RU2014127731A

RU2014127731A - COMBINATION 4- {3- [CIS-HEXAHYDROCYCLOPENT [C] PYRROL-2 (1H) -IL] PROXY} BENZAMIDE AND ANTAGONIST NMDA RECEPTOR AND CONTAINING ITS PHARMACEUTICAL COMPOSITIONS

Info

Publication number: RU2014127731A
Application number: RU2014127731A
Authority: RU
Inventors: Орора Сор; Карин ТРОКМЕ-ТИБЬЕРЖ; Аннетте Мерде
Original assignee: Ле Лаборатуар Сервье
Priority date: 2011-12-09
Filing date: 2012-12-07
Publication date: 2016-01-27
Also published as: GEP20156233B; SV2012004361A

Abstract

1. Комбинация 4-{3-[цис-гексагидроциклопента[с]пиррол-2(1H)-ил]пропокси}бензамида формулы (I):или его соли присоединения фармацевтически приемлемой кислоты или основания, и антагониста глутаматного NMDA-рецептора.2. Комбинация по п. 1, отличающаяся тем, что 4-{3-[цис-гексагидроциклопента[с]пиррол-2(1H)-ил]пропокси}бензамид применяют в форме оксалата или гидрохлорида.3. Комбинация по п. 1 или 2, в которой антагонист глутаматного NMDA-рецептора представляет собой мемантин.4. Комбинация по п. 1 или 2, в которой мемантин применяют в форме гидрохлорида.5. Комбинация по п. 1 или 2, для применения в качестве лекарственного средства, причем: (I) 4-{3-[цис-гексагидроциклопента[с]пиррол-2(1H)-ил]пропокси}бензамид вводят в ежедневной дозе 2 мг, 5 мг или 20 мг (в пересчете на эквивалент основания) в форме гидрохлорида, и (II) антагонист глутаматного NMDA-рецептора представляет собой гидрохлорид мемантина, который вводят в ежедневной дозе 10 мг или 20 мг.6. Фармацевтическая композиция, которая в качестве действующего вещества содержит 4-{3-[цис-гексагидроциклопента[с]пиррол-2(1H)-ил]пропокси}бензамид или его соль присоединения фармацевтически приемлемой кислоты или основания, в комбинации с антагонистом глутаматного NMDA-рецептора по одному из пп. 1-4, в комбинации с одним или несколькими фармацевтически приемлемыми вспомогательными веществами.7. Фармацевтическая композиция по п. 6 для применения в лечении когнитивных нарушений, связанных с церебральным старением и нейродегенеративными заболеваниями.8. Фармацевтическая композиция для применения по п. 7 в лечении когнитивных нарушений, связанных с болезнью Альцгеймера.9. Фармацевтическая композиция по п. 6, отличающая�1. The combination of 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide of formula (I): or a pharmaceutically acceptable acid or base addition salt thereof and a glutamate NMDA receptor antagonist. 2 . The combination according to claim 1, characterized in that 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide is used in the form of oxalate or hydrochloride. 3. The combination of claim 1 or 2, wherein the glutamate NMDA receptor antagonist is memantine. The combination according to claim 1 or 2, in which memantine is used in the form of hydrochloride. The combination according to claim 1 or 2, for use as a medicine, wherein: (I) 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide is administered in a daily dose of 2 mg , 5 mg or 20 mg (in terms of base equivalent) in the form of a hydrochloride, and (II) the glutamate NMDA receptor antagonist is memantine hydrochloride, which is administered in a daily dose of 10 mg or 20 mg. 6. A pharmaceutical composition which contains 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide or a pharmaceutically acceptable acid or base addition salt thereof, in combination with a glutamate NMDA antagonist receptor according to one of paragraphs. 1-4, in combination with one or more pharmaceutically acceptable excipients. 7. The pharmaceutical composition of claim 6 for use in the treatment of cognitive impairment associated with cerebral aging and neurodegenerative diseases. A pharmaceutical composition for use according to claim 7 in the treatment of cognitive impairment associated with Alzheimer's disease. The pharmaceutical composition according to claim 6, characterized

Claims

1. The combination of 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide of the formula (I):

or a pharmaceutically acceptable acid or base addition salt thereof; and a glutamate NMDA receptor antagonist.

2. The combination according to claim 1, characterized in that 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide is used in the form of oxalate or hydrochloride.

3. The combination of claim 1 or 2, wherein the glutamate NMDA receptor antagonist is memantine.

4. The combination according to claim 1 or 2, in which memantine is used in the form of hydrochloride.

5. The combination according to claim 1 or 2, for use as a medicine, wherein: (I) 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide is administered in a daily dose 2 mg, 5 mg or 20 mg (in terms of base equivalent) in the form of a hydrochloride, and (II) the glutamate NMDA receptor antagonist is memantine hydrochloride, which is administered in a daily dose of 10 mg or 20 mg.

6. A pharmaceutical composition which contains 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide or a pharmaceutically acceptable acid or base addition salt thereof, in combination with a glutamate antagonist, as active substance NMDA receptor according to one of claims. 1-4, in combination with one or more pharmaceutically acceptable excipients.

7. The pharmaceutical composition according to claim 6 for use in the treatment of cognitive impairment associated with cerebral aging and neurodegenerative diseases.

8. The pharmaceutical composition for use according to claim 7 in the treatment of cognitive impairment associated with Alzheimer's disease.

9. The pharmaceutical composition according to claim 6, characterized in that it contains 2 mg, 5 mg or 20 mg (in terms of equivalent base) of 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide in the form of hydrochloride, and 10 mg or 20 mg of memantine hydrochloride as an antagonist of the glutamate NMDA receptor.

10. The use of a combination according to one of paragraphs. 1-5 for the preparation of a medicinal product intended for the treatment of cognitive impairment associated with cerebral aging and neurodegenerative diseases.

11. The use of the combination according to one of paragraphs. 1-5 for the preparation of a medicinal product intended for the treatment of cognitive impairment associated with Alzheimer's disease.

12. The combination according to claim 1 or 2, 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide, or a pharmaceutically acceptable acid or base addition salt thereof, and memantine for use in treating cognitive impairment associated with Alzheimer's disease.

13. The use of the combination according to one of paragraphs. 1-5, 4- {3- [cis-hexahydrocyclopenta [c] pyrrole-2 (1H) -yl] propoxy} benzamide or a pharmaceutically acceptable acid or base addition salt thereof and memantine for the preparation of a medicament for the treatment of cognitive impairment associated with Alzheimer's disease.