NO178684B - Process for producing a device for dispensing substances from hot melt adhesives - Google Patents
Process for producing a device for dispensing substances from hot melt adhesives Download PDFInfo
- Publication number
- NO178684B NO178684B NO891507A NO891507A NO178684B NO 178684 B NO178684 B NO 178684B NO 891507 A NO891507 A NO 891507A NO 891507 A NO891507 A NO 891507A NO 178684 B NO178684 B NO 178684B
- Authority
- NO
- Norway
- Prior art keywords
- weight
- hot
- substances
- melt adhesive
- melt
- Prior art date
Links
- 239000004831 Hot glue Substances 0.000 title claims abstract description 53
- 239000000126 substance Substances 0.000 title claims abstract description 33
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 239000000463 material Substances 0.000 claims abstract description 10
- 239000000853 adhesive Substances 0.000 claims description 19
- 230000001070 adhesive effect Effects 0.000 claims description 19
- 239000000945 filler Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 239000013032 Hydrocarbon resin Substances 0.000 claims description 10
- 229920006270 hydrocarbon resin Polymers 0.000 claims description 10
- 230000032683 aging Effects 0.000 claims description 9
- 229920000642 polymer Polymers 0.000 claims description 9
- 239000011814 protection agent Substances 0.000 claims description 9
- 150000001298 alcohols Chemical class 0.000 claims description 7
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 229920002367 Polyisobutene Polymers 0.000 claims description 5
- 229920002635 polyurethane Polymers 0.000 claims description 5
- 239000004814 polyurethane Substances 0.000 claims description 5
- 239000011241 protective layer Substances 0.000 claims description 5
- 239000004014 plasticizer Substances 0.000 claims description 4
- 229920001610 polycaprolactone Polymers 0.000 claims description 4
- 229920000647 polyepoxide Polymers 0.000 claims description 4
- 230000003712 anti-aging effect Effects 0.000 claims description 3
- 238000009826 distribution Methods 0.000 claims description 3
- 229920001289 polyvinyl ether Polymers 0.000 claims description 2
- 238000009828 non-uniform distribution Methods 0.000 abstract 1
- 239000011253 protective coating Substances 0.000 abstract 1
- 238000009827 uniform distribution Methods 0.000 abstract 1
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- KBAYQFWFCOOCIC-GNVSMLMZSA-N [(1s,4ar,4bs,7s,8ar,10ar)-1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,7,8,8a,9,10,10a-dodecahydrophenanthren-1-yl]methanol Chemical compound OC[C@@]1(C)CCC[C@]2(C)[C@H]3CC[C@H](C(C)C)C[C@H]3CC[C@H]21 KBAYQFWFCOOCIC-GNVSMLMZSA-N 0.000 description 9
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/58—Adhesives
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
- G01N33/521—Single-layer analytical elements
-
- 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
-
- 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
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
Abstract
Description
Foreliggende oppfinnelse vedrører en fremgangsmåte for fremstilling av en innretning for avgivelse av stoffer fra varmsmelte-klebemidler med ujevn eller jevn fordeling av stoffene. The present invention relates to a method for producing a device for releasing substances from hot-melt adhesives with uneven or even distribution of the substances.
Typiske representanter for slike innretninger er plastere inneholdende virksomme stoffer, indikatorsystemer, innretninger som avgir duftstoffer og lignende, hvorved disse spesielt ofte anvendes på det medisinske området for kontrollert eller ukontrollert avgivelse av stoffer. Herved 'har de kontrollerte innretningene i form av transdermale kontrollerte systemer fått en spesiell betydning. For disse er det også allerede kjent å påføre et sjikt inneholdende virksomt stoff fra smeiten. Fra EP-OS 0177893 er en ikke-klebende, fra smeiten påførbar celluloseetergel blitt kjent, hvori virksomme stoffer kan fordeles. Denne gelen bearbeides i varm tilstand og er ikke-klebende. Fra DE-OS 32 22 800 er et transdermalt system kjent, hvorved virksomt stoff forpakket i mikrokapsler foreligger i et termisk formbart, klebende matriksmateriale, som påføres fra smeiten. Typical representatives of such devices are plasters containing active substances, indicator systems, devices that release fragrances and the like, whereby these are particularly often used in the medical field for controlled or uncontrolled release of substances. Hereby, the controlled devices in the form of transdermal controlled systems have acquired a special significance. For these, it is also already known to apply a layer containing active substance from the smelting. From EP-OS 0177893, a non-adhesive cellulose ether gel that can be applied from the melt has become known, in which active substances can be distributed. This gel is processed in a warm state and is non-sticky. From DE-OS 32 22 800 a transdermal system is known, whereby active substance packaged in microcapsules is present in a thermally malleable, adhesive matrix material, which is applied from the melt.
Det er også forsøkt å fremstille ikke-klebende matrikser inneholdende virksomt stoff ved romtemperatur for temperatur-følsomme virksomme stoffer med lavt kokepunkt eller også høy dekomponerbarhet. Eksempelvis angis i US-PS 4.379.454 (Campbell et al.) å anvende en oppløsning av virksomt stoff, som er brakt til den ønskede viskositetsverdien ved romtemperatur ved hjelp av et geleringsmiddel, som sjikt av virksomt stoff. Fra US-PS 4.559.222 (Enscore et al.) er det kjent å anvende en ved romtemperatur fremstilt blanding av mineralolje/polyisobutylen og kolloidal silisiumdioksid som viskøst sjikt av virksomt stoff for oljeoppløselige virksomme stoffer, hvorved disse sjiktene også kan gjøres klebende. DE-OS 32 22 800 (ALZA) beskriver et sjikt av virksomt stoff av en ved hjelp av et reologisk middel, som cellulose, et polysakkarid eller en silisiumforbindelse avtettet oppløsning av virksomt stoff som ikke er klebende og som er egnet for rask avgivelse av virksomt stoff. Attempts have also been made to produce non-adhesive matrices containing active substance at room temperature for temperature-sensitive active substances with a low boiling point or also high decomposability. For example, in US-PS 4,379,454 (Campbell et al.) it is stated to use a solution of active substance, which has been brought to the desired viscosity value at room temperature by means of a gelling agent, as a layer of active substance. From US-PS 4,559,222 (Enscore et al.) it is known to use a room-temperature mixture of mineral oil/polyisobutylene and colloidal silicon dioxide as a viscous layer of active substance for oil-soluble active substances, whereby these layers can also be made adhesive. DE-OS 32 22 800 (ALZA) describes a layer of active substance of a solution of active substance sealed by means of a rheological agent, such as cellulose, a polysaccharide or a silicon compound, which is not sticky and which is suitable for rapid release of active substance fabric.
Fra US-PS 3.923.939 er det kjent å forme virksomme stoffer, som tetracyklin, i et etylen-vinylacetat-kopolymersjikt ved smeltepressing. Ifølge EP-OS 86 468 fylles et oralt anti-diabetes-sulfonylureaderivat i en ikke-klebende varmsmelte-masse med et smeltepunkt på 30 til 90°C i på forhånd bestemte doser fra smeiten i kapsler. I US-PS 3.957.966 beskrives at virksomme stoffer kan bearbeides i ikke-klebende varmsmelte-masse. From US-PS 3,923,939 it is known to form active substances, such as tetracycline, in an ethylene-vinyl acetate copolymer layer by melt pressing. According to EP-OS 86 468, an oral anti-diabetic sulfonylurea derivative is filled in a non-sticky hot-melt mass with a melting point of 30 to 90°C in predetermined doses from the melt in capsules. In US-PS 3,957,966 it is described that active substances can be processed into non-sticky hot-melt mass.
Fra DE-OS 30 07 363 er det kjent å anvende en klebende blanding av en termoplastisk elastomer, her fortrinnsvis en blokkpolymer av generell formel Å-B-A, en klebriggjørende harpiks med olje eller høyere fettsyrer og virksomt stoff for fremstilling av et enkelt transdermalt system. Den der omtalte klebeblandingen egner seg bare for relativt tempera-turresistente virksomme stoffer, som tåler temperaturer på 120° C og mer. From DE-OS 30 07 363 it is known to use an adhesive mixture of a thermoplastic elastomer, here preferably a block polymer of general formula Å-B-A, a tackifying resin with oil or higher fatty acids and active substance for the production of a single transdermal system. The adhesive mixture mentioned there is only suitable for relatively temperature-resistant active substances, which can withstand temperatures of 120° C and more.
I US-PS 3.699.963 omfatter en av de vanlige fremgangsmåtene for fremstilling av varmsmelte-klebende plastere, hvorved (se eksempler) det innføres et relativt temperaturbestandig materiale, nemlig oksitocin, i et klebemiddel. I eksempelet i dette patentskriftet beskrives riktignok fremgangsmåter for blanding av varmsmelte-klebemidlet med oksitocin; det antydes på ingen måte at det anvendes et ved lave temperaturer smeltende varmsmelte-klebemiddel, som anvendes ifølge oppfinnelsen. In US-PS 3,699,963, one of the usual methods for the production of hot-melt adhesive plasters includes, whereby (see examples) a relatively temperature-resistant material, namely oxytocin, is introduced into an adhesive. The example in this patent certainly describes methods for mixing the hot-melt adhesive with oxytocin; it is in no way implied that a hot-melt adhesive that melts at low temperatures, which is used according to the invention, is used.
Sammensetningen som generelt beskrives i US-PS 3.699.963 er riktignok et varmsmelte-klebemiddel, dets generelle sammen-setning ville imidlertid måtte endres på en slik måte at det kunne anvendes som varmsmelte-klebemiddel spesielt med lavere smeltetemperatur enn det som hittil er vanlig. For dette formålet er spesielle forholdsregler nødvendige, det gås på ingen måte inn på disse i det nevnte patentskriftet. The composition that is generally described in US-PS 3,699,963 is indeed a hot-melt adhesive, its general composition would, however, have to be changed in such a way that it could be used as a hot-melt adhesive, especially with a lower melting temperature than is usual heretofore. For this purpose, special precautions are necessary, these are not addressed in any way in the aforementioned patent document.
Ifølge US-PS 4.515.909 blandes en flyktig forbindelse (duftstoff) med etylenvinylacetatkopolymer (EVA) ved en temperatur på 50-60°C. Ifølge denne publikasjonen anvendes imidlertid ikke en smeltet polymer, men derimot bare en polymer som i fast tilstand impregneres med det flyktige duftstoffet. According to US-PS 4,515,909, a volatile compound (perfume) is mixed with ethylene vinyl acetate copolymer (EVA) at a temperature of 50-60°C. According to this publication, however, a molten polymer is not used, but instead only a polymer which is impregnated in the solid state with the volatile fragrance.
Fremgangsmåtene ifølge teknikkens stand for fremstilling av slike systemer egner seg ikke for transdermale systemer som omfatter temperaturfølsomme stoffer, som skopolamin. Hittil har derfor klebende sjikt av virksomt stoff med temperatur-følsomme virksomme stoffer fortrinnsvis vært fremstilt fra oppløsning og oppløsningsmidlet fordampet. The methods according to the state of the art for producing such systems are not suitable for transdermal systems that include temperature-sensitive substances, such as scopolamine. Until now, therefore, adhesive layers of active substances with temperature-sensitive active substances have preferably been produced from solution and the solvent evaporated.
Anvendelsen av oppløsningsmidlet ved fremstilling av klebende sjikt inneholdende virksomme stoffer er uheldige av flere grunner. Fremstillingen av oppløsningene krever minst ett ytterligere, omstendelig fremgangsmåtetrinn. Den betinger en større teknisk omstendelighet og kostnader for håndtering av oppløsningsmidlene - videre må det for medisinske formål anvendes meget rene og dermed dyre oppløsningsmidler for, for oppløsningen av klebemidlet henholdsvis dets utgangsmateri-aler, å sikre en tilsvarende restfrihet i innretningen. Et ytterligere problem består i å oppnå oppløsningsmiddelfrihet i innretningen, for dette formålet er dyre tørkestrekninger og avsugningsanlegg påkrevet. Videre opptrer kostnader ved gjenvinning og fraskillelse av oppløsningsmidlet for å unngå miljøbelastning. Videre utgjør brennbarheten for de fleste oppløsningsmidler igjen en ytterligere risiko. Videre er de fleste organiske oppløsningsmidler skadelige for den menneskelige organismen, slik at omstendlige sikkerhetstiltak må treffes for personene som er beskjeftiget med driften. Det er følgelig oppfinnelsens oppgave å unngå de ovenfor angitte ulempene ved fremgangsmåter av denne art ifølge teknikkens stand. The use of the solvent in the production of adhesive layers containing active substances is unfortunate for several reasons. The preparation of the solutions requires at least one further, elaborate process step. It requires greater technical complexity and costs for handling the solvents - furthermore, for medical purposes, very clean and thus expensive solvents must be used to, for the dissolution of the adhesive or its starting materials, ensure a corresponding freedom from residues in the device. A further problem consists in achieving solvent freedom in the device, for this purpose expensive drying lines and extraction systems are required. Furthermore, costs arise when recycling and separating the solvent to avoid environmental impact. Furthermore, the flammability of most solvents again poses an additional risk. Furthermore, most organic solvents are harmful to the human organism, so that extensive safety measures must be taken for the persons involved in the operation. It is therefore the task of the invention to avoid the above-mentioned disadvantages of methods of this kind according to the state of the art.
Oppgaven løses ifølge oppfinnelsen ved en fremgangsmåte for fremstilling av en innretning for avgivelse av stoffer fra varmsmelte-klebemidler med ujevn eller jevn fordeling av stoffene i varmsmelte-klebemidlene, kjennetegnet ved at en smeltet blanding av varmsmelte-klebemiddel, fremstilt på basis av polymer valgt blant styren-isopren-styren-blokkpolymerer , polykaprolaktoner, etylen-vinylacetat-kopolymerer, polyuretan, polyepoksyder, polyisobuten eller polyvinyletere, hydrert alkohol og hydrokarbonharpiks, eventuelt under tilsats av myknere, klebemidler, fyllstoffer, eldingsbeskyttelsesmidler, og/eller tiksotroperingsmidler, og stoff som skal avgis, ved en temperatur for blandingen mellom 40 og 80°C, fortrinnsvis 40 til 60°C, og spesielt foretrukket 45 til 55°C, påføres en bærer og at det eventuelt anbringes et beskyttelsessjiktmateriale på innretningen. The task is solved according to the invention by a method for producing a device for releasing substances from hot-melt adhesives with uneven or even distribution of the substances in the hot-melt adhesives, characterized in that a molten mixture of hot-melt adhesives, produced on the basis of a polymer selected from styrene-isoprene-styrene block polymers, polycaprolactones, ethylene-vinyl acetate copolymers, polyurethane, polyepoxides, polyisobutene or polyvinyl ethers, hydrogenated alcohol and hydrocarbon resins, possibly with the addition of plasticizers, adhesives, fillers, anti-ageing agents, and/or thixotroping agents, and substances to be emitted, at a temperature for the mixture between 40 and 80°C, preferably 40 to 60°C, and particularly preferably 45 to 55°C, a carrier is applied and that a protective layer material is optionally placed on the device.
Herved kan det arbeides ved lave temperaturer uten oppløs-ningsmiddel, hvorved det oppnås en betydelig innsparing av materialer, en raskere fremstilling av innretningen uten de tidkrevende tørketrinnene, samt en for miljøet mindre belastende fremstilling av innretningene, hvilken blant annet fører til et betydelig prisgunstigere og også et oppløsnings-middelfritt produkt. In this way, work can be done at low temperatures without solvents, whereby a significant saving in materials is achieved, a faster production of the device without the time-consuming drying steps, as well as a production of the devices that is less burdensome to the environment, which among other things leads to a significantly more favorable price and also a solvent-free product.
Ved anvendelse av lettflyktige og/eller termisk instabile stoffer som skal avgis, kan de nedenfor angitte spesielle forholdsreglene for bearbeidelse angis: When using highly volatile and/or thermally unstable substances that are to be released, the special precautions for processing specified below can be specified:
Å. arbeide ved lavest mulige temperaturer, Å. work at the lowest possible temperatures,
B. forhøyelse av det ytre trykket for å redusere fordamp-ningen , C. metning av damprom over smeiten med det dampformige stoffet, D. arbeide med de minst mulige mengdene flyktige stoffer, B. increasing the external pressure to reduce evaporation, C. saturating the vapor space above the melt with the vaporous substance, D. working with the smallest possible amounts of volatile substances,
svarende til angivelsene, i- smeiten. corresponding to the specifications, i-smeiten.
Naturligvis er disse forholdsreglene, som eksempelvis arbeide i et innkapslet anlegg, begrenset ved de for fagmannen, ved anvendelsesformålet for innretningen som skal fremstilles og også stofflige forhold, kjente lovmessighetene. Naturally, these precautions, such as working in an enclosed facility, for example, are limited by the laws known to the expert, by the intended use of the device to be produced and also material conditions.
Innretningene ifølge oppfinnelsen, spesielt de transdermale systemene, kan eksempelvis anvendes for lokal eller systemisk transdermal administrering av virksomt stoff innenfor human-og veterinærmedisin eller det kosmetiske området, fortrinnsvis for avgivelse av temperaturfølsomme og/eller lettflyktige stoffer . The devices according to the invention, especially the transdermal systems, can for example be used for local or systemic transdermal administration of active substances within human and veterinary medicine or the cosmetic area, preferably for the delivery of temperature-sensitive and/or volatile substances.
Herved forstås under varmsmelte-klebemiddel et hvert klebemiddel som i varm tilstand er tilstrekkelig flytende til problemløst å kunne påføres ved en temperatur over ca. 40"C. By this, hot-melt adhesive is understood to mean any adhesive which in a hot state is sufficiently fluid to be able to be applied without problems at a temperature above approx. 40"C.
Dannelsen av bestanddelene av innretningen, som oppviser varmsmelte-klebemiddel med bearbeidelsestemperatur mellom 40 og 80°C, kan foregå ved ekstrudering, støping, valsepåføring, knivbestrykning, påsprøyting eller en trykkefremgangsmåte. The formation of the components of the device, which have a hot-melt adhesive with a processing temperature between 40 and 80°C, can take place by extrusion, casting, roller application, knife coating, spraying or a printing process.
En grenseverdi for bearbeidbarheten av varmsmelte-klebemidlet ved mange av disse fremgangsmåtene er gitt ved en viskositet i området på ca. 80 000 Pa. A limit value for the workability of the hot melt adhesive in many of these methods is given by a viscosity in the range of approx. 80,000 Pa.
Dersom underlaget som skal behandles med klebemidlet - en komponent av innretningen - kan skades ved temperaturen av det varmt påførte klebemidlet - enten ved dekomponering, reaksjon eller partiell smelting, kan det anvendes et avkjølt underlag. Avkjølingen kan foregå på i og for seg kjent måte, som ved innføring av kalde inerte gasser eller kontakt med en kjøleflate. If the substrate to be treated with the adhesive - a component of the device - can be damaged by the temperature of the hot applied adhesive - either by decomposition, reaction or partial melting, a cooled substrate can be used. The cooling can take place in a manner known per se, such as by introducing cold inert gases or contact with a cooling surface.
Varmsmelte-klebemidlet kan f.eks. påføres i sjiktform eller i enkelte områder svarende til e.t på forhånd bestemt mønster på beskyttelsessjiktet eller avdekningsmaterialet. The hot melt adhesive can e.g. applied in layers or in certain areas corresponding to a pre-determined pattern on the protective layer or covering material.
Avhengig av anvendelsesformålet - dersom eksempelvis stoffet som skal avgis gjennom det bakre sjiktet, som f.eks. kan være tilfellet ved eteriske oljer, som duftstoffer, kan varmsmelte-klebemidlet være utstyrt med en bærer som er gjennomtrengelig for stoffet/stoffene som skal avgis, mens ved utførelsesformen av innretningen som transdermalt system, hvorved stoffet bare skal avgis til huden, er et bakre sjikt som er ugjennomtrengelig for stoffet som skal avgis foretrukket . Depending on the intended use - if, for example, the substance to be released through the back layer, such as e.g. may be the case with essential oils, such as fragrances, the hot-melt adhesive may be equipped with a carrier that is permeable to the substance/substances to be released, while in the embodiment of the device as a transdermal system, whereby the substance is only to be released to the skin, a rear a layer that is impermeable to the substance to be emitted is preferred.
Ved fremgangsmåten ifølge oppfinnelsen kan anvendelsen av oppløsningsmiddelholdige klebende materialer ved bearbeidelsen av temperaturføl somme og lettflyktige stoffer unngås, hvilket fører til betydelig forhøyelse av sikkerheten av fremstillingen, idet ingen toksiske oppløsningsmiddelrester lenger kan forbli i legemiddel-administreringsformen, hvilket fører til en sterkt forenklet fremgangsmåte for påføring og til betydelige innsparinger av fremstillingskostnadene. Derved kan fremgangsmåten naturligvis også på fordelaktig måte anvendes for mindre temperaturfølsomme stoffer idet det også derved oppnås betydelige kostnadsinnsparinger. With the method according to the invention, the use of solvent-containing adhesive materials in the processing of temperature-sensitive and highly volatile substances can be avoided, which leads to a significant increase in the safety of the production, since no toxic solvent residues can remain in the drug administration form, which leads to a greatly simplified method for application and to significant savings in manufacturing costs. Thereby, the method can of course also be advantageously used for less temperature-sensitive substances, as significant cost savings are also achieved thereby.
Under betegnelsen "stoffer" i forbindelse med foreliggende oppfinnelse forstås kjemiske elementer, organiske og uorganiske forbindelser, som kan vandre ut fra bestanddelene som inneholder dem i en slik innretning og derved fremkalle en ønsket effekt. Under anvendelsesområdene for innretningen ifølge oppfinnelsen er human- og veterinærmedisin av spesiell betydning, hvorved herved en utførelse av oppfinnelsen i plasterform er spesielt foretrukket. The term "substances" in connection with the present invention is understood to mean chemical elements, organic and inorganic compounds, which can migrate out of the components that contain them in such a device and thereby produce a desired effect. Among the areas of application for the device according to the invention, human and veterinary medicine is of particular importance, whereby an embodiment of the invention in plaster form is particularly preferred.
Typiske stoffer som kan administreres ved hjelp av innretningene fremstilt ifølge oppfinnelsen er: aceklidin, amfetaminil, amfetamin, amylnitritt, apofedrin, atebrin, alprostadil, azulen, arecolin, anetol, amylenhydrat, acetylkolin, akridin, adenosintrifosforsyre, L-eplesyre, alimemazin, allitiamin, allyl, isotiocyanat, aminoetanol, apyzin, apiol, azatadin, alprenolol, etinazon, benzoylper-oksid, benzylalkohol, bisabolol, bisnorefedrin, butacetoluid, benactyzin, kamfer, kolekalciferol, kloralhydrat, klemastin, klorbutanol, kapsaicin, cyklopentamin, klobutinol, kamazulen, dimetokain, kodein, klorpromazin, kinin, klortymol, cyklo-fosfamid, cinkokain, klorambuzil, klorfenesin, dietyletan, divinyletan, deksklorfeniramin, dinoproston, dixyrazin, efedrin, etosuksimid, enallylpropymal, emylcamat, erytrol-tetranitrat, emetin, enfluran, eukalyptol, etofenamat, etylmorfin, fentanyl, fluanison, guajazulen, halotan, hyoscyamin, histamin, fenkarbamid, hydroksykain, heksylresor-cin, isoaminilcitrat, isosorbiddinitrat, ibuprofen, jod, jodoform, isoaminil, lidokain, lopirin, levamisol, metadon, metyprylon, metylfenidat, mefenesin, metylefedrin, meklastin, metopromazin, mesuksimid, nicetamid, norpseudoefedrin, mentol, metoksyfluran, metylpentinol, metiksen, misoprostol oksitetrakain, oksiprenolol, oksifenbutazon, oksikinolin, pinen, prolintan, procyklidin, piperazin, pivazid, fensuks-imid, prokain, fenindamin, prometazin, pentetrazol, profen-amin, perazin, fenol, petidin, pilokarpin, prenylamin, fenoksybenzamin, resochin, scopolamin, salicylsyreester, spartein, trikloretylen, timolol, trifluperazin, tetrakain, trimipramin, tranylcypromin, trimetadion, tybamat, tymol, tioridazin, valproinsyre, verapamil, samt ytterligere virksomme stoffer som kan opptas via huden, innbefattende slimhimmene, som er kjente for fagmannen. Naturligvis er denne opplistingen ikke fullstendig. Typical substances that can be administered using the devices manufactured according to the invention are: aceclidine, amphetamine, amphetamine, amyl nitrite, apoephedrine, atebrine, alprostadil, azulen, arecoline, anethole, amylene hydrate, acetylcholine, acridine, adenosine triphosphoric acid, L-malic acid, alimemazine, allitiamine, allyl, isothiocyanate, aminoethanol, apyzine, apiol, azatadine, alprenolol, etinazone, benzoylperoxide, benzyl alcohol, bisabolol, bisnorephedrine, butacetoluid, benactyzine, camphor, cholecalciferol, chloral hydrate, clemastine, chlorobutanol, capsaicin, cyclopentamine, clobutinol, camazulene, dimethocaine, codeine, chlorpromazine, quinine, chlorthymol, cyclo-phosphamide, cinchocaine, chlorambuzil, chlorphenesin, diethylethane, divinylethane, dexchlorpheniramine, dinoprostone, dixyrazine, ephedrine, ethosuximide, enallylpropymal, emylcamate, erythrol tetranitrate, emetine, enflurane, eucalyptol, etofenamate, ethylmorphine, fentanyl, fluanisone, guaiazulene, halothane, hyoscyamine, histamine, phencarbamide, hydroxycaine, hexylresorcin, isoaminyl citrate, isosorbide dinitrate, ibuprofen, iodine, iodoform, isoaminil, lidocaine, lopirin, levamisole, methadone, metyprylone, methylphenidate, mephenesin, methylephedrine, meclastin, metopromazine, mesuximide, nicetamide, norpseudoephedrine, menthol, methoxyflurane, methylpentinol, methixen, misoprostol oxytetracaine, oxyprenolol, oxyphenbutazone , oxyquinoline, pinene, prolintane, procyclidine, piperazine, pivazide, phensuximide, procaine, phenindamine, promethazine, pentetrazole, prophenamine, perazine, phenol, pethidine, pilocarpine, prenylamine, phenoxybenzamine, resochin, scopolamine, salicylic acid ester, sparteine, trichlorethylene . Naturally, this listing is not complete.
Typiske sammensetninger for varmsmelte-klebestoffer som anvendes ifølge oppfinnelsen er slike som er fremstilt av mellom 20 og 80 vekt-#, fortrinnsvis 20 til 50 vekt-# polymer, mellom 1 og 80 vekt-#, fortrinnsvis 1 til 60 vekt-# mykner; mellom 10 og 80 vekt-#, fortrinnsvis 15 til 60 vekt-# klebemiddel, eventuelt 0,1 til 5 vekt-# eldings-beskyttelses-middel og eventuelt 0 til 7.0 vekt-# fyllstoffer, hvorved summen av prosentangivelsene for bestanddelene alltid er 100. Typical compositions for hot-melt adhesives used according to the invention are those made from between 20 and 80 wt-#, preferably 20 to 50 wt-# of polymer, between 1 and 80 wt-#, preferably 1 to 60 wt-# of plasticizer; between 10 and 80 wt-#, preferably 15 to 60 wt-# adhesive, optionally 0.1 to 5 wt-# aging protection agent and optionally 0 to 7.0 wt-# fillers, whereby the sum of the percentages for the components is always 100 .
Foretrukket er at varmsmelte-klebemidlet til 10 til 50 vekt-# styren-isopren-styren-syntesekautsjuk, som eksempelvis er tilgjengelig i handelen under betegnelsen "CARIFLEX TR 1107" fra firmaet SHELL; mellom 10 og 80 vekt-# av en hydrert alkohol, som eksempelvis tilgjengelig under betegnelsen "ABITOL" fra firmaet HERCULES; mellom 10 og 80 vekt-% av en hydrokarbonharpiks, eksempelvis harpiksen "HERCURES C" fra firmaet HERCULES, mellom 1 og 40 vekt-# av estere av vegetabilske fettsyrer, eksempelvis "MIGLYOL 812" fra firmaet-DYNAMIT NOBEL og eventuelt inntil 5 vekt-# eldingsbeskyttelsesmiddel, som hydrokinon osv., samt inntil 70 vekt-# fyllstoffer. It is preferred that the hot melt adhesive for 10 to 50 weight # of styrene-isoprene-styrene synthetic rubber, which is for example commercially available under the name "CARIFLEX TR 1107" from the company SHELL; between 10 and 80% by weight of a hydrated alcohol, such as is available under the name "ABITOL" from the company HERCULES; between 10 and 80% by weight of a hydrocarbon resin, for example the resin "HERCURES C" from the company HERCULES, between 1 and 40% by weight of esters of vegetable fatty acids, for example "MIGLYOL 812" from the company DYNAMIT NOBEL and optionally up to 5% by weight # antiaging agent, such as hydroquinone, etc., as well as up to 70 weight # of fillers.
Ved en ytterligere fordelaktig utførelsesform av oppfinnelsen oppviser varmsmelte-klebemidlet til 10 til 50 vekt-# av en polykaprolakton, eksempelvis "CAPA 650" fra firmaet INTEROX; mellom 10 og 80 vekt-$ av en hydrert alkohol, eksempelvis "ABITOL" fra firmaet HERCULES, mellom 10 og 80 vekt-# av en hydrokarbonharpiks, eksempelvis "HERCURES C" fra firmaet HERCULES, mellom 1 og 40 vekt-# av estere av vegetabilske fettsyrer, som "MIGLYOL 812" fra firmaet DYNAMIT NOBEL og eventuelt inntil 5 vekt-% eldingsbeskyttelsesmiddel, samt inntil 70 vekt-£ fyllstoffer. In a further advantageous embodiment of the invention, the hot-melt adhesive has 10 to 50% by weight of a polycaprolactone, for example "CAPA 650" from the company INTEROX; between 10 and 80 wt-$ of a hydrogenated alcohol, for example "ABITOL" from the company HERCULES, between 10 and 80 wt-# of a hydrocarbon resin, for example "HERCURES C" from the company HERCULES, between 1 and 40 wt-# of esters of vegetable fatty acids, such as "MIGLYOL 812" from the company DYNAMIT NOBEL and possibly up to 5% by weight aging protection agent, as well as up to 70% by weight of fillers.
Det kan også være foretrukket at varmesmelte-klebemidlet til 10 til 50 vekt-# polyetylen-vinylacetat, som "EVATANE 28-25" fra firmaet AT0CHEM, oppviser mellom 10 og 80 vekt-$ av en hydrert alkohol, eksempelvis "ABITOL" fra firmaet HERCULES, mellom 10 og 80 vekt-# av en hydrokarbonharpiks, eksempelvis av harpiksen "HERCURES C" fra firmaet HERCULES, mellom 1 og 40 vekt-# av estere av vegetabilske fettsyrer, eksempelvis "MIGLYOL 812" fra firmaet DYNAMIT NOBEL og eventuelt inntil 5 vekt-* eldingsbeskyttelsesmiddel, som hydrokinon etc. , samt inntil 70 vekt-* fyllstoffer. - It may also be preferred that the hot melt adhesive of 10 to 50 wt-# polyethylene vinyl acetate, such as "EVATANE 28-25" from the company AT0CHEM, exhibits between 10 and 80 wt-$ of a hydrated alcohol, for example "ABITOL" from the company HERCULES, between 10 and 80 wt-# of a hydrocarbon resin, for example of the resin "HERCURES C" from the company HERCULES, between 1 and 40 wt-# of esters of vegetable fatty acids, for example "MIGLYOL 812" from the company DYNAMIT NOBEL and possibly up to 5 weight-* aging protection agent, such as hydroquinone etc., as well as up to 70 weight-* fillers. -
Et egnet varmsmelte-klebemiddel kan til 10 til 50 vekt-* polyuretan; som f.eks. "LUPHEN P 1110" fra firmaet BASF oppvise mellom 10 og 80 vekt-* av en hydrert alkohol, eksempelvis "ABITOL" fra firmaet HERCULES, mellom 10 og 80 vekt-* av en hydrokarbonharpiks, eksempelvis av harpiksen "HERCURES C" fra firmaet HERCULES, mellom 1 og 40 vekt-* av estere av vegetabilske fettsyrer, eksempelvis "MIGLYOL 812" fra firmaet DYNAMIT NOBEL og eventuelt inntil 5 vekt-* eldingsbeskyttelsesmiddel, samt inntil 70 vekt-* fyllstoffer, A suitable hot melt adhesive may be 10 to 50 wt.* polyurethane; like for example. "LUPHEN P 1110" from the company BASF exhibit between 10 and 80 weight-* of a hydrogenated alcohol, for example "ABITOL" from the company HERCULES, between 10 and 80 weight-* of a hydrocarbon resin, for example of the resin "HERCURES C" from the company HERCULES , between 1 and 40 weight-* of esters of vegetable fatty acids, for example "MIGLYOL 812" from the company DYNAMIT NOBEL and possibly up to 5 weight-* aging protection agent, as well as up to 70 weight-* fillers,
Det er også mulig at varmsmelte-klebemidlet til 10 til 50 vekt-* polyamid, som f.eks. "EURELON 930" fra firmaet SCHERING oppviser mellom 10 og 80 vekt-* av en hydrert alkohol, eksempelvis "ABITOL" fra firmaet HERCULES, mellom 10 og 80 vekt-* av en hydrokarbonharpiks, eksempelvis av harpiksen "HERCURES C" fra firmaet HERCULES, mellom 1 og 40 vekt-* av estere av vegetabilske fettsyrer, eksempelvis "MIGLYOL 812" fra firmaet DYNAMIT NOBEL og eventuelt inntil 5 vekt-* eldingsbeskyttelsesmiddel, samt inntil 70 vekt-* fyllstoffer. It is also possible that the hot melt adhesive for 10 to 50 weight* polyamide, such as e.g. "EURELON 930" from the company SCHERING exhibits between 10 and 80 weight-* of a hydrogenated alcohol, for example "ABITOL" from the company HERCULES, between 10 and 80 weight-* of a hydrocarbon resin, for example of the resin "HERCURES C" from the company HERCULES, between 1 and 40 weight-* of esters of vegetable fatty acids, for example "MIGLYOL 812" from the company DYNAMIT NOBEL and possibly up to 5 weight-* aging protection agent, as well as up to 70 weight-* fillers.
Det kan også anvendes et varmsmelte-klebemidlet med 10 til 50 vekt-* epoksyd, eksempelvis "EUREP0X 7001" fra firmaet SCHERING, mellom 10 og 80 vekt-* av en hydrert alkohol, eksempelvis "ABITOL" fra firmaet HERCULES, mellom 10 og 80 vekt-* av en hydrokarbonharpiks, eksempelvis av harpiksen "HERCURES C" fra firmaet HERCULES, mellom 1 og 40 vekt-* av estere av vegetabilske fettsyrer, eksempelvis "MIGLYOL 812" fra firmaet DYNAMIT NOBEL og eventuelt inntil 5 vekt-* eldingsbeskyttelsesmiddel, som hydrokinon etc, samt inntil 70 vekt-* fyllstoffer. A hot-melt adhesive can also be used with 10 to 50 weight-* of epoxy, for example "EUREP0X 7001" from the company SCHERING, between 10 and 80 weight-* of a hydrated alcohol, for example "ABITOL" from the company HERCULES, between 10 and 80 weight-* of a hydrocarbon resin, for example of the resin "HERCURES C" from the company HERCULES, between 1 and 40 weight-* of esters of vegetable fatty acids, for example "MIGLYOL 812" from the company DYNAMIT NOBEL and optionally up to 5 weight-* of aging protection agent, which hydroquinone etc, as well as up to 70 weight* fillers.
Et ytterligere, for fremstillingen av de transdermale systemene ifølge oppfinnelsen anvendbart varmsmelte-klebemiddel, oppviser til 10 til 50 vekt-* polyisobuten med seigklebende kautsjukaktig konsistens, som f.eks. "OPPANOL B 50" fra firmaet BASF, mellom 10 og 80 vekt-* av en hydrert alkohol, eksempelvis "ABITOL" fra firmaet HERCULES, mellom 10 og 80 vekt-* av en hydrokarbonharpiks, eksempelvis av harpiksen "HERCURES C" fra firmaet HERCULES, mellom 1 og 40 vekt-* av estere fra vegetabilske fettsyrer, eksempelvis "MIGLYOL 812" fra firmaet DYNAMIT NOBEL og eventuelt inntil 5 vekt-* eldingsbeskyttelsesmiddel, samt inntil 70 vekt-* fyllstoffer. A further, for the production of the transdermal systems according to the invention applicable hot melt adhesive, has 10 to 50 weight-* polyisobutene with a tough adhesive rubbery consistency, such as e.g. "OPPANOL B 50" from the company BASF, between 10 and 80 weight-* of a hydrogenated alcohol, for example "ABITOL" from the company HERCULES, between 10 and 80 weight-* of a hydrocarbon resin, for example of the resin "HERCURES C" from the company HERCULES , between 1 and 40 weight-* of esters from vegetable fatty acids, for example "MIGLYOL 812" from the company DYNAMIT NOBEL and possibly up to 5 weight-* aging protection agent, as well as up to 70 weight-* fillers.
Endelig er det foretrukket å anvende varmsmelte-klebemidler på polyesterbasis, som eksempelvis oppviser mellom 10 og 80 vekt-* av en hydrert alkohol, eksempelvis "ABITOL" fra firmaet HERCULES, mellom 10 og 80 vekt-* av en hydrokarbonharpiks, eksempelvis av harpiksen "HERCURES C" fra firmaet HERCULES, mellom 1 og 40 vekt-* av estere av vegetabilske fettsyrer, eksempelvis "MIGLYOL 812" fra firmaet DYNAMIT NOBEL og eventuelt inntil 5 vekt-* eldingsbeskyttelsesmiddel, samt inntil 70 vekt-* fyllstoffer. Finally, it is preferred to use polyester-based hot-melt adhesives, which for example have between 10 and 80 weight-* of a hydrogenated alcohol, for example "ABITOL" from the company HERCULES, between 10 and 80 weight-* of a hydrocarbon resin, for example of the resin " HERCURES C" from the company HERCULES, between 1 and 40 weight-* of esters of vegetable fatty acids, for example "MIGLYOL 812" from the company DYNAMIT NOBEL and possibly up to 5 weight-* aging protection agent, as well as up to 70 weight-* fillers.
Innretninger fremstilt ved fremgangsmåten ifølge oppfinnelsen kan videre også ha et eller flere stoffdepoter, hvori stoffet foreligger med forhøyet konsentrasjon sammenlignet med varmsmelte-klebestoffsjiktet inneholdende virksomt stoff, hvorved det kan administreres høyere doser av stoffet og hvormed innretningen derved kan forbli i bruk lengre før den må byttes ut. Typiske utførelser finnes f.eks. i DE-OS 36 29 304.0. Devices produced by the method according to the invention can furthermore also have one or more substance depots, in which the substance is present at a higher concentration compared to the hot-melt adhesive layer containing active substance, whereby higher doses of the substance can be administered and with which the device can thereby remain in use longer before it has to be replaced. Typical designs can be found e.g. in DE-OS 36 29 304.0.
Ytterligere trekk og fordeler ved oppfinnelsen fremgår nedenfor under henvisning til de vedlagte tegningene. Disse viser: Fig. 1 er et skjematisk snitt gjennom sjiktene av en innretning fremstilt ifølge oppfinnelsen med et stoffdepot. Fig. 2 er et skjematisk snitt gjennom en ytterligere innretning fremstilt -ifølge oppfinnelsen med depot for virksomt stoff, og Fig. 3 er et skjematisk snitt gjennom en ytterligere utførelsesform av innretningen fremstilt ifølge oppfinnelsen uten stoffdepot. Further features and advantages of the invention appear below with reference to the attached drawings. These show: Fig. 1 is a schematic section through the layers of a device produced according to the invention with a substance depot. Fig. 2 is a schematic section through a further device made according to the invention with a depot for active substance, and Fig. 3 is a schematic section through a further embodiment of the device made according to the invention without a substance depot.
I fig. 1 er det vist en innretning fremstilt ifølge oppfinnelsen som her er angitt som plasterlignende transdermalt terapeutisk system inneholdende virksomt stoff. Den har et varmsmelte-klebemiddelsjikt 12, et depot 14 for virksomt stoff, hvori det virksomme stoffet minst oppviser en høyere konsentrasjon enn i varmsmelte-klebemiddelsjiktet 12, samt en hærer 10 som er gjennomtrengelig for virksomt stoff hvorpå depotet av virksomt stoff ligger an, og er klebet på huden 18. Kontinuerlig vandrer virksomt stoff med en på forhånd bestemt hastighet gjennom huden 18, hvorved innholdet av virksomt stoff i sjiktet 12 avtar. Reduksjonen av virksomt stoff kompenseres ved ettertilstrømning av virksomt stoff fra depotet 14 av virksomt stoff, slik at det over et på forhånd bestembart tidsrom hersker en 1ikevektskonsentrasjon av det virksomme stoffet i varmsmelte-klebemiddelsjiktet 12, hvilket sørger for avgivelse av en konstant mengde virksomt stoff til huden 18. In fig. 1 shows a device manufactured according to the invention, which is here indicated as a patch-like transdermal therapeutic system containing active substance. It has a hot-melt adhesive layer 12, a depot 14 for active substance, in which the active substance at least exhibits a higher concentration than in the hot-melt adhesive layer 12, as well as a carrier 10 which is permeable to active substance on which the depot of active substance rests, and is glued to the skin 18. Active substance continuously travels at a predetermined speed through the skin 18, whereby the content of active substance in the layer 12 decreases. The reduction of active substance is compensated by subsequent inflow of active substance from the depot 14 of active substance, so that over a predetermined period of time an equilibrium concentration of the active substance prevails in the hot-melt adhesive layer 12, which ensures the release of a constant amount of active substance to the skin 18.
I fig. 2 er det vist en ytterligere utførelsesform av en innretning fremstilt ifølge oppfinnelsen, hvorved depotet 14 av virksomt stoff på alle sider er omgitt av varmsmelte-klebemiddelsj iktet 12. Denne utførelsesformen egner seg spesielt når en stor kontaktflate mellom virksomt stoffdepot/varmsmelte-klebemiddelsjikt er ønsket for en rask avgivelse av virksomt stoff til varmsmelte-klebemiddel-sj iktet. In fig. 2 shows a further embodiment of a device manufactured according to the invention, whereby the depot 14 of active substance is surrounded on all sides by the hot-melt adhesive layer 12. This embodiment is particularly suitable when a large contact surface between the active substance depot/hot-melt adhesive layer is desired for a rapid delivery of active substance to the hot-melt adhesive layer.
I fig. 3 er det vist en ytterligere enkel utførelsesform av en innretning fremstilt ifølge oppfinnelsen, hvorved det på et ugjennomtrengelig bærermateriale 10 er anbrakt et varmsmelte-klebemiddelsjikt 12 inneholdende virksomt stoff på en slik måte at bærermaterialet 10 dekker sjiktet 12 på 3 sider. Med den frie varmesmelte-klebemiddelflaten er innretningen klebet på huden 18, slik at det sikres en kontakt over hele flaten i løpet av tilførselstiden og overgangen av virksomt stoff til huden foregår hele tiden over en konstant flate med en konstant hastighet. In fig. 3 shows a further simple embodiment of a device manufactured according to the invention, whereby a hot-melt adhesive layer 12 containing active substance is placed on an impermeable carrier material 10 in such a way that the carrier material 10 covers the layer 12 on 3 sides. With the free hot-melt adhesive surface, the device is glued to the skin 18, so that a contact is ensured over the entire surface during the delivery time and the transition of active substance to the skin takes place all the time over a constant surface at a constant speed.
I det følgende beskrives den forbedrede fremstillingen ifølge oppfinnelsen av en innretning ifølge oppfinnelsen. In the following, the improved production according to the invention of a device according to the invention is described.
Først fremstilles en blanding av komponentene av varmsmelte-klebemidlet med stoffet som skal administrers. Denne blandingen bringes til bearbeidelsestemperaturen og påføres så fra smeiten på et bærermateriale. Den ytterligere bearbeidelsen, som påføring av et abhesivt utrustet beskyttelsessjiktmateriale foregår på vanlig måte. First, a mixture of the components of the hot melt adhesive is prepared with the substance to be administered. This mixture is brought to the processing temperature and then applied from the melt to a carrier material. The further processing, such as application of an adhesively equipped protective layer material, takes place in the usual way.
EKSEMPLER EXAMPLES
Som hyppig gjentatte forkortelser anvendes: Frequently repeated abbreviations are used:
A = hydroabietylalkohol ("Abitol"/Hercules) A = hydroabiethyl alcohol ("Abitol"/Hercules)
H = alifatisk hydrokarbonharpiks ("HERCULES C"/Hercules) H = aliphatic hydrocarbon resin ("HERCULES C"/Hercules)
M = triglyserider av middelskjedede fettsyrer M = triglycerides of medium-chain fatty acids
("MIGLYOL 812"/Dynamit Nobel) ("MIGLYOL 812"/Dynamite Nobel)
Eksempel 1 Example 1
22,0 vekt-* etylenvinylacetat-kopolymer 22.0 wt* ethylene vinyl acetate copolymer
("EVATANE 28-25"/Atochem ) , ("EVATANE 28-25"/Atochem ),
29,2 vekt-* A, 29.2 wt-* A,
44,0 vekt-* H og 44.0 weight-* H and
4,8 vekt-* M 4.8 weight-* M
smeltes ved ca. 110°C og homogeniseres under omrøring. melts at approx. 110°C and homogenized while stirring.
Etter avkjøling til 50-60°C innarbeides 5,0 vekt-* eukalyptol (på basis av den samlede varmsmelte-klebemassen), og etter homogenisering påføres den oppnådde klebemassen på en silikonisert polyesterfolie og bærerfolien påkasjeres. After cooling to 50-60°C, 5.0 weight-* eucalyptol is incorporated (on the basis of the total hot-melt adhesive mass), and after homogenization, the obtained adhesive mass is applied to a siliconized polyester foil and the carrier foil is encased.
Eksempel 2 Example 2
22,0 vekt-* etylenvinylacetat-kopolymer 22.0 wt* ethylene vinyl acetate copolymer
("EVATANE 28-25"/Atochem), ("EVATANE 28-25"/Atochem),
29,2 vekt-* A, 29.2 wt-* A,
44,0 vekt-* H og 44.0 weight-* H and
4,8 vekt-* M 4.8 weight-* M
smeltes ved 110°C og homogeniseres under omrøring. is melted at 110°C and homogenized with stirring.
Etter avkjøling til 50-60°C innarbeides 1,0 vekt-* clemastin (på basis av den samlede varmsmelte-klebemiddelmassen) og etter homogenisering påføres den oppnådde klebemiddelmassen på en silikonisert polyesterfolie og bærerfolien påkasjeres. After cooling to 50-60°C, 1.0 weight* of clemastine is incorporated (on the basis of the total hot-melt adhesive mass) and after homogenization, the obtained adhesive mass is applied to a siliconized polyester foil and the carrier foil is encased.
Eksempel 3 Example 3
34,6 vekt-* styren-isopren-styren-blokk-kopolymer 34.6 wt* styrene-isoprene-styrene block copolymer
("CARIFLEX TR 1107<M>/Shell), ("CARIFLEX TR 1107<M>/Shell),
23.2 vekt-* A, 23.2 weight-* A,
34,6 vekt-* H og 34.6 weight-* H and
7,6 vekt-* M 7.6 weight-* M
homogeniseres ved 140°C og viderebearbeides som beskrevet i eksempel 1 ved 55°C. Det innarbeides derved 2,5 vekt-* estradiol (på basis av den samlede varmsmelte-klebemiddelmassen ). homogenized at 140°C and further processed as described in example 1 at 55°C. 2.5 weight* of estradiol is thereby incorporated (on the basis of the total hot-melt adhesive mass).
Eksempel 4 Example 4
33,4 vekt-* polyisobutylen ("0PPAN0L B 15"/BASF), 33.4 wt-* polyisobutylene ("0PPAN0L B 15"/BASF),
33.3 vekt-* A, 33.3 weight-* A,
29,8 vekt-* H og 29.8 weight-* H and
3,5 vekt-* M 3.5 weight-* M
homogeniseres ved 120°C og viderebearbeides analogt eksempel 1 ved 78"C. Det innarbeides derved 0,2 vekt-* kamfer (på basis av den samlede massen av. varmsmelte-klebemiddel). is homogenised at 120°C and further processed analogously to example 1 at 78°C. 0.2 weight-* of camphor is thereby incorporated (on the basis of the total mass of hot-melt adhesive).
Eksempel 5 Example 5
19.2 vekt-* lineær polyuretan ("LUPHEN P 1112"/BASF), 19.2 weight-* linear polyurethane ("LUPHEN P 1112"/BASF),
38.3 vekt-* A, 38.3 weight-* A,
38,3 vekt-* H og 38.3 weight-* H and
4,2 vekt-* M 4.2 weight-* M
homogeniseres ved 120°C og viderebearbeides analogt eksempel 1 ved 50-60°C. Derved innarbeides det 0,3 vekt-* capsaicin (på basis av den samlede massen av varmsmelte-klebemiddel). is homogenized at 120°C and further processed analogously to example 1 at 50-60°C. Thereby, 0.3 weight-* capsaicin is incorporated (on the basis of the total mass of hot-melt adhesive).
Eksempel 6 Example 6
22,0 vekt-* polyamid ("EURELON 2095"/Schering) 22.0 weight-* polyamide ("EURELON 2095"/Schering)
29,2 vekt-* A, 29.2 wt-* A,
44,0 vekt-* H og 44.0 weight-* H and
4,8 vekt-* M 4.8 weight-* M
homogeniseres ved 120°C og viderebearbeides analogt eksempel 1 ved 53°C. Derved innarbeides det 15 vekt-* etofenamat (på basis av den samlede massen av varmsmelte-klebemiddel). homogenized at 120°C and further processed analogously to example 1 at 53°C. Thereby, 15% by weight of etofenamate is incorporated (on the basis of the total mass of hot-melt adhesive).
Eksempel 7 Example 7
22,0 vekt-* epoksyharpiks ("EUREPOX 7001"/Schering ) 22.0 wt-* epoxy resin ("EUREPOX 7001"/Schering )
29,2 vekt-* A, 29.2 wt-* A,
44,0 vekt-* H og 44.0 weight-* H and
4,8 vekt-* M 4.8 weight-* M
homogeniseres ved 120°C og viderebearbeides analogt eksempel 1 ved 52°C. Det innarbeides derved 30 vekt-* ibuprofen (på basis av den samlede massen av varmsmelte-klebemiddel). is homogenized at 120°C and further processed analogously to example 1 at 52°C. 30 weight-* of ibuprofen is thereby incorporated (on the basis of the total mass of hot-melt adhesive).
Eksempel 8 Example 8
19.0 vekt-* polykaprolakton ("CAPPA650"/Interox), 19.0 wt-* polycaprolactone ("CAPPA650"/Interox),
38.1 vekt-* A, 38.1 weight-* A,
38,1 vekt-* H og 38.1 weight-* H and
4,8 vekt-* ,M 4.8 weight-* ,M
homogeniseres ved 110°C og viderebearbeides analogt eksempel 1 ved 50-55°C. Derved innarbeides det 1 vekt-* mentol (på basis av den samlede massen av. varmsmelte-klebemiddel). is homogenized at 110°C and further processed analogously to example 1 at 50-55°C. Thereby 1 weight* of menthol is incorporated (on the basis of the total mass of hot melt adhesive).
Eksempel 9 Example 9
19.2 vekt-* lineær polyuretan ("LUPHEN P 1112"/BASF), 19.2 weight-* linear polyurethane ("LUPHEN P 1112"/BASF),
38.3 vekt-* A, 38.3 weight-* A,
38,3 vekt-* H og 38.3 weight-* H and
4,2 vekt-* M 4.2 weight-* M
homogeniseres ved 120°C og viderebearbeides analogt eksempel 1 ved 53°C. Derved innarbeides det 16 vekt-* salisylsyre-metylester (på basis av den samlede massen av varmsmelte-klebemiddel). homogenized at 120°C and further processed analogously to example 1 at 53°C. Thereby, 16 weight-* of salicylic acid methyl ester is incorporated (on the basis of the total mass of hot melt adhesive).
Eksempel 10 Example 10
22,0 vekt-* polyamid ("EURELON 2095"/Schering), 22.0 weight-* polyamide ("EURELON 2095"/Schering),
29,2 vekt-* A, 29.2 wt-* A,
44,0 vekt-* H og 44.0 weight-* H and
4,8 vekt-* M 4.8 weight-* M
homogeniseres ved 120°C og viderebearbeides analogt eksempel 1 ved 53°C. Derved innarbeides det 17 vekt-* timolol (på basis av den samlede massen av varmsmelte-klebemiddel). homogenized at 120°C and further processed analogously to example 1 at 53°C. Thereby, 17% by weight of timolol is incorporated (on the basis of the total mass of hot-melt adhesive).
Eksempel 11 Example 11
22,0 vekt-* epoksyharpiks ("EUREPOX 7001"/Schering), 22.0 wt-* epoxy resin ("EUREPOX 7001"/Schering),
29,2 vekt-* A, 29.2 wt-* A,
44,0 vekt-* H og 44.0 weight-* H and
4,8 vekt-* M 4.8 weight-* M
homogeniseres ved 120°C og viderebearbeides analogt eksempel 1 ved 52°C. Derved innarbeides det 0,2 vekt-* skopolamin (på basis av den samlede massen av varmsmelte-klebemiddel). is homogenized at 120°C and further processed analogously to example 1 at 52°C. Thereby, 0.2 weight-* of scopolamine is incorporated (on the basis of the total mass of hot-melt adhesive).
Claims (3)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3729165 | 1987-09-01 | ||
| DE19873743945 DE3743945A1 (en) | 1987-09-01 | 1987-12-23 | DEVICE FOR DELIVERING SUBSTANCES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
| PCT/DE1988/000477 WO1989001787A1 (en) | 1987-09-01 | 1988-08-03 | Device for release of substances, process for its manufacture and use thereof |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO891507D0 NO891507D0 (en) | 1989-04-12 |
| NO891507L NO891507L (en) | 1989-04-12 |
| NO178684B true NO178684B (en) | 1996-02-05 |
| NO178684C NO178684C (en) | 1996-05-15 |
Family
ID=25859260
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO891507A NO178684C (en) | 1987-09-01 | 1989-04-12 | Process for producing a device for dispensing substances from hot melt adhesives |
Country Status (23)
| Country | Link |
|---|---|
| EP (1) | EP0305756B1 (en) |
| JP (1) | JP2781579B2 (en) |
| KR (1) | KR970006448B1 (en) |
| AT (1) | ATE83655T1 (en) |
| AU (1) | AU636835B2 (en) |
| CA (1) | CA1333688C (en) |
| CZ (1) | CZ281743B6 (en) |
| DE (2) | DE3743945A1 (en) |
| DK (1) | DK175442B1 (en) |
| ES (1) | ES2036242T3 (en) |
| FI (1) | FI96577C (en) |
| GR (1) | GR3006666T3 (en) |
| HU (1) | HU205268B (en) |
| IE (1) | IE62943B1 (en) |
| IL (1) | IL87538A (en) |
| MY (1) | MY103757A (en) |
| NO (1) | NO178684C (en) |
| NZ (1) | NZ225918A (en) |
| PL (1) | PL163710B1 (en) |
| PT (1) | PT88378B (en) |
| SK (1) | SK279300B6 (en) |
| WO (1) | WO1989001787A1 (en) |
| YU (1) | YU47201B (en) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3743946A1 (en) * | 1987-09-01 | 1989-03-09 | Lohmann Gmbh & Co Kg | DEVICE FOR DELIVERING NITROGLYCERIN TO THE SKIN, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
| HU203285B (en) * | 1988-02-01 | 1991-07-29 | Egyt Gyogyszervegyeszeti Gyar | Method for producing transdermal preparation containing vegetable extract |
| JP2758002B2 (en) * | 1988-09-14 | 1998-05-25 | 積水化学工業株式会社 | Patch |
| DE3843237A1 (en) * | 1988-12-22 | 1990-07-05 | Lohmann Therapie Syst Lts | TRANSDERMAL THERAPEUTIC SYSTEM WITH AN ANTIADIPOSITUM AS AN ACTIVE INGREDIENT |
| DE3843239C1 (en) * | 1988-12-22 | 1990-02-22 | Lohmann Therapie Syst Lts | |
| DE3843238C1 (en) * | 1988-12-22 | 1990-02-22 | Lohmann Therapie Syst Lts | |
| DE4031881C2 (en) * | 1990-10-08 | 1994-02-24 | Sanol Arznei Schwarz Gmbh | Solvent-free, oral sustained-release pharmaceutical preparation and process for its preparation |
| DE4237252C2 (en) | 1992-11-04 | 1994-10-13 | Zweckform Buero Prod Gmbh | Flexible, removable, residue-free removable fabric, process for its production and its use |
| DE4301781C2 (en) * | 1993-01-23 | 1995-07-20 | Lohmann Therapie Syst Lts | Patch containing nitroglycerin, process for its production and use |
| DE4332094C2 (en) * | 1993-09-22 | 1995-09-07 | Lohmann Therapie Syst Lts | Active substance plaster which can be produced without solvent and process for its preparation |
| US5380760A (en) * | 1993-11-19 | 1995-01-10 | Minnesota Mining And Manufacturing Company | Transdermal prostaglandin composition |
| DE4403487C2 (en) * | 1994-02-04 | 2003-10-16 | Lohmann Therapie Syst Lts | Pharmaceutical patches with UV-crosslinkable acrylate copolymers |
| DE19650471A1 (en) * | 1996-12-05 | 1998-06-10 | Beiersdorf Ag | Patches containing active ingredient |
| DE19700913C2 (en) * | 1997-01-14 | 2001-01-04 | Lohmann Therapie Syst Lts | Transdermal therapeutic system for the delivery of hormones |
| DE19825499C2 (en) | 1998-06-08 | 2003-07-17 | Beiersdorf Ag | Patches containing active ingredients |
| DE19834496B4 (en) * | 1998-07-31 | 2004-02-26 | Beiersdorf Ag | Improved release of ibuprofen from hotmelt adhesives in plasters containing active ingredients by adding pharmaceutical auxiliaries and using auxiliaries to improve the release of ibuprofen |
| DE19911262C2 (en) * | 1999-03-13 | 2003-04-10 | Scs Skin Care Systems Gmbh | Device for dispensing cosmetic active ingredients |
| FR2810237B1 (en) * | 2000-06-15 | 2002-07-26 | Oreal | FILM-FORMING COSMETIC COMPOSITION |
| FR2810239B1 (en) * | 2000-06-15 | 2002-12-20 | Oreal | FILM-FORMING COSMETIC COMPOSITION |
| FR2810238B1 (en) | 2000-06-15 | 2002-07-19 | Oreal | FILM-FORMING COSMETIC COMPOSITION |
| DE10056009A1 (en) * | 2000-11-11 | 2002-05-16 | Beiersdorf Ag | Well tolerated plaster for controlled delivery of hyperemic agents, having active agent-containing matrix comprising polyisobutylene, amorphous poly-alpha-olefin and filler |
| DE10118282A1 (en) | 2001-04-12 | 2002-12-05 | Lohmann Therapie Syst Lts | Pressure sensitive adhesive based on ethylene-vinyl acetate copolymers and adhesive resins, for medical purposes |
| DE60222701T2 (en) | 2002-01-24 | 2008-07-17 | L'oreal | COMPOSITION COMPRISING A MIXTURE OF PARTIAL CRYSTALLINE POLYMERS AND VOLATILE OIL CONTAINS |
| DE10234673B4 (en) | 2002-07-30 | 2007-08-16 | Schwarz Pharma Ag | Hot-melt TTS for the administration of rotigotine and process for its preparation, and use of rotigotine in the manufacture of a hot-melt TTS |
| DE10236319A1 (en) * | 2002-08-08 | 2004-02-19 | Beiersdorf Ag | Active agent containing matrix plaster for the controlled delivery of an active agent to the skin comprises a pharmaceutical active agent containing a water insoluble adhesive matrix comprising a styrene block copolymer |
| JP2004277345A (en) * | 2003-03-17 | 2004-10-07 | Daikyo Yakuhin Kogyo Kk | Plaster and method for producing the same |
| DE10312062A1 (en) * | 2003-03-18 | 2004-09-30 | Tesa Ag | Low-shrinkage hotmelt pressure sensitive adhesive, process for its production and use |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3923939A (en) * | 1974-06-07 | 1975-12-02 | Alza Corp | Process for improving release kinetics of a monolithic drug delivery device |
| JPS55141408A (en) * | 1979-04-19 | 1980-11-05 | Hisamitsu Pharmaceut Co Inc | Novel plaster containing steroid and its production |
| US4725272A (en) * | 1981-06-29 | 1988-02-16 | Alza Corporation | Novel bandage for administering beneficial drug |
| GB2118040A (en) * | 1982-02-15 | 1983-10-26 | Hoechst Uk Ltd | Oral anti-diabetic preparation |
| JPS58141225A (en) * | 1982-02-16 | 1983-08-22 | Takasago Corp | Resin composition for fragrant material |
| AU560710B2 (en) * | 1983-04-27 | 1987-04-16 | Lohmann Gmbh & Co. Kg. | Pharmaceutical product |
| US4564364A (en) * | 1983-05-26 | 1986-01-14 | Alza Corporation | Active agent dispenser |
| EP0186019B1 (en) * | 1984-12-22 | 1993-10-06 | Schwarz Pharma Ag | Medicated dressing |
| DE3629304A1 (en) * | 1986-08-28 | 1988-03-24 | Lohmann Gmbh & Co Kg | TRANSDERMAL THERAPEUTIC SYSTEM, ITS USE AND METHOD FOR THE PRODUCTION THEREOF |
| JPH0816053B2 (en) * | 1986-12-04 | 1996-02-21 | 大正製薬株式会社 | Method of manufacturing patch |
| DE3743946A1 (en) * | 1987-09-01 | 1989-03-09 | Lohmann Gmbh & Co Kg | DEVICE FOR DELIVERING NITROGLYCERIN TO THE SKIN, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE |
-
1987
- 1987-12-23 DE DE19873743945 patent/DE3743945A1/en active Granted
-
1988
- 1988-08-03 AT AT88112630T patent/ATE83655T1/en not_active IP Right Cessation
- 1988-08-03 AU AU22506/88A patent/AU636835B2/en not_active Ceased
- 1988-08-03 EP EP88112630A patent/EP0305756B1/en not_active Expired - Lifetime
- 1988-08-03 KR KR1019890700772A patent/KR970006448B1/en not_active IP Right Cessation
- 1988-08-03 WO PCT/DE1988/000477 patent/WO1989001787A1/en active IP Right Grant
- 1988-08-03 DE DE8888112630T patent/DE3876898D1/en not_active Expired - Lifetime
- 1988-08-03 JP JP63506544A patent/JP2781579B2/en not_active Expired - Lifetime
- 1988-08-03 ES ES198888112630T patent/ES2036242T3/en not_active Expired - Lifetime
- 1988-08-03 HU HU884702A patent/HU205268B/en not_active IP Right Cessation
- 1988-08-10 MY MYPI88000912A patent/MY103757A/en unknown
- 1988-08-19 CA CA000575201A patent/CA1333688C/en not_active Expired - Lifetime
- 1988-08-22 IE IE255488A patent/IE62943B1/en not_active IP Right Cessation
- 1988-08-23 IL IL8753888A patent/IL87538A/en not_active IP Right Cessation
- 1988-08-24 NZ NZ225918A patent/NZ225918A/en unknown
- 1988-08-31 CZ CS885873A patent/CZ281743B6/en not_active IP Right Cessation
- 1988-08-31 SK SK5873-88A patent/SK279300B6/en unknown
- 1988-08-31 PT PT88378A patent/PT88378B/en not_active IP Right Cessation
- 1988-09-01 YU YU166288A patent/YU47201B/en unknown
- 1988-09-01 PL PL88274486A patent/PL163710B1/en unknown
-
1989
- 1989-04-12 NO NO891507A patent/NO178684C/en unknown
- 1989-04-28 FI FI892053A patent/FI96577C/en not_active IP Right Cessation
- 1989-04-28 DK DK198902102A patent/DK175442B1/en not_active IP Right Cessation
-
1992
- 1992-12-24 GR GR920403040T patent/GR3006666T3/el unknown
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