Nova Patents
MX347901B

Use and composition for treating dementia.

Abstract

There is described a method for increasing the maximal tolerated dose and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia by decreasing concomitant adverse effects by administration of said AChEI in combination with a non-selective, peripheral anticholinergic agent, whereby an enhanced acetyl choline esterase inhibition in the CNS of said patient is achieved and alleviation of the symptoms of Alzheimer type dementia in said patient is thereby improved to a greater extent. The use of a non-selective, peripheral anticholinergic agent (nsPAChA) for the preparation of a pharmaceutical composition for increasing the maximal tolerated dose and thus the efficacy of an acetyl choline esterase inhibitor (AChEI) in a patient suffering from an Alzheimer type dementia and pharmaceutical compositions comprising a non-selective peripheral anticholinergic agent of formula II as illustrated in the description and an acetylcholine esterase inhibitor are also described.

MX347901B, drawing sheet 1
Sheet 1 of 54

Term

2.5 yearsleft in the term

Expires 17 March 2029.

  1. Priority
  2. Filed
  3. Granted
  4. Today
  5. Expires

10 claims: 5 independent, 5 dependent

  1. 1
    CLAIMS REIVINDICACIONES 1. A pharmaceutical unit form, characterized in that it comprises:1. Una forma unitaria farmacéutica, caracterizada porque comprende: (a) an nsPAChA selected from the group consisting of • quaternary ammonium nsPAChAs or sulfonium nsPAChAs represented by formula (II) R1 (a) un nsPAChA seleccionado del grupo que consiste de • nsPAChAs de amonio cuaternario o nsPAChAs de sulfonio representados por la fórmula (II) R1 R2--C— (COO) -— (X) —R (II) R2--C—(COO)-—(X)—R (II) R3 en donde - R es un radical seleccionado del grupo que consiste de aquellos de las fórmulas (a)-(e) R3 where - R is a radical selected from the group consisting of those of formulas (a) - (e) (a) Φ) (c) (d) (e) (a) Φ) (c) (d) (e) A es metilo y A' es un grupo alquilo de 1 a 4 átomos de carbono o 2-fluoroetilo o A y A' forman una cadena de 1,4butileno o 1,5-pentileno, L es hidrógeno o metoxi, Alq y Alq' son cada uno alquilo de 1 a 4 átomos de carbono e Y es un radical bivalente seleccionado del grupo que consiste de 1,2-etileno, 1,3-propileno, 1,4-butileno y 2-oxa-l,3propileno;el contraión correspondiente es un anión farmacéuticamente aceptable, - n y m son, independientemente, cero o 1, - X es un grupo alquileno de A is methyl and A 'is an alkyl group of 1 to 4 carbon atoms or 2-fluoroethyl or A and A' form a 1,4-butylene or 1,5-pentylene chain, L is hydrogen or methoxy, Alk and Alk ' they are each alkyl of 1 to 4 carbon atoms and Y is a bivalent radical selected from the group consisting of 1,2-ethylene, 1,3-propylene, 1,4-butylene and 2-oxa-1,3-propylene;the corresponding counterion is a pharmaceutically acceptable anion, - n and m are independently zero or 1, - X is an alkylene group of
  2. 2
    2 to 3 carbon atoms, 2 a 3 átomos de carbono, Ri and R2 they are each phenyl, Ri y R2 son cada uno fenilo, IMPI IMPI INSTITUTO MEXICANO DE LA PROMBDAL »INDUSTRIAL cyclopentyl, cyclohexyl, 1-cyclohexenyl, 2-thienyl and, when R is a radical (a), they also each represent alkyl of 1 to 4 carbon atoms, - R3 is H or OH or, only when R is a radical (a), also a group COOAlq, Alq is an alkyl group of 1 to 4 carbon atoms, • solifenacin and its pharmaceutically acceptable salts, • propiverine and its pharmaceutically acceptable salts, • oxyphencyclimine and its pharmaceutically acceptable salts, and • tolterodine and its pharmaceutically acceptable salts;and (b) a selected AChEI. from the group consisting of donepezil, pharmaceutically acceptable salts of donepezil, rivastigmine, pharmaceutically acceptable salts of rivastigmine, galantamine and pharmaceutically acceptable salts of galantamine, at a dose level of 1.5 times to 4 times higher than the maximum tolerated dose of said AChEI ;in a mixture with at least one pharmaceutically acceptable carrier. INSTITUTO MEXICANO DE LA PROMBDAL» INDUSTRIAL ciclopentilo, ciclohexilo, 1-ciclohexenilo, 2-tienilo y, cuando R es un radical (a) , también representan cada uno alquilo de 1 a 4 átomos de carbono, - R3 es H u OH o, únicamente cuando R es un radical (a) , también un grupo COOAlq, Alq es un grupo alquilo de 1 a 4 átomos de carbono, • solifenacina y sus sales farmacéuticamente aceptables, • propiverina y sus sales farmacéuticamente aceptables, • oxifenciclimina y sus sales farmacéuticamente aceptables, y • tolterodina y sus sales farmacéuticamente aceptables;y (b) un AChEI seleccionado . del grupo que consiste de donepezilo, sales farmacéuticamente aceptables de donepezilo, rivastigmina, sales farmacéuticamente aceptables de rivastigmina, galantamina y sales farmacéuticamente aceptables de galantamina, a un nivel de dosis de 1.5 veces a 4 veces más alta que la dosis máxima tolerada de dicho AChEI;en una mezcla con por lo menos un portador farmacéuticamente aceptable. 2. The unit form according to claim 1, characterized in that the component (a) of nsPAChA is selected from the group consisting of solifenacin and pharmaceutically acceptable salts thereof, propiverine and pharmaceutically acceptable salts thereof, oxyphencyclimine and pharmaceutically acceptable salts of it, tolterodine and pharmaceutically acceptable salts thereof, and pharmaceutically acceptable quaternary salts of homatropin, trospium, anisotropin, clidinium, benzylonium and 5-glycopyrronium. 2. La forma unitaria de conformidad con la reivindicación 1, caracterizada porque el componente (a) de nsPAChA se selecciona del grupo que consiste de solifenacina y sales farmacéuticamente aceptables de la misma, propiverina y sales farmacéuticamente aceptables de la misma, oxifenciclimina y sales farmacéuticamente aceptables de la misma, tolterodina y sales farmacéuticamente aceptables de la misma, y sales cuaternarias farmacéuticamente aceptables de homatropina, trospio, anisotropina, clidinio, bencilonio y 5 glicopirronio.
  3. 5
    The unit form in accordance with the 5. La forma unitaria de conformidad con la 20 reivindicación 1, caracterizada porque el componente (b) de AChEI se selecciona del grupo que consiste de clorhidrato de donepezilo y rivastigmina como hidrógeno-(2R,3R)tartrato. twenty Claim 1, characterized in that AChEI component (b) is selected from the group consisting of donepezil hydrochloride and rivastigmine as hydrogen- (2R, 3R) tartrate.
  4. 6
    The unit form in accordance with the 6. La forma unitaria de conformidad con la 25 claim 1, characterized in that component (a) of 71 25 reivindicación 1, caracterizada porque el componente (a) de 71 INSTITUTO MEXICANO MEXICAN INSTITUTE DE LA MONEDAD -W* OF THE CURRENCY -W * INDUSTRIAL nsPAChA es cloruro de trospio en una cantidad de 2 0 mg, y dicho componente (b) de AChEI es clorhidrato de donepezilo en una cantidad de 15 mg, o rivastigmina como tartrato de hidrógeno en una cantidad de 9 mg (en base de rivastigmina). INDUSTRIAL nsPAChA is trospium chloride in an amount of 20 mg, and said component (b) of AChEI is donepezil hydrochloride in an amount of 15 mg, or rivastigmine as hydrogen tartrate in an amount of 9 mg (based on rivastigmine ).
  5. 9
    A pharmaceutical unit form, characterized in that it comprises a non-selective, peripheral anticholinergic agent (nsPAChA) in combination with donepezil or a pharmaceutically acceptable salt thereof in an amount of 15 mg to 60 mg. 9. Una forma unitaria farmacéutica, caracterizada porque comprende un agente anticolinérgico, periférico, no selectivo (nsPAChA) en combinación con donepezilo o una sal farmacéuticamente aceptable del mismo en una cantidad de 15 mg a 60 mg.
Independent claims5