JPH06179619A - External agent for treating inflammatory dermatosis - Google Patents

Abstract

PURPOSE:To provide the external agent little in side effects and exhibiting the same or higher pharmacological effects as or than those of external agents containing adenocortical hormones as main ingredients and used for treating inflammatory dermatosis. CONSTITUTION:The external agent for treating inflammatory dermatosis is characterized by containing vitamin E and one kind or more of percutaneous absorption-stimulating agents selected from an N-acylsarcosine (salt); an aliphatic acid amide which is a reaction product of an aliphatic monocarboxylic acid with mono or diethanolamine; a higher aliphatic acid ester which is a reaction product of a 1-18C higher aliphatic acid with a 1-20C alcohol; a 2-10C dicarboxylic acid (salt); a 3-6C hydroxylcarboxylic acid (salt); a polyoxyethylene(n) alkyl ether (n is an integer of 2-30 which is the number of the oxyethylene units which is an addition polymer of ethylene oxide to a 12-22C higher aliphatic alcohol; 10-18C higher aliphatic alcohol sulfuric ester; and a 2-4C lower aliphatic alcohol. The content of the vitamin E is 4-40wt.% in the external agent.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an external preparation for treating inflammatory skin diseases.

[0002]

2. Description of the Related Art Conventionally, an external preparation containing an adrenocortical hormone as an active ingredient has been widely used for the treatment of inflammatory skin diseases, particularly for the treatment of intractable allergic skin diseases, and it is known to have a high pharmacological effect. (Monthly Pharmaceutical Affairs, Volume 26, 8
No., p. 56, 1985). And, JP-A-62-14
Japanese Patent Publication No. 9620 discloses an external preparation containing a corticosteroid as a main active ingredient, and tocopherol acetate (vitamin E 1 is used as an auxiliary agent for enhancing a pharmacological effect).
), And lower alcohols having 2 to 3 carbon atoms, carboxylic acid alkyl esters having 10 to 16 carbon atoms, and the like as solubilizing agents for active ingredients.

However, the external preparation for the treatment of inflammatory skin diseases containing the above-mentioned adrenocortical hormone has an increased susceptibility to infection, thinning of the skin, weakening of the blood vessel wall, and the like.
In addition to possible side effects such as abnormal activation of the pilosebaceous system, percutaneously absorbed drugs may exhibit systemic side effects, so the amount used should be carefully monitored. It Therefore, in the Japanese Pharmacopoeia, the upper limit of the concentration of dexamethasone and prednisolone, which are typical adrenocortical hormones, is limited to about 0.1% by weight in the external preparation.

On the other hand, as an external preparation for treating inflammatory skin diseases with few side effects, there is an external preparation consisting of a nonsteroidal anti-inflammatory drug and an antihistamine, but for intractable allergic skin diseases, it contains an adrenocortical hormone. Its pharmacological effect is weaker than that of (new drug and treatment, 35, 29
8 pages, 1985).

[0005]

The present invention has been made in view of the above-mentioned drawbacks, and its object is to be equivalent to an external preparation for treating inflammatory skin disease containing an adrenocortical hormone as an active ingredient. It is to provide the external preparation having the above pharmacological effects and less side effects.

[0006]

The vitamin E used in the present invention means tocopherol (vitamin E) and its derivatives listed in the Japanese Pharmacopoeia,
Examples of the derivative include tocopheryl acetate (vitamin E acetate ester) and tocopherol succinate (vitamin E succinate ester). When the content of the above-mentioned vitamin E is low, the therapeutic effect on inflammatory skin diseases is not sufficiently expressed, and when it is high, the fluidity becomes too high and it becomes difficult to maintain the dosage form as an external preparation. It is limited to 4 to 40% by weight in the external preparation for treating skin diseases.

The transdermal absorption enhancer used in the present invention is N
-Acyl sarcosine (salt); fatty acid amide which is a reaction product of aliphatic monocarboxylic acid and mono- or diethanolamine; higher fatty acid having 10 to 18 carbon atoms and 1 to carbon atom
Higher fatty acid ester which is a reaction product with 20 alcohols; dicarboxylic acid (salt) having 2 to 10 carbon atoms; 3 carbon atoms
A hydroxycarboxylic acid having 6 to 6; a polyoxyethylene (n) alkyl ether (n represents the number of oxyethylene chains, which is an addition polymer of a higher aliphatic alcohol having 12 to 22 carbon atoms and ethylene oxide; 30 integer); carbon number 10
To 18 higher aliphatic alcohol sulfate ester salts; and one or more compounds selected from the group consisting of lower aliphatic alcohols having 2 to 4 carbon atoms.

Examples of the N-acyl sarcosine (salt) include N-lauroyl sarcosine, N-stearoyl sarcosine, N-oleoyl sarcosine, N-palmitoyl sarcosine, coconut oil fatty acid sarcosine and sodium of these N-acyl sarcosine. Examples thereof include salts, potassium salts, magnesium salts, calcium salts, aluminum salts and the like, and N-lauroylsarcosine is preferably used.

The above-mentioned fatty acid amide is a reaction product of an aliphatic monocarboxylic acid and mono- or diethanolamine, and examples of the aliphatic monocarboxylic acid include caprylic acid, capric acid, lauric acid, myristic acid and palmitin. Acid, coconut oil fatty acid, polyoxyethylene-added lauric acid, polyoxyethylene-added coconut oil fatty acid and the like can be mentioned. Examples of the fatty acid amide include lauric acid dietano-
Lamide is preferably used.

The higher fatty acid ester is a reaction product of a higher fatty acid and an alcohol. The higher fatty acid is liable to volatilize when the carbon number is small, and the transdermal absorption promoting effect is lowered when the carbon number is large. Limited to 10-18,
For example, saturated aliphatic monocarboxylic acids such as capric acid, lauric acid, myristic acid, palmitic acid and stearic acid; unsaturated aliphatic monocarboxylic acids such as palmitoleic acid, oleic acid, vaccenic acid, linoleic acid and linolenic acid. And saturated aliphatic dicarboxylic acids such as sebacic acid.

Further, since the above-mentioned alcohol has a lower effect of promoting percutaneous absorption as the carbon number increases, it is limited to 1 to 20, for example, methyl alcohol and ethyl alcohol.
Aliphatic saturated alcohols such as benzyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol, pentyl alcohol, hexyl alcohol, heptyl alcohol, octyl alcohol, decyl alcohol, cetyl alcohol and the like. There is Le. As the higher fatty acid ester,
For example, isopropyl myristate and isopropyl palmitate are preferably used.

The above dicarboxylic acid having 2 to 10 carbon atoms (salt)
Since the effect of promoting percutaneous absorption decreases as the carbon number increases, it is limited to 2 to 8, and examples thereof include oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid,
Saturated aliphatic dicarboxylic acids such as suberic acid; Unsaturated aliphatic dicarboxylic acids such as fumaric acid and maleic acid; Aromatic dicarboxylic acids such as phthalic acid, isophthalic acid, terephthalic acid and sodium salts, potassium salts, magnesium of these dicarboxylic acids Examples thereof include salts such as salts, calcium salts, and aluminum salts, and fumaric acid and maleic acid are preferably used.

The hydroxycarboxylic acid (salt) having 3 to 6 carbon atoms is easily volatilized when the carbon number is small, and the transdermal absorption promoting effect is deteriorated when the carbon number is large. , Monocarboxylic acids such as glyceric acid; dicarboxylic acids such as malic acid and tartaric acid, and salts of these carboxylic acids such as sodium salts, potassium salts, magnesium salts, calcium salts, and aluminum salts;
Lactic acid and malic acid are preferably used.

The polyoxyethylene (n) alkyl ether (n represents the number of oxyethylene chains) is an addition polymer of a higher aliphatic alcohol and ethylene oxide. The higher aliphatic alcohol is liable to volatilize as the carbon number decreases, and the transdermal absorption-promoting effect decreases as the carbon number increases, so that it is limited to 12 to 22, for example, lauryl alcohol.
And cetyl alcohol, oleyl alcohol and the like. Further, n, which is the number of oxyethylene chains of the polyoxyethylene (n) alkyl ether, is easily volatilized when it is small, and the transdermal absorption promoting effect is reduced when it is large, so it is limited to 2 to 30, and for example, , Polyoxyethylene (20) lauryl ether and polyoxyethylene (20) cetyl ether, and polyoxyethylene (20) cetyl ether is preferably used.

The higher aliphatic alcohol sulfate ester salt is liable to volatilize as the carbon number decreases, and the transdermal absorption-promoting effect decreases as the carbon number increases, so that it is limited to 10 to 18, for example, lauryl sulfate and myristyl. Examples thereof include sodium salts such as sulfuric acid, potassium salts, calcium salts, ammonium salts and the like, and sodium lauryl sulfate is preferably used.

The lower aliphatic alcohol is liable to volatilize when the carbon number is small, and the transdermal absorption promoting effect is deteriorated when the carbon number is large. Therefore, it is limited to 2 to 4, for example, ethyl alcohol and propyl alcohol. Examples thereof include ethyl alcohol, isopropyl alcohol and butyl alcohol, and ethyl alcohol is preferably used.

When the content of the percutaneous absorption enhancer used in the present invention decreases, the effect of promoting percutaneous absorption decreases, and when the content increases, the fluidity becomes too high and it becomes difficult to maintain the dosage form as an external preparation. Therefore, it is preferably 0.3 to 10% by weight in the external preparation for treating inflammatory skin diseases of the present invention, more preferably 0.
It is 5 to 3% by weight.

The external preparation for treating inflammatory skin diseases of the present invention is
Although it contains the above-mentioned active ingredient and percutaneous absorption enhancer, its dosage form is not particularly limited. For example, the above-mentioned active ingredient and percutaneous absorption enhancer are dissolved or mixed and dispersed in a base. Creams, pastes, gels, gels, emulsions, liquids, etc. (ointments, liniments, lotions, etc.); the above pastes, gels on a support -Patterned into a shape (Pap), which is obtained by dissolving or mixing and dispersing the above-mentioned active ingredient and percutaneous absorption enhancer in an adhesive and spread on a support (Plaster- Agents, tapes, etc.) and the like.

The above-mentioned base may be any pharmaceutically acceptable one, and it has hitherto been an ointment, a liniment, a lozenge.
What has been used for cation agents can be used, for example,
Sodium alginate, gelatin, cornstar citragant gum, methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, dextrin,
Polymers such as carboxymethyl starch, polyvinyl alcohol, sodium polyacrylate, methoxyethylene-maleic anhydride copolymer, polyvinyl ether and polyvinylpyrrolidone; beeswax, olive oil, cocoa oil, sesame oil, soybean oil Fats and oils such as camellia oil, camellia oil, peanut oil, beef oil, pork oil and lanolin; white petrolatum; paraffin; plastibase; higher fatty acids such as stearic acid; higher alcohols such as cetyl alcohol, stearyl alcohol; polyethylene Glycol; water and the like.

If desired, inorganic fillers such as kaolin, bentonite, zinc oxide and titanium oxide; viscosity modifiers; antiaging agents; pH modifiers and the like may be added.
Further, when used as a poultice, a humectant such as glycerin or propylene glycol may be added.

The above-mentioned support is appropriately selected according to its dosage form (eg, poultice, plaster, tape, etc.), but the active ingredient is impermeable or hardly permeable. Flexible ones are preferable, for example, cellulose acetate, ethyl cellulose, polyethylene, polypropylene, polyvinyl chloride, vinyl acetate-vinyl chloride copolymer, ethylene-vinyl acetate copolymer, ethylene-vinyl acetate-carbon monoxide. Copolymers, ethylene-butyl acrylate-carbon monoxide copolymers, polyvinylidene chloride, polyurethane, nylon, polyethylene terephthalate, resin films such as polybutylene terephthalate, aluminum sheets and the like. These may be laminated sheets, or may be laminated with a woven fabric or a non-woven fabric.

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

The above-mentioned acrylic pressure-sensitive adhesive is a pressure-sensitive adhesive mainly composed of polyacrylic (meth) acrylate obtained by copolymerizing acrylic (meth) acrylate, and co-polymerized with acrylic (meth) acrylate. It may be a copolymer with a polymerizable polyfunctional monomer or another vinyl monomer. Examples of the acrylic (meth) acrylate include 2-ethylhexyl (meth) acrylate and dodecyl (meth) acrylate, and examples of the polyfunctional monomer include 1,6-hexane. Glycol dimethacrylate, tetraethylene glycol diacrylate, and the like, and other vinyl monomers include
Examples thereof include N-vinyl-2-pyrrolidone and vinyl acetate.

The rubber-based pressure-sensitive adhesives are natural rubber, styrene-
An isoprene-styrene block copolymer, a styrene-olefin-styrene block copolymer and other rubber-containing pressure-sensitive adhesives, which are generally rosin, hydrogenated rosin, rosin ester, terpene resin, terpene phenol resin,
A tackifier such as petroleum resin, coumarone resin, coumarone-indene resin is added.

The composition of the external preparation for treating inflammatory skin diseases of the present invention is as described above, but an adrenocortical hormone may be added within a range not impairing the performance of the external preparation. Examples of the adrenocortical hormones include dexamethasone, prednisolone, cortisone, hydrocortisone, methylprednisolone triamcinolone, betamethasone, fluocinolone, and the like. Since the risk of side effects becomes stronger when the amount is eliminated and increases, for example, in the case of dexamethasone or prednisolone, 0.01 to 10% of the external preparation for treating inflammatory skin diseases of the present invention is used.
0.08% by weight is preferable, more preferably 0.02-
It is 0.06% by weight. The applied amount of the adrenocortical hormone depends on the type and the degree of the inflammatory skin disease, the degree of the symptom, the size of the affected part, the type of the adrenocortical hormone, and the like, but the amount of the adrenocortical hormone is 0.00001 to 0 per day. ．
0005 g / 3.14 cm ² is preferred.

The diseases to be treated by the external preparation for treating inflammatory skin diseases of the present invention include atopic dermatitis, contact dermatitis, seborrheic dermatitis, Vidal lichen, coin-shaped eczema, housewife eczema, and sunlight. Dermatitis, insect bite, pruritus cutis, prurigo, drug eruption,
Poisoning eruption, psoriasis, psoriasis, palmoplantar pustulosis, lichen planus, lichen planus, erythema pityriasis pilaris, gibber rosacea plaque, erythema,
Erythroderma, lupus erythematosus vulgaris, systemic lupus erythematosus, pemphigus, pemphigus vulgaris, Juling herpes dermatitis, alopecia areata, vitiligo vulgaris, sarcoidosis, cutaneous amyloidosis, keloid, hypertrophic scar, etc. Therefore, all of the conventional indication diseases of the external preparation of corticosteroids are targeted. Although the application amount of the external preparation for treating inflammatory skin diseases of the present invention depends on the type of inflammatory skin diseases, the degree of symptoms, the size of the affected area, etc., it is 0.01 to 0 per day as the amount of vitamin E. ．
2 g / 3.14 cm ² is preferred.

[0027]

EXAMPLES Examples of the present invention will be described below. In addition,
Hereinafter, "part" means "part by weight". Examples 1 to 11, Comparative Examples 1 to 5 Predetermined amounts (parts) of plastibase (manufactured by Japan Squibb), vitamin E acetate (manufactured by Wako Pure Chemical Industries) and dexamethasone (Wako Pure Chemical Industries, Ltd.) shown in Table 1. ), Prednisolone (manufactured by Wako Pure Chemical Industries, Ltd.), N-lauroyl sarcosine, isopropyl myristate, dilauranol diamide, fumaric acid, lactic acid, polyoxyethylene (20) cetyl ether, sodium lauryl sulfate and ethyl alcohol-.
The mixture was fed to a mortar and kneaded until other additives were dissolved in the plastic base to obtain an ointment.

[0028]

[Table 1]

Example 12 30 parts of vitamin E acetate ester (manufactured by Wako Pure Chemical Industries), 1 part of dexamethasone (manufactured by Wako Pure Chemical Industries, Ltd.), 0.05 parts of N-lauroyl sarcosine and 68.95 parts of olive oil were added.
The liniment agent was obtained by supplying the mixture to a car and stirring until the whole was homogeneously compatible.

Example 13 A liniment agent was obtained in the same manner as in Example 12 except that prednisolone was used instead of dexamethasone.

Example 14 Synthesis of acrylic adhesive 2-ethylhexyl methacrylate 301.0 parts, 2-
34.9 parts of ethylhexyl acrylate, dodecyl meta
Crylate 48.3 parts, 1,6-hexane glycol
Tacrylate 0.0384 parts and ethyl acetate 256.
0 parts separable flask with stirring device and cooling device
To 70 ° C while stirring and purging with nitrogen.
It was 2.0 parts of lauroyl peroxide and 10 parts of cyclohexane
The solution dissolved in 0.0 parts is divided into 10 parts, and the 1 is separated.
Polymerization was initiated by addition to a bull flask. After the start of polymerization
From the 5th hour, the remaining 9 was added at 1-hour intervals, and the addition was completed.
After that, the reaction was continued for another 19 hours. In addition, reaction to adjust viscosity
After the start, add ethyl acetate 5 times every 5 hours, every 5 hours.
It was After the reaction is complete, cool, then add more ethyl acetate.
An adhesive solution having a solid content concentration of 50% by weight was obtained.

Preparation of Tape Agent Vitamin E, lauroyl sarcosine, and dexamethasone were added to the above solution in a total solid content (acrylic adhesive + vitamin E).
+ Lauroyl sarcosine + dexamethasone) at concentrations of 15% by weight, 3% by weight and 0.05% by weight, respectively, and the whole liquid was uniformly stirred with a dissolver to obtain a mixed liquid. The obtained mixed liquid was treated with a siliconized polyethylene terephthalate film (thickness: 38 μm).
m) and then dried at 60 ° C for 30 minutes to give a thickness of 8
A 0 μm pressure-sensitive adhesive layer was formed. Then, the pressure-sensitive adhesive layer was transferred onto the ethylene-vinyl acetate copolymer layer of the polyethylene terephthalate / ethylene-vinyl acetate copolymer laminated film having a thickness of 34 μm to obtain a tape agent.

Example 15 A tape preparation was obtained in the same manner as in Example 14 except that prednisolone was used instead of dexamethasone. 3% by weight syn and 0.3% prednisolone.
A tape preparation containing 05% by weight was prepared.

The test examples carried out using the external preparation obtained above will be described below. In each test, 5 rats were used, and the results obtained are the average value thereof.

Test Example 1 (Effect on Type III Allergic Reaction) As a model of type III allergic reaction, a 4-hour rat passive skin anaphylaxis- (heterologous PCA) reaction was adopted, and the dye leakage inhibition rate was calculated by the following procedure. , The strength of action of the external preparation of the present invention on type III allergic reaction was evaluated. In this case, the higher the inhibition rate, the stronger the effect, and the higher the therapeutic effect on allergic skin diseases.

Rabbit anti-ovalbumin blood
Preparation of Kiyo et al. Method (Journal of the Japanese Pharmacological Society, 66, 237, 1
970), rabbit anti-ovalbumin serum was prepared by the following method. That is, an equivalent amount of an emulsion of 2 mg / ml ovalbumin (manufactured by Sigma) dissolved in physiological saline and Freund's complete adjuvant (manufactured by Difco) was used as an antigen solution, 0.5 ml each of which was used for male rabbits. (New Zealand White) 4 in the left and right glutes every week
I gave it twice. Seven days after the final injection, blood was collected from the carotid artery and the serum was separated and collected to obtain rabbit anti-ovalbumin serum.

Rat 4 hour heterologous passive skin anaphylaxis
-Effect of external preparation on reaction Dilute the rabbit anti-ovalbumin serum obtained above four-fold with physiological saline, and place it in 0.05 ml each at 2 sites in the dorsal skin of male Wistar rats weighing about 200 g. Was injected into. Then add 0.1 g of the ointment of Example 1 to a radius of 1 cm.
The test agent placed on a piece of circular polyethylene sheet (thickness: 38 μm) was applied to one of the sites of injection of anti-albumin serum on rat skin such that the ointment was in contact with the skin.
As a control for the above test, the test agent in which only 0.1 g of the ointment base was placed on the sheet piece instead of the ointment of the test agent was similarly applied to other parts of the anti-ovalbumin serum injection site. . Next, 4 hours after injection of anti-ovalbumin serum, 0.5 W containing ovalbumin (antigen) 2 mg / ml
/ V% Evans blue (dye) physiological saline solution 2.
The reaction was induced by intravenous administration in 5 ml / kg rat.

The leaking dye at the site where the above-mentioned intradermal reaction is induced is determined by the method of Harada et al. (Japan Journal of Pharmacology, 23.
Vol. 218, 1971). That is, the animals were sacrificed 30 minutes after the injection of the antigen, the skin at the injection site of the anti-ovalbumin serum was peeled off, and the cut pieces were cut into pieces each having a diameter of 2 cm. This was immersed in 10 ml of a mixed solution of 3 volume of 0.3 W / V% sodium sulfate and 7 volume of acetone for 48 hours to extract the leaked dye, and colorimetrically determined at 620 nm. From this quantification result, the dye leakage suppression rate (%) of the test agent was calculated from the control formula (A) and the leak dye amount (B) of the ointment of Example 1 as the test agent by the following formula. I asked. Dye leakage suppression rate (%) = (A−B) / A × 100 Next, instead of the ointment of Example 1, the ointments of Examples 2 to 11 and Comparative Examples 1 to 5 were used in the same manner as above. The respective dye leakage inhibition rates were obtained. Table 2 shows these measurement results.
It was shown to.

Test Example 2 (Effect on Type IV Allergic Reaction) As a model of type IV allergic reaction, rat delayed-type skin hypersensitivity (DHT) reaction was adopted, and the erythema and swelling of the resulting skin are shown below. The erythema inhibition rate and the swelling inhibition rate were determined by the procedure described above, and the strength of the effect of the present invention on type IV allergic reaction was evaluated. In this case, the higher the inhibition rate, the stronger the effect, and the higher the therapeutic effect on allergic skin diseases.

Topical preparation for delayed skin hypersensitivity reaction in rat
Effect of Kuriyama et al. (Journal of the Japanese Pharmacological Society, 94, 113, 1
989) according to the following method. That is, 1 ml of physiological saline solution was added to Bacillus Calmette-Guerin (BC
G) 12 liquids containing 2.5 mg of bacteria (manufactured by Japan BCG)
After heat treatment at 1 ° C. for 5 minutes, 0.2 ml was intraperitoneally injected into a 9-week-old Wistar rat. Seven days after the injection of BCG bacteria, 0.1 ml of a solution prepared by dissolving 200 μg of purified tuberculin (manufactured by Japan BCG Co., Ltd.) in 1 ml of a physiological saline solution was injected into two sites inside the dorsal skin of the cut hair of the rat. In addition, only another physiological saline solution containing no purified tuberculin solution was injected into the other part in the back skin of the shaved hair in the same manner. Then, 0.1 g of the ointment of Example 1 was placed on a piece of circular polyethylene sheet (thickness: 38 μm) having a radius of 1 cm, and the ointment was placed on one part of the tuberculin serum injection site of rat skin so that the ointment contacted the skin. Applied As a control for the above test, the test agent in which only 0.1 g of the ointment base was placed on the sheet piece instead of the ointment of the test agent was similarly applied to the other one site of the tuberculin injection site.

Then, the diameter of the erythema produced 24 hours after the injection of tuberculin was measured, and the erythema diameter (C) of the control ointment base alone was used as the test agent and the ointment of Example 1 as the test agent. The erythema inhibition rate (%) of the test agent was determined from the erythema diameter (D) of Erythema suppression rate (%) = (C−D) / C × 100

Thereafter, the rat was sacrificed, the skin at the tuberculin injection site and the injection site at which only physiological saline solution was injected was peeled off, and the skin was punched to a diameter of 1.6 cm and the weight of this part was measured. The difference in weight between the punched parts of the tuberculin injection site and the injection site of the physiological saline solution alone was determined and used as the swelling weight. From the swelling weight (E) of the control ointment base alone as the test agent and the swelling weight (F) of the ointment of Example 1 as the test agent, the swelling suppression rate of the test agent ( %). Swelling inhibition rate (%) = (E−F) / E × 100 Next, instead of the ointment of Example 1, the ointments of Examples 2 and 3 and Comparative Examples 1 to 4 were used in the same manner to each erythema. The inhibition rate and the swelling inhibition rate were calculated. The results of these measurements are shown in Table 2.

Test Example 3 (Influence of side effects due to adrenal weight change) After killing all the rats used in Test Example 2 and the rats not subjected to the test (untreated), the left and right adrenal glands were removed,
The weight was measured. The total amount of left and right weights is shown in Table 2. In this case, the smaller the weight loss compared to that of the untreated rat, the higher the side effect reducing effect.

[0044]

[Table 2]

[0045]

EFFECTS OF THE INVENTION Since the composition of the external preparation for treating inflammatory skin diseases of the present invention is as described above, it has a high therapeutic effect on inflammatory skin diseases and, in comparison with an external preparation containing a corticosteroid as a main component. And there are few side effects. Therefore, the external preparation of the present invention can be effectively used for various inflammatory skin diseases including allergic skin diseases.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location A61K 9/70 364 9165-4C 47/16 E 7433-4C // (A61K 31/355 31:57 ) 9360-4C

Claims (1)

[Claims] 1. Vitamin E and N as active ingredients
-Acyl sarcosine (salt); fatty acid amide which is a reaction product of aliphatic monocarboxylic acid and mono- or diethanolamine; higher fatty acid having 10 to 18 carbon atoms and 1 to carbon atom
Higher fatty acid ester which is a reaction product with 20 alcohols; dicarboxylic acid (salt) having 2 to 10 carbon atoms; 3 carbon atoms
~ 6 hydroxycarboxylic acid (salt); 12 to 22 carbon atoms
Polyoxyethylene (n) alkyl ether (n) which is an addition polymer of higher aliphatic alcohol and ethylene oxide.
Represents the number of oxyethylene chains and is an integer of 2 to 30); a higher aliphatic alcohol sulfate ester salt having 10 to 18 carbon atoms; and a lower aliphatic alcohol having 2 to 4 carbon atoms. An external preparation for the treatment of inflammatory skin diseases, which comprises one or more percutaneous absorption enhancers, wherein the content of vitamin E is 4 to 40% by weight in the external preparation. Topical agent for disease treatment.