Solid forms of tabernanthalog monofumarate salt for treating neurological disorders and/or psychiatric disorders
Inventors
Assignees
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Publication Number
US-11905295-B2
Publication Date
2024-02-20
Expiration Date
Abstract
Disclosed herein are salt and solid forms of tabernanthalog. Disclosed solid forms may be a polymorph of tabernanthalog fumarate, and/or may have improved properties, such as improved physical, chemical and/or pharmacokinetic properties. Disclosed salts include pharmaceutically acceptable salts of tabernanthalog. Disclosed solid forms include free base and salt forms of tabernanthalog, including amorphous and crystalline forms of tabernanthalog, such as tabernanthalog free base or a salt thereof. Also disclosed are methods for making the salts and solid forms and methods for administering the same. The salt and solid forms of tabernanthalog and salts thereof are useful for treating neurological disease and/or a psychiatric disorder in a subject.
Core Innovation
The invention relates to crystalline polymorph and solid-form patterns of tabernanthalog monofumarate salt defined by Cu Kα1 XRPD peak positions at specified 2θ angles, together with allowable tolerances and counts of XRPD signals. The disclosed solid forms include crystalline polymorphic Pattern #6a, and the XRPD-based definitions are used to distinguish the respective solid forms.
The disclosure also includes tabernanthalog sorbate salt and tabernanthalog hydrate forms, with characterization by X-ray diffraction and thermal behavior. The work includes SCXRD, XRPD, DSC, DVS, TGA, NMR, 19F NMR, and LC-MS as characterization context, together with mixture behavior, hydrogen-bonding/void-space analysis, and conversion behavior under humidity. An HFIPA-related solvate is reported as an additional crystal form, and amorphous forms are referenced with glass transition temperature values.
The disclosure further includes pharmaceutical compositions comprising the tabernanthalog salt or solid form and pharmaceutically acceptable excipients, together with administration route embodiments. Therapeutic use is centered on modulation of the 5-HT2A receptor by the tabernanthalog salts or solid forms, including increasing neuronal plasticity and treating neuropsychiatric or brain disorders.
Claims Coverage
The claim coverage centers on crystalline solid forms of tabernanthalog monofumarate salt defined by crystalline polymorphic Pattern #6a using Cu Kα1 XRPD signal sets at specified 2θ angles. The independent claim features are distinguished by the number of XRPD signals and the allowed angle sets, and the coverage also extends to a pharmaceutical composition and a therapeutic method for modulating 5-HT2A receptor activity.
Crystalline polymorphic pattern #6a defined by two XRPD signals with Cu Kα1
A solid form of tabernanthalog monofumarate salt in which the solid form is crystalline polymorphic Pattern #6a characterized by an X-ray powder diffraction diffractogram comprising two signals at angles (2θ) selected from specified groups, wherein the X-ray powder diffraction is carried out using Cu Kα1 radiation.
Crystalline polymorphic pattern #6a defined by three XRPD signals with Cu Kα1
A solid form of tabernanthalog monofumarate salt in which the solid form is crystalline polymorphic Pattern #6a characterized by an X-ray powder diffraction diffractogram comprising three signals at angles (2θ) selected from specified groups, wherein the X-ray powder diffraction is carried out using Cu Kα1 radiation.
Crystalline polymorphic pattern #6a defined by alternative two-signal XRPD sets with Cu Kα1
A solid form of tabernanthalog monofumarate salt in which the solid form is crystalline polymorphic Pattern #6a characterized by an X-ray powder diffraction diffractogram comprising two signals at angles (2θ) selected from specified groups, wherein the X-ray powder diffraction diffractogram signals are present when the X-ray powder diffraction is carried out using Cu Kα1 radiation.
Pharmaceutical composition including the Pattern #6a solid form
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and the solid form described in the claims.
Method for modulating 5-HT2A receptor activity
A method to modulate 5-hydroxytryptamine 2A (5-HT2A) receptor activity in a subject by administering a therapeutically effective amount of the solid form having crystalline polymorphic Pattern #6a.
Overall, the claim coverage is grounded in tabernanthalog monofumarate crystalline polymorphic Pattern #6a defined by XRPD diffractograms using Cu Kα1 radiation with specified 2θ signal selections. The remaining claim coverage extends the same solid form into pharmaceutical compositions and therapeutic methods for modulating 5-HT2A receptor activity.
Stated Advantages
Improved physical/chemical/pharmacokinetic properties.
The document asserts that Form A is novel and stable.
XRPD-based definitions support characterization and identification of the disclosed crystalline solid forms.
Documented Applications
Treating neurological and/or psychiatric disorders in a subject by administering a therapeutically effective amount of the solid form to modulate 5-HT2A receptor activity.
Therapeutic use examples stated in the description include depression, addiction, anxiety, post-traumatic stress disorder, treatment resistant depression, suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, substance use disorder, stroke, and traumatic brain injury.
A pharmaceutical composition including a pharmaceutically acceptable excipient and the disclosed tabernanthalog solid form.
A method to modulate 5-HT2A receptor activity in a subject by administering a therapeutically effective amount of the disclosed solid form.
Modulating the 5-HT2A receptor using tabernanthalog salt or solid forms to increase neuronal plasticity.
Treating neuropsychiatric or brain disorders using the tabernanthalog salt or solid forms.
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