Use of hydrocortisone or hydrocortisone salt and triclosan in the manufacture of a composition for the prevention and/or treatment of atopic eczema

Abstract: A composition is provided for use in treating atopic eczema comprising a low potency corticosteroid, and a chlorinated phenol antiseptic together with a topically acceptable excipient. Preferably the chlorinated phenol antiseptic is triclosan and the low potency corticosteroid is hydrocortisone or a hydrocortisone salt.

Description: This invention relates to a composition for treating atopic eczema. Atopic eczema (dermatitis) is a common chronic skin disorder, especially in children. The condition is characterized by inflammatory erythematous lesions which in mild cases are localized on the wrists, knees and neck but in severe cases a more widespread distribution is often noted. Traditionally, atopic eczema has been treated with short term topical corticosteroids and maintained with emollients and bath oils. However atopic eczema is not curable at present and most available treatments involve the application of corticosteroids. Hitherto, combinations of topical corticosteroids (in particular high potency steroids such as betamethasone-17-valerate), together with a powerful antibiotic (such as, for example, neomycin, or fusidic acid), have frequently been used to treat atopic eczema. The administration of the steroid was intended to combat the underlying physiological causes of the eczema as such, e.g. by promoting an antiinflammatory response, and the antibiotic was intended to counteract secondary infections. However, the most frequent sufferers of atopic eczema are children and the use of such strong combination therapies is undesirable. Also, topical neomycin and fucidic acid is known to cause hypersensitivity and reactions in the form of rashes and irritations may recur. Accordingly the need for other agents which do not suffer this disadvantage are required. Recently, the presence of Staphylococcus aureus in eczematous lesions has been noted. In particular, high concentrations of S. aureus have been demonstrated in lesions of atopic eczema, even when they did not have the appearance of being infected. Further, the observed levels of S. aureus have been found to correlate with the severity of the eczema and it is now believed that the presence of S. aureus infections is implicated in the aetiology of the disease. It has now been found that a topical composition comprising a low potency corticosteroid in combination with a chlorinated phenol antiseptic is especially effective in treating atopic eczema and does not suffer the disadvantages of known combination therapies. Further the use of a combination of a low potency corticosteroid and a chlorinated phenol antiseptic results in an enhanced activity in combating atopic eczema, compared to the use of a corticosteroid alone. Although chlorinated antiseptics have been used in topical compositions hitherto, their use in the treatment of atopic eczema, particularly in combination with low potency corticosteroid has never been suggested. In fact in view of their nonspecific action and chlorine-content, their use in connection with eczema would have tended to discourage such use. When administered in combination with the chlorinated phenol antiseptic, the low potency corticosteroid has surprisingly been found to promote a sufficiently high antiinflammatory response to result in a significant reduction in the severity of the eczematous lesions, even to the extent of their disappearance. Further, a reduction in levels of S. aureus on and around the site of atopic eczema has been noted, but without total elimination of the normal skin flora. It is thus to be appreciated that the combination therapy according to the invention does not involve as a first effect, an anti-inflammatory action in response to the eczema plus an antibacterial effect on eczematous lesions that happened to be infected. Instead, the efficacy of the therapy of the invention seems to be based upon a synergistic effect whereby a low potency corticosteroid elicits a response (when administered in combination with a chlorinated phenol antiseptic) that hitherto was attainable only by using a high potency corticosteroid. The preferred low potency corticosteroids used according to the invention are classified as having potencies "6" or "7" according to the United States Classification system wherein corticosteroids are classified on a scale of 1 to 7 ("1" being the most potent and "7" being less potent - See Goodman & Gilmans; The Pharmacological Directory of Therapeutics, 8th Edn.; McGraw-Hill Int. Ed.). In the corresponding United Kingdom Classification - see Mims (Monthly Index of Medical Specialities, Sept. 1995, Haymarket Publishing Services Ltd), - "low potency corticosteroids" correspond to those falling within class "7" on the United States scale. I.e. "7" on the US potency scale corresponds to "low potency" on the UK Mims classification). Preferably, the low potency corticosteroid is present in a concentration of 0.1 to 5 % wt., most preferably 0.5 to 2.5 % wt. The chlorinated phenol antiseptic is preferably present in a concentration of 0.1 to 3 % wt., most preferably 0.5 to 1 % wt. Advantageously in accordance with the invention there are provided compositions comprising a low potency corticosteroid and a chlorinated phenol antiseptic in the form of a solution, lotion, cream, ointment or gel suitable for topical application. Compositions according to the invention may contain any conventional incidental adjutants for example emollient, thickening agents, perfumes, colouring agents, stabilizing agents, pH adjusting agents and preservatives. The preferred chlorinated phenol antiseptic used in accordance with the invention is triclosan, i.e. 5-chloro-2-(2,4-dichlorophenoxy)phenol, available e.g. under the Trade Name Irgasan DP300. The preferred low potency corticosteroid is hydrocortisone or a hydrocortisone salt. According to a further aspect of the invention there is provided the use of hydrocortisone or a hydrocortisone salt and triclosan in the manufacture of a composition for the prevention and/or treatment of atopic eczema. In carrying out the method of the invention, the compositions may be applied to affected region at regular intervals of, for example, 1-4 times a day. The following example illustrates a composition according to the invention: HYDROCORTISONE/TRICLOSAN CREAM A. Cetomacrogol 1000 BP 1.000 Mineral Oil 30.000 Lasemul 92AE 3.500 Cetyl Alcohol Pure 1692 3.500 Cutina CP 2.000 Lasemul 130 3.000 Silicone DC200/350 2.000 Irgasan DP300 (triclosan) 0.700 B. Water - deionised 46.834 Glycerine 3.000 EDTA Disodium 0.100 C. Water - deionised 3.000 Chlorhexadine Digluconate 0.250 Hydrocortisone Acetate BP 1.116 100.000

Claims: The use of (i) hydrocortisone or a hydrocortisone salt and (ii) triclosan in the manufacture of a composition for the prevention and/or treatment of atopic eczema. The use according to Claim 1 wherein the hydrocortisone or hydrocortisone salt is present in a concentration of 0.1 to 5 % wt. The use according to Claim 2 wherein the hydrocortisone or hydrocortisone salt is present in a concentration of 0.5 to 2.5 % wt. The use according to any preceding claim wherein the triclosan is present in a concentration of 0.1 to 3 % wt. The use according to Claim 4 wherein the triclosan is present in a concentration of 0.5 to 1 % wt. The use according to any preceding claim in the composition is in the form of a solution, lotion, cream, ointment or gel.

Inventors: POTTS MICHAEL, POTTS, MICHAEL
Applicants: SURTECH INT LTD, SURTECH INTERNATIONAL LTD.
Application year: 1996
Main classification: A61K31
IPC codes: A61K31