SI8811662A

SI8811662A - Process for the production of a plaster with a regulated release of active substances

Info

Publication number: SI8811662A
Application number: SI8811662A
Authority: SI
Inventors: Halvor Jaeger; Hans-Rainer Hoffmann; Reinhold Meconi; Robert-Peter Klein
Original assignee: Lohmann Therapie Syst Lts
Priority date: 1987-09-01
Filing date: 1988-09-01
Publication date: 1997-02-28
Also published as: HRP920857A2; HRP920857B1

Abstract

Izum se nanaša na postopek za izdelavo obliža za sproščanje snovi iz taljivih kontaktnih lepil z enakomerno ali neenakomerno porazdeljenimi snovmi, ki obsega nanašanje, kontinuirano ali diskontinuirano, raztaljenega taljivega kontaktnega lepila, vsebujočega snov, ki se sprošča pri temperaturi taljivega kontaktnega lepila od 40 do 80 stopinj Celzija na nosilo, in po želji nanašanje plasti zaščitne snovi. Naprava, dobljena po postopku v smislu izuma, je uporabna v humani medicini in veterini, diagnostiki ali kozmetiki, za sproščanje snovi, občutljivih na toploto in/ali zelo hlapljivih.The invention relates to a process for making a patch to release substances from fusible contact adhesives with evenly or unevenly distributed substances, comprising application, continuous or continuous, molten fusible contact adhesive, containing substance which is released at temperature fusible contact adhesive from 40 to 80 degrees Celsius on a stretcher, and optionally applying a layer of protective substance. The device obtained by the process of the invention is useful in human and veterinary medicine, diagnostics or cosmetics, for the release of heat-sensitive substances and / or very volatile.

Description

Pronalazak je iz oblasti tehnologije lepkova za farmaceutske primene» a posebno se odnosi na postupak za proizvodnju novih flastera sa regulisanim ispuštanjem aktivnih materija. Prema Medjunarodnoj klasifikaciji patenata pronalazak je svrstan u klase A 61 L 15/03» A-01 Μ-37/Θ0,-fr 0-i J 1/00» G-OlM ^3/Y?The invention is in the field of adhesive technology for pharmaceutical applications »and particularly relates to a process for the production of new patches with regulated release of active substances. According to the International Patent Classification, the invention is classified in Class A 61 L 15/03 »A-01 Μ-37 / Θ0, -fr 0-i J 1/00» G-OlM ^ 3 / Y?

Pronalskom se rešava problem dobijanja specifičnih flastera za farmaceutske primene sa regulisanim ispuštanjem aktivnih materija iz topljivih kontaktnih lepkova podesnog sistema.The invention solves the problem of obtaining specific patches for pharmaceutical applications with regulated release of the active substances from the soluble contact adhesives of a suitable system.

Tipični predstavnici sličnih poznatih sistema su flasteri koji sadrže aktivne materije» indikatorski sistemi,sistemi za ispuštanje parfema i slično, pri čemu se ovi često više koriste u oblasti medicine za regulisano ili neregulisano ispuštanje materija. Poseban značaj je dan regulisanim napravama u vidu kontrolišanih sistema za unošer.je materija kroz kožu. Poznato je, s tim u vezi, da se nanosi sloj koji sadrži aktivnu materiju od jedne rastopine. U EP-CS 0177893 opisan je nelepijivi gel eeluloznog etra koji se može r.aneti iz rastopine i u kome se može raspodeliti aktivna supstanca. Ovaj gel se toplo obraduje i nije letljiv. U DE—CS 22 22 800 opisan ή® jedan sistem za unesenήe materija kroz kožu, kod koga je aktivna materija u mikrokr.psulama smeštena u lepljivu matricu, od materijala koji se oblikuje toplotom, a koji se nanosi iz rastopine.Typical representatives of similar known systems are patches containing the active substances »indicator systems, perfume discharges, and the like, with the latter often being more commonly used in the field of regulated or unregulated discharges of medicine. Particular importance is given to regulated devices in the form of controlled systems for the intake of substances through the skin. It is known in this connection that a layer containing the active substance of one solution is applied. EP-CS 0177893 discloses a non-adhesive cellulose ether gel which can be removed from solution and in which the active substance can be distributed. This gel is warmly processed and non-volatile. DE-CS 22 22 800 describes a ή® one system for the introduction of matter through the skin, in which the active substance in microcapsules is placed in a sticky matrix, made of a heat-formed material that is applied from a solution.

Za aktivne supstance csetljive na temperaturu, sa r.iskom tačkom topljenja, ili koje se mogu lako razlagati, čin jeni su pokušaji da se proizvedu r.elepljive matrice koje sadrže aktivnu materiju na temperaturi okolne sredine. Tako je, na primer, rečeno u američkom patentnom spisu br. 4 379 454 (Campbell i drugi) da se rastvor neke aktivne materije, doveden na željenu vrednost viskoznosti pomoču agensa za geliranje na temperatu-2 sredine, kao viskozni sloj aktivne materije za aktivne materije rastvorljive u ulju, pri čemu ti slojevi mogu biti izvedeni u vidu kontaktnog lepka, tj. lepka koji deluje na dodir. U DE-OS 32 22 800 (ALZA) opisan je sloj aktivne materije od jednog rastvora aktivne materije, zgusnute jednim reološkim agensom, kao što je celuloza, neki polisaharid ili neko jedinjenje silicijuma, koji nije lepljiv i koji je takode pogodan za brzo ispuštanje aktivne materije.For active substances sensitive to temperature, with low melting point, or which can be easily decomposed, attempts have been made to produce adhesive matrices containing the active substance at ambient temperature. Thus, for example, it is said in U.S. Pat. 4 379 454 (Campbell et al.) That a solution of an active substance, brought to the desired value of viscosity by means of a gelling agent at medium temperature-2, as a viscous layer of active substance for active substances soluble in oil, wherein these layers may be carried out in contact adhesive, ie. touch adhesive. DE-OS 32 22 800 (ALZA) describes a layer of active substance from a single solution of the active substance, concentrated by a rheological agent, such as cellulose, a polysaccharide or some non-sticky silicon compound, which is also suitable for the rapid release of the active agent matter.

U američkom patentnom spisu br; 3 923-^939 opisano je oblikovanje aktivne materije, kao što je tetraciklin, u sloj etilen-vinil acetatnog kopolimera presovanjem rastopine. U EP-OS 86 468 antidiabetični derivativ sulfonil uree, koji se uzima oralno, u nelepljivoj rastopljenoj mase, sa tačkom topljenja od 30 do 90°C, puni se u kapsule u unapred odredenim dozama iz rastopine. U američkom patentnom spisu br. 3 957 966 opisano je da se aktivne materije mogu obradivati u nelepljivim topljivim masama.In U.S. Pat. 3 923- 939 describes the formation of an active substance, such as tetracycline, into a layer of ethylene-vinyl acetate copolymer by pressing a solution. In EP-OS 86 468, the antidiabetic derivative of sulfonyl urea, taken orally, in a non-sticky melt mass, with a melting point of 30 to 90 ° C, is filled into capsules at predetermined doses from the solution. In U.S. Pat. 3 957 966 describes that the active substances can be treated in non-sticky soluble masses.

Poznato je iz DE-OS 30 07 363 da se koristi mešavina kontaktnog lepka koja se sastoji od jednog termoplastičnog elastomera, preporučljivo jednog blok polimera opšte formule A-B-A, smole koja daje lepljivost sa uljem ili višim masnim kiselinama i aktivne materije za proizvodnju jednog jednostavnog sistema za unošenje: materije kroz kožu. Opisana mešavina kontaktnog lepka pogodna je samo za aktivne materije relativno otporne na povišene materije, koje mogu da izdrže temperature od 120°C i više. U američkom patentnom spisu 3 699 963 opisano je mešanje oksitocina sa kontaktnim lepkom radi dobijanja terapeutskog sistema koji deluje kroz kožu i njegovo oblikovanje na temperaturi iznad 90°C. Ovako dobijeni sistemi za delovanje kroz kožu jeftini su za proizvodnju i obezbeduju konstantno prenošenje aktivne materije preko celog područja lepljenja sistema na kožu.It is known from DE-OS 30 07 363 to use a mixture of contact adhesive consisting of one thermoplastic elastomer, preferably one block polymer of the general formula ABA, a resin which gives stickiness with oil or higher fatty acids and the active substances to produce a simple system for intake: substances through the skin. The contact adhesive mixture described is only suitable for active substances relatively resistant to elevated substances, which can withstand temperatures of 120 ° C and above. U.S. Patent No. 3,699,963 describes mixing oxytocin with contact adhesive to obtain a therapeutic system that acts through the skin and forms it at temperatures above 90 ° C. The skin-acting systems thus obtained are inexpensive to manufacture and provide the constant transfer of the active substance throughout the adhesive system of the system to the skin.

Poznati postupci za proizvodnju ovakvih sistema nisu pogodni za sistema koji deluju kroz kožu a koji sadrže materije osetljive na temperaturu, kao što je skopolamin. Zbog toga su do sada kontaktno lepljivi slojevi aktivne materije, sa aktivnim materijama osetljivim na temperaturu, najčešče obrazovan! od rastvora, pri čemu je rastvarač isparen.Known methods for producing such systems are not suitable for skin-acting systems containing temperature-sensitive substances such as scopolamine. For this reason, contact adhesive layers of the active substance, with the active substances sensitive to temperature, are the most educated so far! from the solution, the solvent being evaporated.

Primena rastvarača kod priprcme lepljivih slojev« kcji sadrže aktivnu materi ju jiepoaodna je iz nekoliko razloga, priprema rastvora zahteva najmanje još jednu, dopunsku i komplikovanu fazu procesa. To dcvodi do velikog tehničkog naprezanja i troškova u vezi sa rukovar.jem sa rastvaračima, pri čemu je }od dodavanja za medicinske svrhe neophodno da se korist.e izuzetno čisti, a time i skupi rastvarači, kako bi se obezbedilo da ne bude ostataka v. urejaj ima za rastvaranje lepka ili njegovih početnih materijala. Drugi je problem da se otklcni rastvarač iz · naprave za nanošenje aktivne materije, za šta je potrebno koriščenje skupih odeljaka za sušenje i uredaja sa vakuumom. Dodatni troškcvi se javljaju kod pcvračaja ili izdvajanja rastvarača, kako bi se sprečilo zagadivanje okolne sredine. Dodatnu opasnost izaziva zapaljivost večine rastvarača. Pored toga, večina organskih rastvarača je štetna za ljudski organizem, tako da se moraju predtizimati komplikovane i skupe zaštitr.e mere ta osoblje koje radi υ pogonu.The use of solvents in the preparation of adhesive layers containing the active substance is indispensable for several reasons, the preparation of the solution requires at least one additional, additional and complicated phase of the process. This leads to a great deal of technical stress and expense in connection with the handling of the solvents, since the addition for medical purposes necessitates the use of e. Extremely clean, and thus expensive solvents, to ensure that there is no residual v. . the device has to dissolve the adhesive or its starting materials. Another problem is to remove the solvent from the active substance application device, which requires the use of expensive drying compartments and vacuum devices. Additional charges occur when boiling or separating solvents to prevent environmental contamination. The flammability of most solvents causes an additional danger. In addition, most organic solvents are harmful to the human body, so complicated and expensive protective measures must be taken by those operating the facility.

Prema tone je problem prikazanog pronalaska da se izbegnu navedeni >nedostaci takvih naprava i procesa iz do sada poznatih rešenja.According to the invention, it is a problem of the present invention to avoid the aforementioned disadvantages of such devices and processes from the solutions known so far.

Prema pronalasku, gore navedeni problemi rešeni su izvodjenjem postupka za proizvodnju flastera sa ispuštanjem materija iz topijivog kontaktnog lepka sa ravnomernom ili nepravilnom raspodelom materija, gde topljivi kontaktni lepak ima temperaturu obrade od 40-80°C, poželjno od 40-60°C, a najboljd od 40-80°C.According to the invention, the above problems are solved by performing a process for the production of a patch with the release of substances from a soluble contact adhesive with a uniform or irregular distribution of matter, where the soluble contact adhesive has a treatment temperature of 40-80 ° C, preferably 40-60 ° C, and max. 40-80 ° C.

To omogučuje da se radi bez rastvarača na niškim temperaturama, tako da dolazi do znatnih ušteda na materijalu, brže proizvodnje naprava bez dugotrajnih faza sušenja, kao i · proizvodnja naprava prema pronalasku sa manj im zacadivar. j srn okolne sredine, što, izmedu ostalog, dovodi do znatno jeftinijeg proizvoda koji usto ne sadrži rastvarač.'This enables solvent-free operation at low temperatures, resulting in considerable material savings, faster production of devices without prolonged drying phases, and · the production of devices according to the invention with less harmful effects. j deer of the environment, which, among other things, results in a significantly cheaper product that does not even contain a solvent. '

Proces 2a proizvodnju naprave prema pronalasku obuhvata kontninualno ili mestimično nanošenje rastopl jenog topljivog kontaktnog lepka koji sadrži aktivnu materi ju k o'j a ' ‘J θ'-·;· ’ pušta, koje se Vrši na temperaturi tog lepka izmedu 40 ,.£. 8,0 v .Process 2a for the manufacture of the device according to the invention involves the continuous or intermittent application of a molten soluble contact adhesive containing the active substance J θ'- ·; · 'released, which is performed at a temperature of that adhesive between 40,. £ . 8,0 v.

K ·' O‘ ^z poželjno izmedu 40 i 60 C, a posebno izmedu 40 i 55 C, jna;niBk£ nosač i optimalncpanošenje materijala zaštitnog sloja.K · 'O' ^z preferably between 40 and 60 C, and in particular between 40 and 55 C, is a nBk £ support and optimum bearing of the protective layer material.

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Jedan drugi proces prema pronalasku obuhvata kontinualno ili mestimično nanošenje rastopljenog topljivog kontaktnog lepka,koji sadrži materiju koja treba da se ispušta, na temperaturi tog lepka izmedu 40.i 80°C, poželjno izmedu 40 i 60°C, a posebno izmedu 40 i 55°C, na materijal zaštitnog sloja a po želji i nanošenje na jedan nosač.Another process according to the invention comprises the continuous or intermittent application of molten soluble contact adhesive containing the substance to be discharged at a temperature of that adhesive between 40 and 80 ° C, preferably between 40 and 60 ° C, and in particular between 40 and 55 ° C, on a protective layer material and optionally applied to a single support.

Kada se koriste jako isparijive i/ili toplotno nestabilne materije, treba preduzeti sledeče mere u toku procesa:When highly volatile and / or thermally unstable materials are used, the following measures should be taken during the process:

A. raditi na vrlo niškim temperaturama,A. run at very low temperatures,

B. povečati'spoljni pritisak kako bi se smanjilo isparavanje,B. increase the external pressure to reduce evaporation,

C. zasičavanje parne komore iznad rastopine sa isparijivom materijom, iC. saturation of the vapor chamber above the solution with volatile matter, and

D. raditi sa minimalnom količinom isparijive materije u rastopini.D. work with a minimum amount of volatile matter in solution.

Očigledno je da su te mere, kao što je, na primer, rad u hermetički zatvorenom pogonu. ograničene pravilima poznatim stručnjacima, a na osnovu nameravane primene naprave koja se proizvodi kao · i uslova koje postavlja materijal.Obviously, these measures, such as working in a hermetically sealed drive, for example. limited by rules known to those skilled in the art, based on the intended use of the device being manufactured as well as the conditions set by the material.

Naprave prema pronalasku, posebno sistemi za uncše___ nje materija kroz kožu, mcgu se> na primer, koristiti za lokalno ili sistemsko unošenje kroz kožu aktivne materije, u humanoj ili veterinarskoj medicini ili kozmetici, preporučljivo za ispuštanje materija osetljivih na toplotu i/ili veoma isparljivih.The devices of the invention, in particular skin-cleansing systems, may, for example, be used for topical or systemic intake through the skin of the active substance in human or veterinary medicine or cosmetics, recommended for the release of heat-sensitive and / or highly volatile substances. .

Kao topljivi kontaktni, lepkovi^nogu se koristiti svi, stručnjacima poznati, lepkovlj a koji su, izmedu ostalog, opisani u DE-OS 15 94 268 (SUN OIL CO»), DE-OS 24 13 979 (E.I.As the soluble contact adhesive, any adhesive known to those skilled in the art described, inter alia, in DE-OS 15 94 268 (SUN OIL CO »), DE-OS 24 13 979 (E.I.

DU PONT DE NEMOURS), DE-OS 24 35 863 (DVNAMIT NOBEL AG), DE-OS 28 00 302 (CIBA GEIGY), EP-A-104 005 (PERSONAL PRODUCTS CO.,,DU PONT DE NEMOURS), DE-OS 24 35 863 (DVNAMIT NOBEL AG), DE-OS 28 00 302 (CIBA GEIGY), EP-A-104 005 (PERSONAL PRODUCTS CO. ,,

JP 6104 2583 i JP 61 281 810, EP-OS 131 46C (ΕΧΧΟΝ,, EP-OS 234 856 (ΕΧΧΟΝ), EP-OS 185 992 (EASTMAN KODAK), kao i u američkim patentnim spisima 36 99 963 i 4 358 557 (EASTMAN KODAK) i na ova poznata rešenja se posebno poziva kako bi se izbegla ponavljanja.JP 6104 2583 and JP 61 281 810, EP-OS 131 46C (US, EP-OS 234 856 (US), EP-OS 185 992 (EASTMAN KODAK), as well as in U.S. Patent Nos. 36 99 963 and 4 358 557 ( EASTMAN KODAK) and these known solutions are specifically referenced to avoid repetition.

Osnovne polimere mogu da obrazuju, na primer, poliamidi, poliestri, polikaprolaktami, polikaprolaktopi, kopolimeri etilen-vinil acetata (EVA), kopolimeri etilen»etilakrilata (EEA), poliviniletri, estri poliakrilata, polivinilacetali, polivinilacetati, blok polimeri stiren^butadijena, blok polime_ 5 ri izoprena, poliuretani, etilcelulcza, celulozni acetat-butirat, sintetičke gume (na primer neoprenska guma); poliizobutilen, butil guma, kopolimeri akrilonitril-butadijena, epoksidne smole, melaminske smole, fenol-formaldehidne smole ijrescrcinol-formaldehidne smole, a takode se mogu koristiti sledeče smole za modi** fikovanje : hidrogenizovan kolofonijum, polimerizovan kolofonijum, dimerizovanh smola kiseline, disproporcionisani kolofonijum, metil estri kolofonijuma, hidrogenisani glicerolni estri kolofoni juma, metil estri hidrcgenizovanog kolofonijuma, pentalestri, trietilenglikolestri hidrogenizovanog kolofonijuma, glicerinski estri, ditriolestri i pentaestri kiselina smola, pentalestri polimerizovano^ kolofonijuma, pentalestri dimerizovanog kolofonijuma, glicerinski estri dimerizovanog ko2.ofcnijuna, estri maleinske kiseline ili fenolski modifikovanog kolofonijuma,smole arcmatskih i alifatičkih ugljovodonika, hidrogenizovane smole, politerpenske smole, modifikovane terpenske smole, voskovi, polietilen i polipropilen male molekularne težine i kopolimeri alkil stirena. Ovim smolama se mogu, po želji, dodavati plastlfik^pri^kao što su, na primer, estri masne kiseline, estri fosforne kiseline, estri ftaličke kiseline, poliestri, estri mi»snih kiselina, estri limunske kiseline ili epoksidni plastifikatori. Takode se mogu mešati stablJ-lzatori kao što je tokoferol, suptituisani fenoli, hldrokinonl. pirokateholi, arcmatski amini i, po želji, i punioci, kao što je, na primer, dioksid titana, oksid magnezijuma, oksid cinka i silieijum dioksid.Primary polymers may be formed, for example, by polyamides, polyesters, polycaprolactams, polycaprolactopes, ethylene-vinyl acetate (EVA) copolymers, ethylene-ethyl acrylate (EEA) copolymers, polyvinyl ethers, polyacrylate esters, polyvinyl acetals, polyvinyl acetates, polyvinylacetates polymers 5 isoprene, polyurethanes, ethylcellulose, cellulose acetate butyrate, synthetic rubbers (for example neoprene rubber); polyisobutylene, butyl rubber, acrylonitrile-butadiene copolymers, epoxy resins, melamine resins, phenol-formaldehyde resins, and resin-sercinol-formaldehyde resins, and the following resins can be used ** fic: hydrogenated rosin, colophosphorous, polymerizable, polymerizable methyl esters, diminished, methylated, esterified, esterified, esterified, esterified or phenol-modified rosin, arctic and aliphatic hydrocarbon resins, hydrogenated resins, polyterpene resins, modified terpene resins, waxes, low molecular weight polyethylene and polypropylene and alkyl styrene copolymers. These resins may optionally be added to plastics such as, for example, fatty acid esters, phosphoric acid esters, phthalic acid esters, polyesters, mycetic acid esters, citric acid esters or epoxy plasticizers. Stemlators such as tocopherol, substituted phenols, hydroquinone may also be mixed. pyrocatechols, arcmatic amines, and optionally fillers, such as, for example, titanium dioxide, magnesium oxide, zinc oxide and silium dioxide.

Obrazovanje komponenata naprave koja ima topljiv kontaktni lepak sa temperaturem obrade izmedu 40 i 80°C, može se vršiti istiskivanjem, izlivanjem, nanošenjem valjcima, nanošenjem spatulom, raspršivanjem ili štampanjem.The formation of components of a device having a soluble contact adhesive with a treatment temperature between 40 and 80 ° C can be done by extrusion, pouring, roller application, spatula, spray or printing.

Granična vrednost za obradivost topijivog kontaktnog lepka kod mnogih od ovih procesa je za viskozitet od oko 80 000 Pa.The limit of workability of the soluble contact adhesive in many of these processes is for a viscosity of about 80,000 Pa.

Ako se podloga nfc^koju se nanosi lepak, kao komponenta naprave, može oštetiti temperaturom toplo nanesenog lepka, bilo razlaganjem, reakcijom ili deliričnim topljenjem,-može se koristiti hladena podlega. Hladenje se može vršiti poznatim pot stupeima, kao što je dovodenje hladnih inertnih gasova ili dodir sa nekom rashladnom površinom.If the adhesive-applied substrate nfc ^, as a component of the device, can be damaged by the temperature of the hot-applied adhesive, whether by decomposition, reaction, or delirium melting, -cold substrate may be used. Cooling can be done by known pot steps, such as supplying cold inert gases or contact with a cooling surface.

Topljivi kontaktni lepak se može nanositi u vidu sloja, ili na pojedinačnim površinama u skladu sa jednom unapred odredenom mustrom, ili šarom, na zaštitruL.sloj ili na pokrivni materijal.Soluble contact adhesive can be applied as a layer, or on individual surfaces in accordance with a predefined pattern, or pattern, on a protective layer or on a cover material.

U funkciji predvidene namene, na primer ako se materija ispušta kroz noseči sloj, što je slučaj sa esencijalnim uljima, kao što su mirisi, topljivi kontaktni lepak može biti obraden sa nekim nosačem propusti j ivim za materi ju, ili materije koje treba da se ispušta ju, dok kod izvodenja naprave kao sistema za unošenje materija kroz kožu, kod kojih se materija ispušta samo na kožu, preporučl j iv je noseči sloj nepropustl j iv za materiju koja se ispušta.For the intended purpose, for example, if the substance is discharged through the carrier layer, as is the case with essential oils such as odors, the soluble contact adhesive may be treated with a carrier impermeable to the mother, or substances to be discharged. while, while performing the device as a system for introducing matter through the skin, in which matter is discharged only to the skin, it is recommended that the carrier layer be impermeable to the substance being discharged.

Postupak prema pronalasku omogučv.je da se izbegne upotreba kontaktnih lepljivih materijala koji sadrže ra stvarače kot/obrade materija osetl jivih na toplotu i vrlo ispari jivih, sa znatno povečanom bezbednošču proizvodnje, pošto je potpuno sigurno da nikakvi toksični ostatci rastvarača ne mogu ostati u obliku za medicinsku primenu, Fri čemu se dobija veoma pojednostavljen postupak nanošenja i znatno smanjenje proizvodnih troškova. Svakako da se ovaj postupak može pogodne primeni i za materije manje osetljive na toplotu, jer i to dovodi do značajnih ušteda.The process according to the invention avoids the use of contact adhesive materials containing heat-sensitive and highly volatile solubilizers / materials, with significantly increased production safety, since it is absolutely certain that no toxic solvent residues can remain in the form for medical applications, FRI resulting in a very simplified application process and a significant reduction in manufacturing costs. Of course, this process can also be used for less heat-sensitive materials, as this leads to significant savings.

Izralmaterija u vezi sa prikazanim pronalaskom podrazumeva'hemijske elemente, organska i neorganska jedinjenja, koja mogu da izlaze iz komponenata koje ih sadrže u takvo.j jednoj napravi i time megu da ostvare željeni učinak. Kod primena -naprave prema pronalasku, posebni se značaj pridaje humanoj i veterinarskoj medicini, pri čemu je posebno prepoiučljivo iavodenje pronalaska u vidu flastera.Isralmateria in connection with the present invention means' chemical elements, organic and inorganic compounds, which can come out of the components containing them in such a device and thus have the desired effect. In the application of the device according to the invention, particular importance is attached to human and veterinary medicine, with particular reference to the invention in the form of patches.

Tipične materije hoje se mogu davati_ppmoču naprave izvedene prema prončilasku jesu: aceciklidin, amfetaminil, aiafetamin, amilnitrit, apofedrin, atebrin, alprostadil, azulen, arekolin, anetol, amilenhidrat, acetilholin, akridin, adenosintrifosforična kiselina, L-jabučna kiselina, alimemazin, aliti-amin, alil izotiocijanat, aminoetanol, apizin, apiol, azatadin, alprenolol, etinazon, benzoil-peroksid, benzil alkohol, blLsabolol, bisnorefedrJn, bvtaceltoluid, benaktizin, kamfor, kolekalciferol, hloralhjdrat, klemastin, hlorobutanol, kapsaicin, ibo.v u i.2>Lr;Typical walking materials that can be administered by the region of the device according to the invention are: acecyclidine, amphetaminyl, aiafetamine, amylnitrite, apophedrine, athebrin, alprostadil, azulen, arecolin, anetol, amylenhydrate, acetylcholine, acridine, adenosynthinosinazine amine, allyl isothiocyanate, aminoethanol, apizin, apiol, azatadine, alprenolol, ethinazone, benzoyl peroxide, benzyl alcohol, blLsabolol, bisnorefedrJn, bvtaceltoluid, benactizin, camphor, cholecalciferol, chloralinhydrate, kleumutin, ciclobutin > Lr;

tjie

U ciklopentamin, klobutinol, hamazulen, dimetokain, kodein, hloropromazin, kinin, hlorotimol, ciklofosfismid, cinkokai, —hlorambucil, hlorfenezin, diefafclatanr,. .diviniletan, dekshlorfeniraroin, dinoproston, diksirazin, efedrin, etosuksimid, enalilprcpimal, emilkamat, eritroltetranitrat, emetin, urfluran, eukaliptol, etofenamat, etilmorfin, fentanil, fluanison, guajazulene, halotan, hiosciaciin, histamin, fenkarbamid, hidroksikain, heksilresorcinol, izoaminilcitrat., izosorbiddinitrat, ibuprofen, jod, jodoform, izoaminil, lidokain, lopirin, levamisol, metadon, metiprilon, metilfenidat, mefenesin, metil efedrin, roekl.astin, metopromazin, metilpentinol, metiksen, mizoprostol., oksitetrakain, oksiprenolcl, oksifenbutazon, oksikinolin, pinen, prolintan, prociklidin, piperazin, pivazid, fensuksimid, prokain, fenindč«min, prometazin, pentetrazol, profenamin, perazin, fenol, petidun, pilokarpin, prenilamin, fenoksibenzamin, resohin, skopelamin, salicilne kiseline estar, spartein, trihloretilen, tiffiolol, trifluperazin, tetrakin, trimipramin, tranilcipromin, trimetadion, tibamat, timol, tioridazin, valprcična kiselina, verapamil, kao i druge aktivne supstance, odnosno materije, koje se mogu primati kroz kožu. Svakako da to nije konačan spisak.In cyclopentamine, clobutinol, hamazulen, dimethocaine, codeine, chloropromazine, quinine, chlorothymol, cyclophosphismide, zinccai, —chlorambucil, chlorphenezine, diefafclatanr,. .divinethane, dinoprostone, dixirazine, ephedrine, etalylprcpimal, emilkamate, erythrocyte, ethenenamide, ethenenam, fentanil, fluanison, isosorbiddinitrate, ibuprofen, iodine, iodoform, isoaminyl, lidocaine, lopirin, levamisole, methadone, metiprilone, methylphenidate, mefenesin, methyl ephedrine, roecl.astin, metopromazine, methylpentinol, metixen, oisoprostinol prolintane, procyclidine, piperazine, pivazid, phenauximide, procaine, phenindchine min, promethazine, pentetrazole, profenamine, perazine, phenol, pethidun, pilocarpine, prenylamine, phenoxybenzamine, resohin, scopelamine, salicylic acid triester, salicyl ester, trifluoroazol, trifluorophenyl ester, triacetin tetrakin, trimipramine, tranylcypromine, trimethadione, tibamate, thymol, thioridazine, valpricic acid, verapamil, as well as other acts substances or substances that can be administered through the skin. Certainly this is not a definitive list.

Tipični sastavi za topljive kontaktne lepkove koji se koriste, načinjeni su od polimera u količini od 10 do 100% masenih, poželjno 20 do 80%, najpogodnije 20 do 50% masenih, plastifikatora -._>u količini od 10 do 80% masenih, poželjno 15 dd 60% masenih, . sredstva koje daje lepljivost. . ' ) po želji izmedu 0,1 i 5% masenih sredstva protiv starenja i, po želji, 0 do 70% masenih punioca, pri čemu je zbir procenata komponenata uvek jednak 100.Typical compositions for soluble contact adhesives used are made of polymers in an amount of 10 to 100% by weight, preferably 20 to 80%, most preferably 20 to 50% by weight, of plasticizers -. _{> in an} amount of 10 to 80% by weight, preferably 15 dd 60% by weight,. adhesive agents. . ') optionally between 0.1 and 5% by weight of anti-aging agents and, optionally, 0 to 70% by weight of the fillers, with the sum of the percentages of the components always equal to 100.

Poželjno je da topljivi kontaktni lepak s<tdr?i 10 do 50% masenih stiren-izopren-stiren sintetičku gum«, koja se komercionalno može dobiti pod imenom CARIFLEX TR 1107, firme SHELL, izmedu 10 i 80% masenih hidregenizovanog alkohola, koji se komercljalno nabavlja pod nazivom ABITOL, firma HERCULES, izmedu 10 i 80% masenih ugljovodonične smole, na primer HERCURES C (HERCULES)$ izmedu 1 i 4Q%'masfenih, estra kiselina biljnih masti, na pbimer MIGLYOL 812 (DYNAMI.T NOBEL), i po želji do 5% masenih sredstva protiv starenja, kao što je hidrokinon itd., kao i do 70% masenih punioca.It is preferable that the soluble contact adhesive contains <10% to 50% by weight of styrene-isoprene-styrene synthetic gum, commercially available under the name CARIFLEX TR 1107, by SHELL, between 10 and 80% by weight of hydrogenated alcohol, which commercially procures under the name ABITOL, a HERCULES company, between 10 and 80% by weight of hydrocarbon resin, for example HERCURES C (HERCULES) $ between 1 and 4Q% 'of the fatty acid esters of vegetable fats, on the pbimer MIGLYOL 812 (DYNAMI.T NOBEL). and optionally up to 5% by weight anti-aging agents such as hydroquinone etc. as well as up to 70% by weight fillers.

A b o · ll 1 \r > 0 frA b o · ll 1 \ r> 0 fr

Kod jednog drugog preporučljivog izvodenja pronalaska, topljivi kontaktni lepak ima 10 do 50°% masenih polikaprolaktona, na primer, CAPA 650 (INTEROX), izmedu 10 i 80% hidrogenovanog alkohola, na primer ABITOL (HERCULES), izmedu 10 i 80% masenih ABITOL-a (HERCULES), izmedu 10 i 80% masenih jedne ugljovodonične smole, na primer HERCURES C. (HERCULES) izmedu 1 i 40% masenih estra kiselina biljnih masti, kao što je MIGLYOL 812 (DYNAMIT NOBEL), i, po želji, do 5% masenih agensa protiv st.arenja, kao i do 70% masenih punilaca.In another preferred embodiment of the invention, the soluble contact adhesive has 10 to 50% by weight polycaprolactone, for example, CAPA 650 (INTEROX), between 10 and 80% hydrogenated alcohol, for example ABITOL (HERCULES), between 10 and 80% by weight ABITOL -a (HERCULES), between 10 and 80% by weight of one hydrocarbon resin, for example HERCURES C. (HERCULES) between 1 and 40% by weight of vegetable fatty acid esters, such as MIGLYOL 812 (DYNAMIT NOBEL), and, if desired, up to 5% by weight of anti-aging agents, as well as up to 70% by weight of fillers.

Može biti pogodno da topljivi kontaktni lepak ima 10 do 50% masenih polietilen-vinil acetata, kao što je EVATANE 28-25 (ATOCHEM), izmedu 10 i 80% masenih hidrogenizovanog alkohola, na primer ABITOL (HERCULES), izmedu 10 i 80% masenih neke ugljovodonične smole, kao što je HERCURES C (HERCULES), izmedu 1 i 40% masenih estra kiselina biljnih masti, na primer MIGLVOL 812 (DYNAMIT NOBEL), i po želji do 5% masenih sredstva protiv starenja, kao što je hidrokinon, itd. i do 70% masenih punilaca.It may be advantageous for the soluble contact adhesive to have 10 to 50% by weight polyethylene vinyl acetate, such as EVATANE 28-25 (ATOCHEM), between 10 and 80% by weight hydrogenated alcohol, for example ABITOL (HERCULES), between 10 and 80% mass of some hydrocarbon resins, such as HERCURES C (HERCULES), between 1 and 40% by weight of vegetable fatty acid esters, for example MIGLVOL 812 (DYNAMIT NOBEL), and optionally up to 5% by weight anti-aging agents, such as hydroquinone, etc. and up to 70% by weight of fillers.

Jedan pogodan topljivi kontaktni lepak može da sadrži 10 do 50% masenih poliuretana , kao što je LUPHEN P 1110 (BASF), izmedu 10 i 80% masenih hidrogenizovanog alkohola, kao što je ABITOL (HERCULES), izmedu 10 i 80% masenih ugljovodonične smole, na primer HERCURES C (HERCULES), izmedu 1 i 40% masenih estara kiselina biljnih masti, kao što je MIGLYOL 812 (DYNAMIT NOBEL), i po želji do 5% masenih agensa protiv starenja, kao i do 70% masenih punilaca.One suitable soluble contact adhesive may contain from 10 to 50% by weight of polyurethanes, such as LUPHEN P 1110 (BASF), between 10 and 80% by weight of hydrogenated alcohol, such as ABITOL (HERCULES), between 10 and 80% by weight of hydrocarbon resin , for example HERCURES C (HERCULES), between 1 and 40% by weight of vegetable fatty acid esters such as MIGLYOL 812 (DYNAMIT NOBEL), and optionally up to 5% by weight anti-aging agents as well as up to 70% by weight of fillers.

Takode je mogude da topljivi kontaktni lepak sadrži 10 do 50% masenih poliamida, kao što je EURELON 930 (SCHERING), izmedu 10 i 80% meisenih hidrogenizovanog alkohola, kao Što je ABITOL (HERCULES), izmedu 1i 40% masenih estara kiselina biljnih masti, na primer MIGLYOL 812 (DYNAMT.T NOBEL) i po Želji do 5% masenih sredstva protiv starenja, kao i do 70% masenih punilaca.It is also possible that the soluble contact adhesive contains 10 to 50% by weight of polyamides, such as EURELON 930 (SCHERING), between 10 and 80% of mixed hydrogenated alcohol, such as ABITOL (HERCULES), between 1 and 40% of fatty acids of vegetable fats , for example, MIGLYOL 812 (DYNAMT.T NOBEL) and up to 5% by weight of anti-aging agents and up to 70% by weight of fillers.

Takode je moguče da se koristi topljivi kontaktni lepak sa 10 do 5% masenih epoksida, na primer EUREPOX 7001 (SCHERTbJG) , izmedu 10 i 80% masenih hidrogenizovanog alkohola, kao -Što je ABITOL (HERCULES), izmedu 10 i 80% ijiasenih ugljovodonične smole, kao što je HERCURES C (HERCULES), izmedu 1 i 40% masenih estara kiselina biljnih masti, na primer MIGLYOL 812 (DYINAMITIt is also possible to use a soluble contact adhesive with 10 to 5% by weight of epoxies, for example EUREPOX 7001 (SCHERTbJG), between 10 and 80% by weight of hydrogenated alcohol, such as ABITOL (HERCULES), between 10 and 80% of hydrocarbon solids resins, such as HERCURES C (HERCULES), between 1 and 40% by weight of vegetable fatty acid esters, for example MIGLYOL 812 (DYINAMIT

NOBEL) i po želji do 5% masenih sredstva pi*otiv s tar en ja, kao što je hidrokinon, itd., kao i do 70% masenih punilaca.NOBEL) and, if desired, up to 5% by weight of tar, such as hydroquinone, etc., as well as up to 70% by weight of fillers.

Jedan drugi topljivi kontaktni lepak koji se može koristiti kod proizvodnje sistema za unošenje materija kroz kožu, ima 10 do 50% masenih poliizobutena sa lepljivom, gumastom konzisteneijom, kao što je OPPANOI, B 50 (BASF), izmedu 10 i 80% masenih hidrogenovanog alkohola, na primer ABITOL (HERCULES), izmedu 10 i 80% masenih ugljovodonične smole, na primer HERCURES C (HERCULES), izmedu 1 i 40% masenih estara kiselina biljnih masti, na primer MIGLYOL 812 (DYNAMIT NOBEL), i po želji do 5% agensa protiv starenja, kao i do 70% masenih punilaca.Another soluble contact adhesive that can be used in the manufacture of a system for introducing substances through the skin has 10 to 50% by weight of polyisobutene with adhesive, rubbery consistency, such as OPPANOI, B 50 (BASF), between 10 and 80% by weight of hydrogenated alcohol , for example ABITOL (HERCULES), between 10 and 80% by weight of hydrocarbon resin, for example HERCURES C (HERCULES), between 1 and 40% by weight of esters of vegetable fats, for example MIGLYOL 812 (DYNAMIT NOBEL), and optionally up to 5 % anti-aging agent as well as up to 70% by weight fillers.

Najzad je preporučljivo da se koristi topljivi kontaktni lepak sa poliestarskom osnovom, i koji sadrži izmedu 10 i 80% masenih hidrogenovanog alkohola, na primer ABITOL (HERCULES), izmedu 10 i 80% masenih ugljovodonične smole, na primer HERCURES C (HERCULES), izmedu 1 i 40% masenih estara kiselina biljnih masti, na primer MIGLVOL 812 (DYNAMIT NOBEL), i po želji do 5% sredstva protiv starenja, kao i do 70% masenih punilaca.Finally, it is advisable to use a polyester-based soluble contact adhesive containing between 10 and 80% by weight hydrogenated alcohol, for example ABITOL (HERCULES), between 10 and 80% by weight of hydrocarbon resin, for example HERCURES C (HERCULES), between 1 and 40% by weight of vegetable fatty acid esters, for example MIGLVOL 812 (DYNAMIT NOBEL), and optionally up to 5% anti-aging agent as well as up to 70% by weight of fillers.

Naprava prema pronalasku može da sadrži jedem ili više spremnika za materiju, u kojima se materija nalazi u vedoj koncentraciji nego u sloju topljivog kontaktnog lepka koji sadrži aktivnu materiju, tako da se megu cbradivati vede doze materije te tako naprava može da ostane u upotrebi duže vreme pre no što se mora zameniti. Tipična konstrukcija je prikazana u DE-CS 36 29 304. Preporučljive konstrukcije pronalaska date su u podzahtevima, u kojima se posebno pominju.The device according to the invention may contain one or more containers for matter, in which the substance is in a higher concentration than in the layer of soluble contact adhesive containing the active substance, so that more doses of the substance can be etched, so that the device can remain in use for a long time before it has to be replaced. A typical construction is illustrated in DE-CS 36 29 304. Recommended embodiments of the invention are given in the sub-claims, which are specifically mentioned.

Druga svojstva i prednosti pronalaska objašnjene su detaljno u daljem tekstu sa pozivom na erteže, gde:Other features and advantages of the invention are explained in detail below with reference to the drawings, where:

Slikei 1 prikazuje šematski predstavljen presek slojeva naprave prema pronalasku sa spremnikom za materiju,Figure 1 shows a schematic cross-sectional view of layers of the device according to the invention with a container for matter,

Slika 2 prikazuje šematski presek naprave prema pronalasku sa spremnikom za aktivnu materiju,Figure 2 shows a schematic cross-section of the device according to the invention with an active substance container,

Slika 3 prikazuje šematski predstavljen presek još jednog izvodenja naprave prema pronalasku,bez spremnika za aktivnu materiju.Figure 3 shows a schematic cross-sectional view of another embodiment of the device according to the invention, without the active substance container.

Na slici 1 ja prikazana naprava prema pronalasku, koja u ovom slučaju ima oblik terapeutskog sistema oblika flastera, koji sadrži aktivnu materiju koja se daje kroz kožu. Ima šloj 12 topljivog kontaktnog lepka, spreronik 14 aktivne materije u kome aktivna materija ima veču konoentraciju nego u sloju 12 topljivog kontaktnog lepka, kao i nosač 10, nepropust.liiv za aktivnu materiju, ne. koji se oslanja spremnik 14 aktivne materije i koji je zalepljen na kožu 18. Aktivna materija kontinualno prolazi unapred odredencm brzinom kroz kožu 18, tako da se smanjuje sadržaj aktivne materije u sloju 12. Smanjenje količine aktivne materije kompenzuje se dotokom aktivne materije iz spremnika 14 aktivne materije, tako da je posle jednog prividijivog intervala vremena uspostavljena ravnotežna koncentracija aktivne materije u sloju 12 topljivog kontaktnog lepka, što obezbeduje ispuštanje konstantne količine aktivne materije na kožu 18.1 shows a device according to the invention, which in this case takes the form of a therapeutic patch-shaped system containing the active substance administered through the skin. It has a layer of 12 soluble contact adhesive, a barrier 14 of the active substance in which the active substance has a higher concentration than in the layer 12 of the soluble contact adhesive, and a carrier 10, impermeable to the active substance, no. which relies on the container 14 of the active substance and is adhered to the skin 18. The active substance continuously passes a predetermined rate through the skin 18 so that the content of the active substance in the layer 12 is reduced. The reduction of the amount of active substance is compensated by the inflow of the active substance from the container 14 of the active agent. so that after one apparent time interval an equilibrium concentration of the active substance in the layer 12 of the soluble contact adhesive is established, which ensures the release of a constant amount of the active substance onto the skin 18.

Na slici 2 je prikazano drugo izvodenje naprave prema pronalasku, kod kcje je spremnik 14 aktivne materije sa svih strana okruten slojem 12 topljivog kontaktnog lepka. Ovo je izvodenje posebno pogodno ako se želi velika površina dodira izmedu spremnika aktivne materije i sloja topljivog kontaktnog lepka radi brzog ispuštanja aktivne materije u sloj topljivog kontaktnog lepka. NFigure 2 shows a second embodiment of the device according to the invention, wherein the container of the active substance 14 is surrounded on all sides by a layer of soluble contact adhesive. This embodiment is particularly suitable if a large contact surface is desired between the active substance container and the layer of soluble contact adhesive for rapid release of the active substance into the layer of soluble contact adhesive. N

Na slici 3 prikazano je sledeče jednostavno izvodenje naprave prme pronalasku, kod koga je slej topljivog kontaktnog lepka, 12, koji sadrži aktivnu materiju, nanesen na materiN jal 10 nepropustljivog nosača, tako dri ovaj obuhvata sloj 12 sa tri strane. Preko površine topljivog kontaktnog lepka ona se lepi na kožu 18, tetko dk je obezbeden dodir po celo j površini u toku vremana aplikacije^, a prenošenje aktivne materije na kožu Mvek se vrši po konstantnoj površini i konstantnom brzinom.Figure 3 shows the following simple embodiment of the device according to the invention, in which a layer of soluble contact adhesive 12 containing the active substance is applied to the material 10 of the impermeable carrier, thus comprising a layer 12 on three sides. Through the surface of the soluble contact adhesive, it is adhered to the skin 18, the aunt dk is provided touch over the entire surface during application times ^, and the transfer of the active substance to the Mvek skin is carried out at a constant surface and at a constant speed.

Biče opisana, prema pronalasku poboljšana, proizvodnja naprave prema pronalasku. Prvo se pripremi mešavina komI ----- ———- . -^lporienata topljivog kontaktr.og lepka i materije koja se prenosi na kožu. Mešavina se dovede na temperaturu obrade i u i*astop1 jenom stanju nanese na materija! nosača. Dalja obrada,· ke.o i primena lepljivo izvedenog zaštitnog sloja od vi j, cionalan način. ' >The production of the device according to the invention will be described, according to the invention improved. A mixture of COMI ----- ———- is first prepared. - ^{l of the} soluble contact adhesive and skin-borne substances. Bring the mixture to the processing temperature and apply it to the material in a condition! of the carrier. Further processing, · ke.oi and application of a sticky derived protective layer of vi j, the national way. '>

. r·.. r ·.

i i jLb ό ··<*L 3ψ·i i jLb ό ·· <* L 3ψ ·

Pronalazak je ilustrovan sledečim primerima u kojima se, ukoliko nije drugačije naznačeno,- koriste sledeče skračenice : deo = težinski (maseni) deoThe invention is illustrated by the following examples in which, unless otherwise indicated, - the following abbreviations are used: part = weight part

A = hidroabietilalkohol (ABITOL/Hercules)A = Hydroabietyl alcohol (ABITOL / Hercules)

H = alifaticna ugljovodonicna smola (HERCULES C/Hercules)H = aliphatic hydrocarbon resin (HERCULES C / Hercules)

M - Triglicerid (MIGLYOL 812/Dynamit Nobel)M - Triglyceride (MIGLYOL 812 / Dynamit Nobel)

Primer 1Example 1

100 delova etilenvinilacetat-kopolimera (EVATANE 28-25/Atochem), 133 delova A,100 parts ethylene vinyl acetate copolymer (EVATANE 28-25 / Atochem), 133 parts A,

200 delova H i dela M se na oko 110°C stope i uz mešanje homogenizuju. Nakon hladjenja na oko 50-60°C doda se katalizator i posle homogeniziranja dobljena lepljiva masa se nanosi na silikoniziranu poliestarsku foliju i noseča folija kašira.200 parts H and part M are homogenized at about 110 ° C and stirred. After cooling to about 50-60 [deg.] C., the catalyst was added and, after homogenization, the adhesive obtained was applied to a siliconized polyester film and the carrier film lined.

Primer 2Example 2

100 delova stirol-izopren-stirol-blokkopolimera (CARIFLEX TR 1107/ Shell), delova A,100 pieces of styrene-isoprene-styrene-block copolymer (CARIFLEX TR 1107 / Shell), parts A,

100 delova H i dela M se homogeniziraju na 140°C i dalje obradjuju na 55°C kao što je opisano u primeru 1.100 parts H and part M were homogenized at 140 ° C and further processed at 55 ° C as described in Example 1.

Primer 3Example 3

100 delova poliizobutilena (OPPANOL B 15/BASF),100 parts of polyisobutylene (OPPANOL B 15 / BASF),

100 delova A i100 parts A and

100 delova H se homogenizuju na 120°C i dalje obradjuju na 78°C kao što je opisano u primeru 1.100 parts H were homogenized at 120 ° C and further processed at 78 ° C as described in Example 1.

Primer 4Example 4

100 delova linearnog poliuretana (LUPHEN P 1112/BASF), .100 pieces of linear polyurethane (LUPHEN P 1112 / BASF),.

200 delova A, 200 delova H i 22 dela M se homogenizuju na 120°C i dalje obradjuju na 53°C kao što je opisano u primeru 1.200 parts A, 200 parts H and 22 parts M are homogenized at 120 ° C and further processed at 53 ° C as described in Example 1.

Primer 5Example 5

100 delova poliamida (EURELON 2095/Schering),100 pieces of polyamide (EURELON 2095 / Schering),

130 delova A,130 parts A,

200 delova H i 22 dela M se homogenizuju na 120°C i dalje obradjuju kao što je opisano u primeru 1 na 53°C.200 parts H and 22 parts M are homogenized at 120 ° C and further processed as described in Example 1 at 53 ° C.

Primer 6Example 6

100 delova epoksidne smole (EUROPOX 7001/Schering),100 parts of epoxy resin (EUROPOX 7001 / Schering),

133 dela A,133 Part A,

200 delova H i 22 dela M se homogenizuju na 120°C i dalje obradjuju na 52°C kao što je opisano u primeru 1.200 parts H and 22 parts M are homogenized at 120 ° C and further processed at 52 ° C as described in Example 1.

Primer 7Example 7

100 delova polikaprolaktona (CAPPA 50/Interox),100 parts of polycaprolactone (CAPPA 50 / Interox),

200 delova A200 Parts A

200 delova H i 25 delova M se homogenizuju na 110°C i dalje obradjuju na 50-55°C kao što je opisano u primeru 1.200 parts H and 25 parts M were homogenized at 110 ° C and further processed at 50-55 ° C as described in Example 1.

Primer 8Example 8

100 delova etilenvinilacetat kopolimeta (EVATANE 28-25/Atochem), 133 dela poliviniletra (LUTANOL A 100/BASF),100 parts ethylene vinyl acetate copolymer (EVATANE 28-25 / Atochem), 133 parts polyvinyl ether (LUTANOL A 100 / BASF),

200 delova H i dela M se homogenizuju na 120°C i dalje obradjuju na 55-60°C kao što je opisano u primeru 1.200 parts H and part M were homogenized at 120 ° C and further processed at 55-60 ° C as described in Example 1.

LOHMANN GmbH & Co.KG.LOHMANN GmbH & Co.KG.

zastupa .represented.

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vuvu

Primer 9Example 9

100 delova epoksidne smole (EUREPOX 7001/Schering)100 parts epoxy resin (EUREPOX 7001 / Schering)

250 delova hidroabietil alkohola (ABITOK/HERCULES), reagens koji daje lepljivost250 Parts of Hydroabietyl Alcohol (ABITOK / HERCULES), Adhesive-Reagent

200 delova alifatične ugljovodonične smole (HERCURES C/ HERCULES), reagens koji daje lepljivost delova triglicerida (MIGLYOL 812/Dvnamit Nobel), omekšivač delova titan dioksida (punilac) delova butilhidroksi toluola (Merck) se homogenizira ju na 110°C$ a homogenizira ju se uz mešanje. Posle hladjenja na 40°C umeša se aktivna supstanca i posle homogeniziranja dobijena masa za lepljenje se premazuje na pokrivni ili zaštitni sloj od obostrano silikonizirane poliestarske folije Hostaphan RN 100 (KALLE) i posle ovoga se kaŠira noseča folija, ovde jedna 15 um poliestarska folija Hostaphan RN 15 (KALLE).200 parts of aliphatic hydrocarbon resin (HERCURES C / HERCULES), reagent which gives the adhesiveness of parts of triglyceride (MIGLYOL 812 / Dvnamit Nobel), softener of titanium dioxide (filler) parts of butylhydroxy toluene (Merck) is homogenized at 110 ° C. with stirring. After cooling to 40 ° C, the active ingredient is stirred and, after homogenization, the adhesive obtained is coated on a cover or protective layer of Hostaphan RN 100 (KALLE) double-sided siliconized polyester film and then a carrier film is lined here, a 15 µm Hostaphan polyester film here RN 15 (KALLE).

Primer 10Example 10

100 delova etilenvinilacetat kopolimera (EVATANE 28-25/ATOCHEM)100 parts ethylene vinyl acetate copolymer (EVATANE 28-25 / ATOCHEM)

200 delova poliviniletra (LUTONAL A 100/BASF)200 parts polyvinyl ether (LUTONAL A 100 / BASF)

200 delova alifatične ugljovodonične smole (HERCURES C/ HEROLDES) reagens koji daje lepljivost delova triglicerida (MIGLYOL 812/Dynamit Nobel), omekšivač delova cink oksida (punilac) i delova smeše iz butilhidroksitoluola, askorbil palmitata, limunske kiseline, mono i di glicerida jestivih masnih kiselina i propilenglikola (ΟΧΥΝΕΧ 2004/LERCK) se homogenižiraju na 110°C, a homogeniziraju se uz mešanje Posle hladjenja na 40°C se umeša· aktiva supstanca i posle homogeniziranja dobijena masa za lepljenje se premazuje na pokrivni ili zaštitni sloj od obostrano silikonizirane poliestarske folije (Hostaphan R 100 (KALLE)) i posle ovoga se kašira noseča folija, ovde jedna 50 um polipropilenska folija (NONOFOL).200 parts aliphatic hydrocarbon resin (HERCURES C / HEROLDES) reagent which gives the adhesiveness of the triglyceride parts (MIGLYOL 812 / Dynamit Nobel), the softener of the zinc oxide (filler) parts and the mixture of butylhydroxytoluene, ascorbyl palmitate, citric acid, citric acid monohydric acid acids and propylene glycol (ΟΧΥΝΕΧ 2004 / LERCK) are homogenized at 110 ° C and homogenized with stirring. After cooling to 40 ° C the active ingredient is mixed and after homogenisation, the adhesive obtained is coated on a cover or protective layer of double-siliconized polyester foil (Hostaphan R 100 (KALLE)) and after that the carrier foil is lined, here one 50 um polypropylene foil (NONOFOL).

Primer 11Example 11

100 delona poliizobutilena (OPPANOL B 15/BASF)100 delon polyisobutylene (OPPANOL B 15 / BASF)

100 delova hidroabietil alkohola (ABITOK/HERCULES) , reagens koji daje lepljivost100 parts Hydroabetyl Alcohol (ABITOK / HERCULES), a sticky reagent

100 delova alifatične ugljovodonične smole (HERCURES C/HERCULES), reagens koji daje lepljivost delova triglicerida (MIGLYOL 812/Dynamit Nobel), omekšivač delova silicijum oksida (AEROSIL 200/DEGUSSA) (punilac) delova 2>2’-metilen-bis(4-metil-6-cikloheksil£enola) se homogeniziraju na 120°C, a homogeniziraju se uz mešanje.100 parts aliphatic hydrocarbon resin (HERCURES C / HERCULES), reagent that gives the adhesiveness of triglyceride parts (MIGLYOL 812 / Dynamit Nobel), silicon oxide part softener (AEROSIL 200 / DEGUSSA) (filler) parts 2> 2'-methylene-bis (4 -methyl-6-cyclohexyl (enol) are homogenized at 120 ° C and homogenized with stirring.

Posle hladjenja na 80°C umeša se aktivna supstanca i posle homogeniziranja dobijena masa za lepljenje se premazuje na pokrivni ili zaštitni sloj od obostrano silikonizirane poliestarske folije Hostaphan RN 100 (KALLE) i posle ovoga se kašira noseča folija, ovde jedna 19 um poliestarska folija Hostaphan MN 19 (KALLE).After cooling to 80 [deg.] C., the active compound is stirred and after homogenization, the adhesive obtained is coated on a cover or protective layer of Hostaphan RN 100 (KALLE) double-siliconized polyester film and then the carrier film is lined here, a 19 [m] Hostaphan polyester film here. MN 19 (KALLE).

LOHMANN GmbH & Co. KG. zastupa : /ΊLOHMANN GmbH & Co. KG KG. represented by: / Ί

ή 101 BEOGRAD.VI.AJKOVlfEVA 28'ή 101 BELGRADE.VI.AJKOVlfEVA 28 '

TEL.: 331-^0, 346-185 TELEX 12910 MIK1JE1J WTEL .: 331- ^ 0, 346-185 TELEX 12910 MIK1JE1J W

JELENA* 3-154565Deer * 3-154565

Claims

A method for the manufacture of a controlled release patch of an active substance from fusible contact adhesives having an even or unevenly distributed active substance, characterized in that a continuous or discontinuous fusible contact adhesive having a content of 10 to 80% by weight of styrene-isoprene polymer is applied -styrene, polycaprolactone, polypoxide, polyisobutene or polyvinyl ether, between 10 and 80% by weight of a tack-forming agent such as hydroabietyl alcohol or an aliphatic hydrocarbon resin, optionally from 10 to 80% by weight of a plasticizer such as triglyceride, if necessary 0 , 1 to 5% by weight of anti-aging agent and, if necessary, 0 to 70% by weight of the filler, such as titanium oxide, zinc oxide or silicon oxide, with the sum of percentage parts always 100 containing the active substance being released at a temperature of fusible contact adhesive from 40 to 80 ° C to the substrate, which may be a protective layer or a carrier layer.

Method according to claim 1, characterized in that the fusible contact adhesive (s) containing / containing the active substance (s) are applied in one or more layers.

Method according to one of the preceding claims, characterized in that the carrier for the active, active substance / active substances which must / must be released is permeable or impermeable.

Process according to one of the preceding claims, characterized in that the mixing of the fusible contact adhesive with the active substance is carried out by extrusion, casting, roller application, blade application, spray ah and the printing process.