JPH0337523B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an oxidation-resistant and anhydrous composition containing anthralin or one of its derivatives as an active ingredient, which composition is useful for treating skin diseases, especially acne, warts, alopecia, and especially psoriasis. It is used for the treatment of.

Psoriasis is a frequent skin disease that appears as lesions on the elbows, forearms, knees, lower legs, and sacrum-lumbar region, as well as on the scalp.

Among the various drugs conventionally used for the treatment of psoriasis, anthralin or dithranol (1,8,9-trihydroxyanthracene) is particularly commonly used.

Although the medicinal efficacy of this substance has been demonstrated, its use has some drawbacks in that the compound is very easily degraded by oxidation, resulting in dark polymeric products that can stain the skin and clothing. have

To avoid its deterioration, the use of petrolatum in combination with some antioxidants as a carrier has been proposed;
It has been shown that anthralin is dispersed in petrolatum but not dissolved. On the other hand, petrolatum-based formulations are extremely difficult to remove when applied to the scalp.

The inventors have recognized that the use of certain fatty acid esters as carriers, e.g.
- It has been established that anthralin or its derivatives can be stored in excellent conditions without having to resort to the use of antioxidants or stabilizers such as hydroxy acids.

It was shown that when stored in this way, no deterioration by atmospheric oxygen could be detected even in long-term storage tests.
The color of the solution remained unchanged or nearly unchanged, confirming that anthralin or its derivatives retain good stability when tested physicochemically.

That is, according to the present invention, anthralin is dissolved or dispersed in at least one fatty acid alkyl ester consisting of a fatty acid having 5 to 18 carbon atoms and a linear or branched alkyl group having 4 to 18 carbon atoms. or a lysate (or solution) of one of its derivatives
Alternatively, there is provided an oxidation-resistant and anhydrous dermatological treatment composition characterized in that it is in the form of a dispersion (or dispersion).

Preferred examples of fatty acid alkyl esters that meet the above specifications include isodecyl neopentanoate, decyl octoate, stearyl octoate, 2-ethylhexyl palmitate, butyl stearate,
Mention may be made of 2-ethylhexyl stearate, isocetyl stearate or mixtures thereof.

Examples of anthralin derivatives which can also be stabilized by the above-mentioned fatty acid alkyl esters include the anthralin compounds described in French Patent Application Nos. 8022454 and 8022455.

The concentration of anthralin or its derivatives in the compositions of the invention may generally be from 0.01 to 5%, preferably from 0.1 to 3%, based on the total weight of the composition.

The composition according to the present invention can be used as it is to treat skin diseases, particularly psoriasis, by applying it locally.
Preferably silica or polyethylene powder is used as a thickening agent without changing the stability of the composition.
It can be used in combination in an amount of 20% by weight.

In order to prevent the composition of the present invention from migrating from the application site and spreading and irritating healthy areas of the skin, it is preferable to use the composition in a relatively concentrated form.

Among the silica that can be used in the present invention, the average particle size
Silicas having a particle diameter of less than 30 mμ are preferred, especially those commercially available from DEGUSSA under the trade names "AEROSIL 200" and "AEROSIL R 972" or from WACKER under the trade names "HDK", especially "HDK NO 20 E". These silicas may be used alone or in combination.

Among the polyethylene powders that can be used according to the invention, the following are preferred.

(1) Melting point measured by ASTM-D2117-64 method
104-113℃ Also, the volumetric weight at 23℃ measured by the method of ASTM-D2839 is 0.914 to 0.923 (g/
cm ³ ) low-density polyethylene powder. An example of a polyethylene powder that exhibits these properties is C.
"LOTRENE UA 7000S" from DFChimie
and those commercially available under the trade name "LOTRENE UA 4000S".

(2) Softening temperature 128 as measured by ASTM-E28 method
High-density polyethylene powder having a volumetric weight of 0.96 g/cm ³ when measured at −129° C. and according to the method of ASTM-D1505. Examples of polyethylene powders exhibiting these properties include those commercially available from ALLIED CHEMICAL under the names "Polymist B6" and "Polymist B12."

(3) Softening temperature 102 measured by ASTM-E28 method
Polyethylene powder having a volumetric weight of 0.90 to 0.94 g/cm ³ as measured at −117° C. and according to the method of ASTM-D1505. An example of a polyethylene powder exhibiting these properties is the one commercially available from ALLIED CHEMICAAL under the name "Polyethylene AC 6A."

(4) Softening temperature 92− as measured by ASTM-E28 method
Ethylene-acrylic acid copolymer having a volumetric weight of 0.93 g/cm ³ as measured at 108° C. and according to the method of ASTM-D1505. An example of a powder exhibiting these properties is that sold by ALLIED CHEMICAL under the name "Polyethylene AC 540."

Oils, waxes,
Salicylic acids can also be incorporated into the present compositions as long as they do not adversely affect oxidative stability.

Hereinafter, compositions containing anthralin or one kind of its derivative according to the present invention as an active ingredient will be illustrated in Examples, but the present invention is not limited thereto.

Example 1 According to the present invention, a skin treatment composition to be used before shampooing was prepared by mixing the following ingredients.

Anthralin 0.4g Salicylic acid 0.4g Mixture of cetyl octoate and stearyl octoate (50:50). Amount to make the total 100 g Example 2 A composition for use before shampooing was prepared according to the present invention by mixing the following ingredients.

Anthralin 0.1g Isocetyl stearate Amount to make the total 100g Example 3 A gel skin composition was prepared according to the present invention by mixing the following ingredients: Anthralin 0.4g Silica (HDK N 20 E, commercially available from WACKER) Humid silica) 7.0g Isocetyl stearate Amount to make the total amount to 100g Example 4 According to the present invention, a gel-like skin composition was prepared by mixing the following ingredients.

Anthralin 3g Silica (Aerosil R 972) 8g Salicylic acid 0.2g 2-ethylhexyl palmitate
Amount to make a total of 100 g Example 5 A gel composition for skin is prepared according to the present invention by mixing the following ingredients: Anthralin 5 g Silica (Aerosil 200) 8 g Cetyl octoate Amount to make a total of 100 g In this example, silica (Aerosil200) can be replaced with the same amount of silica, HDK N20E.

Example 6 A gel skin treatment composition for the treatment of psoriasis is prepared according to the invention by mixing the following ingredients: Anthralin 1 g Polyethylene AC6A 7.5 g Stearyl octoate Amount to make a total of 100 g As in Examples 1 to 6 above An equivalent amount of cetyl octoate or 2-ethyl hexyl stearate can be used in place of the fatty acid alkyl ester used.

Example 7 A stick-like skin composition for topical application and treatment of psoriasis is prepared according to the invention by blending the following ingredients: Anthralin 0.5g Cocoa butter 12.5g Ozocherito wax 18.75g White paraffin 6.25g White petrolatum 12.50g Octane Mixture of cetyl acid and stearyl octoate (70:30) Total amount to 100 g Example 8 A gel skin composition for the treatment of psoriasis is prepared according to the invention by mixing the following ingredients: Anthralin 1 g Polyethylene AC540 7.5g 2-ethyl hexyl stearate
Amount to make 100 g The compositions of Examples 1 to 8 above, when applied in an amount sufficient to cure ailments occurring in the skin or scalp area, can cure skin diseases, especially after a treatment period of 3 to 5 weeks. Alleviation or cure of psoriasis can be achieved. As mentioned above, it is clear that the composition for treating skin diseases of the present invention contains a specific fatty acid alkyl ester carrier and anthralin, and is useful for treating psoriasis. Its effectiveness in treatment has been proven in the literature ``Hand book of Experimental Pharmacology''.
Dermatologic Pharmacology () Ed.Greases and Shuster
"Anthralin 34" excerpted from "Springer (1989)"
Chapter B. Shroot et al., pp. 459-471 states, ``Since the pioneering work of Unna (1916), anthralin has occupied a crucial role in the clinical treatment of psoriasis.''
(p. 459) and "Short Contact Treatment with Anthralin According to Schaefer et al. (1980), drug-skin contact times of up to 1 hour for 1% anthralin in petrolatum are effective in psoriasis." (p. 468)
It is also disclosed in the literature “Psoriasis”.
Anthralin Chapter 27 B. Shroot et al. 327-334, excerpted from HMRoenick and MIMaidach (1985)
Page” says “Hydroxyanthracene derivatives are 1868
Anthralin or dithranol (1,8-dihydroxy-anthr-9-one) is a widely used and highly effective drug of this type, which has occupied an important role in the treatment of psoriasis since 1999. ” (page 327)
and "Anti-psoriatic efficacy could be established using 1% anthralin in petrolatum for 1 hour per day."
This is clear from the disclosure (page 332).

Testing of Oxidative Stabilizers In order to demonstrate that the dermatological treatment composition of the present invention is stable against oxidation without the use of stabilizing compounds, ie antioxidants, comparative tests were conducted as follows.

Comparative composition 1 contains the following ingredients.

Anthralin 0.05g Oxalic acid 0.1g Acetone 20ml Isopropyl myristate 79.85ml This composition was poured into bottle 1 with a screw cap.
A composition of the invention consisting of an anthralin solution containing the following ingredients: anthralin 0.05 g 2-ethylhexyl palmitate 99.95 ml was poured into a screw cap bottle 2.

Comparative composition 2 versus comparative composition 1, containing the following ingredients, except that the stabilizer oxalic acid was omitted: Anthralin 0.05g Acetone 20ml Isopropyl myristate 79.95ml
and poured it into bottle 3.

Observe these three bottles 1-3 (time 0),
Thereafter, it was kept in a dry oven at a constant temperature of 45°C for one month. Bins 1-3 were observed again after this period (hours + 1 month).

Although Comparative Composition 1 containing oxalic acid was stable, a slight color change (change from colorless to yellow) occurred during storage. Comparative composition 2 changed from colorless (hours) to brown (time + 1 month), compared to comparative composition 1.
This indicates that oxalic acid is required to maintain the stability of However, the compositions of the present invention are nearly unchanged in color and oxidative stability is achieved when anthralin is mixed with certain fatty acid alkyl esters without the use of antioxidants such as oxalic acid.

Claims (1)

[Scope of Claims] 1. A solution or dispersion of anthralin or anthralin derivative dissolved or dispersed in at least one fatty acid alkyl ester consisting of a fatty acid having 5 to 18 carbon atoms and an alkyl group having 4 to 18 carbon atoms. 1. An anhydrous composition for treating skin diseases, characterized in that it is in the form of: 2. The fatty acid alkyl ester is isodecyl neopentanoate, cetyl octoate, stearyl octoate, 2-ethylhexyl palmitate, butyl stearate, 2-ethylhexyl stearate, isocetyl stearate, or a mixture thereof. Claim 1 Compositions as described. 3. The composition according to claim 1 or 2, wherein anthralin or one of the anthralin derivatives is contained as a solution or dispersion thereof in a concentration of 0.01 to 5% by weight based on the total weight of the composition. 4. The composition according to any one of claims 1 to 3, wherein the composition further contains silica or polyethylene powder as a thickening agent in an amount of 0.1 to 20% by weight. 5. The composition according to any one of claims 1 to 4, wherein the composition further contains salicylic acid as a conventional ingredient in agents for skin diseases.