EP1519718A1 - At least partially degradable films containing an active ingredient and method for the production thereof - Google Patents

At least partially degradable films containing an active ingredient and method for the production thereof

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Publication number
EP1519718A1
EP1519718A1 EP03730175A EP03730175A EP1519718A1 EP 1519718 A1 EP1519718 A1 EP 1519718A1 EP 03730175 A EP03730175 A EP 03730175A EP 03730175 A EP03730175 A EP 03730175A EP 1519718 A1 EP1519718 A1 EP 1519718A1
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EP
European Patent Office
Prior art keywords
film according
active ingredient
film
production
active
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
EP03730175A
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German (de)
French (fr)
Inventor
Günter Helling
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
AgfaPhoto GmbH
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AgfaPhoto GmbH
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Filing date
Publication date
Application filed by AgfaPhoto GmbH filed Critical AgfaPhoto GmbH
Publication of EP1519718A1 publication Critical patent/EP1519718A1/en
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the invention relates to an agent containing at least one active ingredient, with which an exact, controlled and controllable release of the at least one active ingredient is possible.
  • Active substances are understood to mean low molecular weight, organic compounds which have a desired effect after their release from the agent, in particular a pharmacological or biocidal effect.
  • Active pharmaceutical ingredients are offered in a variety of dosage forms, which should make it possible for the active pharmaceutical ingredient to be able to develop its effect at the desired location in the organism at the desired time and in the desired dosage. These goals could not always be achieved with the known dosage forms.
  • This object is achieved according to the invention by a film containing the at least one active ingredient, which is at least partially degraded under the conditions of the site of action.
  • the film preferably consists of biological material, for example of an optionally partially degraded polypeptide, in particular of gelatin.
  • the biological material is preferably degraded enzymatically at the site of action and thus releases the at least one active ingredient stored in it.
  • the biological material of the film can be modified, for example by aqueous polymer latices or polymer dispersions, by water-soluble, optionally crosslinkable polymers or copolymers or protein derivatives. Examples of this are in Res. Discl. 38 957 (1996) on p. 598, Chapter II A and Chapter II C described, the z. B. contain a polyacrylamide, a polyacrylic acid derivative, a polyvinylpyrrolidone, a polyvinyl alcohol, a polyvinylimidazole, a polyethylene oxide, a polystyrene sulfonic acid or a cellulose derivative.
  • the biological material can be further hardened to different degrees, that is, cross-linked, e.g. B.
  • the films made of biological material, especially gelatin have many advantages: They can be any biological material, especially gelatin. They can be any biological material, especially gelatin.
  • the production takes place in particular in that the biological material on which the films are based is poured as an aqueous solution onto a carrier film by means of a suitable pouring device and is removed after drying. This is advantageously carried out continuously with a cascade or a curtain caster.
  • Suitable carrier films are, in particular, cellulose acetate film and paper coated on both sides with polyethylene, both of which are known as carrier materials for photographic materials. Films made of polyester (PET or PEN) and polycarbonate are also suitable.
  • the carrier films are not equipped with substrate or adhesive layers, which are known to bind the subsequent cast layers to the carrier film, since the cast layer is to be removed after production.
  • the active ingredients are added to the casting solutions and thus incorporated into the later films. An exact dosage is possible. Furthermore, the active ingredient z. B. distributed in a specific environment, for example in a solution in a high-boiling organic solvent, which is in the aqueous
  • Casting solution is emulsified.
  • the active ingredient can also be introduced in the form of a loaded latex.
  • a latex is impregnated or loaded with the water-soluble active ingredient. This insertion method is for photographic color couplers in Res. Discl. 38 957 (1996), p.
  • the film according to the invention can consist of several layers. This is advantageous if at least two active ingredients which are incompatible with one another are to be contained in a film, since they can be introduced in different layers. It is also possible to provide active substances in different concentrations in the different layers, in order to enable a targeted release of the active substance in different amounts during later use.
  • the film can be cut into small and very small parts and applied in this way, be it in one of these parts containing solid or liquid dosage form, for example in a tablet or in a juice.
  • the release occurs through degradation of the film substance, in the case of gelatin film through enzymatic degradation, in particular through an enzyme of the organism that is to be treated with the active ingredient, for example with trypsin.
  • Betaxolol and 90.0 g of olive oil are dissolved in 80 g of ethyl acetate and emulsified in an aqueous solution of 6.0 g of gelatin, 350 g of water and 0.5 g of dodecylbenzenesulfonate using an emulsifier at 40 ° C. within 12 minutes , The ethyl acetate is evaporated and an O / W emulsion is obtained, which is made up to 500 g with water.
  • emulsion 1 160 g of emulsion 1 are mixed at 40 ° C. with 66 g of 20% by weight gelatin, 90 g of water and 4.0 g of 10% by weight dioctyl sulfosuccinate, sodium salt solution (wetting agent) and water to 350 g filled up.
  • pouring solution 2 160 g of emulsion 1 are mixed at 40 ° C. with 66 g of 20% by weight gelatin, 90 g of water and 4.0 g of 10% by weight dioctyl sulfosuccinate, sodium salt solution (wetting agent) and water to 350 g filled up.
  • pouring solution 2 160 g of emulsion 1 are mixed at 40 ° C. with 66 g of 20% by weight gelatin, 90 g of water and 4.0 g of 10% by weight dioctyl sulfosuccinate, sodium salt solution (wetting agent) and water to 350 g filled up.
  • Pouring solution 2 160 g of e
  • 160 g of emulsion 2 are mixed at 40 ° C. with 70 g of 20% by weight gelatin, 90 g of water and 4.0 g of 10% by weight dioctyl sulfosuccinate, sodium salt solution (wetting agent) and water Replenished 350 g.
  • a cascade caster known from the manufacture of photographic materials is used to add a non-subbed polyethylene terephthalate film
  • the application is chosen so that after drying at 50 ° C a dressing of 3 layers with layer applications of
  • Sample 2 contains metipranolol and betaxolol
  • the test shows that the pieces of film selectively release the active substances one after the other by enzymatic degradation.

Abstract

A novel administration form of active ingredients, especially active ingredients having a pharmacological or biocidal effect, in the form of a film containing at least one active ingredient which is at least partially degraded by the conditions in the place of action.

Description

WIRKSTOFF ENTHALTENDE, ZUMINDEST TEILWEISE ABBAUBARE FOLIEN UND VERFAHREN ZU DEREN HERSTELLUNGFOILS CONTAINING ACTIVE SUBSTANCE, AT LEAST PARTLY DEGRADABLE, AND METHOD FOR THE PRODUCTION THEREOF
Die Erfindung betrifft ein mindestens einen Wirkstoff enthaltendes Mittel, mit dem eine genaue, kontrollierte und regelbare Freisetzung des wenigstens einen Wirkstoffs möglich ist.The invention relates to an agent containing at least one active ingredient, with which an exact, controlled and controllable release of the at least one active ingredient is possible.
Als Wirkstoffe werden dabei niedermolekulare, organische Verbindungen verstanden, die nach ihrer Freisetzung aus dem Mittel eine gewünschte Wirkung entfalten, insbesondere eine pharmakologische oder biozide Wirkung.Active substances are understood to mean low molecular weight, organic compounds which have a desired effect after their release from the agent, in particular a pharmacological or biocidal effect.
Pharmazeutische Wirkstoffe (Arzneimittel) werden in einer Vielzahl von Darreichungsformen angeboten, die es möglich machen sollen, daß der pharmazeutische Wirkstoff am gewünschten Ort eines Organismus zur gewünschten Zeit in der gewünschten Dosierung seine Wirkung entfalten kann. Diese Ziele könnten mit den be- kannten Darreichungsformen nicht immer erfüllt werden.Active pharmaceutical ingredients (pharmaceuticals) are offered in a variety of dosage forms, which should make it possible for the active pharmaceutical ingredient to be able to develop its effect at the desired location in the organism at the desired time and in the desired dosage. These goals could not always be achieved with the known dosage forms.
Es ist daher eine ständige Aufgabe, neue verbesserte Darreichungsformen zu entwickeln, die spezielle Applikationen und Dosierungen ermöglichen.It is therefore a constant task to develop new improved dosage forms that enable special applications and dosages.
Diese Aufgabe wird erfindungsgemäß durch eine den wenigstens einen Wirkstoff enthaltende Folie gelöst, die unter den Bedingungen des Wirkungsortes wenigstens teilweise abgebaut wird.This object is achieved according to the invention by a film containing the at least one active ingredient, which is at least partially degraded under the conditions of the site of action.
Vorzugsweise besteht die Folie aus biologischem Material, beispielsweise aus einem gegebenenfalls partiell abgebauten Polypeptid, insbesondere aus Gelatine. Das biologische Material wird am Wirkort vorzugsweise enzymatisch abgebaut und setzt so den in ihm gespeicherten wenigstens einen Wirkstoff frei.The film preferably consists of biological material, for example of an optionally partially degraded polypeptide, in particular of gelatin. The biological material is preferably degraded enzymatically at the site of action and thus releases the at least one active ingredient stored in it.
Das biologische Material der Folie kann modifiziert sein, beispielsweise durch wässrige Polymerlatices oder Polymerdispersionen, durch wasserlösliche, gegebenenfalls vernetzbare Polymere oder Copolymere oder Proteinderivate. Beispiele dafür sind in Res. Discl. 38 957 (1996) auf S. 598, Kapitel II A und Kapitel II C beschrieben, die z. B. ein Polyacrylamid, ein Polyacrylsäurederivat, ein Polyvinylpyrrolidon, ein Polyvinylalkohol, ein Polyvinylimidazol, ein Polyethylenoxid, eine Polystyrolsulfonsäure oder ein Cellulosederivat enthalten. Das biologische Material kann weiterhin in unterschiedlichem Ausmaß gehärtet, das heißt vernetzt sein, z. B. durch eine Vernetzung über Aminogruppen mittels Bisvinylsulfonen, Aldehyden, Cyanurchloriden oder Epoxiden oder durch eine Vernetzung über Carboxyl- und Aminogruppen mittels Carbodiimiden oder Carbamoylpyridium salzen oder durch eine Vernetzung über Carboxylgruppen mittels Aziridinderivaten. Weitere geeignete Härtungsmittel sind in Res. Discl. 38 957 (1996) auf S. 599, Kapitel II, B beschriebenThe biological material of the film can be modified, for example by aqueous polymer latices or polymer dispersions, by water-soluble, optionally crosslinkable polymers or copolymers or protein derivatives. Examples of this are in Res. Discl. 38 957 (1996) on p. 598, Chapter II A and Chapter II C described, the z. B. contain a polyacrylamide, a polyacrylic acid derivative, a polyvinylpyrrolidone, a polyvinyl alcohol, a polyvinylimidazole, a polyethylene oxide, a polystyrene sulfonic acid or a cellulose derivative. The biological material can be further hardened to different degrees, that is, cross-linked, e.g. B. by crosslinking via amino groups using bisvinylsulfones, aldehydes, cyanuric chlorides or epoxides or by crosslinking via carboxyl and amino groups using carbodiimides or carbamoylpyridium or by crosslinking via carboxyl groups using aziridine derivatives. Other suitable curing agents are in Res. Discl. 38 957 (1996) on p. 599, Chapter II, B.
Die Folien aus biologischem Material, insbesondere aus Gelatine besitzen viele Vor- züge: Sie lassen sichThe films made of biological material, especially gelatin, have many advantages: They can be
als dünne Schichten, als exakte Schichten, mit vielen Schichten, als Schichten mit vorbestimmten Eigenschaften als flexible Schichtenas thin layers, as exact layers, with many layers, as layers with predetermined properties as flexible layers
herstellen.produce.
Die Herstellung erfolgt insbesondere dadurch, daß das den Folien zugrundeliegende biologische Material als wäßrige Lösung mittels einer geeigneten Gießvorrichtung auf eine Trägerfolie gegossen und nach der Trocknung abgezogen wird. Dies wird vorteilhaft mit einem Kaskaden- oder einem Vorhanggießer kontinuierlich durchgeführt.The production takes place in particular in that the biological material on which the films are based is poured as an aqueous solution onto a carrier film by means of a suitable pouring device and is removed after drying. This is advantageously carried out continuously with a cascade or a curtain caster.
Die Gießvorrichtungen sind beispielsweise aus der Herstellung fotografischer Materialien bekannt. Als Trägerfolien kommen insbesondere Cellulosetiiacetatfolie und beidseitig mit Polyethylen beschichtetes Papier in Betracht, die beide als Trägermaterialien für fotografische Materialien bekannt sind. Weiterhin kommen auch Folien aus Polyester (PET oder PEN), Polycarbonat infrage.The casting devices are known, for example, from the production of photographic materials. Suitable carrier films are, in particular, cellulose acetate film and paper coated on both sides with polyethylene, both of which are known as carrier materials for photographic materials. Films made of polyester (PET or PEN) and polycarbonate are also suitable.
Im Gegensatz zu fotografischen Materialien werden die Trägerfolien nicht mit Substrat- oder Haftschichten ausgerüstet, die die nachfolgenden aufgegossenen Schichten bekanntlich an die Trägerfolie binden sollen, da die aufgegossene Schicht nach der Herstellung abgezogen werden soll.In contrast to photographic materials, the carrier films are not equipped with substrate or adhesive layers, which are known to bind the subsequent cast layers to the carrier film, since the cast layer is to be removed after production.
Die Wirkstoffe werden den Gießlösungen zugesetzt und so in die späteren Folien eingebaut. Dabei ist eine exakte Dosierung möglich. Ferner kann der Wirkstoff z. B. verteilt in einer spezifischen Umgebung eingebracht werden, beispielsweise in einer Lösung in einem hochsiedenden organischen Lösungsmittel, das in der wäßrigenThe active ingredients are added to the casting solutions and thus incorporated into the later films. An exact dosage is possible. Furthermore, the active ingredient z. B. distributed in a specific environment, for example in a solution in a high-boiling organic solvent, which is in the aqueous
Gießlösung emulgiert wird.Casting solution is emulsified.
Der Wirkstoff kann auch in Form eines beladenen Latex eingebracht werden. Dabei wird ein Latex mit dem wasserlöslichen Wirkstoff imprägniert oder beladen. Diese Einbringmethode ist für fotografische Farbkuppler in Res. Discl. 38 957 (1996), S.The active ingredient can also be introduced in the form of a loaded latex. A latex is impregnated or loaded with the water-soluble active ingredient. This insertion method is for photographic color couplers in Res. Discl. 38 957 (1996), p.
623 beschrieben.623.
Die erfindungsgemäße Folie kann aus mehreren Schichten bestehen. Dies ist dann von Vorteil, wenn in einer Folie wenigstens zwei Wirkstoffe, die untereinander un- verträglich sind, enthalten sein sollen, da man sie in unterschiedlichen Schichten einbringen kann. Ebenso ist es möglich, in den unterschiedlichen Schichten Wirkstoffe in unterschiedlicher Konzentrationen vorzusehen, um bei der späteren Verwendung eine gezielte Freisetzung des Wirkstoffs in unterschiedlicher Menge zu ermöglichen.The film according to the invention can consist of several layers. This is advantageous if at least two active ingredients which are incompatible with one another are to be contained in a film, since they can be introduced in different layers. It is also possible to provide active substances in different concentrations in the different layers, in order to enable a targeted release of the active substance in different amounts during later use.
Zur Herstellung einer pharmazeutischen Darreichungsform kann die Folie in kleine und kleinste Teile geschnitten und so appliziert werden, sei es in einer dieser Teile enthaltenden festen oder flüssigen Darreichungsform, beispielsweise in einer Tablette oder in einem Saft.To produce a pharmaceutical dosage form, the film can be cut into small and very small parts and applied in this way, be it in one of these parts containing solid or liquid dosage form, for example in a tablet or in a juice.
Weiterhin ist es möglich, größere Folienstücke in Form eines Pflasters zu verwenden.It is also possible to use larger pieces of film in the form of a plaster.
Die Freisetzung geschieht durch Abbau der Foliensubstanz, im Falle einer Gelatinefolie durch enzymatischen Abbau, insbesondere durch ein Enzym des Organismus, der mit dem Wirkstoff behandelt werden soll, beispielsweise mit Trypsin.The release occurs through degradation of the film substance, in the case of gelatin film through enzymatic degradation, in particular through an enzyme of the organism that is to be treated with the active ingredient, for example with trypsin.
Soll eine besonders langsame Wirkstoffgabe und verbunden damit ein besonders langsamer Abbau der Folie erreicht werden, ist es möglich, die Folie beidseitig mit nicht abbaubaren Schutzschichten zu versehen, was bereits bei der Herstellung geschehen kann, um einem Abbau und damit eine Wirkstofffreisetzung nur über die Schnittkanten der kleinen Folienstücke zu ermöglichen.If a particularly slow administration of active ingredient and, in connection therewith, a particularly slow degradation of the film is to be achieved, it is possible to provide the film with protective layers that cannot be degraded on both sides, which can already happen during manufacture, in order to break down and thus release the active ingredient only over the cut edges to enable the small pieces of film.
Aus dem Vorhergesagten ergeben sich zwanglos weitere Möglichkeiten einzelne oder mehrere Wirkstoffe in gewünschter Weise einem Organismus zuzuführen. From what has been said, there are additional options for adding single or multiple active ingredients to an organism in the desired manner.
BeispieleExamples
Herstellung der Wirkstoff-EmulsionenPreparation of the active ingredient emulsions
Emulsion 1Emulsion 1
9 g Metipranolol und 10,0 g Olivenöl werden in 70,0 g Essigester gelöst und in eine wässrige Lösung aus 10,0 g Gelatine, 350 g Wasser und 0,5 g Dodecylbenzolsulfonat mittels einer Emulgiergerätes bei 40°C innerhalb von 10 min einemulgiert. Dabei wird der Essigester verdampft und man erhält eine O/W Emulsion, die mit Wasser auf9 g of metipranolol and 10.0 g of olive oil are dissolved in 70.0 g of ethyl acetate and emulsified in an aqueous solution of 10.0 g of gelatin, 350 g of water and 0.5 g of dodecylbenzenesulfonate using an emulsifier at 40 ° C. within 10 minutes , The ethyl acetate is evaporated and an O / W emulsion is obtained, which is mixed with water
500 g aufgefüllt wird.500 g is filled up.
Emulsion 2Emulsion 2
12,0 g Betaxolol und 90,0 g Olivenöl werden in 80 g Essigester gelöst und in einer wässrigen Lösung aus 6,0 g Gelatine, 350 g Wasser und 0,5 g Dodecylbenzolsufonat mittels eines Emulgiergerätes bei 40°C innerhalb von 12 min einemulgiert. Dabei wird der Essigester verdampft und man erhält ein O/W Emulsion, die mit Wasser auf 500 g aufgefüllt wird.12.0 g of Betaxolol and 90.0 g of olive oil are dissolved in 80 g of ethyl acetate and emulsified in an aqueous solution of 6.0 g of gelatin, 350 g of water and 0.5 g of dodecylbenzenesulfonate using an emulsifier at 40 ° C. within 12 minutes , The ethyl acetate is evaporated and an O / W emulsion is obtained, which is made up to 500 g with water.
Herstellung der WirkstoffgießlösungenPreparation of the active ingredient casting solutions
Gießlösung 1Pouring solution 1
160 g der Emulsion 1 werden bei 40°C mit 66 g 20 gew.-% Gelatine, 90 g Wasser und 4,0 g 10 gew.-%iger Sulfobernsteinsäuredioctylester, Na-Salz-Lösung (Netzmittel) versetzt und mit Wasser auf 350 g aufgefüllt. Gießlösung 2160 g of emulsion 1 are mixed at 40 ° C. with 66 g of 20% by weight gelatin, 90 g of water and 4.0 g of 10% by weight dioctyl sulfosuccinate, sodium salt solution (wetting agent) and water to 350 g filled up. Pouring solution 2
160 g der Emulsion 2 werden bei 40°C mit 70 g 20 gew.-%iger Gelatine, 90 g Wasser und 4,0 g 10 gew.-%iger Sulfobernsteinsäuredioctylester, Na-Salz-Lösung (Netzmittel) versetzt und mit Wasser auf 350 g aufgefüllt.160 g of emulsion 2 are mixed at 40 ° C. with 70 g of 20% by weight gelatin, 90 g of water and 4.0 g of 10% by weight dioctyl sulfosuccinate, sodium salt solution (wetting agent) and water Replenished 350 g.
Härterlösunghardener solution
9,2 g Bisvinylsufonylmethan werden in 450 g einer Mischung aus 30 g Ethanol und 420 g Wasser gelöst und mit 6 g einer 10 gew.-%igen Netzmittel-Lösung auf der9.2 g of bisvinylsufonylmethane are dissolved in 450 g of a mixture of 30 g of ethanol and 420 g of water and with 6 g of a 10% strength by weight wetting agent solution
Basis einer Triterpenverbindung (Saponin) versetzt.Base of a triterpene compound (saponin) added.
Enzymatisch abbaubare FolieEnzymatically degradable film
Mit einem aus der Herstellung fotografischer Materialien bekannten Kaskadengießer wird eine nicht substrierte Polyethylenterephthalat-Folie mitA cascade caster known from the manufacture of photographic materials is used to add a non-subbed polyethylene terephthalate film
1. Gießlösung 11. Casting solution 1
2. Gießlösung 22. Casting solution 2
3. Gießlösung 1 4. Härterlösung3. Casting solution 1 4. Hardening solution
beschichtet. Dabei wird der Auftrag so gewählt, daß nach Trocknung bei 50°C ein Verband aus 3 Schichten mit Schichtaufträgen voncoated. The application is chosen so that after drying at 50 ° C a dressing of 3 layers with layer applications of
Schicht 1 10 g / m2 Layer 1 10 g / m 2
Schicht 2 20 g / m2 Layer 2 20 g / m 2
Schicht 3 10 g / m2 Layer 3 10 g / m 2
erhalten wird. Der nicht haftende Schichtverband wird von der Polyethylenterephthalat-Folie abgezogen und in 1 mm2 große Stücke zerschnitten. Test auf selektive Wirkstoff-Freisetzungis obtained. The non-adherent layer structure is pulled off the polyethylene terephthalate film and cut into 1 mm 2 large pieces. Selective drug release test
1. In 100 g auf pH 8 gepuffertem Wasser wurden 0,5 g der o. g. Folienstücke dispergiert und 1 Stunde bei 20°C gerührt. Anschließend wird filtriert und das Filtrat analysiert. Es wird kein Wirkstoff gefunden.1. In 100 g of water buffered to pH 8, 0.5 g of the above. Pieces of film dispersed and stirred at 20 ° C for 1 hour. It is then filtered and the filtrate is analyzed. No active ingredient is found.
2. In 100 g auf pH 8 gepuffertem Wasser werden 0,5 g der o. g. Folienstücke dispergiert und anschließend mit 10 g einer 3 gew.-%igen Trypsin-Lösung versetzt und bei 20°C gerührt. Es wurden nach 10 min. (Probe 1) und nach 60 min. (Probe 2) Proben genommen, abfiltriert und die Filtrate analysiert Ergebnis: Probe 1 enthält auschließlich Metipranolol2. In 100 g of water buffered to pH 8, 0.5 g of the above. Dispersed pieces of film and then mixed with 10 g of a 3 wt .-% trypsin solution and stirred at 20 ° C. After 10 min. (Sample 1) and after 60 min. (Sample 2) Samples taken, filtered off and the filtrates analyzed. Result: Sample 1 contains only metipranolol
Probe 2 enthält Metipranolol und BetaxololSample 2 contains metipranolol and betaxolol
Der Test zeigt, daß die Folienstücke durch enzymatischen Abbau die Wirkstoffe nacheinander selektiv abgeben. The test shows that the pieces of film selectively release the active substances one after the other by enzymatic degradation.

Claims

Patentansprüche claims
1. Eine wenigstens einen Wirkstoff enthaltende Folie, die unter den Bedingungen des Wirkortes wenigstens teilweise abgebaut wird.1. A film containing at least one active ingredient, which is at least partially degraded under the conditions of the site of action.
2. Folie nach Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff eine niedermolekulare organische Verbindung ist.2. Film according to claim 1, characterized in that the active ingredient is a low molecular weight organic compound.
3. Folie nach Ansprüchen 1 oder 2, dadurch gekennzeichnet, daß der Wirkstoff eine auf einen Organismus gerichtete Wirkung entfaltet.3. Film according to claims 1 or 2, characterized in that the active ingredient has an action directed towards an organism.
4. Folie nach Anspruch 3, dadurchgekennzeichnet, daß die Wirkung eine pharma- kologische Wirkung ist.4. Film according to claim 3, characterized in that the effect is a pharmacological effect.
5. Folie nach Anspruch 1, dadurch gekennzeichnet, daß sie aus biologischem Material besteht.5. A film according to claim 1, characterized in that it consists of biological material.
6. Folie nach Anspruch 5, dadurch gekennzeichnet, daß sie aus einem teilweise abgebauten Polypeptid besteht.6. Film according to claim 5, characterized in that it consists of a partially degraded polypeptide.
7. Folie nach Anspruch 6, dadurch gekennzeichnet, daß sie enzymatisch abbaubar ist.7. Film according to claim 6, characterized in that it is enzymatically degradable.
8. Folie nach Anspruch 1, dadurch gekennzeichnet, daß sie aus einer einzigen Schicht besteht.8. A film according to claim 1, characterized in that it consists of a single layer.
9. Folie nach Anspruch 1, dadurch gekennzeichnet, daß sie aus mehreren Schichten besteht.9. A film according to claim 1, characterized in that it consists of several layers.
10. Folie nach Anspruch 9, dadurch gekennzeichnet, daß die einzelnen Schichten wenigstens einen Wirkstoff in unterschiedlichen Konzentrationen enthalten. 10. A film according to claim 9, characterized in that the individual layers contain at least one active ingredient in different concentrations.
11. Folie nach Anspruch 9, dadurch gekennzeichnet, daß die einzelnen Schichten unterschiedliche Wirkstoffe enthalten.11. A film according to claim 9, characterized in that the individual layers contain different active ingredients.
12. Verfahren zur Herstellung einer Folie nach einem der Ansprüche 1 bis 11, dadurch gekennzeichnet, daß eine wäßrige Lösung des die Folien bildenden Materials, die den wenigstens einen Wirkstoff enthält, mittels einer geeigneten Gießvorrichtung auf eine Trägerfolie gegossen, getrocknet und von der Trägerfolie abgezogen wird. 12. A method for producing a film according to any one of claims 1 to 11, characterized in that an aqueous solution of the material forming the film, which contains the at least one active ingredient, is poured onto a carrier film by means of a suitable casting device, dried and removed from the carrier film becomes.
EP03730175A 2002-05-24 2003-04-04 At least partially degradable films containing an active ingredient and method for the production thereof Withdrawn EP1519718A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10223435 2002-05-24
DE10223435 2002-05-24
PCT/EP2003/050092 WO2003099263A1 (en) 2002-05-24 2003-04-04 At least partially degradable films containing an active ingredient and method for the production thereof

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EP1519718A1 true EP1519718A1 (en) 2005-04-06

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EP03730175A Withdrawn EP1519718A1 (en) 2002-05-24 2003-04-04 At least partially degradable films containing an active ingredient and method for the production thereof

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US (1) US20060134184A1 (en)
EP (1) EP1519718A1 (en)
JP (1) JP2005531569A (en)
CN (1) CN1655771A (en)
AU (1) AU2003240762A1 (en)
WO (1) WO2003099263A1 (en)

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2966275D1 (en) * 1978-11-07 1983-11-10 Beecham Group Plc Device for oral administration to a ruminant animal
JPS5647761A (en) * 1979-09-27 1981-04-30 Fuji Photo Film Co Ltd Laminated analyzing piece and immunity analyzing method using the same
DE69004415D1 (en) * 1990-03-05 1993-12-09 Minnesota Mining & Mfg Device for delayed delivery of pharmacologically active compounds into the ear.
GB2280850B (en) * 1993-07-28 1997-07-30 Johnson & Johnson Medical Absorbable composite materials for use in the treatment of periodontal disease
US5800832A (en) * 1996-10-18 1998-09-01 Virotex Corporation Bioerodable film for delivery of pharmaceutical compounds to mucosal surfaces
DE19646392A1 (en) * 1996-11-11 1998-05-14 Lohmann Therapie Syst Lts Preparation for use in the oral cavity with a layer containing pressure-sensitive adhesive, pharmaceuticals or cosmetics for dosed delivery
DE19960154A1 (en) * 1999-12-14 2001-07-12 Lohmann Therapie Syst Lts Flat pharmaceutical preparation for transmucosal administration of oxycodone or a comparable active ingredient in the oral cavity, for use in pain therapy and addiction therapy
WO2003020191A1 (en) * 2001-09-04 2003-03-13 University Of Iowa Research Foundation Cellulose membranes for biodegradable scaffolds
US7204994B2 (en) * 2003-02-03 2007-04-17 Ashland Licensing And Intellectual Property Llc Juvenile hormone compositions and methods for making same

Non-Patent Citations (1)

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Title
See references of WO03099263A1 *

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AU2003240762A1 (en) 2003-12-12
US20060134184A1 (en) 2006-06-22
CN1655771A (en) 2005-08-17
WO2003099263A1 (en) 2003-12-04
JP2005531569A (en) 2005-10-20

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