Phenethylamine compounds salts, polymorphic forms and methods of use thereof
Inventors
Assignees
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Publication Number
US-11958821-B2
Publication Date
2024-04-16
Expiration Date
Abstract
Disclosed herein are salts and solid forms of MDMA, (R)-MDMA, (S)-MDMA, MDE, S-MDE, R-MDE, MDAI, MBDB, S-MBDB, R-MBDB, MEAI, and 5,6-Dimethoxy-2-aminoindane, including salts, solid forms of the compound and salts thereof, as well as polymorphs of solid forms. The solid forms disclosed herein may have improved properties, such as improved physical, chemical, and/or pharmacokinetic properties. Also disclosed are methods for making the salts and solid forms and methods for administering the same. The disclosed salt and solid forms of MDMA, (R)-MDMA, (S)-MDMA, MDE, S-MDE, R-MDE, MDAI, MBDB, S-MBDB, R-MBDB, MEAI, and 5,6-Dimethoxy-2-aminoindane may be useful for treating neurological disease and/or a psychiatric disorder in a subject.
Core Innovation
The disclosure describes crystalline solid forms of 3,4-methylenedioxy-methamphetamine (MDMA) hemifumarate salt, MDMA succinate, MDMA tosylate, MDMA fumarate Form 2, MDMA maleate Form 2, MDMA tartrate Form 2, and MDMA hydrochloride, along with additional salts. The solid forms are characterized by X-ray powder diffraction (XRPD) using Cu Kα1 radiation, with specific 2θ peak positions, tolerances, and table-referenced peak sets used as identity criteria.
The disclosure further includes polymorphic solid forms of MBDB and related salts, including MBDB tosylate, MBDB HCl Form A and Form B, MBDB maleate Forms 2–3, and related compounds such as MEAI and 5,6-dimethoxy-2-aminoindane HCl. For several solid forms, the document also references similarity to XRPD, nuclear magnetic resonance, TGA, and DSC profiles, and in some embodiments describes crystalline versus amorphous solids, solvate or hydrate forms, and stoichiometric acid to free base ratios.
The document also describes co-therapy and administration contexts in which a serotonin receptor modulator is administered together with or relative to a psychedelic such as 5-methoxy-2-aminoindane hydrochloride or MDMA. The serotonin receptor modulators explicitly include ketanserin, ritanserin, pimavanserin, nelotanserin, pruvanserin, flibanserin, olanzapine, quetiapine, risperidone, eplivanserin, and volinanserin, and the timing may be pretreatment or post-treatment in the same composition or separate compositions.
Claims Coverage
The independent claims cover specific solid forms of MDMA hemifumarate salt defined by XRPD fingerprints using Cu Kα1 radiation, with two or three selected 2θ signals within stated tolerances. Across the provided claim summaries, a total of 4 independent claim feature sets are identified, and the claims also extend to pharmaceutical compositions and methods of treating post-traumatic stress disorder (PTSD) by administration.
XRPD-characterized MDMA hemifumarate salt with 17.3°/18.6°/21.9° signals
A solid form of 3,4-methylenedioxy-methamphetamine (MDMA) hemifumarate salt characterized by two or three XRPD signals selected from 17.3° 2θ, 18.6° 2θ, and 21.9° 2θ (±0.2° 2θ; ±0.1° 2θ; or ±0.0° 2θ; Cu Kα1 radiation).
XRPD-characterized solid form of MDMA hemifumarate salt
A solid form of 3,4-methylenedioxy-methamphetamine (MDMA) hemifumarate salt characterized by two or three XRPD signals selected from 10.9° 2θ, 13.1° 2θ, and 16.7° 2θ (±0.2° 2θ; ±0.1° 2θ; or ±0.0° 2θ; Cu Kα1 radiation).
XRPD-characterized solid form of MDMA hemifumarate salt
A solid form of 3,4-methylenedioxy-methamphetamine (MDMA) hemifumarate salt characterized by two or three XRPD signals selected from 16.7° 2θ, 18.6° 2θ, and 21.8° 2θ (±0.2° 2θ; ±0.1° 2θ; or ±0.0° 2θ; Cu Kα1 radiation).
XRPD-characterized solid form of MDMA hemifumarate salt
A solid form of 3,4-methylenedioxy-methamphetamine (MDMA) hemifumarate salt characterized by two or three XRPD signals selected from 10.9° 2θ, 18.6° 2θ, and 21.9° 2θ (±0.2° 2θ; ±0.1° 2θ; or ±0.0° 2θ; Cu Kα1 radiation).
Overall, the claim coverage is directed to MDMA hemifumarate solid forms defined by XRPD fingerprints comprising two or three specified 2θ signals within stated tolerances using Cu Kα1 radiation. The dependent claim summaries extend these definitions to pharmaceutical compositions and to methods of treating PTSD by administering the specified solid form.
Stated Advantages
The serotonin receptor modulator attenuates serotonin receptor activation.
Improved physical/chemical/pharmacokinetic properties versus amorphous or prior forms.
Provides XRPD-based identity criteria for crystalline solid forms of MDMA salts, using specified 2θ peak sets and tolerances.
Supports identification through tabulated XRPD signal lists and similarity statements referencing figure-based XRPD, nuclear magnetic resonance, and thermal profile comparisons.
Allows alternative identification approaches via substantially similar XRPD patterns to referenced figures and via table-based XRPD signal sets.
Enables formulation as a pharmaceutical composition including a pharmaceutically acceptable excipient.
Supports treating post-traumatic stress disorder (PTSD) by administering the defined solid form to a subject in need.
Post-treatment is intended to attenuate serotonin receptor activation by the psychedelic.
Documented Applications
Method of treating post-traumatic stress disorder (PTSD) in a subject by administering a defined solid form of MDMA hemifumarate salt.
Co-therapy context involving administration of serotonin receptor modulators with the psychedelic 5-methoxy-2-aminoindane hydrochloride.
Method-of-treating contexts including depression, post-traumatic stress disorder (PTSD), fibromyalgia, and chronic widespread pain.
Characterization and identification of crystalline solid forms of MDMA salts using XRPD peak criteria.
Pharmaceutical composition comprising the solid form of MDMA hemifumarate salt together with a pharmaceutically acceptable excipient.
Combination therapy using a serotonin receptor modulator together with a psychedelic, using specified pretreatment and post-treatment timing windows and optionally modified-release schedules.
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