HRP920853A2 - Transdermal therapeutic system releasing active substance - Google Patents
Transdermal therapeutic system releasing active substance Download PDFInfo
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- HRP920853A2 HRP920853A2 HR920853A HRP920853A HRP920853A2 HR P920853 A2 HRP920853 A2 HR P920853A2 HR 920853 A HR920853 A HR 920853A HR P920853 A HRP920853 A HR P920853A HR P920853 A2 HRP920853 A2 HR P920853A2
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- Prior art keywords
- active substance
- therapeutic system
- reservoir matrix
- container
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- 230000001225 therapeutic effect Effects 0.000 title claims description 41
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Description
OPS IZUMA OPS OF THE INVENTION
Oblast tehnike u koju spada izum The technical field to which the invention belongs
Izum spada u oblast uređaja za unošenje sredstava u tijelo ili nanošenje na tijelo, a posebno se odnosi na unošenje lijekova u tijelo difuzijom kroz kožu. Oznaka prema Međunarodnoj klasifikaciji patenata: A 61 M 37/00. The invention belongs to the field of devices for introducing agents into the body or applying them to the body, and especially relates to the introduction of drugs into the body by diffusion through the skin. Designation according to the International Classification of Patents: A 61 M 37/00.
Tehnički problem Technical problem
Izumom se rješava problem proizvodnje terapeutskog sustava sa spremnikom aktivne tvari za apliciranje aktivne tvari kroz kožu, koji će omogućiti primjenu tekućih i isparljivih aktivnih tvari. The invention solves the problem of manufacturing a therapeutic system with an active substance container for applying the active substance through the skin, which will enable the application of liquid and volatile active substances.
Stanje tehnike State of the art
Terapeutski sustavi za davanje lijekova preko kože dovode jednu ili više aktivnih tvari određenom brzinom i na kontinuiran način, u tijelu jednog određenog vremenskog perioda, na datu točku nanošenja na kožu. Ovi sustavi su terapeutski precizni instrumenti koji osiguravaju kontinuirano ispuštanje aktivne tvari. Therapeutic systems for administering drugs through the skin deliver one or more active substances at a certain rate and in a continuous manner, in the body for a certain period of time, to a given point of application to the skin. These systems are therapeutically precise instruments that ensure continuous release of the active substance.
Ovakvi terapeutski sustavi mogu imati i lokalno i opće djelovanje, a veliki broj aktivnih tvari koje se mogu aplicirati na ovaj način i njihove različite kemijske, fizičke i farmakološke karakteristike postavljaju sve novije i novije zahtjeve proizvodnji takvih sustava. Such therapeutic systems can have both local and general action, and the large number of active substances that can be applied in this way and their different chemical, physical and pharmacological characteristics place more and more recent demands on the production of such systems.
Obično ovakvi sustavi za unošenje preparata preko kože imaju najmanje jedan spremnik aktivne tvari, u kojem se aktivne tvari nalaze u čvrstom, tekućem ili molekularnom obliku, kao i jedan ljepljivi sloj pomoću kojeg se sustav prisno povezuje s kožom i kroz koji se vrši prolaz aktivne tvari, zatim jednu regulacijsku membranu i zaštitne/pokrivne slojeve koji su u suštini nepropusni za aktivnu tvar. Usually, such systems for introducing preparations through the skin have at least one container of the active substance, in which the active substances are found in solid, liquid or molecular form, as well as an adhesive layer by means of which the system is intimately connected to the skin and through which the passage of the active substance is carried out , then a regulatory membrane and protective/covering layers that are essentially impermeable to the active substance.
Poznati sustavi su teški za izradu i imaju kompliciranu strukturu. Jedan od problema konvencionalnih sustava je mogu li obrađivati lako isparljive aktivne tvari, jer je u tijeku proizvodnje teško kontrolirati isparavanje aktivne tvari. Known systems are difficult to create and have a complicated structure. One of the problems with conventional systems is whether they can process easily volatile active substances, because it is difficult to control the evaporation of the active substance during production.
Toplinski osjetljive aktivne tvari mogu se koristiti samo u ograničenoj mjeri u sustavu kada je riječ o matricama ili terapeutskim sustavima koji se moraju termički obrađivati i koji se proizvode postupcima koji sadrže termičku obradu. Heat-sensitive active substances can only be used to a limited extent in the system when it comes to matrices or therapeutic systems that must be heat-treated and which are produced by processes that include heat treatment.
Rađeni su pokušaji unošenja čiste aktivne tvari u obliku finih zrnaca pomiješanim kontaktno ljepljivim polimerom, tako da se fino usitnjena, finozrnasta aktivna tvar vremenom otapa kao uskladišteni kristali u sloju ljepljive matrice (DE-OS 35 00 508). Ovaj postupak nije pogodan za isparljive toplinski osjetljive aktivne tvari, budući da sadrži faze toplinske obrade. Attempts were made to introduce the pure active substance in the form of fine grains mixed with a contact adhesive polymer, so that the finely divided, fine-grained active substance dissolves over time as stored crystals in the adhesive matrix layer (DE-OS 35 00 508). This procedure is not suitable for volatile heat-sensitive active substances, since it contains heat treatment steps.
Drugi pokušaj povećavanja mogućnosti takvih terapeutskih sustava obuhvaća ulijevanje u sloj kontaktnog ljepila takvog sustava spremnika aktivne tvari u vidu mikrokapsula koje su obuhvaćene jednom regulacijskom membranom (vidjeti američke patentne spise br. 2 598 123 i 3 731 683). Proizvodnja takvih mikrokapsula obuhvaćenih regulacijskim membranom izuzetno je složena, a i ne može se izvesti za mnoge aktivne tvari. Miješanje mikrokapsula koje sadrže aktivnu supstanciju ispod nekog materijala spremnika predstavlja slijedeću tešku fazu postupka, u tijeku kojega se mikrokapsule mogu lako oštetiti ili razoriti što može dovesti do nezadovoljavajuće konstantnosti sadržaja aktivne tvari u gotovom terapeutskom sustavu. Postupak iz američkog patenta 3 598 123 teško se izvodi sa tekućim aktivnim tvarima, naročito ako je aktivna tvar data u lako isparljivom obliku. Another attempt to increase the possibilities of such therapeutic systems involves pouring into the contact adhesive layer of such a container system an active substance in the form of microcapsules that are covered by a single regulatory membrane (see US Patent Nos. 2,598,123 and 3,731,683). The production of such microcapsules covered by a regulatory membrane is extremely complex, and cannot be performed for many active substances. Mixing microcapsules containing an active substance under some container material represents the next difficult phase of the procedure, during which the microcapsules can be easily damaged or destroyed, which can lead to an unsatisfactory constancy of the content of the active substance in the finished therapeutic system. The process of US Patent 3,598,123 is difficult to perform with liquid active substances, especially if the active substance is given in an easily volatile form.
U njemačkom patentnom spisu 3 424 837 prikazan je flaster sa spremnikom, koji se može koristiti za tekuće materijale i ima jedan pokriveni sloj, neku tekuću aktivnu tvar u jednom području pokrivnog sloja koje je ispupčeno prema van, i jednu regulacijsku membranu koja pokriva aktivnu tvar i nepropusna je za nju. Između pokrivnog sloja i regulacijske membrane nalazi se napravu za raspodjelu aktivne tvari i to netkani tekstilni materijal, koji uniformno raspodjeljuje tekućinu aktivne tvari po regulacijskoj membrani i koji učinkovito djeluje po jednoj velikoj površini. Kod flastera sa spremnikom prema njemačkom patentu 3 424 837 pokrivni sloj i regulacijska membrana spojeni su zavarivanjem duž vanjskih rubova, kako bi se spriječilo isticanje tekućine aktivne tvari. German patent document 3 424 837 shows a reservoir patch, which can be used for liquid materials and has a cover layer, a liquid active substance in a region of the cover layer which bulges outwards, and a regulating membrane covering the active substance and it is impervious to her. Between the cover layer and the regulatory membrane there is a device for distributing the active substance, namely a non-woven textile material, which uniformly distributes the liquid active substance over the regulatory membrane and which works effectively over one large surface. In the container patch according to German patent 3 424 837, the cover layer and the regulation membrane are joined by welding along the outer edges, in order to prevent leakage of the liquid active substance.
Međutim, poznati flaster sa spremnikom je nepogodan zbog toga što u njemu tekućina slobodno teče i može lako iscuriti ako se slijepljeni i zavareni rubovi oštete, a također zahtjeva skupu regulacijsku membranu, koja se mora postaviti uz napravu za raspodjelu aktivne tvari kako bi se kinetički reguliralo ispuštanje aktivne tvari. However, the known reservoir patch is disadvantageous because the liquid in it flows freely and can easily leak if the glued and welded edges are damaged, and also requires an expensive regulating membrane, which must be placed next to the active substance distribution device to kinetically regulate it. release of the active substance.
Problem prikazanog izuma je, prema tome, ostvarivanje novog terapeutskog sustava sa spremnikom aktivne tvari za apliciranje aktivne tvari, koji se može proizvesti jeftinije i pouzdanije nego poznati sustavi, i koji je također pogodan za obradu isparljivih i/ili toplinski nestabilnih komponenti. The problem of the presented invention is, therefore, the realization of a new therapeutic system with an active substance container for applying the active substance, which can be produced more cheaply and more reliably than known systems, and which is also suitable for processing volatile and/or thermally unstable components.
Opis rješenja tehničkog problema Description of the solution to the technical problem
Prema izumu, ovaj je problem riješen jednim terapeutskim sustavom koji je naznačen time što je naprava za raspodjelu aktivne tvari i naprava za reguliranje ispuštanja aktivne tvari jedna rezervoarska matrica, koja ima jedan ili više posebnih spremnika aktivne tvari postavljenih na međusobnom razmaku u prostoru, i koji imaju veću koncentraciju aktivne tvari nego u rezervoarskoj matrici. U tijeku proizvodnje terapeutskog sustava rezervoarska matrica može biti bez aktivne tvari, koja se u nju unosi tijekom jednog vremenskog perioda, tj. u tijeku držanja sustava na skladištu, ili, u slučaju vrlo isparljivih tvari, tijekom proizvodnje sustava. Prema tome, prednost je izuma da se aktivne tvari, koje su toplinski nestabilne i /ili isparljive, mogu unijeti u tijeku proizvodnje sustava za unošenje tvari preko kože u vidu spremnika i bez ikakvog toplinskog naprezanja. Nema potrebe za faze, kao što je miješanje materijala rezervoarske matrice s aktivnom tvari, već spomenuti materijal postaje zasićen aktivnom tvari na sobnoj temperaturi za vrijeme uskladištenja terapeutskog sustava. Proizvodnja je pojednostavljena zbog izostavljanja proizvodnih faza za dobivanje matrice zasićene aktivnom tvari. According to the invention, this problem is solved by a single therapeutic system characterized by the fact that the device for distributing the active substance and the device for regulating the release of the active substance is a reservoir matrix, which has one or more special containers of the active substance placed at a distance from each other in space, and which have a higher concentration of the active substance than in the reservoir matrix. During the production of the therapeutic system, the reservoir matrix can be without an active substance, which is introduced into it during a period of time, i.e. during the storage of the system in the warehouse, or, in the case of highly volatile substances, during the production of the system. Therefore, the advantage of the invention is that active substances, which are thermally unstable and/or volatile, can be introduced during the production of the system for introducing substances through the skin in the form of a container and without any thermal stress. There is no need for steps such as mixing the reservoir matrix material with the active substance, the already mentioned material becomes saturated with the active substance at room temperature during the storage of the therapeutic system. Production is simplified due to the omission of production stages to obtain a matrix saturated with the active substance.
Zbog činjenice da se ovdje koristi rezervoarska matrica s vlastitom regulacijskom funkcijom, koja je, između ostalog, određena brzinom kretanja materijala kroz matricu, nema potrebe za regulacijskom membranom koja zahtjeva dodatne proizvodne faze i materijal za membranu u tijeku proizvodnje. Spremnik se može sastojati od čiste aktivne tvari, koja može biti čvrsta ili tekuća, a također može imati i interno punilo. Pod pojmom “inertan” podrazumijeva se da aktivna tvar i punilo ne reagiraju međusobno. Jedno “inertno” punilo može također biti tvar koja ima fiziološko djelovanje, kao što je, na primjer, DMSO (dimetilsulfooksid) ili slično, koji na primjer, povećavaju propusnost kože. Punilo također može biti od nosećih materijala koji čine spremnik aktivne tvari neosjetljivim u odnosu na aplikacije koje obuhvaćaju pritisak i zatezanje, kao i nosači. Mogu se koristiti aktivne tvari koje se mogu aplicirati preko kože, a tipični primjeri su dati u slijedećem pregledu. Due to the fact that a reservoir matrix with its own regulation function is used here, which, among other things, is determined by the speed of material movement through the matrix, there is no need for a regulation membrane that requires additional production stages and material for the membrane during production. The container may consist of pure active substance, which may be solid or liquid, and may also have an internal filler. The term "inert" means that the active substance and the filler do not react with each other. An "inert" filler can also be a substance that has a physiological effect, such as, for example, DMSO (dimethylsulfoxide) or the like, which for example increase the permeability of the skin. The filler may also be of carrier materials that render the active substance container insensitive to applications involving pressure and tension, as well as carriers. Active substances that can be applied through the skin can be used, and typical examples are given in the following review.
Nikotin Nicotine
Kortikosteroidi: hidrokortizon, prenisolon, beklometakson-proprionat, flumetason, triamcinolon, triamcinolon-acetonid, fluocinolon, fluocinolon-acetonid, fluocinolon-acetonid acetat, klobetasol-proprionat, itd. Corticosteroids: hydrocortisone, prenisolone, beclometaxone proprionate, flumethasone, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol proprionate, etc.
Analgetici, agensi protiv upala: acetaminofen, mefenamička kiselina, flufenamička kiselina, disiklofenak, dicikofenak-natrij-alklofenak, oksifenbutazon, fenilbutazon, ibuprofen, flurbiprofen,slicilička kiselina, 1-mentol, kamfor, sulindak-tolmetin-natrij, anproksen, fenbufen, itd. Analgesics, anti-inflammatory agents: acetaminophen, mefenamic acid, flufenamic acid, dicyclofenac, dicycofenac-sodium-alclofenac, oxyfenbutazone, phenylbutazone, ibuprofen, flurbiprofen, salicylic acid, 1-menthol, camphor, sulindac-tolmetin-sodium, anproxen, fenbufen, etc. .
Hipnotički aktivni sedativi: fenobarbital, amobarbital, ciklobarbital, triazolam, nitrazepan, lorazepam, haloperidol, itd. Hypnotically active sedatives: phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazepan, lorazepam, haloperidol, etc.
Trankilizeri (sredstva za smirivanje): flufenazin, tiorizadin, lorazepam, flunitrazepam, kloropromazin, itd. Tranquilizers: fluphenazine, thiorizadine, lorazepam, flunitrazepam, chlorpromazine, etc.
Sredstva protiv povišenog krvnog tlaka; pindolol: bufralol, indenolol, nipadipin, lofeksidin, nipradinol, bukumolol, itd. Means against high blood pressure; pindolol: bufralol, indenolol, nipadipin, lofexidine, nipradinol, bucumolol, etc.
Diuretici koji djeluju na snižavanje povišenog krvnog tlaka: hidrotiazid, bendroflumentiazid ciklobenziazid, itd. Diuretics that act to lower high blood pressure: hydrothiazide, bendroflumenthiazide, cyclobenziazid, etc.
Antibiotici: penicilin, tetraciklin oksitetraciklin, fradiomicin, sulfat, eritromicin, kloramfenikol, itd. Antibiotics: penicillin, tetracycline, oxytetracycline, fradiomycin, sulfate, erythromycin, chloramphenicol, etc.
Anestetici:lidokain, benzokain, etilaminobenzoat, itd. Anesthetics: lidocaine, benzocaine, ethylaminobenzoate, etc.
Antimikrobiološki agensi: benzalkinij klorid, nitrofurazon, nistatin, acetosulfamin, klotrimazol, itd. Antimicrobial agents: benzalkonium chloride, nitrofurazone, nystatin, acetosulfamine, clotrimazole, etc.
Agensi protiv gljivica: pentamicin, amfotericin B, pirolnitrin, klotrimazol, itd. Antifungal agents: pentamycin, amphotericin B, pyrrolnitrine, clotrimazole, etc.
Vitamini: vitamin A, ergokalciferol, kolekalciferol, oktotiamin, riboflavin butirat, itd. Vitamins: vitamin A, ergocalciferol, cholecalciferol, octothiamine, riboflavin butyrate, etc.
Antiepileptici: nitrazepam, meprobamat, klonazepam, itd. Antiepileptics: nitrazepam, meprobamate, clonazepam, etc.
Koronarni vazodilatatori: dipiridamol, eritriol tetranitrat, pentaeritritol tetranitrat, propatilnitrat, itd. Coronary vasodilators: dipyridamole, erythritol tetranitrate, pentaerythritol tetranitrate, propyl nitrate, etc.
Antihistaminici: difenil hidromin hidroklorid, klorfeniramin, difenilimidazol, itd. Antihistamines: diphenyl hydromine hydrochloride, chlorpheniramine, diphenylimidazole, etc.
Antitusucu: dertrometorfan (hidrobromid), terbutalin (sulfat), efedrin (hidroklorid), salbutanol (sulfat), izoproterenol (hidroklorid, sulfat), itd. Antitussive: dertromethorphan (hydrobromide), terbutaline (sulfate), ephedrine (hydrochloride), salbutanol (sulfate), isoproterenol (hydrochloride, sulfate), etc.
Spolni hormoni: progesteron, itd. Sex hormones: progesterone, etc.
Ostali medikamenti/farmaceutski proizvodi: 5-fluorouracil, fentanil, desmopressin, domperdon, skopolamin (hidrobromid), peptid, itd. Other medications/pharmaceutical products: 5-fluorouracil, fentanyl, desmopressin, domperdone, scopolamine (hydrobromide), peptide, etc.
Očigledno je da ovaj popis nije konačan. Obviously, this list is not exhaustive.
Korisno je ako se rezervoarska matrica za aktivnu tvar može izvesti u vidu slojeva, pri čemu ti slojevi mogu biti isti ili različiti. Rezervoarska matrica može biti ljepljiva na dodir i može biti od nekog gumenog materijala, kao što je stiren/izopren/stiren blok kopolimer, silikonska guma ili sintetičke smole, kao poli(metz)akrilat, poliuretan, polivinileter, poliester itd. Popis pogodnih materijala za matricu dat je, na primjer, u DE-OS 35 00508, koji se spominje kao referenca. Može biti pogodno ako je rezervoarska matrica ljepilo koje djeluje na dodir, budući da time otpada potreba postavljanja posebne naprave za pričvršćivanje lijepljenjem pri dodiru u sustav, primjena takve matrice koja se lijepi na dodir ovisi, između ostalog, od kompatibilnosti materijala matrice s aktivnom tvari. Poznati su materijali za matrice ljepljivi na dodir. It is useful if the reservoir matrix for the active substance can be made in the form of layers, whereby these layers can be the same or different. The reservoir matrix may be tacky to the touch and may be of some rubber material, such as styrene/isoprene/styrene block copolymer, silicone rubber, or synthetic resins, such as poly(meth)acrylate, polyurethane, polyvinylether, polyester, etc. List of suitable materials for matrix is given, for example, in DE-OS 35 00508, which is mentioned by reference. It may be convenient if the reservoir matrix is a contact adhesive, since this eliminates the need to install a special contact adhesive attachment device in the system, the application of such a contact adhesive matrix depends, among other things, on the compatibility of the matrix material with the active substance. There are well-known materials for matrices that are sticky to the touch.
Preporučljivi materijali za matrice, koji nisu ljepljivi na dodir, jesu polimeri koji sadrže poli-(met)akrilat, polivinilpirolidon, etilcelulozu, hidroksipropilcelulozu, hidroksilpropilmetilcelulozni ftalat, polivinilalkohol i njegovi kopolimeri s vinilauratom ili maleičkom kiselinom, polivinileter, butil-guma i polikaprolaktam. Recommended matrix materials, which are not sticky to the touch, are polymers containing poly(meth)acrylate, polyvinylpyrrolidone, ethylcellulose, hydroxypropylcellulose, hydroxylpropylmethylcellulose phthalate, polyvinylalcohol and its copolymers with vinylaurate or maleic acid, polyvinylether, butyl rubber and polycaprolactam.
Tako se na primjer, spremnik, ili spremnici aktivne tvari mogu postaviti između sloja rezervoarske matrice na strani oslonog sloja i sloja rezervoarske matrice na strani kože, pri čemu je odnos debljina slojeva rezervoarske matrice između X:Y=1:DO1:20, a posebno je pogodna vrijednost 1:1 do 1:5. So, for example, the container or containers of the active substance can be placed between the layer of the reservoir matrix on the side of the support layer and the layer of the reservoir matrix on the skin side, where the ratio of the thicknesses of the layers of the reservoir matrix is between X:Y=1:DO1:20, and especially a suitable value is 1:1 to 1:5.
U drugim slučajevima može biti pogodno ako se rezervoarska matrica, ili slojevi od kojih je rezervoarska matrica oblikovana, bar s jedne strane izvedeni s premazom ljepila koje djeluje na dodir. In other cases, it may be convenient if the reservoir matrix, or the layers from which the reservoir matrix is formed, are at least on one side made with a coating of contact adhesive.
Prema jednom drugom pogodnom izvođenju sustava prema izumu, spremnik aktivne tvari može se postaviti između rezervoarske matrice i oslonog sloja, što je, na primjer, pogodno za čvrste aktivne tvari. According to another suitable embodiment of the system according to the invention, the container of the active substance can be placed between the reservoir matrix and the support layer, which is, for example, suitable for solid active substances.
Kod jednog preporučljivog izvođenja izuma, naprava za pričvršćivanje može biti izvedena u obliku ljepljivih dijelova ulivenih u rezervoarsku matricu, kao što je, na primjer, ljepljivi rub po cijelom obimu, ili ljepljive točke. In one preferred embodiment of the invention, the attachment device may be in the form of adhesive parts molded into the reservoir matrix, such as, for example, an adhesive edge around the entire circumference, or adhesive points.
Moguće je, na konvencionalan način, postaviti odvojivi zaštitni sloj za površine terapeutskog sustava okrenute prema koži. It is possible, in a conventional way, to place a removable protective layer for the surfaces of the therapeutic system facing the skin.
Ukupna količina aktivne mase u spremniku i u rezervoarskoj matrici je, najpogodnije, do 20 puta veća od terapeutski potrebne količine aktivne tvari. The total amount of active mass in the container and in the reservoir matrix is, most conveniently, up to 20 times greater than the therapeutically necessary amount of active substance.
Jedan posebno pogodan postupak za proizvodnju takvih sustava obuhvaća izradu rezervoarske matrice od dva sloja, koji mogu biti isti ili različiti, između kojih se stavlja spremnik aktivne tvari. Slojevi, rezervoarske matrice mogu se međusobno spojiti primjenom pritiska i/ili topline. Spremnik se može unijeti u rezervoarsku matricu primjenom pritiska, na primjer ubrizgavanjem unaprijed određene količine ili utiskivanjem tijela aktivne tvari u meki sloj matrice. One particularly suitable process for the production of such systems involves the production of a reservoir matrix of two layers, which may be the same or different, between which the reservoir of the active substance is placed. Layers, reservoir matrices can be connected to each other by applying pressure and/or heat. The reservoir can be introduced into the reservoir matrix by applying pressure, for example by injecting a predetermined amount or pressing a body of active substance into the soft layer of the matrix.
Jedan drugi preporučljivi proces je oblikovanje barem dijela terapeutskog sustava posipanjem čestica. Another recommended process is to form at least part of the therapeutic system by sprinkling particles.
Također je moguća proizvodnja višeslojne matrice za aktivnu tvar. Pokrivni sloj i sloj rezervoarske matrice također se mogu spojiti toplinom ili pritiskom. Sloj ili slojevi rezervoarske matrice mogu se bar djelomično proizvesti od tekućih materijala, na primjer od neke disperzije, taline ili otopine. It is also possible to produce a multilayer matrix for the active substance. The cover layer and the reservoir matrix layer can also be joined by heat or pressure. The layer or layers of the reservoir matrix may be at least partially produced from liquid materials, for example from some dispersion, melt or solution.
Terapeutski sustav prema izumu posebno je pogodan za lokalnu ili opću aplikaciju aktivne tvari koja djeluje preko kože u humanoj ili veterinarskoj medicini, a također se može koristiti u kozmetici. The therapeutic system according to the invention is particularly suitable for local or general application of an active substance that acts through the skin in human or veterinary medicine, and can also be used in cosmetics.
Izum će biti detaljnije opisan u slijedećem tekstu preko izvođenja terapeutskog sustava, koja ne ograničavaju izum, i sa pozivom na shematske crteže, gdje: The invention will be described in more detail in the following text through the implementation of the therapeutic system, which does not limit the invention, and with reference to the schematic drawings, where:
- slika 1 prikazuje presjek kroz jedno preporučljivo izvođenje terapeutskog sustava prema izumu, - figure 1 shows a section through one recommended embodiment of the therapeutic system according to the invention,
- slika 2 predstavlja presjek kroz jedno drugo izvođenje terapeutskog sustava, kod kojeg je spremnik aktivne tvari postavljen između oslonog sloja i rezervoarske matrice, - Figure 2 represents a cross-section through another embodiment of the therapeutic system, in which the container of the active substance is placed between the support layer and the reservoir matrix,
- slika 3 prikazuje presjek kroz još jedno preporučljivo izvođenje sustava izumu, kod kojega je rezervoar aktivne tvari uliven između slojeva matrice, - figure 3 shows a section through another recommended embodiment of the system of the invention, where the reservoir of the active substance is cast between the layers of the matrix,
- slika 4 prikazuje presjek kroz jedan terapeutski sustav prema izumu, s nekoliko spremnika aktivne tvari raspoređenih u jednoj ravnini, - figure 4 shows a cross-section through a therapeutic system according to the invention, with several containers of the active substance arranged in one plane,
- slika 5 prikazuje presjek kroz jedan terapeutski sustav prema izumu sa spremnikom aktivne tvari u vidu jednog sloja, - figure 5 shows a section through a therapeutic system according to the invention with a container of the active substance in the form of a single layer,
- slika 6 prikazuje presjek kroz poludovršeni proizvod u vidu tkanine prema izumu. - Figure 6 shows a section through a semi-finished product in the form of fabric according to the invention.
Slika 1 predstavlja presjek kroz terapeutski sustav prema izumu, koji je pričvršćen na kožu 18 napravom 16 za pričvršćivanje, na primjer poroznim slojem ljepljivim na dodir ili sličnim. Na napravi 16 za pričvršćivanje postavljena je rezervoarska matrica 12 u kojoj, u tijeku proizvodnje, ne bi trebalo biti aktivne tvari (zasićivanje aktivnom tvari vrši se za vrijeme držanja na skladištu). U rezervoacijsku matricu uliven je spremnik 14, koji je ovdje prikazan kao čvrsta aktivna tvar, koja se otapa u materijalu rezervoarske matrice i koja se dovodi na kožu 18 preko naprave 16 za pričvršćivanje. terapeutski sustav je s vanjske strane zatvoren jednim oslonim slojem, koji je nepropustan za aktivnu tvar, a poželjno i za vlagu, a istovremeno vrši ulogu nosača za sustav. Fig. 1 represents a section through the therapeutic system according to the invention, which is attached to the skin 18 by means of an attachment device 16, for example a porous layer that is adhesive to the touch or the like. A reservoir matrix 12 is placed on the fixing device 16, in which, during production, there should be no active substance (saturation with the active substance is done during storage). A container 14 is poured into the reservoir matrix, which is shown here as a solid active substance, which dissolves in the material of the reservoir matrix and which is fed to the skin 18 via the attachment device 16. the therapeutic system is closed on the outside with one supporting layer, which is impermeable to the active substance, and preferably also to moisture, and at the same time acts as a carrier for the system.
Slika 2 prikazuje drugu varijantu sustava prema izumu, kod kojega je spremnik 14 aktivne tvari postavljen na sloj 12 rezervoarske matrice i pokriven je oslonim slojem 10. Na ovom crtežu nije prikazana naprava za pričvršćivanje, a to može biti rub ili brid ljepljiv na dodir, ili slično, koja se nanosi na dodirnu površinu s kožom terapeutskog sustava uz kožu 18. To je pogodno zbog toga što mu je proizvodnja vrlo jednostavna, Potrebno je samo da se nanese jasno određena količina aktivne tvari, u obliku čvrste tvari ili viskozne tekućine na prethodno napravljeni sloj matrice, i da se sve hermetički zatvori ili dovrši osloni slojem 10. Figure 2 shows another variant of the system according to the invention, in which the container 14 of the active substance is placed on the layer 12 of the reservoir matrix and is covered by the support layer 10. In this drawing, the attachment device is not shown, which can be an edge or edge that is sticky to the touch, or similarly, which is applied to the skin contact surface of the therapeutic system next to the skin 18. This is convenient because its production is very simple, it is only necessary to apply a clearly defined amount of the active substance, in the form of a solid substance or a viscous liquid, to the previously made layer of the matrix, and to hermetically seal or complete the rest with layer 10.
Postupak za proizvodnju sustava prema slici 2 jeftiniji je od onog prema slici 1. Međutim, on se može koristiti samo ako je aktivna tvar obložena sa svih strana matricom, na primjer zbog isparljivosti aktivne tvari, ili zbog neophodno velike dodirne površine između aktivne tvari i rezervoarske matrice. Pogodan je, na primjer, za tvari koje se vrlo lako otapaju u spremniku aktivne tvari i bez teškoća difundira u njemu, tako da nema potrebe za veliku dodirnu površinu između aktivne tvari i rezervoarske matrice za aktivnu tvar. The process for producing the system according to Figure 2 is cheaper than the one according to Figure 1. However, it can only be used if the active substance is coated on all sides with a matrix, for example due to the volatility of the active substance, or because of the necessarily large contact surface between the active substance and the reservoir matrices. It is suitable, for example, for substances that dissolve very easily in the reservoir of the active substance and diffuse in it without difficulty, so that there is no need for a large contact surface between the active substance and the reservoir matrix for the active substance.
Slika 3 prikazuje još jedno preporučljivo izvođenje kod koga je terapeutski sustav prema izumu pričvršćen za kožu 18 pomoću ljepljivih čestica ili dijelova ulivenih na koži okrenutom materijalu rezervoarske matrice za aktivnu tvar. Sloj 12 spremnika aktivne tvari obuhvaća gornji sloj X i donji sloj Y, između kojih je postavljena aktivna tvar, koja je na primjer, ovdje u tekućem obliku. Izvođenje sa dva sloja, X i Y, rezervoarske matrice pogodno je ako se sustav proizvodi tako što se prvo postavi donji sloj spremnika aktivne tvari, po želji već prevučen pokrivnim slojem ili sličnim, poslije čega se postavlja u skladu sa unaprijed određenim redoslijedom, sloj X spremnika aktivne tvari, i konačno, na konvencionalan način, osloni sloj, ili po želji, razni ljepljivi slojevi da bi se upotpunio sustav. Također može biti pogodno da se prvo postave dva sloja X i Y spremnika aktivne tvari jedan preko drugog, a zatim ubrizga jedna unaprijed određena količina aktivne tvari između ova dva sloja spremnika, i na taj način isparavanje aktivne tvari svede na minimum. Figure 3 shows another preferred embodiment where the therapeutic system according to the invention is attached to the skin 18 by means of adhesive particles or parts cast on the skin facing material of the reservoir matrix for the active substance. The layer 12 of the active substance container comprises an upper layer X and a lower layer Y, between which the active substance is placed, which is, for example, here in liquid form. The design with two layers, X and Y, of the reservoir matrix is suitable if the system is produced by first placing the bottom layer of the active substance container, if desired already coated with a cover layer or similar, after which layer X is placed in accordance with a predetermined order the container of the active substance, and finally, in a conventional manner, a support layer, or, if desired, various adhesive layers to complete the system. It may also be convenient to first place the two layers X and Y of the active substance container over each other, and then inject a predetermined amount of the active substance between these two container layers, thus minimizing the evaporation of the active substance.
Slika 4 prikazuje jedno izvođenje sustava za aplikaciju medikamenata preko kože prema izumu, koji ima nekoliko spremnika 14 aktivne tvari raspoređenih u jednoj ravnini i postavljenih između sloja 16 ljepljivog na dodir i rezervoarske matrice 12, pri čemu sloj 16 istovremeno pričvršćuje osloni sloj 10 na sustav za aplikaciju medikamenata preko kože. Ovaj je sustav upotpunjen odvojivim zaštitnim slojem 19. Figure 4 shows one embodiment of the transdermal drug delivery system according to the invention, which has a number of active substance reservoirs 14 arranged in one plane and placed between the contact adhesive layer 16 and the reservoir matrix 12, wherein the layer 16 simultaneously attaches the support layer 10 to the delivery system. application of medication through the skin. This system is completed with a detachable protective layer 19.
Slika 5 prikazuje još jedno izvođenje sustava za aplikaciju tvari preko kože prema izumu, kod kojeg je osloni sloj prevučen na jednoj strani ljepljivim slojem 16 i na njemu je postavljena aktivna tvar, po želji s punilom, kao što je materijal za pospješivanje obrade aktivne tvari (na primjer, sredstva za oblikovanje tableta) ili nosači, kao što je neka tkanina ili slično. Na plosnati spremnik aktivne tvari nanesena je rezervoarska matrica koja je pokrivena odvojivim zaštitnim slojem. Figure 5 shows another embodiment of the system for the application of substances through the skin according to the invention, in which the support layer is coated on one side with an adhesive layer 16 and the active substance is placed on it, optionally with a filler, such as a material for accelerating the processing of the active substance ( for example, tablet forming agents) or supports, such as a fabric or the like. A reservoir matrix is applied to the flat container of the active substance, which is covered with a removable protective layer.
Slika 6 prikazuje pripremni materijal za sustav za aplikaciju tvari preko kože prema izumu, koji se dobiva jednim preporučljivim proizvodnim postupkom. Opnasti zaštitni materijal u vidu obloge, kao što je, na primjer, voštani papir ili slično, pokriven je slojem Y rezervoarske matrice, koji je u ovom slučaju ljepljiv na dodir, i na njega je postavljen, prema jednom unaprijed određenom redoslijedu, veći broj spremnika aktivne tvari. Sloj Y matrice pokriven je drugim slojem X matrice, koji može sadržavati, na primjer, materijal koji se razlikuje od materijala sloja Y. Drugi sloj X pokriven je oslonim slojem 10. U smjeru strelice nalaze se crte razdvajanja, duž kojih se ovaj međuproizvod reže ili izrezuje u tijeku proizvodnje sustava prema izumu i zatim priprema na uobičajeni način. Fig. 6 shows a preparation material for a transdermal substance application system according to the invention, which is obtained by one recommended manufacturing process. A membrane protective material in the form of a lining, such as, for example, wax paper or the like, is covered with a layer Y of the reservoir matrix, which in this case is sticky to the touch, and on it is placed, according to a predetermined order, a plurality of reservoirs active substances. The layer Y of the matrix is covered by a second layer X of the matrix, which may contain, for example, a material different from the material of the layer Y. The second layer X is covered by a support layer 10. In the direction of the arrow there are separation lines, along which this intermediate product is cut or is cut during the production of the system according to the invention and then prepared in the usual way.
Tipične debljine za sustave za aplikaciju tvari preko kože prema izumu su slijedeće: ukupna debljina oko 123 do 5550 µm, preporučljivo od 285 do 1550 µm, debljina oslonog sloja od 8 do 150µm, a poželjno od 15 do 100 µm, debljina rezervoara od 100 do 5000 µm, preporučljivo od 200 do 1330 µm, debljina zaštitnog sloja od 15 do 400µm, poželjno od 70 do 150µm. Typical thicknesses for systems for the application of substances through the skin according to the invention are as follows: total thickness from about 123 to 5550 µm, preferably from 285 to 1550 µm, thickness of the support layer from 8 to 150 µm, and preferably from 15 to 100 µm, reservoir thickness from 100 to 5000 µm, recommended from 200 to 1330 µm, protective layer thickness from 15 to 400 µm, preferably from 70 to 150 µm.
Za specijalne primjene moguće je na tržište iznijeti “poludovršeni proizvod” kao takav, tako da korisnici mogu rezati sustav po potrebi, tako da polugotov proizvod služi kao tekuća zaliha. U daljnjem tekstu će biti opisani primjeri izuma. For special applications, it is possible to market the "semi-finished product" as such, so that users can cut the system as needed, so that the semi-finished product serves as a running stock. Examples of inventions will be described below.
Primjeri Examples
Primjer 1 Example 1
Proizvodnja nikotinskog flastera Production of the nicotine patch
Nikotinski flaster se prema izumu može proizvesti na slijedeći način. According to the invention, the nicotine patch can be produced in the following way.
Materijal ljepljiv na dodir, koji sadrži 2,0825 kg 40% otopine samo-unakrsno vezanog akrilatnog kopolimera (DUROTAC 280-2416 poduzeća National Starch/Chemical B.V.) u mješavini etil acetata, etanola, heksana i metanola, 147 g akrilne smole od dimetilaminoetilmetakrilata i neutralnog metakrilata (EUDRAGIT E 100 firme RÖHM PHARMA), kao i 20 g miješanih kiselinskih triglicerida frakcioniranih C8 - C10 kokosovih masnih kiselina (Miglyol 812 firme Dynamit Nobel), nanosi se na zaštitni sloj, na čiju je jednu stranu vakuumskim postupkom nanesen sloj aluminija, i koji je s obje strane obložen ljepilom, a zatim se otapalo isparava na 50 do 80ºC. Dobiva se sloj od oko 300 g/m2. Iz ovako dobivenog sloja ljepljivog na dodir izrezuju se okrugli pripravci promjera 65 mm, čiji se rubovi obrađuju, a na svaki se postavlja središnje jedan kružni obradak od netkanog materijala (vlaknasta mješavina viskozna štapel vlakna/pamuk 50:50 osnovne težine 80 g/m2 - PARATEX II/80 firme LOHMANN GMBH & CO KG) promjera 40 mm. Na njega se nanosi nikotin kao aktivna tvar u otopini (140 g nikotina u 100 g akrilne smole od dimetilaminoetilmetakrila i neutralnog metakrilata (EUDRAGIT E 100 firme RÖHM PHARMA) U 102 mg can/black. Ovako proizvedeni izresci se odmah oblažu oslonim slojem koji ne propušta nikotin, koji je debljine 15µm i na čijoj je jednoj strani vakuumskim postupkom nanesen sloj aluminija, a potom se postavljaju i hermetički zatvaraju u četverokutnu hermetičku vrećicu od odgovarajućeg materijala za pakiranje. A tacky material containing 2.0825 kg of a 40% solution of a self-crosslinked acrylate copolymer (DUROTAC 280-2416 from National Starch/Chemical B.V.) in a mixture of ethyl acetate, ethanol, hexane and methanol, 147 g of dimethylaminoethyl methacrylate acrylic resin and of neutral methacrylate (EUDRAGIT E 100 from RÖHM PHARMA), as well as 20 g of mixed acid triglycerides of fractionated C8 - C10 coconut fatty acids (Miglyol 812 from Dynamit Nobel), is applied to the protective layer, on one side of which a layer of aluminum is applied by a vacuum process, and which is coated on both sides with glue, and then the solvent is evaporated at 50 to 80ºC. A layer of about 300 g/m2 is obtained. Round pieces with a diameter of 65 mm are cut out of the adhesive layer obtained in this way, the edges of which are processed, and one circular piece of non-woven material is placed in the center of each one (fibrous mixture viscose staple fiber/cotton 50:50 basis weight 80 g/m2 - PARATEX II/80 from LOHMANN GMBH & CO KG) with a diameter of 40 mm. Nicotine is applied to it as an active substance in solution (140 g of nicotine in 100 g of acrylic resin from dimethylaminoethyl methacrylate and neutral methacrylate (EUDRAGIT E 100 from RÖHM PHARMA) in 102 mg can/black. The cuttings produced in this way are immediately coated with a non-permeable support layer nicotine, which is 15 µm thick and on one side of which a layer of aluminum is applied by a vacuum process, and then they are placed and hermetically sealed in a rectangular hermetic bag made of the appropriate packaging material.
U ovom slučaju netkani tekstilni materijal služi kao noseći sloj i da potpomaže uniformnu raspodjelu nikotina kao inertno punilo, kako je ranije definirano.U ovom slučaju netkani tekstilni materijal služi kao noseći sloj i da potpomaže uniformnu raspodjelu nikotina kao inertno punilo, kako je ranije definirano. In this case, the non-woven textile material serves as a carrier layer and to support the uniform distribution of nicotine as an inert filler, as defined earlier. In this case, the non-woven textile material serves as a carrier layer and to support the uniform distribution of nicotine as an inert filler, as defined earlier.
Zahvaljujući činjenici da se, prema izumu, otopina aktivne tvari može brzo nanijeti na jedan sloj matrice, a zatim se pokriva pokrivnim slojem koji ne propušta aktivnu tvar, moguće je po prvi put da se na zadovoljavajući način dobiju dobro dozirani nikotinski flasteri. Thanks to the fact that, according to the invention, the solution of the active substance can be quickly applied to one layer of the matrix and then covered with a covering layer that does not let the active substance pass, it is possible for the first time to obtain well-dosed nicotine patches in a satisfactory manner.
Ispitivanje ispuštanja nikotina (in vitro) Nicotine release test (in vitro)
Nikotinski flaster, proizveden prema Primjeru 1, nakon skidanja zaštitnog sloja potapa se u 80 ml izotonične otopine na 37ºC i određuje se ispuštena količina nikotina u tekućini. The nicotine patch, manufactured according to Example 1, after removing the protective layer, is immersed in 80 ml of isotonic solution at 37ºC and the released amount of nicotine in the liquid is determined.
Ta se količina određuje kromatografski poslije unaprijed određenih vremenskih intervala. Volumen medija u kojem se vrši ispuštanje zabrana je tako da su tijekom cijelog perioda ispitivanja ostvareni uvjeti potapanja (ili utapanja). Dobiveni su slijedeći rezultati: This amount is determined chromatographically after predetermined time intervals. The volume of the medium in which the bans are released is such that during the entire test period the conditions of immersion (or drowning) were achieved. The following results were obtained:
[image] [image]
Primjer 2 Example 2
Proizvodnja nikotinskog flastera Production of the nicotine patch
Jedan drugi nikotinski flaster može se, prema izumu, proizvesti na slijedeći način. Another nicotine patch can, according to the invention, be produced in the following way.
Materijal ljepljiv na dodir (ljepilo 1), koji sadrži 1,9768 kg 40% otopine samo-unakrsno vezanog akrilatnog kopolimera (DUROTAC 280 - 2416 firme National Starch/Chemical B:V:) u mješavini etil acetata, etanola, heptana i metanola, 189,7 g akrilne smole od dimetilaminoetilmetakrilata i neutralnog metakrilata (EUDRAGIT e 100 FIRME RÖHM PHARMA), kao i 20 g miješanih kiselinskih triglicerida frakcioniranih C8 - C10 kokosovih masnih kiselina (Miglyol 812 firme Dynamit Nobel), nanesen na zaštitni sloj, na čijoj je jednoj strani vakuumskim postupkom nanesen sloj aluminija, i na koji je s obje strane naneseno ljepilo, a zatim je otapalo ispareno na 50 do 80ºC. Dobiven je sloj od oko 440 g/m2. Od ovako dobivenog sloja ljepljivog na dodir izrezani su okrugli pripravci promjera 51 mm, čiji se rubovi obrađeni, i na svaki od njih je postavljen jedan kružni pripravak od netkanog materijala (vlaknasta mješavina viskoznih štapel vlakana i pamuka 70:30 osnovne težine 40g/m2 - PARETEX II/80 firme LOHMANN GMBH & CO KG) promjera 20 mm. Na njih je nanesen nikotin kao aktivna tvar u otopini (140 g nikotina u 100 g neke akrilne smole od dimetilaminoetilmetakrilata i neutralnih metakrilata (EUDRAGIT E 100 firme RÖHM PHARMA) u 46 mg can/blank. Ovako proizvedeni izresci se odmah oblaže oslonim slojem koji ne propušta nikotin, a koji je 15 µm debeli sloj na čiju je jednu stranu vakuumskim postupkom nanesen sloj aluminija, i koji ima sloj od oko 110 g/m2 ljepila i hermetički je zatvoren u četverokutnoj hermetičko vrećici od odgovarajućeg materijala za pakiranje. A touch-sensitive material (adhesive 1), containing 1.9768 kg of a 40% solution of a self-crosslinked acrylate copolymer (DUROTAC 280 - 2416 from National Starch/Chemical B:V:) in a mixture of ethyl acetate, ethanol, heptane and methanol, 189.7 g of acrylic resin from dimethylaminoethyl methacrylate and neutral methacrylate (EUDRAGIT e 100 FIRME RÖHM PHARMA), as well as 20 g of mixed acid triglycerides fractionated C8 - C10 coconut fatty acids (Miglyol 812 from Dynamit Nobel), applied to a protective layer, on which on one side a layer of aluminum was applied by a vacuum process, and on which an adhesive was applied on both sides, and then the solvent was evaporated at 50 to 80ºC. A layer of about 440 g/m2 was obtained. Round pieces with a diameter of 51 mm were cut from the adhesive layer obtained in this way, the edges of which were processed, and one circular piece of non-woven material was placed on each of them (a fibrous mixture of viscose staple fibers and cotton 70:30 with a basis weight of 40g/m2 - PARETEX II/80 from LOHMANN GMBH & CO KG) with a diameter of 20 mm. Nicotine was applied to them as an active substance in solution (140 g of nicotine in 100 g of some acrylic resin from dimethylaminoethyl methacrylate and neutral methacrylates (EUDRAGIT E 100 from RÖHM PHARMA) in 46 mg can/blank. The cuttings produced in this way are immediately covered with a support layer that does not allows nicotine, which is a 15 µm thick layer on one side of which a layer of aluminum is applied by a vacuum process, and which has a layer of about 110 g/m2 of glue and is hermetically sealed in a rectangular hermetic bag made of suitable packaging material.
U ovom slučaju netkani tekstilni sloj služi kao noseći sloj i potpomaže uniformnu raspodjelu nikotina kao inertno punilo, kako je ranije definirano. In this case, the non-woven textile layer serves as a carrier layer and supports the uniform distribution of nicotine as an inert filler, as defined earlier.
Zahvaljujući činjenici da se, prema izumu, otopina aktivne tvari može brzo nanijeti na jedan sloj matrice, a zatim se pokriva pokrivnim slojem, koji ne propušta aktivnu tvar, moguće je, po prvi put, da se na zadovoljavajući način dobiju dobro dozirani nikotinski flasteri. Thanks to the fact that, according to the invention, the solution of the active substance can be quickly applied to one layer of the matrix, and then covered with a cover layer, which does not let the active substance through, it is possible, for the first time, to obtain well-dosed nicotine patches in a satisfactory manner.
Ispitivanje ispuštanja nikotina (in vitro) Nicotine release test (in vitro)
Nikotinski flaster, proizveden Primjeru 2, nakon skidanja zaštitnog sloja potapa se u 80 ml izotonične otopine na 37°C a ispuštena količina nikotina se određuje tekućom kromatografijom poslije unaprijed određenih vremenskih intervala. Volumen medija u kojem se vrši ispuštanje izabrana je tako da su tijekom cijelog perioda ispitivanja ostvareni uvjeti potapanja. Dobiveni su slijedeći rezultati: The nicotine patch, produced according to Example 2, after removing the protective layer, is immersed in 80 ml of isotonic solution at 37°C, and the released amount of nicotine is determined by liquid chromatography after predetermined time intervals. The volume of the medium in which the discharge is carried out was chosen so that during the entire test period the immersion conditions were achieved. The following results were obtained:
[image] [image]
Podrazumijeva se da izum nije ograničen na nikotinske flastere i na njihovu proizvodnju sa konstrukcijom za koju se traži zaštita, već se i druge tvari, koje su kao preporučljive tvari spomenute u opisu, mogu davati pomoću ovog novog terapeutskog sustava. It is understood that the invention is not limited to nicotine patches and their production with the construction for which protection is sought, but also other substances, which are recommended substances mentioned in the description, can be administered by means of this new therapeutic system.
Navod o najboljem, prijavitelju poznatom, načinu za gospodarsku upotrebu prijavljenog izuma. Statement about the best, known to the applicant, method for the economic use of the reported invention.
Kod terapeutskog sustava prema izumu, debljina cijelog sustava kreće se između 285 i 1550..m. Ljepljivi sloj, koji dolazi uz kožu, izrađuje se, na primjer, od stirena, silkonske gume, poli(mata)akrilata, ili akrilnih kopolimera. Debljine je od oko 10 do 150 µm. Spremnik, čija je debljina od 200 do 1330 µm, obično se sastoji od mješavine šatapel vlakana i pamuka (7:3,5:5, itd.). Osloni sloj je debljine 15 do 400 µm, a izrađuje se, na primjer, od polivinilpirolidina, poliviniletera, butil gume i sl. Osloni sloj se često prevlači tankim slojem aluminija. With the therapeutic system according to the invention, the thickness of the entire system is between 285 and 1550 m. The adhesive layer, which comes next to the skin, is made, for example, of styrene, silicone rubber, poly(mat)acrylate, or acrylic copolymers. It is about 10 to 150 µm thick. The container, whose thickness is from 200 to 1330 µm, usually consists of a mixture of chatapelle fibers and cotton (7:3,5:5, etc.). The support layer has a thickness of 15 to 400 µm, and is made, for example, of polyvinylpyrrolidine, polyvinyl ether, butyl rubber, etc. The support layer is often coated with a thin layer of aluminum.
Claims (14)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19863629304 DE3629304A1 (en) | 1986-08-28 | 1986-08-28 | TRANSDERMAL THERAPEUTIC SYSTEM, ITS USE AND METHOD FOR THE PRODUCTION THEREOF |
| YU158787A YU48299B (en) | 1986-08-28 | 1987-08-26 | PROCEDURE FOR THE PRODUCTION OF A RANSDERMAL THERAPEUTIC SYSTEM FOR Bringing ACTIVE MATERIAL TO THE SKIN |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP920853A2 true HRP920853A2 (en) | 1995-10-31 |
| HRP920853B1 HRP920853B1 (en) | 1999-04-30 |
Family
ID=25846980
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP-1587/87A HRP920853B1 (en) | 1986-08-28 | 1992-10-02 | Transdermal therapeutic system releasing active substance |
Country Status (2)
| Country | Link |
|---|---|
| HR (1) | HRP920853B1 (en) |
| SI (1) | SI8711587A (en) |
-
1987
- 1987-08-26 SI SI8711587A patent/SI8711587A/en unknown
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1992
- 1992-10-02 HR HRP-1587/87A patent/HRP920853B1/en not_active IP Right Cessation
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| Publication number | Publication date |
|---|---|
| SI8711587A (en) | 1996-10-31 |
| HRP920853B1 (en) | 1999-04-30 |
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