Ultrapure tetrahydrocannabinol-11-oic acids
View Patent ↗This application is in the field of medicinal chemistry and relates to ultrapure ajulemic acid, its synthesis, pharmaceutical compositions and methods of use thereof for the treatment and/or prevention of inflammation, pain, and fibrotic diseases including scleroderma, systemic sclerosis, scleroderma-like disorders, sine scleroderma, liver cirrhosis, interstitial pulmonary fibrosis, idiopathic pulmonary fibrosis, Dupuytren's contracture, keloids, chronic kidney disease, chronic graft rejection, and other scarring-wound healing abnormalities, post-operative adhesions, and reactive fibrosis.
1. A method of treating a human subject having a fibrotic disease the method comprising administering once daily, twice daily, or three times daily to the subject an effective amount of a pharmaceutical composition comprising a preparation of ajulemic acid, wherein said preparation of ajulemic acid comprises at least 98% (w/w) ajulemic acid or a pharmaceutically acceptable salt thereof, wherein no significant antinociception is observed in a hot plate test of mice following oral administration to the mice of 10 mg/kg of said preparation of ajulemic acid.
2. The method of claim 1 , wherein said fibrotic disease is selected from the group consisting of scleroderma, systemic sclerosis, sine scleroderma, or a scleroderma-like disorder, liver cirrhosis, interstitial pulmonary fibrosis, idiopathic pulmonary fibrosis, Dupuytren's contracture, keloids, cystic fibrosis, chronic kidney disease, chronic graft rejection, scarring or wound healing abnormalities, post-operative adhesions, reactive fibrosis, dermal fibrosis, lung fibrosis, liver fibrosis, kidney fibrosis, and heart fibrosis.
3. The method of claim 1 , wherein said fibrotic disease is any organ fibrosis.
4. The method of claim 2 , wherein said fibrotic disease is dermal fibrosis.
5. The method of claim 2 , wherein said fibrotic disease is scleroderma.
6. The method of claim 2 , wherein the fibrotic disease is cystic fibrosis.
7. The method of claim 2 , wherein said fibrotic disease is idiopathic pulmonary fibrosis.
8. The method of claim 1 , wherein said pharmaceutical composition is administered orally, intravenously, topically, interstitially, by inhalation, via an implant, via a patch, or by ophthalmic administration.
9. The method of claim 1 , wherein said pharmaceutical composition is administered in combination with one or more compounds.
10. The method of claim 1 , wherein said pharmaceutical composition a unit dosage formulation comprising about 0.15 mg to about 40 mg of said ajulemic acid, or a pharmaceutically acceptable salt thereof, and wherein said unit dosage formulation is administered once daily.
11. The method of claim 1 , wherein said pharmaceutical composition is a unit dosage formulation comprising about 0.15 mg to about 40 mg of said ajulemic acid, or a pharmaceutically acceptable salt thereof, and wherein said unit dosage formulation is administered three times daily.
12. The method of claim 1 , wherein said preparation of ajulemic acid has less than about 0.1% (w/w) of 11-hydroxy-(6aR,10aR)-3-(1′,1′-dimethylheptyl)-Δ8-tetrahydrocannabinol (HU-210).
13. The method of claim 1 , wherein said preparation of ajulemic acid comprises at least 99% (w/w) ajulemic acid.
14. The method of claim 1 , wherein said unit dosage formulation is administered once daily.
15. The method of claim 1 , wherein said unit dosage formulation is administered twice daily.
16. The method of claim 1 , wherein said unit dosage formulation is administered three times daily.
17. The method of claim 8 , wherein said pharmaceutical composition is administered orally.
18. The method of claim 1 , wherein said pharmaceutical composition is a unit dosage formulation comprising about 0.15 mg to about 40 mg of said ajulemic acid, or a pharmaceutically acceptable salt thereof, and wherein said unit dosage formulation is administered twice daily.
19. The method of claim 1 , wherein the pharmaceutical composition is formulated for sustained release.