NO813932L - ANTIMYCOTIC AGENT WITH HIGH EFFICIENT SUBSTANCE RELEASE IN THE FORM OF ELASTIC LIQUID PLASTERS - Google Patents

ANTIMYCOTIC AGENT WITH HIGH EFFICIENT SUBSTANCE RELEASE IN THE FORM OF ELASTIC LIQUID PLASTERS

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Publication number
NO813932L
NO813932L NO813932A NO813932A NO813932L NO 813932 L NO813932 L NO 813932L NO 813932 A NO813932 A NO 813932A NO 813932 A NO813932 A NO 813932A NO 813932 L NO813932 L NO 813932L
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weight
isopropyl
vinylpyrrolidone
fatty acid
contain
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NO813932A
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Norwegian (no)
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Miklos Von Bittera
Karl Heinz Buechel
Manfred Plempel
Erik Regel
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Bayer Ag
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Publication of NO813932L publication Critical patent/NO813932L/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Dispersion Chemistry (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thermotherapy And Cooling Therapy Devices (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Ultra Sonic Daignosis Equipment (AREA)
  • Force Measurement Appropriate To Specific Purposes (AREA)
  • Shovels (AREA)
  • Materials For Medical Uses (AREA)

Abstract

1. Claims for the contracting states : BE, CH, LI, DE, FR, GB, IT, NL, SE Antimycotic agents which have relatively good release of active compounds and contain azole derivatives and customary formulation auxiliaries, characterised in that they contain 2-10% by weight of a spreading agent from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl stearate, caprylates/caproates of saturated fatty alcohols having the chain length of C12 to C18 , wax-like fatty acid esters, such as synthesized duck uropygial gland fat, silicone oils, isopropyl myristate/isorpopyl palmitate/isopropyl stearate mixture, coconut fatty acid isopropyl ester, 1-8% by weight of a solubilising agent and, as a film-forming agent, a quick-drying polyvinylpyrrolidone, a terpolymer of 30% by weight of vinylpyrrolidone, 40% by weight of vinyl acetate and 30% by weight of vinyl propionate, or a vinylpyrrolidone/vinyl acetate copolymer. 1. Claims for the contracting state : AT Process for the production of antimycotics based on azole derivative active compounds and costumary formulation auxiliaries, characterised in that the active compounds and the formulation auxiliaries are formulated together with 2 to 10% by weight of isopropyl myristate, isopropylpalmitate, isopropyl stearate, caprylates/caproates of saturated fatty alcohols having the chain length of C12 to C18 , waxy fatty acid esters, such as synthesized duck uropygial gland fat, silicone oils, isopropyl myristate/isopropyl palmitate/isopropyl stearate mixture or cocount fatty acid isopropylester as spreading agents, 1 to 8% by weight of solubilising agents, based in each case on the total weight, and a quick drying polyvinylpyrrolidone, a terpolymer of vinylpyrrolidone/vinyl acetate/vinyl propionate in a ratio by weight of 30:40:30, or a vinylpyrrolidone/vinylacetate copolymer as the film-forming agent.

Description

Oppfinnelsen vedrører nye formuleringer av de kjente antimykotiske azolderivater som har en depot-virkning på tross av filmdannelse og en høyere biodisponerbarhet av de virksomme stoffer og derved muliggjør en korttidstérapi. The invention relates to new formulations of the known antifungal azole derivatives which have a depot effect despite film formation and a higher bioavailability of the active substances and thereby enable a short-term therapy.

For behandling av mykoser hos mennesker, fremfor alt hud-mykoser er det allerede kjent tilberedninger av antimykotiske derivater. Med disse tilberedninger kreves for en fullstendig sanering over 21 dager terapitid. Preparations of antifungal derivatives are already known for the treatment of mycoses in humans, above all skin mycoses. With these preparations, a complete remediation is required over 21 days of therapy.

For å komme til en nedsettelse ab terapivarigheten kreverTo arrive at a reduction ab the duration of therapy requires

man spesielt for eliminering av kimene, respektiv for å oppnå en mykologisk sanering en viss depotvirkning og en høyere biodisponerbarhet av de virksomme stoffer. Dertil er de kjente formuleringer bare begrenset egnet, fordi av de tilstedeværende virksomme stofftilbud utløses bare en liten del i væskevolumene på infeksjonsstedet. Når man nu uten ytterligere økning av den virksomme stoffkonsentrasjon vil oppnå en nedsettelse av terapivarigheten, f.eks. til 1 dag ved engangs applikasjon, må man sørge for en optimal biodisponerbarhet av det virksomme stoff. one in particular for the elimination of the germs, respectively to achieve a mycological remediation, a certain depot effect and a higher bioavailability of the active substances. The known formulations are only limitedly suitable for this, because only a small part of the available active substances are released into the fluid volumes at the site of infection. When you now want to achieve a reduction in the duration of therapy without further increasing the active substance concentration, e.g. to 1 day in the case of a single application, one must ensure optimal bioavailability of the active substance.

Det ble nå funnet at slike formuleringer av antimykotiske virksomme stoffer som inneholder 2 - 10% spremiddel, It was now found that such formulations of antifungal active substances containing 2 - 10% dispersant,

1- - 8% oppløsningsformidler og som filmdanner en hurtig-tørkende polyvinylpyrrolidon, terpolymerisat av 30% vinylpyrrolidon, 40% vinylacetat og 30% vinylpropionat eller vinylpyrrolidon-vinylacetat-kopolymerisat som såvel er oppløselig i vann som ogsi organiske oppløsningsmidler og dessuten inneholder de vanlige formuleringshjelpestoffer, muliggjør en optimal frigjøring av det virksomme stoff og dermed en til en dag nedsatt terapivarighet ved oppnåelse av høye konsentrasjoner av det virksomme stoff. Denne effekt oppnås ved at virkningen av de i formuleringen inne-holdte virksomme stoffer økes ved spredeoljer og oppløs-ningsf ormidlere og adhererende filmdanner-tilsetninger 1- - 8% solubilizer and which forms a film of a quick-drying polyvinylpyrrolidone, terpolymer of 30% vinylpyrrolidone, 40% vinylacetate and 30% vinylpropionate or vinylpyrrolidone-vinylacetate copolymer which is soluble in water as well as organic solvents and also contains the usual formulation aids , enables an optimal release of the active substance and thus one to one day reduced therapy duration when high concentrations of the active substance are achieved. This effect is achieved by the fact that the effect of the active substances contained in the formulation is increased by spreading oils and solubilizing agents and adherent film-forming additives

og derved kan den virksomme stoff-frigjøring økes til ti ganger. De ifølge oppfinnelsen elastiske væske-plaster-formuleringer er et nytt applikasjonsprinsipp til dermal behandling av mykoser som ved siden av en meget god virkning, lukningen av infeksjonsstedet, betyr en infeksjonsbeskytt-else for omgivelsene. Såesielt godt egnet er formuleringene ifølge oppfinnelsen til behandling av neglmykoser. and thereby the effective substance release can be increased to ten times. The elastic liquid-plaster formulations according to the invention are a new application principle for the dermal treatment of mycoses which, in addition to a very good effect, the closure of the site of infection, means an infection protection for the surroundings. The formulations according to the invention are particularly well suited for the treatment of nail mycoses.

Formuleringen ifølge oppfinnelsen kan være såvel oppløsninger som også sprays. The formulation according to the invention can be both solutions and sprays.

Virksomme stoffer som kan formuleres på denne måte er alle antimykotisk virksomme derivater, spesielt imidazol- og triazolderivater. De er til stede i midlene ifølge oppfinnelsen i mengder på 0,05 - 1%, fortrinnsvis 0,1 - 1%. Active substances that can be formulated in this way are all antifungally active derivatives, especially imidazole and triazole derivatives. They are present in the agents according to the invention in amounts of 0.05 - 1%, preferably 0.1 - 1%.

Eksempelvis skal det nevnes forbindelsene med nedenstående formler: For example, the compounds with the following formulas should be mentioned:

Tallrike ytterligere antimykotisk virksomme azolderivater Numerous additional antifungally active azole derivatives

er kjent i fra DE-OS 24 30 039. De kan likeldes tjene som virksomt stoff i midlene ifølge oppfinnelsen.'are known in from DE-OS 24 30 039. They can also serve as active substance in the agents according to the invention.'

Ved spredemidler forstås oljeaktige væsker som fordelerDispersants are understood as oily liquids that distribute

seg spesielt godt på huden (R. Keymer, Pharm.Ind. 32 (1970), 577 - 581). For midlene ifølge oppfinnelsen egner det seg som spredemidler spesielt følgende forbindelser: particularly well on the skin (R. Keymer, Pharm.Ind. 32 (1970), 577 - 581). For the agents according to the invention, the following compounds are particularly suitable as dispersants:

Silikonolje av forskjellig viskositet.Silicone oil of different viscosity.

Fettsyreester, som metylstearat, di-n-butyl-adipat, laurin-syreheksylester, dipropylen-glykolpelargonat, ester av en forgrenet fettsyre av midlere kjedelengde med mettede fettalkoholer ciq~ ciq' isopropylmyristat, isopropylplamitat, capryl/caprinsyreester av mettede fettalkoholer av kjedelengder c^2-ci8'isopropylstearat, oljesyreoleylester, olje-syredecylester, etyloleat, melkesyreetylester, voksaktige fettsyreestere som kunstig andegumpkjertelfett, dibutyl-ftalat, adipinsyrediisopropylester, til sistnevnte be-slektede esterblandinger og lignende. Fatty acid ester, such as methyl stearate, di-n-butyl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, ester of a branched fatty acid of medium chain length with saturated fatty alcohols ciq~ ciq' isopropyl myristate, isopropyl palmitate, caprylic/capric acid esters of saturated fatty alcohols of chain lengths c^ 2-Ci8'isopropyl stearate, oleic acid oleyl ester, oleic acid decyl ester, ethyl oleate, lactic acid ethyl ester, waxy fatty acid esters such as artificial duck fat, dibutyl phthalate, adipic acid diisopropyl ester, to the latter related ester mixtures and the like.

Triglycerider, som capryl/caprinsyretriglycerid, triglycerid-blanding med platefettsyrer av kjedelengder cq~ ci2°^Triglycerides, such as caprylic/capric triglyceride, triglyceride mixture with plate fatty acids of chain lengths cq~ ci2°^

andre spesielt utvalgte naturlige fettsyrer, partial-glyceridblandinger av mettede eller umettede, eventuelt også hydroksylgruppeholdige fettsyrer, monoglycerider av Cg/C-j^Q-fettsyrer og lignende. other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated, possibly also hydroxyl group-containing fatty acids, monoglycerides of Cg/C-j^Q fatty acids and the like.

Fettalkoholer, som isotridecylalkohol, cetylstearyl-alkohol, oleylalkohol. Fatty alcohols, such as isotridecyl alcohol, cetylstearyl alcohol, oleyl alcohol.

Fettsyrer, som f.eks. oljesyre.Fatty acids, such as oleic acid.

Spesielt godt egnede spredende oljer er følgende: isopropylmyristat, isopropylpalmitat, isopropylstearat, capryl/ caprinsyreestere av mettede fettalkoholer av kjedelengder C^2~C-^g/ voksaktige fettsyreestere som kunstig andregum-kjertelfett, silikonolje, isopropylmyristat-isopropylpalmitat-isopropylstearat-blanding, kokosfettsyreisopropylester. Particularly suitable dispersing oils are the following: isopropyl myristate, isopropyl palmitate, isopropyl stearate, caprylic/ capric acid esters of saturated fatty alcohols of chain lengths C^2~C-^g/ waxy fatty acid esters such as artificial andregum gland fat, silicone oil, isopropyl myristate-isopropyl palmitate-isopropyl stearate mixture, coconut fatty acid isopropyl ester .

Som oppløsningsformidlere egner det seg fremfor alt for midlene ifølge oppfinnelsen: Benzylakohol, 2-octyl-dodecanol, polyetylenglykol, ftalater, adipater, propylenglykol, glycerih, di- og tripropylenglykol, vokser etc. og andre i kosmetikken anvendte tilsetnings-stoffer. As solubilizers, it is suitable above all for the agents according to the invention: Benzyl alcohol, 2-octyl-dodecanol, polyethylene glycol, phthalates, adipates, propylene glycol, glycerih, di- and tripropylene glycol, waxes, etc. and other additives used in cosmetics.

Som gel- og fildannere kommer det på tale slike makro-molekylare forbindelser som kan oppløse seg respektiv svelle såvel i vann som også i organiske oppløsningsmidler og etter tørkningen danne en filmtype. Gel and film formers are such macro-molecular compounds that can dissolve or swell in water as well as in organic solvents and form a film type after drying.

Slike gel- og fildannere er polyvinylpyrrolidon eller vinylpyrrolidon-vinylacetat-kopolymerisater med forskjellig vinylacetat-innhold. De kan også inneholde ytterligere vinylestere, f.eks. vinylpropionat. Som eksempel skal det nevnes et terpolymerisat av 30% vinylpyrolidon, 40% vinylacetat og 30% vinylpropionat. Such gel and film formers are polyvinylpyrrolidone or vinylpyrrolidone-vinyl acetate copolymers with different vinyl acetate content. They may also contain additional vinyl esters, e.g. vinyl propionate. As an example, a terpolymer of 30% vinylpyrrolidone, 40% vinyl acetate and 30% vinyl propionate should be mentioned.

Som oppløsningsmidler er vann og også alle med vann bland-bare oppløsningsmidler egnet. I betraktning kommer f.eks. alkanoler som etanol og isopropylalkohol, propylenglykol, metylcellosol, cellosolv, estere, morfoliner, dioksan, dimetylsulfoksyd, dimetylformamid, tetrahydrofuran, cyklo-heksanon, etc. As solvents, water and also all water-miscible solvents are suitable. Taking into account e.g. alkanols such as ethanol and isopropyl alcohol, propylene glycol, methylcellosol, cellosolv, esters, morpholines, dioxane, dimethylsulfoxide, dimethylformamide, tetrahydrofuran, cyclohexanone, etc.

Det kan ved fremstillingen av formuleringen ifølge oppfinnelsen anvendes et eller flere oppløsningsmidler. In the preparation of the formulation according to the invention, one or more solvents may be used.

Ved ro4søk til å fastslå en optimal formulering kan det f.eks. bl.a. anvendes følgende hjelpestoffer: Glycerol, tyktflytende parafin, tyntflytende parfin, trietanolamin, collagen, allantoin, novantisolsyre, parfymeolje. When ro4search to determine an optimal formulation, it can e.g. blue. the following excipients are used: Glycerol, viscous paraffin, thin paraffin, triethanolamine, collagen, allantoin, novantisolic acid, perfume oil.

Som ytterligere hjelpemidler er det egnet:As additional aids, the following are suitable:

a. Stoffer, som f.eks. kan stabilisere en suspensjon, a. Substances, such as can stabilize a suspension,

f.eks. kolloidal kiselsyre, montmorilloniter og lignende. e.g. colloidal silicic acid, montmorillonites and the like.

b. Tensider (omfattende emulgatorer og fuktemidler), b. Surfactants (including emulsifiers and wetting agents),

f. eks.e.g.

1. anionaktive, som Na-laurylssulfat, fettalkohol-etersulfater, mono/dilkylgpokyglykoleter-orto-fosforsyreester-monoetanolaminsalt\ 1. anion-active, such as Na-lauryl sulfate, fatty alcohol-ether sulfates, mono/dilkylgpokyglycol ether-ortho-phosphoric acid ester-monoethanolamine salt\

2. kationaktive, som cetyltrimetylammoniumkloridJ2. cation active, such as cetyltrimethylammonium chlorideJ

3. amfolyttiske, som di-Na-N-lauryl-B-ininodi-propionat eller lecitin) 4. ikke-ionogene, f.eks. polyoksyetylert rizinusolje, polyoksyetylert sorbitanmonooleat, sorbitan-mono-stearat, cetylalkohol, glycerolmonostearat, poly-oksyetylenstearat, alkylfenolpolyglykoleter. c. Stabilisator til å hindre den ved noen virksomme stoffer inntreden i kjemiske avbygning som antioksydanter, f.eks. tocoferol, butylhydroksyanisol. d. Surt innstilte vandige oppløsninger kan stabiliseres ved tilsetningen av i kosmetikken vanlig konserver-ingsmidler, f.eks. p-hydroksybenzosyreester. 3. ampholytic, such as di-Na-N-lauryl-B-ininodi-propionate or lecithin) 4. non-ionic, e.g. polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, cetyl alcohol, glycerol monostearate, polyoxyethylene stearate, alkylphenol polyglycol ether. c. Stabilizer to prevent some active substances from entering chemical breakdowns such as antioxidants, e.g. tocopherol, butylhydroxyanisole. d. Acidic aqueous solutions can be stabilized by the addition of preservatives common in cosmetics, e.g. p-Hydroxybenzoic acid ester.

Virksomhetsprøve av midlene ifølge oppfinnelsen på trico-fyton-infiserte marsvin. Activity test of the agents according to the invention on trichophyton-infected guinea pigs.

Som prøvemodell til sammenligning virksomhetsundersøkelseAs a sample model for comparison business survey

av midlene ifølge oppfinnelsen ble det anvendt tricofyton-infiserte Pirbright-white-marsvin med en gjennomsnittlig vekt på 600 g. Dyrene ble på ryggen klippet med en elektrisk hårklippemaskin således at det ble bibeholdt ca. 1/10 mm lange hårstumper. of the agents according to the invention, trichophyton-infected Pirbright white guinea pigs with an average weight of 600 g were used. The animals were clipped on their backs with an electric hair clipper so that approx. 1/10 mm long hair stubs.

Infeksjonen med trikofyton mentagrofytes foregikk ved lett utrivning av en 24 timer i Sabouraud-næringsoppløsning kimdannet sporesuspensjon av frembringeren på en ca. 2x2 cm stor flate av den klippede rygg på dyret. Det ble på-ført pr- dyr 0,5 ml kimsuspensjon som inneholdt 1 - 3 x 10<5>infektiøse soppartikler. The infection with trichophyton mentagrophytes took place by lightly pulling out a 24 hours in Sabouraud nutrient solution germinating spore suspension of the producer on an approx. 2x2 cm large area of the clipped back of the animal. 0.5 ml of germ suspension containing 1 - 3 x 10<5> infectious fungal particles was applied per animal.

Ved denne infeksjonsmodus viser det seg 2-3 dager post infectionem de første symptomer av dermatofytose som rødming og skorpedannelse av huden. Ved ubehandlede dyr er ca. 14 dager p.i. dermatofysen maksimalt utpreget: flate-messig håravfall og blodig integument-defekter innen en betent endret, skorpet kantsone. In this mode of infection, the first symptoms of dermatophytosis such as redness and crusting of the skin appear 2-3 days post infection. In untreated animals, approx. 14 days p.i. the dermatophysis is maximally pronounced: superficial hair loss and bloody integument defects within an inflamed, altered, crusted edge zone.

De formuleringer som skulle undersøkes appliseres en gang på annen dag post infectionem lokalt på det rødmende infeksjonssted hos dyret. Det ble hver gang påført 0,5 ml av formuleringen = 5 mg virksomt stoff (l%ig formulering). Vurderngen av infeksjonsforløpet foregikk The formulations to be examined are applied once every other day post infectionem locally to the reddened site of infection in the animal. 0.5 ml of the formulation = 5 mg of active substance (1% formulation) was applied each time. The assessment of the course of the infection took place

daglig inntil 20.dag p.i.daily until the 20th day p.i.

Resultatene angitt ved eksemplene (+ = svak virkning.The results indicated by the examples (+ = weak effect).

++ = virkning, +++ = god virkning, ++++ = meget god virkning). ++ = effect, +++ = good effect, ++++ = very good effect).

I følgende eksempler er det angitt resepturer for midlene ifølge oppfinnelsen. De enkelte komponenter blandes med In the following examples, recipes are indicated for the agents according to the invention. The individual components are mixed together

hverandre ved værelsetemperatur og går derved i oppløsning. each other at room temperature and thereby dissolve.

Anvender man i steden for formuleringen ifølge oppfinnelsen slike som i steden for nevnte polymere inneholder vannuopp-løselige polymere, f.eks. metacrylter, så blir mykosen If one uses instead of the formulation according to the invention those which instead of said polymers contain water-insoluble polymers, e.g. methacrylates, then the mycosis

verre.worse.

Anvender man slike formuleringer som ved siden av det virksomme stoff bare inneholder de nevnte polymere, men hverken spredemiddel eller oppløsningsformidler, oppnår man bare en svak virkning. If such formulations are used which, in addition to the active substance, only contain the aforementioned polymers, but neither a dispersing agent nor a dissolving agent, only a weak effect is achieved.

Eksempel 1 Example 1

Virkning på marsvinprøve +++ = god virkning. Effect on guinea pig test +++ = good effect.

Eksempel 2Example 2

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 3Example 3

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 4Example 4

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 5Example 5

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 6Example 6

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 7Example 7

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 8Example 8

Virkning i marsvinprøve. ++++ = meget god virkning. Effect in guinea pig test. ++++ = very good effect.

Eksempel 9Example 9

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 10Example 10

Virkning i marsvinprøve +++ = god virkning. Effect in guinea pig test +++ = good effect.

Eksempel 11Example 11

Virkning i marsvinprøve ++++ meget god virkning. Effect in guinea pig test ++++ very good effect.

Eksempel 12Example 12

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 13Example 13

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

Eksempel 14Example 14

Virkning i marsvinprøve ++++ = meget god virkning. Effect in guinea pig test ++++ = very good effect.

SpraysSprays

De ifølge eksemplene 1-14 fremstilte virksomme stoff-oppløsninger kan også forarbeides til spray. For dette formål blander man f.eks. 60 - 90% virksom stoffoppløsning med 20 - 40% av det vanlige drivmiddel, f.eks.N2,N2), CC^, butan, halogenhydrokarboner osv. The active substance solutions prepared according to examples 1-14 can also be processed into sprays. For this purpose, you mix e.g. 60 - 90% active substance solution with 20 - 40% of the usual propellant, e.g. N2,N2), CC^, butane, halogen hydrocarbons, etc.

Claims (7)

1. Antimykotisk middel med høyere frigjøring av de virksomme stoffer inneholdende azolderivater og vanlige formuleringshjelpestoffer, karakterisert ved at de inneholder 2 - 10% spredemiddel, 1-8% oppløsnings-formidler og som filmdanner polyvinylpyrrolidon eller vinylpyrrolidon-vinylacetat-kopolymere.1. Antimycotic agent with higher release of the active substances containing azole derivatives and common formulation aids, characterized in that they contain 2 - 10% dispersing agent, 1-8% dissolution agent and film-forming polyvinylpyrrolidone or vinylpyrrolidone-vinylacetate copolymers. 2. Antimykotisk middel ifølge krav 1, karakterisert ved at de som virksomt stoff inneholder clotrimazol med formel 2. Antimycotic agent according to claim 1, characterized in that they contain clotrimazole with the formula as active substance 3. Antimykotisk middel ifølge krav 1, karakterisert ved at de som virksomt stoff inneholder trifonazol med formel 3. Antimycotic agent according to claim 1, characterized in that they contain trifonazole with the formula as active substance 4. Antimykotisk middel ifølge krav 1, karakterisert ved at de som virksomt stoff inneholder lombazol med formel 4. Antimycotic agent according to claim 1, characterized in that they contain as active substance lombazole with the formula 5. Antimykotisk middel ifølge krav 1, karakterisert ved at de inneholder de antimykotiske azolderivater i mengder på 0,05 - 1%, fortrinnsvis på 0,1 - 1%. 5. Antimycotic agent according to claim 1, characterized in that they contain the antifungal azole derivatives in amounts of 0.05 - 1%, preferably of 0.1 - 1%. 6. Antimykotisk middel ifølge krav 1, karakterisert ved at det er en oppløsning.6. Antimycotic agent according to claim 1, characterized in that it is a solution. 7. Antimykotisk middel ifølge krav 1, karakterisert ved at det er en spray.7. Antimycotic agent according to claim 1, characterized in that it is a spray.
NO813932A 1980-12-05 1981-11-19 ANTIMYCOTIC AGENT WITH HIGH EFFICIENT SUBSTANCE RELEASE IN THE FORM OF ELASTIC LIQUID PLASTERS NO813932L (en)

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Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3311701A1 (en) * 1983-03-30 1984-10-04 Bayer Ag ANTIMYCOTIC AGENTS WITH HIGH ACTIVE SUBSTANCE RELEASE IN THE FORM OF CREAM
DE3311700A1 (en) * 1983-03-30 1984-10-04 Bayer Ag ANTIMYCOTIC AGENTS WITH HIGH ACTIVE SUBSTANCE RELEASE IN THE FORM OF SOLUTION AND SPRAY
CA1241602A (en) * 1984-02-23 1988-09-06 Ortho Pharmaceutical Corporation Antifungal aerosol solution
FR2568773B1 (en) * 1984-08-10 1989-03-03 Sandoz Lab NEW NASAL ADMINISTRATIVE PHARMACEUTICAL COMPOSITIONS
EP0175671A1 (en) * 1984-08-23 1986-03-26 Kuhlemann &amp; Co. Pharmaceutical preparation and method for the administration of this pharmaceutical preparation
JPS61151117A (en) * 1984-12-25 1986-07-09 Bayer Yakuhin Kk Gelatinous antimycotic preparation
DE3522550A1 (en) * 1985-06-24 1987-01-02 Klinge Co Chem Pharm Fab SPRAYABLE PHARMACEUTICAL PREPARATION FOR TOPICAL APPLICATION
DE3544983A1 (en) * 1985-12-19 1987-06-25 Hoechst Ag ANTIMYCOTIC EFFECTIVE NAIL POLISH
HU200914B (en) * 1987-03-09 1990-09-28 Horvath Gyoengyi Lengyelne Process for producing new medical dosage unit suitable for local treatment of fungus infection of nails
DE3720147A1 (en) * 1987-06-16 1988-12-29 Hoechst Ag ANTIMYCOTICALLY EFFECTIVE NAIL POLISH AND METHOD FOR THE PRODUCTION THEREOF
JPH01230514A (en) * 1987-11-25 1989-09-14 Osaka Aerosol Ind Corp Aerosol type patch external use
DE3802046A1 (en) * 1988-01-25 1989-08-03 Robert P Hielscher Hygiene paper (prevention of dermatomycosis - mycosis pedis)
US5116603A (en) * 1989-01-31 1992-05-26 Yissum Research Development Company Of The Hebrew University Of Jerusalem Oral antifungal preventative, and method of use
JP2555555B2 (en) * 1991-07-03 1996-11-20 武田薬品工業株式会社 Antifungal topical formulation
FR2732223B1 (en) * 1995-03-30 1997-06-13 Sanofi Sa PHARMACEUTICAL COMPOSITION FOR TRANSDERMAL ADMINISTRATION
FR2742989B1 (en) * 1995-12-29 1998-01-23 Adir BIOADHESIVE PHARMACEUTICAL COMPOSITION FOR THE CONTROLLED RELEASE OF ACTIVE INGREDIENTS
AU1876797A (en) * 1996-03-16 1997-10-10 Hoechst Aktiengesellschaft Topical formulations for the treatment of nail psoriasis
IL138889A0 (en) * 1998-04-17 2001-11-25 Bertek Pharm Inc Topical formulations for the treatment of nail fungal diseases
PT1150661E (en) * 1999-02-05 2004-02-27 Cipla Ltd PRODUCT FOR SPRAYING FOR TOPIC APPLICATION
US6962691B1 (en) 1999-05-20 2005-11-08 U & I Pharmaceuticals Ltd. Topical spray compositions
NZ542904A (en) 2003-03-21 2009-04-30 Nexmed Holdings Inc Antifungal nail coat and method of use
RU2417073C2 (en) 2005-09-29 2011-04-27 Новартис Аг Antimycotic composition
JP4513921B2 (en) * 2008-12-09 2010-07-28 ソニー株式会社 Optical body and manufacturing method thereof, window material, blind, roll curtain, and shoji
US8697753B1 (en) 2013-02-07 2014-04-15 Polichem Sa Method of treating onychomycosis

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3476853A (en) * 1965-04-13 1969-11-04 Colgate Palmolive Co Sprayed opaque bandage composition
DE1642063A1 (en) * 1967-11-16 1970-07-16 Henkel & Cie Gmbh Wound dressing spray
DE2430039C2 (en) * 1974-06-22 1983-11-10 Bayer Ag, 5090 Leverkusen Climbazole in cosmetic products
DE2461406C2 (en) * 1974-12-24 1984-06-14 Bayer Ag, 5090 Leverkusen Azolyl- (1) -methanes and their salts, processes for their preparation and medicaments containing them

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KR830007072A (en) 1983-10-14
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ZA818431B (en) 1982-11-24
DK538281A (en) 1982-06-06
KR880000738B1 (en) 1988-05-04
CA1175355A (en) 1984-10-02
AU7826181A (en) 1982-06-10
AU546449B2 (en) 1985-09-05
DE3045914A1 (en) 1982-07-22
ATE9060T1 (en) 1984-09-15
DE3165710D1 (en) 1984-09-27
FI813885L (en) 1982-06-06
IL64436A (en) 1985-03-31
IL64436A0 (en) 1982-03-31
JPS57122015A (en) 1982-07-29

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