Process for the production of high-purity...

C - Chemistry – Metallurgy – 07 – D

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C07D 295/108 (2006.01) A61K 31/4453 (2006.01)

Patent

CA 2683634

The invention relates to a method for producing highly pure 2,4'-dimethyl-3-piperidino-propiophenone (tolperisone) (formula I) and the pharmaceutically acceptable salts, hydrochlorides, and hydrates thereof. Said method allows the content of the undesired byproduct 2-methyl-1-(4-methyphenyl) propenone (4-MMPPO) to be kept significantly lower than in previously known methods. The invention further relates to active substance formulations which contain tolperisone and are suitable, among other things, for producing combination preparations used for treating patients suffering from Alzheimer's disease. The invention also relates to topical formulations, controlled release (CR) formulations, and transdermal therapeutic systems, such as active substance patches, which contain less than 50 ppm, preferably less than 10 ppm, more preferably less than 7 ppm, and most preferably less than 3 ppm or 0 ppm (i.e. less than the detectable amount) of the undesired byproduct 2-methyl-1-(4-methylphenyl) propenone (4-MMPPO) in relation to 100 percent by weight of active substance.

L'invention concerne un procédé de production de 2,4'-diméthyl-3-pipéridino-propiophénone (tolpérisone), et de ses sels, chlorhydrates et hydrates pharmaceutiquement acceptables, procédé permettant de réduire sensiblement, par rapport aux procédés connus, la fraction de produit secondaire indésirable, 2-méthyl-1-(4-méthylphényl)-propénone (4-MMPPO). L'invention concerne en outre des formulations de principe actif contenant de la tolpérisone, qui sont appropriées entre autres pour la production de préparations de combinaisons pour la thérapie et le traitement de patients atteints de la maladie d'Alzheimer. L'invention concerne en outre des formulations topiques, des formulations à libération contrôlée (CR), et des systèmes transdermiques, thérapeutiques, tels que des timbres à substances actives qui contiennent moins de 50 ppm, de préférence, moins de 10 ppm, voire, moins de 7 ppm, ou mieux, moins de 3 ppm ou 0 ppm ( c'est-à-dire inférieur à la limite détectable) de produit secondaire indésirable, 2-méthyl-1-(4-méthylphényl)-propénone (4-MMPPO) pour 100 % en poids de principe actif.

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