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GB2275191A - Use of tolnaftate and tolciclate in treatment of skin disorder - Google Patents

Use of tolnaftate and tolciclate in treatment of skin disorder Download PDF

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Publication number
GB2275191A
GB2275191A GB9302553A GB9302553A GB2275191A GB 2275191 A GB2275191 A GB 2275191A GB 9302553 A GB9302553 A GB 9302553A GB 9302553 A GB9302553 A GB 9302553A GB 2275191 A GB2275191 A GB 2275191A
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United Kingdom
Prior art keywords
preparation
skin
naphthyl
psoriasis
medicaments
Prior art date
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Application number
GB9302553A
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GB2275191B (en
GB9302553D0 (en
Inventor
Donald John Dear
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Individual
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Individual
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Priority to GB9302553A priority Critical patent/GB2275191B/en
Publication of GB9302553D0 publication Critical patent/GB9302553D0/en
Publication of GB2275191A publication Critical patent/GB2275191A/en
Application granted granted Critical
Publication of GB2275191B publication Critical patent/GB2275191B/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine

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  • Health & Medical Sciences (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

O-2-naphthyl m-N-dimethylthio-carbanilate (tolnaftate) and O-(1,2,3,4-tetrahydro-1,4-methano-6-naphthyl) m-N-dimethylthiocarbanilate (tolciclate) and antifungal analogues thereof are useful in the preparation of (e.g. topical) medicaments for the treatment of attacks of exfoliative or inflammatory skin disorder such as psoriasis. The medicaments can take the form of ointments or creams, or impregnated dressings, bath oils, soap or detergent bars, shampoos, or dusting powders.

Description

PHARMACEUTICAL PREPARATIONS AND THEIR MANUFACTURE AND USE This invention relates to pharmaceutical preparations for use in the treatment of skin disorders; to their manufacture and use in such treatment; and to the use of certain active ingredients in their manufacture. In particular, the invention relates to the preparation and application of pharmaceutical materials for the treatment of psoriasis.
Psoriasis is a skin disorder characterised by epidermal thickening and scaling.
The prior art includes a number of materials and methods for the treatment of psoriasis. For example, in mild cases, it is known to apply emollients, especially ointments, alone.
Another treatment, known for eczema (dermatitis) as well as for psoriasis, comprises an ointment containing coal tar, often accompanied by salicylic acid. Coal tar is considered to be anti-inflammatory, antipruritic and keratolytic in action, It is known that coal tar preparations are sometimes of limited acceptability to patients, e.g. because of their smell and appearance.
Salicylic acid is also considered to be keratolytic, but often somewhat less active than coal tar: both are thought to act by increasing the rate of loss of surface skin scale. It is known that dizziness, tinnitus and deafness may accompany the use of salicylate.
and allergy may also arise.
Alternative known forms of application of these active ingredients include impregnated dressings, bath oils, and other solutions and dispersions for use in bathing.
A further known treatment for psoriasis comprises 1,8-dihydroxyanthrone (synonym dithranol), often apPlied in the form of an ointment or cream, e.g. at 0.25% w!w. Dithranol has been considered the most potent topical agent for psoriasis. However it can cause unacceptable skin irritation, and it is often regarded as otherwise inconvenient, as it can cause burning if it contacts relatively unaffected skin around the psoriatic lesions, and moreover it stains skin and hair and some fabrics, plastics and enamel, e.g. bathroom ware. For hospital in-patient therapy, dithranol can for example be applied in a paste of zinc oxide, starch and soft paraffin, containing 2% salicylic acid, but has the drawbacks of irritancy and of staining skin and clothing.
Other dithranol-containing ointments are known and intended for 'short-contact' regimes in which they are applied to psoriatic plaques and left in contact for up to one hour before being washed off, thus reducing the effects of burning and staining. Some patients are however intolerant of dithranol.
There remains therefore a continuing need for further materials useful in the treatment of inflammatory or exfoliative skin disorders such as psoriasis.
According to the present invention, a useful treatment of inflammatory or exfoliative skin disorder such as psoriasis is based on a pharmaceutical preparation containing O-2-naphthyl m-N-dimethylthiocarbanilate or O-(1,2,3,4-tetrahydro-1,4-methano-6-naphthyl) m-Ndimethylthiocarbanilate or an antifungal analogue thereof, for example in the form of a preparation for topical application such as an ointment or cream or other emollient base containing an effective amount of the abovementioned active ingredient, e.g. 0.3-3% wlw, e.g.
1% w/w.
O-2-naphthyl m-N-dimethylthiocarbanilate is known as an antifungal pharmaceutical under the generic name tolnaftate, and the analogous substance O-(1,2,3,4-tetrahydro-1,4-methano-6-naphthyl) m-N-dimethylthiocarbanilate is also known as an antifungal pharmaceutical under the generic name tolciclate.
It is also known to apply tolnaftate or tolciclate to the skin in an emollient base, more generally in a cream, lotion, or ointment. But the known indications for such use have previously related to cases of fungal skin infection due to Epidermophyton, Microsporum, Trichophyton and Maiassezia, particularly tinea pedis fungal skin infection, and pityriasis versicolor. Since the known function of this active material is as an anti-infective antifunal agent with a somewhat selective spectrum of action (excluding for example Candida and bacteria), the finding that it is useful for exfoliative or inflammatory skin disorder such as psoriasis is a surprising finding.
Thus the invention includes the use of O-2-naphthyl m-N-dimethylthiocarbanilate or O-(1,2,3,4-tetrahydro-1,4-methano-6-naphthyl) m-Ndimethylthiocarbanilate or an antifungal analogue thereof for the preparation of topical medicaments active against attacks of exfoliative or inflammatory skin disorder such as psoriasis.
It has been found in particular, according to the invention, that tolnaftate ointment or cream can be applied to affected areas of the skin in cases of psoriasis, with beneficial effect. It can be useful also to include a pharmaceutically acceptable disinfectant, particularly a skin disinfectant, or substance with preservative action, in such an ointment or cream, especially in a cream, e.g.
benzalkonium chloride, chlorhexidine, or triclosan, e.g. at about 0.05-5X w/w, e.g. 0.1-0.3%. However, some such materials, e.g.
triclosan, can cause unacceptable skin sensitivity in some patients, so it can be preferable to omit such a material for such cases.
The preparations can be manufactured by conventional pharmaceutical technique. They can usefully be applied twice a day or more often and gently rubbed into affected areas of skin. They can sometimes usefully be covered by dressing if desired.
Particular embodiments of the invention are illustrated nonlimitatively by way of example only, as follows.
EXAMPLE 1 A useful ointment for the treatment of psoriasis can be prepared comprising 1% w/w tolnafate compounded into an emollient base which comprises cetomacrogol emulsifying ointment (emulsifying wax 30%, liauid paraffin 20%, white soft paraffin 50%), using conventional pharmacy technique.
A useful version of this ointment and emollient base, especially for use in cases of notable skin sensitivity, is free of sensitising ingredients. (Ingredients which have sometimes been found to cause sensitivity include beeswax, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorocresol. EDTA, ethylene diamine, fragrances, hydroxybenzoates, isopropyl palmitate, polysorbates, propylene glycol, sorbic acid, wool fat and related substances.) EXAMPLE 2 Another useful ointment for the treatment of psoriasis comprises 1% w/w tolnaftate together with 0.1% benzalkonium chloride in an emollient base, commercially available in the form of the preparation marked as Mycil (TM) ointment.
Instructions can be given for the use of such materials (and their analogues including the alternative active ingredients mentioned above) to treat cases of exfoliative or inflammatory skin disorder, particularly psoriasis, substantially as follows: Such ointments can be applied in sufficient quantity to provide a visible skin covering over areas affected by psoriasis, and worked manually into affected areas of psoriatic skin. This application can be carried out twice a day.
This procedure has been observed to give a noticeable beneficial effect within 24 hours and if continued can clear up psoriatic attacks within about 48 to 72 hours. It can also be useful to apply such ointments and then cover the area of application with a dressing.
An advantage of this treatment is the relatively non-irritant nature of the materials used, and that it can be of particular benefit e.g.
where the patient with psoriasis is intolerant of other known treatments.
According to variants of the invention, tolnaftate or tolciclate or their antifungal analogues can be applied to the skin in cases of exfoliative or inflammatory skin disorder in other presentational forms, such as impregnated dressings, bath oils, soaps and detergent bars, shampoos, or dusting powders. As will be apparent to the skilled reader, the present disclosure extends to modifications and variations including the use of combinations and subcombinations of the features mentioned herein.

Claims (8)

Claims:
1. Use of O-2-naphthyl m-N-dimethylthio-carbanilate or 0-(1,2,3,4- tetrahydro-1,4-methano-6-naphthyl) m-N-dimethylthiocarbanilate or an antifungal analogue thereof in the preparation of medicaments, e.g.
topical medicaments, for the treatment of attacks of exfoliative or inflammatory skin disorder such as psoriasis.
2. Use of O-2-naphthyl m-N-dimethylthio-carbanilate or 0-(1,2,3,4- tetrahydro-1,4-methano-6-naphthyl) m-N-dimethylthiocarbanilate or an antifungal analogue thereof, together with a pharmaceutically acceptable disinfectant, e.g. a skin disinfectant, or a substance with preservative action, e.g. benzalkonium chloride, chlorhexidine, or triclosan, in the preparation of medicaments, e.g. topical medicaments, for the treatment of attacks of exfoliative or inflammatory skin disorder such as psoriasis.
3. Preparation method according to claim 1 or 2, wherein the medicament is in the form of an ointment or cream.
4. Preparation method according to claim 1 or 2, wherein the medicament is in the form of an impregnated dressing, a bath oil, a soap or detergent bar, a shampoo, or a dusting powder.
5. Preparation according to claim 1, 2, 3 or 4, wherein the resulting medicament is packaged with instructions for applying the medicament to skin that shows exfoliative or inflammatory disorder such as psoriasis.
6. A topical pharmaceutical preparation manufactured according to claim 1 or 2, which is free from potentially sensitising substances that may be unsuitable for psoriatic skin.
7. A topical pharmaceutical preparation manufactured according to claim 1 or 2, which is free from the potentially sensitising substances beeswax, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorocresol MEDIA, ethylene diamine fragrances, hydroxybenzoates, isopropyl palmitate, polysorbates, propylene glycol, sorbic acid, wool fat and related substances.
8. The invention in all its aspects, substantially as hereinbefore described with reference to any of the features of the foregoing description including the Examples.
GB9302553A 1993-02-10 1993-02-10 Use of antifungal compounds in the treatment of skin disorders Expired - Fee Related GB2275191B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB9302553A GB2275191B (en) 1993-02-10 1993-02-10 Use of antifungal compounds in the treatment of skin disorders

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB9302553A GB2275191B (en) 1993-02-10 1993-02-10 Use of antifungal compounds in the treatment of skin disorders

Publications (3)

Publication Number Publication Date
GB9302553D0 GB9302553D0 (en) 1993-03-24
GB2275191A true GB2275191A (en) 1994-08-24
GB2275191B GB2275191B (en) 1996-11-27

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6391879B1 (en) * 1998-11-16 2002-05-21 Astan, Inc. Therapeutic anti-fungal nail preparation
US9408867B2 (en) 2011-05-11 2016-08-09 Veloce Biopharma, Llc Antifungal compositions for the treatment of skin and nails
US9750683B2 (en) 2012-02-17 2017-09-05 Veloce Biopharma, Llc Antifungal compositions for the treatment of skin and nails
US10314914B2 (en) 2015-01-20 2019-06-11 Veloce Biopharma, Llc Iodophor composition and methods of use

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
J.Invest.Dermatol. 100(3) pages 343-346 (1993) *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6391879B1 (en) * 1998-11-16 2002-05-21 Astan, Inc. Therapeutic anti-fungal nail preparation
US9408867B2 (en) 2011-05-11 2016-08-09 Veloce Biopharma, Llc Antifungal compositions for the treatment of skin and nails
US9750683B2 (en) 2012-02-17 2017-09-05 Veloce Biopharma, Llc Antifungal compositions for the treatment of skin and nails
US10314914B2 (en) 2015-01-20 2019-06-11 Veloce Biopharma, Llc Iodophor composition and methods of use

Also Published As

Publication number Publication date
GB2275191B (en) 1996-11-27
GB9302553D0 (en) 1993-03-24

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Legal Events

Date Code Title Description
PCNP Patent ceased through non-payment of renewal fee

Effective date: 19980210

728V Application for restoration filed (sect. 28/1977)
7281 Application for restoration withdrawn (sect. 28/1977)