SI9010033A - Process for preparing of a superficial therapeutic system containing antineoplastic agent, particularly 5-fluoro uracil - Google Patents

Process for preparing of a superficial therapeutic system containing antineoplastic agent, particularly 5-fluoro uracil Download PDF

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SI9010033A
SI9010033A SI9010033A SI9010033A SI9010033A SI 9010033 A SI9010033 A SI 9010033A SI 9010033 A SI9010033 A SI 9010033A SI 9010033 A SI9010033 A SI 9010033A SI 9010033 A SI9010033 A SI 9010033A
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matrix
adhesive
polyacrylate
active substance
layer
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SI9010033A
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Slovenian (sl)
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SI9010033B (en
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Walter Mueller
Heinrich Kindel
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Lts Lohmann Therapie Systeme Gmbh & Co.Kg
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Publication of SI9010033A publication Critical patent/SI9010033A/en
Publication of SI9010033B publication Critical patent/SI9010033B/en

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Abstract

The invention refers to the procedure for the production of the superficial therapeutic system which consists of an impermeable back layer, a matrix that contains the active substance and of a re-detachable protective layer. It is marked in the way that the following components of the matrix a. antineoplastic active substance, b. self-adhesive polyacrylate, c. water absorber and possibly d. non-adhesive hydrophile polyacrylate, e. softener and/or accelerator of the penetration are homogeneously mixed, possibly with dissolving in a solvent. The homogeneous mixture is applied to the impermeable back layer, the solvent is possibly removed and then the layer of the matrix is covered with the protective layer.

Description

POSTUPAK ZA IZRADU POVRŽINSKOG TERAPIJSKOG SISTEMA SA SADRŽAJEM ANTINEOPLASTICNE AKTIVNE MATERIJE, NAROČITO 5-FLUORURACILAPROCEDURE FOR MAKING A SURFACE THERAPY SYSTEM WITH THE CONTENT OF ANTINEOPLASTIC ACTIVE MATERIAL, ESPECIALLY 5-FLUORURACIL

Oblast tehnike u koju spada pronalazakFIELD OF THE INVENTION

Pronalazak spada u oblast tekucih zivotnih potreba, sekundarno u oblast hemije, a specifično se odnosi na izradu sistema za površinsku primenu lekova, odn. farmaceutskog oblika za površinsko davanje leka.Oznake prema MPK su A 61 L 15/44, A 61 K 31/5o5, A 61 K 15/16 i A .61 K 9/7o.The invention belongs to the field of liquid necessities, secondary to the field of chemistry, and specifically relates to the development of a system for the surface administration of drugs, ie. of the pharmaceutical form for topical administration. The indications according to MPK are A 61 L 15/44, A 61 K 31 / 5o5, A 61 K 15/16 and A .61 K 9 / 7o.

Tehnički problemTechnical problem

Tehnički problem je kako dobiti sistem za površinsko davanje leka, što se postize izradom matriksa na bazi polimernih akrilata u koji se umeša aktivna materija i matriks se postavlja izmedju dva sloja od polimernih materijala od kojih je jedan smolepljiv a drugi služi kao zaštitni sloj čime se postiže ravnomerno odavanje leka na mestu primene.The technical problem is how to get a system for surface drug delivery, which is achieved by making a matrix based on polymer acrylates in which the active substance is mixed and the matrix is placed between two layers of polymeric materials, one of which is resinous and the other serves as a protective layer, thereby achieving delivering the drug evenly at the point of administration.

Stanje tehnikeThe state of the art

Citostatički i/ili citotoksično aktivne supstance u medicinskoj terapiji igraju ulogu, gde se radi o torne, da se regulišuči zahvati u preterani rast čelije. Največu primenu su one stoga.našle u terapiji melignih tumora.Cytostatic and / or cytotoxically active substances in medical therapy play a role, in the case of thorne, in regulating interventions in the overgrowth of the cell. Therefore, they are the most widely used in the treatment of melignant tumors.

Ali lokalno primeno ona se upotrebljavaju takodje i za terapiju ugrožavajučih bolesti kao psorijaze, bradavice virusnog porekla, karatoza, Morbus Bowen-a i bazaliomena blizu površine. Pri tom se postizu za uspešnu terapiju potrebne visoke lokalne koncentracije aktivne materije, a da pri tom ne mora da se uzmu u obzir sporedna delovanja koja nastaju pri sistematičnoj hemoterapiji malignih tumora, koja mogu daBut topically, they are also used to treat threatening diseases such as psoriasis, warts of viral origin, karatosis, Morbus Bowen, and near-surface basaliomen. Successful therapy requires high local concentrations of the active substance without having to take into account the side effects resulting from the systematic chemotherapy of malignant tumors that can

- 2 dznude *prekid terapije i sesvim retko su takodje vodile i do smrtnih slučajeva· Zg lok8lnu primenu u trgovini mogu de se dobiju pomesti,koje kao ektivnu meteriju sedrže 5-fluorutscil (Ef£udix i Effluderm,obe od HS$fmann Le Roche AG).- 2 doses * discontinuation of therapy and, rarely, also leading to fatalities · Zg local use in commerce can be swept, which as 5-fluorutscil (Ef £ udix and Effluderm, both by HS $ fmann Le Roche) AG).

5-fluorurecil se ubreje u tekozvane entimetsbolite i specijslno je antimetabolit pirimidine·5-Fluorourecil is a part of liquid entimetsbolites and is specifically the antimetabolite of pyrimidine ·

Kliničke iskustve sa ovim sktivnom meterijom keo lokalnim citostatikom poštoje več pribl. 25 godine. Ceni se naročito zbog njegovih medicine kih i kozmetičkih rezultate (Goette,D.K», J.AM.AGAD.DERMATOL: 4: 655 649 1981).Clinical experience with this scrotal metric keo local cytostatics is already appreciated. 25 years. It is appreciated especially for its medical and cosmetic results (Goette, D.K », J.AM.AGAD.DERMATOL: 4: 655 649 1981).

Ali primene u obliku pomesti ime nedostetek,što je teško,eko ne i nemoguce de se odredjene površine kože u toku celokupnog trajanja lečenja,koje može da se protegne preko više nedelje opskrbi,s jedne štrene se dovoljnom,eli s druge strane ne predoziranom količinom aktivne materije»But applications in the form of sweep the name of the disadvantage, which is difficult, if not impossible, that certain areas of the skin for the entire duration of treatment, which can extend over several weeks supply, on the one hand enough, or on the other hand not overdose active substances »

Ovaj nedostetek je takodje več primečen i doveo je do sisteme primene koji je opisan u US-PS 5,734,097*^0ji se sastoji iz semolepljive,ravne površine formulacije koja sedrži aktivnu materiju,koje je ne jednoj strani snebdevena nepropusnom nosečem folijom za aktivne materije i pomočne materije i na drugoj strani se folijom koje se skide koja respoleže istim svojstvim8,8li koja dodatno pre upotrebe može de se odstreni.This drawback has also been noted and has led to the application system described in US-PS 5,734,097 * consisting of a self-adhesive, flat surface of the formulation containing the active substance, which is provided on one side with an impermeable carrier film for the active substances and excipients. on the other hand, with a removable foil having the same properties8,8li which can be removed before use.

Zbog iste poz8dine trebe gledati US-PS 5,789,071,kod kog8 se poliureteni uzimeju k80 inerten noseči meterijel za ektivnu meteriju 5-fluor......uracil.............. ......—.....- ........................ ..........- Opis reženje tehničkog probleme se primerima izvodjenja i popisom i kratkim opisom slike načrteDue to the same background, US-PS 5,789,071 should be viewed, in which the polyurethanes are taken k80 inert carrier material for the ective 5-fluorine ...... uracil .............. ..... .. — .....- ........................ ..........- Description Solving a technical problem is exemplified Performing both a listing and a brief description of the image plans

Pronelezsk se odnosi ne postmpak ze izredu površinskog terepijskog sisteme se 8ntineopl88ti&nom sktivnom meterijom,neročito 5-fluorureciloo: Zedetek ovog proneleske je sede bio de se,ne ovoj osnovi razvije sis5 tem,koji poseduje sve prednosti dosadesnjih iorn-ulecija,dodatno poseduje poboljšanja i potvrdjuje se u praktičnim ogledime·Pronelezsk does not relate, however, beyond the superficial terpia system with 8ntineopl88tive tertiary metrics, not readily 5-fluoroureciloo: in practical terms ·

U toku lečenja bb citostatički i citotoksično aktivnim supstancama se čelije sa pojačano® aktivnošču delenje gradualno ječe oštečuju od če£· lija koje se normalno dele. Poželjan je,i ta uspešno lečenje potreban rezultat,da se u području primene dodje do uvečanog odumiranja čeli” ja koje se ektivno dele. Ovo uvečano umiranje čelija je pračeno zapeljivim procesime,koji su opet vezani sa lučenjem sekrete rane· Ovo povišano lučenje sekreta rane otežava sada,da se odredjena površine kože održava u dužem vremenu pod uslovima okluzije,a da sistem ne izgubi svoje prienjanje za kožu* Rešenje ovog probleme,kao predvidjanje ispuštene semolepljive ivice sistema koji sadrži deo sa aktivnom materijom ne treba de se srnatrsju kao optimalna,pošto ona povečevaju ukupnu površinu sistema i stoga otežavaju primenu naročito u području lipa.During treatment with cytostatically and cytotoxically active substances, cells with enhanced® activity of division divide the gradual barrier from normally dividing cells. It is desirable, and this successful treatment, the result required, that in the field of application, an increased extinction of the divisible cells is achieved. This increased cell death is accompanied by seductive processes, which are again associated with the secretion of the wound secretion. · This increased secretion of the wound secretion makes it difficult now to maintain a certain area of the skin for a longer period of time under occlusion conditions, without the system losing its adhesion to the skin. This problem, as a prediction of the leaked self-adhesive edge of the system containing the active ingredient part, should not be deployed as optimal, since they increase the total surface area of the system and therefore make it difficult to apply especially in the area of linden.

Ka iznenadjujuči način je sada otkriveno,da ovaj zadatak može de se reši time,što se polimerni nosač aktivne materije po mogučstvu učini polarnim i doda dodatni tzv»absorber vode»In a surprising way, it has now been discovered that this task can be solved by making the polymeric carrier of the active substance polar and by adding an additional so-called " water absorber "

Predmet pronalaska je prema torne postupak za izradu površinskog terepijskog sisteme,koji se sastoji iz nepropusnog zednjeg sloje,metriksa koji sadrži aktivnu meteriju i ponova odvojivog zeštitnog sloj© koji je naznačen time,što se sledeči sastojci matriksaThe object of the invention is to provide a process for making a surface terepitic system, consisting of an impermeable backing layer, a metric containing an active metric, and a re-separable protective layer ©, characterized in that the following components of the matrix

e. antineoplastične aktivne materije b· šemolepljni poliskrilet c· absorber vode, _________ _______________________ ___________ i u detom slučaju d, hidrofilni poliakrilat koji se ne lepi,e. antineoplastic active substances b · Shell-stick polysacrylate c · Water absorber, _________ _______________________ ___________ and in the case of d, non-adhesive hydrophilic polyacrylate,

e. omekšiveč i/ili ubrziveč penetracije homogeno izmešaju,u detom slučaju rsstveranjem u restvaraču,homogene smeše nanese na nepropusni zadnji sloj,u dstom slučaju odstrani rastvareČ i posle toga se sloj matriksa pokrije se zestitnim slojem· ι Keo re&etivno polerni semolepljivi osnovni polimer primenjuje se poliekrilet,pošto je ove kleše lepkove u medicinsko® području nešle mnogostruke mogučnosti primene i veži keo dobro podnošljive ne koži. Keo neročito pogodan se pri tom pokezeo poliskriletni lepek Durotek 280-2516 firme Netionel Sterch.e. omekšiveč and / or ubrziveč penetration homogeneous izmešaju u detom case rsstveranjem u restvaraču, the homogeneous mixture is applied to nepropusni last layer in dstom case removed rastvareČ and operations rigid the layer of the matrix covers the zestitnim layer · ι Keo re & etivno polerni semolepljivi base polymer primenjuje the poliekrilet , since these adhesive pliers in the medical area did not have multiple application possibilities and a larger keel was well tolerated to the skin. Keo undeniably suitable was the semi-skeletal adhesive Durotek 280-2516 by Netionel Sterch.

Keo poreni poliekrileti koji se ne lepe dolsze u obzir tekvi,koji imeju izvesten sedržej sledečih slobodnih polsrnife grupe: hidroksi grupe, kerboksilnih grupe, emino grupe,kveternernih emonijum grupe itd#Non-stick keo pore polyacrylates, which have certain contents of the following free half-sniffs: hydroxy, carboxyl, emino, quaternary emmonium, etc. #

Zs ovu svrhu dobro mogu de se primene ne pr.poliekrileti Eudregit nize firme RShm-Pherme,pošto su nesli siroku primenu u tehnologiji tebletirenje i mogu de se smetreju keo fiziološki nesumnjivi· Neročito dobro je pogoden Eudregit RL 100,koji hemijski može de se označi k80 kopolimer estere ekrilne kiseline i metakrilne kiseline s8 izvesnim ssdržejem kvetememih emonijum grupe# Odlikuje se time,što bubri u veliko j meri ηβζβνίβηο od pH vrednosti i več time potpotaeže uzimsnje vlage u sistemu· Osim toge kompenzuje se nešto omekševeju» če delovenje dodatnih pomočnih meterijs keo ne pr· 1,2-propendiole·For this purpose, it is not feasible to apply, for example, the RShm-Pherme polyurethanes of Eudregit, as they have been widely used in tabletting technology and can be considered physiologically indisputable. The chemical marking of Eudregit RL 100 is extremely good. k80 copolymer of acrylic acid and methacrylic acid ester s8 with a certain content of quaternary emmonium groups keo not pr · 1,2-propendiol ·

Κβο ebsorbeti vode nude se ne tržištu veliki broj proizvode fae beži prirodnih i sintetskih polimere, Κθ0 podesni pokazali su se ebsorberi vode ne beži neznetno umreŽenih,prethodno neutrelizovenih poliekrilnih kiseline. Nejbolji rezulteti se postižu se proizvodom Aquekeep 10 SH,firme Seitetsu Kegeku. Ne osnovu njihovog poprečnog umreženje tekvi ebsorberi vode se pris?d>dno ne restvereju homogeno u metriksuflestere,eli u potrebnoj količini nemeju neg8tiveauticaj ne koheziju i šilu lepljenje metrikse.Water absorbers are offered to the market for a large number of products of fae escapes of natural and synthetic polymers, Κθ 0 suitable ebsorbers of water do not escape non-crosslinked, previously neutralized polyacrylic acids. The best results are achieved with the product of Aquekeep 10 SH, by Seitetsu Kegeku. On the basis of their transverse networking, the liquid absorbers are usually not homogeneously restrained in the metrixflesters, but they do not have the necessary cohesion and adhesive bonding of the metric in the required amount.

Zednji sloj može de se sestoji od sevitljivog ili ne;evitljivog meterijele i de bude jedno ili dvoslojno opremljen. Supstence,koje mogu de se primene ze njihovu izr8du,su polimerne supstence,k80 ne pr. polietilen,polipropilen, polivinil hlorid, polietilen tereftelet i poliemid. Keo delji meterijeli mogu de se primene tekodjo i metalne folije,kso aluminijuraske folije,seuaili obložene sloje® polimerne obloge. Izvodjenje koje se pretposfcevljs je 10 u debele polietilen teriftalne folije,koja je na štreni metrikse obložena aluminijumom i posle primeno na strani preme spolja okfcenutoj strani je obojena bojo® kože.The backing layer may consist of a radiant or non-volatile meter and be fitted with one or two layers. Substances that can be used for their manufacture are polymeric substances, k80 not e.g. polyethylene, polypropylene, polyvinyl chloride, polyethylene terephtelet and polyemide. Even metal foils, such as aluminum foils, sealed or coated layers of polymer coating, can also be used. The prefabricated embodiment is 10 in thick polyethylene terephthalate foil, which is coated with aluminum on the bar metrics and after application to the outside side, the colored side is colored with skin®.

Cdvojivi zaštitni sloj,koji stoji u oodiru sa saraolepljivin ra&triksom i odstranjuje se pre primene,sestoji se na primer iz istih materijala kako se oni koriste za izradu zadnjeg sloje,uz pretpostavku,de se učine otfvojivim,keo na pr,silikonsko® obredom. Drugi cdvojivi zastitni slojevi su na pr, od tetrefluoretilene»obredjene hartije»celofana i sl.The detachable protective layer, which is in contact with the saraole-adhesive compound and is removed prior to application, consists, for example, of the same materials as they are used to make the backing layer, presumably rendered detachable, e.g., silicone® rite. Other cdopable protective layers are, for example, of tetrafluoroethylene " paper " cellophane and the like.

Sistem u smislu ovog pronalaska pokazuje ^lika 1 u preseku, klika 2 pokazuje povečanje uzimanja vode ekrilatnog lepka dodatkom Eudragit-s RL 100 i Aquakeep-s 10 SH. krive 1 pokazuje praktično zanemarljivo uzimanje vode čistofe ekrilatnog lepka, Knive 2 blago povečanje dodatke® Eudragit-e RL 100 i Kriva 5 gramatičen porast dotokom Aquakeep-a 10 SH. v The system of the present invention shows a cross-sectional view of figure 1, a click 2 shows an increase in the water intake of the acrylic adhesive by the addition of Eudragit-RL 100 and Aquakeep-10 SH. curve 1 shows practically negligible water intake of the purity of the acrylate adhesive, Knive 2 a slight increase in the additives® Eudragit-e RL 100 and curve 5 a grammatical increase with the inflow of Aquakeep 10 SH. v

Krivoj 5 u osnovi leži sledeča formulacija metrikss koja se dobije posle odotranjivanja rastvarača,koja se pokazale takodje i u klinično® ogledu kr-o vic dobro aktivi:?:Curve 5 is basically the following formulation of metrics, which is obtained after solvent removal, which has also been shown to be well activated in the clinical trial:?:

7910 g poličk;il-:tneg lepka (Durotek 280-2pl6,firme National Sterch) 1980 g kopolimera iz estera akrilne i metakriine ki;slino sa izvesnim esdržajera kveternernih amoniju® grupe (Eudregit aL 100, firme Rohra-Lherra?!)7910 g of shelves; il-: glue (Durotek 280-2pl6, from National Sterch) 1980 g of copolymers from acrylic and methacrylic esters; saliva with certain quaternary ammonium® group holders (Eudregit aL 100, Rohra-Lherra ?!)

500 g absorbera vode ne bazi kvaternerne neutralizovane pciiekrilne kiseline (Aauakeep 10 OH, firme oeitetsu kagsku)500 g Quaternary Neutralized Pc Acrylic Acid Water Absorber (Aauakeep 10 OH, Oeitetsu Kagi)

1040 g 1,2-propandiola 85 g 5-fluorurecils p1040 g of 1,2-propanediol 85 g of 5-fluorourecils p

; ovr; inske mase: 11.5 g/®'.; ovr; Inner masses: 11.5 g / ® '.

r-ivoj 2 i 1 je u osnovi iste formulacija i ista povržinck? asa sve- o Apue'-cQ:.-a 10 .Rl odn. bez AO.uekuep-a IG :,Ιϊ i ...vdv cit-e RLr-ivoj 2 and 1 is basically the same formulation and same vegetable? asa all- about Apue'-cQ: .- a 10 .Rl resp. without AO.uekuep IG :, Ιϊ i ... vdv cit-e RL

10( ver en j e su izvedene ηε 32 °G se deminero-iizov eaom vodom i upi jen j<10 (the ver sions were performed ηε 32 ° G were demineroized with water and absorbed with <

vode odredjano gravimetrijski.of water determined gravimetrically.

Ka Klici 3 je pretstevljeno in-vitro oslobadjanje uzorke na besi gor· 2 nje formulacije, Kadržej aktivne meterije iznosi 85 ^tg/cra. Krive oslcbedjanje pokazuje tok kekev je on tipičen ze sisteme matrikse.As in Example 3, the in vitro release of the samples on the anger formulation was assumed to be 85 mg tg / cra. The false curves indicate the flow of keck is typical of matrix systems.

Oslobadjanje je .izvedeno pomoču Rotsting Bottle ur.edjeje ne 32 °C uz primenu fiziološkog rastvora kuhinjske soli kao sredine ze oslobedjonjo,a koncentracijo aktivne meterije je merena fotoroetrijski u res tvorime uzoreke.The release was performed with the help of a Rotsting Bottle at 32 ° C using saline as the middle of the freezer, and the concentration of the active meter was measured photoroetrically to form samples.

Ka sistGmims iste formulacije metriksa,krušne geometrije i veličine pKa sistGmims of the same metric formulation, bread geometry and p size

1,13 cm' izvedeni su klinieki ogledi na 8 pecijenete se indikscijom ektinijske kerstoze i u svim slučajevima mogao je posle primene 6 » 7 sisteme de se zebeleži uspeh terapije. Promene sistema je vršene sve~ ka 2 do 3 dane.1,13 cm 'clinical trials were performed on 8 patients with ectinic kerstosis index and in all cases after the application of 6 »7 systems the success of the therapy could be recorded. Changes to the system took place for 2 to 3 days.

Ne Slici 4 je pokezeno upijanje 5-fluorurecils iz sisteme,kako je ono oaredjeno odradjivenjen ostetke ektivne meterije u nošenim sistemims.No Fig. 4 shows the absorption of 5-fluorourecils from the system, as it is delineated by the remnants of the active meter in the wearing systems.

u proseku (računate iz oglede ne 8 pscijeneta i po 6 sisteme po pacijentu) upijeno je 69,5% odn. 65.8 (ug utrljenih 91.8 pg 5-fluorurecile u toku vremen« nošenja sisteme od 2 ili 3 dane. Ovo odgovare prosečnor, upij-nju od prifcl· 56 ΡΓ š-fluorurecile po po ci . t ntu ,c r nu ή sistemu. Kod ovog izusnredno nalog upijenje ektivne meterije trebe se sigurnešču de so isključc sistemične sporedne selovanja.on average (calculated from the trial of not 8 psiets and 6 systems per patient) absorbed 69.5% or. 65.8 ( ug crushed 91.8 pg of 5-fluorourecile during the course of wearing the 2 or 3 day system. This corresponds to the average absorbance of prifcl · 56 ΡΓ w -fluorourecile per ci. T ntu, cr nu ή system. as a matter of urgency, the order of the effective meter should be secured with the exception of systematic secondary migration.

-eke se još jednom niš·· sežeto ponove naročite prednosti pronalaska:-Eke once more niche ·· recapitulate the particular advantages of the invention:

a. sigurno terapijsko delovenje pri minimelnom upijenju aktivno materijea. safe therapeutic action with minimal absorption of the active substance

b. kratko trsjenje lečenjeb. short shaking treatment

c. aktivne meterije se ostro ogreničeve prir· en j ene šemo ns povr· činu koja trebe da se lečic. active meters are sharply attached to the surface of the cell to be treated

d. visok kapacitet upijenje vode sesterasd. high capacity water absorption today

e. fototoksične reakcije se sprečavaju uslovimae. phototoxic reactions are prevented by the conditions

f. dobri kozmetički rezultati ckludovanjaf. good cosmetic results

g. bitno poboljšanocpristejsnje pacijenata potrebnom primenom samo svaka 2-5 dana novog sistema (pomest 2 x dnevno).Mr Rücker significantly improved the patient experience with the required administration only every 2-5 days of the new system (sweep 2 x daily).

PrimerExample

Postupak izr'de za nribl. 100 nf 5-fluorurecil poizr:'in;. kog terapijskog; sistemeThe procedure is for nribl. 100 nf 5-fluorourecil poizr: 'in ;. whom therapeutic; systems

4.552 g 40%-tnog (g/gjf) rsstvora kopolimera estere akrilne i metekrilne kiseline se izvesnira sadržajem kveternernih amonijum grupa (Eudragit RL 100,firme Rohm P^arsa)u metiletil ketonu dodaju se uz mešanje u 16.697,8 g £2%”tnog (g/g) rastvora poliakrilatnog lepka &Durotek 280-2516,firme National Starch), 456 g sbsorbere vode na ba zi kvaternerne neutralizovane pgliskrilne kiseline (j$quakeep 10 SH, firme Seitetsu Kegeku,veličina cestica «ž=125^um) i na kraju doda rastvor 75 g 5-fluoruracila u 2.755 g 1,2-propendiola.4,552 g of a 40% (g / gjf) solution of the copolymer ester of acrylic and methacrylic acid ester is quenched by the content of quaternary ammonium groups (Eudragit RL 100, Rohm P ^ arsa) in methylethyl ketone added with stirring at 16,697.8 g £ 2% Of (g / g) solution of polyacrylate adhesive & Durotek 280-2516, from National Starch), 456 g of water-based sorption based on quaternary neutralized pgliskrylic acid (j $ quakeep 10 SH, by Seitetsu Kegeku, particle size «w = 125 ^ um ) and finally added a solution of 75 g of 5-fluorouracil in 2.755 g of 1,2-propendiol.

Ova masa se namaže ne 100 p debelu aluminijumizovanu i silikonizovenu poliestersku foliju,teko da se posle odstranjevanja rastvarače dobije filqt sa površinskom masora o* 115 g/m · Ovaj film se pokriva tThis mass is not greased with 100 p thick aluminum and siliconized polyester film, but after removal of the solvent, a surface mass of about 115 g / m is obtained. · This film is covered by t

sa 10 fl debelom poliestarskom folijom i seče i isece u komade željene veličine.with 10 fl thick polyester foil and cut and cut into desired size pieces.

NAVOD O NAJBOLJEM NAČINU SA PRIVREDNU UPOTREBU PRIJAVLJENOG PRONALASKAA Citation on the Best Way to Economically Use a Found Find

Najbolji način za privrednu upotrebu prijavljenog pronalaska, koji je prijaviocu bio poznat u vreme podnošenje ove patentne prijave, jeste način iznet u opisu, i u primeru, a sa konstrukcije kakva je prikazana na ertežima.The best way to commercially use the claimed invention, which was known to the applicant at the time of filing this patent application, is by way of the description, and in the example, and of the construction as shown in the drawings.

Claims (6)

PATENTNI ZAHTEVKIPATENT APPLICATIONS 1 Postopek za izdelavo površinskega terapevtskega sistema z vsebino antineoplastične dejavne snovi, zlasti 5-fluoruracila, sestavljenega iz nepropustnega hrbtnega sloja, dejavno snov vsebujoče matrike in iz ponovno snemljivega varovalnega sloja, označen s tem, da se sestavine matrike kot so antineoplastična dejavna snov, samolepljivi poliakrilat, vodni absorber, nelepljivi hidrofilni poliakrilat in mehčalec in/ali pospeševalec penetracije raztope v topilu in homogeno mešajo, homogeno zmes se nanese na nepropustni sloj, da se odstrani topilo in se na matriko nanese varovalni sloj.A method for producing a surface therapeutic system comprising an antineoplastic active substance, in particular 5-fluoruracil, consisting of an impermeable backing layer, an active matrix-containing material and a re-removable protective layer, characterized in that the matrix components such as the antineoplastic active substance are polyacrylate, aqueous absorber, non-adhesive hydrophilic polyacrylate and softener and / or penetration enhancer dissolve in the solvent and stir homogeneously, homogeneous mixture is applied to the impermeable layer to remove the solvent and a protective layer is applied to the matrix. 2 Postopek po zahtevku 1, označen s tem, da je antineoplastična dejavna snov 5-fluoruracil.The method of claim 1, wherein the antineoplastic active substance is 5-fluorouracil. 3 Postopek po zahtevku 1 ali 2, označen s tem, da sestoji matrika iz najmanj 50%, prednostno 65-75% samolepljivega poliakrilata,The method according to claim 1 or 2, characterized in that the matrix consists of at least 50%, preferably 65-75% self-adhesive polyacrylate, 0-48,8, prednostno 0-35% in zlasti prednostno 15-25% nelepljivega hidrofilnega poliakrilata, 0-20%, predostno 5-15% in zlasti prednostno 5-10% mehčalca ali penetracijskega pospeševalca,0-48.8, preferably 0-35%, and particularly preferably 15-25% of non-adhesive hydrophilic polyacrylate, 0-20%, preferably 5-15%, and especially preferably 5-10% of plasticizer or penetration enhancer, 1-15%, prednostno 1-10% in zlasti prednostno 4-5% vodnega absorberja in 0.2-5%, prednostno 0,3-1 % in zlasti prednostno 0,6-0,9% 5-fluoruracila.1-15%, preferably 1-10%, and particularly preferably 4-5% of the aqueous absorber and 0.2-5%, preferably 0.3-1% and especially preferably 0.6-0.9% of 5-fluorouracil. 4 Postopek po enem od zahtevkov 1 ali 2, označen s tem, da je mehčalec oz. pospeševalec penetriranja 1,2-propandiol.Process according to one of Claims 1 or 2, characterized in that it is a plasticizer or a plasticizer. 1,2-propanediol penetration enhancer. 5 Postopek po enem od zahtevkov 1 ali 2, označen s tem, da se sistempo nanošenju ponovno snemljivega varovalnega sloja razreže v kose krožne oblike premera 0,5 - 3 cm, prednostno 1 - 2 cm, zlasti prednostno 1 -1,2 cm.Method according to one of Claims 1 or 2, characterized in that the system is cut into pieces of circular shape 0.5 - 3 cm in diameter, preferably 1 - 2 cm, especially preferably 1 -1.2 cm, by applying the re-removable protective layer. 6 Postopek po enem od zahtevkov 1 ali 2, označen s tem, da se sistempo nanošenju zaščitne folije razreže v kose pravokotne oblike površine 1 - 200 cm3, prednostno 1 - 50 cm3, zlasti prednostno 2 - 20 cm3.Method according to one of Claims 1 or 2, characterized in that the system is cut into pieces of rectangular surface of 1 - 200 cm 3 , preferably 1 - 50 cm 3 , especially preferably 2 - 20 cm 3 , by applying a protective film.
SI9010033A 1989-01-20 1990-01-09 Process for preparing of a superficial therapeutic system containing antineoplastic agent, particularly 5-fluoro uracil SI9010033B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3901551A DE3901551A1 (en) 1989-01-20 1989-01-20 SUPERFICIAL THERAPEUTIC SYSTEM WITH AN ANTINEOPLASTIC ACTIVE SUBSTANCE, IN PARTICULAR 5-FLUORURACIL
YU3390A YU47339B (en) 1989-01-20 1990-01-09 PROCEDURE FOR THE DESIGN OF A SURFACE THERAPY SYSTEM WITH THE CONTENT OF ANTINEOPLASTIC ACTIVE MATERIAL, ESPECIALLY 5-FLUORURACIL

Publications (2)

Publication Number Publication Date
SI9010033A true SI9010033A (en) 1998-02-28
SI9010033B SI9010033B (en) 1998-12-31

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SI9010033A SI9010033B (en) 1989-01-20 1990-01-09 Process for preparing of a superficial therapeutic system containing antineoplastic agent, particularly 5-fluoro uracil

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HR (1) HRP930667B1 (en)
SI (1) SI9010033B (en)

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HRP930667A2 (en) 1994-10-31
SI9010033B (en) 1998-12-31
HRP930667B1 (en) 1998-10-31

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