CA2248977A1 - Topical formulations for the treatment of nail psoriasis - Google Patents
Topical formulations for the treatment of nail psoriasis Download PDFInfo
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- CA2248977A1 CA2248977A1 CA002248977A CA2248977A CA2248977A1 CA 2248977 A1 CA2248977 A1 CA 2248977A1 CA 002248977 A CA002248977 A CA 002248977A CA 2248977 A CA2248977 A CA 2248977A CA 2248977 A1 CA2248977 A1 CA 2248977A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
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- Cosmetics (AREA)
Abstract
Proposed are formulations suitable for the treatment of nail psoriasis and containing a substance effective against psoriasis, at least one spreading solvent, at least one readily volatile solvent and a film-forming agent.
Description
CA 02248977 1998-09-1~
Description Topical formulations for the treatment of psoriasis of the nail In the case of a psoriatic condition, finger- and toenails are also infected.
Generally, in the literature a frequency of infection of the nails of 10% -50% is assumed in the case of psoriasis.
10 In the case of psoriatic arthritis, it is to be assumed that 86.5% of the patients with psoriatic arthropathy have infection of the nail or changes to the nail.
(G. Lavaroni, F. Kokelj, P. Pauluzzi, G. Trevisan: The nails in psoriatic arthritis, Acta Derm Venereol (Stockh) (Suppl) 186,116-117,1994) Different expressions of the syndrome from depressions of the nail plate (pits on surface) through loosening of the nail plate up to abnormal thickenings of the nail plate and complete or alternatively only partial nail loss are observed.
Occasionally, the expression of the psoriasis is restricted to finger nails.
According to the present state of knowledge, the nails infected by psoriasis are treated with dithranol (local), PUVA, glucocorticoids and vitamin D
25 analogs (local) or systemic methotrexate, retinoids or cyclosporin A.
(Pschyrembel, Klin. Worterbuch [Clin. Dictionary], 257th edition, Walter de GruyterVerlag, Berlin, NewYork, 1994).
EP 0 634 170 describes formulations for the treatment of psoriasis.
30 To date, no simple, effective method for the treatment of psoriasis of the nail has been described. (Zaias, Nardo, The Nail in Health and Disease, MTP press limited, International Medical Publishers, Spectrum Publications Inc.1980).
CA 02248977 1998-09-1~
The disadvantage of the known formulations is that they only act superficially. Since they do not penetrate the nail, therapeutic doses of the pharmaceutical do not reach the nail matrix or the nail bed. The patient must therefore endure a long-lasting treatment, it being possible even a 5 short time after the end of the treatment for the psoriasis to flare up again.
The pharmaceutical formulations used by people who suffer from psoriasis of the nail are generally lipid-rich creams/ointments which have proven suitable in the dermal treatment of psoriasis, since, applied dermally, they 10 offer the patient an anti-drying effect and decreased itching, or alternatively solutions which are used, for example, in the topical application of glucocorticoids.
A further crucial disadvantage of the therapy with topical agents of this type 15 is that when washing, bathing and showering the formulations applied can be removed again from the nail surface or dissolved out of the nail with the incorporated active compound, and consequently thus then have to be newly applied again. Because of this, the treatment with these topical agents is ineffective and additionally extremely uneconomical.
The aim of the invention is to make available a formulation which does not have or only has to a minor extent the disadvantages described above.
The object is achieved by use of a formulation which consists of the active 25 compound, at least one spreading solvent, a readily volatile solvent and a water-insoluble film-forming agent, for the production of a medicament for the treatment of psoriasis of the nail.
Spreading solvents are understood as meaning compounds which in a test 30 system as described in Arzneim. Forschung / Drug Res. 31 (Il), 8a, p. 1334, 1981 impart to the formulations according to the invention a higher spreading number than Example 12 from EP 0 226 984. Readily volatile solvents are understood as meaning compounds which have a boiling point which is under 80~C.
CA 02248977 1998-09-1~
Possible active compounds are, for example: leflunomide and its metabolite A 771726, propentofylline, pentoxifylline, cyclosporin A or glucocorticoids, e.g. alclometasone dipropionate, amcinonide, beclomethasone dipropionate, bendacort, betamethasone benzoate, 5 betamethasone dipropionate, betamethasone valerate, budesonide, chlorquinaldol, clioquinol, clobetasol propionate, clobetasone butyrate, desonide, desoximetasone, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, difluprednate, fluazacort, fluclorolone acetonide, fludroxycortide, flumethasone pivalate, fluocinolone acetonide, 10 fluocinonide, fluocortolone, fluorometholone, flupamesone, fluprednidene, fluprednidene acetate, flurandrenolide, halcinonide, halometasone, hydrocortamate, hydrocortisone butyrate, methylprednisolone aceponate, mometasone furoate, prednicarbate, prednisolone, prednisone, tixocortol, triamcinolone acetonide.
Possibile spreading compounds are, for example: dimethylisosorbitol, isopropyl myristate, isopropyl palmitate, decyl oleate, Cremophor EL.
Penetration-promoting substances are furthermore employed in these 20 formulations, such as, for example, oleyl oleate, n-octanol, N-methylpyrrolidone, hexyl laurate.
Suitable film-forming agents are, for example, substances based on cellulose nitrate or physiologically acceptable polymers, such as are 25 customary, for example, in cosmetics, preferably as a mixture with cellulose nitrate. Mention may be made, for example, of polyvinyl acetate and partially hydrolyzed polyvinyl acetate, copolymers of vinyl acetate on the one hand and acrylic acid or crotonic acid or monoalkyl maleates on the other hand, tertiary copolymers of vinyl acetate on the one hand and 30 crotonic acid and vinyl neodecanoate, or crotonic acid and vinyl propionate on the other hand, copolymers of methyl vinyl ether and monoalkyl maleates, in particular as monobutyl maleate, copolymers of fatty acid vinyl esters and acrylic acid or methacrylic acid, copolymers of N-vinylpyrrolidone, methacrylic acid and alkyl methacrylates, copolymers of CA 02248977 1998-09-1~
acrylic acid and methacrylic acid or alkyl acrylates or alkyl methacrylates, polyvinyl acetals and polyvinyl butyrals, alkyl-substituted poly-N-vinylpyrrolidones, alkyl esters of copolymers of olefins and maleic anhydride and reaction products of colophony with acrylic acid. In the esters, the alkyl radicals are usually short-chain and mostly have no more than four carbon atoms.
Suitable physiologically acceptable solvents are substances such as hydrocarbons, alcohols, ethers, ketones and esters which are customary in 10 cosmetics, in particular ethanol, isopropanol or acetic acid esters of monohydric alcohols, such as ethyl and butyl acetate.
The formulations according to the invention can furthermore contain additives customary in cosmetics, such as emollients based on phthalate 15 or camphor, dyes or dye pigments, pearl luster agents, sedimentation retardants, sulfonamide resins, silicates, perfumes, surface-active substances, e.g. wetting agents such as sodium dioctylsulfosuccinate (DONS) and/or PEG 400 monolaurate, Tween(~) 80, lanolin derivatives, sunscreens, such as 2-hydroxy-4-methoxybenzophenone, substances 20 having antibacterial and antimycotic activity, substances having keratolytic and/or keratoplastic action, such as ammonium sulfite, esters and salts of thioglycolic acid, urea, allantoin, enzymes, salicylic acid, complexing agents such as edetic acid and their salts and pH-adjusting substances 25 Colored or pigmented formulations have the advantage, for example, that they can be tailored to the cosmetic sense of the patient.
The total concentration of the antipsoriatic active compounds is from 0.1 to 10 percent by weight (in the following abbreviated %), in particular from 30 0.5% to 5%. The concentration of the spreadable solvent is from 0.1% to 10%. The concentration of the film-forming agent is from 3.0% to 35%. The total concentration of the volatile solvents is from 50% to 90%.
The formulations according to the invention have the following composltlons:
Example 1 (1) leflunomide 0.1 g (2) isopropyl palmitate 2.0 g (3) isopropanol 33.0 g (4) ethyl acetate 33.0 g (5) Gantrez(~) ES 435 31.9 g 10 Example 2 (1) leflunomide 5.0 g (2) isopropanol 38.5 g (3) ethyl acetate 38.5 g (4) Gantrez(~) ES 435 18.0 g Example 3 (1) leflunomide 10.0 g (2) isopropanol 31.9 9 (3) ethyl acetate 31 .9 g (4) isopropyl myristate 5.0 9 (5) Gantrez(~) ES435 21.2 g Example 4 (1) leflunomide 5.0 9 (2) salicylic acid 5.0 9 (3) hexyl laurate 10.0 g (4) isopropanol 27.0 9 (5) ethyl acetate 27.0 9 (6) Gantrez~ ES 435 26.0 9 . .
CA 02248977 1998-09-1~
Example 5 (1) A771726 0.5g (2) diisopropanolamine 0.3 g (3) dimethylisosorbitol 10.0 g (4) ethyl acetate 39.8 g (5) isopropanol 39.8 g (6) Gantrez(~) ES 435 9.6 g Example 6 (1) pentoxifylline 0.5 g (2) decyl oleate 3.0 g (3) isopropanol 32.5 g (4) ethyl acetate 32.5 g (5) Gantrez(3 ES435 31.5 g Example 7 (1) pentoxifylline 3.0 g (2) N-methylpyrrolidone 2.0 g (3) n-octanol 1.0 g (4) polyoxyethylene laurate1.0 g (5) isopropanol 44.4 g (6) ethyl acetate 44.4 g (7) Gantrez~) ES 435 4.2 g 25 Example 8 (1) pentoxifylline 5.0 g (2) N-methylpyrrolidone 2.0 g (3) n-octanol 1.0 g (4) polyoxyethylene laurate1.0 g (5) isopropanol 43.7g (6) ethyl acetate 43.7 g (7) Gantrez(~) ES 435 3.6 g CA 02248977 1998-09-1~
Example 9 (1) cyclosporin A 1.0 g (2) ethanol abs. 20.0 g (3) isopropanol 26.4 g (4) ethyl acetate 26.4 g (5) Cremophor~)EL 20.0 g (6) Gantrez(~ ES 435 6.2 g Example 10 (1) propentofylline 1.0 9 (2) oleyl oleate 1.0 g (3) ethyl acetate 65.5 9 (4) isopropanol 16.5 g (5) Gantrez(g) ES 435 16.0 g Example 11 (1) propentofylline 1.0 g (2) isopropanol 38.2 g (3) ethyl acetate 38.2 9 (4) hexyl laurate 5.0 g (5) Gantrez(~) ES 435 17.6 g Example 12 (1) Clobetasol-17-propionate 0.5 g (2) isopropyl palmitate 2.0 g (3) isopropanol 33.0 g (4) ethyl acetate 33.0 g (5) Gantrez(~) ES 435 31.5 g 30 The spreading power of the formulations according to the invention was investigated in comparison with Example 12 from EP 0 226 984. The spreading numbers were determined on thin-layer plates using (a) aluminum oxide layer (b) cellulose layer CA 02248977 1998-09-1~
(c) polyamide layer (d) kieselguhr layer (e) silica gel layer according to the process indicated in Arzneim.-Forschung/Drug Res. 31 (Il), 8a, p. 1334, 1981, which was modified as follows for measuring liquid formulations. The application of the liquid formulation to be investigated in each case was carried out in the inner lumen of a glass ring which was mounted in the center of the thin-layer plate. In each case 100 ~I were applied at 21 ~C.
. 10 Evaluation was carried out in the following way:
1. By determination of the final value of Z the total area of the spreading ability - idealized as circular area - was determined.
2. The spreading ability (cm2) characteristic for each formulation decreased by the application area results from this.
3. Relative spreading ability = spreading ability of the formulation divided by spreading ability of the comparison formulation.
4. Spreading number (%) = (relative spreading ability - 1 ) x 100.
Table 1 Thin-layer Example No.
plate Al oxide/RT 28.0 166.7 92.0 128.0 454.628.0 454.6 420.3 400.0 207.9 128.0 Kieselguhr/RT 0 121.7 94.0 32.0 362.7 0 403.9 491.3 362.7 166.5 136.2 D
Silica gel/RT-40.3 206.8 206.8 230.0 745.115.0 820.3 820.3 475.1 162.3 358.5 ~
Cellulose/RT 25.9 107.7 64.4 64.4 194.716.9 343.8 343.8 222.2 96.5 96.5 Polyamide/RT 15.5 107.9 129.4 74.3 175.415.5 322.5 251.9 337.4 129.3 107.9 o CA 02248977 1998-09-1~
It can be inferred from Table 1 that the spreading ability of the formulations according to the invention is greater by the following values than the spreading ability of the comparison formulation from EP 0 226 984, Example 12:
(a) aluminum oxide layer +28.0% to +454.6%
(b) kieselguhr layer + 0 % to + 491.3%
(c) silicagel layer -40.3% to +820.3%
(d) cellulose layer + 16.9% to + 343.8%
(e) polyamide layer + 15.5% to + 337.4%
The names of the formulation constituents used are:
2-Cyano-3-hydroxy-N-(4-trifluoroethylphenyl)crotonamide \~ NH /~\ CH3 CN
DMI: dimethylisosorbitol ~5 IPM: isopropyl myristate myristic acid isopropyl ester IPP: isopropyl palmitate ~0 PEG-35 Castor Oil polyethylene glycol derivative of castor oil containing on average 35 mol of ethylene oxide trade name e.g.: Cremophor~3) EL
CA 02248977 1998-09-1~
polyoxyethylene laurate, e.g.
Laureth-23 lauryl alcohol polyethylene glycol ether of the formula CH3(CH2), o~CH2(0CH2~CH2)n~~H
5 mean numerical value for n: 23; trade name: for example Brij 35(~) Gantrez(~) ES 435 (GAF Corporation New York) 50% strength solution of a copolymer of methyl vinyl ether and monobutyl maleate in isopropyl alcohol ' 10 Preparation process for the formulation An anhydrous, volatile solvent or solvent mixture is initially introduced and 15 a spreading solvent, a film-forming agent and an antipsoriatic active compound are added successively with stirring such that a solution or a suspension is formed.
Description Topical formulations for the treatment of psoriasis of the nail In the case of a psoriatic condition, finger- and toenails are also infected.
Generally, in the literature a frequency of infection of the nails of 10% -50% is assumed in the case of psoriasis.
10 In the case of psoriatic arthritis, it is to be assumed that 86.5% of the patients with psoriatic arthropathy have infection of the nail or changes to the nail.
(G. Lavaroni, F. Kokelj, P. Pauluzzi, G. Trevisan: The nails in psoriatic arthritis, Acta Derm Venereol (Stockh) (Suppl) 186,116-117,1994) Different expressions of the syndrome from depressions of the nail plate (pits on surface) through loosening of the nail plate up to abnormal thickenings of the nail plate and complete or alternatively only partial nail loss are observed.
Occasionally, the expression of the psoriasis is restricted to finger nails.
According to the present state of knowledge, the nails infected by psoriasis are treated with dithranol (local), PUVA, glucocorticoids and vitamin D
25 analogs (local) or systemic methotrexate, retinoids or cyclosporin A.
(Pschyrembel, Klin. Worterbuch [Clin. Dictionary], 257th edition, Walter de GruyterVerlag, Berlin, NewYork, 1994).
EP 0 634 170 describes formulations for the treatment of psoriasis.
30 To date, no simple, effective method for the treatment of psoriasis of the nail has been described. (Zaias, Nardo, The Nail in Health and Disease, MTP press limited, International Medical Publishers, Spectrum Publications Inc.1980).
CA 02248977 1998-09-1~
The disadvantage of the known formulations is that they only act superficially. Since they do not penetrate the nail, therapeutic doses of the pharmaceutical do not reach the nail matrix or the nail bed. The patient must therefore endure a long-lasting treatment, it being possible even a 5 short time after the end of the treatment for the psoriasis to flare up again.
The pharmaceutical formulations used by people who suffer from psoriasis of the nail are generally lipid-rich creams/ointments which have proven suitable in the dermal treatment of psoriasis, since, applied dermally, they 10 offer the patient an anti-drying effect and decreased itching, or alternatively solutions which are used, for example, in the topical application of glucocorticoids.
A further crucial disadvantage of the therapy with topical agents of this type 15 is that when washing, bathing and showering the formulations applied can be removed again from the nail surface or dissolved out of the nail with the incorporated active compound, and consequently thus then have to be newly applied again. Because of this, the treatment with these topical agents is ineffective and additionally extremely uneconomical.
The aim of the invention is to make available a formulation which does not have or only has to a minor extent the disadvantages described above.
The object is achieved by use of a formulation which consists of the active 25 compound, at least one spreading solvent, a readily volatile solvent and a water-insoluble film-forming agent, for the production of a medicament for the treatment of psoriasis of the nail.
Spreading solvents are understood as meaning compounds which in a test 30 system as described in Arzneim. Forschung / Drug Res. 31 (Il), 8a, p. 1334, 1981 impart to the formulations according to the invention a higher spreading number than Example 12 from EP 0 226 984. Readily volatile solvents are understood as meaning compounds which have a boiling point which is under 80~C.
CA 02248977 1998-09-1~
Possible active compounds are, for example: leflunomide and its metabolite A 771726, propentofylline, pentoxifylline, cyclosporin A or glucocorticoids, e.g. alclometasone dipropionate, amcinonide, beclomethasone dipropionate, bendacort, betamethasone benzoate, 5 betamethasone dipropionate, betamethasone valerate, budesonide, chlorquinaldol, clioquinol, clobetasol propionate, clobetasone butyrate, desonide, desoximetasone, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, difluprednate, fluazacort, fluclorolone acetonide, fludroxycortide, flumethasone pivalate, fluocinolone acetonide, 10 fluocinonide, fluocortolone, fluorometholone, flupamesone, fluprednidene, fluprednidene acetate, flurandrenolide, halcinonide, halometasone, hydrocortamate, hydrocortisone butyrate, methylprednisolone aceponate, mometasone furoate, prednicarbate, prednisolone, prednisone, tixocortol, triamcinolone acetonide.
Possibile spreading compounds are, for example: dimethylisosorbitol, isopropyl myristate, isopropyl palmitate, decyl oleate, Cremophor EL.
Penetration-promoting substances are furthermore employed in these 20 formulations, such as, for example, oleyl oleate, n-octanol, N-methylpyrrolidone, hexyl laurate.
Suitable film-forming agents are, for example, substances based on cellulose nitrate or physiologically acceptable polymers, such as are 25 customary, for example, in cosmetics, preferably as a mixture with cellulose nitrate. Mention may be made, for example, of polyvinyl acetate and partially hydrolyzed polyvinyl acetate, copolymers of vinyl acetate on the one hand and acrylic acid or crotonic acid or monoalkyl maleates on the other hand, tertiary copolymers of vinyl acetate on the one hand and 30 crotonic acid and vinyl neodecanoate, or crotonic acid and vinyl propionate on the other hand, copolymers of methyl vinyl ether and monoalkyl maleates, in particular as monobutyl maleate, copolymers of fatty acid vinyl esters and acrylic acid or methacrylic acid, copolymers of N-vinylpyrrolidone, methacrylic acid and alkyl methacrylates, copolymers of CA 02248977 1998-09-1~
acrylic acid and methacrylic acid or alkyl acrylates or alkyl methacrylates, polyvinyl acetals and polyvinyl butyrals, alkyl-substituted poly-N-vinylpyrrolidones, alkyl esters of copolymers of olefins and maleic anhydride and reaction products of colophony with acrylic acid. In the esters, the alkyl radicals are usually short-chain and mostly have no more than four carbon atoms.
Suitable physiologically acceptable solvents are substances such as hydrocarbons, alcohols, ethers, ketones and esters which are customary in 10 cosmetics, in particular ethanol, isopropanol or acetic acid esters of monohydric alcohols, such as ethyl and butyl acetate.
The formulations according to the invention can furthermore contain additives customary in cosmetics, such as emollients based on phthalate 15 or camphor, dyes or dye pigments, pearl luster agents, sedimentation retardants, sulfonamide resins, silicates, perfumes, surface-active substances, e.g. wetting agents such as sodium dioctylsulfosuccinate (DONS) and/or PEG 400 monolaurate, Tween(~) 80, lanolin derivatives, sunscreens, such as 2-hydroxy-4-methoxybenzophenone, substances 20 having antibacterial and antimycotic activity, substances having keratolytic and/or keratoplastic action, such as ammonium sulfite, esters and salts of thioglycolic acid, urea, allantoin, enzymes, salicylic acid, complexing agents such as edetic acid and their salts and pH-adjusting substances 25 Colored or pigmented formulations have the advantage, for example, that they can be tailored to the cosmetic sense of the patient.
The total concentration of the antipsoriatic active compounds is from 0.1 to 10 percent by weight (in the following abbreviated %), in particular from 30 0.5% to 5%. The concentration of the spreadable solvent is from 0.1% to 10%. The concentration of the film-forming agent is from 3.0% to 35%. The total concentration of the volatile solvents is from 50% to 90%.
The formulations according to the invention have the following composltlons:
Example 1 (1) leflunomide 0.1 g (2) isopropyl palmitate 2.0 g (3) isopropanol 33.0 g (4) ethyl acetate 33.0 g (5) Gantrez(~) ES 435 31.9 g 10 Example 2 (1) leflunomide 5.0 g (2) isopropanol 38.5 g (3) ethyl acetate 38.5 g (4) Gantrez(~) ES 435 18.0 g Example 3 (1) leflunomide 10.0 g (2) isopropanol 31.9 9 (3) ethyl acetate 31 .9 g (4) isopropyl myristate 5.0 9 (5) Gantrez(~) ES435 21.2 g Example 4 (1) leflunomide 5.0 9 (2) salicylic acid 5.0 9 (3) hexyl laurate 10.0 g (4) isopropanol 27.0 9 (5) ethyl acetate 27.0 9 (6) Gantrez~ ES 435 26.0 9 . .
CA 02248977 1998-09-1~
Example 5 (1) A771726 0.5g (2) diisopropanolamine 0.3 g (3) dimethylisosorbitol 10.0 g (4) ethyl acetate 39.8 g (5) isopropanol 39.8 g (6) Gantrez(~) ES 435 9.6 g Example 6 (1) pentoxifylline 0.5 g (2) decyl oleate 3.0 g (3) isopropanol 32.5 g (4) ethyl acetate 32.5 g (5) Gantrez(3 ES435 31.5 g Example 7 (1) pentoxifylline 3.0 g (2) N-methylpyrrolidone 2.0 g (3) n-octanol 1.0 g (4) polyoxyethylene laurate1.0 g (5) isopropanol 44.4 g (6) ethyl acetate 44.4 g (7) Gantrez~) ES 435 4.2 g 25 Example 8 (1) pentoxifylline 5.0 g (2) N-methylpyrrolidone 2.0 g (3) n-octanol 1.0 g (4) polyoxyethylene laurate1.0 g (5) isopropanol 43.7g (6) ethyl acetate 43.7 g (7) Gantrez(~) ES 435 3.6 g CA 02248977 1998-09-1~
Example 9 (1) cyclosporin A 1.0 g (2) ethanol abs. 20.0 g (3) isopropanol 26.4 g (4) ethyl acetate 26.4 g (5) Cremophor~)EL 20.0 g (6) Gantrez(~ ES 435 6.2 g Example 10 (1) propentofylline 1.0 9 (2) oleyl oleate 1.0 g (3) ethyl acetate 65.5 9 (4) isopropanol 16.5 g (5) Gantrez(g) ES 435 16.0 g Example 11 (1) propentofylline 1.0 g (2) isopropanol 38.2 g (3) ethyl acetate 38.2 9 (4) hexyl laurate 5.0 g (5) Gantrez(~) ES 435 17.6 g Example 12 (1) Clobetasol-17-propionate 0.5 g (2) isopropyl palmitate 2.0 g (3) isopropanol 33.0 g (4) ethyl acetate 33.0 g (5) Gantrez(~) ES 435 31.5 g 30 The spreading power of the formulations according to the invention was investigated in comparison with Example 12 from EP 0 226 984. The spreading numbers were determined on thin-layer plates using (a) aluminum oxide layer (b) cellulose layer CA 02248977 1998-09-1~
(c) polyamide layer (d) kieselguhr layer (e) silica gel layer according to the process indicated in Arzneim.-Forschung/Drug Res. 31 (Il), 8a, p. 1334, 1981, which was modified as follows for measuring liquid formulations. The application of the liquid formulation to be investigated in each case was carried out in the inner lumen of a glass ring which was mounted in the center of the thin-layer plate. In each case 100 ~I were applied at 21 ~C.
. 10 Evaluation was carried out in the following way:
1. By determination of the final value of Z the total area of the spreading ability - idealized as circular area - was determined.
2. The spreading ability (cm2) characteristic for each formulation decreased by the application area results from this.
3. Relative spreading ability = spreading ability of the formulation divided by spreading ability of the comparison formulation.
4. Spreading number (%) = (relative spreading ability - 1 ) x 100.
Table 1 Thin-layer Example No.
plate Al oxide/RT 28.0 166.7 92.0 128.0 454.628.0 454.6 420.3 400.0 207.9 128.0 Kieselguhr/RT 0 121.7 94.0 32.0 362.7 0 403.9 491.3 362.7 166.5 136.2 D
Silica gel/RT-40.3 206.8 206.8 230.0 745.115.0 820.3 820.3 475.1 162.3 358.5 ~
Cellulose/RT 25.9 107.7 64.4 64.4 194.716.9 343.8 343.8 222.2 96.5 96.5 Polyamide/RT 15.5 107.9 129.4 74.3 175.415.5 322.5 251.9 337.4 129.3 107.9 o CA 02248977 1998-09-1~
It can be inferred from Table 1 that the spreading ability of the formulations according to the invention is greater by the following values than the spreading ability of the comparison formulation from EP 0 226 984, Example 12:
(a) aluminum oxide layer +28.0% to +454.6%
(b) kieselguhr layer + 0 % to + 491.3%
(c) silicagel layer -40.3% to +820.3%
(d) cellulose layer + 16.9% to + 343.8%
(e) polyamide layer + 15.5% to + 337.4%
The names of the formulation constituents used are:
2-Cyano-3-hydroxy-N-(4-trifluoroethylphenyl)crotonamide \~ NH /~\ CH3 CN
DMI: dimethylisosorbitol ~5 IPM: isopropyl myristate myristic acid isopropyl ester IPP: isopropyl palmitate ~0 PEG-35 Castor Oil polyethylene glycol derivative of castor oil containing on average 35 mol of ethylene oxide trade name e.g.: Cremophor~3) EL
CA 02248977 1998-09-1~
polyoxyethylene laurate, e.g.
Laureth-23 lauryl alcohol polyethylene glycol ether of the formula CH3(CH2), o~CH2(0CH2~CH2)n~~H
5 mean numerical value for n: 23; trade name: for example Brij 35(~) Gantrez(~) ES 435 (GAF Corporation New York) 50% strength solution of a copolymer of methyl vinyl ether and monobutyl maleate in isopropyl alcohol ' 10 Preparation process for the formulation An anhydrous, volatile solvent or solvent mixture is initially introduced and 15 a spreading solvent, a film-forming agent and an antipsoriatic active compound are added successively with stirring such that a solution or a suspension is formed.
Claims (8)
1. The use of a formulation comprising at least one spreading solvent, at least one readily volatile solvent, a water-insoluble film-forming agent and at least one antipsoriatic active compound, for the production of a medicament for the treatment of psoriasis of the nail.
2. The use of a formulation as claimed in claim 1, wherein the formulation contains as active compound leflunomide, glucocorticoids, 2-cyano-3-hydroxy-N-(4-trifluoromethylphenyl)-crotonamide, cyclosporin A, pentoxifylline or propentofylline or a mixture of these active compounds.
3. The use of a formulation as claimed in claim 2, wherein the formulation contains the active compound in a total concentration of 0.1 to 20%, based on the total weight of the formulation, in particular of 0.5to 10%.
4. The use of a formulation as claimed in one or more of claims 1 to 3, wherein the formulation contains as spreading compound dimethylisosorbitol, isopropyl myristate, oleyl oleate, N-methyl-2-pyrrolidone or polyol fatty acid esters or a mixture of these compounds.
5. The use of a formulation as claimed in claim 1 or 4, wherein the formulation contains the spreading compound in a total concentration of 0.1% to 10%.
6. The use of a formulation as claimed in one or more of claims 1 to 5, wherein the formulation contains the film-forming agent in a concentration of 3.0% to 35%.
7. The use of a formulation as claimed in claims 1 and 6, wherein the formulation contains as film-forming agent a copolymer of methyl vinyl ether and monobutyl maleate.
8. The use of a formulation as claimed in one or more of claims 1,6 and 7, wherein the formulation contains as film-forming agent Gantrez R ES 435.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19610482 | 1996-03-16 | ||
| DE19610482.3 | 1996-03-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2248977A1 true CA2248977A1 (en) | 1997-09-25 |
Family
ID=7788561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002248977A Abandoned CA2248977A1 (en) | 1996-03-16 | 1997-02-26 | Topical formulations for the treatment of nail psoriasis |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP0888138A1 (en) |
| JP (1) | JP2000512265A (en) |
| KR (1) | KR20000064607A (en) |
| AU (1) | AU1876797A (en) |
| BR (1) | BR9708081A (en) |
| CA (1) | CA2248977A1 (en) |
| WO (1) | WO1997034644A1 (en) |
| ZA (1) | ZA972180B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004266053B2 (en) * | 2003-08-25 | 2011-06-09 | Bioequal Ag | Pharmaceutical and cosmetic formulations for treating fingernails |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RO118174B1 (en) * | 1997-08-21 | 2003-03-28 | Aventis Pharma Deutschland Gmbh | Nail polish and use thereof |
| AU2006256860B2 (en) * | 2005-06-10 | 2012-04-19 | Galderma S.A. | Controlled release of a drug through skin on the basis of a topical composition comprising a drug, a film-forming silicone and at least one volatile solvent |
| CA2775393C (en) * | 2012-05-02 | 2014-04-29 | Samy Saad | Topical non-aqueous pharmaceutical formulations |
| KR102327827B1 (en) | 2019-11-01 | 2021-11-18 | 한국과학기술연구원 | Composition for improving psoriasis symptom comprising extract of Curcuma longa L and UV treatment |
| KR102527907B1 (en) | 2020-09-14 | 2023-05-03 | 한국과학기술연구원 | Composition for improving psoriasis symptom comprising extract of Sphallerocaprus gracilis |
| KR102461001B1 (en) | 2020-09-14 | 2022-11-01 | 한국과학기술연구원 | Composition for improving psoriasis symptom comprising extract of Dianthus superbus L. |
| KR102451304B1 (en) | 2020-09-14 | 2022-10-07 | 한국과학기술연구원 | Composition for improving psoriasis symptom comprising extract of Thalictrum squarrosum steph |
| KR20230041255A (en) | 2021-09-17 | 2023-03-24 | 한국과학기술연구원 | Composition for improving psoriasis symptom comprising extract of Aruncus dioicus var. kamtschaticus |
| KR102692893B1 (en) | 2021-09-17 | 2024-08-08 | 한국과학기술연구원 | Composition for improving psoriasis symptom comprising cimicifugolide A |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2002795B (en) * | 1977-07-15 | 1982-03-17 | Mallinckrodt Inc | Nail enamel compositions their preparation and use |
| GB2085297B (en) * | 1980-10-08 | 1984-06-13 | Bernstein Joel Edward | Composition for treating psoriasis of the fingernails |
| DE3045914A1 (en) * | 1980-12-05 | 1982-07-22 | Bayer Ag, 5090 Leverkusen | ANTIMYCOTIC AGENTS WITH HIGH ACTIVE SUBSTANCE RELEASE IN THE FORM OF ELASTIC LIQUID PLASTERS |
| ATE84208T1 (en) * | 1985-11-04 | 1993-01-15 | Owen Galderma Lab Inc | FILM FORMING MEDICATION CARRIERS FOR ADMINISTRATION OF MEDICATIONS TO NAILS; METHOD OF USE. |
| HU219480B (en) * | 1991-05-23 | 2001-04-28 | Novartis Ag. | Process for producing locally applicable pharmaceutical compositions comprising allylamine derivative against fungus infection of nails |
| KR100200447B1 (en) * | 1993-07-28 | 1999-06-15 | 디. 제이. 우드, 스피겔 알렌 제이 | Composition for psoriasis treatment |
| DK128494A (en) * | 1994-11-08 | 1996-05-09 | Edel K Seidenschnur | Treatment of keratinous and psoriatic disease states with nail polish containing vitamin D metabolite, or derivative, and / or vitamin A derivative |
-
1997
- 1997-02-26 AU AU18767/97A patent/AU1876797A/en not_active Abandoned
- 1997-02-26 KR KR1019980707296A patent/KR20000064607A/en not_active Application Discontinuation
- 1997-02-26 EP EP97905085A patent/EP0888138A1/en not_active Withdrawn
- 1997-02-26 CA CA002248977A patent/CA2248977A1/en not_active Abandoned
- 1997-02-26 BR BR9708081A patent/BR9708081A/en not_active Application Discontinuation
- 1997-02-26 WO PCT/EP1997/000905 patent/WO1997034644A1/en not_active Application Discontinuation
- 1997-02-26 JP JP09533072A patent/JP2000512265A/en active Pending
- 1997-03-13 ZA ZA9702180A patent/ZA972180B/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2004266053B2 (en) * | 2003-08-25 | 2011-06-09 | Bioequal Ag | Pharmaceutical and cosmetic formulations for treating fingernails |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20000064607A (en) | 2000-11-06 |
| ZA972180B (en) | 1997-09-16 |
| WO1997034644A1 (en) | 1997-09-25 |
| JP2000512265A (en) | 2000-09-19 |
| EP0888138A1 (en) | 1999-01-07 |
| AU1876797A (en) | 1997-10-10 |
| BR9708081A (en) | 1999-07-27 |
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