JP2003055218A - Skin care composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin care composition having the effect of improving skin barrier function. SOLUTION: This skin care composition contains sodium cromoglycate as the skin barrier function-improving ingredient.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an external composition for skin intended to improve the skin barrier function.

[0002]

2. Description of the Related Art Originally, human skin has a barrier function, that is, a role of preventing foreign substances from entering from the outside. In recent years, in refractory skin diseases such as atopic dermatitis, it has been clarified that the barrier function of the skin is remarkably reduced, and that the easy entry of irritants from the outside is a major cause of the deterioration of the disease state. It's coming. From this, it has been considered that substances that improve the skin barrier function play a major role in the treatment of these diseases.

On the other hand, sodium cromoglycate (1,3
-Bis (2-carboxychromone-5-yloxy)-
2-hydroxypropane sodium salt) is known as a substance that suppresses the release of chemical mediators from mast cells during type I allergic reaction. It is used to treat allergic diseases such as asthma. Further, JP-A-52-44242 discloses that sodium cromoglycate is locally administered to the skin or the tissues of the eye and used for the treatment of chronic skin diseases and eye diseases involving allergic or immune reactions. There is.

However, to date, few substances have been known to improve the barrier function of the skin.
Further, it is not known at all that the above-mentioned sodium cromoglycate has such an action.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a skin external composition having a skin barrier function improving effect.

[0006]

Means for Solving the Problems As a result of intensive studies on the pharmacological action of sodium cromoglycate, the present inventors have found that sodium cromoglycate has a new pharmacological action of improving skin barrier function, and completed the present invention. Came to do.

That is, the external composition for skin of the present invention is characterized by containing sodium cromoglycate as a skin barrier function improving component. Further, it is characterized in that it contains 0.1 to 50% by weight of sodium cromoglycate and is used for improving the skin barrier function.

The present invention will be described in detail below.

The external composition for skin of the present invention contains sodium cromoglycate as a skin barrier function improving component.

When the content of sodium cromoglycate in the above external composition for skin is small, the effect of improving the skin barrier function becomes insufficient, and when it is too large, the effect does not remarkably increase according to the content, and 0.1-50% by weight is preferable, because it causes problems in dosage form, and 0.3-3
0% by weight is more preferable, and 0.5 to 10% by weight is particularly preferable.

The external composition for skin of the present invention may further contain a percutaneous absorption enhancer.

Examples of the above-mentioned percutaneous absorption enhancer include N-acyl sarcosine or its salt, higher fatty acid ester, dicarboxylic acid or its salt, hydroxycarboxylic acid ester, fatty acid ethanolamide, keratin softener, moisturizing agent and the like.

Examples of the N-acyl sarcosine include N-lauroyl sarcosine, N-oleoyl sarcosine, N-palmitoyl sarcosine, and coconut oil fatty acid sarcosine.
-Acylsarcosine sodium salts, potassium salts, magnesium salts, calcium salts, aluminum salts and the like.

Examples of the higher fatty acid ester include isopropyl myristate, isopropyl palmitate, isopropyl laurate, isopropyl stearate and the like.

Examples of the dicarboxylic acid include oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid,
Saturated aliphatic dicarboxylic acids such as pimelic acid and suberic acid; unsaturated aliphatic dicarboxylic acids such as fumaric acid and maleic acid; aromatic dicarboxylic acids such as phthalic acid, isophthalic acid and terephthalic acid, and the like. , For example, sodium salt, potassium salt of the above dicarboxylic acid,
Examples thereof include magnesium salt, calcium salt, aluminum salt and the like.

Examples of the hydroxycarboxylic acid ester include myristyl lactate and cetyl lactate.

Examples of the fatty acid ethanolamide include fatty acid monoethanolamide, fatty acid diethanolamide, and alkylene oxide adducts thereof. Examples of the fatty acid ethanolamide include lauric acid monoethanolamide, lauric acid diethanolamide, lauroyl monoethanolamide, palmitic acid monoethanolamide, palmitic acid diethanolamide, myristic acid monoethanolamide, myristic acid diethanolamide, and lauric acid.
Myristic acid monoethanolamide, coconut oil fatty acid monoethanolamide, coconut oil fatty acid diethanolamide,
Examples thereof include polyoxyethylene-added lauroyl monoethanolamide and polyoxyethylene-added coconut oil fatty acid monoethanolamide.

Examples of the keratin softener include salicylic acid and urea.

Examples of the moisturizer include glycerin, propylene glycol, polyethylene glycol,
Examples thereof include urea and glycyrrhizinic acid.

Among the above, N-lauroylsarcosine, isopropyl myristate, diethanolamide laurate, salicylic acid, glycerin, polyethylene glycol and urea are particularly preferable as the transdermal absorption enhancer.
The above-mentioned percutaneous absorption enhancers are preferable, but not limited to these, and conventionally known ones can be used.

When the above-mentioned percutaneous absorption enhancer is used, the content of the percutaneous absorption enhancer in the external composition for skin is 100 total of sodium cromoglycate and the below-mentioned base.
0.1 to 50 parts by weight is preferable, and 5 to 5 parts by weight.
40 parts by weight is more preferred.

In the external composition for skin of the present invention, if necessary, inorganic fillers such as kaolin, bentonite, zinc oxide and titanium oxide; viscosity modifiers; antiaging agents; pH.
A regulator, a buffer, an antiseptic, a fragrance and the like may be added.

The form of the external composition for skin of the present invention is not particularly limited. For example, the above-mentioned sodium cromoglycate and, if necessary, a percutaneous absorption enhancer are dissolved or mixed and dispersed in a base. Cream, paste,
In the form of jelly, gel, emulsion, liquid, etc. (ointment, liniment, lotion, etc.); the above sodium cromoglycate and, if necessary, the percutaneous absorption enhancer, etc. dissolved in the base Or a mixture and dispersed product spread on a support (such as a poultice); an adhesive is used as a base, and the above sodium cromoglycate and, if necessary, a percutaneous absorption enhancer are dissolved in the adhesive. Or what is mixed and dispersed is spread on a support (plaster agent,
Tapes, etc.) and the like.

As the above-mentioned base, any pharmaceutically acceptable base may be used, and conventionally known bases such as ointments, liniments and lotions can be used.
For example, sodium alginate, gelatin, corn starch, tragacanth gum, methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, dextrin, carboxymethyl starch, polyvinyl alcohol, sodium polyacrylate, methoxyethylene-maleic anhydride copolymer, polyvinyl ether, polyvinylpyrrolidone, etc. Polymers; oils and fats such as beeswax, olive oil, cacao oil, sesame oil, soybean oil, camellia oil, peanut oil, beef oil, pork oil, lanolin; white petrolatum; paraffin; gelled hydrocarbons (for example, trade name Plastibase, Bristol Made by Myers Squibb);
Examples include higher fatty acids such as stearic acid; higher alcohols such as cetyl alcohol and stearyl alcohol; polyethylene glycol; surfactants; water and the like. In particular,
Suitable bases for the present invention include hydrophilic gels composed of sodium polyacrylate, water, glycerin and the like.

Examples of the surfactant include lecithin derivatives, propylene glycol fatty acid esters, glycerin fatty acid esters, polyoxyethylene glycerin fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene. Sorbit fatty acid ester, polyoxyethylene alkylphenyl formaldehyde condensate, polyoxyethylene castor oil / hardened castor oil, polyoxyethylene sterol / hydrogenated sterol, polyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl Ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene lanolin / lano Emissions alcohol beeswax derivatives, polyoxyethylene alkyl amines, fatty acid amides, polyoxyethylene alkyl ether phosphoric acid-phosphate, but such polymeric emulsifiers include, but are not limited thereto.

The above-mentioned support is appropriately selected according to its dosage form, but it is preferable that the support is impermeable to the drug or impermeable to the drug and flexible, such as cellulose acetate, ethyl cellulose,
Polyethylene, polypropylene, polyvinyl chloride, vinyl acetate-vinyl chloride copolymer, ethylene-vinyl acetate copolymer, ethylene-vinyl acetate-carbon monoxide copolymer,
Ethylene-butyl acrylate-carbon monoxide copolymer,
Examples thereof include resin films such as polyvinylidene chloride, polyurethane, nylon, polyethylene terephthalate, and polybutylene terephthalate; aluminum sheets; woven fabrics; nonwoven fabrics; and laminated sheets thereof.

The above-mentioned pressure-sensitive adhesive may be any pharmaceutically acceptable one, and conventionally known ones can be used. For example, acrylic pressure-sensitive adhesive, rubber pressure-sensitive adhesive, silicone pressure-sensitive adhesive, urethane pressure-sensitive adhesive. Examples thereof include acrylic adhesives and rubber adhesives. When spread on the above-mentioned support, the properties of the adhesive are solvent-based,
Any emulsion type or hot melt type can be used.

Examples of the acrylic adhesive include
Examples of the adhesive include a polyalkyl (meth) acrylate mainly obtained by copolymerizing an alkyl (meth) acrylate, and a polyfunctional monomer copolymerizable with the alkyl (meth) acrylate or another vinyl monomer. It may be a polymer.

Examples of the alkyl (meth) acrylate include 2-ethylhexyl (meth) acrylate and dodecyl (meth) acrylate.
Examples of the polyfunctional monomer include 1,6-hexane glycol dimethacrylate and tetraethylene glycol diacrylate, and examples of the other vinyl monomers include N-vinyl-2-pyrrolidone and vinyl acetate. Is mentioned.

Examples of the above-mentioned rubber-based pressure-sensitive adhesives include pressure-sensitive adhesives mainly composed of natural rubber, styrene-isoprene-styrene block copolymer, styrene-olefin-styrene block copolymer, etc. Generally, rosin and hydrogenated A tackifier such as rosin, rosin ester, terpene resin, terpene phenol resin, petroleum resin, coumarone resin, coumarone-indene resin is added.

The external composition for skin of the present invention is used for improving the barrier function of the skin. The "skin barrier function" referred to in the present invention is a function of the skin to prevent foreign substances such as irritants from entering the epidermal layer from the outside, and the effect of improving the skin barrier function is, for example, as described below. It can be evaluated by the change in the amount of pigment that penetrates the epidermal layer.

The external use composition of the present invention may be used, for example, in cosmetics and pharmaceuticals. When used as a cosmetic, it is used as a lotion, emulsion, pack, etc. as a pharmaceutical. In this case, it is used as an external preparation for treating atopic dermatitis.

When the external composition for skin of the present invention is used as an external preparation for the treatment of atopic dermatitis, its use amount varies depending on the kind of disease, the degree of symptoms, the size of the affected area, etc. 1-10 g is preferable, and it is good to apply this to the affected area once or in appropriate times.

[0034]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Sodium cromoglycate (manufactured by Sigma,
Hereinafter, 5 parts by weight of “DSCG”) and 95 parts by weight of hydrophilic ointment (manufactured by Maruishi Pharmaceutical Co., Ltd.) were mixed at 75 ° C. and cooled with shaking to obtain a creamy composition. The following tests were conducted using this creamy composition as a test agent. Further, as a control agent, a hydrophilic ointment (manufactured by Maruishi Pharmaceutical Co., Ltd.) alone was used in the same test instead of the above test agent.

[Test Example] N-lauroyl sarcosine
Effect of dinitrochlorobenzene on rat skin barrier function decline model N-lauroyl sarcosine (manufactured by Nacalai Tesque, Inc.) and gelled hydrocarbon (Bristol-Myers Squibb, product name “Plastibase”) at a weight ratio of 2:98. It was supplied to a mortar and kneaded until the whole became uniform to obtain an ointment (hereinafter, referred to as "2% LS-containing plasty base ointment"). Further, crystal violet (manufactured by Wako Pure Chemical Industries, Ltd.) and hydrophilic ointment (manufactured by Maruishi Pharmaceutical Co., Ltd.) were supplied to a mortar at a weight ratio of 1:99, and kneaded until the whole became uniform, and the ointment (hereinafter, “1% CV-containing hydrophilic ointment ") was obtained.

The backs of 7-week-old male Wistar rats were shaved, and then the plastibase ointment containing 2% LS was added.
1 g was placed on the polyethylene terephthalate surface of a circular polyethylene terephthalate / ethylene / vinyl acetate laminated film having a radius of 1 cm, and the polyethylene terephthalate surface was attached so that this surface was in contact with the shaving part.

The film was peeled off 24 hours after application,
Then, 20% of a 1% by weight acetone solution of 2,4-dinitrochlorobenzene (DNCB, manufactured by Wako Pure Chemical Industries, Ltd.) was applied to the shaved portion.
μL was applied and dried well. Immediately after drying, 0.1 g of the test agent obtained in the above example was placed on the polyethylene terephthalate surface of a circular polyethylene terephthalate / ethylene vinyl acetate laminated film having a radius of 1 cm, and this surface was brought into contact with the shaving part. I attached it.

After 24 hours from application, the film of the test agent was peeled off, and then 0.05 g of the hydrophilic ointment containing 1% CV was added to a circular polyethylene terephthalate / ethylene.
It was placed on the polyethylene terephthalate surface of the vinyl acetate laminated film and attached so that this surface was in contact with the shaving part.

The film was removed 24 hours after application, and the shaving area was tape-striped eight times with cellophane tape (manufactured by Sekisui Chemical Co., Ltd.) to remove the stratum corneum. CR-200, manufactured by Minolta). Blueness of the control agent application site (Formula I
(Represented by (A)) and the blueness of the test agent application site (Formula I)
(Represented by (B) in the above), the bluish suppression rate was calculated by the following formula I.

[0041]

## EQU00001 ## The layered film was placed on the polyethylene terephthalate surface and attached so that this surface was in contact with the shaving part.

After 24 hours from application, the film of the test agent was peeled off, and then 0.05 g of the hydrophilic ointment containing 1% CV was added to a circular polyethylene terephthalate / ethylene.
It was placed on the polyethylene terephthalate surface of the vinyl acetate laminated film and attached so that this surface was in contact with the shaving part.

The film was removed 24 hours after application, and the shaving area was tape-striped eight times with cellophane tape (manufactured by Sekisui Chemical Co., Ltd.) to remove the stratum corneum. CR-200, manufactured by Minolta). Blueness of the control agent application site (Formula I
(Represented by (A)) and the blueness of the test agent application site (Formula I)
(Represented by (B) in the above), the bluish suppression rate was calculated by the following formula I.

[0041]

[Equation 1]

It should be noted that the stronger the bluishness, the greater the amount of crystal violet that has penetrated into the epidermis layer, and the lower the skin barrier function. The suppression of the bluishness means that the skin barrier function is improved. It has been done.

Evaluation of the skin barrier function-improving effect of the compositions of the above-mentioned examples revealed that the suppression rate of bluishness obtained by the formula I was 26.8%, indicating that the composition had a sufficient skin barrier function-improving effect. .

[0044]

EFFECTS OF THE INVENTION Since the external composition for skin of the present invention has the above-mentioned constitution, it can exert a sufficient improving effect on the deterioration of the skin barrier function.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) // C07D 311/24 C07D 311/24 F term (reference) 4C062 EE68 4C083 AC841 AC842 AD70 CC02 DD31 EE12 EE13 4C086 AA01 AA02 BA08 MA01 MA04 NA14 ZA89 ZB13

Claims (2)

[Claims] 1. An external composition for skin, which comprises sodium cromoglycate as a skin barrier function improving component. 2. Sodium cromoglycate 0.1-5
A composition for external use for skin, which comprises 0% by weight and is used for improving the skin barrier function.