WO2000023077A1 - Method for treating schizophrenia and means used in said method - Google Patents

Method for treating schizophrenia and means used in said method Download PDF

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Publication number
WO2000023077A1
WO2000023077A1 PCT/EP1999/007320 EP9907320W WO0023077A1 WO 2000023077 A1 WO2000023077 A1 WO 2000023077A1 EP 9907320 W EP9907320 W EP 9907320W WO 0023077 A1 WO0023077 A1 WO 0023077A1
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Prior art keywords
nicotine
pharmaceutically acceptable
medical device
acceptable salt
period
Prior art date
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PCT/EP1999/007320
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German (de)
French (fr)
Inventor
Reinhold Meconi
Volker Siemund
Original Assignee
Lts Lohmann Therapie-Systeme Ag
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Application filed by Lts Lohmann Therapie-Systeme Ag filed Critical Lts Lohmann Therapie-Systeme Ag
Priority to AU61992/99A priority Critical patent/AU6199299A/en
Priority to CA002341855A priority patent/CA2341855A1/en
Priority to EP99948923A priority patent/EP1121126A1/en
Priority to KR1020017004649A priority patent/KR20010080135A/en
Priority to JP2000576851A priority patent/JP2002527478A/en
Priority to BR9914570-7A priority patent/BR9914570A/en
Publication of WO2000023077A1 publication Critical patent/WO2000023077A1/en

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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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/465—Nicotine; Derivatives thereof
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Definitions

  • the invention is directed to a method and an apparatus for treating schizophrenia.
  • Schizophrenia is a mental illness that was first developed by E. Kraepelin by summarizing individual characteristics, e.g. B. paranoid and catatons
  • Condition pictures has been described as a disease.
  • the main deficit underlying this condition is a division of mental functions.
  • schizophrenia has different faces and the different symptoms appear in different forms and combinations. Typical forms are paranoid-hallucinatory schizophrenia, catatonic schizophrenia, schizophrenia simplex and Hebephrenia.
  • Symptoms of schizophrenia include disorders of the course of thought, content-related thinking disorders, illusions, so-called "ego disorders", disorders of the emotional world (affect disorders) as well as disorders of movement and drive.
  • the schizoaffective psychoses occupy a middle position between the schizophrenia and the cyclothymia.
  • the basic symptoms include disturbances in thinking (embarrassment, termination of thoughts, changes in the chain of thoughts), disturbances in affectivity (indifference, hypersensitivity, irritability, loss of contact, ambivalence of feelings) and disturbances in one's own experience (depersonalization, experiences of alienation and influence, cleavage of personality ).
  • the accessory symptoms include hallucinations (acoustic, visual, olfactory and taste hallucinations), delusion (persecution, poisoning, sexual delusion, etc.), motor and drive disorders (immobility, mutism, drive inhibition) and language changes (mannerisms , playful expressions, word formations, constant repetitions).
  • hallucinations acoustic, visual, olfactory and taste hallucinations
  • delusion persecution, poisoning, sexual delusion, etc.
  • motor and drive disorders immobility, mutism, drive inhibition
  • language changes mannerisms , playful expressions, word formations, constant repetitions.
  • Schizophrenia is considered to be incurable, i.e. causal treatment is considered - as is the case with many organic diseases, such as B. Diabetes - as not possible.
  • a pal ative treatment is possible, so that in a majority of the patients the symptoms can be suppressed at least so much that hospitalization is unnecessary or the patient's regular everyday life is facilitated.
  • the invention is therefore based on the object of providing a method and a medicament which make it possible to treat the symptoms of patients with schizophrenia and which is suitable for use in addition or as part of psychotherapy and / or sociotherapy, as a result of which the Disadvantages of treatment with neuroleptics or other psychologically active substances can be reduced or avoided. Even the weaknesses of the intermittent nicotine intake by means of nicotine chewing gum and the disadvantages of the mucous membrane irritant effect of nicotine when administered orally are to be avoided.
  • the object is achieved by a method and a medicament which is used for the continuous administration of nicotine, preferably to and through the skin over a longer period, for example over a 16 or 24 hour period and preferably over a period of several days, e.g. B. 3-day period is suitable.
  • TTS transdermal therapeutic systems
  • EP 400 078 EP 427 741 and EP 708 627.
  • TTS transdermal therapeutic systems
  • the active ingredient nicotine via a 16th hours (EP 400 078), or a 24-hour period.
  • TTS can be produced which also contain the active ingredient nicotine over a longer period of time, e.g. B. can give 3 days.
  • the active substance content and the thickness of the matrix containing the active substance and the skin contact surface of the TTS types used have to be adapted for the desired application time.
  • the active ingredient nicotine means the naturally occurring (-) - nicotine. Nicotine has two nitrogen atoms.
  • the pharmaceutically acceptable salts of nicotine include the mono salts of saiicylic acid, phenylpropionic acid or dodecanoic acid. Nicotine monoacetate, nicotine sulfate, nicotine hydrochloride, nicotine valerate, nicotine pivalate, nicotine lactate etc. are also preferred as active ingredients. Of course, this list cannot be exhaustive.
  • the mixture of nicotine (as a free base) with a nicotine seed is also suitable as an active ingredient. This can be the case with a longer planned application period. Free nicotine base permeates through the skin faster than many of the nicotine salts. After a certain time, this leads to exhaustion of the nicotine in the active substance reservoir of the TTS. The nicotine salt content in the drug reservoir slows down when the free base in the drug reservoir is exhausted. The salt then plays a greater role in nicotine delivery and maintenance of nicotine blood plasma levels later in the application of the TTS.
  • the constructive elements of the TTS are a backing layer, a layer containing the active ingredient and a layer that causes adhesion to the skin.
  • the TTS can also be constructed in such a way that the functions "layer containing active ingredient” and "layer causing adhesion to the skin” are realized in a single layer.
  • the TTS can have a control membrane, which is between the
  • the control membrane has the function of controlling the rate of release of the active ingredient from the TTS.
  • the active ingredient can also be present in microencapsulated form in the active ingredient-containing layer.
  • the capsule material enveloping the active substance would then take on this function which controls the release.
  • the backing layer is impermeable to the active substance and preferably impermeable to light and oxygen in order to avoid chemical decomposition of the active substance by substances penetrating from outside.
  • the TTS can also have separate drug reservoirs in a surrounding matrix.
  • the TTS is able to reach a nicotine blood plasma level above 2 ng / ml within a period of 4 hours after application.
  • a TTS is suitable to achieve an essentially constant nicotine biutplasma level between 2 and 20 ng / ml after a period of 4 hours after application.
  • a TTS is preferred which is suitable for achieving a substantially constant nicotine blood plasma level of between 2 and 10 ng / ml after a period of 4 hours after application.
  • the method for treating schizophrenia is to stick a TTS according to the invention on the patient's skin and after the remove the intended duration of use.
  • This application time for a single TTS can be 16 hours or 24 hours.
  • Multi-day TTS, e.g. B. are suitable for a three-day application.
  • Long-term therapy is meaningful, ie an application of such nicotine TTS according to the invention, possibly for months or years.
  • This type of long-term drug therapy using transdermal nicotine can be used simultaneously with psychotherapy and / or sociotherapy and / or drug therapy, especially with drugs that specifically block the receptors for dopamine (olanzapine, risperidone, etc.).

Abstract

The invention relates to transdermal administration of nicotine or a nicotine salt or a mixture of nicotine and nicotine salt for the treatment of schizophrenia. Disclosed are a method and a corresponding medical device.

Description

Verfahren zur Behandlung der Schizophrenie sowie Mittel zur Verwendung in diesem VerfahrenMethods of treating schizophrenia and agents for use in the method
Die Erfindung ist auf ein Verfahren und eine Vorrichtung zur Behandlung der Schizophrenie gerichtet.The invention is directed to a method and an apparatus for treating schizophrenia.
Schizophrenie ist eine psychische Erkrankung, die erstmals von E. Kraepelin unter Zusammenfassung einzelner Merkmale, z. B. von paranoiden und katatonenSchizophrenia is a mental illness that was first developed by E. Kraepelin by summarizing individual characteristics, e.g. B. paranoid and catatons
Zustandsbildern als eine Krankheit beschrieben wurde. Das hauptsächliche, diesem Leiden zugrundeliegende Defizit ist eine Spaltung psychischer Funktionen. Die Schizophrenie hat jedoch verschiedene Gesichter, und die unterschiedlichen Symptome treten in unterschiedlicher Ausprägung und Kombination auf. Typische Formen sind paranoid-halluzinatorische Schizophrenie, katatone Schizophrenie, Schizophrenia simplex und Hebephrenie. Symptome der Schizophrenie sind unter anderem Störungen des Denkablaufs, inhaltliche Denkstörungen, Sinnestäuschungen, sog. "Ich-Störungen", Störungen der Gefühlswelt (Affektstörungen) sowie Störungen der Bewegung und des Antriebs. Die schizoaffektiven Psychosen nehmen eine Mittelstellung zwischen den Schizophrenien und den Zyklothymien ein.Condition pictures has been described as a disease. The main deficit underlying this condition is a division of mental functions. However, schizophrenia has different faces and the different symptoms appear in different forms and combinations. Typical forms are paranoid-hallucinatory schizophrenia, catatonic schizophrenia, schizophrenia simplex and Hebephrenia. Symptoms of schizophrenia include disorders of the course of thought, content-related thinking disorders, illusions, so-called "ego disorders", disorders of the emotional world (affect disorders) as well as disorders of movement and drive. The schizoaffective psychoses occupy a middle position between the schizophrenia and the cyclothymia.
Man unterscheidet bei Schizophrenen zwischen Grundsymptomen und akzessorischen Symptomen. Zu den Grundsymptomen gehören Störungen des Denkens (Zerfahrenheit, Gedankeπabbruch, Veränderungen in der Gedankenkette), Störungen der Affektivität (Gleichgültigkeit, Überempfindlichkeit, Reizbarkeit, Kontaktverlust, Ambivalenz der Gefühie) und Störungen des Erlebens der eigenen Person (Depersonalisation, Entfremdungs- und Beeinflussungserlebnisse, Persönlichkeitsspaltung). Zu den akzessorischen Symptomen (Plussymptomen) zählen Halluzinationen (akustische, optische, Geruchs- und Geschmackshalluzinationen), Wahn (Verfolgungs-, Vergiftungs-, sexueller Wahn u. a.), Störungen der Motorik und des Antriebs (Bewegungslosigkeit, Mutismus, Antriebshemmung) sowie Sprachveränderungen (Manierismen, bizarre Ausdrucksweisen, Wortneubildungen, ständige Wiederholungen). Eine vertiefende Beschreibung der Krankheitsbilder findet sich in B Bondy "Was ist Schizophrenie", Verlag C H Beck, München (1994), worauf vollinhaltlich Bezug genommen wirdA distinction is made in schizophrenics between basic symptoms and accessory symptoms. The basic symptoms include disturbances in thinking (embarrassment, termination of thoughts, changes in the chain of thoughts), disturbances in affectivity (indifference, hypersensitivity, irritability, loss of contact, ambivalence of feelings) and disturbances in one's own experience (depersonalization, experiences of alienation and influence, cleavage of personality ). The accessory symptoms (plus symptoms) include hallucinations (acoustic, visual, olfactory and taste hallucinations), delusion (persecution, poisoning, sexual delusion, etc.), motor and drive disorders (immobility, mutism, drive inhibition) and language changes (mannerisms , bizarre expressions, word formations, constant repetitions). A more detailed description of the clinical pictures can be found in B Bondy "What is Schizophrenia", published by CH Beck, Munich (1994), to which full reference is made
Zur Abgrenzung gegen andere Krankheiten wird auf die Diagnosekriterien verwiesen, die in der International Classification of Diseases und im Diagnostic and Statistical Manual of Mental Disorders aufgelistet werden.For differentiation from other diseases, reference is made to the diagnostic criteria listed in the International Classification of Diseases and in the Diagnostic and Statistical Manual of Mental Disorders.
Schizophrenie gilt als nicht heilbar, d h eine ursächliche Behandlung gilt - wie übrigens bei vieien organischen Erkrankungen, wie z. B. Diabetes - als nicht möglich. Jedoch ist eine pal ative Behandlung möglich, so daß bei einer Mehrheit der Patienten die Symptome zumindest so stark unterdrückt werden können, daß eine Hospitalisierung unnötig bzw dem Patienten ein geregeltes Alltagsleben erleichtert wird.Schizophrenia is considered to be incurable, i.e. causal treatment is considered - as is the case with many organic diseases, such as B. Diabetes - as not possible. However, a pal ative treatment is possible, so that in a majority of the patients the symptoms can be suppressed at least so much that hospitalization is unnecessary or the patient's regular everyday life is facilitated.
Vor dem zweiten Weltkrieg bestand eine medikamentöse Behandlung hauptsachlich in der Verabreichung von Schlafmitteln und anderen Substanzen zur Beruhigung Auch körperliche Maßnahmen hatten das Ziel, aufgrund körperlicher Erschöpfung des Patienten zu dessen Ruhigstellung zu führen. Die Patienten wurden dazu überwiegend in psychiatrischen Einrichtungen verwahrtBefore the Second World War, medication mainly consisted of the administration of sleeping pills and other substances to calm down. Physical measures also aimed to calm the patient down due to physical exhaustion. The patients were mostly kept in psychiatric facilities
Mit der Anwendung von Chlorpromazin wurde die medikamentöse Behandlung erweitert, wobei diese Substanz ein Ausgangspunkt zur Entwicklung von antipsychotisch wirkenden Substanzen, sog. Neuroleptika wurde. Allerdings haben diese Stoffe eine Reihe von unerwünschten Nebenwirkungen.With the use of chlorpromazine, the medicinal treatment was expanded, whereby this substance became a starting point for the development of antipsychotic substances, so-called neuroleptics. However, these substances have a number of undesirable side effects.
Neuerdings sind auch Verfahren zur Behandlung der Schizophrenie mittels nikotinhaltiger Kaugummis (L. E. Adler et al., Biol. Psychiatry, 32 (1992) 607-616) bzw. durch intestinale Absorption (Rhodes et al., WO 98/02188) bekanntgeworden.Methods for treating schizophrenia by means of chewing gum containing nicotine (L.E. Adler et al., Biol. Psychiatry, 32 (1992) 607-616) or by intestinal absorption (Rhodes et al., WO 98/02188) have also recently become known.
Der Erfindung liegt also die Aufgabe zugrunde, ein Verfahren und ein Arzneimittel zur Verfügung zu stellen, das eine die Symptome mindernde Behandlung von Patienten mit Schizophrenie ermöglicht und geeignet ist, zusätzlich oder im Rahmen einer Psychotherapie und / oder einer Soziotherapie eingesetzt zu werden, wodurch die Nachteile einer Behandlung mit Neuroleptika oder anderen psychisch wirksamen Substanzen verringert oder vermieden werden können. Auch die Schwächen der intermittierenden Nikotinaufnahme mittels Nikotinkaugummi und die Nachteile der schleimhautreizenden Wirkung von Nikotin bei einer oralen Verabreichung soll vermieden werdenThe invention is therefore based on the object of providing a method and a medicament which make it possible to treat the symptoms of patients with schizophrenia and which is suitable for use in addition or as part of psychotherapy and / or sociotherapy, as a result of which the Disadvantages of treatment with neuroleptics or other psychologically active substances can be reduced or avoided. Even the weaknesses of the intermittent nicotine intake by means of nicotine chewing gum and the disadvantages of the mucous membrane irritant effect of nicotine when administered orally are to be avoided
Gelöst wird die Aufgabe durch ein Verfahren und ein Arzneimittel, das zur kontinuierlichen Verabreichung von Nikotin, bevorzugt an und durch die Haut über einen längeren, beispielsweise über einen 16- oder 24-stündigen und bevorzugt über einen mehrtägigen, z. B. 3-tägigen Zeitraum geeignet ist.The object is achieved by a method and a medicament which is used for the continuous administration of nicotine, preferably to and through the skin over a longer period, for example over a 16 or 24 hour period and preferably over a period of several days, e.g. B. 3-day period is suitable.
Solche Arzneimittel sind bekannt, z. B. aus den Europäischen Patenten EP 261 402, EP 289 342, EP 387 694, EP 400 078, EP 427 741 und EP 708 627. Es handelt sich dabei um transdermale, therapeutische Systeme (TTS), die den Wirkstoff Nikotin über einen 16-stündigen (EP 400 078), oder einen 24-stündigen Zeitraum abgeben. Nach der Lehre dieser Patente, auf die hiermit vollinhaltlich Bezug genommen wird, können TTS hergestellt werden, die den Wirkstoff Nikotin auch über einen längeren Zeitraum, z. B. 3 Tage abgeben können. Hierfür müssen lediglich der Wirkstoffgehalt und die Dicke der wirkstoffhaltigen Matrix sowie die Hautkontaktfläche des verwendeten TTS-Typen für die gewünschte Aπwendungszeit angepaßt werden.Such drugs are known, e.g. B. from the European patents EP 261 402, EP 289 342, EP 387 694, EP 400 078, EP 427 741 and EP 708 627. These are transdermal therapeutic systems (TTS), which the active ingredient nicotine via a 16th hours (EP 400 078), or a 24-hour period. According to the teaching of these patents, to which reference is hereby made in full, TTS can be produced which also contain the active ingredient nicotine over a longer period of time, e.g. B. can give 3 days. For this purpose, only the active substance content and the thickness of the matrix containing the active substance and the skin contact surface of the TTS types used have to be adapted for the desired application time.
Das Freisetzungsverhalten verschiedener, kommerziell erhältlichen Nikotin-TTS wird in H. Ho et al., Drug Development and Industrial Pharmacy, 19 (3), 295-313 (1993) beschrieben.The release behavior of various commercially available nicotine TTS is described in H. Ho et al., Drug Development and Industrial Pharmacy, 19 (3), 295-313 (1993).
Unter dem Wirkstoff Nikotin ist das natürlich vorkommende (-)-Nicotin zu verstehen. Nikotin besitzt zwei Stickstoff-Atome. Zu den pharmazeutisch akzeptablen Salzen von Nikotin zählen die Monosalze der Saiicylsäure, der Phenylpropionsäure oder der Dodecansäure. Bevorzugt als Wirkstoff sind auch Nicotinmonoacetat, Nikotinsulfat, Nikotinhydrochlorid, Nikotinvalerat, Nikotinpivalat, Nikotinlactat etc. Diese Aufzählung kann natürlich nicht vollzählig sein.The active ingredient nicotine means the naturally occurring (-) - nicotine. Nicotine has two nitrogen atoms. The pharmaceutically acceptable salts of nicotine include the mono salts of saiicylic acid, phenylpropionic acid or dodecanoic acid. Nicotine monoacetate, nicotine sulfate, nicotine hydrochloride, nicotine valerate, nicotine pivalate, nicotine lactate etc. are also preferred as active ingredients. Of course, this list cannot be exhaustive.
Auch die Mischung von Nikotin (als freie Base) mit einem Nikotinsaiz ist als Wirkstoff geeignet. Dies kann bei einer länger geplanten Anwendungsdauer der Fall sein. Freie Nikotinbase permeiert nämlich schneller als viele der Nikotinsalze durch die Haut. Dies führt nach einer gewissen Zeit zu einer Erschöpfung des Nikotins in dem Wirkstoffreservoir des TTS. Der Nikotinsalzanteil im Wirkstoffreservoir wird langsamer als die freie Base im Wirkstoffreservoir erschöpft. Das Salz spielt dann zu einem späteren Zeitpunkt der Anwendung des TTS eine größere Rolle bei der Nikotinabgabe und dem Aufrechterhalten des Nikotin-Blutplasmaspiegels.The mixture of nicotine (as a free base) with a nicotine seed is also suitable as an active ingredient. This can be the case with a longer planned application period. Free nicotine base permeates through the skin faster than many of the nicotine salts. After a certain time, this leads to exhaustion of the nicotine in the active substance reservoir of the TTS. The nicotine salt content in the drug reservoir slows down when the free base in the drug reservoir is exhausted. The salt then plays a greater role in nicotine delivery and maintenance of nicotine blood plasma levels later in the application of the TTS.
Die konstruktiven Elemente des TTS sind eine Rückschicht, eine wirkstoffhaltige Schicht und eine die Haftung auf der Haut bewirkende Schicht. Dabei kann das TTS auch so aufgebaut sein, daß die Funktionen "wirkstoffhaltige Schicht" und "Haftung auf der Haut bewirkende Schicht" in einer einzigen Schicht realisiert werden.The constructive elements of the TTS are a backing layer, a layer containing the active ingredient and a layer that causes adhesion to the skin. The TTS can also be constructed in such a way that the functions "layer containing active ingredient" and "layer causing adhesion to the skin" are realized in a single layer.
Weiterhin kann das TTS eine Kontrollmembran besitzen, die zwischen demFurthermore, the TTS can have a control membrane, which is between the
Wirkstoffreservoir und der die Haftung auf der Haut bewirkende Schicht angeordnet ist. Die Koπtrollmembran hat die Funktion, die Geschwindigkeit der Freisetzung des Wirkstoffs aus dem TTS zu kontrollieren.Drug reservoir and the layer causing the adhesion on the skin is arranged. The control membrane has the function of controlling the rate of release of the active ingredient from the TTS.
Der Wirkstoff kann auch in mikroverkapselter Form in der wirkstoffhaltigen Schicht vorliegen. Damit würde dann das den Wirkstoff umhüllende Kapseimaterial diese die Freisetzung kontrollierende Funktion übernehmen.The active ingredient can also be present in microencapsulated form in the active ingredient-containing layer. The capsule material enveloping the active substance would then take on this function which controls the release.
Die Rückschicht ist undurchlässig für den Wirkstoff und bevorzugt undurchlässig für Licht und Sauerstoff, um eine chemische Zersetzung des Wirkstoffs durch von außen eindringende Substanzen zu vermeiden.The backing layer is impermeable to the active substance and preferably impermeable to light and oxygen in order to avoid chemical decomposition of the active substance by substances penetrating from outside.
Das TTS kann auch separate Wirkstoffreservoire in einer umgebenden Matrix besitzen.The TTS can also have separate drug reservoirs in a surrounding matrix.
Das TTS ist befähigt, innerhalb eines Zeitraumes von 4 Stunden nach Applikation einen Nikotin-Blutplasmaspiegel oberhalb von 2 ng/mi zu erreichen.The TTS is able to reach a nicotine blood plasma level above 2 ng / ml within a period of 4 hours after application.
Weiterhin ist ein TTS geeignet, nach Ablauf eines Zeitraums von 4 Stunden nach Applikation einen im wesentlichen konstanten Nikotin-Biutplasmaspiegel zwischen 2 und 20 ng/ml zu erreichen. Bevorzugt ist ein TTS, welches geeignet ist, nach Ablauf eines Zeitraums von 4 Stunden nach Applikation einen im wesentlichen konstanten Nikotin-Blutplasmaspiegel zwischen 2 und 10 ng/ml zu erreichen.Furthermore, a TTS is suitable to achieve an essentially constant nicotine biutplasma level between 2 and 20 ng / ml after a period of 4 hours after application. A TTS is preferred which is suitable for achieving a substantially constant nicotine blood plasma level of between 2 and 10 ng / ml after a period of 4 hours after application.
Das Verfahren zur Behandlung der Schizophrenie besteht darin, ein erfindungsgemäßes TTS auf der Haut des Patienten aufzukleben und nach der beabsichtigten Anwendungsdauer wieder zu entfernen. Diese Anwendungsdauer eines einzelnen TTS kann 16 Stunden oder 24 Stunden betragen. Auch Mehrtages-TTS, z. B. für eine dreitägige Anwendung sind geeignet. Sinnvoll ist eine Dauertherapie, d. h. eine ggf. über Monate oder Jahre angelegte Anwendung solcher erfindungsgemäßer Nikotin- TTS.The method for treating schizophrenia is to stick a TTS according to the invention on the patient's skin and after the remove the intended duration of use. This application time for a single TTS can be 16 hours or 24 hours. Multi-day TTS, e.g. B. are suitable for a three-day application. Long-term therapy is meaningful, ie an application of such nicotine TTS according to the invention, possibly for months or years.
Diese Art der medikamentösen Dauertherapie mittels transdermal zugeführtem Nikotin kann gleichzeitig zu einer Psychotherapie und / oder einer Soziotherapie und / oder einer medikamentösen Therapie, insbesondere mit Medikamenten, die spezifisch die Rezeptoren für Dopamin blockieren (Olanzapin, Risperidon etc.) angewandt werden. This type of long-term drug therapy using transdermal nicotine can be used simultaneously with psychotherapy and / or sociotherapy and / or drug therapy, especially with drugs that specifically block the receptors for dopamine (olanzapine, risperidone, etc.).

Claims

Patentansprüche claims
1 Verwendung von Nikotin und / oder eines pharmazeutisch akzeptablen Salzes von Nikotin zur Herstellung eines Arzneimittels für die transdermale Verabreichung von Nikotin und / oder eines pharmazeutisch akzeptablen Salzes von Nikotin zur Behandlung der Schizophrenie. 1 Use of nicotine and / or a pharmaceutically acceptable salt of nicotine for the manufacture of a medicament for the transdermal administration of nicotine and / or a pharmaceutically acceptable salt of nicotine for the treatment of schizophrenia.
2. Medizinische Vorrichtung zur transdermalen Verabreichung von Nikotin und / oder eines pharmazeutisch akzeptablen Salzes von Nikotin für die Verwendung bei der Behandlung der Schizophrenie. 2. Medical device for transdermal administration of nicotine and / or a pharmaceutically acceptable salt of nicotine for use in the treatment of schizophrenia.
3. Medizinische Vonrichtung nach Anspruch 2, dadurch gekennzeichnet, daß das3. Medical device according to claim 2, characterized in that the
Nikotin und / oder ein pharmazeutisch akzeptables Salz von Nikotin kontinuierlich über einen Zeitraum von mindestens 16 Stunden abgegeben wird.Nicotine and / or a pharmaceutically acceptable salt of nicotine is continuously released over a period of at least 16 hours.
4. Medizinische Vorrichtung nach Anspruch 2, dadurch gekennzeichnet, daß das Nikotin und / oder ein pharmazeutisch akzeptables Salz von Nikotin kontinuierlich über einen Zeitraum von mindestens 24 Stunden abgegeben wird.4. Medical device according to claim 2, characterized in that the nicotine and / or a pharmaceutically acceptable salt of nicotine is continuously released over a period of at least 24 hours.
5. Medizinische Vorrichtung nach Anspruch 2, dadurch gekennzeichnet, daß das Nikotin und / oder ein pharmazeutisch akzeptables Salz von Nikotin kontinuierlich über einen Zeitraum von mindestens drei Tagen abgegeben wird.5. Medical device according to claim 2, characterized in that the nicotine and / or a pharmaceutically acceptable salt of nicotine is continuously released over a period of at least three days.
6. Medizinische Vorrichtung nach Anspruch 2, dadurch gekennzeichnet, daß sie geeignet ist, innerhalb eines Zeitraums von 4 Stunden nach Applikation einen6. Medical device according to claim 2, characterized in that it is suitable within a period of 4 hours after application
Nikotin-Blutplasmaspiegel oberhalb von 2 ng/ml zu erreichen.To achieve nicotine blood plasma levels above 2 ng / ml.
7. Medizinische Vorrichtung nach Anspruch 2, dadurch gekennzeichnet, daß sie geeignet ist, nach Ablauf eines Zeitraums von 4 Stunden nach Applikation einen im wesentlichen konstanten Nikotin-Blutplasmaspiegel zwischen 2 und 20 ng/ml zu erreichen.7. Medical device according to claim 2, characterized in that it is suitable to achieve a substantially constant nicotine blood plasma level between 2 and 20 ng / ml after a period of 4 hours after application.
8. Medizinische Vorrichtung nach Anspruch 2, dadurch gekennzeichnet, daß sie eine für Nikotin und / oder eines pharmazeutisch akzeptablen Salzes von Nikotin undurchlässige Rückschicht und eine Nikotin und / oder ein pharmazeutisch akzeptables Salz von Nikotin enthaltende Schicht enthält. 8. Medical device according to claim 2, characterized in that it contains a layer which is impermeable to nicotine and / or a pharmaceutically acceptable salt of nicotine and a layer containing nicotine and / or a pharmaceutically acceptable salt of nicotine.
9. Medizinische Vorrichtung nach Anspruch 2, dadurch gekennzeichnet, daß sie eine Schicht enthält, die das Haften der Vorrichtung auf der Haut des Patienten bewirkt. 9. Medical device according to claim 2, characterized in that it contains a layer which causes the device to adhere to the patient's skin.
10. Verfahren zur Behandlung der Schizophrenie, dadurch gekennzeichnet, daß10. A method of treating schizophrenia, characterized in that
Nikotin und / oder ein pharmazeutisch akzeptables Salz von Nikotin transdermal verabreicht wird. Nicotine and / or a pharmaceutically acceptable salt of nicotine is administered transdermally.
11. Verfahren nach Anspruch 10, dadurch gekennzeichnet, daß Nikotin und / oder ein pharmazeutisch akzeptables Salz von Nikotin kontinuierlich über einen Zeitraum von mindestens 16 Stunden verabreicht wird.11. The method according to claim 10, characterized in that nicotine and / or a pharmaceutically acceptable salt of nicotine is administered continuously over a period of at least 16 hours.
12. Verfahren nach Anspruch 10, dadurch gekennzeichnet, daß Nikotin und / oder ein pharmazeutisch akzeptables Salz kontinuierlich über einen Zeitraum von mindestens 24 Stunden verabreicht wird.12. The method according to claim 10, characterized in that nicotine and / or a pharmaceutically acceptable salt is administered continuously over a period of at least 24 hours.
13. Verfahren nach Anspruch 10, dadurch gekennzeichnet, daß Nikotin und / oder ein pharmazeutisch akzeptables Salz von Nikotin kontinuierlich über einen Zeitraum von mindestens 3 Tagen verabreicht wird. 13. The method according to claim 10, characterized in that nicotine and / or a pharmaceutically acceptable salt of nicotine is administered continuously over a period of at least 3 days.
14. Verfahren zur Behandlung der Schizophrenie, dadurch gekennzeichnet, daß eine medizinische Vorrichtung gemäß Anspruch 2 auf die Haut des Patienten appiiziert und nach 16 Stunden Tragezeit wieder abgezogen wird.14. A method of treating schizophrenia, characterized in that a medical device according to claim 2 is applied to the patient's skin and is removed after 16 hours of wearing.
15. Verfahren zur Behandlung der Schizophrenie, dadurch gekennzeichnet, daß eine medizinische Vorrichtung gemäß Anspruch 2 zur transdermalen oder transmucosalen Verabreichung von Nikotin und / oder eines pharmazeutisch akzeptablen Salzes von Nikotin auf die Haut des Patienten appiiziert und nach 24 Stunden Tragezeit wieder abgezogen wird.15. A method of treating schizophrenia, characterized in that a medical device according to claim 2 for transdermal or transmucosal administration of nicotine and / or a pharmaceutically acceptable salt of nicotine is administered to the patient's skin and is removed again after 24 hours of wearing.
16. Verfahren zur Behandlung der Schizophrenie, dadurch gekennzeichnet, daß eine medizinische Vorrichtung gemäß Anspruch 2 auf die Haut des Patienten appiiziert und nach 3 Tagen Tragezeit wieder abgezogen wird.16. A method of treating schizophrenia, characterized in that a medical device according to claim 2 is applied to the patient's skin and is removed after 3 days of wearing.
17. Verfahren zur Behandlung der Schizophrenie, dadurch gekennzeichnet, daß eine medizinische Vorrichtung nach Anspruch 6 appiiziert wird.17. A method of treating schizophrenia, characterized in that a medical device according to claim 6 is administered.
18. Verfahren zur Behandlung der Schizophrenie, dadurch gekennzeichnet, daß eine medizinische Vorrichtung nach Anspruch 7 appiiziert wird. 18. A method of treating schizophrenia, characterized in that a medical device according to claim 7 is administered.
19. Verfahren nach Anspruch -10, dadurch gekennzeichnet, daß es gleichzeitig zu einer Psychotherapie und / oder einer Soziotherapie und / oder einer medikamentösen Therapie angewandt wird. 19. The method according to claim -10, characterized in that it is applied simultaneously to psychotherapy and / or sociotherapy and / or drug therapy.
PCT/EP1999/007320 1998-10-16 1999-10-02 Method for treating schizophrenia and means used in said method WO2000023077A1 (en)

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AU61992/99A AU6199299A (en) 1998-10-16 1999-10-02 Method for treating schizophrenia and means used in said method
CA002341855A CA2341855A1 (en) 1998-10-16 1999-10-02 Method for treating schizophrenia, and means for use in this method
EP99948923A EP1121126A1 (en) 1998-10-16 1999-10-02 Method for treating schizophrenia and means used in said method
KR1020017004649A KR20010080135A (en) 1998-10-16 1999-10-02 Method for treating schizophrenia and means used in said method
JP2000576851A JP2002527478A (en) 1998-10-16 1999-10-02 Method for treating schizophrenia and means for use in the method
BR9914570-7A BR9914570A (en) 1998-10-16 1999-10-02 Process for the treatment of schizophrenia as well as agents for use in this process

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DE19847715A DE19847715A1 (en) 1998-10-16 1998-10-16 Treatment of schizophrenia symptoms without side effects, by transdermal administration of nicotine or its salt

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DE19847715A1 (en) 2000-04-20
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AU6199299A (en) 2000-05-08
CN1323210A (en) 2001-11-21
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KR20010080135A (en) 2001-08-22
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