JPH08208487A - Agent for external use for treating inflammatory dermatosis - Google Patents

Abstract

PURPOSE: To obtain the subject agent for external use lowered in side effects by reducing the containing amount of a synthetic adrenocortical hormones and containing a large amount of the other active ingredients, containing each specified amount of aspirin, a synthetic adrenocortical hormone and propylene glycol and a percutaneous absorbefacient. CONSTITUTION: This agent for external use contains (A) 1-80wt.% of aspirin or sodium cromoglycate, (B) 0.02-0.5wt.% of a synthetic adrenocortical hormone, (C) 1-30wt.% of propylene glycol, and (D) a percutaneous absorbefacient such as a higher fatty acid ester, amide linkage-contg. compound or a 2-10C divalent carboxylic acid (salt). The formulation of this agent is e.g. cream, paste, gel, ointment, milky lotion, lotion, solution or cataplasm. As for the dose of this agent, it is preferable that the daily amounts of the ingredients A and B to be used be 0.1-1g and 0.0001-0.005g, respectively.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to an external preparation for treating inflammatory skin diseases. More specifically, a large amount of active ingredient
The present invention relates to an external preparation in which side effects are reduced by reducing the amount of synthetic adrenocortical hormone.

[0002]

2. Description of the Related Art Conventionally, an external preparation consisting of a synthetic corticosteroid has been widely used for the treatment of inflammatory skin diseases, and its pharmacological effect is known to be high (Monthly Pharmaceutical Affairs; 26, 8, 1985). Although external preparations composed of non-steroidal anti-inflammatory drugs and antihistamines are also used, their effects on intractable allergic dermatitis are not sufficient compared with external preparations of corticosteroids (new drug and treatment; 35,298,1985).

However, synthetic external agents for corticosteroids may cause side effects at the site of application, such as increased infectivity, thinning of the skin, weakening of the blood vessel wall, and abnormal activation of the pilosebaceous system. In addition, the transdermally absorbed drug may cause systemic side effects, and conversely, if the dose is reduced, the effect is reduced, so that the administration period is extended and the side effects may be exacerbated.

By the way, aspirin has been used as an analgesic and antipyretic drug for a long time, and it is safe with few side effects.
It is also disclosed to be used as an external preparation (for example, JP-A-3-72426 and JP-B-61-58450). Further, JP-A-6-32728 discloses an external preparation for skin in which vitamin A and an anti-inflammatory agent such as aspirin or prednisolone are used in combination to improve the rough skin improving effect of vitamin A. However, there is no disclosure about the combined use of vitamin A and an anti-inflammatory agent such as aspirin or prednisolone for inflammatory skin diseases.

Further, sodium cromoglycate is highly safe and is widely used for allergic diseases and chronic dermatitis as disclosed in, for example, Japanese Patent Publication No. 5-501714 and Japanese Unexamined Patent Publication No. 3-118321. Has been. However, the combined use of DSCG and adrenocortical hormone has not been disclosed for use in inflammatory skin diseases.

[0006]

DISCLOSURE OF THE INVENTION The present invention is intended to solve the above-mentioned problems, and an object thereof is an inflammatory skin disease having few side effects and having the same or higher efficacy as an external preparation of corticosteroids. The purpose is to provide a therapeutic external preparation.

[0007]

The external preparation for treating inflammatory skin diseases of the present invention comprises aspirin, synthetic adrenocortical hormone,
It contains propylene glycol and a transdermal absorption enhancer. The external preparation for treating inflammatory skin diseases of the present invention 2 contains sodium cromoglycate (cromolyn, disodium cromoglycate; hereinafter referred to as "DSCG"), synthetic adrenocortical hormone, propylene glycol, and transdermal absorption enhancer. To do.

The aspirin is a hypothermic analgesic, an anti-inflammatory drug,
As an anti-rheumatic drug, the above DSCG is listed in the Japanese Pharmacopoeia as an anti-allergic drug and an asthma drug, and the content in the external preparation varies depending on the type and amount of the synthetic adrenocortical hormone mixed at the same time. In that case, it will not dissolve in the base, and especially in the case of ointments and creams, the dosage form will not be able to be retained, and if the amount decreases, the effect will not be sufficient.
It is 0% by weight, preferably 5 to 60% by weight, more preferably 5 to 40% by weight, and further preferably 10 to 30% by weight.

If the content of the above synthetic adrenocortical hormone in the external preparation increases, there is a high risk that side effects will occur.
If it is less, the effect will not be sufficient, so 0.02-
It is 0.5% by weight, preferably 0.02-0.3% by weight. In particular, the content when the adrenocortical hormone is dexamethasone is 0.02-0.05% by weight, preferably 0.02-0.03% by weight, and in the case of prednisolone, it is 0.2-0.5% by weight. % By weight, preferably 0.2-0.3
% By weight, and in the case of betamethasone valerate 0.02-
It is 0.06% by weight, preferably 0.025 to 0.035% by weight.

As the synthetic adrenocortical hormone, in addition to dexamethasone, prednisolone, and betamethasone valerate, those used as an external preparation for skin can be appropriately used. For example, diflorazone acetate is classified as the strongest one according to its efficacy. , Very strong diflucortron valerate, fluocinonide, etc., strong
Examples thereof include dexamethasone valerate and fluocinolone acetonide, medium examples include triamcinolone acetonide, weak examples include hydrocortisone acetate, methylprednisolone acetate and the like. The above-mentioned dexamethasone, prednisolone, and betamethasone valerate are classified into medium, weak, and strong, respectively.

The above-mentioned propylene glycol is a dissolving agent for aspirin or DSCG, and the content in the external preparation varies depending on the amount of aspirin or DSCG. Since DSCG does not dissolve, it is 1 to 30% by weight.

If the content of the above-mentioned absorption enhancer in the external preparation is increased, the inflammatory therapeutic effect of aspirin or DSCG and synthetic adrenocortical hormone is not particularly enhanced, and on the contrary, it may cause skin irritation, etc. Since the transdermal absorption effect of is not sufficient, it is preferably 0.3 to 10% by weight, more preferably 0.5 to 3% by weight.

Examples of the percutaneous absorption enhancer include higher fatty acid esters, compounds having an amide bond, divalent carboxylic acids having 2 to 10 carbon atoms and salts thereof, polyoxyethylene alkyl ether phosphate esters and salts thereof, Lactic acid, lactic acid ester, citric acid and the like can be mentioned.

The higher fatty acid ester has 10 to 10 carbon atoms.
It is a reaction product of 18 higher fatty acids and an alcohol having 1 to 20 carbon atoms. Examples of the higher fatty acid having 10 to 18 carbon atoms include saturated fatty acids such as capric acid, undecylic acid, lauric acid, tridecylic acid, myristic acid, palmitic acid and stearic acid; oleic acid, linoleic acid, linolenic acid and the like. Examples include saturated fatty acids.

Examples of the alcohol having 1 to 20 carbon atoms include methanol, ethanol, propanol,
Isopropanol, butanol, isobutanol, amyl alcohol, isoamyl alcohol, hexanol,
Aliphatic saturated alcohols such as heptanol, octanol, capryl alcohol, nonyl alcohol, decyl alcohol, lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol; aliphatic unsaturated alcohols such as allyl alcohol; alicyclic alcohols such as cyclohexanol And aromatic alcohols such as benzyl alcohol and cinnamyl alcohol. Examples of the higher fatty acid ester include isopropyl laurate, isopropyl stearate, isopropyl myristate, isopropyl palmitate and the like.

The compound having an amide bond is
Examples thereof include N-acyl sarcosine, fatty acid mono- or diethanolamide and alkylene oxide adducts thereof. As the above N-acyl sarcosine,
For example, N-lauroyl sarcosine and the like can be mentioned. Examples of the fatty acid mono- or diethanolamide and alkylene oxide adducts thereof include lauroyl monoethanolamide, palmitic acid monoethanolamide, myristic acid diethanolamide, and lauric acid.
Examples thereof include myristic acid diethanolamide, coconut oil fatty acid monoethanolamide, polyoxyethylene-added lauroyl monoethanolamide, polyoxyethylene-added coconut oil fatty acid monoethanolamide, and the like.

Examples of the divalent carboxylic acid having 2 to 10 carbon atoms and salts thereof include oxalic acid, malonic acid, fumaric acid, maleic acid, tartaric acid, malic acid, succinic acid, glutaric acid, adipic acid and fumaric acid. , Isophthalic acid, terephthalic acid and the like, and salts thereof such as sodium salt, potassium salt, magnesium salt and aluminum salt.

The above polyoxyethylene alkyl ether phosphoric acid ester and its salt are phosphoric acid ester and its salt of a derivative obtained by addition-polymerizing ethylene oxide to alcohol. Examples of the alkyl group include a methyl group and an ethyl group. Group, propyl group, isopropyl group, butyl group, t-butyl group, pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, dodecyl group, lauryl group, stearyl group, palmityl group, myristyl group, cetyl group And the like. Examples of the salt include sodium salt, potassium salt, magnesium salt, aluminum salt and the like. Examples of the lactic acid ester include esters of lactic acid and alcohols having 1 to 20 carbon atoms, such as myristyl lactate and cetyl lactate. As the transdermal absorption enhancer, higher fatty acid ester and N-acyl sarcosine are particularly preferable among the above.

The dosage form of the external preparation of the present invention is not particularly limited, and examples thereof include creams, pastes, gels, ointments, emulsions, lotions or solutions, and patches. Cream, paste, gel, ointment, emulsion,
In the case of molding into a lotion or solution form, a conventionally known one can be used as a base, if necessary,
Examples thereof include petroleum jelly, beeswax, ointment bases such as hydrocarbon gel ointment (for example, trade name Plastibase, manufactured by Taisho Pharmaceutical Co., Ltd.), liquid paraffin, polyethylene glycol, cellulose, alcohol, water, starch, olive oil and the like.

The external preparation of the present invention is produced by a usual method such as well kneading each component and, if necessary, a base,
Further, it is used by a usual use method such as being applied directly to an affected area or impregnated with a cloth or the like.

The applied amount of the external preparation for treating inflammatory skin diseases of the present invention varies depending on the type of disease, the degree of symptoms, the size of the affected area, etc., but is preferably 0.1 to 0.1 per day as the amount of aspirin or DSCG. It is 1 g. Although the amount of the synthetic adrenocortical hormone varies depending on the type, it is preferably 0.0001 to 0.005 g per day, which is half the usual amount or less.

Examples of the inflammatory skin diseases to be treated by the external preparation of the present invention include inflammatory skin diseases including conventional adaptation diseases of synthetic adrenocortical hormone external preparations, such as atopic dermatitis and contact. Dermatitis, seborrheic dermatitis, Vidal lichen, coin-shaped eczema, housewife eczema, photodermatitis, insect bite, pruritus dermatitis, prurigo, drug eruption, poisoning rash, psoriasis, psoriasis,
Palmoplantar pustulosis, lichen planus, lichen planus, erythema erythematosus piriformis,
Gibber rose schizophrenia, erythema, erythroderma, lupus erythematosus lupus, systemic lupus erythematosus, pemphigus, pemphigus vulgaris, alopecia areata vulgaris, vitiligo vulgaris, sarcoidosis, Examples include cutaneous amyloidosis, keloids and hypertrophic scars.

The pharmacological action of the external preparation for the treatment of inflammatory skin diseases of the present invention is, as described in the Examples below, as a model animal for type I allergy in rats, a 4-hour allogeneic passive skin anaphylaxis (homorologous PCA) reaction and a type IV allergy. A dose of aspirin or D was demonstrated in the rat delayed cutaneous hypersensitivity reaction (DTH) as an experimental animal model of allergy
The external preparation for skin containing SCG and synthetic adrenocorticoid hormone is more effective than the external preparation containing only adrenocortical hormone, and the amount of synthetic adrenocortical hormone used can be suppressed to half or less of the usual amount. It has become possible.

[0024]

EXAMPLES The present invention will be described with reference to examples. (Example 1) The components were well kneaded in the following proportions to obtain an ointment containing aspirin and dexamethasone. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Dexamethasone (Wako Pure Chemical Industries, Ltd.) 0.025 Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 68.975 (total amount 100)

(Example 2) The components were well mixed in the following proportions to obtain a liquid preparation containing aspirin and dexamethasone. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Dexamethasone (Wako Pure Chemical Industries, Ltd.) 0.025 Propylene glycol 10 Isopropyl myristate 1 Olive oil 68.975 (total 100)

(Example 3) The components were well kneaded in the following proportions to obtain an ointment containing aspirin and prednisolone. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Prednisolone (Wako Pure Chemical Industries, Ltd.) 0.25 Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 68.75 (total amount 100)

(Example 4) The components were well mixed in the following proportions to obtain a liquid preparation containing aspirin and prednisolone. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Prednisolone (Wako Pure Chemical Industries, Ltd.) 0.25 Propylene glycol 10 Isopropyl myristate 1 Olive oil 68.75 (total amount 100)

(Example 5) The components were well kneaded in the following proportions to obtain an ointment containing aspirin and betamethasone valerate. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Betamethasone valerate (Wako Pure Chemical Industries, Ltd.) 0.03 Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 69.97 (total amount 100)

(Example 6) The components were mixed well in the following proportions to obtain a liquid preparation containing aspirin and betamethasone valerate. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Betamethasone valerate (Wako Pure Chemical Industries, Ltd.) 0.03 Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 69.97 (total amount 100)

(Example 7) The components were well kneaded in the following proportions to obtain an ointment containing aspirin and dexamethasone. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 1 (g) Dexamethasone (Wako Pure Chemical Industries, Ltd.) 0.025 Propylene glycol 1 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 96.975 (total amount 100)

(Example 8) The components were well kneaded in the following proportions to obtain an ointment containing aspirin and prednisolone. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 1 (g) Prednisolone (Wako Pure Chemical Industries, Ltd.) 0.25 Propylene glycol 1 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 96.75 (total amount 100)

(Example 9) The components were well kneaded in the following proportions to obtain an ointment containing aspirin and betamethasone valerate. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 1 (g) Betamethasone valerate (Wako Pure Chemical Industries, Ltd.) 0.03 Propylene glycol 1 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 96.97 (total amount 100)

(Example 10) The components were well kneaded in the following proportions to obtain an ointment containing aspirin and dexamethasone. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Dexamethasone (Wako Pure Chemical Industries, Ltd.) 0.025 Propylene glycol 10 N-lauroyl sarcosine 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 68.975 (total amount 100)

(Example 11) The components were well kneaded in the following proportions to obtain an ointment containing aspirin and prednisolone. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Prednisolone (Wako Pure Chemical Industries, Ltd.) 0.25 Propylene glycol 10 N-lauroyl sarcosine 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 68.75 (total amount 100)

(Example 12) Each component was well kneaded in the following proportions to obtain an ointment containing aspirin and betamethasone valerate. Aspirin (manufactured by Maruishi Pharmaceutical Co., Ltd.) 20 (g) Betamethasone valerate (manufactured by Wako Pure Chemical Industries, Ltd.) 0.03 Propylene glycol 10 N-lauroyl sarcosine 1 Ointment base: Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.) 69.97 (total amount 100) )

Example 13 The same procedure as in Example 1 was repeated except that DSCG was used as aspirin.
An ointment containing CG and dexamethasone was obtained.

Example 14 The same procedure as in Example 2 was repeated except that aspirin was replaced by DSCG.
A liquid preparation containing CG and dexamethasone was obtained.

Example 15 A DS was prepared in the same manner as in Example 3 except that DSCG was used as aspirin.
An ointment containing CG and prednisolone was obtained.

Example 16 A DS was obtained in the same manner as in Example 4 except that DSCG was used as aspirin.
A liquid preparation containing CG and prednisolone was obtained.

Example 17 The same procedure as in Example 5 was repeated except that aspirin was replaced by DSCG.
An ointment containing CG and betamethasone valerate was obtained.

Example 18 The same procedure as in Example 6 was repeated except that DSCG was used as aspirin.
A liquid preparation containing CG and betamethasone valerate was obtained.

Example 19 The same procedure as in Example 7 was repeated except that DSCG was used as aspirin.
An ointment containing CG and dexamethasone was obtained.

Example 20 The same procedure as in Example 8 was repeated except that DSCG was used as aspirin.
An ointment containing CG and prednisolone was obtained.

(Embodiment 21) The same procedure as in Embodiment 9 was repeated except that DSCG was used as aspirin.
An ointment containing CG and betamethasone valerate was obtained.

(Embodiment 22) In the above-mentioned Embodiment 10,
D except that aspirin is DSCG
An ointment containing SCG and dexamethasone was obtained.

(Example 23) In the above Example 11,
D except that aspirin is DSCG
An ointment containing SCG and prednisolone was obtained.

(Embodiment 24) In the above-mentioned Embodiment 12,
D except that aspirin is DSCG
An ointment containing SCG and betamethasone valerate was obtained.

(Comparative Example 1) The components were well kneaded in the following proportions to obtain an ointment containing dexamethasone. Dexamethasone (manufactured by Wako Pure Chemical Industries, Ltd.) 0.05 (g) Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.) 88.95 (total amount 100)

(Comparative Example 2) The components were well kneaded in the following proportions to obtain an ointment containing dexamethasone. Dexamethasone (Wako Pure Chemical Industries, Ltd.) 0.025 (g) Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 88.975 (total 100)

(Comparative Example 3) The components were well kneaded in the following proportions to obtain an ointment containing prednisolone. Prednisolone (manufactured by Wako Pure Chemical Industries, Ltd.) 0.5 (g) Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.) 88.5 (total amount 100)

(Comparative Example 4) The components were well kneaded in the following proportions to obtain an ointment containing prednisolone. Prednisolone (manufactured by Wako Pure Chemical Industries, Ltd.) 0.25 (g) Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.) 88.75 (total amount 100)

(Comparative Example 5) The components were well kneaded in the following proportions to obtain an ointment containing betamethasone valerate. Betamethasone valerate (manufactured by Wako Pure Chemical Industries, Ltd.) 0.06 (g) Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.) 88.94 (total amount 100)

(Comparative Example 6) The components were well kneaded in the following proportions to obtain an ointment containing betamethasone valerate. Betamethasone valerate (manufactured by Wako Pure Chemical Industries, Ltd.) 0.03 (g) Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.) 88.97 (total amount 100)

(Comparative Example 7) The components were well kneaded in the following proportions to obtain an ointment containing aspirin. Aspirin (Maruishi Pharmaceutical Co., Ltd.) 20 (g) Propylene glycol 10 Isopropyl myristate 1 Ointment base: Plastibase (Taisho Pharmaceutical Co., Ltd.) 69 (total amount 100)

(Comparative Example 8) An ointment containing DSCG was obtained in the same manner as in Comparative Example 7, except that DSCG was used as aspirin.

Test Example 1 Effect of PCA Reaction on Type I Allergic Reaction (1) Preparation of Rat Anti-DNP-As Serum Tada and Okumura Method (Journal of
Immunology; 106,1002,1971), rat anti-DNP
-As serum was prepared. The extract of Ascaris suum was prepared according to the method of Strejan and Campbell (Journal of American Chemical Society; 75,4583,195.
3), 2,4-dinitrophenyl sulfate (DN
P) and DNP-bound Ascarisum (D
NP-As) was obtained.

1 mg of the above DNP-As was dissolved in 1 ml of physiological saline in which 1 × 10 ¹⁰ pertussis killed bacteria were suspended, and the solution was subcutaneously injected into the footpad of a female rat weighing about 200 g. Five days later, 0.5 mg of DNP-As was dissolved in 0.5 ml of physiological saline and injected into the left and right muscles. Eight days after the first injection, blood was collected from the abdominal aorta and the serum was separated to obtain rat anti-DNP-As serum.

(2) PCA reaction The above-mentioned rat anti-DNP-As serum was diluted with physiological saline, and 0.05 ml thereof was injected into the dorsal skin of male rats weighing 120 to 200 g. Then, 0.1 mg of the ointment and 0.1 ml of the solution obtained in the above Examples and Comparative Examples.
Each of the test agents of 1. was applied to the anti-DNP-As serum injection site of rat skin so that the ointment was placed on a circular polyethylene sheet piece with a radius of 1 cm so as to come into contact with the skin, and the solution was dropped directly onto the skin It was applied covered with a piece of circular polyethylene sheet with a radius of 1 cm.

Forty-eight hours later, 0 .. containing DNP-As antigen.
A 5% Evans' blue physiological saline solution was intravenously injected at a rate of 2.5 mg / kg to induce a PCA reaction. After 30 minutes, the animals were sacrificed, and the pigment leaked to the skin at the reaction site was analyzed by the method of Harada et al. (Journal of Pharm).
aceutics Pharmacology; 23,218,1971), the reaction skin was finely cut, and the leaked pigment was extracted by immersing the reaction skin in a mixed solution of 0.3% sodium sulfate: acetone = 3: 7 (volume ratio) for 48 hours or more. . The extracted dye was then colorimetrically determined at 620 nm. As a control, only the ointment base was applied in the same manner instead of the above-mentioned test agent, and then the same operation was performed to perform colorimetric quantification of the extracted pigment. The dye leakage inhibition rate was calculated by the following formula from the quantitative results of the above-mentioned amount of extracted pigment (A) at the control application site and the amount of extracted pigment (B) at the test agent application site. The results are shown in Tables 1 and 2. Dye leakage suppression rate (%) = {(A−B) / A} × 100

[Test Example 2] Effect of DTH reaction on type IV allergic reaction 5 weeks old Wistar rat ventral skin was shaved, and then 20% 2,4-dinitrochlorobenzene (DNCB,
20 μl of acetone solution (manufactured by Wako Pure Chemical Industries, Ltd.) was applied and left for 2 weeks for sensitization. After creating the feeling, the back skin was shaved and 0.
20 μl of 5% DNCB acetone solution was applied to induce contact dermatitis.

Then, 0.1 mg each of the ointments obtained in the above Examples and Comparative Examples and 0.1 ml of the liquid preparations were tested in the same manner as in (2) PCA reaction of Test Example 1 above.
It was applied to the rat skin DNCB reaction induction site. Twenty-four hours after the reaction was induced, the erythema intensity at the reaction site was measured by a color difference meter (CR
-200, manufactured by Minolta). As a control, only the ointment base was applied in the same manner instead of the above test agent, and the same operation was performed thereafter to measure the erythema intensity. From the measurement results of the erythema intensity (C) of the control application site and the erythema intensity (D) of the test agent application site, the erythema inhibition rate was calculated by the following formula. The results are shown in Tables 1 and 2. Erythema suppression rate (%) = {(C−D) / C} × 100

[Test Example 3] Effect on whole body due to change in body weight The body weight of the rat used in Test Example 2 above was measured,
The effects of side effects on the whole body were examined. The results are shown in Tables 1 and 2.
Shown in

[0063]

[Table 1]

[0064]

[Table 2]

In the table, "%" means "% by weight", "A"
“P” represents “aspirin”, “DM” represents “dexamethasone”, “PD” represents “prednisolone”, and “BV” represents “betamethasone valerate”.

The concentrations of dexamethasone, prednisolone, and betamethasone valerate used in the external preparation were 0.
05, 0.5, 0.06 wt%, but Table 1 and Table 2
From Examples 1, 3, 5, 10 to 13, 15, 17, 2
In 2 to 24, since aspirin or DSCG was contained in a large amount, although the synthetic adrenocortical hormone was half amount, the pigment leakage inhibition rate and the erythema inhibition rate were equal to or higher than those of Comparative Examples 1, 3 and 5, respectively. The effect was recognized. Moreover, there was no side effect of weight loss as seen in the comparative example.

At the concentrations of the synthetic adrenocortical hormones used in the above Examples, when compared with Comparative Examples 2, 4, and 6,
A higher effect was obtained in the pigment leakage inhibition rate and the erythema inhibition rate than in the case of only the synthetic adrenocortical hormone.

[0068]

The external preparation for treating inflammatory skin diseases of the present invention is as described above, and by adding aspirin or DSCG in a large amount, it is possible to reduce the amount of synthetic adrenocortical hormone to a side effect-less level. And as a result,
An external preparation useful for the treatment of inflammatory skin diseases is obtained, which has a sufficient therapeutic effect equivalent to or more than that of an external corticosteroid hormone and has few side effects.

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Claims (2)

[Claims] 1. Inflammatory property, which comprises 1 to 80% by weight of aspirin, 0.02 to 0.5% by weight of synthetic adrenocortical hormone, 1 to 30% by weight of propylene glycol, and a percutaneous absorption enhancer. Topical for treating skin diseases. 2. It is characterized by containing 1-80% by weight of sodium cromoglycate, 0.02-0.5% by weight of synthetic adrenocortical hormone, 1-30% by weight of propylene glycol, and a transdermal absorption enhancer. An external preparation for treating inflammatory skin diseases.