ES2629317T3 - Tratamiento de tumores cerebrales sólidos con un derivado de rapamicina - Google Patents

Tratamiento de tumores cerebrales sólidos con un derivado de rapamicina Download PDF

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Publication number
ES2629317T3
ES2629317T3 ES14164565.5T ES14164565T ES2629317T3 ES 2629317 T3 ES2629317 T3 ES 2629317T3 ES 14164565 T ES14164565 T ES 14164565T ES 2629317 T3 ES2629317 T3 ES 2629317T3
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combination
treatment
administration
brain tumors
rapamycin derivative
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ES14164565.5T
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Heidi Lane
Terence O'reilly
Jeanette Marjorie Wood
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Novartis AG
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Novartis AG
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Priority claimed from GB0104072A external-priority patent/GB0104072D0/en
Priority claimed from GB0124957A external-priority patent/GB0124957D0/en
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    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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    • A61K31/365Lactones
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    • A61K31/41Heterocyclic 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
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    • A61K31/436Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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Abstract

40-O-(2-hidroxietil)-rapamicina para su uso como principio activo único en el tratamiento de tumores cerebrales sólidos distintos de cáncer linfático.

Description

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hipertermia leve prolongada de todo el cuerpo y/o terapia de irradiación.
La administración de una combinación farmacéutica de la descripción no solo da como resultado un efecto beneficioso, por ejemplo, un efecto terapéutico sinérgico, por ejemplo con respecto a la ralentización, detención o inversión de la formación de neoplasias o una duración más larga de la respuesta frente al tumor, sino también efectos beneficiosos sorprendentes adicionales, por ejemplo menos efectos secundarios, una calidad de vida mejorada o una mortandad y morbilidad disminuidas, en comparación con una monoterapia que aplica solo uno de los principios farmacéuticamente activos usados en la combinación de la descripción, en particular en el tratamiento de un tumor que es refractario a otros agentes quimioterápicos conocidos como agentes anticancerígenos. En particular, se observa una absorción aumentada del coagente (b) en el tejido tumoral y las células tumorales, cuando se aplica en combinación con el primer agente (a).
Un beneficio adicional es que pueden usarse dosis más bajas de los principios activos de la combinación de la invención, por ejemplo, que las dosificaciones a menudo no sólo tienen que ser más pequeñas, sino que también se aplican con menor frecuencia, o pueden usarse para disminuir la incidencia de los efectos secundarios, mientras se controla el crecimiento de la formación de neoplasias. Esto es según los deseos y requerimientos de los pacientes que van a tratarse.
Los términos “coadministración” o “administración combinada” o similares tal como se usan en el presente documento se entiende que abarcan la administración de los agentes terapéuticos seleccionados a un solo paciente, y se pretende que incluyan regímenes de tratamiento en los que los agentes no se administran necesariamente por la misma vía de administración o al mismo tiempo.
Las composiciones farmacéuticas para la administración separada del primer agente a) y el coagente b) y para la administración en una combinación fija, es decir, una única composición galénica que comprende al menos dos componentes de combinación a) y b), según la invención pueden prepararse de manera conocida per se y son las adecuadas para la administración entérica, tal como oral o rectal, y parenteral a mamíferos (animales de sangre caliente), incluyendo seres humanos, que comprende una cantidad terapéuticamente eficaz de al menos un componente de combinación farmacológicamente activo solo, por ejemplo tal como se indica anteriormente, o en combinación con uno o más portadores o diluyentes farmacéuticamente aceptables, especialmente adecuados para la aplicación entérica o parenteral.
Las composiciones farmacéuticas adecuadas contienen, por ejemplo, de desde aproximadamente el 0,1% hasta aproximadamente el 99,9%, preferiblemente desde aproximadamente el 1% hasta aproximadamente el 60%, del/de los principio(s) activo(s). Las preparaciones farmacéuticas para la terapia de combinación para la administración entérica o parenteral son, por ejemplo, aquellas en formas de dosificación unitarias, tales como comprimidos recubiertos con azúcar, comprimidos, cápsulas o supositorios, o ampollas. Si no se indica lo contrario, estos se preparan de manera conocida per se, por ejemplo por medio de procesos de mezclado, granulación, recubrimiento con azúcar, disolución o liofilización convencionales. Se apreciará que el contenido unitario de un componente de combinación contenido en una dosis individual de cada forma de dosificación no necesita por sí mismo constituir una cantidad eficaz puesto que la cantidad eficaz necesaria puede alcanzarse mediante la administración de una pluralidad de unidades de dosificación.
Una cantidad terapéuticamente eficaz de cada uno de los componentes de combinación de la combinación dada a conocer en el presente documento puede administrarse simultánea o secuencialmente y en cualquier orden, y los componentes pueden administrarse por separado o como una combinación fija. Por ejemplo, el método de retraso del avance o tratamiento de una enfermedad maligna proliferativa según la descripción puede comprender (i) la administración del primer agente a) en forma de sal libre o farmacéuticamente aceptable y (ii) la administración de un coagente b) en forma de sal libre o farmacéuticamente aceptable, simultánea o secuencialmente en cualquier orden, en cantidades conjuntamente eficaces de manera terapéutica, preferiblemente en cantidades sinérgicamente eficaces, por ejemplo, en dosificaciones diarias o intermitentes correspondientes a las cantidades descritas en el presente documento. Los componentes de combinación individuales de la combinación dada a conocer en el presente documento pueden administrarse por separado en diferentes momentos durante el transcurso de la terapia
o de manera concurrente en formas de combinación divididas o únicas. Además, el término administración también abarca el uso de un profármaco de un componente de combinación que se convierte in vivo en el componente de la combinación como tal. Por tanto, la presente descripción debe entenderse como que abarca todos estos regímenes de tratamiento simultáneo o alternativo y el término “que administra” ha de interpretarse en consecuencia.
La dosificación eficaz de cada uno de los componentes de combinación empleados en la combinación dada a conocer en el presente documento puede variar según el compuesto o composición farmacéutica particular empleada, el modo de administración, el estado que se está tratando, la gravedad del estado que se está tratando. Por tanto, el régimen de dosificación de la combinación dada a conocer en el presente documento se selecciona según una variedad de factores incluyendo la vía de administración y la función renal y hepática del paciente. Un médico, clínico o veterinario experto puede determinar y recomendar fácilmente la cantidad eficaz de los principios activos individuales requeridos para prevenir, contrarrestar o detener el avance del estado. La precisión óptima para
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