Psilocybin and O-acetylpsilocin, salts and solid state forms thereof
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Publication Number
US-11851452-B2
Publication Date
2023-12-26
Expiration Date
Abstract
Disclosed herein are salts and solid state forms of psilocybin, including psilocybin HCl, and salts and solid forms of O-acetylpsilocin, including O-acetylpsilocin fumarate. Also disclosed are methods for making the salts and solid forms and methods for administering the salts and solid forms. The salts and solid forms disclosed herein are useful for treating neurological disease and/or a psychiatric disorder in a subject.
Core Innovation
The invention relates to crystalline forms of psilocybin·HCl, including Form A, characterized by XRPD diffractograms measured with Cu Kα radiation and characteristic peaks at defined 2-Theta values. The crystalline form is further characterized by differential scanning calorimetry and/or thermogravimetric analysis, including a DSC endotherm at about 189.3° C. and TGA mass losses up to 130° C. and from 130° C. to 195° C.
The crystal forms are also characterized by unit cell parameters at 100 K, including a monoclinic crystal system and P21/n space group with defined lattice parameters, volume, and Z. In addition, a psilocybin·HCl co-crystal of psilocybin and hydrochloric acid is disclosed with an overall stoichiometry of two moles of psilocybin to one mole of hydrochloric acid, together with corresponding unit cell parameters at 100 K.
The disclosed crystalline forms are related to pharmaceutical compositions that include pharmaceutically acceptable excipients and to methods of treating neurological and/or psychiatric disorders in a human by administering the crystalline psilocybin·HCl in an amount equivalent to about 10 mg to about 50 mg of psilocybin. The treated conditions include depression, treatment resistant depression, major depressive disorder, suicidal ideation, bipolar disorder, schizophrenia, addiction/substance use disorder, anxiety, post-traumatic stress disorder, stroke, and traumatic brain injury, including combinations thereof.
Claims Coverage
The independent claims cover four main inventive aspects: XRPD-defined crystalline Form A of psilocybin·HCl, XRPD plus thermal-analysis-defined Form A, unit-cell-parameter-defined psilocybin·HCl crystalline form, and a psilocybin–hydrochloric acid co-crystal crystalline form with defined stoichiometry and unit-cell parameters. Across these claims, the core coverage is the specific crystalline form identity, with downstream coverage extending to pharmaceutical compositions and methods of treating neurological and psychiatric disorders.
Xrpd-defined crystalline form of psilocybin·hcl (Form A)
A crystalline form of psilocybin·HCl (Form A) characterized by XRPD diffractograms with characteristic peaks at defined 2-Theta values, measured with Cu Kα radiation.
Xrpd plus thermal-analysis-defined crystalline form of psilocybin·hcl (Form A)
A crystalline form of psilocybin·HCl (Form A) characterized by XRPD diffractograms with characteristic peaks, together with a DSC thermogram with an endotherm at about 189.3° C. and/or a TGA spectrum showing mass losses up to 130° C. and from 130° C. to 195° C.
Unit-cell-parameter-defined crystalline form of psilocybin·hcl (Form A)
A crystalline form of psilocybin·HCl characterized by unit cell parameters substantially equal to monoclinic, P21/n at 100 K, with specified lattice parameters and volume.
Psilocybin–hydrochloric acid co-crystal crystalline form with defined stoichiometry and unit-cell parameters
A crystalline form of psilocybin·HCl that is a co-crystal of psilocybin and hydrochloric acid with an overall stoichiometry of two moles of psilocybin to one mole of hydrochloric acid and corresponding unit cell parameters at 100 K.
Across the independent claims, the patent coverage is anchored in the definition of specific crystalline forms of psilocybin·HCl using XRPD peak sets, thermal-analysis features, monoclinic P21/n unit cell parameters at 100 K, and a psilocybin–hydrochloric acid co-crystal stoichiometry of 2:1. The claim family also covers pharmaceutical compositions with pharmaceutically acceptable excipients and methods of treating specified neurological and psychiatric disorders in a human.
Stated Advantages
Provides solid-state characterization of a crystalline form of psilocybin·HCl (Form A) using XRPD diffractogram characteristic peaks, optionally with DSC/TGA analytical features.
Defines a specific psilocybin·HCl co-crystal identity via overall stoichiometry and unit cell parameters at 100 K.
Attenuates activation of the serotonin receptor.
Documented Applications
Pharmaceutical composition comprising the crystalline form of psilocybin·HCl (Form A) together with a pharmaceutically acceptable excipient.
Method of treating neurological and/or psychiatric disorders in a human by administering the crystalline form of psilocybin·HCl in an amount equivalent to about 10 mg to about 50 mg of psilocybin, including depression, treatment resistant depression, major depressive disorder, suicidal ideation, bipolar disorder, schizophrenia, addiction/substance use disorder, anxiety, post-traumatic stress disorder, stroke, traumatic brain injury, or combinations.
Combination timing regimens using a serotonin receptor modulator with psilocybin mesylate Form A or other psilocybin solid/salt forms, including other psychedelic forms such as O-acetylpsilocin.
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