JP2021014448A - Skin external preparation for introduction and method for using external preparation for introduction - Google Patents

Abstract

To provide a skin external preparation for introduction to be used by being applied to skin before use of another skin external preparation to satisfy all of the refreshing feeling of use, stable high moisturizing effect, and stably maintained emulsified state and to promote the percutaneous absorption ability of an active ingredient contained in the another skin external preparation.SOLUTION: A skin external preparation for introduction comprises a high internal phase W/O type emulsified composition containing an oil gelling agent and has an aqueous phase proportion of 70 mass% or more. The skin external preparation for introduction is used by being applied to the skin before use of another skin external preparation to promote the percutaneous absorption of an active ingredient contained in the another skin external preparation.SELECTED DRAWING: None

Description

The present invention contains a high internal phase W / O type emulsifying composition and is applied to the skin before use of other external preparations for skin in order to promote transdermal absorption of the active ingredient contained in other external preparations for skin. Regarding the introduction skin external preparation to be used.

A W / O-type emulsified composition in which an aqueous phase is dispersed in an oil phase and a high proportion of dispersed phases is called a high internal phase emulsified composition (see, for example, Patent Document 1). .. In general, the merit of the high internal phase emulsified composition is that as a W / O type emulsified cosmetic in which the aqueous phase is dispersed in the oil phase, both a refreshing feeling and a high moisturizing effect can be obtained. Be done. The disadvantages are that it is difficult to maintain the emulsified state and the stability over time is low.
On the other hand, many external preparations for skin such as cosmetics are provided with useful functions by blending active ingredients having various actions such as moisturizers and whitening agents. For example, various moisturizers, whitening agents, anti-acne agents, anti-wrinkle agents, anti-inflammatory agents, antioxidants, etc. are blended with cosmetics (cosmetics) and quasi-drugs to act on the skin. (See, for example, Non-Patent Document 1). In general, in order to effectively exert the action of these active ingredients, it is important to penetrate each layer of the skin epidermis.
Therefore, in order to enhance the transdermal absorbability of the active ingredient, development of various transdermal absorption promoters and methods for promoting transdermal absorption are being studied.

Japanese Unexamined Patent Publication No. 57-81827

New Cosmetics Handbook (2006) Nikko Chemicals

However, a skin external preparation that can satisfy all of a refreshing feeling of use, a high moisturizing effect, and a stable maintenance of an emulsified state has not been provided conventionally.
In addition, a skin external preparation containing a high internal phase W / O type emulsifying composition that satisfies all of these has the effect of promoting the transdermal absorbability of the active ingredient contained in other skin external preparations. , Was not known.

Therefore, the present invention can satisfy all of a refreshing feeling of use, a high moisturizing effect, and stable maintenance of an emulsified state, and promotes transdermal absorbability of an active ingredient contained in other external preparations for skin. It is an object of the present invention to provide an introduction skin external preparation to be applied to the skin before use of the skin external preparation.

As a result of intensive studies to solve the above problems, the present inventor has found that an external preparation for skin containing a high internal phase W / O type emulsifying composition containing an oil gelling agent has a refreshing feel and a high feeling. It was found that all of the moisturizing effect and the stable maintenance of the emulsified state can be satisfied. Furthermore, it has been found that such an external preparation for skin can enhance the transdermal absorbability of the active ingredient contained in other external preparations for skin. As a result, the skin external preparation containing the high internal phase W / O type emulsifying composition containing the oil gelling agent is effective as an introduction skin external preparation to be applied to the skin before the use of other skin external preparations. We have found that it can be used for the above, and have completed the present invention.

That is, the present invention includes the following aspects.
[1] An introduction skin external preparation containing an oil gelling agent and a high internal phase W / O type emulsifying composition in which the proportion of the aqueous phase is 70% by mass or more.
An introduction skin external preparation, which is applied to the skin before use of the other skin external preparation in order to promote transdermal absorption of the active ingredient contained in the other skin external preparation.
[2] The skin external preparation for introduction according to the above [1], wherein the oil gelling agent contains at least one selected from the group consisting of a dextrin fatty acid ester and a glycerin fatty acid ester.
[3] The oil gelling agent comprises at least one selected from the group consisting of dextrin palmitate, dextrin myristate, glyceryl behenate, and glyceryl (behenic acid / eicosanedioic acid). 2] The introduction skin external preparation according to.
[4] The skin external preparation for introduction according to any one of [1] to [3] above, wherein the active ingredient is an oil-soluble active ingredient.
[5] The oil-soluble active ingredient is glycyrrhetinic acid derivative, fat-soluble vitamins, fat-soluble vitamin derivative, carotinoids, ubiquinones, thioctic acid and its derivative, carnitine derivative, ceramide, sphingolipid, fat-soluble provitamin. The introduction skin external preparation according to any one of the above [1] to [4], which comprises at least one selected from the group consisting of a fat-soluble provitamin derivative.
[6] An introduction skin external preparation containing an oil gelling agent and a high internal phase W / O type emulsifying composition in which the proportion of the aqueous phase is 70% by mass or more.
A method for using an introduction skin external preparation, which comprises applying the active ingredient to the skin before use of the other skin external preparation in order to promote transdermal absorption of the active ingredient contained in the other skin external preparation.
[7] The method for using an external preparation for introduction according to the above [6], wherein the oil gelling agent contains at least one selected from the group consisting of a dextrin fatty acid ester and a glycerin fatty acid ester.
[8] The oil gelling agent comprises at least one selected from the group consisting of dextrin palmitate, dextrin myristate, glyceryl behenate, and glyceryl (behenic acid / eicosanedioic acid). 7] How to use the introduction skin external preparation according to.
[9] The method for using an external preparation for introduction according to any one of [6] to [8] above, wherein the active ingredient is an oil-soluble active ingredient.
[10] The oil-soluble active ingredient is glycyrrhetinic acid derivative, fat-soluble vitamins, fat-soluble vitamin derivative, carotinoids, ubiquinones, thioctic acid and its derivative, carnitine derivative, ceramide, sphingolipid, fat-soluble provitamin. The method for using an external preparation for introduction according to any one of [6] to [9] above, which comprises at least one selected from the group consisting of a fat-soluble provitamin derivative.

According to the present invention, in order to satisfy all of a refreshing feeling of use, a high moisturizing effect, and stable maintenance of an emulsified state, and to promote transdermal absorbability of an active ingredient contained in other external preparations for skin. It is possible to provide an introduction skin external preparation to be applied to the skin before use of the skin external preparation.

FIG. 1 is a diagram showing the results of examining the content of DL-α-tocopherol acetate contained in the skin substitute membrane in Test Example 1. FIG. 2 is a diagram showing the results of examining the content of stearyl glycyrrhetinate contained in the skin substitute membrane in Test Example 6. FIG. 3 is a diagram showing the results of examining the content of retinol palmitate contained in the skin substitute membrane in Test Example 7.

Hereinafter, the skin external preparation for introduction of the present invention will be described in detail, but the description of the constituent requirements described below is an example as an embodiment of the present invention, and is not specified in these contents.

(Skin external preparation for introduction)
The skin external preparation for introduction of the present invention contains an oil gelling agent and contains a high internal phase W / O type emulsified composition in which the proportion of the aqueous phase is 70% by mass or more.
The introduction skin external preparation of the present invention is applied to the skin before use of other skin external preparations in order to promote the transdermal absorption of the active ingredient contained in other skin external preparations.

<< High internal phase W / O type emulsified composition >>
The emulsified composition used in the present invention is a W / O type emulsified composition in which the aqueous phase is dispersed in the oil phase.
In the present invention, the proportion of the aqueous phase in the W / O type emulsified composition is 70% by mass or more. Such a W / O type emulsified composition in which the aqueous phase accounts for 70% by mass or more is referred to as a "high internal phase W / O type emulsified composition" in the present invention.
The proportion of the aqueous phase in the high internal phase W / O type emulsified composition is typically 70% by mass or more and 99% by mass or less, and more typically 74% by mass or more and 95% by mass or less. Even more typically, it is 74% by mass or more and 90% by mass or less.
Here, it can be confirmed by a method well known to those skilled in the art whether or not the emulsified state of the emulsified composition generally forms a W / O type emulsified state in which the aqueous phase is dispersed in the oil phase. .. For example, if the emulsion is dropped into water placed in a test tube and not dispersed, it can be determined that the emulsified state is W / O type (dilution method). Further, for example, it can be confirmed that the emulsion is in a W / O type emulsified state by bringing the electrode portion of the tester into contact with the emulsion and measuring the electrical conductivity (electrical conductivity method). Further, for example, a water-soluble or oil-soluble dye can be added, and a W / O type emulsified state can be confirmed by a microscope image (dye method).

<< Oil gelling agent >>
The high internal phase W / O type emulsified composition used in the present invention contains an oil gelling agent.
The highly internal phase W / O type emulsified composition containing the oil gelling agent can stably maintain the emulsified state as shown in the following examples.
As the oil gelling agent, an oil gelling agent that can be generally used for cosmetics and the like can be appropriately selected and used, and there is no particular limitation and the oil gelling agent can be selected according to the purpose. For example, esters of polysaccharides and fatty acids such as dextrin palmitate, dextrin myristate, (palmitic acid / ethylhexanoic acid) dextrin, inulin stearate, glyceryl (behenic acid / eicosandiic acid) glyceryl, glyceryl behenate and other glycerin fatty acid esters, Examples thereof include higher alcohols such as batyl alcohol and behenic alcohol, and organically modified viscous minerals. Among them, it is preferable to use dextrin fatty acid ester or glycerin fatty acid ester, and more specifically, it is preferable to use dextrin palmitate, dextrin myristic acid, glyceryl (behenic acid / eicosanic acid), glyceryl behenate and the like.
One type of oil gelling agent may be used alone, or two or more types may be used in combination.
The content of the oil gelling agent in the high internal phase W / O type emulsified composition is the relationship with the type and blending amount of other components contained in the high internal phase W / O type emulsified composition, or used. Although it is not unconditional depending on the type of oil gelling agent, for example, it is preferably 0.05% by mass or more. Within this range, it is possible to contribute to the stabilization of the emulsified state of the high internal phase W / O type emulsified composition.
The content of the oil gelling agent in the high internal phase W / O type emulsified composition is more preferably 0.1% by mass or more, further preferably 0.1% by mass or more and 10% by mass or less. It is particularly preferable that it is 0.1% by mass or more and 5% by mass or less. If the content of the oil gelling agent in the high internal phase W / O type emulsified composition is less than the above range, the effect of stabilizing the emulsified state of the high internal phase W / O type emulsified composition may be reduced. is there. Further, even if the oil gelling agent is contained beyond the above range, the emulsified state cannot be expected to be stabilized according to the content thereof, but rather the emulsified state of the high internal phase W / O type emulsified composition is stabilized. The effect of conversion may be reduced.

<< Specific aspects of the high internal phase W / O type emulsified composition >>
As a preferable specific embodiment of the high internal phase W / O type emulsified composition used in the present invention, for example, the high internal phase W / O containing the above-mentioned oil gelling agent and further containing various components described below. Examples include mold emulsified compositions.
In other words
Emulsifier as component (A),
Oil as component (B),
An oil gelling agent as the component (C)
Examples thereof include a high internal phase W / O type emulsified composition containing water as the component (D) and having a dispersed phase composed of an aqueous phase accounting for 70% by mass or more. As shown in the following examples, this high internal phase W / O type emulsified composition contains the oil gelling agent of the component (C), so that the emulsified state is stabilized. It is an O-type emulsified composition.
In the high internal phase W / O type emulsified composition composed of the above components, the proportion of the dispersed phase composed of the aqueous phase is preferably 70% by mass or more and 99% by mass or less, and 74% by mass or more and 95% by mass or more. % Or less, and even more preferably 74% by mass or more and 90% by mass or less.
Hereinafter, each component will be described.

As the emulsifier of the component (A), an emulsifier that can be generally used for cosmetics and the like can be appropriately selected and used, and can be selected according to the purpose without particular limitation, but particularly constitutes an ester. A lipophilic surfactant in which the fatty acid is unsaturated is preferable.
Examples of unsaturated fatty acids include oleic acid, erucic acid, linoleic acid, ricinoleic acid and the like, and examples of the hydrophilic portion of the surfactant include sucrose, glycerin, sorbitan and oxyethylene. Of these, sucrose oleate and sucrose erucate are preferably used.
Further, from the viewpoint of usability, stability and viscosity of the emulsified composition, a surfactant in which the fatty acids constituting the ester are saturated fatty acids palmitic acid and stearic acid may be used in combination. Of these, sucrose palmitate and sucrose stearate are preferably used.
Further, from the viewpoint of usability, it is preferable to use a polyglycerin fatty acid ester, particularly condensed pentaglycerin ricinoleate.
The emulsifier generally refers to a substance having a function of emulsifying water and oil. For example, even if it is called a surfactant, it can be used as an emulsifier as long as it has such a function. is there.
As the component (A), one type of emulsifier may be used alone, or two or more types may be used in combination.
The content of the component (A) is related to the blending amount of the components (B) to (D) and the blending amount of other raw materials, and is not unconditional depending on the type of emulsifier used, but is, for example, high. The total amount of the internal phase W / O type emulsified composition is preferably 0.1% by mass or more and 30% by mass or less, and more preferably 0.5% by mass or more and 5.0% by mass or less. Within this range, the emulsified state of the high internal phase W / O type emulsified composition can be stably maintained.

As the oil of the component (B), an oil that can be generally used for cosmetics and the like can be appropriately selected and used, and there is no particular limitation and the oil can be selected according to the purpose.
For example, from the viewpoint of preparing a high internal phase W / O type emulsified composition, it is preferable to use an oil that becomes liquid at the preparation temperature (for example, 80 ° C.). Further, from the viewpoint of making an emulsified liquid cosmetic that has low viscosity and is easy to apply to the skin, it is preferable to use an oil that becomes liquid at room temperature (25 ° C.).
Specifically, for example, it is an ester oil formed by ester-bonding fatty acids and alcohols. Examples of the ester oil include cetyl 2-ethylhexanoate, isononyl isononanoate, isopropyl myristate, glyceryl tri2-ethylhexanoate, 2-octyldodecyl myristate, 2-ethylhexyl palmitate, 2-octyldodecyl oleate, and the like. Examples thereof include neopentyl glycol di2-ethylhexanoate, glyceryl triisostearate, diisostearyl malate, diglyceride 2-ethylhexanoate, and glyceryl tri (caprylic acid / capric acid). From the viewpoint of low viscosity and stability, cetyl 2-ethylhexanoate, isononyl isononanoate, glyceryl tri2-ethylhexanoate, glyceryl tri (caprylic acid / capric acid) and the like are preferable.
Further, for example, it is a hydrocarbon-based non-ester oil. Examples of the non-ester oil include mineral oil (liquid paraffin), squalane, squalene, selecin and the like. From the viewpoint of low viscosity and stability, mineral oil and squalane are preferable.
Further, for example, it is a silicone-based silicone oil. Examples of the silicone oil include diphenylsiloxytrimethicone, dimethicone (dimethylpolysiloxane), phenyltrimethicone, cyclopentasiloxane and the like. Diphenylsiloxytrimethicone and cyclopentanesiloxane are preferable from the viewpoint of familiarity with makeup and compatibility with other oil phase components when two or more kinds of oils are used.
Also, for example, vegetable oil. Examples of the vegetable oil include jojoba oil, olive oil, macadamia nut oil, camellia oil, avocado oil, rose hip oil, kukui nut oil, hazelnut oil, meadowfoam oil and the like. From the viewpoint of stability, macadamia nut oil and meadowfoam oil are preferable.
As the oil of the component (B), one kind of the above-mentioned oil may be used alone, or two or more kinds may be used in combination.

The oil of the component (B) belongs to an oil that becomes liquid at the temperature (for example, 80 ° C.) at which the high internal phase W / O type emulsified composition is prepared, or an oil that becomes liquid at room temperature (25 ° C.). Other oils, that is, higher melting point oils (hereinafter referred to as "other oils") may be used in combination as appropriate. As other oils, an emulsifier that can be generally used for cosmetics and the like may be appropriately selected and used. For example, from the viewpoint of adjusting the feeling of use of cosmetics, for example, cholesteryl hydroxystearate and dimer dilinole. Examples thereof include semi-solid oils such as acids (phytosteryl / isostearyl / cetyl / stearyl / behenyl) and dilauroyl glutamate (octyldodecyl / phytosteryl / behenyl), and solid oils such as batyl stearate, behenyl alcohol, beeswax and cholesterol.
As the above-mentioned other oil, one kind of the oil of the component (B) may be used alone, or two or more kinds may be used in combination.
However, from the viewpoint of using a liquid liquid at the preparation temperature (for example, 80 ° C.) of the high internal phase W / O type emulsified composition, or from the viewpoint of making an emulsified liquid cosmetic which has low viscosity and is easy to apply to the skin, The content of the above-mentioned other oil in the total amount of the oil of the component (B) is preferably more than 0% by mass and 50% by mass or less, and more preferably more than 0% by mass and 25% by mass or less. It is more preferably more than 0% by mass and 10% by mass or less. In some cases, it is most preferable that it is not included.

The content of the component (B) (when the above-mentioned other oils are contained or when two or more kinds of oils are contained, as the total amount thereof) includes the components (A), (C), and (D). Although it is not unconditional depending on the type of oil used and the relationship between the amount of the oil and the amount of other raw materials, for example, 0.1% by mass or more in the total amount of the high internal phase W / O type emulsified composition. It is preferably 30% by mass or less, and more preferably 5% by mass or more and 25% by mass or less. Within this range, the occupancy ratio of the dispersed phase composed of the aqueous phase can be easily maintained, and the emulsified state of the high internal phase W / O type emulsified composition can be stably maintained.

The types that can be used as the oil gelling agent for the component (C) are as described above.
The content of the component (C) has a relationship with the blending amount of the components (A), (B), and (D) and the blending amount of other raw materials, and also depends on the type of oil gelling agent used. Although it is not unconditional, for example, it is preferably 0.05% by mass or more in the total amount of the high internal phase W / O type emulsified composition. Within this range, it is possible to contribute to the stabilization of the emulsified state of the high internal phase W / O type emulsified composition.
The content of the oil gelling agent in the high internal phase W / O type emulsified composition is more preferably 0.1% by mass or more, further preferably 0.1% by mass or more and 10% by mass or less. It is particularly preferable that it is 0.1% by mass or more and 5% by mass or less. If the content of the oil gelling agent in the high internal phase W / O type emulsified composition is less than the above range, the effect of stabilizing the emulsified state of the high internal phase W / O type emulsified composition may be reduced. is there. Further, even if the oil gelling agent is contained beyond the above range, the emulsified state cannot be expected to be stabilized according to the content thereof, but rather the emulsified state of the high internal phase W / O type emulsified composition is stabilized. The effect of conversion may be reduced.

As the water of the component (D), for example, purified water, distilled water, ion-exchanged water, RO water, sterilized treated water and the like, which can be generally used for cosmetics and the like, can be appropriately selected and used. There are no restrictions and it can be selected according to the purpose.
The content of the component (D) is not unconditional depending on the relationship with the blending amounts of the other components (A) to (C), but for example, 70 in the total amount of the high internal phase W / O type emulsified composition. It is preferably mass% or more and 99 mass% or less, and more preferably 74 mass% or more and 90 mass% or less. Within this range, the occupancy ratio of the dispersed phase composed of the aqueous phase can be easily maintained, and the emulsified state of the high internal phase W / O type emulsified composition can be stably maintained.

In addition to the above components (A) to (D), the highly internal phase W / O type emulsified composition used in the present invention is generally blended with external preparations for skin such as cosmetics as long as the effects of the present invention are not impaired. Ingredients such as alcohols, organic acids, salts, preservatives, fragrances, pigments and the like can be blended. Further, a thickener for thickening may be blended.
As alcohols, from the viewpoint of giving a moist feeling to the skin and improving the usability, for example, sugar alcohols such as sorbitol, xylitol and maltitol, and trihydric or higher polyhydric alcohols such as glycerin and diglycerin are used. It may be blended as appropriate. From the viewpoint of antiseptic activity, for example, divalent alcohols such as dipropylene glycol, 1,3-butylene glycol, 1,2-pentylene glycol and 1,2-hexylene glycol, ethanol, propanol and isopropanol. , Butanol, phenoxyethanol and other monohydric alcohols may be appropriately blended.
Further, from the viewpoint of adjusting the usability of cosmetics, an aqueous thickener such as xanthan gum, hydroxyethyl cellulose, carboxymethyl cellulose, silicic acid (Al / Mg), carboxyvinyl polymer, acrylic acid / alkyl methacrylate polymer is appropriately used. It may be blended.

As one of the preferable specific embodiments of the present invention, an embodiment containing a microbial fermentation product can be mentioned as another material. As microbial fermentation products, cultures obtained by fermenting components generally contained in cosmetics or the like with lactic acid bacteria (including bifidobacteria) or yeast, culture supernatants, the cultures and / or water-containing alcohols from the culture supernatants. Examples thereof include extracts extracted by the above. For example, a lactic acid bacterium / milk fermented liquid as described in Japanese Patent Publication No. 02-040643, a lactic acid bacterium / milk fermented liquid as described in Japanese Patent No. 4512265, and a patent No. 3795011. Lactic acid bacterium / aloe vera fermented liquor, soymilk / bifidus bacterium fermented liquor as described in Japanese Patent No. 3184114, lactic acid bacterium culture in a milk component-containing medium as described in JP-A-2017-21284. Examples thereof include a culture obtained by fermenting Cryberomyces maxianus and a culture obtained by fermenting a lactic acid bacterium culture in a milk component-containing medium as described in WO2016 / 117489 with Wickerhamomyces pijuperi. Not limited to.
The content of the microbial fermented product is related to the blending amount of the components (A) to (D) and the blending amount of other raw materials, and is not unconditional depending on the type and purpose of blending the microbial fermented product to be used. For example, the dry solid content in the total amount of the high internal phase W / O type emulsified composition is preferably 0.001% by mass or more and 0.4% by mass or less, and 0.01% by mass or more and 0.2% by mass or less. The following is more preferable. Within this range, the effect of blending the microbial fermentation product can be expected, and the emulsified state of the high internal phase W / O type emulsified composition can be stably maintained.

As described above, the high internal phase W / O type emulsified composition used in the present invention generally contains, in addition to the above components (A) to (D), cosmetics and the like as long as the effects of the present invention are not impaired. Ingredients to be blended in external preparations for skin can be blended. The high internal phase W / O type emulsified composition used in the present invention may contain an active ingredient contained in other external preparations for skin as described later. However, from the viewpoint of providing a cheaper skin external preparation for introduction (skin pretreatment agent), the high internal phase W / O type emulsified composition used in the present invention is contained in other skin external preparations. The active ingredient may not be contained as long as it contains an ingredient capable of promoting the transdermal absorbability of the active ingredient.

<< Method for producing high internal phase W / O type emulsified composition >>
The high internal phase W / O type emulsified composition used in the present invention is usually composed mainly of the oil of the component (B) as a preparation method well known to those skilled in the art, and is a raw material that can be well dissolved or dispersed in the oil. Is mixed or dispersed to prepare an oil phase as a raw material (hereinafter, may be referred to as “oil phase as a raw material”), and the component (D) is mainly composed of water and is well dissolved or dispersed in water. The raw materials that can be used are mixed or dispersed to prepare an aqueous phase as a raw material (hereinafter, may be referred to as a “water phase as a raw material”), and if necessary, under appropriate temperature conditions, for example, from room temperature to. It can be prepared by adding an aqueous phase little by little to the oil phase as a raw material at 80 ° C. and dispersing the aqueous phase with a stirring mixer or the like. Once the emulsified state is formed, it may be cooled to room temperature or the like as it is, or a stirring cooling step may be adopted in which stirring is continued while gradually lowering the temperature. At the time of such preparation, the oil gelling agent of the component (C) generally has an affinity for oil, so it is preferable to mix or disperse it in an oil-based raw material.

<External skin preparation>
The high internal phase W / O type emulsified composition used in the present invention can be used for external preparations for skin represented by cosmetics.
The external preparation for skin of the present invention contains the above-mentioned high internal phase W / O type emulsified composition.
Here, examples of the external preparation for skin include cosmetics (cosmetics), pharmaceuticals, quasi-drugs, and the like. Among them, the high internal phase W / O type emulsified composition used in the present invention can be suitably used as a mode of cosmetics.
The high internal phase W / O type emulsified composition used in the present invention may be used as it is in the form of a cosmetic, or may be blended in the form of a raw material for a cosmetic in the manufacturing process of the cosmetic. You may use it. Specific examples include skin care cosmetics (skin water, serum, milky lotion, cream, whitening cosmetics, etc.), sunscreen cosmetics, makeup base creams, foundations, makeup cosmetics such as lipstick, and the like. it can.
In addition to the above-mentioned high internal phase W / O type emulsified composition, a component that can be added to the external preparation for skin can be appropriately added to the external preparation for skin of the present invention, if necessary.

<Use as an external preparation for introduction skin>
The introduction skin external preparation of the present invention has a transdermal absorption promoting effect on the active ingredient contained in other skin external preparations, as shown in the following examples.
Therefore, the external preparation for skin of the present invention can be suitably used as an external preparation for introduction (skin pretreatment agent) by applying it to the skin before using another external preparation for skin.

<< Active ingredient >>
The active ingredient contained in other external preparations for skin refers to an active ingredient that exerts some action when applied to the skin, etc., and is not particularly limited, but for example, a moisturizer, a whitening agent, an anti-acne agent, and an anti-inflammatory agent. Examples include wrinkles, anti-inflammatory agents, antioxidants, vitamins, various amino acids, hair growth agents, antibacterial agents, hormone agents, enzymes, various plant extracts, activators, blood circulation promoters and the like. These may be contained in two or more kinds.
More specifically, whitening agents such as vitamins such as vitamins A, B, C (ascorbic acid), D, E, P, U, derivatives thereof or salts thereof, tranexamic acid, derivatives thereof or salts thereof; Moisturizers such as amino acids, sugars, glycerin; anti-inflammatory agents such as glycyrrhizinic acid, derivatives thereof or salts thereof, glycyrrhetinic acid, allantin, tranexamic acid, derivatives thereof or salts thereof; cysteine, derivatives thereof or salts thereof, nicotine , Derivatives thereof or salts thereof. As the component to be absorbed transdermally, two or more kinds may be used in combination.

In the present invention, an oil-soluble substance is more preferable as the active ingredient contained in other external preparations for skin that promote transdermal absorption.
In the present invention, the term "oil-soluble" means, for example, water-soluble substances that maintain a uniform appearance when mixed with pure water at 1 atm and 20 ° C., and oil-soluble substances other than the water-soluble substances. be able to.

In the present invention, the molecular weight of the oil-soluble active ingredient contained in other external preparations for skin is, for example, preferably 200 to 1500, more preferably 300 to 1000.
In the present invention, the ratio of the inorganic value and the organic value of the oil-soluble active ingredient contained in other external preparations for skin (Inorganic Organic Balance: hereinafter referred to as IOB value) is generally influenced by the molecular structure. Although it cannot be said, for example, it is preferably 0.01 to 1.5, and more preferably 0.05 to 1.0.
The IOB value is also referred to as an I / O value, and is well known as a value representing the ratio of an inorganic value (Inorganic Value: IV) and an organic value (Organic Value: OV) obtained based on an organic conceptual diagram, and is oily. Indicates the degree of polarity of the base. The IOB value can be obtained by the following formula (I) according to, for example, "Collection of Raw Materials for Organic Conceptual Diagrams" Nippon Emulsion Co., Ltd.
IOB value = Inorganic value (IV) / Organic value (OV) (I)
In the present invention, the ClogP value (oil-water partition coefficient) of the oil-soluble active ingredient contained in other external preparations for skin is preferably, for example, 0.5 to 30.0, preferably 1.0 to 15.0. Is more preferable.
The ClogP value is a value obtained by calculation of the common logarithm logP of 1-octanol and the partition coefficient P to water. Known methods and software can be used for calculating the ClogP value, and can be obtained by, for example, chemexper.

In the present invention, specific examples of oil-soluble active ingredients contained in other external preparations for skin include glycyrrhetinic acid derivatives such as glycyrrhetinic acid and stearyl glycyrrhetinate; fat-soluble vitamins such as tocopherol, retinol, retinal and retinoic acid. Classes; fat-soluble vitamin derivatives such as DL-α-tocopherol acetate, tocopherol nicotinic acid ester, retinol palmitate, ascorbyl stearate, ascorbyl palmitate; carotenoids such as β-carotene; ubiquinones; thioctic acid and its derivatives; At least one selected from the group consisting of carotenoid derivatives; ceramides; sphingolipids; fat-soluble provitamins; fat-soluble provitamin derivatives can be mentioned.
In the present invention, DL-α-tocopherol acetate, stearyl glycyrrhetinate, and retinol palmitate are more preferable from the viewpoint of further enhancing the percutaneous absorption promoting property.

In the present invention, "transdermal absorption" means that the above-mentioned active ingredient is taken into a living body through the skin. Further, "transdermal absorbability" means the ease of uptake of the above-mentioned active ingredient when it is taken up by a living body through the skin.
In the present invention, "having the effect of promoting transdermal absorption" means the amount of the active ingredient contained in the other external preparation for skin absorbed by the skin when the other external preparation for skin is applied to the skin. It means that the amount (ratio) of the active ingredient absorbed into the skin can be increased with respect to (ratio).

By applying the introduction skin external preparation of the present invention to the skin before other skin external preparations, the transdermal absorbability of the active ingredient contained in the other skin external preparations is as shown in the following examples. Can be improved.
Therefore, the introduction skin external preparation of the present invention is used before the use of the other skin external preparation in order to promote the percutaneous absorption of the active ingredient contained in the other skin external preparation (skin pre-treatment). It can be suitably used as a treatment agent).
In particular, the introduction skin external preparation of the present invention shall be suitably used as an introduction skin external preparation (skin pretreatment agent) for promoting transdermal absorption of an oil-soluble active ingredient, as shown in the following examples. Can be done.
Further, by utilizing the percutaneous absorption promoting property of the external preparation for introduction of the present invention with respect to the active ingredient, for example, the amount of the active ingredient used in one dose in other external preparations for skin can be reduced. As a result, for example, by suppressing the content of an expensive active ingredient, the cost of other external preparations for skin can be reduced, or by suppressing the one-time use of other external preparations for skin, other external preparations for skin can be used. It is also possible to increase the number of times the agent is used.

The present invention will be described in more detail with reference to Examples below, but the scope of the present invention is not limited to these Examples.

(Test Example 1)
A cosmetic consisting of a high internal phase oil-in-water type (also referred to as HIPE-W / O) emulsified composition and an oil-in-water type (also referred to as O / W) emulsified composition having the formulations shown in Table 1 below. A cosmetic consisting of was prepared.
Specifically, the raw materials of the oil phase and the aqueous phase were weighed and dissolved by heating at 70 to 80 ° C. in the formulation shown in Table 1.
Then, in the HIPE-W / O type emulsified composition, the aqueous phase component is mixed while stirring the oil phase component with a disper mixer (TK Robomix manufactured by Primix Corporation, stirring blade φ40 mm, rotation speed 2,500 rpm). An emulsion was formed by gradually adding and then stirring and cooling to 35 ° C.
In the O / W type emulsified composition, an emulsion was formed by gradually adding the oil phase component while stirring the aqueous phase component with the same disper mixer as described above and then stirring and cooling.

The emulsified type of the prepared emulsified composition was determined by confirming the energization of the bulk using a tester (YX-361TR manufactured by Sanwa Electric Instrument Co., Ltd.). That is, when the tester terminal was brought into contact with the bulk and energization was confirmed, the emulsified type of the preparation was determined to be O / W type, and when energization was not confirmed, it was determined to be W / O type.

The active ingredient (DL-α-tocopherol acetate) shown in Table 2 below is further added to the cosmetic (O / W type cosmetic) composed of the O / W type emulsified composition having the formulation shown in Table 1, and the active ingredient is added. A cosmetic (O / W-VEK2 type cosmetic) composed of the contained O / W type (also referred to as O / W-VEK2) emulsified composition was formed.

In Table 1, as sucrose pentaerucate, Surf Hope SE COSME C2102 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used. As isononyl isononanoate, Saracos 99 manufactured by Nisshin Oillio Group Co., Ltd. was used. As pentaerythrityl tetraethylhexanoate, NS-408 manufactured by Nippon Fine Chemical Co., Ltd. was used. As the cholesteryl hydroxystearate, Saracos HS manufactured by Nisshin Oillio Group Co., Ltd. was used. As the dextrin palmitate, Leopard KL2 manufactured by Chiba Flour Milling Co., Ltd. was used. As the sucrose monostearate, Surf Hope SE COSME C1815 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used.

In Table 2, as DL-α-tocopherol acetate, RIKEN E acetate 960 manufactured by RIKEN Vitamin Co., Ltd. was used.
The physical characteristics of DL-α-tocopherol acetate used are as follows.
DL-α-tocopherol acetate: molecular weight (473), organic value (590), inorganic value (135), IOB value (inorganic value / organic value) (0.23), ClogP value (oil-water partition coefficient) (10.678)
Among the above physical property values, the molecular weight, the organic value, the inorganic value, and the IOB value were determined according to "Collection of Raw Materials for Organic Conceptual Diagrams" (Nippon Emulsion Co., Ltd.). The ClogP value was determined by chemexper.

The obtained cosmetics were subjected to a transdermal absorption test using a skin substitute membrane according to a conventional method. Specifically, the test conditions were as follows.
[Transdermal absorption test]
Franz type diffusion cell (manufactured by Permegia, receiver cell volume 8.0 cm ³ , permeation area 1.0 cm) in which water for skin permeability test (Strat-M (registered trademark) manufactured by Merck Group) is circulated at 32 ° C. ^It was set in ² ).
The inside of the receiver cell was filled with a PBS solution containing 5% bovine serum albumin (pH = 7.4).
10 μL of HIPE-W / O type cosmetics and O / W type cosmetics containing no active ingredient are applied to Strat-M in advance, dried at room temperature for 15 minutes, and then O / W-VEK2 type. 10 μL of cosmetic was applied to Strat-M and a transdermal absorption test was performed. In addition, a transdermal absorption test was also performed when 10 μL of O / W-VEK2 type cosmetic was applied to Strat-M without applying the cosmetic in advance. The transdermal absorbability of the active ingredient was evaluated 24 hours after the application of the O / W-VEK type 2 cosmetic. The amount of the active ingredient in Strat-M was measured as follows.
After completion of the transdermal absorption test, Strat-M was washed with PBS and the front and back surfaces were wiped with absorbent cotton. After performing this step three times, the active ingredient was extracted by infiltrating 1.0 mL of an 85% ethanol aqueous solution overnight.
Strat-M is centrifuged (CF-16RN manufactured by Koki Holdings Co., Ltd., 15,000 rpm, 10 minutes) and then quantitatively analyzed by UHPLC (Ultimate 3000 manufactured by Thermo Fisher Scientific Co., Ltd.). The amount of active ingredient in it was calculated.
The UHPLC conditions when the active ingredient was quantitatively analyzed using UHPLC are as shown in Table 3 below.

When O / W-VEK2 type cosmetics are applied after applying HIPE-W / O type cosmetics (denoted as HIPE-W / O + O / W-VEK2), after applying O / W type cosmetics, When O / W-VEK2 type cosmetics are applied (denoted as O / W + O / W-VEK2), and when O / W-VEK2 type cosmetics are applied without applying the cosmetics in advance (O / The amount of the active ingredient of the O / W-VEK2 type cosmetics absorbed into Strat-M in (denoted as W-VEK2) was measured. The result is shown in FIG.
As shown in FIG. 1, in the case of HIPE-W / O + O / W-VEK2, as compared with the case of O / W + O / W-VEK2, Strat-M of DL-α-tocopherol acetate (oil-soluble active ingredient) The amount absorbed into was significantly higher. The results shown in FIG. 1 were obtained as the amount of DL-α-tocopherol acetate per skin substitute membrane, and the average value and standard deviation thereof were shown. In addition, the risk factor P was obtained by the Tukey method, which is a statistical method, and those with P <0.001 are shown in FIG.

As shown in FIG. 1, the HIPE-W / O type cosmetic is transdermal with respect to DL-α-tocopherol acetate (oil-soluble active ingredient), which is an active ingredient in the O / W-VEK2 type cosmetic. It was confirmed that it shows an absorption promoting effect.
As shown in FIG. 1, O / W + O / W-VEK2, which did not show a transdermal absorption promoting effect on the active ingredient in O / W-VEK2 type cosmetics, and O / W-VEK2. In both cases, no significant difference was confirmed in the absorption amount of DL-α-tocopherol acetate. Therefore, the transdermal absorbability of the active ingredient was obtained by pre-applying the constituent ingredients contained in the O / W type cosmetics. Was confirmed not to be inhibited.
As described above, when the HIPE-W / O type cosmetic is applied in advance, when another cosmetic containing the active ingredient is applied after that, the active ingredient (particularly oil-soluble) contained in the other cosmetic is applied. It was confirmed that the HIPE-W / O type cosmetics can be effectively used as introduction cosmetics because the transdermal absorbability of the active ingredient) can be improved.

(Test Example 2)
An attempt was made to prepare a high internal phase W / O type emulsified composition in which the proportion of the dispersed phase composed of the aqueous phase was 90% by mass with the formulations shown in Table 4. Specifically, after weighing the raw materials of the oil phase and the aqueous phase, each of them is dissolved and mixed at 80 ° C., and the aqueous phase is added little by little to the oil phase at 80 ° C. It was dispersed at a stirring blade rotation speed of 600 rpm by a three-one motor BLh600, stirring blade φ40 mm), and then cooled to 35 ° C.
The obtained preparation was subjected to a swing rotor type centrifuge under room temperature conditions and centrifuged at 720 × g for 30 minutes to emulsify the preparation without separating it into an oil phase and an aqueous phase. The stability was evaluated by visually observing whether to keep it.
In addition, as the bulk hardness one day after preparation, a rheometer (CR-3000EX-S manufactured by Sun Scientific Co., Ltd.) was used to move a cylindrical probe with a diameter of 25 mm from the sample surface to the bottom surface of the filling container at an approach speed of 58 mm / min. The average stress (unit: g (gram)) at the time of entry was measured.

In Table 4, as sucrose pentaerucate, Surf Hope SE COSME C2102 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used. As the dextrin palmitate, Leopard KL2 manufactured by Chiba Flour Milling Co., Ltd. was used. As the sucrose palmitate, Surf Hope SE COSME C1616 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used.

[Stability evaluation criteria]
◯: Not separated into oil phase and aqueous phase after centrifugation.
Δ: Partially separated into an oil phase and an aqueous phase after centrifugation.
X: Completely separated into an oil phase and an aqueous phase after centrifugation.
As a result, it was clarified that when 0.05% by mass of dextrin palmitate, which is known as an oil gelling agent, was added to the whole preparation, a partially stable high internal phase W / O type emulsified composition was obtained. It was clarified that when dextrin palmitate was blended in an amount of 0.1% by mass or more in the whole preparation, a highly internal phase W / O type emulsified composition having a stable emulsified state could be obtained. In addition, the bulk hardness of the preparation increased with increasing the amount of dextrin palmitate, which is an oil gelling agent.

(Test Example 3)
An attempt was made to prepare a high internal phase W / O type emulsified composition in which the proportion of the dispersed phase composed of the aqueous phase was 90% by mass by the same preparation method as in Test Example 2 with the formulation shown in Table 5, and Test Example 2 In the same manner as in the above, it was tested whether or not a highly internal phase W / O type emulsified composition having a stable emulsified state could be obtained.

In Table 5, as sucrose pentaerucate, Surf Hope SE COSME C2102 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used. As glyceryl (behenic acid / icosanedioic acid), Nomcoat HK-G manufactured by Nisshin Oillio Group Co., Ltd. was used. As the sucrose palmitate, Surf Hope SE COSME C1616 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used.

[Stability evaluation criteria]
◯: Not separated into oil phase and aqueous phase after centrifugation.
Δ: Partially separated into an oil phase and an aqueous phase after centrifugation.
X: Completely separated into an oil phase and an aqueous phase after centrifugation.
As a result, when 0.05% by mass of glyceryl (behenic acid / icosane diic acid) known as an oil gelling agent is blended in the whole preparation, a partially stable high internal phase W / O type emulsified composition is obtained. When 0.1% by mass or more of glyceryl (behenic acid / icosane diic acid) is added to the whole preparation, a highly internal phase W / O type emulsified composition having a stable emulsified state can be obtained. Became clear. In addition, the bulk hardness of the preparation increased with increasing the amount of glyceryl (behenic acid / icosanedioic acid), which is an oil gelling agent.

(Test Example 4)
An attempt was made to prepare a high internal phase W / O type emulsified composition in which the proportion of the dispersed phase composed of the aqueous phase was 90% by mass by the same preparation method as in Test Example 2 with the formulation shown in Table 6, and Test Example 2 In the same manner as in No. 3 and 3, it was tested whether or not a highly internal phase W / O type emulsified composition having a stable emulsified state could be obtained.

In Table 6, as sucrose pentaerucate, Surf Hope SE COSME C2102 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used. As the dextrin myristate, Leopard MKL2 manufactured by Chiba Flour Milling Co., Ltd. was used. As the sucrose palmitate, Surf Hope SE COSME C1616 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used.

[Stability evaluation criteria]
◯: Not separated into oil phase and aqueous phase after centrifugation.
Δ: Partially separated into an oil phase and an aqueous phase after centrifugation.
X: Completely separated into an oil phase and an aqueous phase after centrifugation.
As a result, it was clarified that when 0.05% by mass of dextrin myristate, which is known as an oil gelling agent, was added to the whole preparation, a partially stable high internal phase W / O type emulsified composition was obtained. It has been clarified that when dextrin myristate, which is known as an oil gelling agent, is blended in an amount of 0.1% by mass or more in the whole preparation, a highly internal phase W / O type emulsified composition having a stable emulsified state can be obtained. .. In addition, the bulk hardness of the preparation increased with increasing the amount of dextrin myristate, which is an oil gelling agent.

(Test Example 5)
Cosmetics were prepared according to the formulations shown in Table 7. Specifically, after weighing the raw materials of the oil phase and the aqueous phase, each of them is dissolved and mixed at 80 ° C., and the aqueous phase is added little by little to the oil phase at 80 ° C. TK ROBOMICS manufactured by TK ROBOMICS, stirring blade φ35 mm), the stirring blade was dispersed at a rotation speed of 2500 rpm, and then cooled to 35 ° C.

In Table 7, as sucrose pentaerucate, Surf Hope SE COSME C2102 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used. As the dextrin palmitate, Leopard KL2 manufactured by Chiba Flour Milling Co., Ltd. was used. As the sucrose stearate, Surf Hope SE COSME C1815 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used.

As a result, the obtained cosmetic was a high internal phase W / O type emulsified composition in which the proportion of the dispersed phase composed of the aqueous phase was 75% by mass. In addition, the emulsified state was stable as a result of the stability evaluation by the centrifugation treatment described in Test Example 2.

(Test Example 6)
The active ingredient of DL-α-tocopherol acetate used in Test Example 1 was changed to the active ingredient of stearyl glycyrrhetinate, and the same experiment as in Test Example 1 was carried out.
A cosmetic consisting of a high internal phase oil-in-water type (also referred to as HIPE-W / O) emulsified composition and an oil-in-water type (also referred to as O / W) emulsified composition having the formulations shown in Table 8 below. A cosmetic consisting of was prepared.
Specifically, the raw materials of the oil phase and the aqueous phase were weighed and dissolved by heating at 70 to 80 ° C. according to the formulations shown in Table 8.
Then, in the HIPE-W / O type emulsified composition, the aqueous phase component is mixed while stirring the oil phase component with a disper mixer (TK Robomix manufactured by Primix Corporation, stirring blade φ40 mm, rotation speed 2,500 rpm). An emulsion was formed by gradually adding and then stirring and cooling to 35 ° C.
In the O / W type emulsified composition, an emulsion was formed by gradually adding the oil phase component while stirring the aqueous phase component with the same disper mixer as described above and then stirring and cooling.

The emulsified type of the prepared emulsified composition was determined by confirming the energization of the bulk using a tester (YX-361TR manufactured by Sanwa Electric Instrument Co., Ltd.). That is, when the tester terminal was brought into contact with the bulk and energization was confirmed, the emulsified type of the preparation was determined to be O / W type, and when energization was not confirmed, it was determined to be W / O type.

The active ingredient (stearyl glycyrrhetinate) shown in Table 9 below was further added to the cosmetic (O / W type cosmetic) composed of the O / W type emulsified composition shown in Table 8 to contain the active ingredient. A cosmetic (O / W-CO type cosmetic) composed of an O / W type (also referred to as O / W-CO) emulsified composition was formed.

In Table 8, as sucrose pentaerucate, Surf Hope SE COSME C2102 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used. As isononyl isononanoate, Saracos 99 manufactured by Nisshin Oillio Group Co., Ltd. was used. As pentaerythrityl tetraethylhexanoate, NS-408 manufactured by Nippon Fine Chemical Co., Ltd. was used. As the cholesteryl hydroxystearate, Saracos HS manufactured by Nisshin Oillio Group Co., Ltd. was used. As the dextrin palmitate, Leopard KL2 manufactured by Chiba Flour Milling Co., Ltd. was used. As the sucrose monostearate, Surf Hope SE COSME C1815 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used.

In Table 9, as stearyl glycyrrhetinate, Sea Augretinol manufactured by Maruzen Pharmaceuticals Co., Ltd. was used.

The obtained cosmetics were subjected to a transdermal absorption test using a skin substitute membrane according to a conventional method. Specifically, the test conditions were as follows.
[Transdermal absorption test]
Franz type diffusion cell (manufactured by Permegia, receiver cell volume 8.0 cm ³ , permeation area 1.0 cm) in which water for skin permeability test (Strat-M (registered trademark) manufactured by Merck Group) is circulated at 32 ° C. ^It was set in ² ).
The inside of the receiver cell was filled with a PBS solution containing 5% bovine serum albumin (pH = 7.4).
10 μL of HIPE-W / O type cosmetics and O / W type cosmetics containing no active ingredient are applied to Strat-M in advance, dried at room temperature for 15 minutes, and then O / W-CO type. 10 μL of cosmetic was applied to Strat-M and a transdermal absorption test was performed. In addition, a transdermal absorption test was also performed when 10 μL of O / W-CO type cosmetic was applied to Strat-M without applying the cosmetic in advance. The transdermal absorbability of the active ingredient was evaluated 90 minutes after the application of the O / W-CO type cosmetic. The amount of the active ingredient in Strat-M was measured as follows.
After completion of the transdermal absorption test, Strat-M was washed with PBS and the front and back surfaces were wiped with absorbent cotton. After performing this step three times, the active ingredient was extracted by infiltrating 1.0 mL of a 90% ethanol aqueous solution overnight.
Strat-M is centrifuged (CF-16RN manufactured by Koki Holdings Co., Ltd., 15,000 rpm, 10 minutes) and then quantitatively analyzed by UHPLC (Ultimate 3000 manufactured by Thermo Fisher Scientific Co., Ltd.). The amount of active ingredient in it was calculated.
The UHPLC conditions when the active ingredient was quantitatively analyzed using UHPLC are as shown in Table 10 below.

When O / W-CO type cosmetics are applied after applying HIPE-W / O type cosmetics (denoted as HIPE-W / O + O / W-CO), after applying O / W type cosmetics, When O / W-CO type cosmetics are applied (denoted as O / W + O / W-CO) and when O / W-CO type cosmetics are applied without applying the cosmetics in advance (O / The amount of the active ingredient of the O / W-CO type cosmetics absorbed into Strat-M in (denoted as W-CO) was measured. The result is shown in FIG.
As shown in FIG. 2, in the case of HIPE-W / O + O / W-CO, it is absorbed by Strat-M of stearyl glycyrrhetinate (oil-soluble active ingredient) as compared with the case of O / W + O / W-CO. The amount was significantly higher. The results shown in FIG. 2 were obtained as the amount of stearyl glycyrrhetinate per skin substitute membrane, and the average value and standard deviation were shown. In addition, the risk factor P was calculated by the Tukey method, which is a statistical method, and those with P <0.001 are shown in FIG.

As shown in FIG. 2, the HIPE-W / O type cosmetic has a transdermal absorption promoting effect on stearyl glycyrrhetinate (oil-soluble active ingredient), which is an active ingredient in the O / W-CO type cosmetic. It was confirmed that
As shown in FIG. 2, the case of O / W + O / W-CO which did not show the effect of promoting transdermal absorption with respect to the active ingredient in the O / W-CO type cosmetics and the case of O / W-CO. In both cases, no significant difference was confirmed in the absorption amount of stearyl glycyrrhetinate. Therefore, the transdermal absorbability of the active ingredient was inhibited by pre-applying the constituent ingredients contained in the O / W type cosmetics. It was confirmed that it was not.
As described above, when the HIPE-W / O type cosmetic is applied in advance, when another cosmetic containing the active ingredient is applied after that, the active ingredient (particularly oil-soluble) contained in the other cosmetic is applied. It was confirmed that the HIPE-W / O type cosmetics can be effectively used as introduction cosmetics because the transdermal absorbability of the active ingredient) can be improved.

(Test Example 7)
The active ingredient of DL-α-tocopherol acetate used in Test Example 1 was changed to the active ingredient of retinol palmitate, and the same experiment as in Test Example 1 was carried out.
A cosmetic consisting of a high internal phase oil-in-water type (also referred to as HIPE-W / O) emulsified composition and an oil-in-water type (also referred to as O / W) emulsified composition having the formulations shown in Table 11 below. A cosmetic consisting of was prepared.
Specifically, the raw materials of the oil phase and the aqueous phase were weighed and dissolved by heating at 70 to 80 ° C. in the formulation shown in Table 11.
Then, in the HIPE-W / O type emulsified composition, the aqueous phase component is mixed while stirring the oil phase component with a disper mixer (TK Robomix manufactured by Primix Corporation, stirring blade φ40 mm, rotation speed 2,500 rpm). An emulsion was formed by gradually adding and then stirring and cooling to 35 ° C.
In the O / W type emulsified composition, an emulsion was formed by gradually adding the oil phase component while stirring the aqueous phase component with the same disper mixer as described above and then stirring and cooling.

The emulsified type of the prepared emulsified composition was determined by confirming the energization of the bulk using a tester (YX-361TR manufactured by Sanwa Electric Instrument Co., Ltd.). That is, when the tester terminal was brought into contact with the bulk and energization was confirmed, the emulsified type of the preparation was determined to be O / W type, and when energization was not confirmed, it was determined to be W / O type.

The active ingredient (retinyl palmitate) shown in Table 12 below was further added to the cosmetic (O / W type cosmetic) composed of the O / W type emulsified composition having the formulation shown in Table 11, and the active ingredient was contained. A cosmetic (O / W-VA type cosmetic) composed of an O / W type (also referred to as O / W-VA) emulsified composition was formed.

In Table 11, as sucrose pentaerucate, Surf Hope SE COSME C2102 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used. As isononyl isononanoate, Saracos 99 manufactured by Nisshin Oillio Group Co., Ltd. was used. As pentaerythrityl tetraethylhexanoate, NS-408 manufactured by Nippon Fine Chemical Co., Ltd. was used. As the cholesteryl hydroxystearate, Saracos HS manufactured by Nisshin Oillio Group Co., Ltd. was used. As the dextrin palmitate, Leopard KL2 manufactured by Chiba Flour Milling Co., Ltd. was used. As the sucrose monostearate, Surf Hope SE COSME C1815 manufactured by Mitsubishi Chemical Foods Co., Ltd. was used.

In Table 12, as the retinol palmitate, RIKEN A palmitate 1000 manufactured by RIKEN Vitamin Co., Ltd. was used.

The obtained cosmetics were subjected to a transdermal absorption test using a skin substitute membrane according to a conventional method. Specifically, the test conditions were as follows.
[Transdermal absorption test]
Franz type diffusion cell (manufactured by Permegia, receiver cell volume 8.0 cm ³ , permeation area 1.0 cm) in which water for skin permeability test (Strat-M (registered trademark) manufactured by Merck Group) is circulated at 32 ° C. ^It was set in ² ).
The inside of the receiver cell was filled with a PBS solution containing 5% bovine serum albumin (pH = 7.4).
10 μL of HIPE-W / O type cosmetics and O / W type cosmetics containing no active ingredient are applied to Strat-M in advance, dried at room temperature for 15 minutes, and then O / W-VA type. 10 μL of cosmetic was applied to Strat-M and a transdermal absorption test was performed. In addition, a transdermal absorption test was also performed when 10 μL of O / W-VA type cosmetic was applied to Strat-M without applying the cosmetic in advance. The transdermal absorbability of the active ingredient was evaluated 90 minutes after the application of the O / W-VA type cosmetic. The amount of the active ingredient in Strat-M was measured as follows.
After completion of the transdermal absorption test, Strat-M was washed with PBS and the front and back surfaces were wiped with absorbent cotton. After performing this step three times, the active ingredient was extracted by infiltrating 1.0 mL of a 90% ethanol aqueous solution overnight.
Strat-M is centrifuged (CF-16RN manufactured by Koki Holdings Co., Ltd., 15,000 rpm, 10 minutes) and then quantitatively analyzed by UHPLC (Ultimate 3000 manufactured by Thermo Fisher Scientific Co., Ltd.). The amount of active ingredient in it was calculated.
The UHPLC conditions when the active ingredient was quantitatively analyzed using UHPLC are as shown in Table 13 below.

When O / W-VA type cosmetics are applied after applying HIPE-W / O type cosmetics (denoted as HIPE-W / O + O / W-VA), after applying O / W type cosmetics, When O / W-VA type cosmetics are applied (denoted as O / W + O / W-VA) and when O / W-VA type cosmetics are applied without applying the cosmetics in advance (O / The amount of the active ingredient of the O / W-VA type cosmetics absorbed into Strat-M in (denoted as W-VA) was measured. The result is shown in FIG.
As shown in FIG. 3, in the case of HIPE-W / O + O / W-VA, it is absorbed by Strat-M of retinol palmitate (oil-soluble active ingredient) as compared with the case of O / W + O / W-VA. The amount was significantly higher. The results shown in FIG. 3 were obtained as the amount of retinol palmitate per skin substitute membrane, and the average value and standard deviation were shown. In addition, the risk factor P was obtained by the Tukey method, which is a statistical method, and those with P <0.001 are shown in FIG.

As shown in FIG. 3, the HIPE-W / O type cosmetic has a transdermal absorption promoting effect on retinol palmitate (oil-soluble active ingredient), which is an active ingredient in the O / W-VA type cosmetic. It was confirmed that
As shown in FIG. 3, O / W + O / W-VA did not show a transdermal absorption promoting effect on the active ingredient in O / W-VA type cosmetics, and O / W-VA. In both cases, no significant difference was confirmed in the absorption amount of retinol palmitate. Therefore, the transdermal absorbability of the active ingredient was inhibited by pre-applying the constituent ingredients contained in the O / W type cosmetics. It was confirmed that it was not.
As described above, when the HIPE-W / O type cosmetic is applied in advance, when another cosmetic containing the active ingredient is applied after that, the active ingredient (particularly oil-soluble) contained in the other cosmetic is applied. It was confirmed that the HIPE-W / O type cosmetics can be effectively used as introduction cosmetics because the transdermal absorbability of the active ingredient) can be improved.

As shown in each of the above examples, according to the present invention, a high internal phase W / O type emulsified composition having a refreshing feeling of use and a high moisturizing effect, which can further satisfy the stable maintenance of the emulsified state. It was possible to provide an external preparation for skin containing an internal phase W / O type emulsified composition.
Further, according to the present invention, a highly internal phase W / O type emulsified composition capable of promoting percutaneous absorption with respect to an active ingredient contained in other external preparations for skin, particularly an oil-soluble active ingredient, can be obtained. It was possible to provide an external preparation for skin contained. As a result, the external preparation for skin containing the high internal phase W / O type emulsifying composition of the present invention is an external preparation for other skin in order to improve the transdermal absorbability of the active ingredient contained in the other external preparation for skin. Can be effectively used as an introduction skin external preparation to be applied to the skin before use.

Claims (10)

An introduction skin external preparation containing an oil gelling agent and a high internal phase W / O type emulsifying composition in which the proportion of the aqueous phase is 70% by mass or more.
An introduction skin external preparation, which is applied to the skin before use of the other skin external preparation in order to promote transdermal absorption of the active ingredient contained in the other skin external preparation. The skin external preparation for introduction according to claim 1, wherein the oil gelling agent contains at least one selected from the group consisting of dextrin fatty acid ester and glycerin fatty acid ester. The introduction according to claim 1 or 2, wherein the oil gelling agent comprises at least one selected from the group consisting of dextrin palmitate, dextrin myristate, glyceryl behenate, and glyceryl (behenic acid / eicosandioic acid). External preparation for skin. The introduction skin external preparation according to any one of claims 1 to 3, wherein the active ingredient is an oil-soluble active ingredient. The oil-soluble active ingredients are glycyrrhetinic acid derivatives, fat-soluble vitamins, fat-soluble vitamin derivatives, carotenoids, ubiquinones, thioctic acids and their derivatives, carnitine derivatives, ceramides, sphingolipids, fat-soluble provitamins, and fats. The introduction skin external preparation according to any one of claims 1 to 4, which comprises at least one selected from the group consisting of soluble provitamin derivatives. An introduction skin external preparation containing an oil gelling agent and a high internal phase W / O type emulsifying composition in which the proportion of the aqueous phase is 70% by mass or more.
A method for using an introduction skin external preparation, which comprises applying the active ingredient to the skin before use of the other skin external preparation in order to promote transdermal absorption of the active ingredient contained in the other skin external preparation. The method for using an external preparation for introduction according to claim 6, wherein the oil gelling agent contains at least one selected from the group consisting of a dextrin fatty acid ester and a glycerin fatty acid ester. The introduction according to claim 6 or 7, wherein the oil gelling agent comprises at least one selected from the group consisting of dextrin palmitate, dextrin myristate, glyceryl behenate, and glyceryl (behenic acid / eicosanidiate). How to use external preparations for skin. The method for using an external preparation for skin for introduction according to any one of claims 6 to 8, wherein the active ingredient is an oil-soluble active ingredient. The oil-soluble active ingredients are glycyrrhetinic acid derivatives, fat-soluble vitamins, fat-soluble vitamin derivatives, carotenoids, ubiquinones, thioctic acids and their derivatives, carnitine derivatives, ceramides, sphingolipids, fat-soluble provitamins, and fats. The method for using an external preparation for introduction according to any one of claims 6 to 9, which comprises at least one selected from the group consisting of soluble provitamin derivatives.

Images