D-amphetamine compounds, compositions, and processes for making and using the same
Inventors
Guenther, Sven • Chi, Guochen • Mickle, Travis
Assignees
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Publication Number
US-12091386-B2
Publication Date
2024-09-17
Expiration Date
Abstract
Disclosed are d-amphetamine compounds and compositions comprising at least one organic acid covalently bound to d-amphetamine, having the structure of a salt thereof, a derivative thereof, or a combination thereof. Methods of making and using the same are also disclosed.
Core Innovation
The invention relates to d-amphetamine conjugates in which an organic moiety is covalently linked to d-amphetamine. The organic moiety includes heterocyclic nitrogen compounds and amino acids, and the conjugates are described using defined structure families including Formula IB, Formula ID, Formula IIB, and Formula IID with variable substituents X and R, including stereochemical possibilities at a chiral carbon using R/S stereoisomers and mixtures.
The document provides example conjugates that include AMP-CO2CH2-nicotinate esters and amino-acid/nicotinoyl conjugates, together with corresponding pharmaceutically acceptable salts. It also describes nicotinate and nicotinoyl-conjugate forms and corresponding isonicotinoyl analogs for comparison.
The conjugates and their salts are described as configured for pharmaceutical use, including oral administration and controlled/sustained-release concepts intended to modulate pharmacological exposure over time. The disclosure states that oral dosing enables hydrolysis-dependent activation after administration and reports comparative pharmacokinetic outcomes across oral, parenteral, and intranasal routes relative to d-amphetamine sulfate, lisdexamfetamine, and corresponding isonicotinoyl analogs.
Claims Coverage
Two independent claim groups are identified. The claims center on structurally defined compound selections and corresponding pharmaceutically acceptable salt forms, with further coverage for pharmaceutical compositions, oral or suppository administration, multiple oral dosage forms, unit-dose amount ranges, kit formats, and additional pharmaceutical substances.
Conjugate compound structures selected from a group
A compound having a structure selected from the group consisting of a set of structures defined by substituent variables and structure families.
Pharmaceutically acceptable salts of the selected conjugate compounds
A compound having a structure selected from the group consisting of a set of structures, or a pharmaceutically acceptable salt thereof.
Pharmaceutical composition containing the compound or its salt
A pharmaceutical composition that includes the compound of the independent claim or a pharmaceutically acceptable salt of that compound.
Oral or suppository administration composition
A composition formulated for either oral administration or suppository administration.
Oral dosage form selected from listed oral dosage types
An orally administrable composition provided in one of several specified oral dosage forms selected from a detailed list of solid and liquid oral dosage types.
Per-unit-dose amount range for the compound
A composition in which the specified compound is present per unit dose at an amount between about 0.1 mg and about 2000 mg.
Kit providing individual doses containing a therapeutically effective amount
A kit that provides individual doses of a composition containing the compound at a therapeutically effective amount.
Additional pharmaceutical substances in the composition
A composition further including one or more specified additional pharmaceutical substances, optionally including stimulants, anti-depressants, and combinations and prodrugs thereof.
Specific pharmaceutically acceptable salt forms
The pharmaceutically acceptable salt is selected from a specified group of many salt forms or mixtures thereof.
The claim set centers on d-amphetamine-related conjugate structures selected from a group, optionally in pharmaceutically acceptable salt forms, and further defines pharmaceutical compositions for oral or suppository use, specified oral dosage forms, unit-dose amount ranges, kit formats with individual therapeutically effective doses, and enumerated salt types with optional additional pharmaceutical substances.
Stated Advantages
Lower or similar AUC/Cmax versus unconjugated d-amphetamine.
Longer Tmax versus unconjugated d-amphetamine.
Reduced plasma levels of released d-amphetamine after parenteral routes.
Unexpected and/or improved exposure behavior in rats based on Cmax, AUC, and Tmax comparisons with isonicotinoyl analogs.
Documented Applications
Pharmaceutical composition use for oral administration or suppository administration of the d-amphetamine conjugate compound.
Kit format use providing individual doses containing a composition comprising the compound at a therapeutically effective amount.
Abuse-potential related use described through pharmacokinetic and abuse-potential advantages of the d-amphetamine conjugates versus unconjugated d-amphetamine.
Pharmacokinetic evaluation in rats following oral, intravenous, and intranasal administration, with Cmax, AUC, and Tmax reporting for d-amphetamine nicotinoyl conjugates and comparisons to isonicotinoyl analogs.
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