JPWO2023089132A5 - - Google Patents

Claims (21)

1. A pharmaceutical formulation suitable for intramuscular injection and/or nebulized inhalation, comprising:
a. A salt of an optionally substituted dimethyltryptamine compound comprising a Bronsted acid having a pKa of about 3 to about 5 and a compound of formula IB;
(In the formula,
R ^1b is independently selected from —R ^4b , —OH, —OR ^4b , —O(CO)R ^4b , monohydrogen phosphate, —F, —Cl, —Br, and —I;
n is selected from 0, 1, 2, 3 or 4;
R ^2b is C( ^xbH ) ₃ ;
R ^3b is C( ^xbH ) ₃ ;
Each R ^4b is independently selected from C ₁ -C ₄ alkyl; and
Each ^xb H, ^yb H, and ^z H is independently selected from protium or deuterium.
b. a base agent;
c. water, and
d. optionally a buffering agent separate from said salt, wherein said formulation comprises:
having a pH of about 5 to about 6.5, a concentration of about 10 mg/ml or greater as the free base, and an osmolality of about 250 to about 350 mOsm/Kg; and
a dose of an optionally substituted dimethyltryptamine compound in a volume of 5 ml or less;
Pharmaceutical preparations. The formulation of claim 1, having a pH of about 5 to about 6. The salt of an optionally substituted dimethyltryptamine compound is prepared by reacting a compound of formula IB, where n is 1 and R ^1b is at the 4th or 5th position, and R ^1b -OH, -OMe, -OCD ₃ 3. The formulation of claim 1 or 2, comprising a phosphate group selected from -OAc, -O(CO)Me, and monohydrogen phosphate. The salt of an optionally substituted dimethyltryptamine compound may be prepared by reacting a compound of formula IB, where R ^2b is a CD ₃ and R ^3b is a CD ₃ 3. The formulation of claim 1 or 2, comprising: 3. The formulation of claim 1 or 2, wherein the salt of the optionally substituted dimethyltryptamine compound comprises a compound of formula IB, wherein each ^yb H is D. 3. The formulation of claim 1 or 2, wherein n is 0. n is 1 and R ^1b The formulation of claim 3, wherein is 5-methoxy or trideutero-5-methoxy. 3. The formulation of claim 1 or 2, wherein the optionally substituted dimethyltryptamine compound is selected from N,N-dimethyltryptamine, α,α-dideutero-N,N-dimethyltryptamine, N,N-di(trideuteromethyl)tryptamine, α,α-dideutero-N,N-di(trideuteromethyl)tryptamine, α,α,β,β-tetradeutero-N,N-dimethyltryptamine, and α,α,β,β-tetradeutero-N,N-di(trideuteromethyl)tryptamine. 3. The formulation of claim 1 or 2, wherein the acid is fumaric acid. 3. The formulation of claim 1 or 2, wherein the concentration of the optionally substituted dimethyltryptamine is from about 15 mg/mL to about 70 mg/mL (as free base equivalent). a buffering agent separate from the salt;
the buffer comprises acetate and acetic acid; or citrate and citric acid; or phosphate and phosphoric acid; or the buffer comprises acetate, citrate, or phosphate;
3. The formulation according to claim 1 or 2. 3. The formulation according to claim 1 or 2, wherein the base agent is sodium hydroxide or potassium hydroxide. 3. The formulation of claim 1 or 2, further comprising a tonicity agent and/or a pH adjusting agent. A kit suitable for preparing the formulation of claim 1, comprising: a salt of an optionally substituted dimethyltryptamine compound; optionally an isotonicity agent and/or a pH adjuster; a base agent; and optionally a buffer agent separate from the salt. 3. A method for preparing the pharmaceutical formulation of claim 1 or 2, comprising contacting a salt of an optionally substituted dimethyltryptamine compound, water, a base agent, and optionally a buffer other than the salt, and optionally a tonicity agent and/or a pH adjuster. 15. A formulation according to claim 1 or 2 or a kit according to claim 14 for use as a medicine or for use in combination with psychotherapy. 15. A formulation according to claim 1 or 2 or a kit according to claim 14 for use in a method for treating a psychiatric or neurological disorder in a patient. 18. The formulation for use or kit for use according to claim 17, wherein the psychiatric or neurological disorder is selected from the group consisting of: (i) obsessive-compulsive disorder, (ii) depressive disorder, (iii) anxiety disorder, (iv) substance abuse and gambling disorder, and (v) anorexia disorder. A lyophilized powder formulation comprising the formulation of claim 1 which has been lyophilized. A method for preparing a lyophilized powder formulation, comprising drying the formulation of claim 1 by lyophilization. 21. A method for preparing an aqueous formulation, comprising mixing the lyophilized powder formulation of claim 19 or the lyophilized powder formulation prepared by the method of claim 20 with water,
A method for preparing an aqueous formulation comprising a salt of an optionally substituted dimethyltryptamine compound, a base, water, and optionally a buffer other than the salt, the method comprising providing a formulation having a pH of about 5 to about 6.5, a concentration of about 10 mg/ml or more as a free base, and an osmolality of about 250 to about 350 mOsm/kg.