WO2003013520A1 - Pramipexole for the treatment of adhd - Google Patents
Pramipexole for the treatment of adhd Download PDFInfo
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- WO2003013520A1 WO2003013520A1 PCT/EP2002/008500 EP0208500W WO03013520A1 WO 2003013520 A1 WO2003013520 A1 WO 2003013520A1 EP 0208500 W EP0208500 W EP 0208500W WO 03013520 A1 WO03013520 A1 WO 03013520A1
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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- the invention relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, its (+) or (-) enantiomer, its pharmacologically acceptable acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of ADHD.
- the 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzo-thiazole is a dopamine agonist which is also known in the art as pramipexole.
- Pramipexole and processes for its production are known for example from EP-A-186 087 and US 4,886,812.
- the utility of pramipexole for the treatment of schizophrenia and in particular for the treatment of Parkinson's is known.
- the prior art also discloses, for example, that pramipexole lowers the prolactin serum level (DE 38 43 227).
- pramipexole can be used in therapeutically effective doses for the prevention and / or treatment of ADHD.
- the present invention relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, optionally in the form of its (+) or its (-) enantiomer, optionally in the form of the pharmacologically acceptable one Acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of ADHD.
- ADHD stands for "attention deficit hyperactivity disorder”. It describes a disorder that occurs in both children and adults in the form of an attention deficit. ADHD is also understood to be a hyperactivity disorder that can also be observed in both children and adults. Depending on which of the above-mentioned disorders dominates, ADHD can be observed in different forms. There is the mixed type, in which both a deficit in attention and a hyperactivity disorder can be observed, the predominantly inattentive type and the predominantly hyperactive-impulsive type.
- the mixed type occurs when at least six out of nine symptoms of attention deficit disorder and hyperactivity / impulsivity persist for at least six months. Have at least six symptoms of Attention deficit, but less than six of the hyperactivity / impulsivity persisted for at least six months is the predominantly inattentive type.
- the predominantly hyperactive-impulsive type is when at least six symptoms from the area of hyperactivity / impulsivity but less than six from the area of inattentiveness have been present over a period of at least six months.
- Inattentiveness a) often disregards details or makes careless mistakes in school work, work or other activities; (b) often has difficulty keeping attention on tasks or playing for long periods of time; c) often does not seem to listen when others address him / her; d) often does not fully complete instructions from others and cannot complete schoolwork, other work or duties at the workplace; e) often has difficulty organizing tasks and activities; f) often avoids, dislike, or is reluctant to undertake tasks that require prolonged mental effort; (g) often loses items that he / she needs for tasks or activities; h) can easily be distracted by external stimuli; i) is often forgetful in everyday activities;
- Hyperactivity a) often fidgets with hands or feet or slips around on the chair; b) stands up frequently in class or in other situations where sitting is expected; c) often runs around or climbs excessively in situations where it is inappropriate (in adolescents or adults this can be limited to a subjective feeling of restlessness); d) often has difficulty playing quietly or engaging in leisure activities; e) is often "on the move” or often acts as if he / she was “driven”; (f) often talks excessively; Impulsiveness;
- the present invention further relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, optionally in the form of its (+) or its (-) enantiomer, optionally in the form of the pharmacological one compatible acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of attention deficits.
- the present invention further relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, optionally in the form of its (+) or its (-) enantiomer, optionally in the form of the pharmacologically acceptable one Acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of hyperactivity disorders.
- Another aspect of the present invention relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, optionally in the form of its (+) or (-) enantiomer, optionally in the form of the pharmacologically acceptable acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of hyperactivity disorders associated with attention deficits.
- a combination therapy of pramipexole with one or more, preferably another, pharmaceutically active compound can alternatively be carried out.
- the combination with active substances selected from the group consisting of ⁇ -sympatomimetics and antidepressants, preferably tricyclic antidepressants, antidepressants of the SSRI or MAO type can prove to be effective.
- pramipexole in a sensible manner for the treatment of the aforementioned conditions, preferably with one or more, preferably one of the following substances: Methylphenidate, amphethamine, amphetaminil, metamphetamine, pemoline, tomoxetine, desipramine, imipramine, bupropion and modafinil, methylphenidate, amphetamine, pemolin, tomoxetine and modafinil being particularly preferred.
- pramipexole can be used as a racemate, in the form of its (+) - or in the form of its (-) - enantiomer. Pramipexole can also be used in the form of its pharmaceutically acceptable acid addition salts and, if appropriate, in the form of its hydrates and / or solvates.
- pharmaceutically acceptable acid addition salts are understood to be those salts which are selected from the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid and maleic acid, the salts of hydrochloric acid, hydrobromic acid, sulfuric acid , Phosphoric acid, and acetic acid are particularly preferred.
- the salts of hydrochloric acid are of particular importance here. Accordingly, the hydrochlorides of pramipexole are particularly preferably used in the context of the present invention, the pramipexole dihydrochloride being of particular importance. Of the hydrates of the pramipexole, the pramipexole dihydrochloride monohydrate is particularly preferred.
- Pramipexole is naturally very dependent on the clinical picture.
- pramipexole can be used in doses of about 0.05 to 7.5 mg, preferably 0.1 to 5 mg, per day. These dosages are based on pramipexole in the form of its free base. Based on the preferred salt form pramipexole dihydrochloride monohydrate, the above-mentioned dosages correspond to about 0.07 to 10 t 65 mg, preferably 0.14 to 7.1 mg pramipexole dihydrochloride monohydrate per day.
- Pramipexole can be administered orally, transdermally, intrathecally, by inhalation or parenterally in the context of the use according to the invention. Suitable forms of use are, for example, tablets, capsules, suppositories, solutions, juices, emulsions, dispersible powders or plasters. With regard to possible embodiments of a transdermal one which can be used according to the invention
- Corresponding tablets can be mixed, for example, by mixing the active ingredient (s) with known auxiliaries, for example inert diluents such as calcium carbonate, calcium phosphate or milk sugar, and disintegrants
- the tablets can also consist of several layers.
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Abstract
Description
Pramipexol zur Behandlung von ADHD Pramipexole for the treatment of ADHD
Die Erfindung betrifft die Verwendung von 2-Amino-4,5,6,7-tetrahydro-6-n- propylamino-benzothiazol, sein (+) oder (-) Enantiomer, deren pharmakologisch verträgliche Saureadditionssalze sowie Hydrate und Solvate zur Herstellung eines Arzneimittels zur Vorbeugung und/oder Behandlung von ADHD.The invention relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, its (+) or (-) enantiomer, its pharmacologically acceptable acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of ADHD.
Hintergrund der Erfindung Das 2-Amino-6-n-propylamino-4,5,6,7-tetrahydrobenzo-thiazol ist ein Dopaminagonist der auch unter dem Namen Pramipexol im Stand der Technik bekannt ist. Pramipexol, sowie Verfahren zu dessen Herstellung sind beispielsweise aus EP-A-186 087 und US 4,886,812 bekannt. Vor allem die Verwendbarkeit von Pramipexol zur Behandlung der Schizophrenie und insbesondere zur Behandlung des Parkinsons ist bekannt. Der Stand der Technik offenbart beispielsweise ferner, daß Pramipexol den Prolactinserumspiegel senkt (DE 38 43 227).Background of the Invention The 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzo-thiazole is a dopamine agonist which is also known in the art as pramipexole. Pramipexole and processes for its production are known for example from EP-A-186 087 and US 4,886,812. The utility of pramipexole for the treatment of schizophrenia and in particular for the treatment of Parkinson's is known. The prior art also discloses, for example, that pramipexole lowers the prolactin serum level (DE 38 43 227).
Beschreibung der Erfindung Überraschenderweise wurde gefunden, daß Pramipexol in therapeutisch wirksamen Dosen zur Vorbeugung und/oder Behandlung von ADHD eingesetzt werden kann.Description of the invention Surprisingly, it has been found that pramipexole can be used in therapeutically effective doses for the prevention and / or treatment of ADHD.
Dementsprechend betrifft die vorliegende Erfindung die Verwendung von 2-Amino- 4,5,6,7-tetrahydro-6-n-propylamino-benzothiazol, gegebenenfalls in Form seines (+) oder seines (-) Enantiomers, gegebenenfalls in Form der pharmakologisch verträgliche Saureadditionssalze sowie Hydrate und Solvate zur Herstellung eines Arzneimittels zur Vorbeugung und/oder Behandlung von ADHD.Accordingly, the present invention relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, optionally in the form of its (+) or its (-) enantiomer, optionally in the form of the pharmacologically acceptable one Acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of ADHD.
Die Bezeichnung ADHD steht für "attention deficit hyperactivity disorder". Sie beschreibt eine sowohl bei Kindern als auch bei Erwachsenen in Form eines Aufmerksamkeitsdefizits auftretende Störung. Unter ÄDHD wird ferner eine ebenfalls sowohl bei Kindern als auch bei Erwachsenen beobachtbare Hyperaktivitätsstörung verstanden. ADHD kann, je nachdem welche der vorstehend genannten Störungen dominiert, in unterschiedlichen Ausprägungen beobachtet werden. Es gibt den Mischtyp, bei dem sowohl ein Aufmerksamkeitsdefizit als auch eine Hyperaktivitätsstörung beobachtbar ist, den vorwiegend unaufmerksamen Typ sowie den vorwiegend hyperaktiven-impulsiven Typus.The term ADHD stands for "attention deficit hyperactivity disorder". It describes a disorder that occurs in both children and adults in the form of an attention deficit. ADHD is also understood to be a hyperactivity disorder that can also be observed in both children and adults. Depending on which of the above-mentioned disorders dominates, ADHD can be observed in different forms. There is the mixed type, in which both a deficit in attention and a hyperactivity disorder can be observed, the predominantly inattentive type and the predominantly hyperactive-impulsive type.
Der Mischtyp liegt vor, wenn jeweils mindestens sechs von neun Symptomen der Aufmerksamkeitsstörung und der Hyperaktivität/Impulsivität über mindestens sechs Monate persistieren. Haben wenigstens sechs Symptome des Aufmerksamkeitsdefizits, aber weniger als sechs der Hyperaktivität/Impulsivität über mindestens sechs Monate bestanden liegt der vorwiegend unaufmerksame Typ vor. Der vorwiegend hyperaktiv-impulsiven Typ liegt vor, wenn über einen Zeitraum von mindestens sechs Monaten wenigstens sechs Symptome aus dem Bereich Hyperaktivität/Impulsivität aber weniger als sechs aus dem Bereich Unaufmerksamkeit vorgelegen haben.The mixed type occurs when at least six out of nine symptoms of attention deficit disorder and hyperactivity / impulsivity persist for at least six months. Have at least six symptoms of Attention deficit, but less than six of the hyperactivity / impulsivity persisted for at least six months is the predominantly inattentive type. The predominantly hyperactive-impulsive type is when at least six symptoms from the area of hyperactivity / impulsivity but less than six from the area of inattentiveness have been present over a period of at least six months.
Als Symptome der Unaufmerksamkeit und der Hyperaktivität, die zur Klassifizierung der vorstehend genannten Typen der ADHD zugrunde gelegt werden, gelten die folgenden Beurteilungskriterien (gemäß DSM IV = diagnostisches und statistisches Manual psychischer Störungen Version IV):The symptoms of inattention and hyperactivity that are used to classify the above types of ADHD are the following assessment criteria (according to DSM IV = Diagnostic and Statistical Manual of Mental Disorders Version IV):
Unaufmerksamkeit a) beachtet häufig Einzelheiten nicht oder macht Flüchtigkeitsfehler bei den Schularbeiten, bei der Arbeit oder bei anderen Tätigkeiten; (b) hat oft Schwierigkeiten, längere Zeit die Aufmerksamkeit bei Aufgaben oder beim Spielen aufrechtzuerhalten; c) scheint häufig nicht zuzuhören, wenn andere ihn/sie ansprechen; d) führt häufig Anweisungen anderer nicht vollständig durch und kann Schularbeiten, andere Arbeiten oder Pflichten am Arbeitsplatz nicht zu Ende bringen; e) hat häufig Schwierigkeiten, Aufgaben und Aktivitäten zu organisieren; f) vermeidet häufig, hat eine Abneigung gegen oder beschäftigt sich häufig nur widerwillig mit Aufgaben, die länger andauernde geistige Anstrengungen erfordern; (g) verliert häufig Gegenstände, die er/sie für Aufgaben oder Aktivitäten benötigt; h) lässt sich öfter durch äußere Reize leicht ablenken; i) ist bei Alltagstätigkeiten häufig vergesslich;Inattentiveness a) often disregards details or makes careless mistakes in school work, work or other activities; (b) often has difficulty keeping attention on tasks or playing for long periods of time; c) often does not seem to listen when others address him / her; d) often does not fully complete instructions from others and cannot complete schoolwork, other work or duties at the workplace; e) often has difficulty organizing tasks and activities; f) often avoids, dislike, or is reluctant to undertake tasks that require prolonged mental effort; (g) often loses items that he / she needs for tasks or activities; h) can easily be distracted by external stimuli; i) is often forgetful in everyday activities;
Hyperaktivität a) zappelt häufig mit Händen oder Füßen oder rutscht auf dem Stuhl herum; b) steht in der Klasse oder in anderen Situationen, in denen Sitzen bleiben erwartet wird, häufig auf ; c) läuft häufig herum oder klettert exzessiv in Situationen, in denen dies unpassend ist (bei Jugendlichen oder Erwachsenen kann dies auf ein subjektives Unruhegefühl beschränkt bleiben); d) hat häufig Schwierigkeiten, ruhig zu spielen oder sich mit Freizeitaktivitäten ruhig zu beschäftigen; e) ist häufig „auf Achse" oder handelt oftmals, als wäre er/sie „getrieben"; (f) redet häufig übermäßig viel; Impulsivität;Hyperactivity a) often fidgets with hands or feet or slips around on the chair; b) stands up frequently in class or in other situations where sitting is expected; c) often runs around or climbs excessively in situations where it is inappropriate (in adolescents or adults this can be limited to a subjective feeling of restlessness); d) often has difficulty playing quietly or engaging in leisure activities; e) is often "on the move" or often acts as if he / she was "driven"; (f) often talks excessively; Impulsiveness;
(g) platzt häufig mit den Antworten heraus, bevor die Frage zu Ende gestellt ist; (h) kann nur schwer warten, bis er an der Reihe ist;(g) often blurts out the answers before the question is finished; (h) has a hard time waiting for his turn;
(i) unterbricht und stört andere häufig (platzt z.B. in Gespräche oder in Spiele anderer hinein);(i) often interrupts and disturbs others (e.g. bursts into conversations or other people's games);
Dementsprechend betrifft die vorliegende Erfindung ferner die Verwendung von 2- Amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazol, gegebenenfalls in Form seines (+) oder seines (-) Enantiomers, gegebenenfalls in Form der pharmakologisch verträgliche Saureadditionssalze sowie Hydrate und Solvate zur Herstellung eines Arzneimittels zur Vorbeugung und/oder Behandlung von Aufmerksamkeitsdefiziten.Accordingly, the present invention further relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, optionally in the form of its (+) or its (-) enantiomer, optionally in the form of the pharmacological one compatible acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of attention deficits.
Ferner betrifft die vorliegende Erfindung die Verwendung von 2-Amino-4,5,6,7- tetrahydro-6-n-propylamino-benzothiazol, gegebenenfalls in Form seines (+) oder seines (-) Enantiomers, gegebenenfalls in Form der pharmakologisch verträgliche Saureadditionssalze sowie Hydrate und Solvate zur Herstellung eines Arzneimittels zur Vorbeugung und/oder Behandlung von Hyperaktivitätsstörungen.The present invention further relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, optionally in the form of its (+) or its (-) enantiomer, optionally in the form of the pharmacologically acceptable one Acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of hyperactivity disorders.
Ein weiterer Aspekt der vorliegenden Erfindung betrifft die Verwendung von 2- Amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazol, gegebenenfalls in Form seines (+) oder seines (-) Enantiomers, gegebenenfalls in Form der pharmakologisch verträgliche Saureadditionssalze sowie Hydrate und Solvate zur Herstellung eines Arzneimittels zur Vorbeugung und/oder Behandlung von Hyperaktivitätsstörungen, die mit Aufmerksamkeitsdefiziten einhergehen.Another aspect of the present invention relates to the use of 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, optionally in the form of its (+) or (-) enantiomer, optionally in the form of the pharmacologically acceptable acid addition salts and hydrates and solvates for the manufacture of a medicament for the prevention and / or treatment of hyperactivity disorders associated with attention deficits.
Zur Behandlung und/oder Vorbeugung in oben genannten medizinischen Indikationen kann neben einer Monotherapie mittels Pramipexol alternativ auch eine Kombinationstherapie von Pramipexol mit einer oder mehreren, bevorzugt einer anderen pharmazeutisch wirksamen Verbindung durchgeführt werden. Hierbei kann sich beispielsweise die Kombination mit Wirkstoffen ausgewählt aus der Gruppe bestehend aus α-Sympatomimetika und Antidepressiva, bevorzugt tricyclische Antidepressiva, Antidepressiva des SSRI- oder auch des MAO-Typs als wirksam erweisen.For treatment and / or prevention in the medical indications mentioned above, in addition to monotherapy using pramipexole, a combination therapy of pramipexole with one or more, preferably another, pharmaceutically active compound can alternatively be carried out. Here, for example, the combination with active substances selected from the group consisting of α-sympatomimetics and antidepressants, preferably tricyclic antidepressants, antidepressants of the SSRI or MAO type can prove to be effective.
Im Falle einer Kombinationstherapie kann Pramipexol zur Behandlung der vorstehend genannten Zustände bevorzugt mit einer oder mehrerer, bevorzugt einer der nachfolgenden folgenden Substanzen sinnvoll zum Einsatz gelangen: Methylphenidat, Amphethamin, Amphetaminil, Metamphetamin, Pemolin, Tomoxetine, Desipramine, Imipramine, Bupropion und Modafinil, wobei Methylphenidat, Amphetamin, Pemolin, Tomoxetine und Modafinil besonders bevorzugt sind.In the case of a combination therapy, pramipexole can be used in a sensible manner for the treatment of the aforementioned conditions, preferably with one or more, preferably one of the following substances: Methylphenidate, amphethamine, amphetaminil, metamphetamine, pemoline, tomoxetine, desipramine, imipramine, bupropion and modafinil, methylphenidate, amphetamine, pemolin, tomoxetine and modafinil being particularly preferred.
Pramipexol kann im Rahmen der vorliegenden Erfindung als Racemat, in Form seines (+)- oder in Form seines (-)-Enantiomers zum Einsatz gelangen. Ferner kann Pramipexol in Form seiner pharmazeutisch verträglichen Saureadditionssalze sowie gegebenenfalls in Form seiner Hydrate und/oder Solvate verwendet werden. Unter pharmazeutisch verträglichen Säureadditionssalzen werden erfindungsgemäß solche Salze verstanden, die ausgewählt sind aus den Salzen der Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, Methansulfonsäure, Essigsäure, Fumarsäure, Bernsteinsäure, Milchsäure, Zitronensäure, Weinsäure und Maleinsäure, wobei die Salze der Salzsäure, Bromwasserstoffsäure, Schwefelsäure, Phosphorsäure, und Essigsäure besonders bevorzugt sind. Eine besondere Bedeutung kommt hierbei den Salzen der Salzsäure zu. Besonders bevorzugt gelangen im Rahmen der vorliegenden Erfindung dementsprechend die Hydrochloride des Pramipexols zum Einsatz, wobei dem Pramipexoldihydrochlorid eine besondere Bedeutung zukommt. Von den Hydraten des Pramipexols ist das Pramipexoldihydrochlorid-monohydrat besonders bevorzugt.In the context of the present invention, pramipexole can be used as a racemate, in the form of its (+) - or in the form of its (-) - enantiomer. Pramipexole can also be used in the form of its pharmaceutically acceptable acid addition salts and, if appropriate, in the form of its hydrates and / or solvates. According to the invention, pharmaceutically acceptable acid addition salts are understood to be those salts which are selected from the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid and maleic acid, the salts of hydrochloric acid, hydrobromic acid, sulfuric acid , Phosphoric acid, and acetic acid are particularly preferred. The salts of hydrochloric acid are of particular importance here. Accordingly, the hydrochlorides of pramipexole are particularly preferably used in the context of the present invention, the pramipexole dihydrochloride being of particular importance. Of the hydrates of the pramipexole, the pramipexole dihydrochloride monohydrate is particularly preferred.
Die Dosierung von Pramipexol ist naturgemäß stark abhängig vom Krankeitsbild. Beispielsweise und ohne den Gegenstand der vorliegenden Erfindung darauf zu beschränken kann Pramipexol pro Tag in Dosierungen von etwa 0,05 bis 7,5 mg, bevorzugt 0,1 bis 5 mg Verwendung finden. Diese Dosierungen sind bezogen auf Pramipexol in Form seiner freien Base. Bezogen auf die bevorzugt zum Einsatz gelangende Salzform Pramipexoldihydrochlorid-monohydrat entsprechen die vorstehend genannten Dosierungen etwa 0,07 bis 10t65 mg, bevorzugt 0,14 bis 7,1 mg Pramipexoldihydrochlorid-monohydrat pro Tag.The dosage of Pramipexole is naturally very dependent on the clinical picture. For example, and without restricting the subject matter of the present invention thereto, pramipexole can be used in doses of about 0.05 to 7.5 mg, preferably 0.1 to 5 mg, per day. These dosages are based on pramipexole in the form of its free base. Based on the preferred salt form pramipexole dihydrochloride monohydrate, the above-mentioned dosages correspond to about 0.07 to 10 t 65 mg, preferably 0.14 to 7.1 mg pramipexole dihydrochloride monohydrate per day.
Eine mögliche und nur als beispielhaft erläuternd zu verstehende Vorgehensweise zur Dosierung ist nachfolgend bezogen auf Pramipexol in Form seiner freien Base ausgeführt: Individuelle Dosistitration in wöchentlichen Abständen je nach Wirkung und Verträglichkeit. 1. Woche: 3mal täglich 1 Tablette enthaltend 0,088 mg Pramipexol;A possible procedure for dosing, which is only to be understood as an example, is described below in relation to pramipexole in the form of its free base: Individual dose titration at weekly intervals depending on the effect and tolerability. 1st week: 1 tablet containing 0.088 mg pramipexole 3 times a day;
2. Woche: 3mal täglich 1 Tablette enthaltend 0,18 mg Pramipexol;2nd week: 1 tablet 3 times a day containing 0.18 mg pramipexole;
3. Woche und folgende: 3mal täglich 1/2 Tablette enthaltend 0,7 mg Pramipexol. Pramipexol kann im Rahmen der erfindungsgemäßen Anwendung oral, transdermal, intrathecal, inhalativ oder parenteral verabreicht werden. Geeignete Anwendungsformen sind beispielsweise Tabletten, Kapseln, Zäpfchen, Lösungen, Säfte, Emulsionen, dispersible Pulver oder Pflaster. Bezüglich möglicher Ausführungsformen einer erfindungsgemäß einsetzbaren transdermalenWeek 3 and following: 1/2 tablet containing 0.7 mg pramipexole 3 times a day. Pramipexole can be administered orally, transdermally, intrathecally, by inhalation or parenterally in the context of the use according to the invention. Suitable forms of use are, for example, tablets, capsules, suppositories, solutions, juices, emulsions, dispersible powders or plasters. With regard to possible embodiments of a transdermal one which can be used according to the invention
Applikationsform wird an dieser Stelle auf die Ausführungsbeispiele gemäß US 5112842 verwiesen, auf die hiermit ausdrücklich Bezug genommen wird. Entsprechende Tabletten können beispielsweise durch Mischen des oder der Wirkstoffe mit bekannten Hilfsstoffen, beispielsweise inerten Verdünnungsmitteln, wie Calciumcarbonat, Calciumphosphat oder Milchzucker, Sprengmitteln, wieApplication form is referred to the embodiments according to US 5112842, to which reference is hereby expressly made. Corresponding tablets can be mixed, for example, by mixing the active ingredient (s) with known auxiliaries, for example inert diluents such as calcium carbonate, calcium phosphate or milk sugar, and disintegrants
Maisstärke oder Alginsäure, Bindemitteln, wie Stärke oder Gelatine, Schmiermitteln, wie Magnesiumstearat oder Talk, und/oder Mitteln zur Erzielung des Depoteffektes, wie Carboxymethylcellulose, Celluloseacetatphthalat, oder Polyvinylacetat erhalten werden. Die Tabletten können auch aus mehreren Schichten bestehen.Corn starch or alginic acid, binders such as starch or gelatin, lubricants such as magnesium stearate or talc, and / or agents for achieving the depot effect, such as carboxymethyl cellulose, cellulose acetate phthalate, or polyvinyl acetate can be obtained. The tablets can also consist of several layers.
Im Folgenden sind einige Beispiele für erfindungsgemäß einsetzbare pharmazeutische Zubereitungen angegeben. Diese dienen lediglich der beispielhaften Erläuterung, ohne den Gegenstand der Erfindung auf selbige zu beschränken.Some examples of pharmaceutical preparations which can be used according to the invention are given below. These serve only as an example, without restricting the subject matter of the invention to the same.
Tablette 1 :Tablet 1:
Bestandteile: mgComponents: mg
Pramipexoldihydrochlorid-monohydrat 1 ,00Pramipexole dihydrochloride monohydrate 1.00
Mannitol 121 ,50Mannitol 121, 50
Maisstärke 79,85Corn starch 79.85
Hochdisperses Siliciumdioxid, wasserfrei 2,30Highly disperse silicon dioxide, anhydrous 2.30
Polyvidon K25 2,35 Magnesiumstearat 3,00Polyvidon K25 2.35 magnesium stearate 3.00
Gesamt 210,00Total 210.00
Tablette 2:Tablet 2:
Bestandteile: mgComponents: mg
Pramipexol 0,5Pramipexole 0.5
Mannitol 122,0Mannitol 122.0
Maisstärke, getrocknet 61 ,8 Maisstärke 18,0Corn starch, dried 61, 8 Corn starch 18.0
Hochdisperses Siliciumdioxid, wasserfrei 2,4Highly disperse silicon dioxide, anhydrous 2.4
Polyvidon K25 2,3Polyvidon K25 2.3
Magnesiumstearat 3,0 Gesamt 210,0Magnesium stearate 3.0 total 210.0
Tablette 3:Tablet 3:
Bestandteile: mgComponents: mg
Pramipexol 0,25Pramipexole 0.25
Mannitol 61 ,00Mannitol 61, 00
Maisstärke 39,90 Hochdisperses Siliciumdioxid, wasserfrei 1 ,20Corn starch 39.90 Highly disperse silicon dioxide, anhydrous 1, 20
Polyvidon K25 1 ,15Polyvidon K25 1, 15
Magnesiumstearat 1 ,5Magnesium stearate 1, 5
Gesamt 105,00Total 105.00
Tablette 4:Tablet 4:
Bestandteile: mgComponents: mg
Pramipexol 0,125 Mannitol 49,455Pramipexole 0.125 mannitol 49.455
Maisstärke getrocknet 25,010Corn starch dried 25.010
Maisstärke 7,300Corn starch 7,300
Hochdisperses Siliciumdioxid, wasserfrei 0,940Highly disperse silicon dioxide, anhydrous 0.940
Polyvidon K25 0,940 Magnesiumstearat 1 ,230Polyvidon K25 0.940 magnesium stearate 1, 230
Gesamt 85,000Total 85,000
Lösung zur Injektion:Solution for injection:
Pramipexoldihydrochlorid-monohydrat 0,3 mgPramipexole dihydrochloride monohydrate 0.3 mg
Natriumchlorid 0,8 mgSodium chloride 0.8 mg
Benzalkoniumchloήd 0,01 mg Aqua ad injectionem ad 100 ml Benzalkoniumchloήd 0.01 mg Aqua ad injectionem ad 100 ml
Claims
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002453485A CA2453485A1 (en) | 2001-08-03 | 2002-07-31 | Pramipexole for the treatment of adhd |
| JP2003518529A JP2005500368A (en) | 2001-08-03 | 2002-07-31 | Pramipexole for ADHD treatment |
| EP02762417A EP1416930A1 (en) | 2001-08-03 | 2002-07-31 | Pramipexole for the treatment of adhd |
| MXPA04001001A MXPA04001001A (en) | 2001-08-03 | 2002-07-31 | Pramipexole for the treatment of adhd. |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10137633.2 | 2001-08-03 | ||
| DE10137633A DE10137633A1 (en) | 2001-08-03 | 2001-08-03 | Treatment or prophylaxis of attention deficit hyperactivity disorder, using the dopamine agonist pramexipol or its salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2003013520A1 true WO2003013520A1 (en) | 2003-02-20 |
Family
ID=7693957
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2002/008500 Ceased WO2003013520A1 (en) | 2001-08-03 | 2002-07-31 | Pramipexole for the treatment of adhd |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1416930A1 (en) |
| JP (1) | JP2005500368A (en) |
| AR (1) | AR035273A1 (en) |
| CA (1) | CA2453485A1 (en) |
| DE (1) | DE10137633A1 (en) |
| MX (1) | MXPA04001001A (en) |
| UY (1) | UY27408A1 (en) |
| WO (1) | WO2003013520A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2308464A1 (en) * | 2009-10-06 | 2011-04-13 | Sanovel Ilac Sanayi ve Ticaret A.S. | Orally disintegrating compositions of pramipexole |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TR200906997A1 (en) | 2009-09-11 | 2011-03-21 | Sanovel �La� San. Ve T�C. A. �. | Pramipexole pharmaceutical compositions. |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5621133A (en) * | 1989-05-31 | 1997-04-15 | Deninno; Michael P. | Dopamine agonists |
| WO2001089453A2 (en) * | 2000-05-19 | 2001-11-29 | Wayne State University | Derivatives of 2-aminotetralins and pharmaceutical analogs thereof exhibiting differential cns receptor activity and behavior |
| EP1177798A2 (en) * | 2000-07-31 | 2002-02-06 | Pfizer Products Inc. | A pharmaceutical composition for the treatment of attention deficit hyperactivity disorder(ADHD) comprising a nicotine receptor partial agonist and anti-ADHD agent |
| US20020058009A1 (en) * | 2000-09-19 | 2002-05-16 | Advanced Inhalation Research, Inc. | Pulmonary delivery in treating disorders of the central nervous system |
-
2001
- 2001-08-03 DE DE10137633A patent/DE10137633A1/en not_active Withdrawn
-
2002
- 2002-07-31 MX MXPA04001001A patent/MXPA04001001A/en not_active Application Discontinuation
- 2002-07-31 WO PCT/EP2002/008500 patent/WO2003013520A1/en not_active Ceased
- 2002-07-31 EP EP02762417A patent/EP1416930A1/en not_active Withdrawn
- 2002-07-31 CA CA002453485A patent/CA2453485A1/en not_active Abandoned
- 2002-07-31 JP JP2003518529A patent/JP2005500368A/en active Pending
- 2002-08-02 AR ARP020102946A patent/AR035273A1/en not_active Application Discontinuation
- 2002-08-02 UY UY27408A patent/UY27408A1/en not_active Application Discontinuation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5621133A (en) * | 1989-05-31 | 1997-04-15 | Deninno; Michael P. | Dopamine agonists |
| WO2001089453A2 (en) * | 2000-05-19 | 2001-11-29 | Wayne State University | Derivatives of 2-aminotetralins and pharmaceutical analogs thereof exhibiting differential cns receptor activity and behavior |
| EP1177798A2 (en) * | 2000-07-31 | 2002-02-06 | Pfizer Products Inc. | A pharmaceutical composition for the treatment of attention deficit hyperactivity disorder(ADHD) comprising a nicotine receptor partial agonist and anti-ADHD agent |
| US20020058009A1 (en) * | 2000-09-19 | 2002-05-16 | Advanced Inhalation Research, Inc. | Pulmonary delivery in treating disorders of the central nervous system |
Non-Patent Citations (5)
| Title |
|---|
| EMILIEN ET AL.: "Dopamine D3 agonists", EXPERT OPINION THERAPEUTICS PATENTS, vol. 11, no. 11, pages 1713 - 1728, XP001057496 * |
| INOUE: "Strategy for Modulation of Central Dopamine Transmission Based on the Partial Agonist Concept in Schizophrenia Therapy", JAPANESE JOURNAL OF PHARMACOLOGY, vol. 86, no. 4, 2001, pages 376 - 380, XP009001165 * |
| MAJ ET AL.: "Antidepressant effects of pramipexole, a novel dopamine receptor agonist", JOURNAL NEURAL TRANSMISSION, vol. 104, pages 525 - 533, XP002101636 * |
| MAY ET AL.: "The effect of repeated treatment with pramipexole on the central dopamine D3 system", J NEURAL TRANSMISSION, vol. 107, pages 1369 - 1379, XP002225409 * |
| See also references of EP1416930A1 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2308464A1 (en) * | 2009-10-06 | 2011-04-13 | Sanovel Ilac Sanayi ve Ticaret A.S. | Orally disintegrating compositions of pramipexole |
| TR200907554A1 (en) * | 2009-10-06 | 2011-04-21 | Sanovel İlaç San.Ve Ti̇c.A.Ş. | Orally dispersible pramipexole compositions. |
Also Published As
| Publication number | Publication date |
|---|---|
| UY27408A1 (en) | 2003-02-28 |
| MXPA04001001A (en) | 2004-04-20 |
| CA2453485A1 (en) | 2003-02-20 |
| DE10137633A1 (en) | 2003-02-20 |
| JP2005500368A (en) | 2005-01-06 |
| EP1416930A1 (en) | 2004-05-12 |
| AR035273A1 (en) | 2004-05-05 |
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