product. Some commercially available organically modified clay minerals are used for an external skin care product such as a cosmetic composition. Preferred examples of a commercially available organically modified clay mineral include dimethyldystearylammonium modified hectorite sold under the trade name "Bentone 38V" Elementis and benzyldimethyl stearylammonium modified hectorite sold under the trade name "Bentone 27" Elementis.

The content of the organically modified clay mineral in an external skin preparation of the present invention is preferably from 0.5 to 10% by weight, more preferably from 1 to 5% by weight. Meanwhile, the content of organically modified clay minerals is preferably from 0.01 to 100 times the mass, more preferably from 0.05 to 50 times the mass of ceramide.

An organically modified clay mineral acts to form a water-in-oil emulsion with a high internal phase.

(3) N-acylated Glutamic Acid Diester

An external skin preparation of the present invention contains a diester of N-acylated glutamic acid as an essential component. The number of carbon atoms of the acyl group in the diester of N-acylated glutamic acid is preferably from 10 to 30, and more preferably from 12 to 18. In addition, the acyl group may be a saturated or unsaturated group. For example, a 2-ethylhexanoyl group, a lauroyl group, myristoyl group, palmitoyl group, stearoyl group, behenoyl group, oleoyl group, isostearoyl group, linolenoyl group are preferred. A lauroyl group is particularly preferred.

Additionally, the N-acylated glutamic acid diester is an N-acylated glutamic acid dialkyl ester. The number of carbon atoms of each alkyl group forming a dialkyl ether is preferably from 1 to 30, and more preferably from 12 to 18. The alkyl groups in one molecule of the diester can be the same or different. The alkyl group may form branched, linear or cyclic structures. For example, an octyl group, a lauryl group, a cetyl group, a stearyl group, an isostearyl group, a behenyl group, an octyldodecyl group, phytosterol groups such as a campesterol group and a sitosteryl group, and a cholesterol group are preferred.

An external skin preparation of the present invention may contain one type or combination of two or more types of N-acylated glutamic acid diester. For example, di (cholesteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate, di (cholesteryl / octyldodecyl) N-lauroyl-L-glutamate, di (phytosteryl / behenyl / octyldodecyl) N-lauroyl-L-glutamate, di ( phytosteryl / octyldodecyl) N-lauroyl-L-glutamate is preferred. Di (cholesteryl / octyldodecyl) N-lauroyl-L-glutamate is particularly preferred.

An N-acylated glutamic acid diester can be prepared by condensing glutamic acid and acyl chloride in the presence of alkali to produce N-acylglutamic acid and dehydrating the condensate between N-acylglutamic acid and an alcohol corresponding to the group which forms an ester with N-acyl acid bases or acids, and, if necessary, in the presence of a solvent. The N-acylated glutamic acid diester can be synthesized as described above and can be commercially available as a cosmetic substance, and such a commercially available product can be purchased and used. Examples of particularly preferred commercially available products include “Eldew PS-203” (di (phytosteryl / octyldecyl) N-lauroyl-L-glutamate, “Eldew CL-301” di (cholesteryl / behenyl / octyldodecyl) N-lauroylglutamate, “Eldew C1 -202 "di (cholesteryl / octyldodecyl) N-lauroylglutamate and Eldew PS-304" di (phytosteryl / behenyl / octyldodecyl) N-lauroylglutamate sold by Ajinomoto Co., Inc., and among them, "Eldew PS-203" is most preferred .

The content of the diester of N-acylated glutamic acid in the composition of the present invention for skin care for external use is preferably from 0.005 to 10% by weight, more preferably from 0.01 to 5% by weight. At the same time, the content of the diester of N-acylated glutamic acid is preferably from 0.01 to 100 times the mass, preferably from 0.1 to 70 times the mass of ceramide.

The diester of N-acylated glutamic acid has an effect, significantly improving the delivery of ceramide contained in the skin care product to the dermis.

(4) Phytosterol

An external skin preparation of the present invention contains phytosterol as an essential component. Phytosterol is a compound having a sterol skeleton derived from plants, and examples thereof include β-sitosterol, stigmasterol and campesterol. A mixture of these compounds can be obtained from plants by extraction and purification. Such mixtures are available for sale and can be purchased and used. Preferred product examples include Phytosterol S (a mixture of β-sitosterol, stigmasterol and campesterol) sold by Tama Biochemical Co., Ltd.

These components may be contained separately or in combination of two or more. Meanwhile, β-sitosterol, stigmasterol and campesterol are preferably used in combination. The phytosterol content in an external skin preparation of the present invention is preferably from 0.01 to 1% by weight, more preferably from 0.05 to 0.2% by weight. Meanwhile, the phytosterol content in an external skin preparation of the present invention is preferably from 0.5 to 5% by weight, more preferably from 1 to 2% by weight. ceramide.

The specified component stabilizes ceramide in the preparation of the present invention for skin care for external use.

(5) Crosslinked Dimethicone

An external skin preparation of the present invention contains cross-linked dimethicone as an essential component. Crosslinked dimethicone has a crosslinked structure of the polymerization chain of dimethylpolysiloxane, which is associated with other polymerization chains. Crosslinked dimethicone can be obtained by mixing methyltrialkoxysilane in dimethylalkoxysilane to obtain dimethylpolysiloxane.

Crosslinked dimethicone products are commercially available and can be purchased and used. Examples of such products include Silicone KSG-16 manufactured by Shin-Etsu Chemical Co., Ltd. (cyclomethicone solution containing 25% crosslinked dimethicone), and such a product can be purchased and used.

The crosslinked dimethicone content of the external skin preparation of the present invention is preferably from 0.1 to 10% by weight, more preferably from 0.5 to 5% by weight. Meanwhile, the content of crosslinked dimethicone is preferably from 0.01 to 50 times the mass, more preferably from 0.1 to 30 times the mass of ceramide.

Crosslinked dimethicone exhibits the effect of improving storage stability of an external skin preparation of the present invention.

(6) Topical Skin Care Product of the Invention

An external skin preparation of the present invention may contain ceramide in a well-known form, preferably in the form of a liposome or a niosome, especially preferably in the form of a liposome.

Both the liposome and the niosome are microspheres having a cavity and a bilayer lipid membrane. The term "liposome" means a microsphere containing a phospholipid as a component of a bilayer lipid membrane, and the term "niosome" means a microsphere not containing a phospholipid as a component of a lipid bilayer membrane.

The ceramide contained in the external skin preparation of the present invention in the form described above can be easily transferred through the stratum corneum when applying the external skin care preparation to the skin surface. The phospholipid, which is part of the liposome, is not particularly limited, as it can be used in conventional skin care products for external use, and preferred examples include lecithin, phosphatidic acid, phosphatidylethanolamine, phosphatidylinositol, fofatidylserine, phosphatidylglycerol iserin yolks or beans of soy and lysoform, hydrogenated products and their hydroxides.

The phospholipid content in the liposome is preferably from 0.5 to 10 times the mass, more preferably from 1 to 3 times the mass of ceramide. Moreover, the content of phospholipid is preferably from 0.01 to 5% by mass., More preferably from 0.1 to 2% by mass. in a skin care product for external use.

In addition, the liposome preferably contains a polyol as a component. Examples of the polyol include 1,3-butanediol and glycerol.

In addition, the polyol content in the liposome is preferably from 0.05 to 70 times the mass, more preferably from 0.1 to 50 times the mass of ceramide. Meanwhile, the amount of polyol in the liposome is preferably from 0.5 to 10% by weight, more preferably from 1 to 5% by weight. the amount of skin care product for external use.

In addition, the liposome preferably contains a sterol other than the above phytosterols as a component. For example, the liposome preferably contains cholesterol or the like, and its content is from 0.5 to 5 times the mass, more preferably from 1 to 2 times the mass of ceramide.

A liposome and a niosome can be obtained by melting the above components, decanting the melt in an aqueous carrier with stirring to obtain untreated liposomes or untreated nios, and granulating the product using a belt press, microfluidizer and the like.

The liposome and niosome can be dispersed in an external oil phase or in an internal aqueous phase of an external skin care preparation of the present invention, and dispersion in an internal aqueous phase is particularly preferred.

The skin care product of the present invention for external use contains an organically modified clay mineral in an external oil phase in the form of a water-in-oil emulsion.

An external skin preparation of the present invention may comprise a diester of N-acylated glutamic acid in the external oil phase in the form of a water-in-oil emulsion.

In the case where a topical skin preparation of the present invention contains ceramide in the form of a liposome or niosome, the N-acylated glutamic acid diester may be contained in the membrane of the liposome or niosome or in the external oil phase in the form of a water-in-oil emulsion , or both of them. The diester of N-acylated glutamic acid is preferably contained both in the liposome or niosome membrane and in the external oil phase in the form of a water-in-oil emulsion.

An external skin preparation of the present invention may contain phytosterol in the external oil phase in the form of a water-in-oil emulsion.

In addition, in the case where a topical skin preparation of the present invention contains ceramide in the form of a liposome or niosome, phytosterol is preferably contained in the membrane of the liposome or niosome.

An external skin preparation of the present invention contains cross-linked dimethicone in an external oil phase in the form of a water-in-oil emulsion.

An external skin preparation of the present invention may contain ceramide in the internal aqueous phase in the form of a water-in-oil emulsion with high stability. When an external skin preparation of the present invention is applied to the skin surface, an oil film is formed on the skin surface, and the blocking property of the oil film facilitates the delivery of ceramide through the stratum corneum.

The form of an external skin care preparation of the present invention is not particularly limited as long as the preparation can be applied externally to the skin, and preferred examples include cosmetics including quasi-drugs, topical drugs for the skin and products for skin care for external use. Of these, cosmetics or topical preparations for external use for the skin are particularly preferred.

At the same time, an external skin preparation of the present invention is particularly preferred for protecting the skin from external chemical irritation and mitigating or preventing atopic dermatitis. The term “warning,” as used herein, means both preventing the onset of symptoms and preventing the intensification of symptoms.

A topical skin care preparation of the present invention may contain an arbitrary component generally used in topical skin care preparations other than the above components. Examples of optional components include oils and waxes such as Australian 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, traces of paraffin, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibota wax, lanolin, reduced lanolin, solid lanolin, jojoba wax, dimeti con and polyoxyethylene-modified dimethylpolysiloxane; hydrocarbons such as liquid paraffin, squalane, pristan, ozokerite, paraffin, ceresin, petroleum jelly and microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauryl acid, myristic acid, palmitic acid, stearic acid, behenyl acid and undecylenic acid; higher alcohols such as cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol and cetostearyl alcohol; synthetic ester oils such as tsetilizoktanoat, triglitseridizoktanoat, isopropyl myristate, geksidetsilizostearat, diisopropyl adipate, di-2-ethylhexylsebacate, cetyl lactate, diisostearyl malate, ethylene glycol di-2-ethylhexanoate, neopentylglycol dicaprate, glyceryl di-2-heptyl undecanoate, glyceryl tri-2- ethyl hexanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate and pantaneerythritol tetra-2-ethylhexanoate; silicone oils, including chain polysiloxanes, such as dimethylpolysiloxane, methylphenylpolysiloxane and diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamtylcyclohexanesiloxane; and modified siloxanes, such as amine-modified polysiloxanes, polyether-modified polysiloxane, alkyl-modified polysiloxane, and fluorinated polysiloxane; anionic surfactants such as fatty acid soaps (including sodium laurate and sodium palmitate), potassium lauryl sulfate and triethanolamine alkyl sulfate; cationic surfactants such as trimethylammonium stearyl chloride, benzalkonium chloride and laurylamine oxide; amphoteric surfactants such as imidazoline-based amphoteric surfactants (including 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy-2-sodium salt), betaine-based surfactants (including alkyl betaine, betainamide and sulfobetaine) and acylmethyl taurine; non-ionic surfactants, such as sorbitol fatty acid esters (including sorbitan monostearate and one and a half sorbitan oleate), glycerol and fatty acid (including glycerol monostearate), propylene glycol and fatty acid (including propylene glycol monostearate), hydroginized derivatives of castor oil ether, alkyl ester, sorbitol and fatty acids (including POE sorbitol monooleate and polyoxyethylene sorbitol monostearate), POE esters of sorbitol and fatty acid (including POE-sorbitol monolaurate), POE esters g lycerol and fatty acid (including POE-glycerol monostearate), POE fatty acid esters (including polyethylene glycol monooleate and POE distearate), POE alkyl esters (including POE2-octyldodecyl ether), POE alkyl phenylethers, POE nonylphenyl ethers, (including POE / POP2-decyltetradecyl ether), tetron types, POE derivatives of castor oil / hydrogenated castor oil (including POE castor oil and POE hydrogenated castor oil), sucrose fatty acid ester and alkyl gluco ester zid; polyols such as polyethylene glycol, glycerin, 1,3-butanediol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprenglycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol and 1, 2-octanediol; moisturizing components such as sodium pyrrolidone carboxylate, lactate and sodium lactate; fine particles such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicon anhydride (silica), alumina and barium sulfate, whose surfaces may be exposed; inorganic pigments such as red iron oxide, yellow iron oxide, black iron oxide, cobalt oxide, blue ultramarine, Prussian blue, titanium oxide and zinc oxide, the surfaces of which can be processed; pearlescent substances such as titanated mica, foil flakes and bismuth oxychloride, the surfaces of which can be processed; organic dyes such as Red No. 202, Red No. 228, Red No. 226, Yellow No. 4, Blue No. 404, Yellow No. 5, Red No. 505, Red No. 230, Red No. 223, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201 and Red No. 204, which may be lacquered; fine particles, such as polyethylene powder, polymethyl methacrylate, polyamide powder and organopolysiloxane elastomer; p-aminobenzoate-based ultraviolet absorbers; Anthropilate-based UV absorbents; salicylate-based ultraviolet absorbents; cinnamate-based ultraviolet absorbents; benzophenone-based ultraviolet absorbents; sugar based ultraviolet absorbents; UV absorbers such as 2- (2'-hydroxy-5'-tert-octylphenyl) benzotriazole and 4-methoxy-4'-tert-butyldibenzoylmethane; lower alcohols such as ethanol and isopropanolol; vitamin A or its derivatives; types of vitamin B, such as vitamin B ₆ hydrochloride, vitamin B ₆ tripalmitate, vitamin B ₆ dioctanoate, vitamin B ₂ or its derivatives, vitamin B ₁₂ , and vitamin B ₁₅ or its derivatives; vitamins including types of vitamin E, such as α-tocopherol, β-tocopherol, γ-tocopherol, and vitamin E acetate, types of vitamin D, vitamin H, pantothenic acid, pantetin, and pyrroloquinolinequinone; and antifungal agents such as phenoxyethanol. An external skin preparation of the present invention can be obtained by treating said components in accordance with a conventional method.

Hereinafter, the present invention will be described in more detail by examples, but will not be limited by the examples given.

[Example 1]

The preparation of the present invention for skin care for external use was obtained in the form of a cream in accordance with the following formulation. First, components (A) and (B) were preheated to 70 ° C, and component (B) was added to component (A) with stirring to obtain untreated liposomes. The untreated liposomes were then processed using an extruder, followed by granulation, to obtain a liquid containing dispersed liposomes. A liquid containing dispersed liposomes was added to component (C) heated to 80 ° C, and the mixture was gradually added to component (D), which turned into a gel, with stirring to emulsify the mixture, followed by cooling with stirring, thus obtaining a cream 1 in the form of a water-in-oil emulsion having droplets in which liposomes are contained in the oil phase (in the form of a liposome-containing water-in-oil emulsion). The same procedure was repeated except that dimethicone (not crosslinked) was used instead of Silicone KSG-16, thus obtaining cream 2 in the form of a liposome-containing water-in-oil emulsion.

The same procedure was repeated except that hydrogenated lecithin was used instead of Ceramide-TIC, thus obtaining Comparative Example 1 in a form containing liposomes of a water-in-oil emulsion; except that bentonite, which is an organic unmodified clay mineral, was used instead of “Bentone 38V”, thus Comparative Example 2 was obtained in a form containing liposomes of a water-in-oil emulsion; except that hydrogenated lecithin was used instead of “Eldew PS-203”, thus Comparative Example 3 was obtained in a form containing liposomes of a water-in-oil emulsion; except that hydrogenated lecithin was used in place of Phytosterol, Comparative Example 4 was thus obtained in a form containing liposomes of a water-in-oil emulsion.

Table 1 Component % of the mass. (BUT) Ceramide-TIC 0.5 Phytosterol 0.5 (Phytosterol S Tama Biochemical Co., Ltd .; a mixture of β-sitosterol, stigmasterol and campesterol) Hydrogenated lecithin one Macadamia Nut Oil one "Eldem PS-203" four (Ajimoto Co., Inc .;
di (octyldodecyl / phytosteryl) N-lauroylglutamate) 1,3-butanediol 10 Glycerol 10 (AT) Water 73 (Intermediate amount) one hundred (FROM) Squalane 2 Triglyceride isooctanoate one Sucrose and fatty acid ester 0.2 "Eldew PS-203" four

Dimethicone 27 Silicone KSG-16 7 (Shin-Etsu Chemical Co., Ltd .; cyclomethicone solution containing 25% crosslinked dimethicone) Polyoxyethylene Modified Dimethyl Polysiloxane four "Benton 38V" 2.5 Glycerol 17 1,3-butanediol 8 (D) "Liquid with dispersed liposomes ((A) + (B))" twenty Water 7.3 Total one hundred

Test case 1

For creams 1 and 2 of comparative examples 1 to 4, the effects of improving the barrier function of the skin on the medial surface of the shoulder were investigated. Got seven sections on the medial surface of the shoulder (2 cm × 4 cm), which were stripped three times using adhesive plaster. Then, 40 mg of cream 1 was applied to one area and rubbed with a cotton ball soaked in ethanol every 30 minutes; 40 mg of cream 2 was applied to one area and rubbed with a cotton ball soaked in ethanol every 30 minutes; 40 mg of the composition of comparative example 1 was applied to one area and rubbed with a cotton ball soaked in ethanol every 30 minutes; 40 mg of the composition of comparative pimer 2 was applied to one area and rubbed with a cotton ball soaked in ethanol every 30 minutes; 40 mg of the composition of comparative example 3 was applied to one area and rubbed with a cotton ball soaked in ethyl alcohol every 30 minutes; 40 mg of the composition of comparative example 4 was applied to one area and rubbed with a cotton ball soaked in ethanol every 30 minutes; and the other site was left untreated for 30 minutes and rubbed with a cotton ball soaked in ethanol every 30 minutes. Ten minutes after wiping, transdermal water loss (TEWL) was determined using a Tewameter (manufactured by Integral Corporation). The results are shown in table 2. The delivery of cream of ceramide 1 and 2 directly to the dermis was found, which made it impossible to wipe it with ethanol, causing the effects of improving the barrier functions of the skin.

table 2 Sample Tewl Cream 1 18.7 Cream 2 17.8 Comparative Example 1 25.6 Reference Example 2 23.1 Reference Example 3 25,4 Reference Example 4 24.4 The control 27.3

Test example 2

Then, stability was studied for cream 1 and 2. These creams were obtained and allowed to stand at 5 ° C, 20 ° C and 40 ° C, and individual conditions were observed after one day and one month. Evaluation criteria were as follows.

AA: no change in condition immediately upon receipt

A: lack of separation, but a slight decrease in viscosity

B: partial separation and viscosity reduction

The results are shown in table 3. In cream 1, there was no separation even when stored at low and high temperatures and excellent storage stability was found under adverse conditions compared to cream 2. Therefore, it was found that cross-linked dimethicone provides an improvement in maintaining the stability of the preparation for the skin for external use. application.

Table 3 Cream 1 Cream 2 one day later 5 ° C AA AA 20 ° C AA AA 40 ° C AA AA one month later 5 ° C AA BUT 20 ° C AA AA 40 ° C AA AT

Example 2

A similar study with test example 1 was performed for creams that were obtained using various types of ceramides in cream 1 (creams 3 through 5). The evaluation results were obtained by the method of test example 1, shown in table 5. The results reveal that the effects of ceramide delivery are improved in the case of all types of ceramides.

Table 4 Component % of the mass. (BUT) Ceramide described in table 4 0.5 Phytosterol 0.5 (Phytosterol S Tama Biochemical Co., Ltd .; a mixture of β-sitosterol, stigmasterol and campesterol) Hydrogenated lecithin one Macadamia Nut Oil one "Eldem PS-203" four (Ajimoto Co., Inc .; di (octyldodecyl / phytosteryl) N-lauroylglutamate) 1,3-butanediol 10 Glycerol 10 (AT) Water 73 (Intermediate amount) one hundred (FROM) Squalane 2 Triglyceride isooctanoate one Sucrose and fatty acid ester 0.2 "Eldew PS-203" four Dimethicone 27 Silicone KSG-16 7

(Shin-Etsu Chemical Co., Ltd .; cyclomethicone solution containing 25% crosslinked dimethicone) Polyoxyethylene Modified Dimethyl Polysiloxane four "Benton 38V" 2.5 Glycerol 17 1,3-butanediol 8 (D) "Liquid with dispersed liposomes" twenty Water 7.3 Total one hundred

Table 5 Sample Ceramide Tewl Cream 3 Ceramide I 19,2 Cream 4 Ceramide III 19.7 Cream 5 Ceramide IIIA 21.1 The control 28.7

Example 3

A similar study with test example 1 was performed for creams that were obtained using various types of phospholipids in cream 1 (creams 5 through 8). The evaluation results were obtained by the method of test example 1, shown in table 7. The results reveal that the effects of ceramide delivery are improved in the case of all types of phospholipids.

Table 6 Component % of the mass. (BUT) Ceramide-TIC 0.5 Phytosterol 0.5 (Phytosterol S Tama Biochemical Co., Ltd .; a mixture of β-sitosterol, stigmasterol and campesterol) Phospholipid described in table 6 one Macadamia Nut Oil one "Eldem PS-203" four (Ajimoto Co., Inc .; di (octyldodecyl / phytosteryl) N-lauroylglutamate) 1,3-butanediol 10 Glycerol 10 (AT) Water 73 (Intermediate amount) one hundred (FROM) Squalane 2 Triglyceride isooctanoate one Sucrose and fatty acid ester 0.2 "Eldew PS-203" four Dimethicone 27 Silicone KSG-16 7

(Shin-Etsu Chemical Co., Ltd .; cyclomethicone solution containing 25% crosslinked dimethicone) Polyoxyethylene Modified Dimethyl Polysiloxane four "Benton 38V" 2.5 Glycerol 17 1,3-butanediol 8 (D) "Liquid with dispersed liposomes" twenty Water 7.3 Total one hundred

Table 7 Sample Phospholipid Tewl Cream 6 Soya lecithin 18.8 Cream 7 Egg Yolk Lecithin 19.1 Cream 8 Hydroxylated lecithin 17.8 The control 25.9

Example 4

The study was performed on a dosage form containing ceramide in the usual form of an emulsion instead of a dosage form of cream 1 containing ceramide in liposome form. First, components (A) and (B) were heated to 70 ° C, and component (B) was added to component (A) with stirring to obtain an untreated emulsion. Then, the untreated emulsion was processed using a homogenizing mixer, followed by granulation, thereby obtaining an oil-in-water emulsion. The emulsion was added to component (C), heated to 80 ° C, and the mixture was gradually added to component (D), which turned into a gel, with stirring, until an emulsion of the mixture was obtained, followed by cooling with stirring, thus obtaining a cream 9 in the form of an emulsion water-in-oil (having drops of an oil-in-water emulsion in an external oil phase). The control was the same as in example 1. In the evaluation by the method of test example 1, the TEWL value of the control was 26.9, while the value of cream 9 was 19.8, which represents a good result similar to cream 1. Found that ceramide is more preferably contained in the form of a liposome.

Table 8 Component % of the mass. (BUT) Ceramide-TIC 0.5 Phytosterol 0.5 (Phytosterol S Tama Biochemical Co., Ltd .; a mixture of β-sitosterol, stigmasterol and campesterol) Hydrogenated lecithin one Macadamia Nut Oil one Behenyl alcohol 0.5 "Eldem PS-203" four (Ajimoto Co., Inc .; di (octyldodecyl / phytosteryl) N-lauroylglutamate) 1,3-butanediol 10 Glycerol 10

(AT) Water 72.5 (Intermediate amount) one hundred (FROM) Squalane 2 Triglyceride isooctanoate one Sucrose and fatty acid ester 0.2 "Eldew PS-203" four Dimethicone 27 Silicone KSG-16 7 (Shin-Etsu Chemical Co., Ltd .; cyclomethicone solution containing 25% crosslinked dimethicone) Polyoxyethylene Modified Dimethyl Polysiloxane four "Benton 38V" 2.5 Glycerol 17 1,3-butanediol 8 (D) "Liquid with dispersed liposomes" ((A) + (B)) twenty Water 7.3 Total one hundred

Industrial applicability

The present invention can be applied in a skin preparation for external use, such as a cosmetic composition.

Claims (2)

1. A cosmetic product for external use in the form of a water-in-oil emulsion containing ceramide in the form of liposomes, hectorite modified with a quaternary ammonium salt, di (phytosteryl / octyldodecyl) N-lauroylglutamate and phytosterol. 2. The skin care product for external use according to claim 1, further comprising crosslinked dimethicone.