Provided are inclusion complexes comprising fulvestrant and a cyclodextrin. The complexes may be useful for treating various conditions, such as cancer and systemic lupus erythematosus. Also provided are methods of producing the inclusion complexes, methods of using the inclusion complexes in therapy, and kits and unit dosages comprising the complexes.

The invention relates to compounds of formula (II),

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and pharmaceutically acceptable salts thereof,
wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Provided are inclusion complexes comprising fulvestrant and a cyclodextrin. The complexes may be useful for treating various conditions, such as cancer and systemic lupus erythematosus. Also provided are methods of producing the inclusion complexes, methods of using the inclusion complexes in therapy, and kits and unit dosages comprising the complexes.

Disclosed is a pharmaceutical composition, comprising: a) at least one sorbitan unsaturated fatty acid ester having a polar head with at least two or more OH (hydroxyl) groups; b) at least one phospholipid; c) at least one liquid crystal hardener which is free of an ionizable group and has a triacyl group with 15 to 40 carbon atoms or a carbon ring structure in a hydrophobic moiety; and d) at least one GnRH (gonadotropin-releasing hormone) analogue as a pharmacologically active substance, wherein said lipid pre-concentrate exists as a liquid phase in absence of aqueous fluid and forms into a liquid crystal in presence of aqueous fluid. The pharmaceutical composition is configured to enhance the sustained release of the pharmacologically active substance GnRH analogue.

The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof ##STR00001##
wherein R1 to R4 are as defined in the claims. The invention further relates to their use as inhibitors of 17-HSD1 and in treatment or prevention of steroid hormone dependent diseases or disorders, such as steroid hormone dependent diseases or disorders requiring the inhibition of the 17-HSD1 enzyme and/or requiring the lowering of the endogenous estradiol concentration. The present invention also relates to the preparation of the aforementioned compounds and to pharmaceutical compositions comprising as an active ingredient(s) one or more of the aforementioned compounds or pharmaceutically acceptable salts thereof.

Fulvestrant formulations suitable for intramuscular injection at concentration in excess of 40 mg/ml in the absence of castor oil and castor oil derivatives are disclosed.

Provided is a pharmaceutical composition which contains fulvestrant in an amount of 4.5% by mass to 10.0% by mass with respect to the entire mass of the pharmaceutical composition, at least one kind of polyhydric alcohol selected from propylene glycol or 1,3-butylene glycol in an amount of 8% by mass to 23% by mass with respect to the entire mass of the pharmaceutical composition, benzyl alcohol in an amount of 5% by mass to 24% by mass with respect to the entire mass of the pharmaceutical composition, benzyl benzoate in an amount of 8% by mass to 19% by mass with respect to the entire mass of the pharmaceutical composition, and castor oil, and in which a content of ethanol is less than 1% by mass with respect to the entire mass of the pharmaceutical composition, and a content of benzoic acid is less than 1% by mass with respect to the entire mass of the pharmaceutical composition.

Provided is a pharmaceutical composition which contains fulvestrant in an amount of 4.5% by mass to 10.0% by mass with respect to the entire mass of the pharmaceutical composition, at least one kind of polyhydric alcohol selected from propylene glycol or 1,3-butylene glycol in an amount of 8% by mass to 23% by mass with respect to the entire mass of the pharmaceutical composition, benzyl alcohol in an amount of 5% by mass to 24% by mass with respect to the entire mass of the pharmaceutical composition, benzyl benzoate in an amount of 8% by mass to 19% by mass with respect to the entire mass of the pharmaceutical composition, and castor oil, and in which a content of ethanol is less than 1% by mass with respect to the entire mass of the pharmaceutical composition, and a content of benzoic acid is less than 1% by mass with respect to the entire mass of the pharmaceutical composition.

The present disclosure provides compounds of Formula (I) and Formula (II). The compounds described herein may be useful in treating proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein. ##STR00001##

The disclosure provides methods of use of certain compounds that are useful for treating certain symptoms of endocrine disturbances, and in particular those associated with hot flashes.