AT393959B - METHOD FOR INCREASING THE STABILITY OF ANTHRALINE-CONTAINING AQUEOUS COMPOSITIONS - Google Patents

Description

AT393 959 B

Anthralin, also known as dithranol, is a common ingredient in preparations used for the percutaneous treatment of psoriasis, a skin condition characterized by thickened, reddened, silvery-scaly patches of skin that appear in a few small areas or large areas of the body can cover.

Although dermatologists have made a number of recent attempts to treat psoriasis in recent years, the large number of therapeutic agents and prescriptions demonstrate the lack of true effectiveness in the majority of them. Psoriasis was treated using a wide variety of topically applicable medications, for example tars, tar derivatives, anthralin, mercury compounds, corticosteroids and keratolytics.

Anthralin is still the treatment of choice for many dermatologists to treat psoriasis. In general, anthralin is therefore used in most hospitals as the main means of inpatient and outpatient treatment. For such purposes, the anthralin is generally used in concentrations of 0.05 to 5% by weight based on the total weight of the composition. Unless otherwise stated,% by weight hereinafter means the percent by weight based on the total weight of the composition. When used carefully, anthralin is extremely effective and its use is accompanied by minimal to no reactions

Although generally recognized as an extremely effective treatment for psoriasis, anthralin still has three distinct disadvantages: instability, skin and clothing staining, and skin irritation. Anthralin undergoes light catalyzed oxidation, dimerization and / or chemical decomposition, in which 1,8-dihydroxyanthraquinone and 1,8, r, 8'-tetrahydroxy-10, ΙΟ'-dianthrone and other unidentified by-products are formed.

It has been found that anthralin is capable of autooxidative degradation (free radical oxidation). Its breakdown products are believed to be ineffective in chemotherapy for psoriasis. The "irritation" or the "anthralinery topic" of the skin is likely to be caused primarily by the initial free radical intermediates of the anthralin. The formation of spots on the skin by anthralin is probably due to its oxidation products, namely the 1,8-dihydroxyanthraquinone or its dimer.

Many proposals for solving the problem of anthralin instability have become known in the art, but none have so far been satisfactory. Typical prior art solutions are those published in U.S. Patent Nos. 4,203,969 and 4,287,214. U.S. Patent 4,203,969 critically describes the use of a water-soluble, oil-insoluble acidic antioxidant or a combination of an acid and a water-soluble, oil-insoluble antioxidant in the continuous aqueous phase of a cream. U.S. Patent 4,287,214 mentions 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 alpha-hydroxy acids do. Ponce-Waelsch and Hulsebosch, Arch. Derm. Forsch. 249, 141-152 (1974) report an anthralin-containing Lactacyd pH2® cream carrier. Table 1 of this reference shows the low stability of such a formulation when analyzed by UV spectroscopy and thin-layer chromatography. Although Caron and Shroot, J. Pharm. Sei., 70: 11, 1205-1207 (1981) describe salicylic acid in a composition containing 0.44% anthralin, which also contains cetyl alcohol, sodium lauryl sulfate, paraffin and petrolatum, there is no clear indication here that the composition also contains water, nor is any effect on the stability of the anthralin indicated by any of the components of the composition or by concentration ranges in which these components are to be used to produce a stable composition containing water and anthralin at antipsoriatic levels .

High pressure liquid chromatography (HPLC) can be used to determine the stability of anthralin using the method described by Caron et al. in J. Pharm. 70: 11, 1205 (1981) or that is described in Pharmacopeial Forum, May-June 1982, pp. 1956-1957. Even when using the United States Pharmacopeial Convention, Inc. method instead of the more commonly used United States Pharmacopeia (USP) method to determine stability, it has been found that the prior art methods for stabilizing anthralin are not entirely satisfactory because they are generally result in less stability than originally planned. In contrast to the USP method, which is not at all satisfactory for determining anthralin stability, the HPLC method proved to be a selective, sensitive and reproducible method for determining the stability of anthralin. More recent publications referred to above have seriously considered whether the USP and British Pharmacopeia (BP) methods actually indicate the stability of anthralin. It is believed that both USP and BP will shortly switch their test methods to HPLC for all formulations containing anthralin.

For most commercial preparations, concentrations of anthralin above 0.5% by weight for outpatient use are rare, if at all on the market, since these compositions cause a rapid loss of the -2-

AT 393 959 B

Show effectiveness and oxidation of anthralin. If the psoriasis spots make up more than 20% of the body surface, an inpatient hospital treatment to avoid irritation of the healthy skin in contact with the more concentrated anthralin formulations and a stability control of the product during the rapid treatment was necessary. A major «: disadvantage of formulations with lower concentrations, i. H. about 0.5% or less by weight, is that they are unsuitable for rapid treatment, which is possible with more concentrated formulations of anthralin.

The prior art therefore states: a) anthralin is capable of autooxidative degradation (oxidation via free radicals) and its degradation products are ineffective in chemotherapy d psoriasis; b) the irritation or the anthralin theme of the skin is mainly caused by the initial, biologically active, free radical intermediates of the anthralin; c) The staining of the skin and clothing by the anthralin is due to its oxidation products, such as its colored dimer or the 1,8-dihydroxyanthraquinone.

The prior art attempts to stabilize the anthralin against oxidation include the usual methods, such as the use of ascorbic acid, BHA, BHT, EDTA (ethylenediaminetetraacetic acid), citric acid, adjustment of the pH to an acidic pH, Reduce process temperature, remove peroxides and protect from light. However, none of the previous attempts to stabilize anthralin have been satisfactory.

From what has been said above, the anthralinod degradation products "cause the initial free radical intermediates to cause irritation and staining, which have previously been thought to be an unavoidable side effect of anthralin therapy. If the stability of the anthralin could be improved, the problems of irritation and staining caused indirectly by the anthralin degradation products would be solved at the same time.

Although new formulations of anthralin products were developed for better tolerability by the patient, for better use and less discoloration, the instability of anthralin remained in these formulations, which resulted from a loss of effectiveness and a color change from light yellow to brown to black manifests a previously unsolved problem. No anthralin formulation has so far been available which shows long-term stability of the anthralin itself and a physical stability of the formulation, combined with an acceptable appearance and color. It is generally known that the commercially available anthralin products discolour in a very short time and at the same time acquire an extremely unattractive and unacceptable appearance for the end user.

According to US Pat. No. 4,203,969, the addition of a water-soluble antioxidant is required in anthralin formulations in the presence of water in order to improve long-term stability.

FR-OS 2 515 036 relates to anthralin compositions in which the anthralin is present as a solution in a fatty alkyl ester and which are said to be stable against oxidation by adding an antioxidant.

GB-PS 2 107 587 is based on the priority of this FR application, according to which these solutions or dispersions, together with aqueous solutions, are formulated to form a two-part hair shampoo, the components of which are mixed before use. A pH of 3-7 is set by adding an acid to the aqueous component. The finished anthralin compositions contain 0.01-5% by weight of anthralin.

However, these preparations are still unsatisfactory and also cannot be used for skin treatment itself.

Regardless of this, numerous publications deal with the creation of basic compositions as carriers for pharmaceutical preparations. Ointment and cream bases can consist of high fatty alcohols, glycols, plasticizers and optionally surface-active agents. Cationic, anionic or nonionic substances were used as such. Oily preparations containing oil-soluble surface-active substances are also known for the formulation of dermatological treatment agents.

The present invention relates to a method for increasing the stability of aqueous compositions containing anthralin, preferably in a concentration of 0.05 to 5.0% by weight, in the form of water-containing creams, gels or ointments for the topical treatment of psoriasis, which is an acid-resistant, water-soluble anionic surface-active agent for Stabilization of the anthralin and an oil-soluble antioxidant and optionally a water-soluble antioxidant, in addition to any other additives.

The compositions preferably contain 0.5 to 3.0% by weight and in particular 0.5 to 2.0% by weight of anthralin.

One or more non-soap, anionic surface-active agents are used as surface-active agents.

AT 393 959 B from the group alkyl sulfates, alkyl sulfonates, alkyl benzene sulfonates, sulfonyl fatty acids, alkyl phosphates, dioctyl sulfosuccinates, isethionates, alkyl ether sulfates and methyl sarcosines, preferably sodium lauryl sulfate. The concentration of this surfactant is preferably 0.05 to 10% by weight, preferably 0.1 to 5.0% by weight and in particular 03 to 1.0% by weight, based on the total weight of the composition. Surprisingly, it has been found that the stability of such anthralin compositions can be significantly increased if, according to the invention, the composition is prepared as a one-piece oil-in-water or water-in-oil emulsion with a pH of at most 5.3, the oil phase being the oil-soluble Antioxidant is added in an amount sufficient to increase the anthralin stability.

In contrast to the teaching of US Pat. No. 4,203,969, it was thus found that the presence of a water-soluble antioxidant in the aqueous phase is not important for the long-term stability of the anthralin in the formulations prepared according to the invention. Although the presence of such a water-soluble antioxidant is not necessary, it may be desirable in some cases.

Of course, higher concentrations of anthralin can be stabilized by the method according to the invention, but care must be taken when using such compositions that the irritation of healthy skin is avoided.

The pH of the one-piece aqueous compositions containing improved anthralin according to the invention, which according to the present invention necessarily contain an acid-resistant, water-soluble anionic surfactant, is 5.3 and below. Lower pH values are preferably used, the limit being given by the skin irritation. A pH of 4.0, in particular less than 3.4, is preferably used. The use of citric acid or salicylic acid is favorable.

The process according to the invention results in an anthralin product which has long-term stability of the anthralin, better tolerability by the patient and a cosmetically elegant appearance and shows practically no discoloration after storage in a suitably packaged form. It can be used successfully both in long-term outpatient treatment with a low concentration and in short-term inpatient treatment with a high concentration against psoriasis.

The process of the invention is believed to work because oil particles or droplets emulsified in liquid media are charged in one of two ways. The first type occurs through the reactive adsorption of special ions present in the solution. In the case of water, it can be the hydronium or the hydroxyl ion. Most of the oil particles or droplets emulsified in an aqueous medium are given a negative charge by the preferred adsorption of the hydroxyl ions. In the second type, charges appear on the oil particles or droplets resulting from the ionization of functional groups of the surfactants, e.g. B. the phosphates, carboxylates, sulfates and sulfonates, which may be present on the surface of the particle or at the interface since oil-water phases.

Molecules and ions that are adsorbed on surfaces or interfaces are called surfactants. Another term is amphiphilic, which indicates that the molecule or ion has a certain affinity for both polar and non-polar solvents. It is the amphiphilic nature of surfactant molecules or ions that is the cause of their adsorption at the interface, which is both can be a gas-liquid interface as well as a liquid-liquid interface.

The chemical structure of anthralin is shown as follows;

Anthralin is an amphiphilic molecule; in other words, anthralin has a certain affinity for both polar and non-polar bullheads. The amphiphilic nature of anthialin molecules also causes them to accumulate at the surface or interface where they can be more easily attacked. Under such conditions, oxidation initiators such as oxygen, light, hydrogen ions or metal ions can easily attack the anthralin and / or accelerate its degradation by free-radical auto-oxidation. High surface or interfacial concentration of the anthralin molecules also accelerates dimer formation through the intramolecular interaction. -4-

AT 393 959 B

The process of the present invention is believed to create oil particles or droplets or micelles which have a predominantly anionic surface charge that is caused either by the anionic surfactant or by the combination of nonionic surfactant (s) with anionic surfactant (s) are. The negatively charged surface is replaced by the functional groups, e.g. B. the sulfonates, phosphates, carboxylates etc. of the (r) anionic surface active «! Medium (s) evoked. The anionic groups of the acid-resistant surfactants are adsorbed on the surface at the oil-water interface and create a negatively charged surface for the oil droplets, particles or micelles. The cations of the aqueous phase are attracted to the negatively charged surface, which also repels all anions of the solution, such as hydroxyl, once the initial adsorption is complete. In addition to these electrical forces, thermal motion tends to produce 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 is in favor of the oil phase and is 5000 to 10,000 to 1. Therefore, the anthralin molecules in the case of preparations based on an oil-in-water emulsion, e.g. B. in creams, gels etc. or in emulsified ointments in the oil phase and are mainly retained in this. Once the initial adsorption on the surface is complete, the surface is occupied by anionic and / or nonionic surfactant molecules.The anthralin molecules cannot accumulate on the surfaces and are caused by the negatively charged surface, which rejects the approach of hydroxyl ions or other degradation initiators fully protected

Such a situation can be described by the diagram given in the drawing as Fig. 1, where the anthralin molecules are retained in the oil phase and the line (a-a ') represents the surface of the particle, oil drop or micelle. The adsorbed ions that give the surface their negative charge are called potential-determining ions and come from the (n) anionic surface-active agent. Immediately following this surface layer is an area of firmly bound molecules that continuously «! Water phase together with some positive ions, mostly hydronium ions, which are also firmly attached to the surface. The boundary of this area is given by the line (b-b '). The potential at line (b-b ') is still negative, but there are fewer "cations than there is a negative layer bound to d" in the area delimited by lines (b-b') and (c-c ') an excess of negative ions. Beyond the line (c-c ') the ion distribution is uniform and electrical neutrality is reached. The line (d-d') shows the outer limit.

The anionic surfactant (s) used in the present invention as stabilizers for the anthralin composition causes a dramatic increase in anthralin stability. It is believed that the anionic (s) ) Surfactant (s) protect the anthralin molecules from any attack by producing a negatively charged 'micelle-forming surface or surface detachment. Although the anionic surfactant (s), when used in an anthralin stabilizing amount, produce the above-mentioned advantages of the present invention, stabilization can still be achieved through the use of antioxidants be further improved, as was also used in the past for compositions containing anthralin.

The acid-resistant, water-soluble, anionic and surface-active agents used according to the invention are readily available compounds which are selected from non-soap surfactants, namely from alkyl sulfates, alkyl sulfonates, alkyl benzene sulfonates, alpha sulfonyl fatty acids, alkyl phosphates, dioctyl sulfosuccinates, isethionates and alkyl ether sulfates, alkyl ether sulfates. Sodium lauryl sulfate, sodium octoxynol-3-sulfonate, sodium dodecylbenzenesulfonate, sodium lauryl sulfonate, DEA-oleth-3-phosphate, sodium dioxtylsulfosuccinate, sodium cocyl isothionate, sodium laureth sulfate and sodium lauryl sarcosinate, mixtures of these, and surfactant surfactants can also be used.

In contrast to the prior art, the compositions produced according to the invention show long-term stability even without the addition of water-soluble antioxidants, although these can also be used to improve the results.

It has also been found that the anionic surfactants added in accordance with the present invention greatly increase the stability of anthralin when used in combination with oil soluble antioxidants. Typical such antioxidants are ascorbyl palmitate, hydroquinone, propyl gallate, nordihydroguaiaretsäure / ΒΉΤ, BHA, alpha-tocopherol, phenyl-alpha-naphthylamine and lecithin. It has also been found that water-soluble antioxidants can additionally 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, thioglycerin, thiosorbitol, thiourea, thioglycolic acid and cysteine hydrochloride.

The anionic surfactants used according to the invention can also be used with nonionic -5-

AT 393 959 B

Surfactants such as polyalkoxy ethers, polyalkoxy esters, polyacuoxy amides, fatty acid esters of polyhydric alcohols and fatty alcohols are used which minimize the possible skin stimulation caused by anions to a minimum. 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). The term CFTA mentioned above and below means that the name mentioned is used in the nomenclature of the CTFA Cosmetic Ingredient Directory, 3rd edition, published by the CTFA Association, Inc.

In the past, the anthralin-containing compositions were rarely, if ever, sold in dermatological compositions with anthralin concentrations of more than 0.5% by weight. As a result of the anthralin stability improved by the present invention, it is now possible to produce extremely stable one-piece preparations both in terms of anthralin concentration and the physical stability of the preparations themselves, these formulations being extremely effective in the topical treatment of psoriasis. Such preparations can contain anthralin concentrations of 0.1 to 0.5% by weight or more and are also suitable for the outpatient treatment of psoriasis. In addition, the results of the studies on the accelerated high-temperature shelf life and the Arrhenius curves of the results enable the were obtained with these formulations, a prediction of stability of both anthralin and the preparation for a period of more than two years under storage conditions at room temperature, the stability being examined by the HPLC method. For the purposes of these studies, remaining less than 90% of the anthralin concentration was considered unacceptable

To demonstrate the stability of the anthralin-containing products made in accordance with the present invention, gel compositions containing 1% by weight of anthralin (plus an excess weight of 0.05%) were made according to the base gel composition shown in Example 1 below Prepared All of these gel compositions corresponding to the base gel composition were identical except for the surfactant used. In addition to the gel compositions prepared according to the invention with the acid-resistant, water-soluble anionic surfactants, other gel compositions were made in which cationic amine surfactants, Richamate 1655, were a product Richardson Company, and triethanolamine stearate, a non-acid-resistant, water-soluble anionic surfactant, to demonstrate the lack of anthralin stability in gels containing such surfactants. The samples were examined under storage conditions at room temperature, at 35 and 45 ° C.

Example 1:

Basic gel composition

Part A gram

Mineral oil (USP) 164

Propyl gallate 0.5 BHT 2.0

Salicylic acid 2.0

Oleth-2 (CTFA) 60.0

Isoceteth-20 (CTFA) 200.0

Ascorbyl palmitate 1.0

Anthralin 10.5

Part B PEG-8 (CTFA) 50.0

Sorbitol solution (70%) 20.0 EDTA 1.0

Sodium bisulfite 1.0

Ascorbic acid 10.0

Surfactant 5.0 purified water (USP) ad 1000.0

The compositions were prepared by mixing the components of Part A and heating to a temperature of 90 ° C. Stirring continued until all solids were mixed. The ingredients of Part B were mixed in a separate vessel and heated to 90 ° C, stirring also until all solids -6-

AT 393 959 B were solved. Part B was added to Part A and the resulting mixture was stirred. The mixture was then stirred for a further 10 min, the temperature being kept at 90 ° C. The resulting gel was cooled to packaging temperature and packed under inert gas in aluminum tubes which were coated on the inside to avoid reactions with the product.

Table I

Anthralin stability

Composition of storage beginning after the surfactant temperature 45 215 days A. Sodium lauryl sulfate RT 1.05% 1.027% 1.09% 35 ° C 1.05% * 0.96% 45 ° C 1.05% 1.006% 0.718% B. Cationic amine RT 1.05% 0.529% 0.42% (Richamat 1655) 35 ° C 1.05% 0% 0% 45 ° C 1.05% 0% 0% C. Triethanolamine RT 1.05% 0.599% 0.084% stearate 35 ° C 1.05% * 0% 45 ° C 1.05% 0.00343% 0.058% D. sodium dioctyl RT 1.05% 1.045% 1.07% sulfosuccinate 35 ° C 1.05% * 0.989% 45 ° C 1.05% 0.978% 0.762% E. Sodium alkyl RT 1.05% 1.080% 1.06% olefin sulfonate 35 ° C 1.05% * 0.935% 45 ° C 1.05% 1.012% 0.800% F. Sodium Cocyl RT 1.05% 1.076% 1.09% 1 2 isothionate 35 ° C 1.05% * 0.958% 45 ° C 1.05% 1.026% 0.833% G. DEA Oleth-3 RT 1 , 05% 1.091% 1.09% phosphate 35 ° C 1.05% * 0.989% 45 ° C 1.05% 1.049% 0.777% H. sodium laureth-RT 1.05% 1.089% 1.094% sulfate 35 ° C 1, 05% * 0.982% 45 ° C 1.05% 1.046% 0.585% I. Sodium Lauryl RT 1.05% 1.069 % 1.054% sulfonate 35 ° C 1.05% * 0.928% 45 ° C 1.05% 0.943% 0.781% J. sodium octoxynol RT 1.05% 1.378% 0.994% 3-sulfonate 35 ° C 1.05% * 0.936 % 45 ° C 1.05% 1.019% 0.785% -7- 1 No determination was made 2 although the values for 45 and 215 days sometimes indicate that the samples had a greater stability after 215 days than after 45 days this is due to the fact that the analytical method is not sensitive enough to detect such small differences in concentration.

AT 393 959 B

The base gel composition of Example 1 was used with higher concentrations of surfactants to show the upper limits of the range at which the acid-resistant water-soluble surfactant according to the present invention can be used. Although higher concentrations are possible, a limiting factor is skin irritation. The following Table II illustrates the results of this study.

Table Π

Surfactant storage start after

Composition temperature 45 215

Days

Sodium lauryl RT 1.05% 1.068% 1.09% sulfate (5%) 35 ° C 1.05% * * 45 ° C *** 1.05% 0.978% 0.136% sodium lauryl RT 1.05% 1.01% 1.03% sulfate (10%) 35 ° C 1.05% * 0.932% 45 ° C *** 1.05% 0.389% 0.119% *** It is believed that the loss of activity of these samples is due to leaks in the tubes is due to poor sealing of the tubes, whereby the viscosity has decreased at the high temperature; * no determination made

Example 2:

A satisfactory gel composition was made according to the following recipe:

Part A gram

Anthralin (including 15% excess) 1.15

Isoceteth-20 (CTFA) 20.0

Mineral oil (USP) 16.0

Oleth-2 (CTFA) 6.0

Salicylic acid 0.2

Ascorbyl palmitate 0.1 BHT 0.1

Propyl gallate 0.01

Part B 5.0 2.0 1.0 0.3 0.1 0.05 0.01 ad 100.00 PEG-8 (CTFA)

Sorbitol solution (70%)

Ascorbic acid

Sodium lauryl sulfate

Citric acid

Sodium bisulfite

EDTA purified water (USP)

The gel was made by mixing the components of Part A and heating to a temperature of 90 ° C. Stirring continued until all solids were mixed. In a separate vessel, the components of Part B were mixed while heating to 90 ° C and continued to stir until all solids dissolved -8- 4

AT393 959 B. Part B was mixed into Part A and further stirred for 10 minutes while maintaining the temperature at 90 ° C. The resulting gel was cooled to packaging temperature and packed in aluminum tubes which had an inert inner coating under an inert gas atmosphere.

The composition of Example 2 was subjected to clinical review. The same composition was used in all cases, only the anthralin concentration was varied. The clinical trials were conducted by clinic dermatologists who have extensive experience in evaluating medications used to treat psoriasis.

These clinical studies show that the gel compositions made according to the invention containing 0.5-2% by weight of anthralin gave particularly good results to patients with a once-daily short-term therapy of 10 to 20 minutes during a six-week treatment period. The patients treated in this way had psoriasis, which ranged from localized infestation to an affection over the main part of their body area. The patients were assessed after six weeks. The results of this assessment are given in the following table ΠΙ and clearly show the effectiveness of the gel stabilized according to the invention with an anthralin content of 0.5-2% by weight.

Tables!

Anthralin (%) Treatment skin contact time (min.) Applied to: Clinical result ** Number of d. Patient test leader 1% 1st week 20 total good 9 Dr.H. 2% 5 weeks 10 body 1% 1st week 20 only ex- 10 Dr.H. rich draws 2% 5 weeks 10 0.5% 1st week 20 only ex- 10 Dr.E. rich * records 1% 5 weeks 10 0.5% 1st week 20 only ex- 20 Dr.V / E rich * records 1% 5 weeks 10 0.5% 1st week 20 only ex- 11 Dr .B 1% 5 weeks 10 rich * marks * application to the whole body at the beginning, but due to the extent of skin irritation of the healthy skin, treatment instructions changed to area-specific treatment - no problems. * * The rating "good" means moderate to significant healing and "excellent" means significant to complete healing.

It should be emphasized here that solving the problem of anthralin stability by means of the compositions produced according to the invention facilitates the use of short-term therapy and is extremely advantageous for the treatment of psoriasis. -9-

AT 393 959 B

Example 3:

A satisfactory cream preparation was prepared according to the following recipe:

Part A Gram of Petrolatum Mineral Oil (USP) Steareth-2 (CTFA) Steareth-100 (CTFA) Anthralin Salicylic Acid Propyl Gallate BHT Ascorbyl Palmitate Part B 200.0 50.0 12.5 2.5 11.5+ (including 15% overweight) 3.5 0.05 0 , 0.5 0.5 sodium lauryl sulfate ascorbic acid PEG-8 (CTFA) Dried sodium phosphate EDTA sorbic acid xanthan gum (USP) 1.50 2.0 60.0 0.75 0.5 0.5 3.25

Purified water (USP) ad 500.00

The cream was prepared by mixing the ingredients of Part A and heating to a temperature of 70 ° C. Stirring continued until all solids were mixed. In another vessel, the components of Part B were mixed and heated to 70 ° C, stirring continuously until all solids were dissolved. Part B was mixed into Part A with further stirring, keeping the temperature at 70 ° C until both parts were mixed thoroughly. The resulting cream was cooled to packaging temperature and packaged.

Example 4:

A satisfactory composition for a stick was made according to the following recipe:

Grams of Syncrowax HGL-C (Croda) Syncrowax ERL-C (Croda) petrolatum mineral oil (USP) salicylic acid propyl gallate BHT ascorbyl palmitate sodium lauryl sulfate ascorbic acid anthralin purified water (USP) 45.0 15.0 310.0 120.0 0.5 0.05 0.25 0.5 2. 5 0.25 5.75 4.0

Sodium lauryl sulfate and ascorbic acid were dissolved in water and added to the other ingredients which had been premixed at 80 ° C and then cooled to 75 ° C. The composition was poured into molds, allowed to cool, removed and packaged -10-

Claims (1)

AT 393 959 B Example 5: A satisfactory ointment composition was prepared according to the following recipe: Cetostearyl alcohol, gram 280.0 White soft paraffin 500.0 Liquid paraffin 200.0 Sodium lauryl sulfate 5.0 Salicylic acid 2.0 Ascoibyl palmitate 1.0 BHA 03 EDTA 0.05 Ascorbic acid 0.05 Anthralin 113 Purified Water 4.0 All ingredients except anthralin were vigorously mixed with the water at 75 ° C until the bubbling stopped. Then the anthralin was added and stirring was continued for a further 30 minutes. The composition was cooled to 55 ° C and packaged. Although the anthralin compositions according to the present invention can be formulated and used in cream, gel, ointment or stick form, the cream or gel forms are preferred because of their ease of use. PATENT CLAIM Process for increasing the stability of aqueous anthralin, preferably in a concentration of 0.1 to 5.0% by weight, particularly preferably 0.5 to 3.0% by weight and in particular 0.5 to 2.0% by weight % containing compositions in the form of water-containing creams, gels or ointments for the topical treatment of psoriasis, which is an acid-resistant, water-soluble anionic surface-active agent for stabilizing the anthralin, preferably in a concentration of 0.05 to 10% by weight, preferably 0.1 to 5.0% by weight and in particular 0.3 to 1.0% by weight, based on the total weight of the composition, namely one or more non-soap, anionic surface-active agents from the group consisting of alkyl sulfates, alkyl sulfonates, alkylbenzenesulfonates, sulfonyl fatty acids, alkyl phosphates, Dioctyl sulfosuccinates, isethionates, alkyl ether sulfates and methyl sarcosines, preferably sodium lauryl sulfate, as well as an oil-soluble antioxidant and optionally a water-soluble one hes antioxidant, optionally containing other additives, characterized in that the composition is prepared as a one-piece oil-in-water or water-in-oil emulsion with a pH of at most 53, the oil phase containing the oil-soluble antioxidant in one Sufficient amount is added to increase the anthralin stability. Add 1 sheet of drawing -11-