CH659945A5 - ANTHRALINE PHARMACEUTICAL COMPOSITIONS AND METHOD FOR THE PRODUCTION THEREOF. - Google Patents

Description

The present invention accordingly relates to the pharmaceutically acceptable composition defined in claim 1.

The anthralin is preferably used in a concentration of 5.0% by weight. Anthralin is more preferably used in compositions which can be used for topical application in a proportion of 0.1-3.0% by weight and particularly preferably in a proportion of 0.5-2.0% by weight.

Of course, higher concentrations of anthralin can also be stabilized by the agents of the present invention; however, caution must be exercised with such compositions to avoid irritation to normal skin.

The anionic surfactant is used in an amount sufficient to stabilize the anthralin. Anionic surfactants are preferably used in a proportion of 0.5-10% by weight, more preferably 0.1-5.0% by weight and particularly preferably 0.3-1.0% by weight.

Despite the fact that it is known that anthralin is more stable at an acidic pH and that the pH of anthralin containing compounds can be controlled by adding any dermatologically acceptable acid, citric acid or salicylic acid are preferred as such acids. The pH of anthralin-containing compositions according to the invention which contain an acid-stable, water-soluble anionic surfactant is 5.3 and less. It is preferred that lower pH values be used, the limiting factor being skin irritation. Preferably a pH of s less than 4.0 and more preferably a pH of less than 3.4 is used.

The present invention provides an anthralin product which has long-term anthralin stability, cosmetic elegance, better patient tolerance and essentially no discoloration in suitable packaging. It can be used successfully in the treatment of psoriasis, both in the long-term external treatment of low strength and in the internal short-term treatment of higher strength.

15 It is hypothesized that the present invention works because particles or droplets of oil dispersed in the liquid medium can be charged, with two theories to choose from. The first involves the reactive adsorption of special ions that are present in the solution. In the case of water, it can be the hydronium or the hydroxyl ion. The majority of the particles or droplets of oil dispersed in the aqueous medium are negatively charged because of the preferred adsorption of the hydroxyl ion. According to the second theory, charges of particles or droplets are included, the charges of which come from the ionization of functional groups of surface-active agents, such as phosphates, carboxylates, sulfates and sulfonates, which are present on the surface of the particles or on the interface of the oil-water Phases.

Molecules and ions that are adsorbed on the surfaces or interfaces are called surface-active agents or surfactants. Alternatively, they are also referred to as amphiphiles, which expresses the fact that the molecule or the ion has a certain activity for both polar and non-polar solvents. It is the amphiphilic nature of the surfactant molecules or ions that causes them to be adsorbed at the interface, which can be liquid / gaseous or liquid / liquid 40.

The chemical structure of anthralin is as follows

OH OH OH

Anthralin is an amphiphilic type of a molecule; in other words, the anthralin has certain affinity for both polar and non-polar groups. The amphiphilic nature of the anthralin molecules also causes them to easily accumulate on the surface or at the interface, where they can be particularly easily attacked. Under such conditions, oxidation inhibitors such as oxygen, light, hydrogen ions or metal ions easily attack the anthralin and / or accelerate its decomposition through free radical auto-oxidation. High surface or whole surface concentrations of anthralin molecules also accelerate dimer formation due to intramolecular interaction.

It is hypothesized that the present invention produces particles, oil droplets or

Micelles, the surface of which predominantly has an anionic charge which is produced either by the only anionic surfactant or by the combination of the non-ionic surfactant or surfactants with the anionic surfactant or surfactants. The negatively charged surface is caused by functional groups such as sulfonates, sulfates, phosphates 60 and carboxylates of the anionic surfactant (s). The anionic groups of acid stable surface active agents are adsorbed on the surface of the oil / water interface and create a negatively charged surface against the oil particles, droplets 65 or micelles. In the aqueous phase, the cations are attracted to the negatively charged surface, which at the same time forces anions, such as hydroxyl, back into the solution until the original adsorption is complete. To

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659 945

In addition to these electrical forces, the thermal movement causes an even distribution of all ions in the solution. As a result, an equilibrium situation is created and the system as a whole is electrically neutral.

The distribution ratio of anthralin between oil and water on the oily phase side is approximately 5000-10,000 to 1. Accordingly, in the case of preparations based on oil-in-water emulsions such as creams, gels or emulsified Ointments, the anthralin molecules dissolved in the oil phase and actually retained in it. Once the initial adsorption to the surface is complete, the surface is populated by anionic and / or non-ionic surfactant molecules. The anthralin molecules are no longer concentrated on the surface and are completely protected by the negatively charged surfaces, which prevent the hydroxyl ions and other decomposition initiators from approaching. Such a situation is shown by the accompanying drawing, in which the anthralin molecules remain in the oily phase and the line a, a 'is the surface of the particles, oil droplets or micelles. The adsorbed ions, which give the surface its negative charge, are called potential-determining ions and come from the anionic surfactants. Immediately adjacent to this surface layer is a range of tightly bound molecules of the continuous water phase together with some positive ions, mainly hydronium ions, which are also tightly bound to the surface. The boundary of this area is indicated by line b, b '. The potential at line b, b 'is still negative, but there are fewer cations than are bound to the negative layer. In the area connected by lines b, b 'and c, c' there is an excess of negative ions. Beyond line c, c ', the distribution of the ions is uniform, with electrical neutrality being obtained. The line c, d 'shows the outer limit.

According to the present invention, the anionic surfactants are used as stabilizing agents for anthralin compositions, a dramatic improvement in the stability of anthralin being achieved. The anionic surfactants are believed to protect the anthralin molecules from attack by forming a negatively charged surface, forming micelles or by surface separation. Despite the fact that the anionic surfactants, when used in an anthralin-stabilizing amount, bring about the described advantages of the present invention, the stabilization can be further improved by using antioxidants, as have been used in the past in anthralin-containing compounds.

The acid stable, water soluble, anionic surfactants used in the present invention are readily available compounds which can typically be selected from such non-soapy surfactants such as alkyl sulfates, alkyl sulfonates, alkyl benzene sulfonates, α-sulfonyl fatty acid alkyl phosphates, dioctyl sulfosuccinates, Isoethionates, alkyl ether sulfates and methyl sarcosines. Mixtures of such surfactants can also be used.

Contrary to the teachings of the prior art, the compositions of the present invention show long-term stability without the addition of water-soluble antioxidants, although they can be added for improved results.

It has also been found that the anionic surfactants that can be used in accordance with the present invention when used in conjunction with oil soluble antioxidants dramatically increase anthralin stability. Typical such antioxidants are ascorbyl palmate, hydroquinone, propyl gallate, nordihydroguaiaretinic acid, BHT, BHA, a-tocopherol, phenyl-a-naphthylamine and lecithin. It has also been found that water-soluble antioxidants can also be used in the aqueous phase. Typical such antioxidants are sodium sulfite, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, sodium formaldehyde sulfoxylate, acetone sodium metabisulfite, ascorbic acid, isoascorbic acid, thio-glycerol, thiosorbitol, thiourea, thioglycolic acid and cysteine hydrochloride.

According to the present invention, the anionic surfactants can also be used with nonionic surfactants, such as polyalkoxy ethers, polyalkoxy esters, poly alkoxy amides, fatty acid esters of polyhydric alcohols and fatty alcohols, which minimize the possibility of skin irritation caused by anions. If desired, the anionic surfactants can also be used in combination with compatible thickeners, such as methyl cellulose, tragacanth, sodium alginate, Carbopol 934 (CTFA), bentonite, carboxymethyl cellulose and vee-gum (CTFA). As used above and elsewhere in this description, (CTFA) indicates that the name of the nomenclature from “CTFA Cosmetic Ingredient Directory, 3rd Ed.”, Published by CTFA Association Inc., was used.

Because of the poor stability of anthralin in dermatological compositions, anthralin-containing compositions were rare, but when sold, they had anthralin concentrations greater than 0.5% by weight. As a result of the improved anthralin stability of the present invention, it is now possible to offer highly stable preparations with regard to both the anthralin concentration and the physical stability of the formulations themselves. Such formulations are extremely effective in the topical treatment of psoriasis. Such preparations have anthralin concentrations of 0.1-5.0% by weight or more and are useful for the external treatment of psoriasis in patients. Furthermore, the results of studies on accelerated high temperature storage and Arrhenius diagrams of the data from such formulations allowed stability requirements of anthralin and formulations for a period of time exceeding two years at room temperature, the stability being determined by the HPLC method. For the purposes of these studies, retention of less than 90% anthralin concentration was considered unacceptable.

To demonstrate the stability of anthralin-containing products according to the present invention, gel compositions containing 1% by weight of anthralin (plus 0.05% by weight excess) were made in accordance with the base gel composition outlined below in Example 1 is explained. All such gel compositions corresponded to the base gel composition and were identical with the exception of the surfactant used. In addition to the gel compositions made with the acid-stable, water-soluble anionic surfactant according to the present invention, gel compositions were made using the cationic amine surfactant Richamate 1655, a product of the Richardson Company, and using triethanolamine stearate, an acid-stable, water-soluble anionic surfactant to demonstrate the lack of anthralin stability in gels containing members of such classes of surfactants. The samples were evaluated under storage conditions at room temperature, at 35 C and at 45 C.

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659 945

Example 1 Base Gel Composition:

Part A

Mineral oil (USP)

Propyl gallate

BHT

Salicylic Acid Oleth-2 (CTFA)

Isoceteth-20 (CTFA) ascorbyl parmacy anthralin

part B

PEG-8 (CTFA)

Sorbitol solution (70%)

EDTA

Sodium bisulfite

Ascorbic acid surfactant purified water (USP)

164 0.5 2.0 2.0 60.0 200.0 1.0 10.5

50.0 20.0 1.0 1.0

10.0 5.0

q.s. 1000.0

s The compositions were made by mixing the components of Part A and warming to a temperature of 90 ° C. The stirring was continued until all solid parts were mixed. The compositions of Part B were mixed in a separate vessel and heated to 90 ° C with constant stirring until all solids were dissolved. Part B was added to Part A and the resulting mixture was stirred. Stirring was continued for 10 minutes while maintaining the temperature at 90 ° C. The resulting gel was cooled to the packaging temperature and packed under an inert gas in aluminum tubes which were suitably coated on the inside so that no reaction with the product was possible.

Table 1

Anthralin stability

Surfactant composition

Stock originally,

Equivalent to

Equivalent to

temperature

%

for 45 d,%

for 215 d,%

A. Sodium lauryl sulfate

RT

1.05 ° C

1,027

1.09

35 ° C

1.05 ° C

*

0.96

45 ° C

1.05 ° C

1,006

0.718

B. Cationic Amine (Richamate 1655)

RT

1.05 ° C

0.529

0.42

35 ° C

1.05 ° C

0.0

0.0

45 ° C

1.05 ° C

0.0

0.0

C. Triethanolamine stearate

RT

1.05 ° C

0.599

0.084

35 ° C

1.05 ° C

*

0.0

45 ° C

1.05 ° C

0.00343

0.058

D. Sodium dioctyl sulfosuccinate

RT

1.05 ° C

1,045

1.07

35 ° C

1.05 ° C

*

0.989

45 ° C

1.05 ° C

0.978

0.762

E. Sodium alkyl olefin sulfonate

RT

1.05 ° C

1,080

1.06

35 ° C

1.05 ° C

*

0.935

45 ° C

1.05 ° C

1,012

0.800

F. Sodium cocyl isothionate

RT

1.05 ° C

1,076 **

1.09 **

35 ° C

1.05 ° C

*

0.958

45 ° C

1.05 ° C

1,026

0.833

G. DEA olet-3-phosphate

RT

1.05 ° C

1,091

1.09

35 ° C

1.05 ° C

*

0.989

45 ° C

1.05 ° C

1,049

0.777

H. Sodium Laureth Sulfate

RT

1.05 ° C

1,089

1,094

35 ° C

1.05 ° C

*

0.982

45 ° C

1.05 ° C

1,046

0.585

I. sodium lauryl sulfonate

RT

1.05 ° C

1,069

1,054

35 ° C

1.05 ° C

*

0.928

45 ° C

1.05 ° C

0.943

0.781

J. Sodium octoxynol 3-sulfonate

RT

1.05 ° C

1,378

0.994

35 ° C

1.05 ° C

*

0.936

45 ° C

1.05 ° C

1,019

0.785

* Determination was not made

** Although the data for 45 d and 215 d indicate that the 215 d samples were more stable than those of 45 d, this is attributed to the fact that the analytical method was not sensitive enough to detect differences from such low concentrations to distinguish.

The base gel compositions of Example 1 were used with higher surfactant concentrations to show the upper limits of the range in which the acid-stable water-soluble anionic surfactants according to

65 lying invention can be used. Despite the fact that even higher concentrations are possible, skin irritation is a limiting factor. Table 2 below explains the results of this study.

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Table 2

659 945

Composition of surfactants

Stock originally,

Equivalent to

Equivalent to

temperature

%

for 45 d,%

for 215 d,%

Sodium lauryl sulfate (5%)

RT

1.05 ° C

1,068

1.09

35 ° C

1.05 ° C

*

*

45

1.05 ° C

0.978

0.136

Sodium lauryl sulfate (10%)

RT

1.05 ° C

1.01

1.03

35 ° C

1.05 ° C

*

0.932

45 ° c ***

1.05 ° C

0.389

0.119

*** The loss of activity is believed to be caused by tube leaks due to defective covering and loss of viscosity at high temperatures.

* No determination was made.

Example 2

A satisfactory gel composition was made from the following formula:

Part A g

Anthralin (including excess) 1.15

Isoceteth-20 (CTFA) 20.0

Mineral oil (USP) 16.0

Oleth-2 (CFTA) 6.0

Salicylic acid 0.2

Ascorbyl palmitate 0.1

BHT 0.1

Propyl gallate 0.01

part B

PEG-8 (CTFA) 5.0

Sorbitol solution (70%) 2.0

Ascorbic acid 1.0

Sodium lauryl sulfate 0.3

Citric acid 0.1

Sodium bisulfite 0.05

EDTA 0.01 purified water (USP) q.s. 100.00

The gel was made by mixing the components of Part A and heating to a temperature of 90 ° C. Stirring was continued until all solids were mixed. In a separate vessel, the components from Part B were mixed and heated to 90 ° C, stirring continuously until all solids were dissolved. Part B was mixed with Part A and held at 20 90 ° C for 10 min with continued stirring. The gel obtained was cooled to packaging temperature and packaged in an inert gas atmosphere in aluminum tubes which had a non-reactive inner coating.

The composition of Example 2 was subjected to clinical evaluation. The same composition was used in all cases, except that the anthralin concentration was varied. The clinical trials were conducted by clinical dermatologists with extensive experience in evaluating drugs used in the treatment of psoriasis.

The clinical studies show that the gel compositions of the present invention containing 0.5-2% by weight of anthralin gave particularly good results in patients 35 who received a once-daily short-term therapy of 10-20 minutes for a period of 6 weeks. The patients treated in this way had psoriasis ranging from localized injuries to injuries over most of their body surface. Patients 40 were evaluated after six weeks. The results of such evaluations are shown in Table 3 below and clearly show the effectiveness of gels containing 0.5-2% by weight of anthralin which have been stabilized by means of the present invention.

Table 3

Anthralin

Skin contact

place of

Clinical

No. of

Head of

%

Time min

application

Answer**

Patient

investigation

1% 1st week

20th

overall good

9

Dr. H

2% 5 weeks

10th

body

1% 1st week

20th

only from

10th

Dr. R

2% 5 weeks

10th

Injuries drawn

0.5% 1st week

20th

only from

10th

Dr. E

1% 5 weeks

10th

Injuries *

drawn

0.5% 1st week

20th

only from

20th

Dr. V / E

1% 5 weeks

10th

Injuries *

drawn

0.5% 1st week

20th

only from

11

Dr. B

1% 5 weeks

10th

Injuries *

drawn

* The entire body application was started here, but the irritation of the non-involved skin was so great that the protocol was changed so that the treatment was only limited to the injuries - after that no problems occurred.

** Used here means good to moderate exemption and excellent means significant to complete exemption.

659 945

It is worth noting that the clinical evaluation started with the compound of Example 6. Preliminary results showed no difference in clinical efficacy in short-term psoriasis treatments between the composition of Example 2 (containing a water-soluble antioxidant in the aqueous phase) and the composition of Example 6 (containing no water-soluble antioxidant in the aqueous phase).

It should be emphasized here that solving the problem of anthralin stability with the compositions according to the invention facilitates the use of short-term therapy and is extremely advantageous for the treatment of psoriasis.

Example 3

A satisfactory cream preparation was made by the following formula

Part A g

Petrolatum 200.0

Mineral Oil (USP) 50.0 Steareth-2 (CTFA) 12.5 Steareth-100 (CTFA) 2.5 Anthralin '11.5+

Anthralin Purified Water (USP)

q.s.

5.75 4.0

Syncrowax HGL-C (Croda)

Syncrowax ERL-C (Croda)

Petrolatum

Mineral oil (USP)

Salicylic acid

Propyl gallate

BHT

Ascorbyl palmitate

Sodium lauryl sulfate

Ascorbic acid

45.0 15.0 310.0 120.0 0.5 0.05 0.25 0.5 2.5. 0.25

10th

The sodium lauryl sulfate and ascorbic acid were dissolved in the water and added to the other components, which were premixed at 80 ° C and then cooled to 75 ° C. The composition was then poured into molds, cooled to solidify and packaged.

Example 5

A satisfactory ointment composition was made from the following formula:

20th

(including 15% surplus

Salicylic acid 3.5

Propyl gallate 0.05

BHT 0.5

Ascorbyl palmitate 0.5

part B

Sodium lauryl sulfate 1.50

Ascorbic acid 2.0

PEG-8 (CTFA) 60.0

dried sodium phosphate 0.75

EDTA 0.5

Sorbic acid 0.5

Xanthan Gum (USP) 3.25

purified water q.s. 500.00

The cream was made by mixing the components of Part A and heating to a temperature of 70 ° C. Stirring was continued until all solids were mixed. In a separate vessel, the components from Part B were mixed and heated to 70 ° C, stirring continuously until all solids were dissolved. Part B was mixed with Part A and stirring continued while maintaining the temperature at 70 ° C until both parts were thoroughly mixed. The cream obtained was cooled to packaging temperature and packaged.

Example 4

A satisfactory pen composition was made from the following formula:

Cetostearyl alcohol white soft paraffin liquid paraffin

Sodium lauryl sulfate

Salicylic acid

Ascorbyl palmitate

BHA

EDTA

Ascorbic Acid Anthralin Purified Water (USP)

q.s.

280.0 500.0 200.0 5.0 2.0 1.0 0.5 0.05 0.05 11.5 4.00

All components, except anthralin, were mixed extensively with water at 75 ° C until the blistering stopped. Then the anthralin was added and stirring continued for an additional 30 minutes. The composition was cooled to 55 ° C and packaged.

Examples 6 and 7 set out two further gel compositions that can be prepared according to the method described in Example 1 and are extremely stable under extended storage conditions.

35

Part A anthralin

Isoceteth-20 (CTFA) 40 Oleth-2 (CTFA) mineral oil (USP) propyl gallate BHT

Salicylic acid 45 ascorbyl palmitate

part B

PEG-8 (CTFA)

Sorbitol (70% solution) according to EDTA

Citric acid sodium lauryl sulfate purified water (USP)

Example 6

Example 7

60

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Part A anthralin

Isoceteth-20 (CTFA) Oleth-2 (CTFA) mineral oil (USP) propyl gallate BHT

Salicylic acid ascorbyl palmitate

part B

PEG-8 (CTFA) sorbitol (70% solution)

G

11.5 200.0 60.0 165.0 0.1 1.0 2.0 1.0

50.0 20.0 0.2 5.5 5.0

q.s. 1000.0

10.5 200.0 60.0 160.0 0.5 2.0 2.0 1.0

50.0 20.0

Ascorbic acid 10.0

Sodium bisulfite 1.0

EDTA 1.0

Sodium lauryl sulfate 5.0

purified water (USP) q.s. 1000.0

659 945

Although the anthralin compositions of the present inventions can be formulated and used as creams, gels, ointments or stick form, the cream or gel forms are preferred for ease of application.

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1 sheet of drawings

Claims (4)

659 945 PATENT CLAIMS 1. Pharmaceutically acceptable composition which is suitable for the topical treatment of psoriasis and contains water, an oil-soluble antioxidant and anthralin in sufficient amounts to achieve an antipsoriatic effect, characterized in that the composition contains an acid-stable water-soluble anionic surfactant an amount sufficient to stabilize the anthralin. 2nd s io 15 20th 25th 30th 35 40 45 50 55 60 65 2-5, characterized in that it contains 0.5-2.0% by weight of anthralin and that the surfactant is selected from the non-soapy anionic surfactants from the group consisting of alkyl sulfates, sulfonates, alkylbenzenesulfonates, sulfonyl fatty acids, alkyl phosphates, dioctyl sulfosuccina -ten, isoethionates, alkyl ether sulfates and methyl sarcosines, the% by weight being based on the total weight of the composition. 11. Composition according to any one of claims 2-5, characterized in that it contains 0.1-5.0% by weight of anthralin and 0.05-10.0% by weight of the surfactant, the surfactant being a non-soapy anionic Surfactant is selected from the group consisting of alkyl sulfates, sulfonates, alkyl benzene sulfonates, sulfonyl fatty acids, alkyl phosphates, dioctyl sulfosuccinates, isoethionates, alkyl ether sulfates and methyl sarcosines, the weight percent being based on the total weight of the composition. 12. The composition according to claim 9, characterized in that it contains 0.1-5.0% by weight of the surfactant. 13. The composition according to claim 10, characterized in that it contains 0.3-1.0% by weight of the surfactant. 14. The composition according to claim 11, characterized in that the surfactant is sodium lauryl sulfate. 15. The composition according to claim 1, characterized in that it is an oil-in-water emulsion and that the emulsion contains no antioxidant in the aqueous phase. 16. The composition according to any one of claims 1-15, characterized in that it is in solid form. 17. The composition according to any one of claims 1-15, characterized in that it is a cream. 18. The composition according to any one of claims 1-15, characterized in that it is a gel. 19. The composition according to any one of claims 1-15, characterized in that it is an ointment. 20. The composition according to claim 1, characterized in that it is an oil-in-water or a water-in-oil emulsion and that the oil phase has a proportion of oil-soluble antioxidant which is sufficient to ensure the stability of the anthralin to increase. 21. The composition according to claim 20, characterized in that it is an oil-in-water emulsion. 22. The composition according to claim 20, characterized in that it additionally contains a proportion of water-soluble antioxidant in the aqueous phase which is sufficient to increase the stability of the anthralin. 23. The composition according to claim 1, characterized in that the anionic surfactant comprises a mixture of two or more anionic surfactants. 24. A process for the preparation of a pharmaceutically acceptable composition according to claim 1, characterized in that a proportion of acid-stable, water-soluble anionic surfactant is added to a composition which contains water, an oil-soluble antioxidant and anthralin. 25. The method according to claim 24, characterized in that the pH of the composition is adjusted to 5.3 or below. 26. The method according to claim 24, characterized in that the composition is an oil-in-water emulsion. 27. The method according to claim 26, characterized in that a water-soluble antioxidant is additionally added. Anthralin, also known as dithranol, was a well-known component in formulations used for the percutaneous treatment of psoriasis, a dermatological condition characterized by thick red-colored, silvery, scaly patches of skin, and which may or may appear as a few narrow injuries can cover large areas of the body. Despite the fact that dermatologists have followed a number of new ways of treating psoriasis in recent years, the large number of therapeutic agents and diets confirm the lack of recognized effectiveness of the majority of them. Treatment for psoriasis included the use of a variety of topical medications such as tars, tar derivatives, anthralin, mercury compounds, corticosteroids and keratolytics. Anthralin remains the treatment of choice for some dermatologists when treating psoriasis. In most hospitals, anthralin serves as the "main method" for the internal and external treatment of patients. For this purpose, anthralin is generally used in concentrations in the range of 0.05-5% by weight based on the total weight of the composition. In the following, the percentages by weight always mean the percentages by weight based on the total weight of the composition, 2. Composition according to claim 1, characterized in that the surfactant is stable at a pH of 5.3 and below. 3rd 659 945 unless otherwise stated. When used correctly, anthralin is extremely effective and its use is accompanied by minimal to no adverse reactions. Although anthralin is generally recognized to be highly effective in treating psoriasis, it has three main disadvantages: instability, skin and clothes coloring, and skin irritation. Anthralin is subjected to light-catalyzed oxidation, dimerization and / or chemical decomposition, producing 1,8-dihydroxyanthraquinone and 1,8, r, 8'-tetrahydroxy-10,10'-dianthrone and other unidentified by-products. Anthralin is known to be sensitive to decomposition by auto-oxidation (namely free radical oxidation). Its decomposition products are believed to be inactive in psoriasis chemotherapy. The "irritation" or "anthralin erythema" of the skin is primarily attributed to the original free radical intermediates of anthralin. The "coloring" of the skin by anthralin is attributed to its oxidation products, namely 1,8-dihydroxyanthraquinone or the dimer. Many solutions have been described in the literature to stabilize anthralin, but none has been sufficiently satisfactory. Typical prior art solutions are those described in US-A-4,203,969 and US-A-4,287,214. From US-A-3 203 969 it can be seen that the use of a water-soluble, oil-insoluble antioxidant or a combination of an acid and a water-soluble, oil-insoluble antioxidant in the continuous aqueous phase of a cream is critical. US-A-4,287,214 discloses that antioxidants such as ascorbic acid, BHA (butylated hydroxyanisole) and BHT (butylated hydroxytoluene) and other chemicals such as salicylic acid do not sufficiently stabilize anthralin while certain a-hydroxy acids do. Ponce-Waelsch and Hulsebosch, «Arch. Derm. Forsch., 249, 141-152 (1974) describe a Lactacyd pH 2® cream vehicle which contains anthralin. Table 1 of the cited publication shows that such a formulation has a lack of stability when it is analyzed by UV spectroscopy and thin-layer chromatography. Caron and Shroot, «J. Pharm. Sci., 70: 11. 1205-1207 (1981), describe salicylic acid in a composition containing 0.44% anthralin, which also contains cetyl, sodium lauryl sulfate, paraffin and petrolatum, although it is not clear here whether the composition Contains water and there is also no information regarding an anthralin-stabilizing effect, is caused by the components of the composition or in the concentration ranges in which such components can be used to produce a stable water and anthralin containing composition with effective anti-psoriatic concentrations. The methods were used to determine the stability of anthralin by means of high pressure liquid chromatography (HPLC), in Caron et al., «J. Pharm. Sci., 70: 11. 1205 (1981) or that described in "Pharmacopeial Forum", May-June 1982, pp. 1956-1957; "The United States Pharmacopeial Convention, Inc." are described. Instead of the commonly used “United States Pharma-copeia” (USP) method for determining stability, it was found that the prior art methods for stabilizing anthralin were not completely satisfactory, since they generally cause less stability than before was accepted. In contrast to the USP method, which is less than satisfactory for the determination of anthralin stability, the HPCL- Method a selective, sensitive and reproducible method for the determination of anthralin stability. Recent publications, like the ones mentioned earlier, have raised serious questions as to whether the USP and the British Pharmacopeia (BP) methods actually indicate the stability of anthralin. USP and BP are expected to soon replace their test method for all formulations containing anthralin with HPLC. For most commercial applications, concentrations of anthralin greater than 0.5% by weight are rare, but when sold for external use to patients, such compositions are subject to rapid loss of activity and oxidation of the anthralin. Where plaque psoriasis has spread over 20% of the body's surface, internal hospital treatment was required to avoid irritation to normal skin from contact with higher concentrations of anthralin formulations and to increase the stability of the product during rapid treatment check. A major disadvantage of low concentration formulations, i.e. about 0.5% or less, is that it is impossible to achieve a rapid treatment that is possible with formulations containing higher concentrations of anthralin. State of the art evidence indicates the following: a) Anthralin is sensitive to decomposition by auto-oxidation (free radical oxidation) and its decomposition products are inactive in the chemotherapy of psoriasis; b) the irritation or the anthralin erythema of the skin is mainly caused by originally biologically active free radical intermediates of anthralin; c) the coloring of skin and clothes by anthralin is based on its oxidation products, such as by its colored dimer or 1,8-dihydroxyanthraquinone. Previous attempts to stabilize anthralin against oxidation include the usual prevention methods, such as the use of ascorbic acid, BHA, BHT, EDTA (ethylenediaminetetraacetic acid), citric acid, adjusting the pH to an acidic value, reducing the process temperature, removing peroxides and sunscreen. However, none of the previous attempts to stabilize anthralin as described in the prior art have been useful. It is clear from the above that that the decomposition products of anthralin or the originally free radical intermediates are responsible for the irritation and coloring problems, which were considered inevitable in connection with anthralin therapy. If the anthralin stability could be increased, the irritation and coloring problems that are indirectly caused by the anthralin decomposition products would be solved at the same time. Although new anthralin formulations have been developed for better patient tolerance, more comfort and less discoloration, the instability of anthralin in such formulations as the loss of activity and a change in color from light yellow to brown to black is manifested as an unsolved problem previously remained. So far, no anthralin formulation has been known which has long-term stability of the anthralin and a physical stability of the formulation combined with an attractive appearance and an acceptable color. It is known that commercially available anthralin products discolour in a short time, the resulting appearance being very unattractive and unacceptable to the end user. It has now been found that the desired stabilization of anthralin is suitable for topical application5 10th 15 20th 25th 30th 35 40 45 50 55 60 65 659 945 3. Composition according to claim 1, characterized in that the surfactant is stable at a pH of 4 and below. 4. Composition according to claim 1, characterized in that the surfactant is stable at a pH of 3-4. 5. Composition according to claim 1, characterized in that the surfactant is stable at a pH of about 3.2. 6. Composition according to any one of claims 2-5, characterized in that it contains 0.5-5.0% by weight of anthralin and 0.05-10% by weight of surfactant, the% by weight on the total weight of the composition based. 7. Composition according to one of claims 2-5, characterized in that it contains 0.1-3.0% by weight of anthralin and 0.1-5.0% by weight of surfactant, the% by weight on the total weight based on the composition. 8. Composition according to one of claims 2-5. characterized in that it contains 0.5-2.0% by weight of anthralin and 0.3-1.0% by weight of surfactant, the% by weight being based on the total weight of the composition. 9. Composition according to one of claims 2-5, characterized in that it contains 0.1-3.0% by weight of anthralin and that the surfactant is selected from the non-soap anionic surfactants from the group consisting of alkyl sulfates, alkyl sulfonates, alkyl benzene sulfonates, Sulphonyl fatty acids, alkyl phosphates, dioctyl sulfone succinates, isoethionates, alkyl ether sulfates and methyl sarcosines, the weight percent being based on the total weight of the composition. 10. Composition according to one of the claims 4th Compositions for the treatment of psoriasis can be achieved by adding an anthralin-stabilizing portion of an acid-stable, water-soluble anionic surfactant to a composition which contains water, anthralin and an oil-soluble antioxidant and has a pH of 5.3 or less, whereby the composition optionally additionally contains a water-soluble antioxidant in the aqueous phase. In contrast to the teaching of US Pat. No. 4,203,969, the presence of a water-soluble antioxidant in the aqueous phase has now proven to be non-critical for the long-term stability of anthralin in formulations of the present invention. Although not critical, the presence of a water soluble antioxidant may be desirable.