EP0888138A1 - Topical formulations for the treatment of nail psoriasis - Google Patents

Topical formulations for the treatment of nail psoriasis

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Publication number
EP0888138A1
EP0888138A1 EP97905085A EP97905085A EP0888138A1 EP 0888138 A1 EP0888138 A1 EP 0888138A1 EP 97905085 A EP97905085 A EP 97905085A EP 97905085 A EP97905085 A EP 97905085A EP 0888138 A1 EP0888138 A1 EP 0888138A1
Authority
EP
European Patent Office
Prior art keywords
formulation
formulation according
spreading
film former
treatment
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP97905085A
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German (de)
French (fr)
Inventor
Walter Petri
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hoechst AG
Original Assignee
Hoechst AG
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Filing date
Publication date
Application filed by Hoechst AG filed Critical Hoechst AG
Publication of EP0888138A1 publication Critical patent/EP0888138A1/en
Withdrawn legal-status Critical Current

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Classifications

    • 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
    • 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
    • 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
    • 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
    • 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

Definitions

  • Dithranol (local), PUVA, glucocorticoids and vitamin D analogues (local) or systemic methotrexate, retinoids, cyclosporin A treated.
  • EP 0 634 170 describes formulations for the treatment of psoriasis.
  • the invention aims to provide a formulation which does not have the disadvantages described above or has them only to a minor extent.
  • the object is achieved by using a formulation which consists of the active ingredient, at least one spreading solvent, a volatile solvent and a water-insoluble film former for the manufacture of a medicament for the treatment of nail psoriasis.
  • Spreading solvents are understood to mean compounds which are found in a test system, as in Pharm. Research / Drug Res. 31 (II), 8a, p. 1 334, 1981, give the formulations according to the invention a higher spread number than Example 12 from EP 0 226 984.
  • Volatile solvents are understood to mean compounds which have a boiling point which is below 80 ° C.
  • active ingredients come e.g. in question: leflunomide and its metabolite A 77 1726, propentofylline, pentoxifylline, cyclosporin A or glucocorticoids, e.g. Alclometasone dipropionate, amcinonide, beclomethasone dipropionate, Bendacort, betamethasone benzoate, betamethasone dipropionate, betamethasone valerate, budesonide, chlorquinaldol, clioquinol, clobetasol propionate, clobetasone butyrate, desonide, desoximetasone, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone, difluprednate, fluazacort, flucinolone acetonide, fluclorolone, fludroxycortide, Flumathasonpivalat, Fluocinolonacetonide, Fluocino
  • Penetration-promoting substances are also used in these formulations, e.g. Oleyl oleate, n-octanol, N-methylpyrrolidone, hexyl laurate.
  • Suitable film formers are, for example, substances based on cellulose nitrate or physiologically harmless polymers, as are customary, for example, in cosmetics, preferably as a mixture with cellulose nitrate.
  • Examples include polyvinyl acetate and partially saponified 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 crotonic acid and vinyl neodecanoate, or crotonic acid and vinyl propionate on the other hand, copolymers of methyl vinyl ether and monoalkyl maleate, in particular as monobutyl maleate, copolymers of Fettklavinylester and acrylic acid or methacrylic acid, copolymers of N-vinylpyrrolidone, methacrylic acid and alkyl methacrylate, copolymers of acrylic acid and methacrylic acid
  • Suitable physiologically acceptable solvents are substances such as hydrocarbons, alcohols, ethers, ketones and esters customary in 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 phthalate or camphor-based plasticizers, dyes or colored pigments, pearlescent agents, sedimentation retardants, sulfonamide resins, silicates, fragrances, surface-active substances, for example wetting agents such as sodium dioctylsulfosuccinate (DONS) and / or PEG-400 monolaurate, Tween ® 80, lanolin derivatives, photoprotective agents such as 2-hydroxy-4-methoxybenzophenone, antibacterial and antimycotic active substances, substances with a 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 its salts and pH-adjusting substances.
  • Colored or pigmented formulations have the advantage, for example, that they can be
  • the total concentration of the antipsoriatic active ingredients is from 0.1 to 10 percent by weight (hereinafter abbreviated as%), in particular from 0.5% to 5%.
  • the concentration of the spreading solvent is from 0.1% to 10%.
  • the concentration of the film former is from 3.0% to 35%.
  • the total concentration of volatile solvents is from 50% to 90%.
  • compositions according to the invention have the following compositions:
  • silica gel layer determined according to the method given in Pharmaceutical Research / Drug Res. 31 (II), 8a, p. 1334, 1981, which was modified for measuring liquid formulations as follows.
  • the liquid formulation to be examined was applied into the inner lumen of a glass ring which was placed in the center of the thin-layer plate. In each case 100 ⁇ l were applied at 21 ° C.
  • the total area of the spreading capacity - idealized as a circular area - was determined by determining the final value of Z.
  • Relative spreading capacity spreading capacity of the formulation divided by spreading capacity of the comparison formulation.
  • IPP isopropyl palmitate
  • An anhydrous, volatile solvent or solvent mixture is introduced and, with stirring, a spreading solvent, a film former and an antipsoriatic active ingredient are added in succession so that a solution or a suspension is formed.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Materials Engineering (AREA)
  • Birds (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (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

Beschreibungdescription
Topische Formulierungen zur Behandlung von Nagel-PsoriasisTopical formulations for the treatment of nail psoriasis
Im Falle einer Erkrankung an Psoriasis werden auch Finger- und Fußnägel befallen. Allgemein geht man in der Literatur von 10 % - 50 % Befallshäufigkeit der Nägel im Falle einer Psoriasis aus.In the case of psoriasis, fingernails and toenails are also affected. In general, the literature assumes a 10% - 50% frequency of nails in the case of psoriasis.
Im Falle von "psoriatic arthritis" ist davon auszugehen, daß 86,5 % derIn the case of "psoriatic arthritis" it can be assumed that 86.5% of the
Patienten mit Psoriasis-Arthropathie einen Nagelbefall bzw. Nagelveränderungen aufweisen.Patients with psoriatic arthropathy have a nail infection or changes.
(G. Lavaroni, F. Kokelj, P. Pauluzzi, G. Trevisan: The nails in psoriatic arthritis,(G. Lavaroni, F. Kokelj, P. Pauluzzi, G. Trevisan: The nails in psoriatic arthritis,
Acta Derm Venereol (Stockh) (SuppI) 186, 1 16-1 17, 1 994)Acta Derm Venereol (Stockh) (SuppI) 186, 1 16-1 17, 1 994)
Man beobachtet unterschiedliche Ausprägungen des Krankheitsbildes von Vertiefungen der Nagelplatte (pits on surface) über Lockerung der Nagelplatte bis zu abnormen Verdickungen der Nagelplatte und vollständigem oder auch nur teilweisem Nagelverlust.Different manifestations of the clinical picture are observed, from pits on the surface of the nail plate to loosening of the nail plate to abnormal thickening of the nail plate and complete or only partial nail loss.
Gelegentlich ist die Ausprägung der Psoriasis auf Fingernägel beschränkt.Occasionally, the expression of psoriasis is limited to fingernails.
Nach heutigem Kenntnisstand werden die von Psoriasis befallenen Nägel mitAccording to the current state of knowledge, the nails affected by psoriasis also become
Dithranol (lokal), PUVA, Glukokorticoiden und Vitamin D-Analoga (lokal) oder systemisch Methotrexat, Retinoiden, Cyclosporin A behandelt.Dithranol (local), PUVA, glucocorticoids and vitamin D analogues (local) or systemic methotrexate, retinoids, cyclosporin A treated.
(Pschyrembel, Klin. Wörterbuch, 257. Auflage, Walter de Gruyter Verlag, Berlin,(Pschyrembel, Klin. Wörterbuch, 257th edition, Walter de Gruyter Verlag, Berlin,
New York, 1994).New York, 1994).
EP 0 634 170 beschreibt Formulierungen zur Behandlung von Psoriasis.EP 0 634 170 describes formulations for the treatment of psoriasis.
Bisher ist keine einfache, effektive Methode zur Behandlung der Nagelpsoriasis beschrieben. (Zaias, Nardo, The Nail in Health and Disease, MTP press limited, International Medical Publishers, Spectrum Publications Inc. 1980). Nachteil der bekannten Formulierungen ist, daß sie nur oberflächig wirken. Da sie den Nagel nicht penetrieren, gelangen keine therapeutischen Dosen des Arzneistoffes an die Nagelmatrix oder an das Nagelbett. Der Patient muß deshalb eine lang andauernde Behandlung erdulden, wobei bereits kurze Zeit nach Ende der Behandlung die Psoriasis wieder aufflammen kann.So far, no simple, effective method for treating nail psoriasis has been described. (Zaias, Nardo, The Nail in Health and Disease, MTP press limited, International Medical Publishers, Spectrum Publications Inc. 1980). The disadvantage of the known formulations is that they only act on the surface. Since they do not penetrate the nail, no therapeutic doses of the drug reach the nail matrix or the nail bed. The patient must therefore endure long-term treatment, and the psoriasis may flare up again shortly after the end of the treatment.
Als pharmazeutische Formulierungen benutzen Personen, die an Nagel-Psoriasis erkrankt sind, in der Regel lipoidreiche Cremes/Salben, die sich bei der dermalen Behandlung der Psoriasis bewährt haben, da sie dermal angewendet für den Patienten einen anti-austrocknenden Effekt und verminderten Juckreiz bringen, oder auch Lösungen, die z.B. bei der topischen Applikation von Glukokorticoiden zur Anwendung gelangen.As a pharmaceutical formulations, people suffering from nail psoriasis generally use lipoid-rich creams / ointments that have proven their worth in dermal treatment of psoriasis, because when applied dermally they have an anti-drying effect and reduced itching for the patient. or solutions that, for example in the topical application of glucocorticoids.
Ein weiterer entscheidender Nachteil der Therapie mit Topika dieser Art ist, daß beim Waschen, Baden und Duschen die aufgetragenen Formulierungen mit dem inkorporierten Wirkstoff von der Nageloberfläche wieder entfernt bzw. aus dem Nagel herausgelöst werden können, mithin also danach wieder neu aufgetragen werden müssen. Die Behandlung mit diesen Topika ist infolgedessen ineffektiv und zudem höchst unökonomisch.Another decisive disadvantage of therapy with topicals of this type is that the formulations applied with the incorporated active ingredient can be removed from the nail surface or detached from the nail surface during washing, bathing and showering, and must therefore be reapplied afterwards. As a result, treatment with these topicals is ineffective and also highly uneconomical.
Die Erfindung bezweckt eine Formulierung zur Verfügung zu stellen, die vorstehend beschriebene Nachteile nicht oder nur in untergeordnetem Maße besitzt.The invention aims to provide a formulation which does not have the disadvantages described above or has them only to a minor extent.
Die Aufgabe wird gelöst durch Verwendung einer Formulierung, die aus dem Wirkstoff, mindestens einem spreitenden Lösungsmittel, einem leicht flüchtigen Lösungsmittel und einem wasserunlöslichen Filmbildner besteht, zur Herstellung eines Medikaments zur Behandlung von Nagelpsoriasis.The object is achieved by using a formulation which consists of the active ingredient, at least one spreading solvent, a volatile solvent and a water-insoluble film former for the manufacture of a medicament for the treatment of nail psoriasis.
Unter spreitenden Lösungsmitteln werden Verbindungen verstanden, die in einem Testsytem, wie in Arzneim. Forschung / Drug Res. 31 (II), 8a, S. 1 334, 1981 beschrieben, den erfindungsgemäßen Formulierungen eine höhere Spreitzahl verleihen als Beispiel 12 aus EP 0 226 984. Unter leicht flüchtigen Lösungsmitteln werden Verbindungen verstanden, die einen Siedepunkt besitzen, der unter 80°C liegt.Spreading solvents are understood to mean compounds which are found in a test system, as in Pharm. Research / Drug Res. 31 (II), 8a, p. 1 334, 1981, give the formulations according to the invention a higher spread number than Example 12 from EP 0 226 984. Volatile solvents are understood to mean compounds which have a boiling point which is below 80 ° C.
Als Wirkstoffe kommen z.B. in Frage: Leflunomid und sein Metabolit A 77 1726, Propentofyllin, Pentoxifyllin, Cyclosporin A oder Glukokorticoide, z.B. Alclometasondipropionat, Amcinonid, Beclomethasondipropionat, Bendacort, Betamethasonbenzoat, Betamethasondipropionat, Betamethasonvalerat, Budesonid, Chlorquinaldol, Clioquinol, Clobetasolpropionat, Clobetasonbutyrat, Desonid, Desoximetason, Dexamethason, Dichlorison, Diflorasondiacetat, Diflucortolonvalerat, Difluprednat, Fluazacort, Flucinolonacetonid, Fluclorolonacetonid, Fludroxycortid, Flumathasonpivalat, Fluocinolonacetonide, Fluocinoid, Fluocortolon, Fluormetholon, Flupameson, Flupredniden, Fluprednidenacetat, Flurandrenolid, Halcinonid, Halometason, Hydrocortamat, Hydrocortisonbutyrat, Methylprednisonolonaceponat, Mometasonfuroat, Prednicarbat, Prednisolon, Prednison, Tixocortol, Triamcinolonacetonid.As active ingredients come e.g. in question: leflunomide and its metabolite A 77 1726, propentofylline, pentoxifylline, cyclosporin A or glucocorticoids, e.g. Alclometasone dipropionate, amcinonide, beclomethasone dipropionate, Bendacort, betamethasone benzoate, betamethasone dipropionate, betamethasone valerate, budesonide, chlorquinaldol, clioquinol, clobetasol propionate, clobetasone butyrate, desonide, desoximetasone, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone, difluprednate, fluazacort, flucinolone acetonide, fluclorolone, fludroxycortide, Flumathasonpivalat, Fluocinolonacetonide, Fluocinoid, Fluocortolon, Fluormetholon, Flupameson, Flupredniden, Fluprednidenacetat, Flurandrenolid, Halcinonid, Halometason, Hydrocortamat, Hydrocortisonbutyrat, Methylprednisonolonaceponat, Mometasonfuroat, Prednicocortonon, Trisonolonolonolon, Prednisolonone, Prednisolonone.
Als spreitende Verbindungen kommen z.B. in Frage: Dimethylisosorbit, Isopropylmyristat, Isopropylpalmitat, Ölsäuredecylester, Cremophor EL.As spreading connections come e.g. in question: dimethyl isosorbitol, isopropyl myristate, isopropyl palmitate, oleic acid decyl ester, Cremophor EL.
Weiterhin werden penetrationsfördernde Substanzen in diesen Formulierungen eingesetzt, wie z.B. Oleyloleat, n-Octanol, N-Methylpyrrolidon, Laurinsäurehexylester.Penetration-promoting substances are also used in these formulations, e.g. Oleyl oleate, n-octanol, N-methylpyrrolidone, hexyl laurate.
Als Filmbildner eignen sich z.B. Stoffe auf der Basis von Cellulosenitrat oder physiologisch unbedenkliche Polymerisate, wie sie z.B. in Kosmetika üblich sind, vorzugsweise als Gemisch mit Cellulosenitrat. Genannt seien z.B. Polyvinylacetat und partiell verseiftes Polyvinylacetat, Mischpolymerisate aus Vinylacetat einerseits und Acrylsaure oder Crotonsaure oder Maleinsäuremonoalkylester andererseits, tertiäre Mischpolymerisate aus Vinylacetat einerseits und Crotonsaure und Vinylneodecanoat, oder Crotonsaure und Vinylpropionat andererseits, Mischpolymerisate aus Methylvinylether und Maleinsäuremonoalkylester, insbesondere als Maleinsäuremonobutylester, Mischpolymerisate aus Fettsäurevinylester und Acrylsaure oder Methacrylsäure, Mischpolymerisate aus N-Vinylpyrrolidon, Methacrylsäure und Methacrylsäurealkylester, Mischpolymerisate aus Acrylsaure und Methacrylsäure oder Acrylsäurealkylester oder Methacrylsäurealkylester, Polyvinylacetale und Polyvinylbutyrale, alkylsubstituierte Poly-N- vinylpyrrolidone, Alkylester aus Mischpolymerisaten aus Olefinen und Maleinsäureanhydrid und Umsetzungsprodukte von Kolophonium mit Acrylsaure. In den Estern sind die Alkylreste gewöhnlich kurzkettig und haben meistens nicht mehr als vier C-Atome.Suitable film formers are, for example, substances based on cellulose nitrate or physiologically harmless polymers, as are customary, for example, in cosmetics, preferably as a mixture with cellulose nitrate. Examples include polyvinyl acetate and partially saponified 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 crotonic acid and vinyl neodecanoate, or crotonic acid and vinyl propionate on the other hand, copolymers of methyl vinyl ether and monoalkyl maleate, in particular as monobutyl maleate, copolymers of Fettsäurevinylester and acrylic acid or methacrylic acid, copolymers of N-vinylpyrrolidone, methacrylic acid and alkyl methacrylate, copolymers of acrylic acid and methacrylic acid or acrylic acid alkyl ester or methacrylic acid alkyl ester, polyvinyl acetals and polyvinyl butyrals, alkyl-substituted poly-N-vinyl pyrrolidones, alkyl esters from copolymers of olefins and maleic anhydride and reaction products of rosin with acrylic acid. In the esters, the alkyl radicals are usually short-chain and usually have no more than four carbon atoms.
Als physiologisch unbedenkliche Lösemittel kommen Stoffe wie in Kosmetika übliche Kohlenwasserstoffe, Alkohole, Ether, Ketone und Ester in Betracht, insbesondere Ethanol, Isopropanol oder Essigsäureester von einwertigen Alkoholen, wie Ethyl- und Butylacetat.Suitable physiologically acceptable solvents are substances such as hydrocarbons, alcohols, ethers, ketones and esters customary in cosmetics, in particular ethanol, isopropanol or acetic acid esters of monohydric alcohols, such as ethyl and butyl acetate.
Die erfindungsgemäßen Formulierungen können weiterhin in Kosmetika gebräuchliche Zusätze enthalten, wie Weichmacher auf Phthalat- oder Campherbasis, Farbstoffe bzw. Farbpigmente, Perlglanzmittel, Sedimentationsverzögerer, Sulfonamidharze, Silikate, Riechstoffe, oberflächenaktive Stoffe, z.B. Netzmittel wie Natriumdioctylsulfosuccinat (DONS) und/oder PEG-400-Monolaurat, Tween® 80, Lanolinderivate, Lichtschutzmittel, wie 2-Hydroxy-4-methoxybenzophenon, antibakteriell und antimykotisch wirksame Substanzen, Stoffe mit keratolytischer und/oder keratoplastischer Wirkung, wie Ammoniumsulfit, Ester und Salze der Thioglykolsäure, Harnstoff, Allantoin, Enzyme, Salizylsäure, Komplexbildner wie Edetinsäure und deren Salze und pH-Wert-einstellende Substanzen. Gefärbte bzw. pigmentierte Formulierungen haben z.B. den Vorteil, daß sie dem Schönheitsempfinden des Patienten angepaßt werden können.The formulations according to the invention can furthermore contain additives customary in cosmetics, such as phthalate or camphor-based plasticizers, dyes or colored pigments, pearlescent agents, sedimentation retardants, sulfonamide resins, silicates, fragrances, surface-active substances, for example wetting agents such as sodium dioctylsulfosuccinate (DONS) and / or PEG-400 monolaurate, Tween ® 80, lanolin derivatives, photoprotective agents such as 2-hydroxy-4-methoxybenzophenone, antibacterial and antimycotic active substances, substances with a 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 its salts and pH-adjusting substances. Colored or pigmented formulations have the advantage, for example, that they can be adapted to the patient's sense of beauty.
Die Gesamtkonzentration der antipsoriatischen Wirkstoffe beträgt von 0, 1 bis 10 Gewichtsprozent (im folgenden % abgekürzt), insbesondere von 0,5 % bis 5 %. Die Konzentration des spreitenden Lösungsmittels beträgt von 0, 1 % bis 10 %. Die Konzentration des Filmbildners beträgt von 3,0 % bis 35 %. Die Gesamtkonzentration der flüchtigen Lösungsmittel beträgt von 50 % bis 90 %.The total concentration of the antipsoriatic active ingredients is from 0.1 to 10 percent by weight (hereinafter abbreviated as%), in particular from 0.5% to 5%. The concentration of the spreading solvent is from 0.1% to 10%. The concentration of the film former is from 3.0% to 35%. The total concentration of volatile solvents is from 50% to 90%.
Die erfindungsgemäßen Formulierungen weisen folgende Zusammensetzungen auf:The formulations according to the invention have the following compositions:
Beispiel 1example 1
(1 ) Leflunomid 0, 1 g(1) Leflunomide 0.1 g
(2) Isopropylpalmitat 2,0 g(2) Isopropyl palmitate 2.0 g
(3) Isopropanol 33,0 g(3) Isopropanol 33.0 g
(4) Ethylacetat 33,0 g(4) Ethyl acetate 33.0 g
(5) Gantrez® ES 435 31 ,9 g(5) Gantrez ® ES 435 31.9 g
Beispiel 2Example 2
(1 ) Leflunomid 5,0 g(1) Leflunomide 5.0 g
(2) Isopropanol 38,5 g(2) Isopropanol 38.5 g
(3) Ethylacetat 38,5 g(3) Ethyl acetate 38.5 g
(4) Gantrez® ES 435 18,0 g(4) Gantrez ® ES 435 18.0 g
Beispiel 3Example 3
(1 ) Leflunomid 10,0 g(1) Leflunomide 10.0 g
(2) Isopropanol 31 ,9 g(2) Isopropanol 31.9 g
(3) Ethylacetat 31 ,9 g(3) Ethyl acetate 31.9 g
(4) Isopropylmyristat 5,0 g(4) isopropyl myristate 5.0 g
(5) Gantrez® ES 435 21 ,2 g Beispiel 4(5) Gantrez ® ES 435 21, 2 g Example 4
(1 ) Leflunomid 5,0 g(1) Leflunomide 5.0 g
(2) Salicylsäure 5,0 g(2) salicylic acid 5.0 g
(3) Laurylsäurehexylester 1 0,0 g(3) Lauryl acid hexyl ester 1 0.0 g
(4) Isopropanol 27,0 g(4) Isopropanol 27.0 g
(5) Ethylacetat 27,0 g(5) Ethyl acetate 27.0 g
(6) Gantrez® ES 435 26,0 g(6) Gantrez ® ES 435 26.0 g
Beispiel 5Example 5
(1 ) A 77 1726 0,5 g(1) A 77 1726 0.5 g
(2) Diisopropanolamin 0,3 g(2) Diisopropanolamine 0.3 g
(2) Dimethylisosorbit 10,0 g(2) Dimethyl isosorbitol 10.0 g
(3) Ethylacetat 39,8 g(3) Ethyl acetate 39.8 g
(4) Isopropanol 39,8 g(4) Isopropanol 39.8 g
(5) Gantrez® ES 435 9,6 g(5) Gantrez ® ES 435 9.6 g
Beisp iel 6Example 6
(1 ) Pentoxifyllin 0,5 g(1) pentoxifylline 0.5 g
(2) Ölsäuredecylester 3,0 g(2) 3.0 g of oleic acid
(3) Isopropanol 32,5 g(3) isopropanol 32.5 g
(4) Ethylacetat 32,5 g(4) Ethyl acetate 32.5 g
(5) Gantrez® ES 435 31 ,5 g(5) Gantrez ® ES 435 31.5 g
Beispiel 7Example 7
( 1 ) Pentoxifyllin 3,0 g(1) Pentoxifylline 3.0 g
(2) N-Methylpyrrolidon 2,0 g(2) N-methylpyrrolidone 2.0 g
(3) n-Octanol 1 ,0 g(3) n-octanol 1.0 g
(4) Polyoxyethylenlaurat 1 ,0 g(4) Polyoxyethylene laurate 1.0 g
(5) Isopropanol 44,4 g(5) Isopropanol 44.4 g
(6) Ethylacetat 44,4 g(6) ethyl acetate 44.4 g
(7) Gantrez® ES 435 4,2 g Beispiel 8(7) Gantrez ® ES 435 4.2 g Example 8
(1) Pentoxifyllin 5,0 g(1) Pentoxifylline 5.0 g
(2) N-Methylpyrrolidon 2,0 g(2) N-methylpyrrolidone 2.0 g
(3) n-Octanol 1,0g(3) n-octanol 1.0 g
(4) Polyoxyethylenlaurat 1,0g(4) Polyoxyethylene laurate 1.0g
(5) Isopropanol 43,7 g(5) Isopropanol 43.7 g
(6) Ethylacetat 43,7 g(6) ethyl acetate 43.7 g
(7) Gantrez® ES 435 3,6 g(7) Gantrez ® ES 435 3.6 g
Beispiel 9Example 9
(1) Cyclosporin A 1,0g(1) Cyclosporin A 1.0g
(2) Ethanol abs. 20,0 g(2) ethanol abs. 20.0 g
(3) Isopropanol 26,4 g(3) Isopropanol 26.4 g
(4) Ethylacetat 26,4 g(4) Ethyl acetate 26.4 g
(5) Cremophor® EL 20,0 g(5) Cremophor ® EL 20.0 g
(6) Gantrez® ES 435 6,2 g(6) Gantrez ® ES 435 6.2 g
Beispiel 10Example 10
(1) Propentofyllin 1,0g(1) propentofylline 1.0g
(2) Oleyloleat 1,0 g(2) Oleyl oleate 1.0 g
(3) Ethylacetat 65,5 g(3) ethyl acetate 65.5 g
(4) Isopropanol 16,5 g(4) isopropanol 16.5 g
(5) Gantrez® ES 435 16,0 g(5) Gantrez ® ES 435 16.0 g
Beispiel 11Example 11
(1) Propentofyllin 1,0g(1) propentofylline 1.0g
(2) Isopropanol 38,2 g(2) Isopropanol 38.2 g
(3) Ethylacetat 38,2 g(3) ethyl acetate 38.2 g
(4) Laurinsäurehexylester 5,0 g(4) lauric acid hexyl ester 5.0 g
(5) Gantrez® ES 435 17,6 g Beisp iel 12(5) Gantrez ® ES 435 17.6 g Example 12
(1 ) Clobetasol-17-propionat 0,5 g(1) Clobetasol 17-propionate 0.5 g
(2) Isopropylpalmitat 2,0 g(2) Isopropyl palmitate 2.0 g
(3) Isopropanol 33,0 g(3) Isopropanol 33.0 g
(4) Ethylacetat 33,0 g(4) Ethyl acetate 33.0 g
(5) Gantrez® ES 435 31 ,5 g(5) Gantrez ® ES 435 31.5 g
Das Spreitvermögen der erfindungsgemäßen Formulierungen wurde im Vergleich zu Beispiel 12 aus EP 0 226 984 untersucht. Die Spreitzahlen wurden auf Dünnschichtplatten mitThe spreadability of the formulations according to the invention was investigated in comparison to Example 12 from EP 0 226 984. The spreading numbers were recorded on thin-layer plates
(a) Aluminiumoxidschicht(a) Alumina layer
(b) Celluloseschicht(b) cellulose layer
(c) Polyamidschicht(c) polyamide layer
(d) Kieselgurschicht(d) Diatomaceous earth layer
(e) Kieselgelschicht nach dem in Arzneim.-Forschung/Drug Res. 31 (II), 8a, S. 1334, 1981 angegebenen Verfahren bestimmt, das zum Messen von flüssigen Formulierungen wie folgt modifiziert wurde. Der Auftrag der jeweils zu untersuchenden flüssigen Formulierung erfolgte in das innere Lumen eines Glasringes hinein, der im Zentrum der Dünnschichtplatte aufgesetzt war. Es wurden jeweils 100 μl bei 21 °C aufgetragen.(e) silica gel layer determined according to the method given in Pharmaceutical Research / Drug Res. 31 (II), 8a, p. 1334, 1981, which was modified for measuring liquid formulations as follows. The liquid formulation to be examined was applied into the inner lumen of a glass ring which was placed in the center of the thin-layer plate. In each case 100 μl were applied at 21 ° C.
Die Auswertung wurde folgendermaßen vorgenommen:The evaluation was carried out as follows:
1. Durch Bestimmung des Endwertes von Z wurde die Gesamtfläche des Spreitvermögens - idealisiert als Kreisfläche - bestimmt.1. The total area of the spreading capacity - idealized as a circular area - was determined by determining the final value of Z.
2. Vermindert um die Auftragsfläche ergibt sich daraus das für jede Formulierung charakteristische Spreitvermögen (cm2). 3. Relatives Spreitvermögen = Spreitvermögen der Formulierung dividiert durch Spreitvermögen der Vergleichsformulierung.2. Reduced by the application area, this results in the characteristic spreading capacity (cm 2 ) for each formulation. 3. Relative spreading capacity = spreading capacity of the formulation divided by spreading capacity of the comparison formulation.
4. Spreitzahl (%) = (Relatives Spreitvermögen - 1 ) x 100. 4. Spreading rate (%) = (relative spreading capacity - 1) x 100.
3 o3 o
Tabelle 1 SO ö * O-s 4- 4-.Table 1 SO ö * O-s 4- 4-.
sofl sofl
OO
$ $
Aus Tabelle 1 ist abzulesen, daß das Spreitvermögen der erfindungsgemäßen Formulierungen um folgende Werte größer ist, als das Spreitvermögen der Vergleichsformulierung aus EP 0 226 984, Beispiel 12 :It can be seen from Table 1 that the spreadability of the formulations according to the invention is greater by the following values than the spreadability of the comparative formulation from EP 0 226 984, Example 12:
(a) Aluminiumoxidschicht + 28,0 % bis + 454,6 %(a) aluminum oxide layer + 28.0% to + 454.6%
(b) Kieselgurschicht + 0 % bis + 491 ,3 %(b) diatomaceous earth layer + 0% to + 491.3%
(0 Kieselgelschicht - 40,3 % bis + 820,3 %(0 silica gel layer - 40.3% to + 820.3%
(d) Celluloseschicht + 16,9 % bis + 343,8 %(d) cellulose layer + 16.9% to + 343.8%
(e) Polyamidschicht + 15,5 % bis + 337,4 %(e) polyamide layer + 15.5% to + 337.4%
Die verwendeten Namen der Formulierungsbestandteile bedeuten:The names of the formulation components used mean:
A 77 1726 2-Cyan-3-hydroxy-N-(4-trifluormethyl-phenyl)-crotonsäureamidA 77 1726 2-cyano-3-hydroxy-N- (4-trifluoromethyl-phenyl) -crotonamide
DMI: DimethylisosorbitDMI: dimethyl isosorbitol
IPM: IsopropylmyristatIPM: isopropyl myristate
Myristinsäure-isopropylesterMyristic acid isopropyl ester
IPP: IsopropylpalmitatIPP: isopropyl palmitate
PEG-35 Castor Oil [Castor Oil = Ricinusöl] = Polyethylenglykolderivat von Castor Oil mit im Mittel 35 Molen Ethylenoxid = Handelsname z.B.: Cremophor® EL Polyoxyethylenlaurat, z.B.PEG-35 Castor Oil [Castor Oil = castor oil] = polyethylene glycol derivative of Castor Oil with an average of 35 moles of ethylene oxide = trade name eg: Cremophor ® EL Polyoxyethylene laurate, e.g.
Laureth-23Laureth-23
Lauryl-Alkohol-polyethylenglykolether der FormelLauryl alcohol polyethylene glycol ether of the formula
CH3(CH2)10-CH2(OCH2-CH2)n-OH Mittlerer Zahlenwert für n: 23; Handelsname: beispielsweise Brij 35® CH 3 (CH 2 ) 10 -CH 2 (OCH 2 -CH 2 ) n -OH Mean numerical value for n: 23; Trade name: for example Brij 35 ®
Gantrez® ES 435 (GAF Corporation New York)Gantrez ® ES 435 (GAF Corporation New York)
50 %ige Lösung eines Mischpolymerisates aus Methylvinylether und50% solution of a copolymer of methyl vinyl ether and
Maleinsäuremonobutylester in IsopropylalkoholMaleic acid monobutyl ester in isopropyl alcohol
Herstellverfahren für die FormulierungManufacturing process for the formulation
Man legt ein wasserfreies, flüchtiges Lösungsmittel oder Losungsmittelgemisch vor und gibt unter Rühren nacheinander ein spreitendes Lösungsmittel, einen Filmbildner und einen antipsoriatischen Wirkstoff so zu, daß eine Lösung bzw. eine Suspension entsteht. An anhydrous, volatile solvent or solvent mixture is introduced and, with stirring, a spreading solvent, a film former and an antipsoriatic active ingredient are added in succession so that a solution or a suspension is formed.

Claims

Patentansprüche: Claims:
1 . Verwendung einer Formulierung, enthaltend mindestens ein spreitendes Lösungsmittel, mindestens ein leicht flüchtiges Lösungsmittel, einen wasserunlöslichen Filmbildner und mindestens einen antipsoriatischen Wirkstoff, zur Herstellung eines Medikaments zur Behandlung von Nagelpsoriasis.1 . Use of a formulation containing at least one spreading solvent, at least one volatile solvent, a water-insoluble film former and at least one antipsoriatic active ingredient for the manufacture of a medicament for the treatment of nail psoriasis.
2. Verwendung einer Formulierung gemäß Anspruch 1 , dadurch gekennzeichnet, daß die Formulierung als Wirkstoff Leflunomid, Glukokorticoide, 2-Cyan-3-hydroxy-N-(4-trifluormethyl-phenyl)- crotonsäureamid, Cyclosporin A, Pentoxifyllin oder Propentofyllin oder eine Mischung dieser Wirkstoffe enthält.2. Use of a formulation according to claim 1, characterized in that the formulation as the active ingredient leflunomide, glucocorticoids, 2-cyano-3-hydroxy-N- (4-trifluoromethyl-phenyl) crotonic acid amide, cyclosporin A, pentoxifylline or propentofylline or a mixture contains these active substances.
3. Verwendung einer Formulierung gemäß Anspruch 2, dadurch gekennzeichnet, daß die Formulierung den Wirkstoff in einer Gesamtkonzentration von 0, 1 bis 20 %, bezogen auf das Gesamtgewicht der Formulierung, insbesondere von 0,5 bis 10 % enthält.3. Use of a formulation according to claim 2, characterized in that the formulation contains the active ingredient in a total concentration of 0.1 to 20%, based on the total weight of the formulation, in particular 0.5 to 10%.
4. Verwendung einer Formulierung gemäß einem oder mehreren der Ansprüche 1 bis 3, dadurch gekennzeichnet, daß die Formulierung als spreitende Verbindung Dimethylisosorbit, Isopropylmyristat, Oleyloleat, N-Methyl-2-Pyrrolidon oder Polyolfettsäureester oder eine Mischung dieser Verbindungen enthält.4. Use of a formulation according to one or more of claims 1 to 3, characterized in that the formulation contains as a spreading compound dimethyl isosorbitol, isopropyl myristate, oleyl oleate, N-methyl-2-pyrrolidone or polyol fatty acid ester or a mixture of these compounds.
5. Verwendung einer Formulierung gemäß Anspruch 1 oder 4, dadurch gekennzeichnet, daß die Formulierung die spreitende Verbindung in einer Gesamtkonzentration von 0, 1 % bis 10 % enthält. WO 97/346445. Use of a formulation according to claim 1 or 4, characterized in that the formulation contains the spreading compound in a total concentration of 0.1% to 10%. WO 97/34644
1414
6. Verwendung einer Formulierung gemäß einem oder mehreren der Ansprüche 1 bis 5, dadurch gekennzeichnet, daß die Formulierung den Filmbildner in einer Konzentration von 3,0 % bis 35 % enthält.6. Use of a formulation according to one or more of claims 1 to 5, characterized in that the formulation contains the film former in a concentration of 3.0% to 35%.
7. Verwendung einer Formulierung gemäß den Ansprüchen 1 und 6, dadurch gekennzeichnet, daß die Formulierung als Filmbildner ein Mischpolymerisat aus Methylvinylether und Maieinsäuremonobutylester enthält.7. Use of a formulation according to claims 1 and 6, characterized in that the formulation as a film former contains a copolymer of methyl vinyl ether and monobutyl maleate.
8. Verwendung einer Formulierung gemäß einem oder mehreren der Ansprüche 1 , 6 und 7, dadurch gekennzeichnet, daß die Formulierung als Filmbildner Gantrez® ES 435 enthält. 8. Use of a formulation according to one or more of claims 1, 6 and 7, characterized in that the formulation contains Gantrez ® ES 435 as a film former.
EP97905085A 1996-03-16 1997-02-26 Topical formulations for the treatment of nail psoriasis Withdrawn EP0888138A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19610482 1996-03-16
DE19610482 1996-03-16
PCT/EP1997/000905 WO1997034644A1 (en) 1996-03-16 1997-02-26 Topical formulations for the treatment of nail psoriasis

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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)

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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
PT1680076E (en) * 2003-08-25 2008-10-03 Bioequal Ag Pharmaceutical and cosmetic formulations for treating fingernails
RU2008100037A (en) * 2005-06-10 2009-07-20 Галдерма С.А. (Ch) METHOD FOR REGULATED RELEASE OF MEDICINES THROUGH SKIN
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
KR102451304B1 (en) 2020-09-14 2022-10-07 한국과학기술연구원 Composition for improving psoriasis symptom comprising extract of Thalictrum squarrosum steph
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.
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

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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
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KR20000064607A (en) 2000-11-06
JP2000512265A (en) 2000-09-19
AU1876797A (en) 1997-10-10

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