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IL312859A - Injectable and inhaled formulations - Google Patents

Injectable and inhaled formulations

Info

Publication number
IL312859A
IL312859A IL312859A IL31285924A IL312859A IL 312859 A IL312859 A IL 312859A IL 312859 A IL312859 A IL 312859A IL 31285924 A IL31285924 A IL 31285924A IL 312859 A IL312859 A IL 312859A
Authority
IL
Israel
Prior art keywords
formulation
dimethyltryptamine
salt
compound
optionally substituted
Prior art date
Application number
IL312859A
Other languages
Hebrew (he)
Inventor
Meghan Good
Carol Routledge
Benway Tiffanie
James Ellen
Joel Zelah
Claire Layzell Marie
Rands Peter
Original Assignee
Cybin Uk Ltd
Meghan Good
Carol Routledge
Benway Tiffanie
James Ellen
Joel Zelah
Claire Layzell Marie
Rands Peter
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from TW110143066A external-priority patent/TWI891942B/en
Priority claimed from GBGB2119021.0A external-priority patent/GB202119021D0/en
Application filed by Cybin Uk Ltd, Meghan Good, Carol Routledge, Benway Tiffanie, James Ellen, Joel Zelah, Claire Layzell Marie, Rands Peter filed Critical Cybin Uk Ltd
Publication of IL312859A publication Critical patent/IL312859A/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Addiction (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dispersion Chemistry (AREA)
  • Otolaryngology (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Claims (54)

1. PCT/EP2022/0824
2. CLAIMS 1. A pharmaceutical formulation suitable for intramuscular injection and/or nebuliser inhalation, comprising a salt of an optionally substituted dimethyltryptamine compound, a base agent, water and optionally a buffer which is separate to the salt; wherein the formulation has a pH of from about 5 to about 6.5, a concentration of about 10 mg/ml as freebase or greater, and an osmolality of from about 250 to about 350 mOsm/Kg; and wherein the formulation comprises a dose of the optionally substituted dimethyltryptamine compound within a volume of ml or less. 2. The formulation of claim 1, wherein the formulation has a pH of from about 5 to about 6.
3. The formulation of claim 1 or claim 2, wherein the formulation is suitable for intramuscular injection.
4. The formulation of any preceding claim, wherein the formulation comprises an effective dose of an optionally substituted dimethyltryptamine compound for use in psychedelic assisted therapy within a volume of 5 ml or less.
5. The formulation of any preceding claim, wherein the volume is 3 ml or less.
6. The formulation of any preceding claim, wherein the volume is 2.5 ml or less.
7. The formulation of any preceding claim, wherein the formulation has an osmolality of from about 275 to about 325 mOsm/Kg.
8. The formulation of any one of claims 1 to 7, wherein the salt of the optionally substituted dimethyltryptamine compound comprises a Brønsted acid having a pKa of from about 3 to about 5 and a compound of Formula IB: PCT/EP2022/0824 Formula IB wherein: R1b is independently selected from –R4b, -OH, -OR4b, -O(CO)R4b, monohydrogen phosphate, -F, -Cl, -Br and –I; n is selected from 0, 1, 2, 3 or 4; R2b is C(xbH)3; R3b is C(xbH)3; each R4b is independently selected from C1-C4alkyl; and each xbH, ybH and zH is independently selected from protium or deuterium.
9. The formulation of claim 8, wherein the salt of the optionally substituted dimethyltryptamine compound comprises a compound of Formula IB, wherein n is 0; or n is 1 and R1b is in the 4- or 5-position.
10. The formulation of claim 8 or claim 9, wherein the salt of the optionally substituted dimethyltryptamine compound comprises a compound of Formula IB, wherein each R1b is independently selected from -OH, -OMe, -OCD3, -OAc, -O(CO)Me, and monohydrogen phosphate.
11. The formulation of any one of claims 8 to 10, wherein the salt of the optionally substituted dimethyltryptamine compound comprises a compound of Formula IB, wherein R2b is CD3 and R3b is CD3.
12. The formulation of any one of claims 8 to 11, wherein the salt of the optionally substituted dimethyltryptamine compound comprises a compound of Formula IB, wherein each ybH is D.
13. The formulation of any one of claims 8, 9, 11 or 12 wherein n is 0. PCT/EP2022/0824
14. The formulation of any one of claims 8 to 12 wherein n is 1 and R1b is 4-acetoxy.
15. The formulation of any one of claims 8 to 12 wherein n is 1 and R1b is 5-methoxy or trideutero-5-methoxy.
16. The formulation of any one of claims 1 to 8, wherein the optionally substituted dimethyltryptamine compound is N,N-dimethyltryptamine.
17. The formulation of any one of claims 1 to 8, wherein the optionally substituted dimethyltryptamine compound is α,α-dideutero-N,N-dimethyltryptamine.
18. The formulation of any one of claims 1 to 17, wherein the salt of the optionally substituted dimethyltryptamine compound is of an optionally substituted dimethyltryptamine compound and an acid selected from the group consisting of fumaric acid, tartaric acid, citric acid, acetic acid, lactic acid and gluconic acid.
19. The formulation of claim 18, wherein the acid is fumaric acid.
20. The formulation of any one of claims 1 to 19 comprising a drug substance which comprises the salt of the optionally substituted dimethyltryptamine compound at a purity of greater than or equal to 99% when measured by HPLC.
21. The formulation of any one of claims 1 to 20, wherein the concentration of the optionally substituted dimethyltryptamine is from about 10 mg/mL to about 1mg/mL (as the freebase equivalent).
22. The formulation of any one of claims 1 to 20, wherein the concentration of the optionally substituted dimethyltryptamine is from about 15 mg/mL to about mg/mL (as the freebase equivalent).
23. The formulation of any one of claims 1 to 20, wherein the concentration of the optionally substituted dimethyltryptamine compound is from about 20 mg/mL to about 40 mg/mL (as the freebase equivalent). PCT/EP2022/0824
24. The formulation of any one of claims 1 to 20, wherein the concentration of the optionally substituted dimethyltryptamine compound is about 25 mg/mL (as the freebase equivalent).
25. The formulation of any preceding claim, wherein the formulation comprises a buffer which is separate to the salt.
26. The formulation of claim 25, wherein the buffer comprises an acetate salt and acetic acid; or a citrate salt and citric acid; or a phosphate salt and phosphoric acid; or the buffer comprises an acetate salt, a citrate salt, or a phosphate salt.
27. The formulation of any preceding claim, wherein the base agent is sodium hydroxide or potassium hydroxide.
28. The formulation of any one of claims 1 to 27, wherein the formulation further comprises a tonicity agent and/or a pH adjuster.
29. The formulation of any preceding claim, wherein the formulation consists essentially of the salt of the optionally substituted dimethyltryptamine compound, water, and the base agent, and optionally one or more agents selected from a pH adjuster, a tonicity agent, a buffer, a co-solvent, a preservative, and an antioxidant.
30. The formulation of any preceding claim, wherein the formulation consists essentially of the salt of the optionally substituted dimethyltryptamine compound, water, the base agent and optionally a buffer and/or a tonicity agent and/or a pH adjuster.
31. The formulation of any preceding claim, wherein the formulation consists of the salt of the optionally substituted dimethyltryptamine compound, water, the base agent and optionally a buffer and/or a tonicity agent and/or pH adjuster.
32. The formulation of any one of claims 28 to 31, wherein the tonicity agent is sodium chloride or dextrose. 35 PCT/EP2022/0824
33. The formulation of any one of claims 1 to 32, having an oxygen content of less than 5 ppm, preferably less than 2 ppm.
34. The formulation of any one of claims 1 to 33, stored in a container having a volume of 5 ml or less.
35. The formulation of any one of claims 1 to 33, stored in a container having a volume of 2 ml or less.
36. The formulation of any one of claims 1 to 35, comprising a salt of an optionally substituted dimethyltryptamine compound, a base agent, water, a buffer which is separate to the salt, and a tonicity agent or pH adjuster
37. The formulation of claim 36, comprising a salt of an optionally substituted dimethyltryptamine compound; a base agent selected from potassium hydroxide and sodium hydroxide; water; a buffer which is a citrate salt; and a tonicity agent or pH adjuster which is an acid.
38. A kit suitable for preparing a formulation of any one of claims 1 to 37, said kit comprising a salt of an optionally substituted dimethyltryptamine compound; optionally a tonicity agent and/or a pH adjuster; a base agent and optionally a buffer which is separate to the salt.
39. A method of preparing a pharmaceutical formulation as defined in any one of claims 1 to 37, comprising contacting the salt of the optionally substituted dimethyltryptamine compound, water, a base agent and optionally a buffer which is separate to the salt, and optionally a tonicity agent and/or pH adjuster.
40. The method of claim 39 wherein an aqueous solution of the buffer is contacted with the salt of the optionally substituted dimethyltryptamine compound, wherein the aqueous solution has a pH as defined in claim 1.
41. The method of claim 39 or 40, wherein the method comprises contacting the optionally substituted dimethyltryptamine compound with water and optionally a buffer and/or tonicity agent and/or pH adjuster. 35 PCT/EP2022/0824
42. The method of any one of claims 39 to 41, further comprising adjusting the pH of the formulation.
43. The method of claim 42 wherein the pH is adjusted with a base agent which is sodium hydroxide or potassium hydroxide.
44. The method of any one of claims 39 to 43 further comprising sparging the formulation with an inert gas.
45. A formulation as defined in any one of claims 1 to 37 or the kit of claim 38 for use as a medicament, or in combination with psychotherapy.
46. A formulation as defined in any one of claims 1 to 37 or the kit of claim 38 for use in a method of treating a psychiatric or neurological disorder in a patient.
47. The formulation for the use, or kit for use, of claim 46 wherein the psychiatric or neurological disorder is selected from the group consisting of (i) an obsessive compulsive disorder, (ii) a depressive disorder, (iii) an anxiety disorder, (iv) substance abuse and gambling disorders, and (v) an avolition disorder.
48. A method of treating a psychiatric or neurological disorder comprising administering to a patient in need thereof a formulation as defined in any one of claims 1 to 37.
49. The method of claim 48, wherein the psychiatric or neurological disorder is as defined in claim 47.
50. The method of claim 48, wherein the formulation as defined in any one of claims to 37 is administered in combination with psychotherapy.
51. A lyophilised powder formulation comprising the formulation according to any one of claims 1 to 37 which has been lyophilised.
52. A method of preparing a lyophilised powder formulation comprising drying the formulation according to any one of claims 1 to 37 by lyophilisation. PCT/EP2022/0824
53. A method of preparing an aqueous formulation comprising mixing the lyophilised powder formulation as defined in claim 51 or as prepared by the method of claim into water to provide a formulation comprising the salt of an optionally substituted dimethyltryptamine compound, the base agent, water, and optionally the buffer which is separate to the salt to provide a formulation having a pH of from about 5 to about 6.5, a concentration of about 10 mg/ml as freebase or greater, and an osmolality of from about 250 to about 350 mOsm/Kg.
54. The method of claim 53, wherein the method provides a formulation having a pH of from about 5 to about 6.
IL312859A 2021-11-18 2022-11-18 Injectable and inhaled formulations IL312859A (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
TW110143066A TWI891942B (en) 2020-12-01 2021-11-18 Deuterated compounds
PCT/EP2021/082227 WO2022117359A1 (en) 2020-12-01 2021-11-18 Deuterated or partially deuterated n,n-dimethyltryptamine compounds
GBGB2119021.0A GB202119021D0 (en) 2021-11-18 2021-12-24 Injectable and inhalable formulations
US202217574424A 2022-01-12 2022-01-12
EP2022055324 2022-03-02
PCT/EP2022/082486 WO2023089132A1 (en) 2021-11-18 2022-11-18 Injectable and inhalable formulations

Publications (1)

Publication Number Publication Date
IL312859A true IL312859A (en) 2024-07-01

Family

ID=84440034

Family Applications (1)

Application Number Title Priority Date Filing Date
IL312859A IL312859A (en) 2021-11-18 2022-11-18 Injectable and inhaled formulations

Country Status (11)

Country Link
EP (1) EP4433049A1 (en)
JP (1) JP2024540527A (en)
KR (1) KR20240110836A (en)
AU (1) AU2022393234A1 (en)
CA (1) CA3238583A1 (en)
CL (1) CL2024001452A1 (en)
CO (1) CO2024007518A2 (en)
IL (1) IL312859A (en)
MX (1) MX2024005955A (en)
WO (1) WO2023089132A1 (en)
ZA (1) ZA202403906B (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PH12022553135A1 (en) 2020-05-19 2024-03-04 Cybin Irl Ltd Deuterated tryptamine derivatives and methods of use

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2666149A1 (en) * 2006-10-19 2008-04-24 Auspex Pharmaceuticals, Inc. Substituted indoles
US20220071958A1 (en) * 2019-02-22 2022-03-10 GH Research Ireland Limited 5-methoxy-n,n-dimethyltryptamine (5-meo-dmt) for treating depression
GB201907871D0 (en) 2019-06-03 2019-07-17 Small Pharma Ltd Therapeutic compositions
PT3873883T (en) 2019-11-07 2023-03-24 Small Pharma Ltd SYNTHESIS METHOD
EP3902541B1 (en) 2020-06-02 2022-09-14 Small Pharma Ltd Therapeutic compositions comprising deuterated or partially deuterated n,n-dimethyltryptamine compounds
AU2021334933B2 (en) * 2020-08-28 2023-01-19 Cybin Uk Ltd Injectable formulation
IL303288A (en) * 2020-12-01 2023-07-01 Small Pharma Ltd N,N-Dimethyltryptamine compounds partially or fully deuterated

Also Published As

Publication number Publication date
ZA202403906B (en) 2025-08-27
KR20240110836A (en) 2024-07-16
EP4433049A1 (en) 2024-09-25
WO2023089132A1 (en) 2023-05-25
AU2022393234A1 (en) 2024-06-06
CL2024001452A1 (en) 2024-09-27
MX2024005955A (en) 2024-06-11
CA3238583A1 (en) 2023-05-25
JP2024540527A (en) 2024-10-31
CO2024007518A2 (en) 2024-07-29

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