METHODS FOR THE PREVENTION AND TREATMENT OF CEREBRAL ISCHEMIA
The present invention provides methods for the treatment, amelioration, or prevention of a symptom of neuronal damage associated with cerebral ischemia comprising administering compositions comprising a compound of Formula I.
1 . A method for treating or reducing neuronal damage associated with a cerebral ischemic event in a mammalian subject in need of such treatment, comprising administering to the subject a composition comprising a single cytoprotective agent present in an effective amount, wherein the cytoprotective agent present in an effective amount consists of alpha-tocotrienol quinone,
or a stereoisomer or mixture of stereoisomers thereof;
with the proviso that said subject does not suffer from a mitochondrial disease where stroke is one of the symptoms of the mitochondrial disease.
2 .- 3 . (canceled)
4 . The method according to claim 1 , wherein the cerebral ischemic event is secondary to an occlusion of the cerebral vasculature.
5 . The method according to claim 4 , wherein the occlusion is due to a thromboembolus.
6 . The method according to claim 1 , wherein the cerebral ischemia is due to a spasm of the coronary vasculature.
7 . The method according to claim 1 , wherein the cerebral ischemic event is secondary to a cessation of cardiac function.
8 . The method according to claim 1 , wherein the cerebral ischemic event is secondary to a cardiopulmonary bypass procedure.
9 . The method according to claim 1 , wherein the cerebral ischemic event is secondary to a hemorrhagic event in the cerebral vasculature.
10 .- 11 . (canceled)
12 . The method according to claim 1 , wherein said composition comprises at least about 85% alpha-tocotrienol quinone or a stereoisomer or mixture of stereoisomers thereof.
13 . The method according to claim 1 , wherein said composition comprises at least about 90% alpha-tocotrienol quinone or a stereoisomer or mixture of stereoisomers thereof.
14 . The method according to claim 1 , wherein said composition comprises at least about 95% alpha-tocotrienol quinone or a stereoisomer or mixture of stereoisomers thereof.
15 . The method according to claim 1 , wherein said composition additionally comprises a pharmaceutically acceptable carrier.
16 . The method according to claim 1 , wherein said composition is administered orally.
17 . The method according to claim 1 , wherein said composition is administered parenterally.
18 . The method according to claim 1 , wherein said composition comprises alpha-tocotrienol quinone, or a stereoisomer or mixture of stereoisomers thereof, in a range of about 1 to about 1000 mg per kg body weight of said mammalian subject.
19 . (canceled)
20 . The method according to claim 1 , wherein said neuronal damage is selected from the group consisting of neuronal cell death, cerebral ischemic damage, cerebral tissue edema, and cognitive dysfunction.
21 . A method for treating a cerebral ischemic event in a mammalian subject in need of such treatment, comprising administering to the subject a composition comprising a single cytoprotective agent present in an effective amount, wherein the cytoprotective agent present in an effective amount consists of alpha-tocotrienol quinone,
or a stereoisomer or mixture of stereoisomers thereof;
with the proviso that said subject does not suffer from a mitochondrial disease where stroke is one of the symptoms of the mitochondrial disease.
22 .- 23 . (canceled)
24 . A method for treating a cerebral ischemic event in a mammalian subject in need of such treatment, comprising administering to the subject a composition comprising a single cytoprotective agent present in an effective amount, wherein the cytoprotective agent present in an effective amount consists of alpha-tocotrienol quinone,
or a stereoisomer or mixture of stereoisomers thereof;
with the proviso that said subject has not been administered a compound of Formula I:
where R 1 , R 2 , and R 3 are independently of each other hydrogen, (C 1 -C 6 )alkyl, or (C 1 -C 6 )alkoxy; and
m is an integer between 1 and 12, inclusive;
or a stereoisomer or mixture of stereoisomers thereof;
within the month prior to the cerebral ischemic event.
25 .- 26 . (canceled)
27 . The method according to claim 1 , wherein said subject does not suffer from a mitochondrial disease.
28 . The method according to claim 21 , wherein said composition additionally comprises a pharmaceutically acceptable carrier.
29 . A method for prophylactically treating or reducing neuronal damage associated with a cerebral ischemic event in a mammalian subject at risk for a cerebral ischemic condition, comprising administering to the subject a composition comprising a single cytoprotective agent present in an effective amount, wherein the cytoprotective agent present in an effective amount consists of alpha-tocotrienol quinone, or a stereoisomer or mixture of stereoisomers thereof; with the proviso that said subject does not suffer from a mitochondrial disease where stroke is one of the symptoms of the mitochondrial disease.
30 . The method according to claim 1 , wherein the method comprises reducing total cerebral infarct volume.
31 . The method according to claim 1 , wherein alpha-tocotrienol quinone, or a stereoisomer or mixture of stereoisomers thereof, is the sole active ingredient present in an effective amount in the composition.
32 . The method according to claim 1 , wherein alpha-tocotrienol quinone, or a stereoisomer or mixture of stereoisomers thereof, is the sole active ingredient in the composition.
33 . A method for treating or reducing neuronal damage associated with a cerebral ischemic event in a mammalian subject in need of such treatment, comprising administering to the subject a composition comprising alpha-tocotrienol quinone, or a stereoisomer or mixture of stereoisomers thereof, wherein the alpha-tocotrienol quinone, or a stereoisomer or mixture of stereoisomers thereof is the sole agent in an effective amount used to treat the disorder.
34 . A method for treating and/or ameliorating neuronal damage associated with hypoxia in a mammalian subject in need of such treatment, comprising administering to the subject an effective amount of a composition comprising a single cytoprotective agent present in an effective amount, wherein the cytoprotective agent present in an effective amount consists of alpha-tocotrienol quinone or a stereoisomer or mixture of stereoisomers thereof; with the proviso that said subject does not suffer from a mitochondrial disease where stroke is one of the symptoms of the mitochondrial disease.
35 . The method according to claim 1 , wherein the single cytoprotective agent in an effective amount consists of alpha-tocotrienol quinone.