JP2008239493A - External preparation for skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an external preparation for the skin, preventing dryness of the skin and reducing various kinds of irritation to the skin by combining a keratinocyte differentiation promoter and a barrier function regulator. <P>SOLUTION: The external preparation for the skin contains one or more kinds of keratinocyte differentiation promoters selected from sea weeds of Codium fragile, Laminaria japonica, Undaria pinnatifida, Gloiopeltis forcata, Enteromorpha prolifera and extract of Ceramium kondoi, and one or more kinds of barrier function regulators selected from linseed oil, perilla oil, kiwi seed oil and Perilla frutescens oil to prevent the dryness of the skin, and to reduce the various kinds of the irritation to the skin. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

The present invention relates to an external preparation for skin suitable for sensitive skin, and in particular, by combining a keratinocyte differentiation promoting agent and a barrier function adjusting agent, skin dryness is suppressed, and inflammation such as skin irritation and itching is reduced. It is related with the skin external preparation which can suppress various irritation | stimulation with respect to skin.

In recent years, an increasing number of people complain of modulation of skin due to stress, environmental pollution, and the like. In such people, the barrier function of the skin has become abnormal, so it is easy to feel allergens such as chemical substances, mites, dust, etc., and ultraviolet rays, etc. Or in pathological cases, it leads to diseases such as atopic dermatitis and contact dermatitis. Such a skin condition is generally defined as sensitive skin. Until now, various approaches have been made to improve sensitive skin. For example, in order to reduce irritation to the skin, use a topical skin preparation that does not contain substances that can irritate the skin, such as preservatives and alcohol, or use a topical skin preparation that contains many moisturizing ingredients. Or, external preparations for skin containing various anti-inflammatory agents have been used.
JP 10-182332 A JP 2000-212203 A

However, these external preparations for skin do not have sufficient effects on symptoms such as itching, rough skin, and inflammation that occur in sensitive skin, and improvements have been desired.

Since people with sensitive skin can easily feel even with a slight stimulus due to abnormalities in the barrier function of the skin, the present inventors have conducted intensive studies to solve such problems, and as a result, The present inventors have found that various symptoms of sensitive skin can be remarkably improved by combining a barrier function regulator, and the present invention has been completed.

That is, this invention provides the skin external preparation characterized by containing a keratinocyte differentiation promoter and a barrier function regulator.

Seaweed mill (Codium fragile (Suringar) Hariot), Macombu (Laminaria japonica Areschoug), Seaweed (Undaria pinnatifida), Fukuronori (Gloiopeltis furcata Postels et Ruprecht), Suooriori (Enteromorpha prolifera (Muller) J. Agardhera Yendo emend. Nakamura) combined with one or more keratinocyte differentiation promoters and one or more barrier function regulators selected from linseed oil, perilla oil, kiwi seed oil, and sesame oil This suppresses various irritation to the skin, protects the skin from inflammation, and is excellent in restoring normal skin function.

The skin barrier function is a function that regulates the moisture permeability of the skin, and the keratin intercellular lipid plays an important role. Ceramide, fatty acid, cholesterol, phospholipid and the like are listed as main constituents of keratin intercellular lipid, and ceramide plays a particularly important role among them. In patients with atopic dermatitis and dry skin, the skin barrier function is lowered due to a significant decrease in the amount of ceramide, and therefore, it is easy to receive external stimuli and skin problems such as inflammation are likely to occur.

In skin with an abnormal barrier function, there are many undifferentiated keratinocytes, and normal stratum corneum is not formed. For this reason, skin inflammation tends to occur, and this inflammation causes a vicious cycle in which the barrier function becomes abnormal. We have found that an abnormal skin barrier function can be recovered by applying a keratinocyte differentiation regulator to such skin with a reduced barrier function.
Further, the present inventors have found that the abnormal skin barrier function is dramatically improved by simultaneously using the keratinocyte differentiation promoting agent and the barrier function adjusting agent, thereby completing the present invention.

The keratinocyte differentiation regulator used in the present invention has the action of acting on epidermal cells to promote cell differentiation and causing normal keratinization. Specifically, seaweed mill (Codium fragile (Suringar) Hariot), Macombu (Laminaria japonica Areschoug), seaweed (Undaria pinnatifida), Fukuronori (Gloiopeltis furcata Postels et Ruprecht), Sugioonori (Enteromorpha prolifera (Muller) J. Agardh , Extract obtained from Igis (Ceramium kondoi Yendo emend. Nakamura).

The mill (Codium fragile (Suringar) Hariot) used in the present invention is a seaweed belonging to the genus Myrraceae of the green algal plant and inhabits almost all areas of Japan.

Macombu (Laminaria japonica Areschoug) used in the present invention is a seaweed belonging to the genus Kombu family of the brown alga plant, and is distributed mainly in Hokkaido and reaches a length of 2-6 m.

The wakame (Undaria pinnatifida) used in the present invention is a seaweed belonging to the genus Wakame of the brown alga plant, and has inhabited almost all areas of Japan and has been used for food since ancient times.

Fukuronori (Gloiopeltis furcata Postels et Ruprecht) used in the present invention is a seaweed belonging to the genus Fukuronori of the brown alga plant and grows on rocks and seaweeds.

Sugioona (Enteromorpha prolifera (Muller) J. Agardh) used in the present invention is a seaweed belonging to the genus Aonori of the green alga plant, and grows in estuaries and the like of inner bays throughout Japan and is used for food.

The cypress (Ceramium kondoi Yendo emend. Nakamura) used in the present invention is a seaweed belonging to the genus Igisaceae, a red algae plant, and grows on rocks and seaweeds in Honshu, Hokkaido.

Examples of the barrier function regulator used in the present invention include linseed oil, perilla oil, kiwi seed oil, and sesame oil, but the synthesis method, extraction method, and purification method are not particularly limited.

Linseed oil used in the present invention is also called linseed oil, and is a dry oil obtained from the seeds of the genus flaxaceae (Linum usitatissimus), which is rich in α-linolenic acid and its triglycerides, Used for edible and paint binders.

The perilla oil used in the present invention is an oil obtained from the seeds of Prilla frutescens, and is rich in α-linolenic acid and its triglycerides.

The kiwi seed oil used in the present invention is an oil obtained from the seeds of the deciduous vine plant of the genus Matatabidae (Actinidia deliciosa or Actinidia chinensis), rich in α-linolenic acid and its triglycerides. contains.

The sesame used in the present invention is a dry oil obtained from the seeds of Prilla frutescens var. Frutescens, and is rich in α-linolenic acid and its triglycerides.

As the various parts of each seaweed used in the present invention, one or more selected from stems, leaves, branches, branches and leaves, trunks, bark, rhizomes, root barks, roots, whole grasses and the like can be used. The extract may be obtained by extracting directly from these various extraction sites using a solvent, or may be extracted by adding a solvent to the squeezed solution and / or residue obtained after the squeezing treatment.

The linseed oil, perilla oil, kiwi seed oil, and sesame oil used in the present invention are not particularly limited as long as they are oils obtained from the respective seeds. Obtained by extraction.

The extraction solvent for obtaining the seaweed extract and plant seed oil used in the present invention may be selected in consideration of the intended purpose and type of the product to be provided, or the processing performed later. For example, water; Lower monohydric alcohols such as methyl alcohol and ethyl alcohol; Liquid polyhydric alcohols such as glycerin, propylene glycol and 1,3-butylene glycol; Ketones such as acetone and methyl ethyl ketone; Alkyl esters such as ethyl acetate; Carbonization such as benzene and hexane Extraction is performed using one or more of hydrogen; ethers such as diethyl ether; halogenated alkanes such as dichloromethane and chloroform;

The seaweed and plant seeds to be extracted are collected at the site of use, dried and pulverized, using a solvent having a weight ratio of 1 to 1000 times, particularly 10 to 100 times, and 0 ° C. in the case of room temperature extraction. As described above, it is particularly preferable to carry out at 20 ° C. to 40 ° C. for 1 hour or longer, particularly 3 to 7 days. Moreover, you may heat-extract at 60-100 degreeC for 1 hour.

Each of the above-mentioned extracts obtained under the above conditions may be used as an extracted solution. However, if necessary, use a product that has been refined, filtered, concentrated, and powdered as necessary. I can do it.

The form of the seaweed and plant seed extract used in the present invention may be any form such as liquid, solid, powder, paste, gel, etc., and any shape that is optimal for configuring the final product is arbitrary. Can be selected.

The dosage form of the external preparation for skin of the present invention is arbitrary, and is capsule, powder, granule, pill, tablet, solid, liquid, gel, foam, emulsion, cream, ointment, sheet The shape can be in the form of an aerosol or aerosol. Furthermore, it can mix | blend and use for pharmaceuticals, quasi-drugs, cosmetics, or food-drinks. In particular, it is applied to external preparation compositions such as pharmaceuticals, quasi-drugs, and cosmetic compositions applied to the outer skin.

Specific use forms of the present invention include aqueous components, oily components, plant extracts, animal extracts, powders, excipients, surfactants, oils, alcohols, pH adjusters, preservatives, antioxidants, A lotion, a milky lotion, a cream, a pack, a powder, a spray, an ointment, a dispersion, and a liquid form of the composition for external use by mixing thickeners, sweeteners, pigments, fragrances, and the like as necessary. It can be made into various dosage forms such as paste and powder.

The blending amount of the keratinocyte differentiation promoter in the skin external preparation of the present invention is slightly different depending on the expected degree of action and is not particularly limited, but is usually 0.0001% by mass or more in terms of solid content in the total amount of the preparation, It is effective to set the concentration range to 0.01 to 10.0% by mass.

Further, the blending amount of the barrier function regulator in the external preparation for skin of the present invention is slightly different depending on the degree of expected action and is not particularly limited, but is usually 0.0001% by mass in terms of solid content in the total amount of the preparation. As mentioned above, it is effective to set it as the concentration range of 0.01-10.0 mass% preferably.

Hereinafter, test examples relating to the keratinocyte differentiation promoting effect and barrier function adjusting effect according to the present invention will be shown and application formulation examples to external preparations using the materials will be described, but the invention is not limited to the examples described herein. Needless to say.

Examples of the present invention will be described in detail below, but the present invention is not limited thereto.

[Example 1]
(1) Preparation of seaweed extract 50 ml of purified water was added to 1 g of pulverized mill, macomb, wakame, fukuronori, sujionori, igis and dried at 80 ° C. for 1 hour. The extract was filtered and the residue dried under reduced pressure at 40 ° C. was dried. The dried product was prepared to be a 1% aqueous solution and used as a sample solution.
(2) Preparation of Barrier Function Adjusted Products Linseed oil, perilla oil, and kiwi seed oil used commercially available products (Alfresa Pharma Co., Ltd.) obtained by refining oils obtained by pressing each seed.

[Example 2]
(Cell culture)
Cell: NHEK-Neo-Epidermal Kera (CAMBREX)
Medium: Epilife KG2 (Ca concentration: 0.06 mM)
D-MEM (Ca concentration: 1.8 mM)
Fixing solution: Mildform 10NM (Wako Pure Chemical Industries)
Staining: 0.05% naphthol blue black solution (9% acetic acid, 0.1M Na acetate)
NHEK-Neo-Epidermal Kera (CAMBREX), a normal human epidermal cell, was cultured in Epilife KG2 (Kurabo) medium.
Cells were planted and cultured in a 12 well plate at about 50% confluence. The next day, each plant extract was added. 24 hours after the addition, the cells were fixed, stained with a naphthol blue black solution, the morphology of the cells was observed, and the degree of differentiation was determined.

When keratinocytes differentiate, cells adhere to each other and take an amorphous form. On the other hand, undifferentiated cells do not adhere to each other independently. Differentiation of keratinocytes is promoted by the Ca concentration in the medium. As shown in the photograph in FIG. 1, almost completely differentiated at a Ca concentration of 0.5 mM, and below that, partially undifferentiated cells were observed.

Photo 2 of FIG. 2 shows the differentiated state of the cells when the mill extract was added to the medium at 200 ppm, and the macombu, wakame, fukuronori, sugioonori, and igisu extract were added to the medium at 400 ppm. The Ca concentration in each sample was measured. The Ca concentration in seaweed was 0.27 mM at 200 ppm of the mill extract, and other seaweed extracts were 0.22 mM to 0.26 mM at 400 ppm. From the photograph shown in FIG. 2, even when compared to the differentiation state of the cell having a Ca concentration of 0.23 mM in the photograph 1 shown in FIG. 1, the addition of the mill, macombu, wakame, fukuronori, sujionori and igisu extract extracts I knew it was going.

Example 3
In the skin irritation test, the emulsion composition shown in Paragraph 0040 (the blending amount was% by weight) was applied to a sensitive skin paneler, and a panelist that felt irritation was selected. Then, the additive of the composition shown in Table 1 was added to the prescription except the preservative / antioxidant, and emulsions of Examples 1 to 12 and Comparative Examples 1 to 16 were prepared. After the selected sensitive skin panelists applied each test product for 1 week, the emulsion composition shown in paragraph 0040 was applied, and the skin irritation was evaluated according to the criteria shown in Table 1. The results are shown in Table 2. From Table 2, it became clear that the skin irritation was significantly improved by applying the additive according to the present invention.

[Emulsion composition]
(Ingredient name)
a) Beeswax: 0.5
b) Petrolatum: 2.0
c) Squalane: 8.0
d) Sorbitan sesquioleate: 0.8
e) Polyoxyethylene oleyl ether (20E.O.): 1.2
f) 1,3-Butylene glycol: 7.0
g) Carboxyvinyl polymer: 0.2
h) Potassium hydroxide: 0.1
i) Purified water: balance
j) Preservatives and antioxidants: appropriate amount
k) Ethanol: 7.0

Example 4
(Manufacture of various compositions)
Various compositions according to the present invention were prepared. Although the formulation example is shown below, this invention is not necessarily limited to these. In addition, a compounding quantity is shown by weight%.

(1) Cream composition
a) Beeswax: 2.0
b) Stearyl alcohol: 5.0
c) Stearic acid: 8.0
d) Squalane: 7.0
e) Self-emulsifying glyceryl monostearate: 3.0
f) Polyoxyethylene cetyl ether (20E.O.): 1.0
g) Linseed oil 1.0
h) Mill extract: 2.0
i) 1,3-butylene glycol: 5.0
j) Potassium hydroxide: 0.3
k) Preservatives and antioxidants: appropriate amount
l) Purified water: Remainder manufacturing method: Heat up to a) to g) and keep at 80 ° C. h) to l) are heated and dissolved,
Maintain at 80 ° C., emulsify in addition to a) to g), cool to 40 ° C. with stirring.

(2) Cream composition
a) Beeswax: 3.0
b) Stearyl alcohol: 5.0
c) Stearic acid: 8.0
d) Squalane: 1.0
e) Self-emulsifying glyceryl monostearate: 4.0
f) Polyoxyethylene cetyl ether (20E.O.): 2.0
g) Kiwi seed oil: 10.0
h) Macombe extract: 10.0
i) 1,3-butylene glycol: 5.0
j) Potassium hydroxide: 0.3
k) Preservatives and antioxidants: appropriate amount
l) Purified water: Remainder manufacturing method: Heat up to a) to g) and keep at 80 ° C. h) to l) are heated and dissolved,
Maintain at 80 ° C., emulsify in addition to a) to g), cool to 40 ° C. with stirring.

(3) Emulsion composition
a) Beeswax: 0.5
b) Petrolatum: 2.0
c) Squalane: 8.0
d) Sorbitan sesquioleate: 0.8
e) Polyoxyethylene oleyl ether (20E.O.): 1.2
f) Mill extract: 0.0001
g) Perilla oil: 0.0001
h) 1,3-butylene glycol: 7.0
i) Carboxyvinyl polymer: 0.2
j) Potassium hydroxide: 0.1
k) Purified water: balance
l) Preservatives and antioxidants: appropriate amount
m) Ethanol: 7.0
Process: Heat up to a) to e) and keep at 80 ° C. f) to l) are heated and dissolved,
Maintain at 80 ° C., emulsify in addition to a) to e), and cool to 50 ° C. with stirring.
Add m) at 50 ° C and cool to 40 ° C.

(4) Emulsion composition
a) Beeswax: 0.5
b) Petrolatum: 2.0
c) Squalane: 8.0
d) Sorbitan sesquioleate: 0.8
e) Polyoxyethylene oleyl ether (20E.O.): 1.2
f) Igis extract: 0.001
g) Sesame oil: 0.001
h) 1,3-butylene glycol: 7.0
i) Carboxyvinyl polymer: 0.2
j) Potassium hydroxide: 0.1
k) Purified water: balance
l) Preservatives and antioxidants: appropriate amount
m) Ethanol: 7.0
Manufacturing method
Heat up to a) to e) and keep at 80 ° C. f) to l) are heated and dissolved,
Maintain at 80 ° C., emulsify in addition to a) to e), and cool to 50 ° C. with stirring.
Add m) at 50 ° C and cool to 40 ° C.

(5) Lotion-like composition
a) Igis extract: 0.01
b) Sesame: 0.01
c) Glycerin: 5.0
d) Polyoxyethylene sorbitan monolaurate (20E.O.): 1.0
e) Ethanol: 6.0
f) Fragrance: appropriate amount
g) Preservatives and antioxidants: appropriate amount
h) Purified water: The remaining preparation method: a) to h) are mixed and dissolved uniformly.

(6) Lotion-like composition
a) Macombe extract: 0.1
b) Glycerin: 5.0
c) Polyoxyethylene sorbitan monolaurate (20E.O.): 1.0
d) Linseed oil: 0.1
e) Ethanol: 6.0
f) Fragrance: appropriate amount
g) Preservatives and antioxidants: appropriate amount
h) Purified water: The remaining preparation method: a) to h) are mixed and dissolved uniformly.

(7) Packing agent
a) Mill extract: 1.0
b) Igis extract: 1.0
c) Vinyl acetate resin emulsion: 15.0
d) Polyvinyl alcohol: 10.0
e) Kiwi seed oil: 0.5
f) Glycerin: 5.0
g) Titanium oxide: 8.0
h) Kaolin: 7.0
i) Ethanol: 8.0
j) Fragrance: appropriate amount
k) Preservatives and antioxidants: appropriate amount
l) Purified water: Mix the remaining manufacturing method: a) to l), stir well and disperse uniformly.

Since this invention has the effect which suppresses drying of skin and suppresses various irritation | stimulation with respect to skin, it can anticipate application to a skin external preparation widely.

The cell photograph which image | photographed the grade of the differentiation of the keratinocyte by Ca concentration.

The cell photograph which image | photographed the grade of the differentiation of the keratinocyte at the time of adding Ca and an active ingredient.

Claims (3)

An external preparation for skin, comprising a keratinocyte differentiation promoter and a barrier function regulator. Keratinocyte differentiation regulators include seaweed mills (Codium fragile (Suringar) Hariot), macaques (Laminaria japonica Areschoug), wakame (Undaria pinnatifida), Fukuronori (Gloiopeltis furcata Postels et Ruprecht), Suoaoori (Enteromorpha prolifera. Agarer) ), Or one or more extracts selected from Igis (Ceramium kondoi Yendo emend. Nakamura). The skin external preparation according to claim 1, wherein the barrier function adjusting agent is one or more selected from linseed oil, perilla oil, kiwi seed oil and sesame oil.