Drug – bio-affecting and body treating compositions – Topical sun or radiation screening – or tanning preparations
Patent
1993-11-15
1995-07-18
Knode, Marion C.
Drug, bio-affecting and body treating compositions
Topical sun or radiation screening, or tanning preparations
424 63, 424639, 424630, 424648, 424944, A61K 3844, A61K 3334, A61K 3332, A61K 742
Patent
active
054339421
DESCRIPTION:
BRIEF SUMMARY
This application was filed under 35 USC .sctn. 371 through PCT/GB92/00878, filed May 15, 1992.
The present invention relates to the treatment of tyrosinase-positive depigmentation disorders and has particular application to the treatment of vitiligo. It provides compositions for said treatment and methods of said treatment.
Vitiligo is a chronic depigmentation disorder in which the patient has unsightly white patches or spots which are caused by localized loss of pigment and are very liable to sunburn. Although the condition is not debilitating, it is often emotionally stressful to the patient. The cause presently is unknown but it has been speculated that it results from an autoimmune response, involvement of the nervous system or a toxic effect on melanocytes. Usually, the only treatment is the use of skin-colouring cosmetics to disguise the patches or, in the case of Blacks and Indians, of depigmenting agents such as hydroquinone to depigment the remaining pigmented skin. Some limited success in treatment has been reported using the so-called PUVA method.
In the PUVA method, methoxsalen (ie. 8-methoxy psoralen) or, less usually, other psoralens is administered orally and the patient subsequently exposed to UVA light. Psoralens are plant extracts and have been known since ancient Egyptian times to act as photosensitizers. The psoralen is given systemically and hence the photosensitizing effect is not localized and, since this effect is in the UVA range (320-400 nm), the patient must wear special glasses during everyday life in order to prevent eye damage. Further, side effects of PUVA include nausea, erythema, oedema, dizziness, headache, vesiculation, bulla formation, onycholysis, acneiform eruption and severe skin pain. Long term risks include skin cancer, epidermal dystrophy, premature skin aging, cataract formation, and alterations in the immune system. The treatment is believed to be toxic to normal lymphocytes and Langerhans' cells. Accordingly, the treatment usually is limited to elderly patients or to two years duration. It has recently been proposed to mitigate some of the risks of PUVA by bathing the patient in a psoralen bath.
Other tyrosinase-positive depigmentation disorders include Hermansky-Pudlak Syndrome.
It has now surprisingly been found that vitiligo and other tyrosinase-positive depigmentation disorders can be effectively treated by exposing a patient to UVB light (290-320 nm) after topical application of manganese (II) bicarbonate or other pseudocatalase. Further, it has been found that, following pigmentation by said treatment, a level of pigmentation in affected areas can be retained, at least for a period of time, by topical application of the pseudocatalase without UVB exposure.
We have disclosed in a co-pending Patent Application of the same priority and filing dates and corresponding to UK Patent Application No. 9110651 that pseudocatalase can be used topically to enhance sun tanning.
By pseudocatalase, we mean a plasma membrane permeable physiologically acceptable compound which catalyzes the dismutation of H.sub.2 O.sub.2 in vivo in analogous manner to catalase.
Without wishing to be bound to any particular hypothesis, it is believed that vitiligo and other tyrosinase-positive depigmentation disorders are caused by a deficiency of catalase which permits a higher than normal peroxide ion concentration in melanocytes. Since tyrosinase is inactivated by peroxide ion, the tyrosinase-catalyzed oxidation of 1-tyrosine to 1-dopa required for melanin biosynthesis is inhibited. Further, since peroxide ion is photochemically reduced to hydroxyl ion, there is a concomitant increase in hydroxyl ion production.
Exposure of the skin to UVB radiation generates superoxide anion radicals which is a preferred substrate for human tyrosinase (40 times better than oxygen) thereby promoting melanin formation. However, the superoxide anion radicals are dismutated into dioxygen and peroxide ion causing an undesirable increase in hydroxyl ion concentration unless catalase or some other competing mec
REFERENCES:
patent: 4129644 (1978-12-01), Kalopissis et al.
Kono et al., J. Biol. Chem. 258(10): 6015-6019 (1983).
Kono et al., Chemical Abstracts, 114(21):202133d, 2(1), pp. 18-26 (1990).
Schallreuter Karin U.
Wood John M.
Knode Marion C.
Stiefel Laboratories, Inc.
Witz Jean C.
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