Opioid-nornicotine codrugs combinations for pain management
AssigneeUniversity of Kentucky Research Foundation
InventorsJoseph R. Holtman, Peter A. Crooks, Ujjwal Chakraborty
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Abstract
The present invention relates to the field of pain management, and more particularly to synergistic codrugs comprising an opioid and nornicotine which have been combined to form a single chemical codrug entity. When the codrug is administered it produces a synergistic analgesic response to pain.
Claims34
A codrug of the following formula:
A codeine-S-nornicotine codrug comprising the formula:
A 3-acetylmorphine-S-nornicotine codrug comprising the formula:
A pharmaceutical composition comprising an analgesically effective amount of a compound selected from the group consisting of:
- a compound of the formula Ia:
- wherein R is H or CH3, R1-CO— (where R1=alkyl);
- X is a bond, S, O, NH, NR2 (where R2=alkyl);
- and * represents a racemic nornicotine, S-nornicotine, or R-nornicotine moiety;
- a compound of the formula Ib:
- wherein Y is O, S;
- R is H or CH3 or R1-CO— (where R1=alkyl);
- and * represents a racemic nornicotine, S-nornicotine, or R-nornicotine moiety;
- and analogs and stereoisomers thereof,
- a compound of the formula II:
- and a compound of the formula III:
- and at least one pharmaceutically acceptable excipient.
A method of synthesis of a codrug comprising a linker, an opioid and a nornicotine, said method comprising:
- a) covalently bonding a first attachment point of the linker to the opioid;
- b) covalently bonding a second attachment point of the linker to the nornicotine;
- and
- c) recovering the codrug,
- wherein the nornicotine is selected from the group consisting of S-nornicotine, R-nornicotine, and racemic nornicotine.
A method of treatment comprising:
- joining an opioid together with a nornicotine using a linker to form a cleavable codrug;
- and
- administering an analgesically effective amount of the codrug to a human patient in need thereof,
- wherein the nornicotine is selected from the group consisting of S-nornicotine, R-nornicotine, and racemic nornicotine.
Dependencies are inferred from the claim text.