NO158922B - PROCEDURE FOR THE MANUFACTURE OF AZOLD DERIVATIVE ANTIMYCOTIC AGENT WITH HIGH RELEASE OF ACTIVE SUBSTANCES. - Google Patents
PROCEDURE FOR THE MANUFACTURE OF AZOLD DERIVATIVE ANTIMYCOTIC AGENT WITH HIGH RELEASE OF ACTIVE SUBSTANCES. Download PDFInfo
- Publication number
- NO158922B NO158922B NO813930A NO813930A NO158922B NO 158922 B NO158922 B NO 158922B NO 813930 A NO813930 A NO 813930A NO 813930 A NO813930 A NO 813930A NO 158922 B NO158922 B NO 158922B
- Authority
- NO
- Norway
- Prior art keywords
- isopropyl
- weight
- derivative
- acid esters
- azole
- Prior art date
Links
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- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
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Abstract
Description
Oppfinnelsen .vedrører en fremgangsmåte til fremstilling The invention relates to a method for manufacturing
av azolderivatholdig antimykotisk middel med høy frigjøring av virksomme stoffer, inneholdende vanlige formuleringshjelpestoffer, hvorved det muliggjøres en kort-tids terapi. of an azole-derivative antifungal agent with a high release of active substances, containing common formulation excipients, whereby a short-term therapy is made possible.
For behandling av mykoser hos mennesker, fremfor alt mykosen av hud og hudvedhengningsstrukturene, er det allerede kjent tilberedninger av antimykotiske derivater. Med disse tilberedninger krevdes for en fullstendig sanering 14-21 dagers terapitid. Preparations of antifungal derivatives are already known for the treatment of mycoses in humans, above all the mycoses of the skin and the skin attachment structures. With these preparations, 14-21 days of therapy are required for complete remediation.
For f .eks:, ved vaginal- eller bukalmykoser eller dermatomy-koser å komme til en nedsettelse av terapivarigheten krever man spesielt for eliminering av kimene resp. for å oppnå For e.g., in the case of vaginal or buccal mycosis or dermatomycosis, a reduction in the duration of therapy is required especially for the elimination of the germs or to achieve
en mykologisk sikret sanering en høyere frigjøring av det Virksomme stoff i vandig miljø. Dertil er de kjente formuleringer bare begrenset egnet fordi av det tilstedeværende virksomme, stofftilbud, løser bare en liten del seg i væske-vplumet på inspeksjonsstedet. Når man nå ved eller uten ytterligere økning av virksom stoffkonsentrasjon vil oppnå en nedsettelse av terapivarigheten, f.eks. til en dag ved en gangs applikasjon, må man sørge for en optimal biodispo-nerba.rh.et av det virksomme stoff. a mycologically assured remediation a higher release of the active substance in the aqueous environment. For this, the known formulations are only limitedly suitable because of the active, substance supply present, only a small part dissolves in the liquid plume at the inspection site. When, with or without a further increase in active substance concentration, a reduction in the duration of therapy will be achieved, e.g. to a day with a single application, one must ensure optimal biodisposability of the active substance.
Oppfinnelsen vedrører en fremgangsmåte til fremstilling The invention relates to a method for production
av azolderivatholdig antimykotisk middel med høy frigjøring av virksomme stoffer inneholdende vanlige formuleringsstof-fer, idet fremgangsmåten erkarakterisert vedat til 75°C varmt avmineralisert vann eventuelt tilsatt formuleringshjelpestoffer settes en til 70°C oppvarmet blanding av formuleringshjelpestoffer og spredemiddel, under omrøring, of an azole-derivative antifungal agent with a high release of active substances containing common formulation substances, the method being characterized by adding a mixture heated to 70°C of formulation aids and dispersing agent to 75°C hot demineralized water, possibly with added formulation aids, while stirring,
idet det til denne blanding etter langsom avkjøling til 40°C under omrøring settes azolderivatet oppløst i benzylalkohol, hvoretter råemulsjonen homogeniseres ved 20-25°C whereby, after slow cooling to 40°C with stirring, the azole derivative dissolved in benzyl alcohol is added to this mixture, after which the crude emulsion is homogenized at 20-25°C
i høytrykks homogenisator, idet mengdeforholdene velges slik at det samlede antimykotiske middel får et innhold på 3-5% benzylalkohol og 2,5-20% spredemidler. in a high-pressure homogenizer, the proportions being chosen so that the total antifungal agent has a content of 3-5% benzyl alcohol and 2.5-20% dispersants.
Ved en foretrukket utførelsesform ifølge oppfinnelsen anvendes som azolderivat klortrimazol med formel In a preferred embodiment according to the invention, chlortrimazole with formula is used as azole derivative
Den ytterligere foretrukkede utførelse av fremgangsmåten ifølge oppfinnelsen anvendes som azolderivat trifonazol med formel Ved en ytterligere foretrukket utførelsesform av fremgangsmåten ifølge oppfinnelsen, anvendes som azolderivat lombazol med formelen The further preferred embodiment of the method according to the invention uses trifonazole as an azole derivative with the formula In a further preferred embodiment of the method according to the invention, lombazole is used as an azole derivative with the formula
I fremgangsmåten ifølge oppfinnelsen velges mengdeforholdene fortrinnsvis slik at midlet får et innhold av antimykotisk azolderivat på 0,05-1%, fortrinnsvis 0,1-1%. In the method according to the invention, the quantity ratios are preferably chosen so that the agent has a content of antifungal azole derivative of 0.05-1%, preferably 0.1-1%.
Tallrike ytterligere antimykotisk virksomme azolderivater Numerous additional antifungally active azole derivatives
er kjent fra DE-OS 24 30 039. De kan likeldes tjene som virksomme stoffer i midlene fremstilt ifølge oppfinnelsen. are known from DE-OS 24 30 039. They can also serve as active substances in the agents produced according to the invention.
Med spredemidler forståes oljeaktige væsker som fordeler Dispersants are understood as oily liquids that distribute
seg spesielt godt på huden [R. Keymer, Pharm. Ind. 32 feels particularly good on the skin [R. Keymer, Pharm. Ind. 32
[197Q], 577-581]. For midlene ifølge oppfinnelsen egner det seg som spredemidler spesielt følgende forbindelser: [197Q], 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.
Fsttsyreestere, som etylstearat, Di-n-butyl-adipat, laurin-syreheksylester, dipropylen-glykolpelargonat, estere av forgrenet fettsyre av midlere kjedelengde med mettede fettalkoholer ci£_C^g, isopropylmyristat, isopropylpalmitat, capryl/caprinsyreestere av mettede fettalkoholer av kjedelengde Ci2-C18' isopropylestearat, oljesyreoleylester, oljesyredecylester, etyloleat, melkesyreetylester, voks-aktige fettsyreestere som kunstig andegrøOTpkjertelfett, di-butylftalat, adipinsyrediisopropylester, sistnevnte beslekta ede. es*terb.landinger o.l. Fatty acid esters, such as ethyl stearate, di-n-butyl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, medium chain branched fatty acid esters of saturated fatty alcohols ci£_C^g, isopropyl myristate, isopropyl palmitate, caprylic/capric acid esters of saturated fatty alcohols of chain length Ci2 -C18' 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, the latter related ede. es*terb.landinger etc.
5E.i2iZ£SEi4§E'som capryl/caprinsyretriglycerid, triglycerid-blandinger med plantefettsyrer av kjedelengde cq~ c^ 2 eller andre spesielt utvalgte naturlige fettsyrer, partialglycerid-blandinger av mettede eller umettede eventuelt også hydrok-sylgruppeholdige fettsyrer, monoglycerider av Cg/<C->^<->fettsyrer o.l. 5E.i2iZ£SEi4§E'as caprylic/capric acid triglyceride, triglyceride mixtures with plant fatty acids of chain length cq~ c^ 2 or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids possibly also containing hydroxyl groups, monoglycerides of Cg/ <C->^<->fatty acids etc.
E§i$alkoholé£ i som isotridecylalkohol, 2-oktyldodecanol, cetyls-tearyl-alkohol, oleylalkohol. E§i$alkoholé£ i as isotridecyl alcohol, 2-octyldodecanol, cetyls-tearyl alcohol, oleyl alcohol.
E§£ts.y;£er, SOItl f-eks. oljesyre. E§£ts.y;£er, SOItl e.g. oleic acid.
Spesielt godt egnede spredende oljer er følgende: isopropylmyristat, isopropylpalmitat, capryl/caprinsyreester av mettede fettalkoholer av kjedelengde C±2~ C18' v°kaktige fettsyreestere som kunstig andegompkjertelfett, silikonolje, isopropylmyristat/isopropylestearat/isopropylpalmitat-blanding. Particularly well-suited spreading oils are the following: isopropyl myristate, isopropyl palmitate, caprylic/capric acid esters of saturated fatty alcohols of chain length C±2~ C18' v°kactic fatty acid esters such as artificial duck goiter fat, silicone oil, isopropyl myristate/isopropyl stearate/isopropyl palmitate mixture.
Følgende ytterligere hjelpe- og/eller formulerings-grunn-hjelpemidler kan anvendes ved fremstilling av midlene ifølge oppfinnelsen: The following additional aids and/or formulation-based aids can be used in the preparation of the agents according to the invention:
Videre kan det også anvendes følgende formuleringshjelpe-mi.dler: Glycerol, parafin tyktflytende, parafin tyntflytende, trietanolamin, kollagen, allantoin, novantisolsyre, parfymeolje. Furthermore, the following formulation aids can also be used: Glycerol, viscous paraffin, thin paraffin, triethanolamine, collagen, allantoin, novantisolic acid, perfume oil.
Videre er det egnet: Furthermore, it is suitable:
a. Stoffer som f.eks. kan stabilisere en suspensjon, f.eks. a. Substances such as can stabilize a suspension, e.g.
kolloidal kiselsyre, montmorilloniter o.l. colloidal silicic acid, montmorillonite etc.
b. Tensider (omfattet emulgatorer og fuktemidler),f.eks. b. Surfactants (including emulsifiers and wetting agents), e.g.
1. anioneaktive, som Na-laurylsulfat, fettalkohol-etersulfater, mono/dialkylpolyglykoleter-ortofosfor-syreester-monoetano1aminsa1t, 1. anion-active, such as Na-lauryl sulfate, fatty alcohol-ether sulfates, mono/dialkyl polyglycol ether-orthophosphoric acid ester-monoethane1aminsa1t,
2. kationaktive, som cetyltrimetylammoniumklorid, 2. cation active, such as cetyltrimethylammonium chloride,
3. amfolytiske, som Di-Na-N-lauryl-£S.-ininodipropionat eller lecitin, 4. ikke-ionogene, f.eks. polyoksyetylert rizinusolje, polyoksyetylert sorbitan-monooleat, sorbitan-monostearat, cetylalkohol, glycerolmonostearat, polyoksyetylenstearat, alkylfenolpolyglykoleter. c. Stabilisatorer for å hindre den ved noen virksommeStoffer inntredende kjemiske avbygning som antioksy-danter, f.eks. tokoferol, butylhydroksyanisol. 3. ampholytic, such as Di-Na-N-lauryl-£S.-ininodipropionate 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. Stabilizers to prevent the chemical breakdown that occurs with some active substances such as antioxidants, e.g. tocopherol, butylhydroxyanisole.
d. Mykningsmidler, f. eks. propylenglykol, glycerol, D.i- d. Softeners, e.g. propylene glycol, glycerol, D.i-
og tripropylenglykol, trietanolamin, voks;'.etc. and tripropylene glycol, triethanolamine, wax;'.etc.
Som geldannere kommer det på tale i slike makromolekylære forbindelser som såvel oppløser seg respektivt kan svelle i. vann som også i organiske oppløsningsmidler og etter tørking danner en filmtype. As gel formers, such macromolecular compounds that dissolve or swell in water also form a type of film in organic solvents and after drying.
Følger man en inndeling av de makromolekylære hjelpestoffer [Keipert et al., Die Pharmazie 28, 145-183 (1973)], så kommer det fremfor alt til anvendelse ioniske makromolekyler i deres saltform. Disse er bl.a. natriumkarboksy-metylcellulose, polyacrylsyre, polymetacrylsyre og deres salter, natrimamylopektinsemiglykolat, alginsyre og propylenglykol-alginat som natriumsalt, arabisk gummi, xantan-gummi, guar-gummi. If one follows a division of the macromolecular excipients [Keipert et al., Die Pharmazie 28, 145-183 (1973)], then above all ionic macromolecules are used in their salt form. These are i.a. sodium carboxymethylcellulose, polyacrylic acid, polymethacrylic acid and their salts, sodium amylopectin semiglycolate, alginic acid and propylene glycol alginate as sodium salt, gum arabic, xanthan gum, guar gum.
Amfotære makromolekyler som proteinderivater, f.eks. gela-tiner, er likeledes egnet som ikke-ioniske polymere, f.eks. metylcellulose, hydroksypropylcellulose og oppløselige stivelser som oppfyller ovennevnte krav. Amphoteric macromolecules such as protein derivatives, e.g. gelatins, are also suitable as non-ionic polymers, e.g. methyl cellulose, hydroxypropyl cellulose and soluble starches that meet the above requirements.
Som oppløsningsmiddel er det egnet vann og også alle med vann Blandbare oppløsningsmidler. I betraktning kommer det f.eks. alkanoler som etanol og isopropylalkohol, propylenglykol, metylcellooppløsningsmidler, celluloseoppløsnings-midler, estere, morfoliner, dioksan, dimetylsulfoksyd, dimetylformamid, tetrahydrofuran, cykloheksanon. As a solvent, water is suitable and also all water-miscible solvents. Taking into account e.g. alkanols such as ethanol and isopropyl alcohol, propylene glycol, methylcello solvents, cellulose solvents, esters, morpholines, dioxane, dimethylsulfoxide, dimethylformamide, tetrahydrofuran, cyclohexanone.
Det kan ved fremstillingen av formuleringene ifølge oppfinnelsen anvendes et eller flere oppløsningsmidler. In the preparation of the formulations according to the invention, one or more solvents may be used.
Ekaemge.1^1 Emulsjon, O/V Ekaemge.1^1 Emulsion, O/W
Fase 1 Phase 1
Blandingen omrøres og smeltes ved 70°C. The mixture is stirred and melted at 70°C.
Fase jr Phase jr
Avmi.neralisert vann 58,00 g Fase III Demineralized water 58.00 g Phase III
Til til 75°C oppvarmet fase II tilsettes den til 70°C opp-varmede fase I under omrøring. Man lar. det langsomt avkjøle til 40°C, tilsetter fase III og lar det avkjøle under omrør-ing til værel sestemperatur. Råemulsjonen homogeniseres ved 20-25°C i høytrykkhomogenisator. To phase II heated to 75°C, phase I heated to 70°C is added while stirring. One lets. it slowly cools to 40°C, adds phase III and allows it to cool with stirring to room temperature. The raw emulsion is homogenized at 20-25°C in a high-pressure homogenizer.
På analog måte forarbeides eksemplene 2 og 2. Examples 2 and 2 are processed in an analogous way.
Eksempel_2 Emulsjon, O/V Example_2 Emulsion, O/W
Eksemgel_3 Emulsjon O/V Eksemgel_3 Emulsion O/W
Trifonazol mlcron. Eksempel_4_ Krem, myk konsistens O/V Trifonazole mlcron. Example_4_ Cream, soft consistency O/W
Eksemrj§l_5_ Krem, myk konsistens O/V Eksemgel_6 Krem, myk konsistens O/V Eksemrj§l_5_ Cream, soft consistency O/W Eczema gel_6 Cream, soft consistency O/W
Eksem<pe>l_7 Emulsjon, ikke-fetende O/V Eczema<pe>l_7 Emulsion, non-greasy O/W
Fase. I Phase. IN
Fase II Phase II
Man dispergerer med Turrax, lar det svelle i 2 timer og nøy-traliserer deretter med 0,155 g 45%-ig natronlut. Disperse with Turrax, let it swell for 2 hours and then neutralize with 0.155 g of 45% caustic soda.
Til 75°C varm fase II setter man den 70°C varme fase I unde: omrøring og avkjøler til 45°C. Ved 45°C innrører karbopol-slim og avkjøles til 40°C videre. Ved 40°C tilsettes 1,00 ■ kollagen og avkjøles til 25°C. 1,0 g lombazol oppløses i 3,Q g henzylalkohol og tilsettes til fase I og II'. To 75°C warm phase II, the 70°C warm phase I is placed under: stirring and cooled to 45°C. At 45°C, carbopol slime is stirred in and cooled to 40°C further. At 40°C, 1.00 ■ collagen is added and cooled to 25°C. 1.0 g of lombazole is dissolved in 3.0 g of henzyl alcohol and added to phases I and II'.
Deretter tilsettes 0,600 g parfyme og råemulsjonen homogeniseres under omrøring ved 20°C-25°C i høytrykkshomogenisator På analog måte forarbeides eksemplene 8, 9, 10 og 11. Then 0.600 g of perfume is added and the raw emulsion is homogenised while stirring at 20°C-25°C in a high-pressure homogeniser. Examples 8, 9, 10 and 11 are processed in an analogous way.
Eks.emp_e.l_8 Emulsjon, ikke-fetendeO/VEx.emp_e.l_8 Emulsion, non-greasy O/W
Ek§emj3el__ Emulsjon, ikke-f etende O/V Ek§emj3el__ Emulsion, non-fatty O/W
Eksemgel_10 Emulsjon, ikke-fetende O/V Eksemgel_10 Emulsion, non-greasy O/W
Ek_'emgel_ll Emulsjon, ±kke-fetende O/V. Ek_'emgel_ll Emulsion, non-greasy O/W.
__<&emgel>_12 Krem, myk konsistens O/V __<&emgel>_12 Cream, soft consistency O/W
Eksem_e___3 Krem, myk konsistens O/V Eczema_e___3 Cream, soft consistency O/W
E<_>s<_>mpel_l<_>(Krem, myk konsistens O/V) EIS.§§S!E§i._iå (Krem, transparent i gelform) E<_>s<_>mpel_l<_>(Cream, soft consistency O/W) EIS.§§S!E§i._iå (Cream, transparent in gel form)
Virkningsundersøkelse av middel ifølge oppfinnelsen på trikofyton-infiserte marsvin. Effect investigation of the agent according to the invention on trichophyton-infected guinea pigs.
Som prøvemodell til sammenlignende virkningsundersøkelse av formuleringene fremstilt ifølge oppfinnelsen ble det anvendt trikofyton—infiserte Pirbright-hvite marsvin med en gjennomsnittlig vekt på 600 g. Dyrene ble barbert på ryggen med en elektrisk barbermaskin, således at det ble tilbake ca. 1/10 mm lange hårstumper. Trichophyton-infected Pirbright white guinea pigs with an average weight of 600 g were used as a test model for comparative effectiveness research of the formulations produced according to the invention. The animals were shaved on their backs with an electric shaver, so that approx. 1/10 mm long hair stubs.
Infeksjonen med trikofyton mentagrofytes foregikk ved lett utdrivning av en 24 timer i Sabouraud-næringsoppløs- ning podet sporesuspensjon av frembringere på en ca. 2 x 2 c: stor flate av den barberte rygg på dyrene. Det ble påført pr. dyr 0,5 ml kimsuspensjon som inneholdt 1-3 x 10 5 infekti øse sopp-partikler. The infection with Trichophyton mentagrophytes took place by light expulsion of a 24-hour Sabouraud nutrient solution inoculated spore suspension of producers of approx. 2 x 2 c: large area of the shaved back of the animals. It was applied per animal 0.5 ml germ suspension containing 1-3 x 10 5 infectious fungal particles.
Ved denne infeksjonsmodus viser det seg ved 2-3 dager post infectionem de første symptomer på dermatofytose som rødning og skorpedannelse av huden. Ved ubehandlede dyr er ca. 14 dager p.i. dermatofytosen utpreget maksimalt: flataktig håravfall og blodig integument-defekter innen en betent endret, skorpet kantsone. With this mode of infection, the first symptoms of dermatophytosis such as reddening and crusting of the skin appear 2-3 days post-infection. In untreated animals, approx. 14 days p.i. the dermatophytosis was maximally pronounced: flat hair loss and bloody integument defects within an inflamed altered crusted border zone.
Formuleringene som skulle undersøkes ble en gang på andre dag post infectionem applisert lokalt på de irriterte infeksjonssteder av dyrene og utdrevet lett med en horn-spatel. Det ble hver gang påført 0,5 ml av formuleringen er lik. 5 mg virksomt stoff (1%-ig formulering). Vurderingen a<y>infeksjonsforløpet foregikk daglig inntil 20. dag p.i. The formulations to be examined were once on the second day post infectionem applied locally to the irritated infection sites of the animals and expelled lightly with a horn spatula. It was applied each time 0.5 ml of the formulation is equal. 5 mg of active substance (1% formulation). The assessment of the infection course took place daily until the 20th day p.i.
Prøveresultatene fremgår av nedenstående tabell. The test results appear in the table below.
Anvender man istedet for formuleringene fremstilt ifølge oppfinnelsen formuleringer som ikke inneholder benzylalkohol og ikke spredemiddel, så oppnås en effekt som tilsvarer den med formuleringene fremstilt ifølge oppfinnelsen først etter tre gangers applikasjon. If, instead of the formulations produced according to the invention, formulations which do not contain benzyl alcohol and no dispersant are used, then an effect corresponding to that with the formulations produced according to the invention is only achieved after three applications.
Claims (5)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19803045913 DE3045913A1 (en) | 1980-12-05 | 1980-12-05 | ANTIMYCOTIC AGENTS WITH HIGH ACTIVE SUBSTANCE RELEASE |
Publications (3)
Publication Number | Publication Date |
---|---|
NO813930L NO813930L (en) | 1982-06-07 |
NO158922B true NO158922B (en) | 1988-08-08 |
NO158922C NO158922C (en) | 1988-11-23 |
Family
ID=6118422
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO813930A NO158922C (en) | 1980-12-05 | 1981-11-19 | PROCEDURE FOR THE MANUFACTURE OF AZOLD DERIVATIVE ANTIMYCOTIC AGENT WITH HIGH RELEASE OF ACTIVE SUBSTANCES. |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP0054205B1 (en) |
JP (1) | JPS57120516A (en) |
KR (1) | KR880000724B1 (en) |
AT (1) | ATE11219T1 (en) |
AU (1) | AU546451B2 (en) |
CA (1) | CA1180661A (en) |
DE (2) | DE3045913A1 (en) |
DK (1) | DK538481A (en) |
ES (1) | ES8400241A1 (en) |
FI (1) | FI813883L (en) |
IL (1) | IL64434A0 (en) |
NO (1) | NO158922C (en) |
ZA (1) | ZA818430B (en) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH655656B (en) * | 1982-10-07 | 1986-05-15 | ||
DE3244027A1 (en) * | 1982-11-27 | 1984-05-30 | Bayer Ag, 5090 Leverkusen | ANTIMYCOTIC AGENTS WITH HIGH ACTIVE SUBSTANCE RELEASE IN THE FORM OF GEL SYSTEMS |
DE3311700A1 (en) * | 1983-03-30 | 1984-10-04 | Bayer Ag | ANTIMYCOTIC AGENTS WITH HIGH ACTIVE SUBSTANCE RELEASE IN THE FORM OF SOLUTION AND SPRAY |
DE3311701A1 (en) * | 1983-03-30 | 1984-10-04 | Bayer Ag | ANTIMYCOTIC AGENTS WITH HIGH ACTIVE SUBSTANCE RELEASE IN THE FORM OF CREAM |
DE3323832A1 (en) * | 1983-07-01 | 1985-01-03 | Troponwerke Gmbh & Co Kg | OVEN AMATE PREPARATION |
DE3323833A1 (en) * | 1983-07-01 | 1985-01-03 | Troponwerke Gmbh & Co Kg | OVEN AMATE PREPARATION |
US4731384A (en) * | 1983-07-01 | 1988-03-15 | Troponwerke Gmbh & Co, Kg | Etofenamate formulation |
JPS6058914A (en) * | 1983-09-12 | 1985-04-05 | Shionogi & Co Ltd | Antimycotic gel preparation for external use containing imidazoles |
CS253719B2 (en) * | 1984-03-07 | 1987-12-17 | Janssen Pharmaceutica Nv | Emulsible concentrate with fungicide activity and process for preparing thereof |
DE3520098A1 (en) * | 1985-06-05 | 1986-12-11 | Bayer Ag, 5090 Leverkusen | FORMULAS CONTAINING AZOLE DERIVATIVES AND THEIR USE FOR ATRAUMATIC NAIL REMOVAL |
JPS6261915A (en) * | 1985-09-10 | 1987-03-18 | Taisho Pharmaceut Co Ltd | Antimycotic agent for external use |
DE3600947A1 (en) * | 1986-01-15 | 1987-07-16 | Kali Chemie Pharma Gmbh | ANTIMYCOTIC EMULSIONS |
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 |
JPH01246219A (en) * | 1988-03-25 | 1989-10-02 | Nippon Nohyaku Co Ltd | Antimycotic cream composition for external use |
JPH0725675B2 (en) * | 1989-05-08 | 1995-03-22 | ホーユー株式会社 | Liquid mycosis agent |
YU2792A (en) * | 1991-01-19 | 1995-01-31 | Hoechst A Ktiengesellschaft | DISPERSIONS OF FINE PARTICLES, ANTIHELMINTENTALLY EFFECTIVE DERIVATIVES, BENZIMIDAZOLE OR BENZTIAZOLE OR PRO-BENZIMIDAZOLE IN WATER |
KR20020045152A (en) * | 2000-12-08 | 2002-06-19 | 류정열 | Clamp-holder for hose-clamp |
WO2006005120A1 (en) * | 2004-07-09 | 2006-01-19 | Pandura Farms Pty Ltd | Sequential cooling methods and apparatus |
US9687429B2 (en) | 2007-06-20 | 2017-06-27 | The Trustees Of Columbia University In The City Of New York | Antimicrobial compositions containing low concentrations of botanicals |
US9511040B2 (en) | 2007-06-20 | 2016-12-06 | The Trustees Of Columbia University In The City Of New York | Skin and surface disinfectant compositions containing botanicals |
WO2008157092A1 (en) | 2007-06-20 | 2008-12-24 | The Trustees Of Columbia University In The City Of New York | Bio-film resistant surfaces |
US9981069B2 (en) | 2007-06-20 | 2018-05-29 | The Trustees Of Columbia University In The City Of New York | Bio-film resistant surfaces |
JP2012532141A (en) * | 2009-06-30 | 2012-12-13 | ザ トラスティース オブ コロンビア ユニバーシティ イン ザ シティ オブ ニューヨーク | Antimicrobial / preservative composition containing plant components |
US9968101B2 (en) | 2011-11-03 | 2018-05-15 | The Trustees Of Columbia University In The City Of New York | Botanical antimicrobial compositions |
EP2773334B1 (en) | 2011-11-03 | 2019-08-28 | The Trustees of Columbia University in the City of New York | Composition with sustained antimicrobial activity |
WO2013086094A1 (en) | 2011-12-06 | 2013-06-13 | The Trustees Of Columbia University In The City Of New York | Broad spectrum natural preservative composition |
CN111423328B (en) * | 2020-04-02 | 2022-04-15 | 广州隽沐生物科技股份有限公司 | Preparation method of decyl oleate |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3502594A (en) * | 1965-12-28 | 1970-03-24 | Gerhard W Ahrens | Synergistic antioxidant composition for natural oleaginous materials |
US3483008A (en) * | 1966-08-01 | 1969-12-09 | Daniel A Naeve | Method of preparing a water-soluble protein lotion |
DE2333355C2 (en) * | 1973-06-30 | 1984-01-19 | Bayer Ag, 5090 Leverkusen | Antimicrobial agents |
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 |
DE2628421A1 (en) * | 1976-06-24 | 1978-01-05 | Bayer Ag | ANTIMICROBIAL AGENTS |
DE2811916A1 (en) * | 1978-03-18 | 1979-09-27 | Bayer Ag | Antimycotic 1-phenoxy-1-azolyl-4-halo-2-acyloxy-butane derivs. - prepd. by acylation of corresp. 1-imidazolyl-or 1-triazolyl-2-butanol derivs. |
-
1980
- 1980-12-05 DE DE19803045913 patent/DE3045913A1/en not_active Withdrawn
-
1981
- 1981-11-19 NO NO813930A patent/NO158922C/en unknown
- 1981-11-27 DE DE8181109946T patent/DE3168402D1/en not_active Expired
- 1981-11-27 EP EP81109946A patent/EP0054205B1/en not_active Expired
- 1981-11-27 AT AT81109946T patent/ATE11219T1/en not_active IP Right Cessation
- 1981-12-02 IL IL64434A patent/IL64434A0/en not_active IP Right Cessation
- 1981-12-03 FI FI813883A patent/FI813883L/en not_active Application Discontinuation
- 1981-12-04 AU AU78263/81A patent/AU546451B2/en not_active Ceased
- 1981-12-04 JP JP56194672A patent/JPS57120516A/en active Granted
- 1981-12-04 DK DK538481A patent/DK538481A/en not_active Application Discontinuation
- 1981-12-04 CA CA000391479A patent/CA1180661A/en not_active Expired
- 1981-12-04 ES ES507726A patent/ES8400241A1/en not_active Expired
- 1981-12-04 ZA ZA818430A patent/ZA818430B/en unknown
- 1981-12-05 KR KR1019810004748A patent/KR880000724B1/en active
Also Published As
Publication number | Publication date |
---|---|
EP0054205B1 (en) | 1985-01-16 |
DE3045913A1 (en) | 1982-07-08 |
ES507726A0 (en) | 1983-11-01 |
CA1180661A (en) | 1985-01-08 |
FI813883L (en) | 1982-06-06 |
KR830007071A (en) | 1983-10-12 |
AU7826381A (en) | 1982-06-10 |
ZA818430B (en) | 1982-11-24 |
ATE11219T1 (en) | 1985-02-15 |
IL64434A0 (en) | 1982-03-31 |
NO158922C (en) | 1988-11-23 |
EP0054205A1 (en) | 1982-06-23 |
JPS57120516A (en) | 1982-07-27 |
NO813930L (en) | 1982-06-07 |
DE3168402D1 (en) | 1985-02-28 |
DK538481A (en) | 1982-06-06 |
ES8400241A1 (en) | 1983-11-01 |
KR880000724B1 (en) | 1988-04-29 |
AU546451B2 (en) | 1985-09-05 |
JPH0380775B2 (en) | 1991-12-26 |
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