COMPOSITIONS FOR TREATMENT OF NEURODEGENERATIVE CONDITIONS
Disclosed herein is a pharmaceutical composition comprising solid state forms of 17-ethynyl-10R, 13S-dimethyl 2, 3, 4, 7, 8R, 9S, 10, 11, 12, 13, 14S, 15, 16, 17-hexadecahydro-1H-cyclopenta[a]phenanthrene-3R, 7R, 17S-triol. Also disclosed herein is a method for using the solid state forms for the treatment of conditions related to neurodegenerative conditions including Parkinson's disease.
1 . A method to treat a neurodegenerative condition, the method comprising administering to a patient in need thereof an effective amount of a pharmaceutical composition comprising 17α-ethynylandrost-5-ene-3β,7β,17β-triol and at least one pharmaceutically acceptable excipient.
2 . The method of claim 1 , wherein the neurodegenerative condition is Parkinson's disease.
3 . The method of any one of claims 1 to 2 , wherein the method further comprises administering at least one additional medicament to the patient.
4 . The method of claim 3 , wherein the additional medicament comprises at least one dopamine agonist.
5 . The method of any one of claims 3 to 4 , wherein the additional medicament comprises at least one dopamine precursor.
6 . The method of any one of claims 3 to 5 , wherein the additional medicament comprises L-dopa.
7 . The method of any one of claims 3 to 6 , wherein the additional medicament is administered at a delay time after a first administration of the composition.
8 . The method of claim 7 , wherein the delay time is equal to or greater than 2 years.
9 . The method of any one of claims 1 to 8 , wherein at least one motor symptom and/or at least one motor complication develops in the patient.
10 . The method of claim 9 , wherein the motor symptom is selected from tremor and/or shaking in the extremities, slowed movement (bradykinesia), muscle stiffness, rigidity, immobility (freezing), muscle cramps, impaired posture and/or balance, falls, dizziness, loss of automatic movements such as blinking or smiling, changes in speech and/or writing, motor fluctuations, dystonia, and any combination of the foregoing.
11 . The method of claim 9 , wherein the motor complication is selected from wearing off, dose failure, beginning of dose worsening, end-of-dose rebound, unpredictable off-periods, freezing of gait, on-period failure, acute akinesia, dyskinesia, and any combination of the foregoing.
12 . The method of any one of claims 9 to 11 , wherein the motor symptom and/or the motor complication develops at a time equal to or greater than 2 years after the additional medicament is administered.
13 . The method of any one of claims 1 to 12 , wherein the 17α-ethynylandrost-5-ene-3β,7β,17β-triol is a solid state form of 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
14 . The method of claim 13 , wherein the solid state form of 17α-ethynylandrost-5-ene-3β,7β,17β-triol is crystalline solvate of 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
15 . The method of claim 14 , wherein the crystalline solvate is crystalline methanolate 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
16 . The method of claim 14 , wherein the crystalline solvate is crystalline ethanolate 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
17 . The method of claim 14 , wherein the crystalline solvate is crystalline hydrate 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
18 . The method of claim 14 , wherein the crystalline solvate is Form III 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
19 . The method of claim 14 , wherein the crystalline solvate is Form IV 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
20 . The method of claim 14 , wherein the crystalline solvate is Form V 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
21 . The method of claim 13 , wherein the solid state form of 17α-ethynylandrost-5-ene-3β,7β,17β-triol is amorphous 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
22 . The method of any one of claims 1 to 21 , wherein the pharmaceutical composition contains less than about 3% by weight of impurities.
23 . The method of any one of claims 1 to 22 , wherein the patient is a human or mammal.
24 . A pharmaceutical composition comprising 17α-ethynylandrost-5-ene-3β,7β,17β-triol and at least one pharmaceutically acceptable excipient for use in treating a neurodegenerative condition.
25 . The use of a pharmaceutical composition comprising 17α-ethynylandrost-5-ene-3β,7β,17β-triol and at least one pharmaceutically acceptable excipient for treating a neurodegenerative condition.
26 . The use of 17α-ethynylandrost-5-ene-3β,7β,17β-triol in the manufacture of a medicament for treating a neurodegenerative condition, wherein the medicament comprises at least one pharmaceutically acceptable excipient.
27 . The pharmaceutical composition of claim 24 or the use of claim 25 or 26 , wherein the neurodegenerative condition is Parkinson's disease.
28 . The pharmaceutical composition of claims 24 or 27 , or the use of claims 25 - 27 , wherein the composition, or the use, comprises at least one additional medicament.
29 . The pharmaceutical composition of claims 24 or 27 - 28 or the use of claims 25 - 28 , wherein the additional medicament comprises L-dopa.
30 . The pharmaceutical composition of claims 24 or 27 - 29 or the use of claims 25 - 29 , wherein the additional medicament is used at a delay time after use of the pharmaceutical composition begins.
31 . The pharmaceutical composition of claims 24 or 27 - 30 or the use of claims 25 - 30 , wherein the delay time is equal to or greater than 2 years.
32 . The pharmaceutical composition of claims 24 or 27 - 31 or the use of claims 25 - 31 , wherein development of at least one motor symptom and/or at least one motor complication occurs.
33 . The pharmaceutical composition of claims 24 or 27 - 32 or the use of claims 25 - 32 , wherein the motor symptom is selected from tremor and/or shaking in the extremities, slowed movement (bradykinesia), muscle stiffness, rigidity, immobility (freezing), muscle cramps, impaired posture and/or balance, falls, dizziness, loss of automatic movements such as blinking or smiling, changes in speech and/or writing, motor fluctuations, dystonia, and any combination of the foregoing.
34 . The pharmaceutical composition of claims 24 or 27 - 33 or the use of claims 25 - 33 , wherein the motor complication is selected from wearing off, dose failure, beginning of dose worsening, end-of-dose rebound, unpredictable off-periods, freezing of gait, on-period failure, acute akinesia, dyskinesia and any combination of the foregoing.
35 . The pharmaceutical composition of claims 24 or 27 - 34 or the use of claims 25 - 34 , wherein the motor symptom and/or the motor complication develops at a time equal to or greater than 2 years after the use of the pharmaceutical composition begins.
36 . The pharmaceutical composition of claims 24 or 27 - 35 or the use of claims 25 - 35 , wherein the motor symptom and/or the motor complication develops at a time equal to or greater than 2 years after the use of the additional medicament begins.
37 . The pharmaceutical composition of claims 24 or 27 - 36 or the use of claims 25 - 36 , wherein the 17α-ethynylandrost-5-ene-3β,7β,17β-triol is a solid state form of 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
38 . The pharmaceutical composition of claims 24 or 27 - 37 or the use of claims 25 - 37 , wherein the solid state form is a crystalline solvate of 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
39 . The pharmaceutical composition of claims 24 or 27 - 38 or the use of claims 25 - 38 , wherein the crystalline solvate is crystalline methanolate 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
40 . The pharmaceutical composition of claims 24 or 27 - 39 or the use of claims 25 - 39 , wherein the crystalline solvate is crystalline ethanolate 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
41 . The pharmaceutical composition of claims 24 or 27 - 40 or the use of claims 25 - 40 , wherein the crystalline solvate is crystalline hydrate 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
42 . The pharmaceutical composition of claims 24 or 27 - 41 or the use of claims 25 - 41 , wherein the crystalline solvate is Form III 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
43 . The pharmaceutical composition of claims 24 or 27 - 42 or the use of claims 25 - 42 , wherein the crystalline solvate is Form IV 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
44 . The pharmaceutical composition of claims 24 or 27 - 43 or the use of claims 25 - 43 , wherein the crystalline solvate is Form V 17α-ethynylandrost-5-ene-3β,7β,17β-triol.
45 . The pharmaceutical composition of claims 24 or 27 - 44 or the use of claims 25 - 44 , wherein the solid state form is amorphous 17α-ethynylandrost-5-ene-3β,7β,17β-triol.