JPWO2022069690A5

JPWO2022069690A5 -

Info

Publication number: JPWO2022069690A5
Application number: JP2023519831A
Authority: JP
Publication date: 2024-07-29

Claims

A pharmaceutical composition for use in medicine comprising a hallucinogen , wherein the pharmaceutical composition is administered to a patient in need thereof by inhalation as an aerosol comprising the hallucinogen in a carrier .

2. The pharmaceutical composition for use according to claim 1, wherein the carrier is air, oxygen, or a mixture of helium and oxygen.

2. The pharmaceutical composition for use according to claim 1, wherein the hallucinogen comprises one or more of dimethyltryptamine (DMT), 5-methoxy-dimethyltryptamine (5-MeO-DMT) , 5 -hydroxy-dimethyltryptamine ( 5 -OH-DMT) , psilocybin, or psilocin .

A pharmaceutical composition for use according to claim 1, comprising:
The hallucinogen is a compound of formula (I):
In the formula,
X _１1 and X _２2 are independently selected from hydrogen, deuterium, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl;
Y _１1 and Y _２2 are independently selected from hydrogen and deuterium,
R _２2 are independently selected from hydrogen, unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl;
R _４4 and R _５5 is independently selected from hydrogen, hydroxyl, and unsubstituted or substituted alkoxy;
R _６6 and R _７7 is selected from hydrogen and halogen;
R _９9 and R _１０10 is independently selected from unsubstituted or substituted alkyl, unsubstituted or substituted aryl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted aryl, and unsubstituted or substituted heteroaryl;
or an optically pure stereoisomer, a pharma- ceutically acceptable salt, solvate, or prodrug thereof.

X _１1 and X _２2 The pharmaceutical composition for use according to claim 4, wherein is deuterium.

2. The pharmaceutical composition for use according to claim 1, wherein the hallucinogen is delivered to the central nervous system of the patient by pulmonary absorption.

2. The pharmaceutical composition for use according to claim 1, wherein the carrier is a mixture of helium and oxygen.

(i) the mixture of helium and oxygen is heated to about 50° C. to about 60° C.;
(ii) the helium is present in the mixture of helium and oxygen at about 50%, 60%, 70%, 80%, or 90%, and the oxygen is present in the mixture of helium and oxygen at about 50%, 40%, 30%, 20%, or 10%, or
Both (i) and (ii),
A pharmaceutical composition for use according to claim 7.

2. The pharmaceutical composition for use according to claim 1, further comprising administering a pre-treatment inhalation regimen prior to administration of the aerosol comprising the hallucinogen and the carrier , the pre-treatment inhalation regimen comprising administering to the patient by inhalation a mixture of helium and oxygen heated to about 90°C to about 120°C .

2. The pharmaceutical composition for use according to claim 1, wherein the hallucinogen is delivered to the central nervous system of the patient and provides at least a 25% improvement in bioavailability of the drug compared to oral delivery, at least a 25% increase in _Cmax compared to oral delivery, at least a 50% decrease in _Tmax compared to oral delivery, or a combination thereof.

2. The pharmaceutical composition for use according to claim 1, used to treat a central nervous system (CNS) disorder or a psychological disorder in a patient.

The CNS disorder is selected from the group consisting of melancholic depression, atypical depression, dysthymia, anxiety disorder, obsessive-compulsive disorder, addictive disorder, alcohol use disorder, opioid use disorder, amphetamine use disorder, nicotine use disorder, cocaine use disorder, post-traumatic stress disorder (PTSD), major depressive disorder (MDD), treatment-resistant depression (TRD), suicidal ideation or suicide attempt, bipolar I disorder, bipolar II disorder, cyclothymic disorder, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), social anxiety disorder, Alzheimer's disease, and group 12. The pharmaceutical composition for use according to claim 11, wherein the therapeutic agent is at least one member selected from the group consisting of: episodic headache, migraine, attention deficit hyperactivity disorder (ADHD), pain and neuropathic pain, anorexia, childhood onset hyperactivity disorder, dementia, mild neurocognitive disorder, sexual dysfunction, gambling disorder, eating disorders, anorexia nervosa, bulimia nervosa, binge eating disorder, paraphilia, pedophilic disorder, conduct disorder, voyeuristic disorder, fetishistic disorder, sexual masochistic disorder, sexual sadistic disorder, and cross-dressing disorder.

The pharmaceutical composition for use according to any one of claims 1 to 12 , wherein the aerosol is a mist.

14. The pharmaceutical composition for use according to claim 13 , wherein the aerosol is prepared by atomization of the pharmaceutical composition .

The pharmaceutical composition for use according to claim 14 , wherein the nebulization is performed using a component selected from the group consisting of a jet nebulizer, an ultrasonic nebulizer, an exhalation actuated nebulizer, and a vibrating mesh nebulizer.

15. The pharmaceutical composition for use according to claim 14 , wherein said nebulization is carried out using nitrous oxide as a driving gas for entrainment of said nebulized hallucinogen.

The pharmaceutical composition for use according to claim 16 , wherein said nitrous oxide is present in a concentration of 15-25% by volume of the gas used.

The pharmaceutical composition for use according to any one of claims 1 to 12, wherein the pharmaceutical composition is administered to a patient as a dry powder comprising said hallucinogen via a dry powder inhaler.

20. The pharmaceutical composition for use according to claim 18 , wherein said dry powder comprises a particulate carrier having said hallucinogen on its surface.

20. The pharmaceutical composition for use according to claim 19 , wherein the hallucinogen is releasably absorbed onto the surface of the particulate carrier such that the hallucinogen is released from the particulate carrier within the patient upon inhalation by the patient.

20. The pharmaceutical composition for use according to claim 18 , wherein said dry powder is formed from said hallucinogen in solid particulate form.