SI8711587A - Transdermal theraupetic system for applaying therapeutical substances throught skin. - Google Patents

Transdermal theraupetic system for applaying therapeutical substances throught skin. Download PDF

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SI8711587A
SI8711587A SI8711587A SI8711587A SI8711587A SI 8711587 A SI8711587 A SI 8711587A SI 8711587 A SI8711587 A SI 8711587A SI 8711587 A SI8711587 A SI 8711587A SI 8711587 A SI8711587 A SI 8711587A
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active substance
therapeutic system
layer
skin
container
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SI8711587A
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Slovenian (sl)
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Annegrete Hoffmann
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Lohmann Therapie Syst Lts
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Abstract

Izum se nanaša na sistem vnašanja aktivne snovi na kožo, s hrbtno plastjo na odmiku od kože, z najmanj enim vsebnikom za aktivno snov, napravo za porazdelitev aktivne snovi, ki je povezana z vsebnikom za aktivno snov, napravo za uravnavanje sproščanja aktivne snovi, ki uravnava tok aktivne snovi skozi sistem, in z napravo za pritrditev z lepljenjem na dotik za pritrditev sistema na kožo, pri čemer napravo za porazdelitev aktivne snovi in napravo za uravnavanje sproščanja aktivne snovi tvori rezervoarna matrica (12), v kateri je eden ali več ločenih vsebnikov (14) aktivne snovi razporejenih na določen način v medsebojnem prostorskem razmerju in v katerih je večja koncentracija aktivne snovi kot v rezervoarni matrici.The invention relates to the system of administration of the active substances on the skin, with the back layer at a distance from the skin, z at least one active substance container, device for distribution of the active substance bound to the container for the active substance, the regulating device release of the active substance that regulates the flow of the active substance substances through the system, and with an attachment device with touch gluing to secure the system to the skin, at providing a device for distributing the active substance and forms a device for regulating the release of the active substance a reservoir matrix (12) comprising one or more separate containers (14) of the active substance allocated to a certain way in their spatial relationship and in which the concentration of the active substance is greater than in reservoir matrices.

Description

Terapevtski sistem vnašanja aktivnih snovi na kožoTherapeutic system for the introduction of active substances into the skin

Področje tehnike, na katero spada izumFIELD OF THE INVENTION

Izum spada na področje naprav za vnos aktivnih sredstev v telo ali za nanos na telo, posebno pa se nanaša na vnašanje zdravil z difuzijo preko kože. Oznaka po Mednarodni razvrstitvi patentov: A 61M 37/00.The invention relates to the field of devices for the introduction of active agents into the body or for application to the body, and in particular relates to the introduction of drugs by diffusion through the skin. International Patent Classification Code: A 61M 37/00.

Tehnični problemA technical problem

Z izumom se rešuje problem, kako narediti terapevtski sistem z vsebnikom za aktivno snov za izdajanje aktivne snovi skozi kožo, ki bo omogočal uporabo tekočih in hlapnih aktivnih snovi.The invention solves the problem of how to make a therapeutic system with an active substance container for dispensing the active substance through the skin, which will allow the use of liquid and volatile active substances.

Stanje tehnikeThe state of the art

Terapevtski sistemi za dajanje zdravil preko kože dovedejo eno ali več aktivnih snovi z določeno hitrostjo in na neprekinjen način tekom določenega časa v dani točki nanašanja na koži. Ti sistemi so terapevtski precizni instrumenti, ki zagotavljajo kontinuirno sproščanje aktivne snovi.Therapeutic drug delivery systems deliver one or more active substances at a fixed rate and continuously over a period of time at a given point of application to the skin. These systems are therapeutic precision instruments that ensure the continuous release of the active substance.

Taki terapevtski sistemi imajo lahko tako namenski kot tudi sistemski vpliv, veliko število aktivnih snovi, ki se lahko dajejo na tak način, in njihove različne kemijske, fizikalne in farmakološke značilnosti pa postavljajo vedno znova nove zahteve izdelavi takih sistemov.Such therapeutic systems can have both intentional and systemic effects, and the large number of active substances that can be administered in this way, and their various chemical, physical and pharmacological characteristics, are constantly placing new demands on the manufacture of such systems.

Običajno imajo taki sistemi za vnašanje snovi preko kože vsaj en vsebnik za aktivno snov, v katerem se aktivna snov nahaja v trdni obliki, tekoči obliki ali obliki disperzije molekul, in lepilno plast, preko katere je sistem spojen s kožo in preko katere poteka potovanje aktivne snovi, regulacijsko opno in zaščitne/pokrivne plasti, ki so v bistvu neprepustne za aktivno snov.Typically, such skin injection systems have at least one active substance container in which the active substance is in solid, liquid or molecular dispersion, and an adhesive layer through which the system is coupled to the skin and through which the active substance travels substances, regulatory membrane and protective / covering layers that are substantially impermeable to the active substance.

Znane sisteme je težko narediti in njihova zgradba je zamotana. Eden od problemov običajnih sistemov je zvezan z vprašanjem, ali so le-ti v stanju obdelovati lahko hlapne aktivne snovi, kajti uparjanje aktivne snovi je med proizvodnjo težko kontrolirati.Known systems are difficult to make and their structure is intricate. One of the problems of conventional systems is the question of whether they are able to process volatile active substances, since evaporation of the active substance is difficult to control during production.

Toplotno občutljive aktivne snovi se da v sistemu v primeru matric ali terapevtskih sistemov, ki jih je treba obdelati s toploto in se izdelujejo s stopnjami, ki vključujejo toplotno obdelavo, uporabljati samo v omejenem obsegu.Thermally sensitive active substances may only be used in the system in the case of matrices or therapeutic systems that need to be heat treated and manufactured at rates involving heat treatment, only to a limited extent.

Poskušali so že, da bi čisto aktivno snov v obliki drobnih zrn vnesli v dotikalni lepilni polimer, tako da se na drobno zdrobljena, drobnozrnata aktivna snov sčasoma stopi kot zalogovni kristali v plasti lepilne matrice (DE-OS 35 00 508). Ta postopek ni primeren za hlapne in toplotno občutljive aktivne snovi, saj vsebuje stopnje toplotne obdelave.Attempts have already been made to incorporate a pure active substance in the form of fine grains into a touching adhesive polymer, so that the finely divided, fine-grained active substance eventually melts as storage crystals in the adhesive matrix layer (DE-OS 35 00 508). This process is not suitable for volatile and heat-sensitive active substances as it contains stages of heat treatment.

Drug poskus z namenom povečati zmogljivost takih terapevtskih sistemov obsega zalitje v plast kontaktnega lepila takega sistema vsebnikov z aktivno snovjo v obliki mikrokapsul, ki so obdane z regulacijsko opno (glej patenta US 3 598 123 in 3 731 683). Izdelava takih, z regulacijsko opno omejenih mikrokapsul je skrajno zamotana in draga in odpove pri mnogih aktivnih snoveh. Mešanje mikrokapsul, vsebujočih aktivno snov, pod materialom rezervoarja predstavlja nadaljnjo težavno stopnjo postopka, v kateri se male kapsule zlahka lahko poškodujejo ali uničijo, kar lahko vodi k nezadovoljivi stalnosti vsebnosti aktivne snovi v končnem terapevtskem sistemu. Postopek po patentu US 3 598 123 je težko izvedljiv s tekočimi aktivnimi snovmi, posebno če gre za hitro hlapno obliko tekoče snovi.Another attempt to increase the capacity of such therapeutic systems involves pouring into the contact adhesive layer of such a system of active substance containers in the form of microcapsules, which are surrounded by a regulatory membrane (see US Pat. Nos. 3 598 123 and 3 731 683). The manufacture of such microcapsules, which are regulated by the control membrane, is extremely complicated and expensive and fails in many active substances. Mixing microcapsules containing the active substance under the reservoir material represents a further difficult step in the process in which small capsules can be easily damaged or destroyed, which can lead to unsatisfactory constant of the active substance content in the final therapeutic system. The process of US Pat. No. 3,598,123 is difficult to carry out with liquid active substances, especially in the case of a fast volatile liquid form.

Patent DE 34 24 837 razkriva obliž z vsebnikom, ki je uporabljiv za tekoča gradiva in ima pokrivni film, tekočo aktivno snov v navzven štrlečem območju pokrivnega filma ter regulacijsko opno, ki pokriva aktivno snov in je prepustna za slednjo. Med pokrivnim filmom in regulacijsko opno je predvidena naprava za porazdeljevanje aktivne snovi, namreč netkana tkanina, ki enakomerno porazdeljuje aktivno snov v obliki tekočine na regulacijski opni in je učinkovita na velikem površinskem polju. V primeru obliža z vsebnikom po patentu DE 34 24 837 sta pokrivni film in regulacijska membrana medsebojno zvarjena v njunih zunanjih območjih, da se prepreči iztekanje tekoče aktivne snovi.Patent DE 34 24 837 discloses a patch with a container that is usable for liquid materials and has a cover film, a liquid active substance in the outwardly projecting region of the cover film, and a control membrane that covers the active substance and is permeable to the latter. An active substance distribution device is provided between the covering film and the control membrane, namely a non-woven fabric which distributes the active substance uniformly in the form of a liquid on the control membrane and is effective over a large surface area. In the case of the patch container according to DE 34 24 837, the cover film and the regulating membrane are welded to one another in their outer regions to prevent the leakage of the liquid active substance.

Znani obliž z vsebnikom pa je neugoden, saj tekočina v njem prosto teče in lahko zlahka uide, če je lepilo ali so zvarni robovi poškodovani, tudi pa teija drago regulacijsko opno, ki mora biti tam poleg naprave za porazdeljevanje aktivne snovi, da se kinetično uravnava izdajanje aktivne snovi.The known container patch, however, is disadvantageous as the fluid inside it flows freely and can easily escape if the adhesive or welding edges are damaged, as well as the expensive control membrane that must be there next to the active substance distribution device to kinetically regulate release of the active substance.

Zato je zdaj problem, na katerem temelji predloženi izum, ustvariti nov terapevtski sistem z vsebnikom za aktivno snov za dajanje aktivne snovi, katerega izdelava bo cenejša in ki bo zanesljivejši od sistemov iz stanja tehnike ter bo primeren tudi za obdelavo hlapnih in/ali toplotno nestabilnih sestavin.Therefore, the problem underlying the present invention is to create a new therapeutic system with an active substance container for the manufacture of the active substance, the manufacture of which will be cheaper and more reliable than the prior art systems and will also be suitable for the treatment of volatile and / or heat-unstable ingredients.

Opis rešitve tehničnega problemaDescription of solution to a technical problem

Po izumu je ta problem rešen s terapevtskim sistemom, ki je značilen po tem, da napravo za porazdeljevanje aktivne snovi in napravo za uravnavanje sproščanja aktivne snovi tvori rezervoarna matrica, v kateri je eden ali več ločenih vsebnikov aktivne snovi razporejenih na določen način v medsebojnem prostorskem razmerju in v katerih je večja koncentracija aktivne snovi kot v rezervoami matrici. Med izdelavo terapevtskega sistema je rezervoarna matrica lahko brez aktivnih snovi; s temi se obogati v določenem časovnem obdobju, t.j. med skladiščenjem sistema, v primeru zelo hlapnih snovi pa med izdelavo sistema. Na dlani je prednost izuma, da zdaj lahko aktivne snovi, ki so temperaturno neobstojne in/ali hlapne, lahko vnašamo med izdelavo v transdermalne sisteme v obliki vsebnikov in brez kakršnih koli toplotnih obremenitev. Zdaj ni potrebe po stopnjah, kot je mešanje gradiva rezervoarne matrice z aktivno snovjo, razen tega pa omenjeno gradivo med skladiščenjem terapevtskega sistema zasitimo z aktivno snovjo pri sobni temperaturi. Ker ni izdelovalne stopnje za matrico, zasičeno z aktivno snovjo, je izdelava poenostavljena.According to the invention, this problem is solved by a therapeutic system, characterized in that the device for distributing the active substance and the device for regulating the release of the active substance are formed by a reservoir matrix, in which one or more separate containers of the active substance are arranged in a certain way in space with each other. ratio and in which the concentration of the active substance is higher than in the matrix reservoirs. During the construction of the therapeutic system, the reservoir matrix may be free of active substances; these are enriched over a period of time, i.e. during system storage, and in the case of highly volatile substances during system construction. In the palm of the hand, it is an advantage of the invention that now active substances which are temperature and / or volatile can be introduced during production into transdermal systems in the form of containers and without any heat load. There is now no need for steps such as mixing the reservoir matrix material with the active substance, except that the said material is saturated with the active substance at room temperature during storage of the therapeutic system. Since there is no manufacturing stage for the matrix saturated with the active substance, manufacturing is simplified.

Ker je tu uporabljena rezervoarna matrica s svojo lastno regulacijsko funkcijo, ki je določena med drugim s hitrostjo potovanja gradiva skozi matrico, ni potrebe po regulacijski opni, ki v proizvodnji terja dodatne izdelovalne stopnje in gradivo za membrano. Vsebnik lahko sestoji iz čiste aktivne snovi, ki je lahko trdna ali tekoča, pa tudi iz inertnih polnil. Beseda inerten je tu razumljena v pomenu, da aktivna snov in polnilo druga z drugim ne reagirata. Inertno polnilo je tudi lahko snov, ki fiziološko učinkuje, kot npr. dimetilsulfooksid (DMSO) ali podobno, ki denimo povečuje prepustnost kože. Polnila so tudi lahko narejena iz nosilnih gradiv, ki naredijo vsebnik aktivne snovi neobčutljivega za uporabo tlaka in natega, kot tudi iz nosilcev na splošno.Since a reservoir matrix is used here with its own regulating function, which is determined, inter alia, by the speed of material travel through the matrix, there is no need for a regulating membrane, which requires additional manufacturing steps and membrane material in production. The container may consist of a pure active substance, which may be solid or liquid, as well as inert fillers. The word inert is understood here to mean that the active substance and the filler do not react with each other. An inert filler may also be a physiologically active substance, such as e.g. dimethylsulfoxide (DMSO) or the like, for example increasing skin permeability. Fillers may also be made of carrier materials that render the container of the active substance insensitive to pressure and strain, as well as of the carriers in general.

Uporabimo lahko aktivne snovi, ki se uporabijo na transdermalni način in katerih tipični primeri so navedeni spodaj.We can use transdermal active agents, typical examples of which are given below.

NikotinNicotine

Kortikosteroidi: hidrokortizon, prednizolon, beklometazon-proprionat, flumetazon, triamkinolon, tramkinolon-acetonid, fluokinolon, fluokinolin-acetonid, fluokinolonacetonid acetat, klobetazol-proprionat itd.Corticosteroids: hydrocortisone, prednisolone, beclomethasone-propionate, flumetazone, triamquinolone, tramquinolone-acetonide, fluoquinolone, fluoquinoline-acetonide, fluoquinolone-acetonide acetate, clobetazole-propionate, etc.

Analgetiki, protivnetna sredstva: acetaminofen, mefenaminska kislina, flufenaminska kilsina, diciklofenak, diciklofenak-natrij-alklofenak, oksifenbutazon, fenilbutazon, ibuprofen, flurbiprofen, salicilna kislina, 1-mentol, kafra, sulindak-tolmetin-natrij, naproksen, fenbufen itd.Analgesics, anti-inflammatory agents: acetaminophen, mefenamic acid, flufenamic acid, dicyclofenac, dicyclofenac-sodium-alklofenac, oxyphenebutazone, phenylbutazone, ibuprofen, flurbiprofen, salicylic acid, 1-menthol, tolphacin, caffeine, caffeine

Hipnotično aktivni sedativi: fenobarbital, amobarbital, ciklobarbital, triazolam, nitrazepam, lorazepam, haloperidol itd.Hypnotically active sedatives: phenobarbital, amobarbital, cyclobarbital, triazolam, nitrazepam, lorazepam, haloperidol, etc.

Pomirjevala: flufenazin, tioridazin, lorazepam, flunitrazepam, kloropromazin itd.Sedatives: flufenazine, thioridazine, lorazepam, flunitrazepam, chloropromazine, etc.

Antihipertenziki: pindolol, bufralol, indenolol, nidapin, lofeksidin, nipradinol, bukumolol itd.Antihypertensives: pindolol, bufralol, indenolol, nidapine, lofexidine, nipradinol, bucumolol, etc.

Antihipertenzivno delujoči diuretiki: hidrotiazid, bendroflumentiazid, ciklobentiazid itd.Antihypertensive-acting diuretics: hydrothiazide, bendroflumentiazide, cyclobenthiazide, etc.

Antibiotiki: penicilin, tetraciklin, oksitetraciklin, fradiomicin sulfat, eritromicin, kloramfenikol itd.Antibiotics: penicillin, tetracycline, oxytetracycline, fradiomycin sulfate, erythromycin, chloramphenicol, etc.

Anestetiki: lidokain, benzokain, etilaminobenzoat itd.Anesthetics: lidocaine, benzocaine, ethylaminobenzoate, etc.

Antimikrobiološka sredstva: benzalkonijev klorid, nitrofurazon, nistatin, acetosulfamin, klotrimazol itd.Antimicrobial agents: benzalkonium chloride, nitrofurazone, nystatin, acetosulfamine, clotrimazole, etc.

Protiglivična sredstva: pentamicin, amfotericin B, pirolnitrin, klotrimazol itd.Antifungal agents: pentamycin, amphotericin B, pyrrolnitrin, clotrimazole, etc.

Vitamini: vitamin A, ergokalciferol, klolkalciferol, oktotiamin, riboflavin butirat itd.Vitamins: Vitamin A, ergocalciferol, clolcalciferol, octothiamine, riboflavin butyrate, etc.

Antiepileptiki: nitrazepam, meprobamat, klonazepam itd.Antiepileptic drugs: nitrazepam, meprobamate, clonazepam, etc.

Koronarni vazodilatatorji: dipiridamol, eritriol tetranitrat, pentaeritriol tetranitrat, propatilnitrat itd.Coronary vasodilators: dipyridamole, erythriol tetranitrate, pentaerythriol tetranitrate, propatyl nitrate, etc.

Antihistaminiki: difenil hidromin hidroklorid, klorfeniramin, difenilimidazol itd.Antihistamines: diphenyl hydromine hydrochloride, chlorpheniramine, diphenylimidazole, etc.

Sredstva proti kašlju: dertrometorfan (hidrobromid), terbutalin (sulfat), efedrin (hidroklorid), salbutanol (sulfat), izoproterenol (sulfat, hidroklorid) itd.Cough suppressants: dertromethorphan (hydrobromide), terbutaline (sulfate), ephedrine (hydrochloride), salbutanol (sulfate), isoproterenol (sulfate, hydrochloride), etc.

Spolni hormoni: progesteron itd.Sex hormones: progesterone, etc.

Timoleptiki: doksepin itd.Thymoleptics: doxepin, etc.

Nadaljnja zdravila/farmacevtiki: 5-fluorouracil, fentanil, dezmopresin, domperdon, skopolamin (hidrobromid), peptid itd.Further medicines / pharmaceuticals: 5-fluorouracil, fentanyl, desmopressin, domperdon, scopolamine (hydrobromide), peptide, etc.

Očitno je, da ta seznam ni dokončen.Obviously, this list is incomplete.

Rezervoama matrica za aktivno snov je smotrno lahko zgrajena v plasteh, pri čemer so plasti lahko enake ali različne. Rezervoama matrica je lahko kontaktno lepljiva in je lahko npr. gumeno gradivo, kot so blok kopolimeri stirena/izoprena/stirena, silikonski gumi ali umetne smole, kot so poli(met)akrilat, poliuretan, polivinileter, poliester itd. - spisek primernih gradiv za matrico je razviden npr. iz DE-OS 35 00 508, na katerega se tu sklicujemo. Lahko je smotrno, če je rezervoama matrica dotikalno lepljiva, saj s tem v sistemu odpade potreba po ločeni napravi za fiksiranje z dotikalnim lepljenjem. Uporaba take matrice z dotikalno lepljivostjo je odvisna med drugim od združljivosti materiala matrice z aktivno snovjo. Gradiva za matrice z dotikalnim lepljenjem so znana.The reservoir matrix for the active substance may conveniently be constructed in layers, with the layers being the same or different. The reservoir matrix can be contact sticky and can be e.g. rubber material such as styrene / isoprene / styrene block copolymers, silicone rubbers or synthetic resins such as poly (meth) acrylate, polyurethane, polyvinyl ether, polyester, etc. - a list of suitable materials for the matrix can be seen e.g. from DE-OS 35 00 508 referred to herein. It can be useful if the reservoir matrix is touch-sticky, as this eliminates the need for a separate touch-bonded fixing device in the system. The use of such a touch-sensitive matrix depends, inter alia, on the compatibility of the matrix material with the active substance. Materials for touch-bonded stencils are known.

Prednostni nekontaktini adhezivni matrični materiali so polimeri, ki obsegajo poli(met)akrilat, polivinil pirolidon, etilcelulozo, hidroksipropilcelulozo, ftalat hidroksipropil metilceluloze, polivinil alkohol ali njihove kopolimere z vinillavratom ali maleinsko kislino, vinilacetat ali njegove kopolimere z vinillavratom ali maleinsko kislino, polivinileter, butilgumi ali polikaprolaktam.Preferred non-contact adhesive matrix materials are polymers comprising poly (meth) acrylate, polyvinyl pyrrolidone, ethylcellulose, hydroxypropylcellulose, phthalate hydroxypropyl methylcellulose, polyvinyl alcohol or their copolymers with vinyl laurate, or maleic vinyl or vinyl butyrylate, or vinyl ester, butylgum or polycaprolactam.

Vsebnik, vsebnika ali vsebnike za aktivno snov lahko vložimo naprimer med plast, ki jo tvori rezervoarna matrica na hrbtni strani, in plast, ki jo tvori rezervoama matrica na strani kože, pri čemer razmerje debelin X, Y plasti, ki ju tvori rezervoama matrica, prednostno znaša med okoli Χ/Υ = 1/1 do 1/20, v posebno prednostni izvedbi pa 1/1 do 1/5.The container, containers or containers for the active substance can be inserted, for example, between a layer formed by a reservoir matrix on the back side and a layer formed by a reservoir matrix on the skin side, the ratio of the thicknesses X, Y of the layer formed by the reservoir matrix, preferably between about Χ / Υ = 1/1 to 1/20, and in a particularly preferred embodiment, 1/1 to 1/5.

V drugih primerih je lahko primerno, če je rezervoarna matrica ali če sta plasti rezervoame matrice, iz katerih je omenjena matrica narejena, vsaj na eni strani opremljeni z dotikalno lepljivima prevlekama.In other cases, it may be appropriate if the reservoir matrix or the reservoir matrix layers from which said matrix is made are provided with touching adhesive coatings on at least one side.

Po nadaljnji koristni zasnovi sistema po izumu je vsebnik za aktivno snov lahko razporejen med rezervoarno matrico in podporno plastjo, ki je primerna npr. za trdne aktivne snovi.After further useful design of the system according to the invention, the container for the active substance may be arranged between a reservoir matrix and a support layer that is suitable e.g. for solids.

V prednostnem izvedbenem primeru izuma fiksirno napravo lahko tvorijo lepljivi deli, ki so zaliti v rezervoarno matrico, kot je npr. po vsem obodu potekajoč lepljiv rob ali lepljive točke.In a preferred embodiment of the invention, the fixing device may be formed by adhesive parts that are poured into a reservoir matrix, such as e.g. sticky edge or sticky points running around the perimeter.

Na običajen način je mogoče narediti odstranljivo zaščitno plast za površine terapevtskega sistema, obrnjene h koži.In the usual way, a removable protective layer can be made for the surfaces of the therapeutic system facing the skin.

Seštevek aktivne snovi v vsebniku in rezervoarni matrici seže smotrno do 20-kratnika terapevtsko potrebne količine aktivne snovi.The sum of the active substance in the container and in the reservoir matrix reaches up to 20 times the therapeutically necessary amount of the active substance.

Posebno prednosten postopek izdelave takih sistemov obsega rezervoarno matrico, narejeno iz dveh plasti rezervoarne matrice, ki sta lahko enaki ali različni, med kateri je vložen vsebnik aktivne snovi. Plasti rezervoarne matrice sta lahko medsebojno spojeni z uporabo pritiska in/ali toplote. Vsebnik tudi lahko vložimo v rezervoarno matrico z uporabo pritiska, npr. z injiciranjem vnaprej določene količine ali vtisnjenjem telesa aktivne snovi v mehko plast matrice.A particularly preferred method of manufacturing such systems comprises a reservoir matrix made of two reservoir matrix layers, which may be the same or different, between which an active substance container is inserted. The reservoir matrix layers may be interconnected using pressure and / or heat. The container can also be inserted into the reservoir matrix using pressure, e.g. by injecting a predetermined amount or by injecting the body of the active substance into the soft layer of the matrix.

Nadaljnji prednostni postopek je oblikovanje vsaj dela terapevtskega sistema z natrosenjem delcev.A further preferred process is to design at least part of the therapeutic system by particle spraying.

Tudi je mogoče narediti večplastno matrico aktivne snovi. Pokrivno plast in plast rezervoarne matrice tudi lahko združimo s pomočjo toplote ali tlaka. Plast, plasti ali plasti rezervoarne matrice lahko vsaj delno naredimo iz tekočih gradiv, npr. iz disperzije, taline ali raztopin.It is also possible to make a multilayer matrix of the active substance. The coating layer and the reservoir matrix layer can also be combined by heat or pressure. The layer, layers or layers of the reservoir matrix can be made at least in part from liquid materials, e.g. from dispersion, melt or solutions.

Terapevtski sistem po izumu je posebno primeren za lokalno ali sistemsko transdermalno uporabo aktivnih snovi v človeški medicini ali veterini, lahko pa ga uporabimo tudi v kozmetiki.The therapeutic system of the invention is particularly suitable for topical or systemic transdermal use of the active substances in human medicine or veterinary medicine, but can also be used in cosmetics.

Izum je v nadaljnjem bolj podrobno opisan na osnovi neomejujočih izvedbenih primerov terapevtskega sistema po izumu in pripetih dvodimenzijskih skic, v katerih kaže sl. 1 prednosten izvedben primer terapevtskega sistema po izumu, v prerezu, sl. 2 nadaljnji prednosten izvedben primer terapevtskega sistema, pri katerem je vsebnik aktivne snovi razporejen med hrbtno plastjo in rezervoarno matrico, v prerezu, sl. 3 nadaljnji prednosten izvedben primer terapevtskega sistema, pri katerem je vsebnik aktivne snovi zalit med plasti matrice, v prerezu, sl. 4 terapevtski sistem po izumu z vsebniki z raznimi aktivnimi snovmi, razporejenimi v eni ravnini, v prerezu, sl. 5 terapevtski sistem po izumu z vsebnikom za aktivne snovi v obliki plasti, v prerezu, sl. 6 blagu podoben polizdelek po izumu, v prerezu.The invention is further described in more detail based on non-limiting embodiments of the therapeutic system of the invention and the attached two-dimensional sketches in which FIG. 1 is a preferred embodiment of the therapeutic system of the invention, in cross section, FIG. 2 is a further preferred embodiment of a therapeutic system in which the container of the active substance is arranged between the back layer and the reservoir matrix, in cross section, FIG. 3 is a further preferred embodiment of a therapeutic system in which the container of the active substance is sandwiched between the layers of the matrix, in cross section, FIG. 4 is a cross-sectional view of a therapeutic system of the invention with containers with various active substances arranged in a single plane; 5 is a cross-sectional view of a therapeutic system of the invention with a container for active substances in the form of a layer; 6 is a sectional view of a slightly similar semi-finished product of the invention.

Skica sl. 1 je prerez terapevtskega sistema po izumu, ki je s pritrdilno napravo 16, npr. porozno dotikalno lepljivo plastjo ali podobno, pritrjen na kožo 18. Na pritrdilni napravi 16 je razporejena rezervoarna matrica 12, ki je v času izdelave prednostno brez aktivne snovi (zasičenje z aktivno snovjo pride na vrsto pri skladiščenju). V rezervoarno matrico je zalit vsebnik 14, ki je tu predstavljen kot trdna aktivna snov, ki je raztopljena v gradivu rezervoarne matrice in se koži 18 dovaja preko pritrdilne naprave 16. Terapevtski sistem je navzven zaključen s hrbtno plastjo, kije za aktivno snov in prednostno tudi za vlago neprepustna in ima hkrati oporno funkcijo za sistem.Sketch of FIG. 1 is a cross-sectional view of a therapeutic system of the invention which, by means of an attachment device 16, e.g. a porous touching adhesive layer or the like attached to the skin 18. A reservoir die 12 is arranged on the attachment 16, which is preferably devoid of the active substance at the time of manufacture (saturation with the active substance occurs during storage). A container 14 is poured into the reservoir matrix, which is presented here as a solid active substance, which is dissolved in the reservoir matrix material and is fed to the skin 18 via the attachment device 16. The therapeutic system is externally terminated with a back layer, which is active and preferably also moisture-proof and at the same time has a supportive function for the system.

Sl. 2 kaže drugo različico sistema po izumu, pri kateri je vsebnik 14 aktivne snovi razporejen na plasti 12 rezervoarne matrice in je pokrit s hrbtno plastjo 10. Pritrdilna naprava na tej skici ni predstavljena, lahko pa je npr. dotikalno lepljiv pas ali rob ali podobno, ki površino terapevtskega sistema, predvideno za stik s kožo, združi s kožoFIG. 2 shows a second embodiment of the system according to the invention, in which the container 14 of the active substance is arranged on the layer 12 of the reservoir matrix and is covered by the back layer 10. The attachment device is not shown in this drawing, but may e.g. a touching adhesive band or edge or the like that integrates the surface of the therapeutic system intended for skin contact with the skin

18. Smotrnost tega je, da je izdelava skrajno enostavna. Treba je samo nanesti jasno določene količine aktivne snovi, bodisi v obliki trdnine ali viskozne tekočine, v vnaprej izdelano matrično plast in zapečatiti ali zakriti le-to s hrbtno plastjo 10.18. The advantage of this is that manufacturing is extremely easy. It is only necessary to apply clearly defined amounts of the active substance, whether in the form of a solid or a viscous liquid, to a pre-fabricated matrix layer and to seal or cover it with a backing layer 10.

Postopek izdelave sistema po sl. 2 je cenejši od postopka izdelave sistema po sl. 1. Toda lahko ga uporabimo, samo če je aktivna snov, npr. zaradi hlapnosti aktivne snovi ali zaradi potrebne velike stične površine med aktivno snovjo in rezervoamo matrico, obdana na vseh straneh z matrico. Smotrn je npr. za snovi, ki se zlahka topijo v rezervoarju aktivne snovi in brez težav difundirajo vanj, tako da ni potrebe po veliki dotikalni površini med aktivno snovjo in rezervoamo matrico aktivne snovi.The process of manufacturing the system of FIG. 2 is less expensive than the system manufacturing process of FIG. 1. But it can only be used if it is an active substance, e.g. due to the volatility of the active substance or due to the required large contact surface between the active substance and the matrix reservoir surrounded on all sides by the matrix. It is appropriate, for example. for substances that readily dissolve in the reservoir of the active substance and diffuse easily into it, so that there is no need for a large contact surface between the active substance and the reservoir matrix of the active substance.

Sl. 3 kaže nadaljnjo prednostno izvedbo, pri kateri je terapevtski sistem po izumu pritrjen na kožo 18 s pomočjo lepilnih delcev ali delov, zalitih na strani kože v material rezervoarne matrice aktivne snovi. Plast 12 rezervoarja aktivne snovi tu obsega zgornjo plast X in spodnjo plast Y, med kateri je vložena aktivna snov, ki je tu npr. v tekoči obliki. Obstoj dveh plasti X, Y rezervoarne matrice je smotrn, če sistem izdelujemo tako, da najprej pripravimo spodnjo rezervoamo plast aktivne snovi, po potrebi z že nanjo nanesenim pokrivnim filmom ali podobno, in zatem v skladu z vnaprej določenim vzorcem rezervoamo plast X aktivne snovi in slednjič na običajen način hrbtno plast ali po potrebi razne lepljive plasti, da je sistem popoln. Tudi pride v poštev, da najprej postavimo drugo na drugo obe rezervoarni plasti X, Y aktivne snovi, nakar med rezervoarni plasti vbrizgnemo vnaprej določeno količino aktivne snovi in s tem ohranimo na minimumu uparjanje aktivne snovi.FIG. 3 shows a further preferred embodiment in which the therapeutic system of the invention is attached to the skin 18 by means of adhesive particles or parts embedded on the skin side into the reservoir matrix material of the active substance. The layer 12 of the active substance reservoir here comprises the upper layer X and the lower layer Y, between which is inserted an active substance, e.g. in liquid form. The existence of two layers X, Y of the reservoir matrix is advantageous if the system is fabricated by first preparing the lower reservoir layer of the active substance, if necessary with a coating film or the like, and then in accordance with a predetermined sample, reserve the layer X of the active substance and the latter in the usual way the back layer or, if necessary, the various adhesive layers to make the system complete. It is also appropriate to first place the two reservoir layers X, Y of the active substance on top of each other, and then inject a predetermined amount of the active substance between the reservoir layers and thus minimize the evaporation of the active substance.

Sl. 4 kaže izvedben primer transdermalnega sistema po izumu z več vsebniki 14 aktivne snovi, razporejenimi v eni ravnini in nameščenimi med plastjo 16 dotikalne lepljivosti in rezervoamo matrico 12, pri čemer plast 16 hkrati fiksira hrbtno plast 10 v transdermalni sistem. Transdermalni sistem se konča z odstranljivo zaščitno plastjoFIG. 4 shows an embodiment of a transdermal system according to the invention with several containers 14 of the active substance arranged in a single plane and placed between the touch adhesive layer 16 and the die 12, with the layer 16 simultaneously fixing the back layer 10 in the transdermal system. The transdermal system ends with a removable protective layer

19.19.

Sl. 5 kaže drugo izvedbo transdermalnega sistema po izumu, pri katerem je hrbtna plast 10 prekrita na eni strani z lepljivo plastjo 16, na kateri se nahaja aktivna snov, po potrebi s polnili, kot so gradiva za olajšanje obdelave aktivne snovi (npr. za lažje tabletiranje) ali nosilci, kot so tkanine in podobno. Na ploskem vsebniku aktivne snovi se nahaja rezervoama matrica, ki je z druge strani prekrita z odstranljivim zaščitnim filmom.FIG. 5 shows another embodiment of the transdermal system of the invention in which the back layer 10 is coated on one side with a sticky layer 16 on which the active substance is placed, with fillers, if necessary, such as materials to facilitate processing of the active substance (e.g., for easier tableting ) or carriers such as fabrics and the like. On the flat container of the active substance there is a reservoir matrix, which on the other hand is covered with a removable protective film.

Skica sl. 6 kaže predizdelek za izdelavo transdermalnega sistema po izumu, kakršnega dobimo po prednostnem postopku izdelave. Vlakninsko zaščitno prekrivno gradivo, kot je denimo voskan papir ali podobno, je prekrito s plastjo Y rezervoarne matrice, ki je tu zgrajena na dotikalno lepljiv način in na kateri so po vnaprej določenem vzorcu razporejena telesa vsebnikov aktivne snovi. Matrična plast Y je prekrita z drugo matrično plastjo X, ki lahko vsebuje npr. gradivo, ki je drugačno od gradiva plasti Y. Druga matrična plast Y se konča s hrbtnim filmom 10. Vzdolž puščic so razporejene delilne ali ločilne linije, po katerih vmesni izdelek razrežemo ali razsekamo, da dobimo transdermalne sisteme po izumu, ki jih nato pripravimo na običajen način.Sketch of FIG. 6 shows a pre-product for the manufacture of a transdermal system according to the invention obtained by the preferred manufacturing process. Fiber-protective overlays, such as wax paper or the like, are covered with a layer Y of the reservoir matrix, which is constructed here in a touchingly adhesive manner and in which the bodies of the active substance containers are arranged according to a predetermined pattern. The matrix layer Y is covered by another matrix layer X, which may contain e.g. material different from the material of layer Y. The second matrix layer Y ends with a back film 10. Along the arrows there are dividing or separating lines along which the intermediate is cut or cut to obtain the transdermal systems of the invention, which are then prepared for the usual way.

Tipične debeline transdermalnih sistemov po izumu v primeru skupne debeline znašajo okoli 123 do 5550 μιη, prednostno 285 do 1550 μτη; debelina hrbtne plasti znaša 8 do 150 μτη, prednostno 15 do 100 μτη; debelina rezervoarja znaša 100 do 5000 μηι, prednostno 200 do 1330 μτη; debelina zaščitne plasti znaša 15 do 400 μτη, prednostno 70 do 150 μτη.Typical thicknesses of the transdermal systems of the invention in the case of total thickness are about 123 to 5550 μιη, preferably 285 to 1550 μτη; the back layer thickness is 8 to 150 μτη, preferably 15 to 100 μτη; the thickness of the tank is 100 to 5000 μηι, preferably 200 to 1330 μτη; the thickness of the protective layer is 15 to 400 μτη, preferably 70 to 150 μτη.

Za posebne potrebe pridejo tržno v poštev tudi polizdelki kot taki, tako da uporabnik sam lahko sisteme loči drugega od drugega, medtem ko polizdelek služi kot zalogovni paket.For special needs, semi-finished products are also commercially available, so that the user can separate the systems from one another while the semi-finished product serves as a stock package.

Prednostni primeri izuma so opisani spodaj.Preferred examples of the invention are described below.

Primer 1Example 1

Izdelava nikotinskega obližaMaking a nicotine patch

Nikotinski obliž po izumu lahko na inventivni način izdelamo, kot sledi.The nicotine patch of the invention can be inventively produced as follows.

Na dotik lepljivo gradivo, vsebujoče 2,0825 kg 40%-ne raztopine samopremre10 žujočega se akrilatnega kopolimera (DUROTAC 280 - 2416 tvrdke National Starch / Chemical B.V.) v mešanici etil acetata, etanola, heksana in metanola, 147 g akrilne smole iz dimetilaminoetilmetakrilata in nevtralnega metakrilata (EUDRAGIT E 100 tvrdke ROHM Pharma) in 20 g mešanega kislinskega triglicerida frakcioniranih Cg Cw kokosovih maščobnih kislin (Miglyol 812 tvrdke Dynamit Nobel), je naneseno na zaščitno plast, na katere eno stran je vakuumsko nanesen aluminij, na obe pa lepilna snov, pri čemer topilo upaijamo pri 50 do 80 °C. Dobimo plast z gramaturo okoli 300 g/m2. Iz tako narejene dotikalno lepljive plasti izsekamo rondele premera 65 mm. Štrleče robove obdelamo, na sredo vsake rondele pa položimo okrogel kos netkane tkanine (vlakenska zmes umetnega prediva/bombaža = 50/50 z gramaturo 80 g/m2 PARATEX 11/80 tvrdke LOHMANN GmbH & Co. KG) premera 40 mm. Nanj nanesemo nikotin kot aktivno snov v raztopini (140 g nikotina v 100 g akrilne smole iz dimetilaminoetilmetakrilata in nevtralnih metakrilatov (EUDRAGIT E 100 tvrdke ROHM Pharma) v 102 mg-skih odmerkih/rondelo. Tako narejene osnove takoj obložimo z za nikotin neprepustno hrbtno plastjo, poliestrskim filmom debeline 15 μτη, na katerega eno stran je z uparjanjem nanesen aluminij, in jih zapečatimo v štirirobo neprodušno vrečo iz primernega embalažnega gradiva.Touch-sticky material containing 2.0825 kg of 40% solution of self-curing 10 acrylic acrylate copolymer (DUROTAC 280 - 2416 hard National Starch / Chemical BV) in a mixture of ethyl acetate, ethanol, hexane and methanol, 147 g of acrylic resin from dimethylaminoethylmethyl methacrylmethylmethyl methacrylmethylacetylmethyl methacrylate. of neutral methacrylate (EUDRAGIT E 100 of ROHM Pharma hard) and 20 g of mixed acid triglyceride of fractionated C g C w of coconut fatty acids (Miglyol 812 of Dynamit Nobel hardcover) is applied to a protective layer on one side of which aluminum is vacuum applied on both sides. adhesive, the solvent being absorbed at 50 to 80 ° C. A layer of about 300 g / m 2 is obtained. 65 mm diameter pruners are cut from the so-called touch-sticky layer. The protruding edges are machined and a round piece of non-woven fabric (fiber yarn / cotton = 50/50 fiber with 80 g / m 2 PARATEX 11/80 hardcover LOHMANN GmbH & Co. KG) 40 mm in diameter is placed in the middle of each round. Nicotine is applied as an active substance in solution (140 g of nicotine in 100 g of acrylic resin made of dimethylaminoethyl methacrylate and neutral methacrylates (EUDRAGIT E 100 hard ROHM Pharma) in 102 mg doses / round. The base so formed is immediately coated with a nicotine impermeable layer , 15 μτη thick polyester film on which aluminum is deposited on one side and sealed in a four-sided airtight sack of suitable packaging material.

V tem primeru netkana tkanina služi kot nosilna plast in za pomoč pri enakomerni porazdelitvi nikotina kot inertno polnilo, kot je bilo povedano zgoraj.In this case, the non-woven fabric serves as a carrier layer and to assist in the even distribution of nicotine as an inert filler, as discussed above.

Ker po izumu lahko raztopino aktivne snovi hitro nanesemo na matrično plast in jo zatem prekrijemo z za aktivno snov neprepustno plastjo, je zdaj prvikrat možno na zadovoljiv način doseči primemo dozirane nikotinske obliže.Since, according to the invention, the solution of the active substance can be quickly applied to the matrix layer and then coated with the active substance-impermeable layer, it is now possible, for the first time, to obtain a satisfactory dosage of nicotine patches.

Preskus sproščanja nikotina (in vitro).Nicotine release test (in vitro).

Nikotinski obliž, narejen po primeru 1, po odstranitvi zaščitne plasti potopimo v 80 ml izotonične raztopine običajne soli pri 37 °C, po vnaprej določenih presledkih pa kromatografsko ugotavljamo količino sproščenega nikotina v tekočini. Prostornina medija za sproščanje je tako izbrana, da so dani pogoji utapljanja v vsem času testiranja. Dobili smo naslednje rezultate:The nicotine patch made according to Example 1, after removal of the protective layer, is immersed in 80 ml of isotonic saline solution at 37 ° C and chromatographically determined the amount of released nicotine in the liquid at predetermined intervals. The volume of the release medium is so selected that drowning conditions are given throughout the test. We obtained the following results:

po 2 urah: 23,90 mg/obliž po 4 urah: 32,34 mg/obliž po 8 urah: 41,50 mg/obliž po 24 urah: 56,54 mg/obližafter 2 hours: 23.90 mg / patch after 4 hours: 32.34 mg / patch after 8 hours: 41.50 mg / patch after 24 hours: 56.54 mg / patch

Primer 2Example 2

Izdelava nikotinskega obližaMaking a nicotine patch

Drug nikotinski obliž po izumu lahko inventivno izdelamo, kot sledi.Another nicotine patch of the invention can be inventively fabricated as follows.

Na dotik lepljivo gradivo (lepilo 1), vsebujoče 1,9758 kg 40%-ne raztopine samopremrežujočega se akrilatnega kopolimera (DUROTAC 280 - 2416 tvrdke Delft National & Chemical B.V.) v mešanici etil acetata, etanola, heptana in metanola, 189,7 g akrilne smole iz dimetilaminoetilmetakrilata in nevtralnega metakrilata (EUDRAGIT E 100 tvrdke ROHM Pharma) in 20 g mešanega kislinskega triglicerida iz frakcioniranih Cg - C10 kokosovih maščobnih kislin (Miglyol 812 tvrdke Dynamit Nobel), smo nanesli na zaščitno plast, na katere eno stran smo vakuumsko nanesli aluminij, na obe pa lepilo, pri čemer smo topilo uparili pri 50 do 80 °C. Dobili smo plast z gramaturo okoli 440 g/m2. Iz tako narejene dotikalno lepljive plasti izsekamo rondele premera 51 mm. Štrleče robove obdelamo, na sredo vsake rondele pa položimo okrogel kos netkane tkanine (vlakenska zmes umetnega prediva/bombaža = 70/30 z gramaturo 40 g/m2 - PARATEX III/40 tvrdke LOHMANN GmbH & Co. KG) premera 42 mm. Nanj nanesemo nikotin kot aktivno snov v raztopini (140 g nikotina v 100 g akrilne smole iz dimetilaminoetilmetakrilata in nevtralnih metakrilatov (EUDRAGIT E 100 tvrdke ROHM Pharma) v 46 mg-skih odmerkih/rondelo. Tako narejene osnove takoj obložimo z za nikotin neprepustno hrbtno plastjo, poliestrskim filmom debeline 15 μτη, na katerega eno stran je z uparjanjem nanesen aluminij, ki ima približno 110 g/m2 prevleke iz lepila 1, in jih zapečatimo v štirirobo nepredušno vrečo iz primernega embalažnega gradiva.Touch-sticky material (adhesive 1) containing 1,9758 kg of 40% solution of self-cross-linked acrylate copolymer (DUROTAC 280 - 2416 by Delft National & Chemical BV) in a mixture of ethyl acetate, ethanol, heptane and methanol, 189.7 g acrylic resins of dimethylaminoethyl methacrylate and neutral methacrylate (EUDRAGIT E 100 hard ROHM Pharma) and 20 g mixed acid triglyceride from fractionated C g - C 10 coconut fatty acids (Miglyol 812 hard Dynamit Nobel) were applied to one side of the protective layer vacuum applied aluminum and adhesive on both, evaporating the solvent at 50 to 80 ° C. A layer of about 440 g / m 2 was obtained. 51 mm diameter pellets are cut out of the so-called touch-adhesive layer. The protruding edges are machined and a round piece of non-woven fabric (fiber yarn / cotton = 70/30 with 40 g / m 2 - PARATEX III / 40 hardcover LOHMANN GmbH & Co. KG) 42 mm in diameter is placed in the middle of each round. Nicotine is applied as an active substance in solution (140 g of nicotine in 100 g of acrylic resin from dimethylaminoethyl methacrylate and neutral methacrylates (EUDRAGIT E 100 hard ROHM Pharma) in 46 mg doses / round. The base so formed is immediately coated with a nicotine impermeable layer , 15 μτη thick polyester film, on one side of which aluminum is applied by evaporation, having about 110 g / m 2 of adhesive 1 coating, and sealed in a four-sided airtight bag of suitable packaging material.

V tem primeru netkana tkanina služi kot nosilna plast in za pomoč pri enakomerni porazdelitvi nikotina kot inertno polnilo, kot je bilo povedano zgoraj.In this case, the non-woven fabric serves as a carrier layer and to assist in the even distribution of nicotine as an inert filler, as discussed above.

Ker po izumu lahko raztopino aktivne snovi hitro nanesemo na matrično plast in jo zatem prekrijemo z za aktivno snov neprepustno plastjo, je zdaj prvikrat možno na zadovoljiv način doseči primerno dozirane nikotinske obliže.Since, according to the invention, the solution of the active substance can be quickly applied to the matrix layer and then covered with an impermeable layer for the active substance, it is now possible, for the first time, to obtain satisfactorily dosed nicotine patches.

Preskus sproščanja nikotina (in vitro).Nicotine release test (in vitro).

Nikotinski obliž, narejen po primeru 2, po odstranitvi zaščitne plasti potopimo v 80 ml izotonične raztopine običajne soli pri 37 °C, po vnaprej določenih presledkih pa kromatografsko ugotavljamo količino sproščenega nikotina v tekočini. Prostornina medija za sproščanje je tako izbrana, da so dani pogoji utapljanja v vsem času testiranja. Dobili smo naslednje rezultate:After removing the protective layer, the nicotine patch made in Example 2 is immersed in 80 ml of isotonic saline solution at 37 ° C and the amount of nicotine released in the liquid is determined chromatographically at predetermined intervals. The volume of the release medium is so selected that drowning conditions are given throughout the test. We obtained the following results:

po 2 urah: 5,1 mg/obliž po 4 urah: 7,2 mg/obliž po 8 urah: 10,1 mg/obliž po 24 urah: 16,5 mg/obližafter 2 hours: 5.1 mg / patch after 4 hours: 7.2 mg / patch after 8 hours: 10.1 mg / patch after 24 hours: 16.5 mg / patch

Razumeti je treba, da izum z zgradbo, kot je definirana v patentnih zahtevkih, ni omejen na nikotinske obliže in izdelavo le-teh, saj je s tem novim terapevtskim sistemom moč dajati druge snovi kot prednostne snovi, ki so omenjene v opisu.It is to be understood that the invention with the structure as defined in the claims is not limited to the nicotine patches and the manufacture thereof, since this new therapeutic system is capable of administering other substances than the preferred substances mentioned in the description.

Navedba o najboljšem prijaviteljici znanem načinu za gospodarsko izkoriščanje prijavljenega izumaAn indication of the best applicant known method for the economic exploitation of the claimed invention

Pri terapevtskem sistemu po izumu se debelina sistema kot celote giblje med 285 in 1550 /xm. Lepilna plast, ki pride na kožo, je izdelana naprimer iz stirena, silikonskega gumija, poli(meta)akrilata ali akrilnih kopolimerov. Debelina le-te znaša okoli 10 do 150 gm. Rezervoar, katerega debelina znaša 200 do 1330 μ,ιη, je običajno narejen iz zmesi umetnega prediva in bombaža (7:3, 5:5 itd.). Debelina hrbtne plasti znaša 15 do 400 μτη, naredimo pa jo npr. iz polivinilpirolidina, poliviniletra, butil gumija ipd. Hrbtno plast pogosto prevlečemo s tanko plastjo aluminija.In the therapeutic system of the invention, the thickness of the system as a whole ranges between 285 and 1550 / xm. The adhesive layer that gets on the skin is made of, for example, styrene, silicone rubber, poly (meth) acrylate or acrylic copolymers. It is about 10 to 150 gm thick. The tank, whose thickness is 200 to 1330 μ, ιη, is usually made from a mixture of artificial yarn and cotton (7: 3, 5: 5, etc.). The thickness of the back layer is 15 to 400 μτη. from polyvinylpyrrolidine, polyvinyl ether, butyl rubber and the like. The back layer is often coated with a thin layer of aluminum.

Claims (14)

Patentni zahtevkiPatent claims 1. Terapevtski sistem vnašanja aktivnih snovi na kožo, s hrbtno plastjo na odmiku od kože, z najmanj enim vsebnikom za aktivno snov, napravo za porazdelitev aktivne snovi, ki je povezana z vsebnikom za aktivno snov, napravo za uravnavanje sproščanja aktivne snovi, ki uravnava izdajanje aktivne snovi skozi sistem, in z napravo za pritrditev z lepljenjem na dotik za pritrditev terapevtskega sistema na kožo, značilen po tem, da napravo za porazdeljevanje aktivne snovi in napravo za uravnavanje sproščanja aktivne snovi tvori rezervoarna matrica (12), v kateri je eden ali več medsebojno ločenih vsebnikov (14) aktivne snovi razporejenih na določen način v medsebojnem prostorskem razmerju in v katerih je večja koncentracija aktivne snovi kot v rezervoarni matrici.1. A therapeutic system for the introduction of active substances into the skin, with a back layer at a distance from the skin, with at least one active substance container, an active substance distribution device associated with the active substance container, an active substance release regulating device dispensing the active substance through the system, and by means of a touch-adhesive device for attaching the therapeutic system to the skin, characterized in that the active substance distribution device and the active substance release control device comprise a reservoir matrix (12) in which one or more mutually separated containers (14) of the active substance arranged in a specific spatial relationship and in which the concentration of the active substance is greater than in the reservoir matrix. 2. Terapevtski sistem po zahtevku 1, značilen po tem, da vsebnik ali vsebniki za aktivno snov vsebujejo čisto aktivno snov ali snovi.The therapeutic system according to claim 1, characterized in that the container or containers for the active substance contain a pure active substance or substances. 3. Terapevtski sistem po zahtevku 1, značilen po tem, da ima vsebnik ali vsebniki (14) za aktivno snov inertne polnilce.The therapeutic system according to claim 1, characterized in that the active substance container (s) (14) have inert fillers. 4. Terapevtski sistem po enem od predhodnih zahtevkov, značilen po tem, da je vsaj delno zasnovan v obliki plasti.The therapeutic system according to one of the preceding claims, characterized in that it is at least partially designed in the form of a layer. 5. Terapevtski sistem po zahtevku 4, značilen po tem, da rezervoarna matrica (12) obsega najmanj dve plasti, pri čemer je prednostno med plastjo (X) rezervoarne matrice ob hrbtni plasti in plastjo (Y) rezervoarne matrice na strani kože razporejen eden ali več vsebnikov (14) za aktivno snov in pri čemer je razmerje debelin plasti X:Y rezervoarne matrice v razponu od okoli 1:1 do 1:20, smotrno 1:1 do 1:5.5. The therapeutic system according to claim 4, characterized in that the reservoir matrix (12) comprises at least two layers, preferably one or more layers are arranged between the reservoir matrix layer (X) along the back layer and the reservoir matrix layer (Y) on the skin side. multiple containers (14) for the active substance, and wherein the thickness ratio of the reservoir matrix X: Y is in the range from about 1: 1 to 1:20, preferably 1: 1 to 1: 5. 6. Terapevtski sistem po enem od predhodnih zahtevkov, značilen po tem, da je rezervoarna matrica (12) lepljiva na dotik.The therapeutic system according to one of the preceding claims, characterized in that the reservoir matrix (12) is adhesive to the touch. 7. Terapevtski sistem po enem od predhodnih zahtevkov, značilen po tem, da ima rezervoarna matrica (12) ali ena ali več plasti (X, Y) rezervoarne matrice naprave (16), ki se lepijo na dotik vsaj enostransko.The therapeutic system according to one of the preceding claims, characterized in that the reservoir matrix (12) or one or more layers (X, Y) of the reservoir matrix (16) are at least one-sided. 8. Terapevtski sistem po enem od predhodnih zahtevkov 1 do 4 in 6 ter 7, značilen po tem, da je vsebnik (14) za aktivno snov razporejen med rezeivoarno matrico (12) in hrbtno plastjo (10).The therapeutic system according to one of the preceding claims 1 to 4 and 6 and 7, characterized in that the container (14) for the active substance is arranged between the resuscitation matrix (12) and the back layer (10). 9. Terapevtski sistem po enem od predhodnih zahtevkov, značilen po tem, da je vsebnik ali vsebniki (14) za aktivno snov na voljo v trdni ali tekoči obliki.The therapeutic system according to one of the preceding claims, characterized in that the container or containers (14) for the active substance are available in solid or liquid form. 10. Terapevtski sistem po zahtevku 8, značilen po tem, da je vsebnik ali so vsebniki za aktivno snov zasnovani v obliki plasti.The therapeutic system according to claim 8, characterized in that the container or containers for the active substance are designed in the form of a layer. 11. Terapevtski sistem po enem od predhodnih zahtevkov, značilen po tem, da je naprava (16) za pritrjevanje narejena iz v rezervoamo matrico (12) ulitih lepljivih delov.The therapeutic system according to one of the preceding claims, characterized in that the attachment device (16) is made of molded parts (12) cast into the reservoir. 12. Terapevtski sistem po enem od predhodnih zahtevkov, značilen po tem, da obsega odstranljivo zaščitno plast (19) za proti koži obrnjene površine sistema, ki jo je treba pred uporabo odstraniti.The therapeutic system according to one of the preceding claims, characterized in that it comprises a removable protective layer (19) for the skin-facing surface of the system to be removed before use. 13. Terapevtski sistem po enem od predhodnih zahtevkov, značilen po tem, da vsebuje do okoli dvajsetkrat večje količine aktivne snovi od terapevtsko potrebne količine.The therapeutic system according to one of the preceding claims, characterized in that it contains up to about twenty times the amount of active substance than the therapeutically necessary amount. 14. Terapevtski sistem po enem od predhodnih zahtevkov, značilen po tem, da je aktivna snov nikotin.The therapeutic system according to one of the preceding claims, characterized in that the active substance is nicotine.
SI8711587A 1986-08-28 1987-08-26 Transdermal theraupetic system for applaying therapeutical substances throught skin. SI8711587A (en)

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

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SI8711587A true SI8711587A (en) 1996-10-31

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HRP920853B1 (en) 1999-04-30

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