JP2949236B2 - External preparation - Google Patents

Description

Description: FIELD OF INDUSTRIAL APPLICATION The present invention relates to an external preparation for skin, and more particularly to an external preparation for skin which normally contains adrenocortical hormone at the following concentration and has excellent therapeutic effects.

BACKGROUND ART Adrenal corticosteroids are used in the eczema/dermatitis group, represented by acute/chronic eczema, contact dermatitis, and atopic dermatitis,
It shows excellent effects on many skin diseases such as pruritus such as strophulus and urticaria, pruritus, and psoriasis, and is widely used clinically as an external preparation.

As mentioned above, adrenocortical hormones have excellent pharmacological effects, but even external preparations may cause systemic side effects such as suppression of pituitary and adrenocortical system functions when used extensively over a long period of time. It also has side effects such as localized skin infections and skin symptoms such as acne peculiar to adrenocortical hormones. Therefore, in order to ensure the safety of
It is desirable to use as low a concentration as possible. However, treatment with external preparations containing low-concentration adrenocortical hormones cannot be expected to have a sufficient therapeutic effect on the aforementioned intractable diseases. Therefore, in order to increase the percutaneous absorption of adrenocortical hormones, it is necessary to use external preparations containing percutaneous absorption enhancers such as urea and propylene glycol, as well as ODT tapes such as drainisone tape (Dainippon Pharmaceutical Co., Ltd.). (manufactured by a company, Japan) are considered, but there are many problems such as skin irritation and usability. Under these circumstances, there has been a demand for the development of an external preparation that is highly safe and excellent in usability. Therefore, the present inventors have extensively studied a method of obtaining sufficient therapeutic effects using an external preparation containing a low-concentration of adrenocortical hormone, and as a result, added hyaluronic acid to an external preparation containing a low-concentration of adrenocortical hormone. By
The present invention was completed based on the finding that a topical preparation containing adrenocortical hormone alone at a concentration normally used clinically can provide a therapeutic effect equal to or greater than that obtained when using an external preparation.

DISCLOSURE OF THE INVENTION The present invention provides an external preparation for skin comprising adrenocortical hormone and hyaluronic acid at concentrations below those usually used clinically.

Detailed Description of the Invention The present invention provides an adrenocortical hormone-containing preparation for external use in which hyaluronic acid is added to reduce the amount of adrenocortical hormone content from the usual amount. That is, the present invention relates to an external skin preparation containing adrenocortical hormone and hyaluronic acid. Examples of adrenocortical hormones in the present invention include prednisolone,
methylprednisolone, methylprednisolone acetate, prednisolone acetate valerate, hydrocortisone, hydrocortisone acetate, hydrocortisone butyrate, hydrocortisone butyrate propionate, flumethasone pivalate, triamcinolone, triamcinolone acetonide, dexamethasone, dexamethasone acetate, dexamethasone valerate, dexamethasone propionate, fluocinolone, fluocinolone acetonide, betamethasone, betamethasone valerate,
betamethasone dipropionate, beclomethasone propionate, clobetasone butyrate, fludroxycortide, fluocinonide, halcinonide, amcinonide, difluprednate, diflucortolone valerate, diflorazone acetate, clobetasol propionate, preferably prednisolone, methylprednisolone , hydrocortisone acetate, hydrocortisone butyrate, flumethasone pivalate, dexamethasone acetate, fluocinolone, betamethasone valerate, betamethasone dipropionate, clobetasone butyrate, difluprednate, diflorasone acetate, and clobetasol propionate.

Hyaluronic acid as used in the present invention is used as a concept including its salts, for example, medically acceptable salts such as sodium salts. good.

By adding hyaluronic acid to the topical skin preparation at a concentration of usually about 0.005-0.1% (by weight), the amount of adrenocortical hormone can be reduced below the usual amount used, for example, about 1/2 to 1/10.

Taking hydrocortisone butyrate as an example, the content of hydrocortisone butyrate in external preparations is usually 0.1% by weight.
(11th revision, Japanese Pharmacopoeia), but the weight concentration is 0.01%
of hyaluronic acid, the hydrocortisone butyrate content can be reduced to 0.03% by weight.

The external preparation for skin of the present invention can be prepared by mixing hyaluronic acid, adrenocortical hormone, or, if desired, suitable excipients used in the preparation of preparations for external use, according to conventional preparation methods for external preparations for skin.

The human diseases to be treated with the topical preparations for external use include, for example, hand eczema, progressive keratoderma palmaris, Bidar's lichen, atopic dermatitis and cheilitis, which are treated by conventional topical adrenocortical hormone preparations. Eczema/dermatitis group such as, psoriasis, prurigo group,
Diseases such as insect bites, lichen planus and palmar pustulosis are included.

Also, since hyaluronic acid is non-irritating and non-toxic, it can be used according to the usual usage of adrenocortical hormone agents.

Next, the effectiveness of the external preparation for skin of the present invention will be described with reference to experimental examples.

Experimental Example 1 As test samples, a cream containing 0.1% hydrocortisone butyrate (hydrophilic ointment base, sample 1), a cream containing 0.03% hydrocortisone butyrate (hydrophilic ointment base, sample 2), and a cream containing 0.03% hydrocortisone butyrate and 0.01% hyaluronic acid. Using 3 samples of cream (hydrophilic ointment base, sample 3) (each value indicates weight concentration), each sample was subjected to a skin paleness test by a patch test commonly used to examine the clinical pharmacological efficacy of external skin preparations. made a comparison.

That is, adhesive plaster for patch test (manufactured by Torii Pharmaceutical Co., Ltd.,
Japan), approximately 60 mg of each sample was applied and applied to the back of a healthy adult male. After 4 hours of application, the bandage was removed and the degree of pallor of the skin at the application site was determined by visual observation 30 minutes, 2 hours and 4 hours later. As the criteria for evaluation, the four-level evaluation shown in Table 1 is usually used, but in this experiment, the uniformity and non-uniformity of pallor were taken into consideration, and evaluation was further subdivided between each level in order to ensure more accuracy.

Table 2 shows the results of the comparative test.

As is clear from Table 2, sample 2 showed a clearly weaker pallor effect than sample 1, while sample 3 showed a similar level of pallor effect as sample 1.

This experimental result is also supported by the results of Experimental Examples 2 to 4 shown below.

Experimental Example 2 In the same manner as in Experimental Example 1, materials shown in Table 3 were prepared.

That is, adhesive plaster for patch test (manufactured by Torii Pharmaceutical Co., Ltd.,
Approximately 50 mg of each sample was applied to each sample in Japan) and applied to the back of a healthy adult male. Six hours after application, the adhesive bandage was removed, and the degree of pallor of the skin at the application site was determined by visual observation 0.5, 2, and 4 hours later. As with the case of Experimental Example 1, the 4-level evaluation shown in Table 1 was used as the criteria for evaluation, and the uniformity and non-uniformity of the pallor were taken into account to further subdivide the evaluation between each level in order to ensure accuracy.

Table 4 shows the results of the comparative test.

Experimental Example 3 In the same manner as in Experimental Example 1, samples shown in Table 5 were prepared.

Adhesive plaster for patch test (manufactured by Torii Pharmaceutical Co., Ltd., Japan)
Approximately 50 mg of each sample was applied to each sample and applied to the back of a healthy adult male. Six hours after application, the bandage was removed, and the degree of pallor of the skin at the application site was determined by visual observation 0.5, 2, and 4 hours later. As with the case of Experimental Example 1, the 4-level evaluation shown in Table 1 was used as the criteria for evaluation, and the uniformity and non-uniformity of the pallor were taken into account to further subdivide the evaluation between each level in order to ensure accuracy.

Table 6 shows the results of the comparison.

Experimental Example 4 In the same manner as in Experimental Example 1, samples shown in Table 7 were prepared.

Adhesive plaster for patch test (manufactured by Torii Pharmaceutical Co., Ltd., Japan)
Approximately 50 mg of each sample was applied to each sample and applied to the back of a healthy adult male. Six hours after application, the bandage was removed, and the degree of pallor of the skin at the application site was determined by visual observation 0.5, 2, and 4 hours later. As with the case of Experimental Example 1, the 4-level evaluation shown in Table 1 was used as the criteria for evaluation, and the uniformity and non-uniformity of the pallor were taken into account to further subdivide the evaluation between each level in order to ensure accuracy.

Table 8 shows the results of the comparative test.

EXAMPLES Next, the present invention will be described in more detail with reference to examples, but the scope of the present invention is not limited by these examples.

Example [Composition] a) White petrolatum 250 g b) Stearyl alcohol 200 g c) Glycerin monostearate 10 g d) Polyoxyethylene hydrogenated castor oil 60 40 g e) Propylene glycol 120 g f) Methyl paraoxybenzoate 1 g g) Propyl paraoxybenzoate 1 g h) Hyaluronic acid 0.1 g i) Hydrocortisone butyrate 0.3 g j) Purified water 377.6 g Total amount 1000 g Keep the mixture of a) to d) at about 75°C and stir to make a uniform liquid of about Keep at 75 ° C, f) to j) in advance
Add to e) and heat to dissolve if necessary. Add to j) and add the liquid heated to about 75°C. was prepared. When 3 patients with contact dermatitis were treated with the cream prepared as described above, the symptoms of skin inflammation disappeared in 3 to 7 days in all 3 patients.

Continuation of the front page (58) Researched field (Int.Cl. ⁶ , DB name) A61K 31/57 A61K 47/36 CA (STN)

Claims (6)

(57) [Claims] 1. Hyaluronic acid and hydrocortisone butyrate are mixed together with excipients, and the amount of hydrocortisone butyrate is 1/2 to 1/10 of the usual amount of 0.1% (by weight). A method for producing an external preparation for skin comprising: 2. The method according to claim 1, wherein hyaluronic acid is mixed so that the external preparation for skin contains 0.005 to 0.1% (by weight) of hyaluronic acid. 3. The method according to claim 1, wherein the external skin preparation is a cream for external skin preparation. 4. The method according to claim 1, wherein the external preparation for skin is an external cream for treating dermatitis. 5. The method according to claim 1, wherein the hyaluronic acid is sodium hyaluronate. [Claim 6] 0.005 to 0.1% (by weight), characterized by adding hyaluronic acid and hydrocortisone butyrate to a cream base that has been stirred until uniform, and further stirring;
of hyaluronic acid and 0.1% (by weight), which is the usual amount
A method for producing a skin cream for external use containing hydrocortisone butyrate in an amount of 1/2 to 1/10 of the above.