Memantine combinations and use

Abstract

A pharmaceutical combination of memantine and a non-anticholinergic antiemetic agent for the treatment of hypocholinergic disorders in further combination with high doses of donepezil and with solifenacin, and kits comprising said combination. A pharmaceutical combination of memantine and solifenacin for the treatment of hypocholinergic disorders, including Alzheimer type dementia, in further combination with high doses of donepezil, and kits comprising said combination.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority benefit of U.S. Provisional Patent Application Ser. No. 62 / 414,359 filed Oct. 28, 2016, U.S. Provisional Patent Application Ser. No. 62 / 424,085 filed Nov. 18, 2016, and U.S. Provisional Patent Application Ser. No. 62 / 423,999 filed Nov. 18, 2016; the disclosures of which are herein incorporated by reference in their entirety.FIELD OF THE INVENTION[0002]This invention pertains to the field of the treatment of patients suffering from a hypocholinergic disorder in the brain such as Alzheimer disease, Lewy body disease, Parkinson's disease, and related disorders in humans. The invention provides a combination of memantine with a non-anticholinergic antiemetic agent (naAEA) to be safely administered to a patient suffering from a hypocholinergic disorder in further combination with donepezil high doses and solifenacin, thus inducing neuroprotection in said patient. The invention also provides a combination of mem...

AI Technical Summary

Benefits of technology

[0031]It has surprisingly been found that, by treating said patients under treatment with memantine with solifenacin and donepezil, instead of the expected, additive synergy as previously seen when memantine was added on to a moderately severe Alzheimer patient on a stable dose of donepezil, higher doses of donepezil were even more effective in patients also taking memantine, despite the fact that the memantine dose remained constant.

[0079]These kits, which contain donepezil or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition in dosage unit form wherein said ChEI is in admixture with a pharmaceutical carrier, can simplify the administration of the above combination to patients suffering from hypocholinergic disorders of the CNS, who are often not sufficiently able to manage multiple packages.

Problems solved by technology

However, results from some randomized controlled trials in patients with moderate to severe AD have failed to show that the combination of donepezil plus memantine confers significant efficacy advantages over donepezil alone, regardless of whether donepezil was given at the standard 10 mg / day or the 23 mg / day dose (Porsteinsson A P, Grossberg G T, Mintzer J, Olin J T; Memantine MEM-MD-12 Study Group, “Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial”, Curr Alzheimer Res. 2008 February; 5(1):83-9; Doody R S, Geldmacher D S, Farlow M R, Sun Y, Moline M, Mackell J, “Efficacy and safety of donepezil 23 mg versus donepezil 10 mg for moderate-to-severe Alzheimer's disease: a subgroup analysis in patients already taking or not taking memantine”, Dement Geriatr Cogn Disord.

Moreover, there is no generally accepted rationale for any symptomatic benefit gained by combining these drugs.

Thus, to date, there is scant experimental support for this view and thus no basis to expect a synergistic or additive effect of memantine on cholinergic function.