Experimental contribution to the dithranol-brown problem

Abstract

Dithranol is well known to dermatologists: during antipsoriatic therapy with dithranol, a brownish staining frequently occurs in the lesions as well as the surrounding non-involved skin, and there have been various efforts [5] to eliminate or to diminish this side effect. The present study is concerned with dithranol brown located in the brown psoriatic scales obtained from patients undergoing dithranol therapy (dithranol with 2% salicylic acid in white soft paraffin).Microscopic examination showed that dithranol brown is deposited in the form of well-defined brownish particles in the stratum corneum. These particles were isolated using a micromanipulator and introduced into a 311A mass spectrometer via a heated inlet system (90° C, 120° C). High resolution revealed the presence of hydrocarbons [C 18 H 36 , C 2 8^5^L C27H44 (cholestadiene)] and an oxygenated steroid C 2 7H 46 0 (cholestenol or cholestanone). When the inlet system of a CH5 mass spectrometer was heated to 450° C, we obtained a very weak signal at m/z = 446 from a dimethylsulfoxide (DMSO) extract of brown scales, which might be attributable to tetrahydroxyhelianthrone [2]; under these conditions, however, the formation of artifacts cannot be excluded.The proteolytic degradation of brown scales using Pronase followed by CHC1 3 extraction revealed the molecular ions of dithranol, chrysazine and 1,8,1',8'-tetrahydroxybisanthrone (m/z = 450; <1%), and the corresponding fragment ions (Fig. 1).The excitation of a single brown particle to an ionized state under microscopic control using a (Fig. 2) [6]. When we heated brown scales to 300° C in a TAS apparatus (DESAGA, Heidelberg, FRG), we obtained a yellow sublimate which contained chrysazine. Van Duuren et al. [8] have prepared complexes of chrysazine with various metals including copper. Although copper and chrysazine are found in the same compartment, the identity of Van Duuren's complex and dithranol brown cannot be deduced from

Use of solid dispersions to increase stability of dithranol in topical formulations

“…This drug readily undergoes oxidation to a range of degradation products, including danthron and dithranol dimmer, which are thought to contribute to the undesired effects and are inactive or less active in terms of anti-psoriatic potency (Thoma, Holzmann, 1998;Mahrle, 1997). Dithranol has a yellow color, while its oxidation products are brown to black (Ashton, Andre, Lowe, 1983;Wiegrebe, Plumier, Mayer, 1985). So, the color can be a good parameter to study the stability of new formulations.…”

Potent Antipsoriatic Agents: A Facile Preparation of Acylated Derivatives from Dithranol in a Mild Basic Reaction

“…Dithranol is not quite stable, and it undergoes spontaneous oxidation enhanced by day-light, ultraviolent (UV)-light, exposure to air and molecular oxygen, temperature increases, the presence of trace metals or tar, alkaline solutions, etc. Intermediate products, such as dithranol anions 1a and 1b, dithranol radicals 1c, and oxygen radicals are thought to be responsible for both the antipsoriatic effect and dithranol dermatitis, 2 whereas the brown staining is due to the anthraquinone dimers 4 and polymers, 1,3 and both danthron (1,8-dihydroxyanthraquinone) 2 and dithranol dimer 3 are not active for the treatment of psoriasis, although they have no inflammatory effect of the skin. 4 Fig.…”

Dithranol: A Review of the Mechanism of Action in the Treatment of Psoriasis vulgaris

“…In accor dance with this, microscopic examination revealed that dithranol brown is deposited in the form of well-defined brownish particles in the stratum comeum of dithranol-treated skin [29]. However, not only these particles may be responsible for the staining, since dithranol stains living cells in vitro as well [111]; furthermore, oxidation products of di thranol have been demonstrated intracellularly too [44], Since both dithranol and danthrone readily form complexes with copper [143], and tyrosinase is a Cu protein.…”

“…The changes in the absorption spectrum of dithranol in the suction blister fluid obtained from dithranol-treated skin suggest that this dithranol-HSA complex may be formed in vivo as well [28], During treatment with dithranol, the main metabolites in the skin are danthrone, dithranol dimer [29] and a further etherinsoluble oxidation product [30]. Danthrone can be detected in the urine following local treatment with dithranol, and the urine ex cretion may be used to measure the metabo lism and excretion of the drug [26].…”