SOLID FORMS OF ALPHA-1062 GLUCONATE
In one aspect, the invention relates to a crystalline solid form of Alpha-1062 gluconate (Form B), wherein the crystalline form has prominent peaks at 10.69, 17.17, 21.00 and 24.67 degrees 2-theta (±0.2) in a powder X-ray diffraction pattern. In another aspect, the invention relates to a preparation including the crystalline solid form (Form B), wherein the preparation includes additionally one or more additional crystalline solid forms of Alpha-1062 gluconate, including at least a crystalline solid form according to Form C, wherein Form C has prominent peaks at 3.90, 9.74, 10.35 and 21.43 degrees 2-theta (±0.2) in a powder X-ray diffraction pattern. Also disclosed are methods for treating a brain disease associated with cognitive impairment and/or with a cholinergic deficit in a subject, including administering the crystalline forms of Alpha-1062 gluconate to a subject in need thereof. 60577388
1 . A crystalline solid form of Alpha-1062 gluconate (Form B), wherein said crystalline form has prominent peaks at 10.69, 17.17, 21.00 and 24.67 degrees 2-theta (±0.2) in a powder X-ray diffraction pattern.
2 . The crystalline solid form according to claim 1 , wherein said crystalline form has one or more additional peaks at 12.92, 13.26, 14.56, 16.45, degrees 2-theta (±0.2) in a powder X-ray diffraction pattern.
3 . The crystalline solid form according to claim 1 , wherein said crystalline form has an additional peak at 15.46 degrees 2-theta (±0.2).
4 . The crystalline solid form according to claim 1 , wherein said crystalline form exhibits an onset of melting at a temperature of 60-70° C. when assessed using differential scanning calorimetry (DSC).
5 . The crystalline solid form according to claim 4 , wherein said crystalline form exhibits an onset of melting at a temperature of 66° C.
6 . The crystalline solid form according to claim 1 , wherein said crystalline form exhibits a weight loss of 3-4% up to 114° C. when assessed using Thermo-Gravimetric Analysis (TGA).
7 . The crystalline solid form according to claim 6 , wherein said crystalline form exhibits a weight loss of 3.3%.
8 . A preparation comprising the crystalline solid form according to claim 1 (Form B), wherein said preparation comprises additionally one or more additional crystalline solid forms of Alpha-1062 gluconate, comprising at least a crystalline solid form according to Form C:
wherein said Form C has prominent peaks at 3.90, 9.74, 10.35 and 21.43 degrees 2-theta (±0.2) in a powder X-ray diffraction pattern.
9 . A pharmaceutical composition in solid form, comprising the crystalline solid form according to claim 1 (Form B), wherein said composition additionally comprises one or more pharmaceutically acceptable excipients.
10 . A pharmaceutical composition comprising the preparation according to claim 8 .
11 . The pharmaceutical composition according to claim 9 , wherein the composition is suitable for oral or transmucosal administration.
12 . A method of treating a brain disease associated with cognitive impairment and/or with a cholinergic deficit in a subject, comprising administering the pharmaceutical composition according to claim 9 to a subject in need thereof.
13 . The method according to claim 12 , wherein the brain disease is selected from the group consisting of a brain disease with a cholinergic deficit, Alzheimer's disease, Parkinson's disease, dementia, schizophrenia, epilepsy, stroke, poliomyelitis, neuritis, myopathy, oxygen and nutrient deficiencies in the brain after hypoxia, anoxia, asphyxia, cardiac arrest, chronic fatigue syndrome, poisoning, anaesthesia, spinal cord disorders, central inflammatory disorders, autism, Rett's syndrome, postoperative delirium, neuropathic pain, abuse of alcohol and drugs, addictive alcohol and/or nicotine craving, and effects of radiotherapy.
14 . The pharmaceutical composition according to claim 10 , wherein the composition is suitable for oral or transmucosal administration.
15 . A method of treating a brain disease associated with cognitive impairment and/or with a cholinergic deficit in a subject, comprising administering the pharmaceutical composition according to claim 10 to a subject in need thereof.
16 . The method according to claim 15 , wherein the brain disease is selected from the group consisting of a brain disease with a cholinergic deficit, Alzheimer's disease, Parkinson's disease, dementia, schizophrenia, epilepsy, stroke, poliomyelitis, neuritis, myopathy, oxygen and nutrient deficiencies in the brain after hypoxia, anoxia, asphyxia, cardiac arrest, chronic fatigue syndrome, poisoning, anaesthesia, spinal cord disorders, central inflammatory disorders, autism, Rett's syndrome, postoperative delirium, neuropathic pain, abuse of alcohol and drugs, addictive alcohol and/or nicotine craving, and effects of radiotherapy.