Methods for making and using endoxifen
AssigneeAtossa Therapeutics, Inc.
InventorsSteven C. Quay, Yao-Lin Sun, LungHu Wang, ChangJung Wu, ChuanDer Huang
Life of this patent
Estimating the term…
Abstract
The present disclosure provides industrially scalable methods of making (Z)-endoxifen or a salt thereof, crystalline forms of endoxifen, and compositions comprising them. The present disclosure also provides methods for treating hormone-dependent breast and hormone-dependent reproductive tract disorders.
Claims100
An enteric oral formulation comprising a free base of a compound of Formula (III):
- wherein:
- at least 90% by weight of the compound of Formula (III) is (Z)-endoxifen;
- and
- the enteric oral formulation has an aerobic bacterial plate count of not more than 20,000 g/mL.
An enteric oral formulation comprising a free base of a compound of Formula (III):
- wherein:
- at least 90% by weight of the compound of Formula (III) is (Z)-endoxifen;
- and
- the enteric oral formulation has a water content of not more than 1.0% as tested by Method Ic of USP 921.
An enteric oral formulation comprising a free base of a compound of Formula (III):
- wherein:
- at least 90% by weight of the compound of Formula (III) is (Z)-endoxifen;
- and
- the enteric oral formulation has a water activity (Aw) of less than 0.9.
An enteric oral formulation comprising a free base of a compound of Formula (III):
- wherein:
- at least 90% by weight of the compound of Formula (III) is (Z)-endoxifen;
- and
- the enteric oral formulation has a residue on ignition of not more than 0.1% as tested by a method of USP 281.
An enteric oral formulation comprising a free base of a compound of Formula (III):
- wherein:
- at least 90% by weight of the compound of Formula (III) is (Z)-endoxifen;
- and
- the enteric oral formulation has a heavy metal content of not more than 20 ppm as tested by Method II of USP 231.
An enteric oral formulation comprising a free base of a compound of Formula (III):
- wherein:
- at least 90% by weight of the compound of Formula (III) is (Z)-endoxifen;
- and
- the enteric oral formulation has:
- a methanol content of not more than 3000 ppm;
- a tetrahydrofuran content of not more than 720 ppm;
- an isopropanol content of not more than 5000 ppm;
- an ethyl acetate content of not more than 5000 ppm;
- a n-heptane content of not more than 5000 ppm;
- and
- an ethanol content of not more than 5000 ppm,
- as tested by a validated HPLC method.
A method of treating a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an enteric oral formulation comprising a free base of a compound of Formula (III):
- wherein:
- at least 90% by weight of the compound of Formula (III) is (Z)-endoxifen;
- and
- the enteric oral formulation has one or more of the following properties:
- (a) an aerobic bacterial plate count of not more than 20,000 g/mL;
- (b) a water content of not more than 1.0% as tested by Method Ic of USP 921;
- (c) a water activity (Aw) of less than 0.9;
- (d) a residue on ignition of not more than 0.1% as tested by a method of USP 281;
- (e) a heavy metal content of not more than 20 ppm as tested by Method II of USP 231;
- and
- (f) a methanol content of not more than 3000 ppm, a tetrahydrofuran content of not more than 720 ppm, an isopropanol content of not more than 5000 ppm, an ethyl acetate content of not more than 5000 ppm, a n-heptane content of not more than 5000 ppm, and an ethanol content of not more than 5000 ppm, as tested by a validated HPLC method.
Dependencies are inferred from the claim text.