Treatment of Cognitive Impairment with Combination Therapy
Treatment of varying degrees of cognitive impairment associated with Alzheimer's disease with a combination of a phosphodiesterase 4 inhibitor and an acetylcholinestase inhibitor, including roflumilast and donepezil hydrochloride.
1 . A method of treating cognitive impairment in a mammal in need of such treatment, comprising administering to a mammal suffering from cognitive impairment a therapeutically effective amount of a combination of
(1) a phosphodiesterase 4 inhibitor; and
(2) an acetylcholinesterase inhibitor;
wherein the phosphodiesterase 4 inhibitor is selected from the group consisting of roflumilast, a pharmaceutically acceptable salt of roflumilast, roflumilast-N-oxide and a pharmaceutically acceptable salt of roflumilast-N-oxide, and the acetylcholinesterase inhibitor is selected from the group consisting of donepezil, a pharmaceutical acceptable salt of donepezil, galantamine, a pharmaceutically acceptable salt of galantamine, rivastigmine, and a pharmaceutically acceptable salt of rivastigmine.
2 . The method according to claim 1 , wherein treating cognitive impairment is any one of
(a) treating mild cognitive impairment;
(b) delaying progression from mild cognitive impairment to cognitive impairment associated with Alzheimer's disease; and
(c) treating cognitive impairment associated with Alzheimer's disease.
3 . The method according to claim 1 , wherein the phosphodiesterase 4 inhibitor is selected from the group consisting of roflumilast and a pharmaceutically acceptable salt of roflumilast.
4 . The method according to claim 1 , wherein the phosphodiesterase 4 inhibitor is roflumilast.
5 . The method according to claim 1 , wherein the acetylcholinesterase inhibitor is donepezil hydrochloride.
6 . The method according to claim 1 , wherein the phosphodiesterase 4 inhibitor is roflumilast and the acetylcholinesterase inhibitor is donepezil hydrochloride.
7 . The method according to claim 4 , wherein the phosphodiesterase 4 inhibitor is administered at a daily dose of between 50 and 150 mcg.
8 . The method according to claim 6 , wherein the phosphodiesterase 4 inhibitor is roflumilast and wherein the phosphodiesterase 4 inhibitor is administered at a daily dose of between 50 and 150 mcg.
9 . The method according to claim 6 , wherein roflumilast is administered at a daily dose of between 50 and 150 mcg and donepezil hydrochloride is administered at a daily dose of between 5 and 23 mg.
10 . The method according to claim 6 , wherein roflumilast is administered at a daily dose selected from 50, 75, 100 or 125 mcg and donepezil hydrochloride is administered at a daily dose selected from 5 or 10 mg.
11 . The method according to claim 1 , wherein the phosphodiesterase 4 inhibitor and the acetylcholinesterase inhibitor are administered in one single dosage form.
12 . The method according to claim 1 , wherein the phosphodiesterase 4 inhibitor and the acetylcholinesterase inhibitor are administered concurrently or sequentially in two separate dosage forms.
13 . A pharmaceutical composition, comprising:
a. a phosphodiesterase 4 inhibitor in combination with
b. an acetylcholinesterase inhibitor, and
c. a pharmaceutically acceptable carrier,
wherein the phosphodiesterase 4 inhibitor is selected from the group consisting of roflumilast, a pharmaceutically acceptable salt of roflumilast, roflumilast-N-oxide and a pharmaceutically acceptable salt of roflumilast-N-oxide, the acetylcholinesterase inhibitor is selected from the group consisting of donepezil, a pharmaceutical acceptable salt of donepezil, galantamine, a pharmaceutically acceptable salt of galantamine, rivastigmine, and a pharmaceutically acceptable salt of rivastigmine.
14 . The pharmaceutical composition according to claim 13 , wherein the phosphodiesterase 4 inhibitor is selected from the group consisting of roflumilast and a pharmaceutically acceptable salt of roflumilast.
15 . The pharmaceutical composition according to claim 13 , wherein the phosphodiesterase 4 inhibitor is roflumilast.
16 . The pharmaceutical composition according to claim 13 , wherein the acetylcholinesterase inhibitor is donepezil hydrochloride.
17 . The pharmaceutical composition according to claim 13 , wherein the phosphodiesterase 4 inhibitor is roflumilast and the acetylcholinesterase inhibitor is donepezil hydrochloride.
18 . The pharmaceutical composition according to claim 15 , wherein the phosphodiesterase 4 inhibitor is present in an amount of between 50 and 150 mcg.
19 . The pharmaceutical composition according to claim 17 , wherein the phosphodiesterase 4 inhibitor is roflumilast and wherein the phosphodiesterase 4 inhibitor is present in an amount of between 50 and 150 mcg.
20 . The pharmaceutical composition according to claim 17 , wherein roflumilast is present in an amount of between 50 and 150 mcg and donepezil hydrochloride and is present in an amount of between 5 and 23 mg.
21 . The pharmaceutical composition according to claim 17 , wherein roflumilast is present in an amount selected from 50, 75, 100 or 125 mcg and donepezil hydrochloride is present in an amount selected from of 5 or 10 mg.
22 . The pharmaceutical composition according to claim 13 , wherein the phosphodiesterase 4 inhibitor and the acetylcholinesterase inhibitor are to be administered concurrently in one single dosage form.
23 . The pharmaceutical composition according to claim 13 , wherein the phosphodiesterase 4 inhibitor and the acetylcholinesterase inhibitor are to be administered concurrently or sequentially in two separate dosage forms.