JP2016088902A - Sustained release carrier - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a sustained release carrier which has high permeability into epidermis and can continuously exhibit the efficacy of an active ingredient near the stratum basal epidermidis.SOLUTION: The invention provides a sustained release carrier consisting of a micelle, vesicle, or liquid crystal containing one or more kinds of surfactants selected from the group consisting of oleic acid polyglyceryl and sucrose fatty acid ester of a fatty acid of carbon number 10 or more to 20 or less.SELECTED DRAWING: None

Description

  The present invention relates to a sustained release carrier comprising micelles, vesicles or liquid crystals containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters.

  The skin changes with age and changes the impression given to people. For this reason, various studies have been actively conducted in search of “beautiful skin”. For example, there are approaches to search for effective ingredients such as new whitening ingredients and wrinkle improving ingredients that are more effective and safe, and to extract new extracts from plants to find new actions. In recent years, attention has been paid to the mechanism of stain and wrinkle generation itself, and an approach to suppress it has also been made. For example, a tyrosinase induction inhibitor and a melanin synthesis inhibitor have been proposed for pigmentation (Patent Document 1).

JP 2014-97945 A

In the basal layer of the epidermis, there are cells that become the parent of keratinocytes (epidermal cells) and melanocytes that produce melanin that is important for whitening. That is, the epidermis basal layer is considered to be a very important part in maintaining healthy skin.
Recent studies have shown that keratinocytes in the basal epidermis are involved in melanin production. In order to effectively act on a phenomenon that occurs in the vicinity of the epidermal basal layer, such as the formation of a melanin cap, it is required that the active ingredient be allowed to act continuously in the vicinity of the epidermal basal layer.
The present inventor has found a problem that if the active ingredient is penetrated to the vicinity of the epidermis basal layer so as to increase the permeability to the epidermis, the diffusivity of the active ingredient quickly passes through the epidermis basal layer.
In view of the above points, an object of the present invention is to provide a sustained-release carrier that has high permeability to the epidermis and can exert the effect of an active ingredient continuously in the vicinity of the epidermal base layer.

  The inventor conducted intensive research and obtained the knowledge that micelles, vesicles, and liquid crystals containing specific surfactants not only have high permeability to the skin epidermis but also accumulate in keratinocytes in the basal layer of the epidermis. And based on the said knowledge, the use as the sustained release support | carrier of the micelle, vesicle, and liquid crystal containing a specific surfactant was discovered. Further, it has been conceived that an external preparation capable of continuously exhibiting the effect of the active ingredient in the epidermis can be provided by using the sustained release carrier complex in which the active ingredient is supported on the sustained release carrier.

That is, the present invention is as follows.
[1] A sustained release carrier comprising micelles, vesicles, or liquid crystals containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters of fatty acids having 10 to 20 carbon atoms.
[2] The sustained release carrier according to [1], wherein the polyglyceryl oleate and / or the sucrose fatty acid ester of a fatty acid having 10 to 20 carbon atoms has an HLB value of 9 or more and 18 or less.
[3] The sustained release carrier according to [1] or [2], wherein the polyglyceryl oleate is decaglyceryl monooleate.
[4] The description of [1] or [2], wherein the fatty acid of the sucrose fatty acid ester includes at least one selected from the group consisting of oleic acid, stearic acid, isostearic acid, palmitic acid, myristic acid, and lauric acid. Sustained release carrier.
[5] A sustained release carrier complex in which an active ingredient is supported on the sustained release carrier according to any one of [1] to [4].
[6] The sustained release carrier complex according to [5], wherein the active ingredient is loquat leaf extract.
[7] A composition comprising one or more sustained-release carriers or sustained-release carrier complexes according to any one of [1] to [6].
[8] The composition according to [7], which is an external preparation for skin.
[9] The composition according to [7] or [8], which is a cosmetic (including a quasi-drug). [10] Active ingredient in sustained release carrier comprising micelle, vesicle or liquid crystal containing one or more surfactant selected from the group consisting of polyglyceryl oleate and sucrose fatty acid ester of fatty acid having 10 to 20 carbon atoms Preparing a formulation carrying
A method of storing the sustained-release carrier in the epidermal basal layer by applying the preparation to the skin.
[11] An active ingredient in a sustained release carrier comprising micelles, vesicles, or liquid crystals containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters of fatty acids having 10 to 20 carbon atoms Preparing a formulation carrying
A method of continuously exerting the effect of the active ingredient in the epidermis by applying the preparation to the skin.

  According to the present invention, there is provided a sustained release carrier that has high permeability to the epidermis and accumulates in keratinocytes in the basal layer of the epidermis. The sustained-release carrier can encapsulate the active ingredient in the inner core of micelles and can release the active ingredient from keratinocytes in the epidermal basal layer, so that the effect of the active ingredient can be exerted continuously in the epidermis. it can.

It is a figure which shows the phase-contrast microscope image of the cross section 24 hours after application | coating of the sample A which contains the sustained release support | carrier of this invention in a human three-dimensional cultured epidermis model. It is a figure which shows the fluorescence-microscope image of the cross section 24 hours after application | coating of the sample A which contains the sustained release support | carrier of this invention in a human three-dimensional cultured epidermis model. It is a figure which shows the fluorescence-microscope image 2 hours after apply | coating the sample B which does not contain the sustained release carrier of this invention to a differentiation keratinocyte. It is a figure which shows the fluorescence-microscope image 2 hours after apply | coating the sample A containing the sustained release carrier of this invention to a differentiation keratinocyte. It is a figure which shows the fluorescence microscope image of the comparative example 1. 2 is a diagram showing a fluorescence microscope image of Example 1. FIG.

  Hereinafter, the present invention will be described in detail according to embodiments. However, the present invention is not limited to the embodiments described explicitly or implicitly in the present specification.

  The sustained-release carrier of the present invention is a micelle, vesicle, or liquid crystal containing one or more surfactants selected from the group consisting of polyglyceryl oleate and fatty acid esters of fatty acids having 10 to 20 carbon atoms. Become.

Surfactants are usually used to exhibit detergency, emulsification ability, and solubilization ability. The inventor has found that micelles, vesicles, and liquid crystals prepared using specific surfactants not only penetrate into the epidermis but also accumulate in keratinocytes of the epidermal basal layer. And based on the storage properties of the micelles, vesicles, and liquid crystals in the epidermal basal layer keratinocytes,
It has been conceived to use as a sustained release carrier, which has not been known so far. Furthermore, it has been conceived that the effect of the active ingredient can be continuously exhibited in the epidermis, particularly in the vicinity of the keratinocytes, by using the sustained release carrier composite in which the active ingredient is supported on the inner core of the micelle, vesicle or liquid crystal.
Although the mechanism by which micelles, vesicles, and liquid crystals, which are sustained-release carriers of the present invention, are stored in keratinocytes is not clear, the sustained-release carrier of the present invention is a nonionic surfactant having a configuration in which a hydrophilic group is an outer periphery. Since it has high permeability to the epidermis and adsorbs and accumulates on the epidermal basal layer keratinocytes, it is presumed that the active ingredient can exert its effect continuously and efficiently in the vicinity of the epidermal basal layer.

Hereinafter, polyglyceryl oleate which is one type of surfactant constituting the sustained-release carrier of the present invention will be described.
The polyglyceryl oleate of the present invention is an ester compound of polyglycerin having an average degree of polymerization of 3 to 15 and oleic acid which is a fatty acid having 18 carbon atoms. With the above configuration, polyglycerin as a hydrophilic group and a fatty acid residue as a lipophilic group, a hydrophilic nonionic surfactant, which penetrates epidermal keratinocytes, but stores micelles in epidermal basal layer keratinocytes, It can be a vesicle or a liquid crystal.

  In this embodiment, the number of moles of fatty acid added to polyglycerin of polyglyceryl oleate may be within a range where polyglyceryl oleate functions as a nonionic surfactant, and the number of moles of fatty acid added is desirably around 1. . That is, it is preferably 0.6 to 2.0 mol, and more preferably 0.8 to 1.5 mol, per 1 mol of polyglycerol. By setting the number of added moles within this range, sufficient hydrophilicity can be obtained when micelles are obtained.

The polyglyceryl oleate can change the HLB value by selecting the polymerization degree and esterification rate of the raw polyglycerol.
The HLB value is usually 9 or more and 18 or less, but varies depending on the dosage form. For example, when the dosage form is a lotion, from the viewpoint of water solubility, it is usually 9 or more, preferably 10 or more, more preferably 12 or more, and usually 18 or less, preferably 15 or less, more preferably 13 or less.
In the present embodiment, the HLB value is a value obtained by a Griffin calculation formula.

  The polyglyceryl oleate of the present embodiment can be produced by a conventional method such as esterification of glycerin and a fatty acid or transesterification of glycerin and a fatty acid ester.

  The polyglycerin constituting the polyglyceryl oleate of the present embodiment is a polyglycerin having a glycerin average polymerization degree of 3 or more and 15 or less. The glycerin average polymerization degree is 3 or more, preferably 5 or more, more preferably 7 or more, 15 or less, preferably 13 or less, more preferably 10 or less. Further, polyglycerin having an average degree of polymerization of less than 3 or greater than 15 may be included as long as the effects of the present invention are not impaired.

Polyglycerin having an average degree of glycerin polymerization of 3 or more can be synthesized by a known method, and examples thereof include a dehydration condensation reaction in which an alkali catalyst such as sodium hydroxide is added to glycerin and heated to 200 ° C. or higher. The average degree of polymerization of polyglycerin is calculated from the hydroxyl value obtained by end group analysis.
Moreover, commercially available polyglycerol can also be used for this embodiment. As a commercially available polyglycerin, product name polyglycerin # 310 (made by Sakamoto Pharmaceutical Co., Ltd.) is mentioned, for example.

  The oleic acid which comprises the polyglyceryl oleate of this embodiment is a C18 monovalent unsaturated fatty acid. In this embodiment, commercially available oleic acid can also be used. As a commercially available oleic acid, product name EXTRA OLEIN 99 (made by NOF Corporation) is mentioned, for example.

Specific examples of the polyglyceryl oleate obtained using the above raw materials include the following. That is, pentaglyceryl monooleate (polyglyceryl-5 oleate) (HLB value 13.0), decaglyceryl monooleate (polyglyceryl oleate-10) (HLB value 12.0), and the like. Of these, decaglyceryl monooleate is preferable because it suppresses melanin production in the vicinity of the keratinocytes of the epidermis by combining with a melanin production inhibitor such as 4-n-butylresorcinol, oil-soluble licorice extract, and loquat leaf extract.
The purity of decaglyceryl monooleate is not particularly limited, but may contain some diesters and triesters in addition to the polyglycerol fatty acid monoester having an average degree of polymerization of 10 due to the properties of production.

Such polyglyceryl oleate is commercially available, for example, trade name SY Glister ML500 (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.), NIKKOL Decaglyn.
1-OV, NIKKOL Decaglyn 1-M (manufactured by Nikko Chemicals Co., Ltd.), and Sunsoft A171E (manufactured by Taiyo Kagaku Co., Ltd.) can be suitably used.

Next, a sucrose fatty acid ester in which the number of carbon atoms of a fatty acid, which is one type of surfactant constituting the sustained-release carrier of the present invention, is 10 or more and 20 or less will be described. Sucrose fatty acid ester is obtained by esterifying a fatty acid with a hydroxyl group of sucrose. It is a nonionic surfactant in which sucrose is a hydrophilic group and fatty acid is a new oil group, and epidermal keratinocytes can penetrate into micelles, vesicles, and liquid crystals that are stored in epidermal basal layer keratinocytes.
The sucrose fatty acid ester of this embodiment can be produced by a conventional method such as transesterification of sucrose and a fatty acid ester.

The sucrose fatty acid ester can change the HLB value by selecting the starting fatty acid and esterification rate.
The HLB value is usually 9 or more and 18 or less, but varies depending on the dosage form. For example, when the dosage form is a lotion, from the viewpoint of water solubility, it is usually 9 or more, preferably 10 or more, more preferably 12 or more, and usually 18 or less, preferably 15 or less, more preferably 12 or less.
In the present embodiment, the HLB value is a value obtained by a Griffin calculation formula.

The sucrose constituting the sucrose fatty acid ester of this embodiment is a disaccharide represented by C ₁₂ H ₂₂ O _{11 in} which glucose and fructose are glycosidically bonded.
The fatty acid which comprises the sucrose fatty acid ester of this embodiment is a C10-C20 fatty acid. The carbon number is 10 or more, preferably 12 or more, usually 20 or less, preferably 18 or less.
The fatty acid used in the present embodiment may be a saturated fatty acid or an unsaturated fatty acid as long as it has 10 to 20 carbon atoms, and may be a linear fatty acid or a branched fatty acid. Good. Specific examples of such fatty acids include capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, arachidic acid, behenic acid, lignoceric acid, lignoceric acid, oleic acid, linoleic acid, and linolenic acid. Arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid. Of these, oleic acid, myristic acid, and lauric acid are preferable.

Specific examples of the sucrose fatty acid ester obtained from the above raw materials include the following. Sucrose monolaurate, sucrose monomyristate, sucrose monopalmitate, sucrose monostearate, sucrose monoisostearate, sucrose monooleate, and the like. Of these, monoesters are preferable and sucrose monoisostearate and sucrose monooleate are more preferable from the viewpoint of easy adsorption to the basal layer keratinocytes.
Some of these sucrose fatty acid esters are commercially available. For example, Ryoto Sugar Ester O-1570 (Mitsubishi Chemical Foods Co., Ltd.), Ryoto Sugar Ester S-1570 (Mitsubishi Chemical Foods Co., Ltd.) ) Can be suitably used.

The sustained-release carrier of the present invention contains a surfactant other than glyceryl oleate and / or a sucrose fatty acid ester in which the fatty acid has 10 to 20 carbon atoms in a range that does not inhibit the effects of the present invention. However, among the total mass of the surfactant constituting the sustained-release carrier, it is preferable that the polyglyceryl oleate and / or the sucrose fatty acid ester in which the fatty acid has 10 to 20 carbon atoms is 50% by mass or more. 70% by mass or more, more preferably 80% by mass or more, and particularly preferably 90% by mass or more.
As the micelle used as the sustained-release carrier of the present invention, from the viewpoint of storage in the epidermal basal layer keratinocytes, from only one of polyglyceryl oleate and sucrose fatty acid ester in which the fatty acid has 10 to 20 carbon atoms Most preferably, it is configured.
As the vesicle serving as the sustained-release carrier of the present invention, the surface layer (outer shell) is composed of only one of polyglyceryl oleate and a sucrose fatty acid ester in which the fatty acid has 10 to 20 carbon atoms. Is most preferred.
As the liquid crystal serving as the sustained release carrier of the present invention, the surface layer is most preferably composed of only one of polyglyceryl oleate and a sucrose fatty acid ester in which the fatty acid has 10 to 20 carbon atoms.

  In the present invention, micelles containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters in which the fatty acid has 10 to 20 carbon atoms can be prepared by a known method. it can. For example, it can be produced by dispersing polyglyceryl oleate and / or sucrose fatty acid ester having 10 to 20 carbon atoms in water, heating to dissolve, and then allowing to stand.

  Vesicles can be obtained by combining one or more surfactants. In the present invention, a vesicle comprising at least one surfactant selected from the group consisting of polyglyceryl oleate and a sucrose fatty acid ester in which the fatty acid has 10 to 20 carbon atoms comprises olein as a constituent surfactant. It contains sucrose fatty acid ester in which carbon number of acid polyglyceryl and / or fatty acid is 10 or more and 20 or less, and can be prepared by a known method. For example, it can be produced by dissolving a surfactant in an organic solvent, removing the solvent from the solution to form a surfactant thin film, and then adding water and allowing to stand.

  The liquid crystal is obtained by preparing a composition in water, oil, and a surfactant three-component system. In the present invention, a liquid crystal containing at least one surfactant selected from the group consisting of polyglyceryl oleate and a sucrose fatty acid ester in which the fatty acid has 10 to 20 carbon atoms has olein as a constituent surfactant. The polyglyceryl acid and / or sucrose fatty acid ester in which the fatty acid has 10 to 20 carbon atoms. Examples of the liquid crystal structure include hexagonal, lamella, and reverse hexagonal. The liquid crystal can be prepared by a known method. For example, it can be prepared by mixing a surfactant and oil and then stirring while gradually adding water.

Further, the sustained release carrier of the present invention can carry an active ingredient to form a sustained release carrier complex. Here, the term “supporting” means that the micelle is included in the inner core of the micelle, the vesicle is included in the inner core of the vesicle, and the liquid crystal is included between the layers of the liquid crystal structure. Note that in this specification, inclusion between layers of a liquid crystal structure is included in liquid crystal. Since the fatty acid residues constituting the micelles, vesicles, or liquid crystals of this embodiment are lipophilic, by making the hydrophilic group the outer peripheral side, the active ingredient with low water solubility (oil-soluble) Between the layers, an active ingredient having high water solubility can be carried on the inner core of the vesicle or between the layers of the liquid crystal. Examples of such active ingredients include whitening ingredients, wrinkle improving ingredients, cell activation ingredients, anti-inflammatory ingredients, animal and plant extracts.
Since the sustained-release carrier of the present invention is adsorbed to the epidermal basal layer keratinocytes, the encapsulated water-soluble and / or oil-soluble active ingredient can be allowed to act continuously in the vicinity of the epidermal basal layer. For this reason, the sustained-release carrier complex of the present embodiment includes an active ingredient that acts on a phenomenon that occurs in the vicinity of the epidermal basal layer, so that the mechanism in the vicinity of the epidermal basal layer is the key, and normal turnover It is very effective for crystallization and pigmentation.
For example, in pigmentation, melanin is produced in melanocytes existing in the basal layer of the epidermis by stimulation with ultraviolet rays or female hormones. The melanosome enveloping melanin is donated to keratinocytes (epidermal cells), and the melanosome forms a structure called a melanin cap. The melanin cap usually falls apart with the differentiation of keratinocytes and peels off from the skin surface. However, metabolism is slowed down by ultraviolet rays, aging, lack of sleep, lack of nutrition, etc., metabolism of melanin also collapses, and melanin accumulates excessively in the epidermis. When the mechanism in the vicinity of the epidermal basal layer is the key as in this pigmentation, it is very effective to let the active ingredient act continuously in the vicinity of the epidermal basal layer.

The whitening component is not particularly limited as long as it is generally used in cosmetics. For example, 4-n-butylresorcinol, ascorbic acid glucoside, 3-O-ethylascorbic acid, tranexamic acid, arbutin, 1-triphenylmethylpiperidine, 1-triphenylmethylpyrrolidine, 2- (triphenylmethyloxy) ethanol, 2- (triphenylmethylamino) ethanol, 2- (triphenylmethyloxy) ethylamine, triphenylmethylamine, triphenylmethanol, triphenylmethane and aminodiphenylmethane, N- (p-toluyl) cysteic acid, N- (p -Methoxybenzoyl) cysteic acid and the like. Furthermore, as other whitening components, N-benzoyl-serine, N- (p-methylbenzoyl) serine, N- (p-ethylbenzoyl) serine, N- (p-methoxybenzoyl) serine, N- (p-fluorobenzoyl) ) Serine, N- (p-trifluoromethylbenzoyl) serine, N- (2-naphthoyl) serine, N- (4-phenylbenzoyl) serine, N- (p-methylbenzoyl) serine methyl ester, N- (p -Methylbenzoyl) serine ethyl ester, N- (2-naphthoyl) serine methyl ester, N-benzoyl-O-methylserine, N- (p-methylbenzoyl) -O-methylserine, N- (p-methylbenzoyl) -O -Acetylserine, N- (2-naphthoyl) -O-methylserine and the like. Among these, 4-n-butylresorcinol is preferable because of its high pigmentation preventing effect.
Some of these whitening components are already on the market, or they can be obtained by synthesis. For example, 3-O-ethylascorbic acid can be synthesized by a known method described in JP-A-8-134055. There are also commercially available products (“VC ethyl” manufactured by Nippon Seika Co., Ltd.), and these can be obtained and used. 1-triphenylmethylpiperidine, 1-triphenylmethylpyrrolidine, 2- (triphenylmethyloxy) ethanol, 2- (triphenylmethylamino) ethanol, 2- (triphenylmethyloxy) ethylamine, triphenylmethylamine, triphenyl Phenylmethanol, triphenylmethane, and aminodiphenylmethane are disclosed in pamphlet of WO2010 / 074052, in which N- (o-toluoyl) cysteic acid, N- (m-toluoyl) cysteic acid, N- (p-toluoyl) cysteic acid, N -(P-methoxybenzoyl) cysteic acid, N- (4-phenylbenzoyl) cysteic acid and N- (p-toluoyl) homocysteic acid are disclosed in WO2011 / 088706, N-benzoyl-serine, N- (p −Me Rubenzoyl) serine, N- (p-ethylbenzoyl) serine, N- (p-methoxybenzoyl) serine, N- (p-fluorobenzoyl) serine, N- (p-trifluoromethylbenzoyl) serine, N- ( 2-naphthoyl) serine, N- (4-phenylbenzoyl) serine, N- (p-methylbenzoyl) serine methyl ester, N- (p-methylbenzoyl) serine ethyl ester, N- (2-naphthoyl) serine methyl ester N-benzoyl-O-methylserine, N- (p-methylbenzoyl) -O-methylserine, N- (p-methylbenzoyl) -O-acetylserine, N- (2-naphthoyl) -O-methylserine, etc. Since the methods for synthesizing them are disclosed in each pamphlet It is possible to follow synthesis.
Content of the whitening component in a composition is 0.01-10 mass% normally, 0.1-5 mass% is preferable and 0.3-2 mass% is more preferable.

  The wrinkle improving component is not particularly limited as long as it is generally used in cosmetics. For example, vitamin A or its derivatives retinol, retinal, retinoic acid, tretinoin, isotretinoin, retinoic acid tocopherol, palmitic acid retinol, retinol acetate, ursolic acid benzyl ester, ursolic acid phosphate ester, betulinic acid benzyl ester , Benzyl phosphate ester. The content of the wrinkle improving component in the composition is usually 0.01 to 30% by mass, preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass.

The extract derived from animals and plants is not particularly limited as long as it is generally used for pharmaceuticals, cosmetics and the like. The extracts derived from animals and plants mean not only animal or plant-derived extracts themselves, but also generic names of extract fractions, purified fractions, extracts or fractions, and solvent-removed products of purified products. Examples of plant-derived extracts include native or grown plants, extracts using products sold as herbal medicine ingredients, and commercially available extracts. For example, akebi extract, asunaro extract, asparagus extract, avocado extract, achacha extract, almond extract, arnica extract, aloe extract, aronia extract, apricot extract, ginkgo biloba extract, Indian mushroom extract, fennel extract, udo extract, ages extract, sorghum extract , Enmezo extract, Ogon extract, Oat extract, Auren extract, Panax ginseng extract, Hypericum extract, Adrianthus extract, Orange extract, Oyster extract, Cuckoo extract, Chamomile extract, Carrot extract, Kawara mugwort extract, Licorice extract, Kiwi extract, Cucumber extract, Guava extract, Kujin extract, Gardenia extract, Kumazasa extract, Clara extract, Walnut extract, Grapefruit extract, Black rice , Chlorella extract, mulberry extract, caquette extract, gentian extract, gentian extract, Gennosho extract, tea extract, burdock extract, rice extract, fermented rice extract, rice fermented extract, rice germ oil, bilberry extract, salvia extract, bonito extract , Sasa extract, Hawthorn extract, Sansha extract, Salamander extract, Shiitake extract, Giant extract, Shikon extract, Perilla extract, Linden extract, Citrus extract, Peonies extract, Pepper extract, Ginger root extract, Birch extract, Japanese cedar extract, Stevia extract, Stevia fermentation , Kizuta extract, Hawthorn extract, Elderberry extract, Yarrow extract, Pepper extract, Sage extract, Mallow Kiss, Senkyu Extract, Sembura Extract, Sakuhakuhi Extract, Daiou Extract, Soybean Extract, Taiso Extract, Thyme Extract, Dandelion Extract, Tea Extract, Clove Extract, Chimpi Extract, Green Tea Extract, Capsicum Extract, Toki Extract, Tokinsenka Extract, Tonin Extract, Spruce Extract , Dokudami extract, tomato extract, natto extract, carrot extract, garlic extract, wild rose extract, hibiscus extract, buckwheat extract, parsley extract, birch extract, hamamelis extract, cypress extract, hinoki extract, loquat extract, loquat leaf extract, dandelion extract, Fukinotou extract, Bukuryu extract, Butcher bloom extract, Grape extract, Grape seed extract, Loofah extract, Safflower extract, Peppermint extract, Bodaiju extract, button extract, hop extract, pine extract, maroonni extract, mizubasho extract, mukuroji extract, melissa extract, mozuku extract, peach extract, cornflower extract, eucalyptus extract, yukinoshita extract, yuzu extract, lily extract, juniper extract, mugwort extract, lavender extract, Preferable extracts include green tea extract, apple extract, rooibos tea extract, litchi extract, lettuce extract, lemon extract, forsythia extract, forsythia extract, rose extract, rosemary extract, roman chamomile extract, royal jelly extract, and bitumen extract. . Among these, loquat leaf extract is particularly preferable. Said extract may contain 1 type and may contain 2 or more types. The content of the animal or plant-derived extract in the cosmetic is usually 0.001% by mass or more, preferably 0.01% by mass or more, and more preferably 0.1% by mass or more. Moreover, it is 10 mass% or less normally, 5 mass% or less is preferable and 3 mass% or less is more preferable.

Examples of the anti-inflammatory component include clarinone, glabrizine, glycyrrhizic acid, glycyrrhetinic acid, pantothenyl alcohol, and the like, and preferably glycyrrhizic acid and its salt, glycyrrhetinic acid alkyl and its salt, and glycyrrhetic acid and its salt.
The content of the anti-inflammatory component in the cosmetic is usually 0.001% by mass or more, preferably 0.005% by mass or more, more preferably 0.01% by mass or more, and usually 10% by mass or less. % By mass or less is preferable, and 3% by mass or less is more preferable.

  The sustained release carrier of this embodiment can be contained in the composition. Preferred examples of the composition include cosmetics and pharmaceuticals. In the present invention, cosmetics include quasi drugs. Since it can be used on a daily basis, cosmetics (however, including quasi drugs) are more preferable.

  In the composition of this embodiment, the content (blending amount) of the sustained-release carrier, when converted by the mass of the surfactant that constitutes micelles, vesicles, or liquid crystals, has a storage property in the keratinocytes of the epidermal basal layer. From the viewpoint, it is usually 0.001% by mass or more, preferably 0.01% by mass, more preferably 0.02% by mass or more, and from the viewpoint of the degree of freedom of formulation of the composition, 5% by mass or less is preferable, and 1% by mass. The following is preferred.

  In the production of the composition, components that are usually used in the preparation of cosmetics, quasi drugs, pharmaceuticals, and the like can be appropriately contained according to each application.

  When applied to cosmetics, it is possible to broadly blend the ingredients normally used in cosmetics, and the dosage forms are usually known lotions, emulsions, essences, creams, gels, mousses, etc. However, from the viewpoint of permeability to the epidermis, a lotion dosage form with low viscosity is preferred. Furthermore, these cosmetics may take various forms such as aqueous, oily, water-in-oil emulsion, oil-in-water emulsion, non-water emulsion, W / O / W and O / W / O. I can do it. Further, the use is not limited.

  Hereinafter, the components that can be contained in the cosmetic when applied to the cosmetic will be described. For example, normal oil components such as hydrocarbons, esters, triglycerides, fatty acids and higher alcohols, surfactants such as anionic surfactants, amphoteric surfactants, and cationic surfactants (Excluding nonionic surfactants constituting release carriers), polyhydric alcohols, thickening / gelling agents, antioxidants, ultraviolet absorbers, colorants, preservatives, powders, etc. it can. In addition, an active ingredient such as a whitening ingredient, a wrinkle-improving ingredient, an anti-inflammatory ingredient, an animal or plant-derived extract can be contained in a superimposed manner with the active ingredient carried on the sustained-release carrier.

  For the cosmetic of this embodiment, a sustained release carrier selected from the group consisting of micelles, vesicles, and liquid crystals composed of other than polyglyceryl oleate and / or sucrose fatty acid ester, or the sustained release carrier of the present invention is effective. It is preferable to contain a sustained-release carrier complex carrying the components.

  In the composition of the present invention, by containing two or more sustained-release carriers of the present invention, two or more active ingredients carried by each in a single preparation continuously act in the vicinity of the epidermal basal layer. be able to. In the composition of this embodiment, the sustained release carrier complex of the present invention contains micelles and vesicles each carrying different active ingredients, so that each of the water-soluble and oil-soluble active ingredients is in the vicinity of the basal layer. The effect can be exhibited continuously, and the synergistic effect of the two active ingredients can be expected.

  In addition to the sustained-release carrier of the present invention, the composition of the present embodiment may contain micelles, vesicles, or liquid crystals composed of other than polyglyceryl oleate and sucrose fatty acid ester. As a result, the active ingredient carried on the sustained-release carrier of the present invention acts continuously in the vicinity of the epidermis basal layer, and other active ingredients act in the epidermis, and also act in the dermis through the epidermis basal layer. It is also possible to expect multiple effects with a single formulation. As such a combination, there is a combination of micelles containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid ester and vesicles other than oleic acid polyglyceryl and sucrose fatty acid ester. An active ingredient having low water solubility acts in the vicinity of the epidermis basal layer, and an active ingredient having high water solubility is preferable in that it acts in the epidermis or dermis. In addition, a combination of a vesicle containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid ester and a micelle composed of other than polyglyceryl oleate and sucrose fatty acid ester has high water solubility. The active ingredient works in the vicinity of the epidermis basal layer, and the active ingredient having low water solubility is preferable in that it works in the epidermis or dermis.

  Micelles composed of other than polyglyceryl oleate and sucrose fatty acid esters can be prepared using other surfactants. Examples of such surfactants include sorbitan monostearate, polyethylene glycol monostearate, polyglyceryl monolaurate, and the like.

A vesicle composed of other than polyglyceryl oleate and sucrose fatty acid ester can be obtained by combining one or more of other surfactants. Specific examples include phospholipids. Examples of the phospholipid include glycerophospholipid and sphingophospholipid.
Glycerophospholipid is a substance having a glycerophosphoric acid skeleton, and has a fatty acid ester, a long-chain alkyl ether, a vinyl ether or the like as a lipophilic group. Specifically, phosphatidylcholine (lecithin), phosphatidylethanolamine, phosphatidylserine, phosphadiylinositol, phosphatidylinositol polyphosphate, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin), phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidyl Examples include serine, lysophosphatidylinositol, lysophosphatidylglycerol, and lysophosphatidic acid.
Sphingophospholipids have long-chain bases or long-chain fatty acids such as sphingosine and phytosphingosine, and phosphoric acid or phosphonic acid. Ceramide 1-phosphate derivatives (such as sphingomyelin), ceramide 1-phosphonic acid derivatives ( Ceramide aminoethylphosphonic acid and the like). The phospholipid used in this embodiment may be a natural product extracted and purified from animals or plants, or may be chemically synthesized, and may be subjected to processing such as hydrogenation or hydroxylation. As a natural product, lecithin, which is an extract / purified product from soybean or egg yolk, is easily available as a commercial product, and specific examples thereof include hydrogenated soybean phospholipid.

  The liquid crystal composed of other than polyglyceryl oleate and sucrose fatty acid ester may be prepared by a known method using another surfactant. As the surfactant constituting the liquid crystal, the above-described surfactant capable of constituting the vesicle can be used.

  In the present embodiment, the micelle, vesicle, or liquid crystal itself may be an active ingredient, or the active ingredient may be contained in the core of the vesicle. Such an active ingredient is the same as the above-described active ingredient that can be carried on a micelle, vesicle, or liquid crystal.

  In the composition of this embodiment, a combination of decaglyceryl oleate as the surfactant constituting the sustained-release carrier complex and hydrogenated soybean phospholipid as the surfactant constituting the vesicle is preferable. The ratio of the content of micelles, vesicles and liquid crystals composed of a surfactant other than the surfactant constituting the sustained release carrier complex and the surfactant constituting the sustained release carrier complex is the ratio of the sustained release carrier complex in the composition. The ratio of mass% of micelles, vesicles, and liquid crystals composed of a surfactant other than the surfactant that constitutes the sustained release carrier complex in the composition is preferably 50: 1 to 1:20, 15: 1 to 1: 5 are more preferable. By setting it as this range, the effect of the active ingredient included in the sustained-release carrier complex and the active ingredient of the vesicle can be synergistically exhibited.

Examples of the oil component include polar oil and hydrocarbon oil.
Polar oils include synthetic ester oils such as isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, octyldodecyl oleate, dimethyloctane Hexyldecyl acid, cetyl lactate, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearylate, ethylene glycol di-2-ethylhexylate, N-alkyl glycol monoisostearate, neopentyl glycol dicaprate , Diisostearyl malate, glycerin di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexylate, triiso Stearate trimethylolpropane, tetra-2-ethylhexyl acid pentane erythritol, tri-2-ethylhexyl glyceryl, may be mentioned trimethylolpropane triisostearate.

  Further, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trimyristate, glyceride tri-2-heptylundecanoate, castor oil fatty acid methyl ester, oleic acid oil, cetostearyl alcohol, oleyl alcohol, stearyl alcohol, Octyldodecanol, acetoglyceride, 2-heptylundecyl palmitate, diisobutyl adipate, N-lauroyl-L-glutamic acid-2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, sebacate diacid 2-ethylhexyl, 2-hexyldecyl myristate, 2-hexyldecyl palmitate, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, acetic acid Chill, butyl acetate, amyl acetate, triethyl citrate, may also be mentioned octyl methoxycinnamate and the like.

  Natural oils include avocado oil, flaxseed oil, eno oil, olive oil, kayak oil, beef tallow, sesame oil, wheat germ oil, rice bran oil, sasanqua oil, safflower oil, squalane, soybean oil, tea seed oil, camellia oil, Cinnagi oil, turtle oil, rapeseed oil, corn oil, germ oil, persic oil, castor oil, jojoba oil, Japanese kiri oil, macadamia nut oil, mink oil, cottonseed oil, coconut oil, peanut oil, egg yolk oil, carnauba wax, bird Examples include glycerin, glycerin trioctanoate, and glycerin triisopalmitate.

Examples of the hydrocarbon oil include linear or branched hydrocarbon oils, which may be volatile hydrocarbon oils or non-volatile hydrocarbon oils. Specific examples of hydrocarbon oils include synthetic squalane, vegetable squalane, squalene, liquid isoparaffin, light isoparaffin, hydrogenated polyisobutene, isododecane, stearic acid, light liquid isoparaffin, isohexadecane, liquid paraffin, pristane, α-olefin oligomer, Examples include ozokerite, ceresin, paraffin, paraffin wax, polyethylene wax, polyethylene / polypropylene wax, (ethylene / propylene / styrene) copolymer, (butylene / propylene / styrene) copolymer, polyisobutylene, microcrystalline wax, petrolatum and the like.

  What is necessary is just to adjust the quantity of the oil-based component contained in the composition of this embodiment suitably according to the dosage form to which it applies.

In the composition of the present embodiment, an interface other than polyglyceryl oleate and fatty acid ester of fatty acid having 10 to 20 carbon atoms constituting the micelle as a sustained release carrier within a range not impairing the effects of the present invention. An active agent can be included.
Surfactants include fatty acid soaps (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, alkylsulfuric triethanolamine ether, sulfosuccinic acid esters, polyoxyethylene alkyl sodium sulfate and other anionic surfactants, stearyl chloride Cationic surfactants such as trimethylammonium, benzalkonium chloride, laurylamine oxide, dialkylammonium salts, betaine surfactants (alkyl betaines, amide betaines, sulfobetaines, etc.), imidazoline amphoteric surfactants (2-cocoyl) -2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt), amphoteric surfactants such as acylmethyltaurine, sorbitan fatty acid esters (sorbitan monostearate) , Sorbitan sesquioleate, etc.), glycerin fatty acids (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hardened castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters ( POE sorbitan monooleate, polysoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbite monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerin monoisostearate, etc.), POE fatty acid ester (Polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-
Octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / cured Nonionic surfactants such as castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), and the like.

  Polyhydric alcohols include polyethylene glycol, glycerin, 1,3-butanediol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4 -Hexylene glycol, 1,2-hexanediol, 1,2-octanediol and the like.

Thickeners include guar gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, Heparan sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, kerato sulfate, locust bean gum, succinoglucan, caronic acid, chitin, chitosan, carboxymethyl Chitin, agar, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, al Le-modified carboxyvinyl polymers, sodium polyacrylate, polyethylene glycol, and bentonite.

  As powders, the surface may be treated, mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic anhydride (silica), aluminum oxide, barium sulfate, etc. May be treated, bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, zinc oxide inorganic pigments, surface may be treated, mica titanium, fish phosphorus foil, Pearl agents such as bismuth oxychloride, red 202, red 228, red 226, yellow 4, blue 404, yellow 5, red 505, red 230, red 223 which may be raked No., Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204, organic dyes, polyethylene powder, polymeta Methyl acrylic acid, nylon powder, organic powders such as organopolysiloxane elastomers.

Examples of the UV absorber include paraaminobenzoic acid UV absorbers, anthranilic acid UV absorbers, salicylic acid UV absorbers, cinnamic acid UV absorbers, benzophenone UV absorbers, sugar UV absorbers, 2- (2 UV absorbers such as'-hydroxy-5'-t-octylphenyl) benzotriazole and 4-methoxy-4'-t-butyldibenzoylmethane.

A method for preparing the composition of the present embodiment is a micelle, vesicle, or liquid crystal containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters of fatty acids having 10 to 20 carbon atoms. If an active ingredient is carry | supported by the sustained release carrier which consists of, it will not specifically limit.
A nonionic surfactant having a relatively low HLB value may be prepared by mixing and dissolving each component at room temperature, or preparing a composition by stirring and dissolving under heating. When it contains, it is preferable to dissolve by stirring under heating. When a nonionic surfactant having a high HLB value is included, it can be dissolved at room temperature.
As a heating condition, for example, a method of using a hot water bath, heating at 80 ° C. for 10 minutes, and then allowing to cool is exemplified.

  As another embodiment of the present invention, “a micelle, vesicle or liquid crystal containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters of fatty acids having 10 to 20 carbon atoms” A step of preparing a preparation in which an active ingredient is supported on a sustained-release carrier comprising: a method of storing the carrier in the epidermal basal layer by applying the preparation to the skin '', `` polyglyceryl oleate and carbon number A step of preparing a preparation in which an active ingredient is supported on a sustained release carrier comprising micelles, vesicles, or liquid crystals containing one or more surfactants selected from the group consisting of sucrose fatty acid esters of 10 to 20 fatty acids And a method of continuously exerting the effect of the active ingredient in the epidermis by applying the preparation to the skin.

The method of storing the carrier in the epidermal basal layer includes a step of preparing a preparation in which the sustained-release carrier of the present invention is loaded with an active ingredient. When the preparation is applied to the skin, olein is used as a surfactant. One or more surfactants selected from the group consisting of polyglyceryl acid and sucrose fatty acid ester are dispersed in water to prepare a surfactant dispersion containing micelles, vesicles, or liquid crystals formed by the surfactant. Then, the preparation produced by the step of preparing the preparation in which the active ingredient is supported on the sustained release carrier of the present invention by mixing the surfactant dispersion and the active ingredient may be applied to the skin.
In addition, the method of continuously exerting the effect of the active ingredient in the epidermis includes a step of preparing a preparation in which the active ingredient is supported on the sustained-release carrier of the present invention, and the preparation is applied to the skin. Is a surfactant in which one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters are dispersed in water, and micelles, vesicles, or liquid crystals formed by the surfactant are dispersed. A preparation produced by the step of preparing a preparation in which an active ingredient is supported on the sustained release carrier of the present invention by preparing a surfactant dispersion containing the mixture and mixing the surfactant dispersion and the active ingredient. Apply to the skin.

  Formulation may be performed according to a conventional method depending on the dosage form. A lotion production method can be prepared, for example, by mixing a composition in which an active ingredient is supported on a sustained-release carrier of the present invention in an aqueous phase containing an optional ingredient. As a method for producing an emulsion, for example, it is prepared by mixing a composition in which an active ingredient is supported on a sustained release carrier of the present invention in an oil phase containing an arbitrary component and passing through a normal emulsification step. Can do.

  Cosmetics (including quasi-drugs) can be applied or sprayed on the skin by various methods and adhered to the skin for use. In this embodiment, in order to apply the preparation to the skin, it may be applied directly to the skin or sprayed, or after impregnating in advance with a cloth, non-woven fabric, paper, etc., this is applied to the skin. Also good. In the case of direct application, an appropriate amount can be taken by hand or finger and spread on the use site for use.

  By the method of the present embodiment, effective ingredients for normalizing turnover, pigmentation, etc., such as the mechanism in the vicinity of the epidermis basal layer are the key, can realize healthy and beautiful bare skin it can.

  EXAMPLES Hereinafter, although an Example demonstrates this invention still in detail, this invention is not limited to a following example, unless the summary is exceeded.

<Preparation of micelle>
According to the following procedure, sample A containing a micelle containing a fluorescent marker as a model of an active ingredient and sample B containing a fluorescent marker not contained in the micelle were prepared.
Sample A uses decaglyceryl monooleate (NIKKOL Decaglyn 1-OV manufactured by Nikko Chemicals Co., Ltd., HLB value = 12) as a surfactant, Nile Red (Wako Pure Chemical Industries, Ltd.) is added as a fluorescent marker, and mixed uniformly Then, it was prepared by adding water to disperse and stand still.
Sample B was prepared by adding water to Nile Red (Wako Pure Chemical Industries, Ltd.) as a fluorescent marker and dispersing and standing.

<Evaluation of permeability to epidermis-1>
Sample A was applied to Labcyte EPI-MODEL24 (manufactured by Japan Tissue Engineering Co., Ltd.) as a human three-dimensional cultured epidermis model, and after 24 hours, the sample remaining on the surface of the human three-dimensional cultured epidermis model was washed and frozen. Embedded. Using a confocal laser scanning microscope “LSM510” (manufactured by Carlzeiss), a phase contrast microscope image and a fluorescence microscope image (measurement of fluorescence intensity at excitation wavelengths of 561 nm and 575 nm) were observed on the cross section prepared with a cryostat.
As a result, in the skin cross section shown in the phase contrast microscope image of FIG. 1, fluorescence was observed from the entire skin cross section as shown in the fluorescence microscopic image of FIG.

<Evaluation of permeability to epidermis-2>
As a model of keratinocytes of the entire epidermis, differentiated keratinocytes (human epidermis keratinocytes Kurashiki Spinning Co., Ltd., “newborn epidermis keratinocytes” added with calcium ions and cultured for 24 hours), each of sample A and sample B was applied for 2 hours. After the surface of the differentiated keratinocytes was washed later, a fluorescence microscope image (measurement of fluorescence intensity at excitation wavelengths of 561 nm and 575 nm) was obtained with a confocal laser scanning microscope “LSM510” (manufactured by Carlzeiss).
As a result, as shown in FIG. 3, fluorescence was observed over the entire surface of Sample B not containing the micelle of the present invention. On the other hand, in the sample A containing the micelle of the present invention, almost no fluorescence was observed as shown in FIG.

<Evaluation of keratinocyte storage ability of epidermal basal layer-1>
Using undifferentiated keratinocytes as the epidermal basal layer keratinocyte model (Kurashiki Spinning Co., Ltd. “Newborn epidermis keratinocytes”), prepared micelles containing Nile Red (Wako Pure Chemical Industries, Ltd.) as a fluorescent marker instead of active ingredients, and undifferentiated The adsorptivity to keratinocytes was evaluated. Table 1 shows the compositions of Examples 1 to 7 and Table 2 shows the compositions of Comparative Examples 1 to 6. In the table, the unit is mass%.
First, undifferentiated keratinocytes (human epidermal keratinocytes) were seeded on 8-well chamber slides and cultured in an incubator under conditions of 37 ° C. and 5% CO ₂ . after that,
Nile red 0.1 mg / g EtOH as a fluorescent marker and the esters of Examples 1 to 7 in Table 1 and Comparative Examples 1 to 6 in Table 2 were mixed and added to a medium (undifferentiated keratinocytes: human epidermal keratinocytes). .
After 2 hours, the surface of undifferentiated keratinocytes was washed, and each fluorescence microscope image (measurement of fluorescence intensity at excitation wavelengths of 561 nm and 575 nm) was obtained with a confocal laser scanning microscope “LSM510” (manufactured by Carlzeiss).
The amount of fluorescence marker adsorbed was quantitatively evaluated by calculating the fluorescence intensity of each pixel using image processing software based on the obtained image and integrating all the pixels.
Specifically, a 200 pixel × 200 pixel JPEG image was randomly cut out from the obtained image. Histogram analysis was performed on the image using image analysis software (ImageJ). 40,000 pixels were assigned to each value of 256 gradations (0 to 255). Next, each tone and the corresponding number of pixels were multiplied to score. When the gradation 2 is 100 pixels, the score is 200. Finally, the scores for each gradation were added to obtain an integrated fluorescence intensity value.
The results are shown in Tables 1 and 2. 5 shows a fluorescence microscope image of Comparative Example 1, and FIG. 6 shows a fluorescence microscope image of Example 1.

<Evaluation of keratinocyte storage ability-2 of epidermal basal layer>
Evaluation of permeability to epidermis-1 In 24 hours after application of the sample, the amount of the fluorescent marker permeated to the receiver under the epidermis was quantified to evaluate the retentivity in the epidermal basal layer keratinocytes. As a result, in the case of the sample containing the fluorescent marker not included in the micelle, the fluorescent marker of the receiver was 2 μg. On the other hand, for the sample containing the fluorescent marker included in the micelle, the fluorescent marker of the receiver was below the detection limit.

  From these experimental results, it was found that the ester forms micelles carrying a fluorescent marker in the inner core, penetrates rapidly into the epidermis, and accumulates in undifferentiated keratinocytes. That is, it is presumed that micelles containing the esters shown in Table 1 stay in the vicinity of the epidermal basal layer, and the fluorescent markers carried on the inner core of micelles are gradually released. It was shown that it can be suitably used as a release carrier.

  The present invention provides a sustained-release carrier that has high permeability to the epidermis and accumulates in keratinocytes in the basal layer of the epidermis. In addition, since a sustained-release carrier complex capable of continuously exhibiting the effect of the active ingredient in the epidermis is provided, it is very useful industrially.

Claims (11)

  A sustained release carrier comprising micelles, vesicles, or liquid crystals, comprising one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters of fatty acids having 10 to 20 carbon atoms.   The sustained release carrier according to claim 1, wherein the HLB value of the sucrose fatty acid ester of the polyglyceryl oleate and / or the fatty acid having 10 to 20 carbon atoms is 9 or more and 18 or less.   The sustained release carrier according to claim 1 or 2, wherein the polyglyceryl oleate is decaglyceryl monooleate.   The sustained release carrier according to claim 1 or 2, wherein the fatty acid of the sucrose fatty acid ester comprises at least one selected from the group consisting of oleic acid, stearic acid, isostearic acid, palmitic acid, myristic acid, and lauric acid.   A sustained-release carrier complex in which an active ingredient is supported on the sustained-release carrier according to claim 1.   6. The sustained release carrier complex according to claim 5, wherein the active ingredient is loquat leaf extract.   The composition formed by including 1 type (s) or 2 or more types of the sustained release carrier or sustained release carrier complex of any one of Claims 1-6.   The composition according to claim 7, which is an external preparation for skin.   The composition according to claim 7 or 8, which is a cosmetic (including quasi-drugs). An active ingredient is supported on a sustained release carrier composed of micelles, vesicles or liquid crystals containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters of fatty acids having 10 to 20 carbon atoms. Preparing a prepared formulation,
A method of storing the sustained-release carrier in the epidermal basal layer by applying the preparation to the skin. An active ingredient is supported on a sustained release carrier composed of micelles, vesicles or liquid crystals containing one or more surfactants selected from the group consisting of polyglyceryl oleate and sucrose fatty acid esters of fatty acids having 10 to 20 carbon atoms. Preparing a prepared formulation,
A method of continuously exerting the effect of the active ingredient in the epidermis by applying the preparation to the skin.