US2016051535A1PendingUtilityA1
Morphinan Derivatives for the Treatment of Drug Overdose
Assignee: ALKERMES PHARMA IRELAND LTDPriority: Dec 4, 2009Filed: Aug 25, 2015Published: Feb 25, 2016
Est. expiryDec 4, 2029(~3.3 yrs left)· nominal 20-yr term from priority
A61P 25/30A61P 25/36A61K 31/485A61K 31/4748C07D 221/28C07D 221/22
48
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Claims
Abstract
The instant application relates to morphinan derivatives of Formula I with sustained effectiveness in treating drug toxicity and overdose:
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of treating drug toxicity or overdose in a subject in need thereof comprising administrating a compound of Formula I:
or a pharmaceutically acceptable salt, ester metabolite or prodrug wherein;
R 1 is —(CH 2 ) n -c-C 4 H 7 , —(CH 2 ) n -c-C 5 H 9 , —(CH 2 ) n —CH═CH 2 or —(CH 2 ) n —CH═C(CH 3 ) 2 wherein n is independently 0, 1, 2 or 3;
R 2 is —CONH 2 or —CSNH 2 ;
R 3 and R 4 are independently H, —OH or together R 3 and R 4 form an —O— or —S— group;
R 5 is H or C 1 -C 8 alkyl; and
R 6 and R 7 are independently H, —OH, OCH 3 or together R 6 and R 7 form a ═O or ═CH 2 group.
2 . The method according to any one of claim 1 , wherein said drug toxicity or overdose is resulting from opioid administration to a non-dependent patient.
3 . The method according to any one of claim 2 , wherein said subject is an opioid experienced, non-dependent opioid user.
4 . The method according to any one of claim 1 , wherein said compound of Formula I is administered in a daily dose of about 3 to about 20 mg/day.
5 . The method according to claim 4 , wherein said daily dose is about 10 mg/day.
6 . The method according to claim 1 , wherein administration of a compound of Formula I reduces symptoms of drug toxicity or overdose over a period of at least about 15 to about 30 minutes.
7 . The method according to claim 6 , wherein symptoms of drug overdose are reduced for a period of at least one hour.
8 . The method according to claim 6 , wherein symptoms of drug overdose are reduced for a period of at least two hours.
9 . The method according to claim 6 , wherein symptoms of drug overdose are reduced for a period of at least three hours.
10 . The method according to claim 6 , wherein symptoms of drug overdose are reduced for a period of at least four hours.
11 . The method according to claim 6 , wherein symptoms of drug overdose are reduced for a period of at least eight hours.
12 . The method according to any one of claim 6 , wherein said administration comprises about 3 mg to about 20 mg of a compound of Formula I.
13 . The method according to any one of claim 6 , wherein said symptoms of overdose is selected from decreased respiratory rate, decreased respiratory depth, apnea, comotosis, hypoxia, delirium hypotension, bradycardia, decreased body temperature, urinary retention and pupil miosis.
14 . A method of treating an opioid toxicity or overdose in a subject in need thereof comprising administrating a first opioid receptor antagonist followed by a compound of Formula I:
or a pharmaceutically acceptable salt, ester or prodrug thereof wherein;
R 1 is —(CH 2 ) n -c-C 4 H 7 , —(CH 2 ) n -c-C 5 H 9 , —(CH 2 ) n —CH═CH 2 or —(CH 2 ) n —CH═C(CH 3 ) 2 wherein n is independently 0, 1, 2 or 3;
R 2 is —CONH 2 or —CSNH 2 ;
R 3 and R 4 are independently H, —OH or together R 3 and R 4 form an —O— or —S— group;
R 5 is H or C 1 -C 8 alkyl; and
R 6 and R 7 are independently H, —OH, OCH 3 or together R 6 and R 7 form a ═O or ═CH 2 group.
15 . The method according to claim 14 , wherein said first opioid receptor antagonist is naloxone.
16 . The method according to claim 15 , wherein said subject is an opioid experienced non-dependent opioid user.
17 . The method according to claim 15 , wherein said administration of compound of Formula I is preceded by said naloxone administration.
18 . The method according to claim 17 , wherein said naloxone administration reduces symptoms of overdose or toxicity prior to administration of compounds of Formula I.
19 . The method according to claim 15 , wherein naloxone is administered concurrently with a compound of Formula I.
20 . A method of treating acute opioid toxicity or overdose for a period of over one hour comprising a single administration of a compound of Formula I to a subject in need thereof:
or a pharmaceutically acceptable salt, ester or prodrug thereof wherein;
R 1 is —(CH 2 ) n -c-C 4 H 7 , —(CH 2 ) n -c-C 5 H 9 , —(CH 2 ) n —CH═CH 2 or —(CH 2 ) n —CH═C(CH 3 ) 2 wherein n is independently 0, 1, 2 or 3;
R 2 is —CONH 2 or —CSNH 2 ;
R 3 and R 4 are independently H, —OH or together R 3 and R 4 form an —O— or —S— group;
R 5 is H or C 1 -C 8 alkyl; and
R 6 and R 7 are independently H, —OH, OCH 3 or together R 6 and R 7 form a ═O or ═CH 2 group.
21 . The method according to claim 20 , wherein said subject is a non-dependent opioid experienced patient.
22 . The method according to claim 20 , wherein symptoms of opioid toxicity or overdose are reduced for a period of more than one hour.
23 . The method according to claim 20 , wherein symptoms of opioid toxicity or overdose are reduced for a period of more than four hours.
24 . The method according to claim 20 , wherein symptoms of opioid toxicity or overdose are reduced for a period of more than eight hours.
25 . The method according to claim 20 , wherein symptoms of opioid toxicity or overdose are reduced for a period of more than twenty four hours.
26 . A method for unmonitored treatment of opioid toxicity or overdose in a patient in need thereof comprising administration of a compound of Formula I:
or a pharmaceutically acceptable salt, ester or prodrug thereof wherein;
R 1 is —(CH 2 ) n -c-C 4 H 7 , —(CH 2 ) n -c-C 5 H 9 , —(CH 2 ) n —CH═CH 2 or —(CH 2 ) n —CH═C(CH 3 ) 2 wherein n is independently 0, 1, 2 or 3;
R 2 is —CONH 2 or —CSNH 2 ;
R 3 and R 4 are independently H, —OH or together R 3 and R 4 form an —O— or —S— group;
R 5 is H or C 1 -C 8 alkyl; and
R 6 and R 7 are independently H, —OH, OCH 3 or together R 6 and R 7 form a ═O or ═CH 2 group.
27 . The method according to claim 26 , wherein said unmonitored treatment is effective for a period of over one hour.Join the waitlist — get patent alerts
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