DE19646392A1 - Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden Schicht - Google Patents
Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden SchichtInfo
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- DE19646392A1 DE19646392A1 DE19646392A DE19646392A DE19646392A1 DE 19646392 A1 DE19646392 A1 DE 19646392A1 DE 19646392 A DE19646392 A DE 19646392A DE 19646392 A DE19646392 A DE 19646392A DE 19646392 A1 DE19646392 A1 DE 19646392A1
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- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0208—Tissues; Wipes; Patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/731—Cellulose; Quaternized cellulose derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/817—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions or derivatives of such polymers, e.g. vinylimidazol, vinylcaprolactame, allylamines (Polyquaternium 6)
- A61K8/8176—Homopolymers of N-vinyl-pyrrolidones. Compositions of derivatives of such polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/90—Block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
- A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nutrition Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Emergency Medicine (AREA)
- Physiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pulmonology (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- General Preparation And Processing Of Foods (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Absorbent Articles And Supports Therefor (AREA)
- Materials For Medical Uses (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Dental Preparations (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Description
Zubereitung zur Anwendung in der Mundhöhle mit einer an
der Schleimhaut haftklebenden, Pharmazeutika oder
Kosmetika zur dosierten Abgabe enthaltenden Schicht.
Derartige an der Mundschleimhaut haftklebende Dosier
systeme zur Anwendung in der Mundhöhle sind bekannt.
Die US 5,047,244 beschreibt einen an der Mund
schleimhaut haftklebenden Träger zur kontrollierten
Abgabe eines therapeutischen Wirkstoffs durch das
Schleimhautgewebe, der eine wasserfreie, aber
hydratisierbare Polymermatrix und amorphes Siliciumdioxid
enthält.
Fakultativ kann ein wasserunlöslicher Film beigefügt
werden, um die Oberfläche nichtadhäsiv zu gestalten.
Die WO 91/06270 des gleichen Erfinders offenbart einen
dreischichtigen Film zur verlängerten Abgabe eines
aktiven Wirkstoffs in der Mundhöhle.
In gleicher Weise offenbart US 4,876,092 eine
flächenförmige, adhäsive Zubereitung, umfassend eine
adhäsive Schicht, welche bestimmte wasserlösliche und
wasserunlösliche Polymere und einen wasserunlöslichen
Träger enthält, welcher an der Mundschleimhaut haftet und
dabei einen aktiven Wirkstoff an die Mundhöhle abgibt.
Alle diese vorgenannten Vorrichtungen sind nicht
vollständig wasserlöslich und verbleiben in der
Mundhöhle, selbst nach Erreichen des therapeutischen
Ziels, und bereiten dem Patienten ein gewisses Unbehagen
im Mund, das hauptsächlich durch die Trägerschicht
verursacht wird, welche einen unlöslichen Rückstand im
Mund zurückläßt.
Eine Reihe von Versuchen wurde unternommen, um das ungute
Gefühl in der Mundhöhle zu verringern, welches durch die
Starrheit und mangelnde Flexibilität der
Trägerschicht verursacht wurde, indem man weiche
Filmträger einführte. Die Dokumente EP 0 200 508 und
EP 0 381 194 schlagen die Verwendung von Polyethylen
filmen, Polyvinylacetat, Ethylen-Vinylacetat-Copolymeren,
Metallfolien, Stofflaminaten, Papier- oder Plastikfilm
und ähnlichen Materialien als weiche Träger vor, wobei
synthetische Harze wie Polyethylen, Vinylacetat-
Homopolymere und Ethylen-Vinyl-Acetat bevorzugte
Materialien sind. In gleicher Weise offenbart
CA-PS 1 263 312 die Verwendung von Polyolefinen wie
Polyethylen, Polypropylen, Polyester, PVC, sowie
Vliesstoffen als weiche Trägermaterialien.
Dennoch hinterlassen diese beim Patienten eine
beträchtliche Menge von Rückständen des wasser
unlöslichen Trägerfilms und verursachen dabei immer noch
ein unbehagliches Gefühl. Eine naheliegende Lösung zur
Überwindung dieses Problems war die Entwicklung
schleimhauthaftender Filme, welche vollständig zerfallen
oder sich im Speichel auflösen.
Fuchs und Hilmann (DE 24 49 865.5) stellten homogene,
wasserlösliche Filme für buccale Zuführung von Hormonen
her. Sie schlugen die Verwendung von wasserlöslichen
Cellulosederivaten wie Hydroxyethylcellulose, Hydroxy
propylcellulose oder Methylhydroxypropylcellulose als
Filmbildner vor.
Die beiden Patentschriften DE 36 30 603 und EP 0 219 762
offenbaren die Verwendung von quellbaren Polymeren wie
Gelatine oder Maisstärke als Filmbildner, welche nach
Applikation in der Mundhöhle langsam zerfallen, wobei sie
einen aktiven Wirkstoff freisetzen, der im Film enthalten
ist. Die gleichen Polymere können ebenfalls verwendet
werden, um Filme herzustellen, die zur Zahnpflege dienen
sollen, entsprechend der Beschreibung in EP 0 452 446.
Aber auch diese Zubereitungen rufen ebenfalls ein ungutes
Gefühl im Mund hervor, insbesondere verursacht durch ihre
anfängliche Starrheit und verzögerte Erweichung.
Hieraus resultiert ein Bedarf für eine Komposition zur
Verwendung in der Mundhöhle, die dem Erfordernis eines
Wohlgefühls im Mund Rechnung trägt.
Der vorliegenden Erfindung liegt daher die Aufgabe
zugrunde, eine Zubereitung anzugeben, die geeignet ist,
ein angenehmes Gefühl im Mund zu erzeugen, indem sie
einen Film zur Applikation an der Mundschleimhaut
vorsieht, der eine sofortige Benetzbarkeit aufweist und
eine haftklebende Befestigung in der Mundhöhle unter
Abgabe pharmazeutischer oder kosmetischer Wirkstoffe,
ermöglicht, die sich rasch auflöst bzw. zerfällt.
Die Lösung der Aufgabe gelingt bei einer Zubereitung der
im Oberbegriff von Anspruch 1 genannten Art mit der
Erfindung dadurch, daß die haftklebende Schicht eine
homogene Mischung enthält, bestehend aus einem
wasserlöslichen Polymer, einer Mischung nichtionischer
oberflächenaktiver Stoffe, einem Polyalkohol, einem
kosmetischen oder pharmazeutischen Wirkstoff, und einem
Geschmacksstoff.
Mit großem Vorteil ist der daraus resultierende Film
charakterisiert durch eine sofortige Benetzbarkeit,
welche den Film unverzüglich nach Applikation am
Schleimhautgewebe erweichen läßt und beim Patienten ein
unangenehmes Gefühl im Mund verhindert.
Der Film ist unter Verwendung konventioneller
Beschichtungs- und Trocknungstechniken herstellbar, in
Form und Größe nach Anforderungen spezieller Applikation
vereinzelbar und in geeignete Packungen verpackbar.
Eine Ausgestaltung der Erfindung sieht vor, daß das
wasserlösliche Polymer der Zubereitung
Hydroxypropylmethylcellulose, Hydroxy-ethylcellulose,
Hydroxypropylcellulose, Polyvinylpyrrolidon,
Carboxymethylcellulose, Polyvinylalkohol, Natriumalginat,
Polyethylenglycol, Xanthanharz, Traganth, Guarharz,
Akazienharz, Gummiarabicum, Polyacrylsäure,
Methylmethacrylatcopolymer, Carboxyvinylcopolymere oder
deren Mischungen umfaßt.
Dabei ist vorgesehen, daß die Konzentration des wasser
löslichen Polymers in der Trockenmasse der Filmschicht
zwischen 20 und 60 Gew.-% beträgt. Eine bevorzugte
Konzentration beträgt zwischen 30 und 50 Gew.-%.
Weiterhin ist mit der Erfindung vorgesehen, daß die
Mischung der oberflächenaktiven Stoffe vorzugsweise aus
zwei Komponenten besteht. Dabei ist die erste Komponente
ein Polyethoxysorbitan-fettsäureester oder ein α-hydro
ω-hydroxypoly(ethoxy)-poly-(propoxy)-poly(ethoxy)-
Blockcopolymer.
Die zweite Komponente ist ein Polyethoxy-alkylether oder
ein Polyethoxy-rizinusölderivat.
Bevorzugt soll der HLB-Wert der Polyethoxysorbitanfett
säurester zwischen 10 und 20 betragen, wobei ein Bereich
zwischen 13 und 17 besonders bevorzugt ist. Das α
hydro-ω-hydroxypoly(ethoxy)-poly(propoxy)-poly(ethoxy)-
Blockcopolymer soll mindestens 35 Propoxy-Einheiten,
bevorzugt mindestens 50 Propoxy-Einheiten enthalten.
Der Polyethoxyalkylether sollte einen HLB-Wert zwischen
10 und 20 besitzen, bevorzugt nicht weniger als 15. Das
Polyethoxy-rizinusölderivat soll einen HLB-Wert zwischen
14 und 16 besitzen.
Um die erwünschte, sofortige Benetzbarkeit zu erreichen,
soll das Verhältnis zwischen der ersten und der zweiten
Komponente einer binären oberflächenaktiven Mischung
zwischen 1 : 10 und 1 : 1 gehalten werden, bevorzugt zwischen
1 : 5 und 1 : 3.
Die Gesamtkonzentration der oberflächenaktiven Stoffe im
Film hängt ab von den Eigenschaften der anderen
Ingredienzien, soll jedoch üblicherweise zwischen 1 und
5 Gew.-% betragen.
Der Polyalkohol wird benötigt, um den erwünschten
Weichheitsgrad des Filmes zu erreichen. Beispiele von
Polyalkoholen umfassen Glycerin, Polyethylenglycol,
Propylenglycol, Glycerinmonoester mit Fettsäuren, oder
sonstige pharmazeutisch verwendete Polyalkohole. Die
Konzentration von Polyalkohol in der Trockenmasse des
Filmes beträgt üblicherweise 4 bis 25 Gew.-%.
Der Film ist besonders gut geeignet zur Abgabe eines
weiten Bereiches pharmazeutisch aktiver Wirkstoffe durch
die Schleimhautmembranen eines Patienten, insbesondere
durch die buccalen Schleimhäute.
Therapeutische Wirkstoffe, die Absorptionsprobleme
infolge begrenzter Löslichkeit, Abbau im
Gastrointestinaltrakt oder extensiven Metabolismus haben,
sind besonders gut geeignet. Als Beispiele der
einsetzbaren
therapeutischen Wirkstoffe sind zu nennen: Hypnotica,
Sedativa, Antiepileptica, Weckamine, Psychoneurotropica,
Neuro-Muskelblocker, Antispasmodica, Antihistaminica,
Antiallergica, Cardiotonica, Antiarrhythmica, Diuretica,
Hypotensiva, Vasopressoren, Antitussiva, Expectorantia,
Thyroidhormone, Sexualhormone, Antidiabetica, Antitumor-
Wirkstoffe, Antibiotica sowie Chemotherapeutica und
Narcotica. Die im Film einzulagernde Menge von Wirkstoff
hängt von dessen Art ab und beträgt üblicherweise
zwischen 0,01 und 20 Gew.-%.
Kosmetische Wirkstoffe umfassen Atemerfrischer wie
Menthol, andere Geschmacks-, Aroma- oder Duftstoffe, wie
sie üblicherweise für Mundhygiene oder Zahnpflege
verwendet werden, beispielsweise quartäre Ammoniumbasen.
Die Wirkung von Geschmacks- und Aromastoffen kann durch
Geschmacksverstärker wie Weinsäure, Zitronensäure,
Vanillin oder dergleichen verstärkt werden.
Farbstoffe, welche wahlweise dem Film beigemischt werden,
müssen hinsichtlich Toxizität sicher sein und sollten zur
Verwendung in Kosmetika durch die zuständigen Behörden
zugelassen sein.
Der erfindungsgemäße mucoadhäsive Film kann folgender
maßen hergestellt werden:
Wirkstoff, oberflächenaktive Stoffe, Polyalkohol und andere mögliche Bestandteile außer dem wasserdispersiblen Polymer werden mit einer genügenden Menge eines kompatiblen Lösungsmittels gelöst. Beispiele eines kompatiblen Lösungsmittels umfassen Wasser, Alkohole oder deren Mischungen. Nach Bildung einer klaren Lösung wird das wasserdispersible Polymer oder die Mischung wasserdispersibler Polymere langsam unter Rühren zugegeben, bis eine klare und homogene Lösung gebildet ist. Diese wird auf einen Träger aufgetragen und zu einem Film getrocknet. Das Trägermaterial muß eine Oberflächenspannung haben, die es ermöglicht, die Polymerlösung gleichmäßig über die vorgesehene Beschichtungsbreite zu verteilen. Beispiele für geeignete Materialien umfassen nichtsilikonisierte Polyethylen-Terephthalat-Filme, nichtsiliconisiertes Kraftpapier, oder nichtsiliconisierten Polyethylenfilm. Der Auftrag der Lösung auf das Trägermaterial kann mit jeder geeigneten Vorrichtung ausgeführt werden. Eine speziell bevorzugte Auftragstechnik betrifft eine Walzenrakel-Streichmaschine.
Wirkstoff, oberflächenaktive Stoffe, Polyalkohol und andere mögliche Bestandteile außer dem wasserdispersiblen Polymer werden mit einer genügenden Menge eines kompatiblen Lösungsmittels gelöst. Beispiele eines kompatiblen Lösungsmittels umfassen Wasser, Alkohole oder deren Mischungen. Nach Bildung einer klaren Lösung wird das wasserdispersible Polymer oder die Mischung wasserdispersibler Polymere langsam unter Rühren zugegeben, bis eine klare und homogene Lösung gebildet ist. Diese wird auf einen Träger aufgetragen und zu einem Film getrocknet. Das Trägermaterial muß eine Oberflächenspannung haben, die es ermöglicht, die Polymerlösung gleichmäßig über die vorgesehene Beschichtungsbreite zu verteilen. Beispiele für geeignete Materialien umfassen nichtsilikonisierte Polyethylen-Terephthalat-Filme, nichtsiliconisiertes Kraftpapier, oder nichtsiliconisierten Polyethylenfilm. Der Auftrag der Lösung auf das Trägermaterial kann mit jeder geeigneten Vorrichtung ausgeführt werden. Eine speziell bevorzugte Auftragstechnik betrifft eine Walzenrakel-Streichmaschine.
Die Dicke der resultierenden Filmschicht hängt von der
Konzentration der Feststoffe in der Beschichtungslösung
sowie von der Spaltbreite der Beschichtungsmaschine ab
und kann zwischen 5 und 200 µm variieren. Die Trocknung
des Films wird in einem Heißluftbad unter Verwendung
eines Trockenofens, Trockentunnels, Vakuumtrockners oder
anderer geeigneter Trockenvorrichtungen vorgenommen. Um
ein unangenehmes Gefühl im Mund zuverlässig zu vermeiden,
soll die Filmdicke 70 µm nicht überschreiten. Zur
besseren Gebrauchserleichterung kann der Film in Stücke
von geeigneter Größe und Form geschnitten und verpackt
werden.
Die Erfindung wird anhand nachfolgender Beispiele
veranschaulicht.
15 g Sorbit, 6 g Glycerin, 0,5 g Polysorbat 80 (Tween
80), 2 g Brij 35, 25 g Zitronenminzearoma, 3 g Aspartam,
15 g l-Menthol und 3 g Zitronensäure werden bei 60°C in
einer Mixtur von 250 g Wasser und 250 g Ethanol solange
gerührt, bis sich eine klare Lösung gebildet hat.
Zu der Lösung werden 30 g Hydroxypropylmethylcellulose
langsam unter Rühren zugegeben, bis eine klare und
homogene Lösung
gebildet ist. Die resultierende Lösung wird dann bis auf
Raumtemperatur abkühlen gelassen und unter Verwendung
einer üblichen Beschichtungsvorrichtung auf ein
geeignetes Trägermaterial aufgestrichen, beispielsweise
nichtsiliconisiertes polyethylenbeschichtetes
Kraftpapier.
Beschichtungsspalt und Bahngeschwindigkeit müssen so
geregelt werden, daß eine Trockenfilmdicke zwischen 20
und 50 µm erreicht wird. Die Trockentemperatur hängt von
der Länge des Trockenofens und der
Materialgeschwindigkeit ab und soll so eingestellt
werden, daß die Lösungsmittel vollständig, oder zumindest
weitgehend vollständig vom Film entfernt werden. Der
resultierende Film wird vom Träger abgelöst und zum
Gebrauch in Stücke von geeigneter Größe und Form
zerteilt.
3 g Sorbit, 1,5 g Kollidon 30 (Lieferant: BASF), 5 g
Glycerin, 5 g Propylenglycol, 5 g Polyethylenglycol, 4 g
Polysorbat 80 (Tween 80), 8 g Brij 35, 12 g
Pfefferminzaroma, 0,8 g Aspartam werden in einer Mischung
von 400 g Wasser und 400 g Ethanol bei 60°C unter Rühren
aufgelöst. Zu der klaren Lösung werden 28 g
Hydroxypropylmethylcellulose unter Rühren langsam
zugegeben. Nach völliger Auflösung des Polymers wird die
Lösung auf Raumtemperatur abgekühlt und auf einen Träger
unter den gleichen Bedingungen wie in Beispiel 1
aufgestrichen. Der trockene Film wird wieder in Stücke
von geeigneter Größe und Form zerteilt.
15 g Sorbit, 22,5 g Glycerin, 2,5 Propylenglycol, 2,5 g
Brij 35, 2,5 g Poloxamer 407, 3,5 g Cremophor RH 40, 9 g
Kräuterminzearoma, 0,5 g Aspartam werden unter ständigem
Rühren bei 60°C in einer Mischung von 250 g Wasser und
250 g Ethanol gelöst. Zu der klaren Lösung werden 75 g
Hydroxypropylcellulose unter ständigem Rühren langsam
zugegeben. Mit der klaren Lösung wird wiederum
beschichtet und unter den beschriebenen Bedingungen
getrocknet, wie in Beispiel 1; der trockene Film wird in
Stücke von geeigneter Größe und Form zerteilt.
Claims (9)
1. Zubereitung zur Anwendung in der Mundhöhle mit einer
an der Schleimhaut haftklebenden Schicht, dadurch
gekennzeichnet, daß die haftklebende Schicht eine
homogene Mischung enthält, bestehend aus einem
wasserlöslichen Polymer, einer Mischung nichtionischer
oberflächenaktiver Stoffe, einem Polyalkohol, einem
kosmetischen oder pharmazeutischen Wirkstoff, und einem
Geschmacks- oder Aromastoff.
2. Zubereitung nach Anspruch 1, dadurch gekennzeichnet,
daß das wasserlösliche Polymer Hydroxypropyl
methylcellulose, Hydroxyethylcellulose,
Hydroxypropylcellulose, Polyvinylpyrrolidon,
Carboxylmethylcellulose, Polyvinylalkohol,
Natriumalginat, Polyethylenglycol, Xanthanharz, Traganth,
Guarharz, Akazienharz, Gummiarabicum, Polyacrylsäure,
Methylmethacrylatcopolymer, Carboxyvinylcopolymere oder
deren Mischungen umfaßt.
3. Zubereitung nach Anspruch 1, dadurch gekennzeichnet,
daß die Konzentration des wasserlöslichen Polymers in der
Trockenmasse der Filmschicht zwischen 20 und 60 Gew.-%
beträgt.
4. Zubereitung nach Anspruch 1, dadurch gekennzeichnet,
daß die Mischung der oberflächenaktiven Stoffe aus zwei
Komponenten besteht.
5. Zubereitung nach Anspruch 4, dadurch gekennzeichnet
daß die erste Komponente des oberflächenaktiven Stoffs
ein Polyethoxysorbitan-fettsäureester oder ein α-hydro
ωhydroxypoly(ethoxy)-poly(propoxy)-poly(ethoxy)-
Blockcopolymer ist.
6. Zubereitung nach Anspruch 4, dadurch gekennzeichnet,
daß die zweite Komponente des oberflächenaktiven Stoffs
ein Polyethoxy-alkylether oder ein Polyethoxy
rizinusölderivat ist.
7. Zubereitung nach Anspruch 1, dadurch gekennzeichnet,
daß der Polyalkohol ausgewählt ist aus Glycerin,
Polyethylenglycol, Propylenglycol oder Glycerinmonoestern
mit Fettsäuren.
8. Zubereitung nach Anspruch 1, dadurch gekennzeichnet,
daß der therapeutische Wirkstoff ausgewählt ist aus der
Gruppe von Hypnotica, Sedativa, Antiepileptica,
Weckaminen, Psychoneurotropica, Neuro-Muskelblockern,
Antispasmodica, Antihistaminica, Antiallergica,
Cardiotonica, Antiarrhythmica, Diuretica, Hypotensiva,
Vasopressoren, Antitussiva, Expectorantia,
Thyroidhormonen, Sexualhormonen, Antidiabetica,
Antitumor-Wirkstoffen, Antibiotica sowie Chemothera
peutica oder Narcotica.
9. Zubereitung nach Anspruch 1, dadurch gekennzeichnet,
daß der kosmetische Wirkstoff Atemerfrischer wie Menthol,
Geschmacks-, Aroma- oder Duftstoffe, wie sie
üblicherweise für Mundhygiene verwendet werden, und/oder
Wirkstoffe zur Zahn- oder Mundpflege umfaßt, wie
quartäre Ammoniumbasen.
Priority Applications (49)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19646392A DE19646392A1 (de) | 1996-11-11 | 1996-11-11 | Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden Schicht |
| US08/904,607 US5948430A (en) | 1996-11-11 | 1997-08-01 | Water soluble film for oral administration with instant wettability |
| TW086115552A TW533083B (en) | 1996-11-11 | 1997-10-21 | Water soluble film for oral administration with instant wettability |
| TW092105140A TWI250029B (en) | 1996-11-11 | 1997-10-21 | Water soluble film for oral administration with instant wettability |
| AT97911237T ATE247954T1 (de) | 1996-11-11 | 1997-10-22 | Sofortige benetzbarkeit aufweisende(r) wasserlöslicher film oder wasserlösliche schicht zur oralen applikation |
| DK03014213T DK1362584T3 (da) | 1996-11-11 | 1997-10-22 | Umiddelbar befugtning af vandoplöselig film eller vandoplöselig lag til oral anvendelse |
| EP97911237A EP0936905B1 (de) | 1996-11-11 | 1997-10-22 | Sofortige benetzbarkeit aufweisende(r) wasserlöslicher film oder wasserlösliche schicht zur oralen applikation |
| IDW990297A ID22526A (id) | 1996-11-11 | 1997-10-22 | Lapisan tipis yang larut dalam air untuk pemberian secara oral dengan daya pembasahan yang cepat |
| DE59710670T DE59710670D1 (de) | 1996-11-11 | 1997-10-22 | Sofortige benetzbarkeit aufweisende(r) wasserlöslicher film oder wasserlösliche schicht zur oralen applikation |
| KR1020057014063A KR100569847B1 (ko) | 1996-11-11 | 1997-10-22 | 구강에 사용가능한 조성물 |
| PL97333677A PL190376B1 (pl) | 1996-11-11 | 1997-10-22 | Preparat do stosowania w jamie ustnej |
| CZ0164799A CZ297354B6 (cs) | 1996-11-11 | 1997-10-22 | Prípravek pro aplikaci v ústní dutine s filmem nebo fólií s okamzitou smácitelností |
| HU9904207A HU228464B1 (en) | 1996-11-11 | 1997-10-22 | Immediate wettability water soluble film or water soluble layer for oral application |
| PT03014213T PT1362584E (pt) | 1996-11-11 | 1997-10-22 | Película hidrossolúvel ou camada hidrossolúvel de molhabilidade imediata para aplicação oral |
| TR1999/01633T TR199901633T2 (xx) | 1996-11-11 | 1997-10-22 | A��zdan ila� verilmesi i�in an�nda �slanabilen suda eriyebilir zar. |
| PCT/EP1997/005820 WO1998020862A1 (de) | 1996-11-11 | 1997-10-22 | Sofortige benetzbarkeit aufweisende(r) wasserlöslicher film oder wasserlösliche schicht zur oralen applikation |
| KR1019997004145A KR100604995B1 (ko) | 1996-11-11 | 1997-10-22 | 구강에 사용가능한 조성물 |
| AT03014213T ATE422157T1 (de) | 1996-11-11 | 1997-10-22 | Sofortige benetzbarkeit aufweisende(r) wasserlöslicher film oder wasserlösliche schicht zur oralen applikation |
| ES97911237T ES2206692T3 (es) | 1996-11-11 | 1997-10-22 | Pelicula soluble en agua o capa soluble en agua de humectabilidad inmediata para aplicacion oral. |
| HK00101167.5A HK1035316B (en) | 1996-11-11 | 1997-10-22 | Immediate wettability water soluble film or water soluble layer for oral application |
| JP52208898A JP4063331B2 (ja) | 1996-11-11 | 1997-10-22 | 口部に適用される瞬時湿潤性の水溶性薄膜または水溶性層 |
| SK622-99A SK285100B6 (sk) | 1996-11-11 | 1997-10-22 | Prípravok na aplikáciu v ústnej dutine s filmom alebo fóliou s okamžitou zmáčateľnosťou |
| NZ335063A NZ335063A (en) | 1996-11-11 | 1997-10-22 | Immediate wettability water soluble film or water soluble layer for oral application |
| AU48682/97A AU739698B2 (en) | 1996-11-11 | 1997-10-22 | Water soluble film for oral administration with instant wettability |
| PT97911237T PT936905E (pt) | 1996-11-11 | 1997-10-22 | Pelicula soluvel em agua ou camada soluvel em agua que possuem molhabilidade imediata para aplicacao oral |
| DE59712993T DE59712993D1 (de) | 1996-11-11 | 1997-10-22 | Sofortige Benetzbarkeit aufweisende(r) wasserlöslicher Film oder wasserlösliche Schicht zur oralen Applikation |
| IL12981997A IL129819A0 (en) | 1996-11-11 | 1997-10-22 | A mucoadhesive composition |
| DE29724755U DE29724755U1 (de) | 1996-11-11 | 1997-10-22 | Sofortige Benetzbarkeit aufweisende(r) wasserlöslicher Film oder wasserlösliche Schicht zur oralen Applikation |
| SK5041-2005A SK285999B6 (sk) | 1996-11-11 | 1997-10-22 | Orálne aplikovateľný prípravok majúci okamžitú zmáčateľnosť a spôsob jeho výroby |
| CA002265651A CA2265651C (en) | 1996-11-11 | 1997-10-22 | Immediate wettability water soluble film or water soluble layer for oral application |
| HU0500666A HU230022B1 (hu) | 1996-11-11 | 1997-10-22 | Azonnal nedvesedő, vízoldható film vagy vízoldható réteg orális alkalmazás céljára |
| ES03014213T ES2322699T3 (es) | 1996-11-11 | 1997-10-22 | Lamina o capa soluble en agua, que presenta humectabilidad inmediata para la aplicacion oral. |
| SI9730590T SI0936905T1 (en) | 1996-11-11 | 1997-10-22 | Immediate wettability water soluble film or water soluble layer for oral application |
| EP03014213A EP1362584B1 (de) | 1996-11-11 | 1997-10-22 | Sofortige Benetzbarkeit aufweisende(r) wasserlöslicher Film oder wasserlösliche Schicht zur oralen Applikation |
| DK97911237T DK0936905T3 (da) | 1996-11-11 | 1997-10-22 | Vandopløselig film eller vandopløseligt lag med øjeblikkelig befugtelighed til brug ved oral indgivelse |
| MYPI97005325A MY125548A (en) | 1996-11-11 | 1997-11-10 | Water soluble film for oral administration with instant wettability |
| ZA9710093A ZA9710093B (en) | 1996-11-11 | 1997-11-10 | Water soluble film for oral administration with instant wettability. |
| US09/287,181 US6177096B1 (en) | 1996-11-11 | 1999-04-06 | Water soluble film for oral administration with instant wettability |
| NO19991921A NO325073B1 (no) | 1996-11-11 | 1999-04-22 | Preparat for anvendelse i munnhulen med en film eller sjikt som viser oyeblikkelig fuktbarhet. |
| US09/630,562 US6284264B1 (en) | 1996-11-11 | 2000-08-02 | Water soluble film for oral administration with instant wettability |
| US09/927,327 US20010046511A1 (en) | 1996-11-11 | 2001-08-13 | Water soluble film for oral administration with instant wettability |
| US10/143,962 US6709671B2 (en) | 1996-11-11 | 2002-05-14 | Water soluble film for oral administration with instant wettability |
| US10/161,670 US6592887B2 (en) | 1996-11-11 | 2002-06-05 | Water soluble film for oral administration with instant wettability |
| US10/771,388 US8865202B2 (en) | 1996-11-11 | 2004-02-05 | Water soluble film for oral administration with instant wettability |
| JP2005161714A JP4817721B2 (ja) | 1996-11-11 | 2005-06-01 | 口腔内に活性物質であるニコチンを放出するための口部に適用される組成物及びその製造方法 |
| NO20053307A NO20053307D0 (no) | 1996-11-11 | 2005-07-06 | Oralt administrerbart preparat for angivelse av virksomme stoffer i munnhulen og fremgangsmate for fremstilling derav. |
| IL169984A IL169984A (en) | 1996-11-11 | 2005-07-31 | Mucoadhesive composition and a process for the preparation thereof |
| JP2009222637A JP2010006832A (ja) | 1996-11-11 | 2009-09-28 | 口腔内に活性物質であるニコチンを放出するための口部に適用される組成物及びその製造方法 |
| US13/292,590 US20120114705A1 (en) | 1996-11-11 | 2011-11-09 | Water soluble film for oral administration with instant wettability |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19646392A DE19646392A1 (de) | 1996-11-11 | 1996-11-11 | Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden Schicht |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19646392A1 true DE19646392A1 (de) | 1998-05-14 |
Family
ID=7811214
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19646392A Withdrawn DE19646392A1 (de) | 1996-11-11 | 1996-11-11 | Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden Schicht |
| DE59710670T Expired - Lifetime DE59710670D1 (de) | 1996-11-11 | 1997-10-22 | Sofortige benetzbarkeit aufweisende(r) wasserlöslicher film oder wasserlösliche schicht zur oralen applikation |
| DE29724755U Expired - Lifetime DE29724755U1 (de) | 1996-11-11 | 1997-10-22 | Sofortige Benetzbarkeit aufweisende(r) wasserlöslicher Film oder wasserlösliche Schicht zur oralen Applikation |
| DE59712993T Expired - Lifetime DE59712993D1 (de) | 1996-11-11 | 1997-10-22 | Sofortige Benetzbarkeit aufweisende(r) wasserlöslicher Film oder wasserlösliche Schicht zur oralen Applikation |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE59710670T Expired - Lifetime DE59710670D1 (de) | 1996-11-11 | 1997-10-22 | Sofortige benetzbarkeit aufweisende(r) wasserlöslicher film oder wasserlösliche schicht zur oralen applikation |
| DE29724755U Expired - Lifetime DE29724755U1 (de) | 1996-11-11 | 1997-10-22 | Sofortige Benetzbarkeit aufweisende(r) wasserlöslicher Film oder wasserlösliche Schicht zur oralen Applikation |
| DE59712993T Expired - Lifetime DE59712993D1 (de) | 1996-11-11 | 1997-10-22 | Sofortige Benetzbarkeit aufweisende(r) wasserlöslicher Film oder wasserlösliche Schicht zur oralen Applikation |
Country Status (25)
| Country | Link |
|---|---|
| US (8) | US5948430A (de) |
| EP (2) | EP0936905B1 (de) |
| JP (3) | JP4063331B2 (de) |
| KR (2) | KR100569847B1 (de) |
| AT (2) | ATE247954T1 (de) |
| AU (1) | AU739698B2 (de) |
| CA (1) | CA2265651C (de) |
| CZ (1) | CZ297354B6 (de) |
| DE (4) | DE19646392A1 (de) |
| DK (2) | DK1362584T3 (de) |
| ES (2) | ES2322699T3 (de) |
| HU (2) | HU228464B1 (de) |
| ID (1) | ID22526A (de) |
| IL (2) | IL129819A0 (de) |
| MY (1) | MY125548A (de) |
| NO (2) | NO325073B1 (de) |
| NZ (1) | NZ335063A (de) |
| PL (1) | PL190376B1 (de) |
| PT (2) | PT1362584E (de) |
| SI (1) | SI0936905T1 (de) |
| SK (2) | SK285100B6 (de) |
| TR (1) | TR199901633T2 (de) |
| TW (2) | TW533083B (de) |
| WO (1) | WO1998020862A1 (de) |
| ZA (1) | ZA9710093B (de) |
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| DE19911262A1 (de) * | 1999-03-13 | 2000-09-21 | Scs Skin Care Systems Gmbh | Vorrichtung zur Abgabe kosmetischer Wirkstoffe |
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| US6552024B1 (en) | 1999-01-21 | 2003-04-22 | Lavipharm Laboratories Inc. | Compositions and methods for mucosal delivery |
| WO2002066016A3 (de) * | 2001-02-19 | 2003-10-02 | Lohmann Therapie Syst Lts | Mucoadhäsive zerfallsfähige arzneizubereitung |
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