WO2006119540A1

WO2006119540A1 - Preparation for treating psoriasis

Info

Publication number: WO2006119540A1
Application number: PCT/AU2006/000575
Authority: WO
Inventors: Jenny Nicolopoulos
Original assignee: Jenny Nicolopoulos
Priority date: 2005-05-11
Filing date: 2006-05-03
Publication date: 2006-11-16

Abstract

There is disclosed herein a topical preparation for the treatment of psoriasis, the preparation comprising as active ingredients: therapeutically effective amounts of dithranol, tar, beta hydroxy acid, urea and an alpha-hydroxy acid, together with a suitable carrier. There is also disclosed herein the use of dithranol, tar, a beta hydroxy acid, urea and an alpha-hydroxy acid in the preparation of a topical medicament for treating psoriasis or for maintaining psoriasis remission.

Description

PREPARATION FOR TREATING PSORIASIS Technical Field

The present invention relates to a preparation for treating psoriasis and a method of treating psoriasis using the preparation. Background of the Invention

Psoriasis is a chronic skin condition and is thought to be a primary immunologic disorder that leads to secondary epidermal hyperproliferation. Psoriasis is non-contagious and can occur anywhere on the body but typically occurs on the back of elbows and knees, in the umbilicus, natal cleft (between the buttocks), back, hands, feet, nails, knuckles, genitalia, face, chest and in the scalp. Psoriasis is quite common, affecting about 2% of the population.

One form of psoriasis, plaque psoriasis, is characterized by hyperproliferation of skin (hyperplasia) above an erythematous base and results in dry rough, well demarcated, slightly raised patches, plaques or papules on the skin surface with a covering of fine, dry, silvery/white scales most often on the elbows, knees and lower back. Plaque psoriasis results in greatly increased production of epidermal cells (causing a red colour) with rapid turnover of the skin cells (causing lichenification/scaling and shedding). Dilated capillaries underlie the scales producing the erythematous base. Scalp psoriasis is similar to plaque psoriasis and is characterized by one or more scaly plaques in the scalp. Chronic plaque psoriasis and scalp psoriasis comprise greater than 90% of all psoriasis.

The rash may be unsightly, itchy or may result in a burning sensation. Continual scratching due to itching may remove scales and produce bleeding sites. Itchiness may be so severe that the patient may need to be admitted to hospital for treatment when the bleeding is accompanied by trauma and/or infection. Psoriasis is rarely life threatening but may be accompanied by fever, diarrhoea and/or malaise and can cause significant morbidity, social embarrassment, financial cost and disruption in the patient's life. In a small number of cases persons with psoriasis may develop debilitating psoriatic arthritis (a joint disease related to psoriasis). It would be desirable therefore to provide a preparation suitable for treating psoriasis. Various treatments are known for treating psoriasis. However, to date no cure for psoriasis is known. With most presently available preparations, some control may be possible for most patients. Most treatments presently available aim to reduce the rapid rate of cell growth and/or act as keratolyses, antiinflammatories, prostaglandin production inhibitors or DNA synthesis inhibitors. However, psoriasis is difficult to manage in general practice, mainly because the standard treatments produce a number of side effects, or are ineffective in both the short and long term.

Treatments and preparations used by dermatologists and known to date include:

(a) Use of oral or topical steroids, corticosteroids or glucocorticosteroids such as the topical corticosteroids (Diprosone®, Valisone®). However as steroids, corticosteroids and glucocorticosteroids can be absorbed into the blood circulation, the use of steroids, corticosteroids and glucocorticosteroids may result in side effects particularly when treating a large body surface area or using a strong steroid. Side effects include decreased connective tissue synthesis and thinning of the skin, skin atrophy, weakened and dilated blood vessels, stretch marks, acne, bone loss, increased body hair (hypertrichosis), increased susceptibility to infections, suppressed growth in children, rosacea, telangiectasia, perioral dermatitis, bruising, adrenal suppression, progression to more active forms of psoriasis (such as pustular or erythrodermic psoriasis) and flare up of the psoriasis when the medication is discontinued. Also steroids, corticosteroids or glyucocorticosteroids may have associated tachyphylaxis leading to decreased efficacy with continued use. Because of the side effects and possible development of immunity, steroids, corticosteroids or glyucocorticosteroids are typically only used for about one to two weeks and are frequently used in combination with other agents.

(b) Use of topical preparations including dithranol (also called anthralin). Formulations available include Micanol® cream, Dithrocreme®, DithrocremeHP® and

Dithroscalp®. Dithranol causes no systemic or long term side effects but has to be used carefully as it may be irritating if applied to normal skin and can cause purple/brown staining of clothes, hair and skin.

(c) Use of topical preparations including tar such as coal tar ointments and shampoos. The coal tar can be combined with other actives such as dithranol (for example in psorin® ointment or gel), combined with topical corticosteroids or the preparation may be used with UV light therapy. Tar has minimal side effects however it can cause mild skin irritation and has an unpleasant odour and can stain. Side effects include folliculitis and contact allergy. (d) Use of keratolytics such as salicylates including salicylic acid. Salicylic acid may be combined with other actives such as dithranol, tar or corticosteroids. Keratolytics can cause some side effects for example keratolytics may cause tinnitus, nausea and vomiting. (e) Use of oral and topical preparations containing vitamin A (retinoids) or vitamin D derivatives:

(el) Vitamin A derivatives (retinoids) such as topically applied tazarotene have been used to treat psoriasis. Systemic retinoids have been used for the treatment of recalcitrant severe psoriasis. However oral retinoids such as etretinate or acitretin are associated with severe adverse effects such as teratogenicity, serum lipid and transaminase elevations, mucocutaneous toxicity, skeletal changes, mouth ulcers and hair loss. Topical retinoids were developed to avoid these systemic side effects. However topical retinoids are expensive, may be teratogenic, irritating to non-involved skin and may cause redness and burning and pruritus. Also the efficacy of retinoids is slow and begins with reduction of plaque thickness and some improvement in redness and scaling usually occurs after about three months. Retinoids may be used in combination with topical corticosteroids where the effects of the retinoid may be enhanced, skin irritation decreased and some side effects reduced. Retinoids may also be used in combination with vitamin D derivatives or with UV light treatment.

(e2) Oral vitamin D (D2 and D 15) or topical vitamin D analogs such as calcipotrieiie (vitamin D₃) or calcipotriol have been used to treat psoriasis. The ingestion of vitamin D however may cause kidney stones and an irregular heart beat. Similarly to vitamin A derivatives, their action is slow, improvement starting within two to three weeks, the full effect requiring up to two months. Vitamin D derivatives may cause skin irritation in about 15% of patients such as irritant dermatitis and they may cause hypercalcemia with excessive use. Symptoms of an overdose of Dovonex® ointment (topical calcipotriene ointment) include weakness, fatigue, drowsiness, dizziness, headache, decreased appetite, nausea, vomiting, and high levels of calcium in the blood. Vitamin D derivatives are also expensive.

Calcipotriol/calcipotriene may be combined with other topical agents such as a corticosteroid (betamethasone dipropionate (Dovobet®) or halobetosal (Ultravate®)) however vitamin D analogs may inactivate other topicals such as salicylic acid. The use of vitamin D derivatives may be combined with UV therapy or other agents for increased effectiveness.

(f) Other treatments and preparations such as:

(fl) Topical treatments including sulphur ointments, cayenne pepper cream, colloidal silver, boron/zinc/nickel applied orally or topically, eicosapentanoic acid (such as fish oil) taken orally and topical immunomodulators such as tacrolimus ointment and pimecrolimus cream;

(£2) Systemic therapies using drugs such as methotrexate, low dose naltrexone, or cyclosporine (immunosuppressive drug), or biologies such as alefacept, efalizumab, amevive, raptiva and infliximab, which may be taken orally or by injection. Methotrexate has a dramatic response by inhibiting cellular mitosis. Methotrexate and other drugs however have severe side effects such as bone marrow depression and thus their therapeutic benefits must be weighed against these side effects. They typically can only be used for a short time in view of their side effects and toxicity. Other systemic therapies include use of genetic modifiers and thymic supplementation;

(£3) UV light phototherapy. In UV light treatment of psoriasis, the skin is typically coated with a dye that absorbs ultra-violet (UV) light followed by shining UV light (for example by use of an excimer laser) on the coated area. UV treatment decreases the number of skin cells that grow too quickly, kills T cells and reduces inflammation. Use of a topically applied photosensitizing agent, such as psoralen, may also be used (this treatment is known as PUVA). UV treatment may be combined with other treatments such as with topical application of dithranol, tar, vitamin A derivatives, vitamin D derivatives or oral retinoids to increase effectiveness. Goeckerman therapy involves daily application of black tar with daily UV treatment. Ingram therapy involves daily coal tar baths, dithranol paste and UV treatment.

UV treatment however has been found to increase the incidence of skin cancer.

Any of the above psoriasis therapies may be assisted by use of other antiinflammatory drugs such as ibuprofen (a NSAID) to reduce inflammation and pain.

With respect to combining the compounds dithranol, tar and salicylic acid, it is known to combine these three agents in clinical dermatological practice by pharmacies prior to application, by use of a mortar and pestle, which is laborious. Further, whilst there are proprietary premixed formulations such as Micanol® referred to above, either the formulations do not include all of the three actives, are not readily available or include the actives in less effective proportions. There is a need for an off-the-shelf psoriasis preparation which is easy to prepare and is readily available.

It would therefore be desirable to provide a preparation for treating psoriasis which is improved over the presently available formulations. Object of the Invention

It is an object of the present invention to overcome or substantially ameliorate at least one of the above disadvantages or at least provide a suitable alternative.

Summary of the Invention In a first aspect, the present invention provides a topical preparation for the treatment of psoriasis, the preparation comprising as active ingredients: therapeutically effective amounts of dithranol, tar, a beta hydroxy acid, urea and an alpha hydroxy acid, together with a suitable carrier. In one embodiment the preparation comprises: about 0.01 to about 10wt% dithranol; about 0.1 wt% to about 20wt% coal tar; about 0.1 wt% to about 25wt% beta hydroxy acid; about 0.1 wt% to about 40wt% urea; and about 0.1 wt% to about 25wt% alpha hydroxy acid. In one embodiment the preparation comprises: about 0.1 to about 5wt% dithranol; about lwt% to about 12wt% coal tar; about 0.2wt% to about 12wt% beta hydroxy acid; about 10wt% to about 40wt% urea; and about 5wt% to about 15wt% alpha hydroxy acid. hi a second aspect, the present invention provides a method for treating psoriasis or for maintaining psoriasis remission comprising topically applying to a patient in need of such treatment, the preparation of the first aspect.

In a third aspect, the present invention provides the use of dithranol, tar, a beta hydroxy acid, urea and an alpha-hydroxy acid in the preparation of a topical medicament for treating psoriasis or for maintaining psoriasis remission.

Definitions

The following definitions are intended as general definitions and should in no way limit the scope of the present invention to those terms alone, but are put forth for a better understanding of the following description.

Unless the context requires otherwise or specifically stated to the contrary, integers, steps, or elements of the invention recited herein as singular integers, steps or elements clearly encompass both singular and plural forms of the recited integers, steps or elements. Throughout this specification, unless the context requires otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated step or element or integer or group of steps or elements or integers, but not the exclusion of any other step or element or integer or group of elements or integers. Thus, in the context of this specification, the term "comprising" means "including principally, but not necessarily solely".

"Psoriasis" includes "plaque psoriasis" and "scalp psoriasis". The term "treatment" or "treating" includes alleviation, amelioration and or maintenance of remission of psoriasis. Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It is to be understood that the invention includes all such variations and modifications. The invention also includes all of the steps, features, compositions and compounds referred to or indicated in this specification, individually or collectively, and any and all combinations or any two or more of said steps or features.

AU the references cited in this application are specifically incorporated by reference are incorporated herein in their entirety. Inclusion herein of any given reference is not intended to indicate that the reference is generally known in Australia or elsewhere.

Further no statements made in this specification should be construed as forming part of the common general knowledge in the field.

Detailed Description of the Preferred Embodiments

There is disclosed herein a topical preparation for the treatment of psoriasis, the preparation comprising therapeutically effective amounts of dithranol, tar, a beta hydroxy acid, urea and an alpha-hydroxy acid, together with a suitable carrier. Methods of treating psoriasis or maintaining psoriasis remission are also disclosed.

The preparation of the invention comprises as one active, ^" dithranol. In one embodiment the dithranol may be present in the preparation in an amount in the range of about 0.01wt% to about 10wt%, for example in the range 0.1wt% to about 5wt%, or for example in the range of about 0.25wt% to about 4wt% or in the range of about 0.5wt% to about 2wt% (including about 0.01wt%, 0.1wt%, about 0.25wt%, about 0.5wt%, about 0.75wt%, about lwt%, about 1.5wt%, about 2wt% about 2.5wt%, about 3wt%, about 3.5wt%, about 4wt%, about 5wt%, about 6wt%, about 7wt%, about 8wt%, about 9wt% or about 10wt%). In one embodiment the amount of dithranol is less than about lwt%. In another embodiment the amount of dithranol is more than about lwt%. This embodiment may be used in extreme cases of psoriasis. In another embodiment amounts of about 0.1 wt% are present. This embodiment is suitable for preparations to be applied overnight. Dithranol acts on psoriatic lesions by normalizing the growth rate of skin cells (keratinocytes) which decreases the skin's rapid growth rate and reduces inflammation. The preparation of the invention also comprises as a second active, tar. In one embodiment the tar may be present in an amount of about 0.1 wt% to about 20wt%, for example about lwt% to about 12wt%, or for example about 0.1 wt%, about lwt%, about 2wt%, about 3wt%, about 4wt%, about 5wt%, about 6wt%, about 7wt%, about 8wt%, about 9wt%, about 10wt%, about l lwt%, about 12wt%, about 13wt%, about 14wt%, about 15wt%, about 16wt%, about 17wt%, about 18wt%, about 19wt% or about 20wt%. When the preparation is applied to a sensitive area, such as the genitals, the amount may be about lwt% to about 2wt%.

The tar may be coal tar such as whole crude coal tar, coal tar extract, coal tar filtrates, coal tar distillate, coal tar solution, refined extracts of coal tar such as liquor picis carbonis (LPC) or liquor carbonis detergens (LPD), and the like. Coal tar reduces inflammation, penetrates the skin dermis and is keratolytic. Coal tar decreases the rapid growth of the skin cells that cause plaque and helps to slow down or stop the formation of scale as well as thickened lesions and has an anti-inflammatory action.

The preparation of the invention comprises as a third active, a beta hydroxy acid, in one embodiment the beta hydroxyl acid is salicylic acid. In one embodiment the beta hydroxy acid may be contained in an amount in the range of about 0.1 wt% to about 25wt%, for example 0.2wt% to about 12wt%, or for example in the range of about 5wt% to about 10wt%, including about 0.1wt%, 0.2wt%, about 0.5wt%, about lwt%, about 2wt%, about 3wt%, about 4wt% about 5wt%, about 6wt%, about 7wt%, about 8wt%, about 9wt%, about 10wt%, about l lwt%, about 12wt%, about 13wt%, about 14wt%, about 15wt%, about 16wt%, about 17wt%, about 18wt%, about 19wt%, about 20wt%, about 21wt%, about 22wt%, about 23wt%, about 24wt% or about 25wt%. Salicylic acid has keratolytic (removing scale or hyperketatosis) and antioxidant properties. Salicylic acid may prevent oxidation of the other components of the preparation, in particular oxidation of dithranol to an inactive form, hi one embodiment the amount of the beta hydroxy acid is above about 5wt%. In this embodiment clinical benefits with respect to both the keratolytic effect and oxidation prevention are obtained.

The preparation of the invention also comprises as another active, urea. The urea may be present in an amount of about 0.1 wt% to about 40wt%, for example about 10wt% up to about 40wt% or for example in the range about 10wt% to about 20wt% including about 0.1 wt%, about lwt%, about 2wt%, about 3wt%, about 4wt%, about 5wt%, about 6wt%, about 7wt%, about 8wt%, about 9wt%, about 10wt%, about llwt%, about 12wt%, about 13wt%, about 14wt% about 15wt%, about 16wt%, about 17wt%, about 18wt%, about 19wt%, about 20wt%, about 21wt%, about 22wt%, about 23wt%, about 24wt%, about 25wt%, about 26wt%, about 27wt%, about 28wt%, about 29wt%, about 30wt%, about 31wt%, about 32wt%, about 33wt%, about 34wt%, about 35wt%, about 36wt%, about 37wt%, about 38wt%, about 39wt% or about 40wt%. In one embodiment the urea may be available as a colourless to white prismatic crystal or white crystalline powder. The preparation of the invention further comprises as another active, an alpha- hydroxy acid such as lactic acid or another alpha-hydroxy acid such as glycolic acid or a combination thereof. In one embodiment the active is lactic acid. In one embodiment the alpha-hydroxy acid may be present in an amount of about 0.1 wt% to about 25wt%, for example about 5wt% up to about 15wt%, including about 0.1 wt%, about 5wt%, about 6wt%, about 7wt%, about 8wt%, about 9wt%, about 10wt%, about 1 lwt%, about 12wt%, about 13wt%, about 14wt%, about 15wt%, about 16wt%, about 17wt%, about 18wt%, about 19wt%, about 20wt%, about 21wt%, about 22wt%, about 23wt%, about 24wt% or about 25wt%. Urea and lactic acid may have humectants and moisturizing properties, and may retain water on or near the treated area and soften and remove scale. Lactic acid and urea have also unexpectedly been found to enhance absorption of the other active components allowing them to penetrate more deeply into the skin. The lactic acid and urea may enhance the keratolytic properties of the salicylic acid and therefore enhance the efficiency of the preparation.

The preparation may be in the form of a solution, cream, shampoo or salve. A suitable carrier may be water, purified water, a water soluble or water miscible base, a moisturizing base or cream, oil, wax, gel, lotion, liquid suspension, liquid dispersion or emulsion (water-in-oil or oil-in-water). In one embodiment the carrier is an aqueous cream or a water miscible base. In one embodiment the carrier is an aqueous cream or a water miscible base for ease in washing off. For example the base may be a hydrophilic or lipophilic cream which is compatible with the active components of the preparation.

The preparation may contain standard adjuvants, excipients and diluents and other standard additives in amounts up to about 5wt% or more. Types of adjuvants, excipients and diluents include those commonly used in compounding pharmacy. Additional additives may include moisturisers such as vaseline, glycerine, mineral oil and mixtures thereof, petrolatum, surfactants, cetyl alcohols, stearyl alcohols, sodium lauryl sulfate, cholesterol, methylparaben, butylparaben, propylparaben, polyethylene glycol, emollients such as lanolin, fragrances, colouring agents, gelling agents including aluminium hydroxide, petrolatum and anhydrous gelling agents such as acetone gels, glyceryl tris 12- hydroxy stearates, carbopol, silica, methyl cellulose, hydroxyl stearin, propylene carbonate, stearylaluminium hectorite, carboxy methyl cellulose, polyethylene gelled mineral oil, carboxy polymethylenes, hydroxyl methyl carboxy ethyl cellulose, polyvinylpyrrolidone, and the like, glyceryl monolaurate, glyceryl monomyristate, anhydrous citric acid, sodium hydroxide, Vitamin C (ascorbic acid), or mixtures thereof. Wetting agents, preservatives such as ascorbic acid, humectants such as glycerine, sorbitol, manitol or glycols, fillers, anti-oxidants, perfumes, cooling agents such as menthol, soothing agents such as camphor, alcohols, polysorbate (alcohols and polysorbate reduce inflammation), fatty acids (softeners and moisturizers) such as palmitic, palmitoleic, stearic, oleic, linoleic, arachidic, behenic or combinations thereof, other antiinflammatories, antioxidants, antibacterials, antimicrobials, anti-pruritic, antiplatelet adhesion, vosodilation agents or other keratolytic agents may also be included.

The preparation may additionally include other psoriasis medicaments as previously described. The preparation may be used alone or in conjunction with other known therapies described above, such as UV phototherapy. The preparation may be prepared by mixing or compounding the actives together so as to form a smooth cream. Individual components may be premixed prior to combination with the carrier. The mixing may be done by hand, by use of a mortar and pestle or by means of a mechanical mixer. The preparation may be stored in an air tight container. The preparation may be applied topically directly onto any affected areas, such as plaques in any area, for example directly onto the affected nails, skin, elbows, knees or scalp. In accordance with the present invention appropriate care may be taken when applying the preparation to sensitive areas such as the genitals, around the eye, underarm or face, for example by immediate washing after application or by applying protective agents to non-involved skin. For example, petrolatum or other suitable protectant may be applied to unaffected areas, prior to application of the preparation of the invention so as to minimise contact of normal or unaffected skin with the preparation. Alternatively, where the preparation is applied to an area not exhibiting psoriasis, that area may be washed immediately after application of the preparation. In one embodiment the preparation may be applied as a short contact preparation i.e., applied for about 10 minutes up to about 30 minutes (up to one hour when applied to the scalp) and then washed off suitably with cold water or by means of cotton wool soaked in oil or mild detergent. In another embodiment it is possible to vary the amounts/ratios of the actives so that the preparation can be applied for longer periods, such as overnight. The preparation may be applied daily or less frequently for example, every 2 to 4 days when control of the psoriasis has been achieved. In one embodiment benefit may be achieved within as little as one week, hi one embodiment maximum benefit may be achieved within four weeks and maintenance treatment reduced to weekly or less depending on remission. In one embodiment, the preparation may be used long term and may be used only intermittently. In one embodiment the preparation may be applied with a few applications every couple of months to control. The preparation may be applied so as to lightly coat the affected area and the cream may be rubbed into the skin until absorbed. The preparation is suitable for treating chronic psoriasis or scalp psoriasis and regular application may minimise and control the condition. The preparation may not necessarily cure psoriasis.

The invention will now be described with reference to the following examples but which should not be construed as limiting on the invention. EXAMPLE 1

Dithranol lwt%

LPC (coal tar) 10wt%

Salicylic acid 5wt%

Urea 10wt% Lactic acid 5wt%

Aqueous cream to 100wt%

The preparation is prepared by mixing the above ingredients to form a smooth cream. The preparation is then applied for short contact periods of 5 minutes which are increased by 5 minutes to a maximum of 30 minutes for the body and a maximum of one hour for the scalp whilst avoiding application to the face or flexures.

EXAMPLE 2

Dithranol 0.5wt%

LPC (coal tar) 10wt%

Salicylic acid 5wt% Urea 10wt%

Lactic acid 5wt%

Aqueous cream to 100wt%

The preparation is prepared by mixing the above ingredients to form a smooth cream. The preparation is then applied for eight hours overnight on the body or the scalp.

The present invention has the advantages that the absorption of the tar, dithranol and the beta hydroxy acid are enhanced by the inclusion of alpha hydroxy acid such as lactic acid and urea and the preparation is suitable for therapeutic control or maintenance of remission of psoriasis. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein.

Claims

The claims defining the invention are as follows:

1. A topical preparation for the treatment of psoriasis, the preparation comprising as active ingredients: therapeutically effective amounts of dithranol, tar, beta hydroxy acid, urea and 5 an alpha-hydroxy acid, together with a suitable carrier.

2. The preparation according to claim 1, wherein the preparation comprises: about 0.01 to about 10wt% dithranol; about 0.1 wt% to about 20wt% coal tar; about 0.1wt% to about 25wt% beta hydroxy acid; o about 0.1 wt% to about 40wt% urea; and about 0.1 wt% to about 25wt% alpha hydroxy acid.

3. The preparation according to claim 1, wherein the preparation comprises: about 0.1 to about 5wt% dithranol; about lwt% to about 12wt% coal tar; s about 0.2wt% to about 12wt% beta hydroxy acid; about 10wt% to about 40wt% urea; and about 5wt% to about 15wt% alpha hydroxy acid.

4. The preparation according to claim 1, 2 or 3 wherein the amount of dithranol is less than about lwt%. o

5. The preparation according to claim 1, 2 or 3 wherein the amount of dithranol is more than about lwt%.

6. The preparation according to any one of claims 1 to 5 wherein the tar is selected from the group consisting of coal tar, whole crude coal tar, coal tar extract, coal tar filtrates, coal tar distillate, coal tar solution, liquor picis carbonis (LPC) and liquor ₅ carbonis detergens (LPD).

7. The preparation according to any one of claims 1 to 6 wherein the beta hydroxy acid is salicylic acid.

8. The preparation according to any one of claims 1 to 7 wherein the beta hydroxy acid is present in the range of about 5wt% to about 10wt%. 0

9. The preparation according to any one of claims 1 to 8 wherein the amount of beta hydroxy acid is above about 5wt%.

10. The preparation according to any one of claims 1 to 9 wherein urea is present in the range of about 10wt% to about 20wt%.

11. The preparation according to any one of claims 1 to 10 wherein the alpha- hydroxy acid is lactic acid, glycolic acid or a combination thereof.

12. The preparation according to claim 11 wherein the alpha-hydroxy acid is lactic acid.

13. The preparation according to any one of claims 1 to 12 wherein the carrier is an aqueous cream or water miscible base.

14. A method for treating psoriasis or for maintaining psoriasis remission comprising topically applying to a patient in need of such treatment, the preparation of any one of claims 1 to 13.

15. The use of dithranol, tar, a beta hydroxy acid, urea and an alpha-hydroxy acid in the preparation of a topical medicament for treating psoriasis or for maintaining psoriasis remission.

16. The preparation according to claim 1, substantially as hereinbefore described with reference to any one of the Examples.