Crystalline forms of solvates of tryptophan derivatives, compositions comprising them and uses thereof
The invention provides crystalline forms of solvates of tryptophan derivatives of compound (1), compositions comprising them, processes for their preparations and methods of use thereof.
1 . A crystalline form of a solvate salt of compound (I), wherein said solvate is a C 3 -C 4 alcohol thereof, wherein said salt is an alkali salt, wherein said alkali salt is selected from sodium and potassium.
2 . A crystalline form according to claim 1 , wherein said solvate is selected from 1-propanol, 2-propanol, 1-butanol, iso-butanol and any combinations thereof.
3 . A crystalline form according to claim 1 , wherein said solvate salt compound (1), is a compound of formula (I):
Wherein X + is an alkali cation; and R is a C 3 -C 4 alkyl.
4 . A crystalline form according to claim 3 , wherein X+ is sodium (Na+) or potassium (K+) cation.
5 . A crystalline form according to claim 1 wherein said solvate salt compound (1) is a solvated sodium salt selected from:
6 . A crystalline form according to claim 1 wherein said solvate salt compound (1) is a solvated K salt selected from:
7 . A crystalline form according to claim 1 , wherein said crystalline form is selected from a sodium 2-propanol solvate of compound (1) having crystalline form A, a sodium 1-butanol solvate of compound (1) having crystalline form B, or a sodium 1-propanol solvate of compound (1) having crystalline form C.
8 . A crystalline form according to claim 1 having purity of at least 99.7%.
9 . A crystalline form according to claim 1 having water solubility of 2.3 g/ml.
10 . A pharmaceutical composition comprising at least one crystalline form or prepared from at least one crystalline form according to claim 1 .
11 . A pharmaceutical composition according to claim 10 , wherein said composition is suitable for ocular administration, oral administration, nasal administration, or any combination thereof.
12 . A method of treating an amyloid-associated disease in a subject suffering therefrom, said method comprising administering to said subject a pharmaceutical composition comprising at least one crystalline form or prepared from at least one crystalline form of a solvate salt compound (1), wherein said solvate is a C 3 -C 4 alcohol thereof,
13 . A method of treating an amyloid associated disease according to claim 12 , wherein said amyloid-associated disease is selected from type II diabetes mellitus, Alzheimer's disease (AD), early onset Alzheimer's disease, late onset Alzheimer's disease, Alzheimer's dementia, Parkinson's disease, SAA amyloidosis, hereditary Icelandic syndrome, multiple myeloma, medullary carcinoma, aortic medical amyloid, insulin injection amyloidosis, prion-systematic amyloidosis, chronic inflammation amyloidosis, Huntington's disease, senile systemic amyloidosis, pituitary gland amyloidosis, hereditary renal amyloidosis, familial British dementia, Finnish hereditary amyloidosis, familial non-neuropathic amyloidosis, amyloid-related ocular diseases and disorders such as glaucoma and age-related macular degeneration (AMD, dry form and wet form), prion diseases including prion-related encephalopathies, scrapie of sheep and goats and bovine spongiform encephalopathy (BSE) of cattle and human prion diseases including Kuru disease, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia (FFI).