Treatment methods using pharmaceutical solid state forms
Inventors
White, Steven K • Ivanisevic, Igor • Stephens, Kyle • Andres, Mark • Wolfe, Brenton Skylar
Assignees
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Publication Number
US-9877972-B2
Publication Date
2018-01-30
Expiration Date
Abstract
The invention provides and describes solid state 17α-ethynyl-androst-5-ene-3β, 7β,17β-triol including amorphous and crystalline forms and specific polymorphic forms thereof. Anhydrates and solvates of 17α-ethynyl-androst-5-ene-3β, 7β,17β-triol include Form I anhydrate and Form IV and Form V solvates. The invention further relates to solid and suspension formulations containing 17α-ethynyl-androst-5-ene-3β,7β,17β-triol in a described solid state form and use of the formulations to treat hyperglycemic conditions, such as type 2 diabetes and metabolic syndrome, and autoimmune conditions, such as rheumatoid arthritis, ulcerative colitis and type 1 diabetes, among other inflammation related conditions in subjects or human patients. The invention also relates to methods to make liquid formulations from solid state forms of 17α-ethynyl-androst-5-ene-3β, 7β,17β-triol and uses of such formulations in treating the described conditions.
Core Innovation
The invention relates to methods to treat an inflammation condition in a subject by administering an effective amount of crystalline 17α-ethynylandrost-5-ene-3β,7β,17β-triol, including crystalline Form I, Form II, crystalline Form III hydrate, and crystalline Form IV solvate. The solid-state forms are characterized and defined for crystalline anhydrate and crystalline solvate and for amorphous material, including XRPD and Raman characterizations.
The solid-state variants of 17α-ethynyl-androst-5-ene-3β,7β,17β-triol (Compound 1) are described, including amorphous material and crystalline polymorphic and pseudopolymorphic forms. The crystalline solid-state forms include Form I, Form II, Form III, and Form IV, with additional mentions of anhydrate and solvate or hydrate forms, including Form III hydrate and Form IV solvate.
Pharmaceutical solid and liquid formulations use these solid-state forms of Compound 1. Form I to Form IV are characterized and identified using XRPD, Raman spectroscopy, IR/ATR-FTIR, DSC, DTA, TGA, TG-IR, and solid-state NMR (SS-NMR), and are distinguished using XRPD peak lists and Raman assignments.
Claims Coverage
The provided independent claims are directed to administering specific crystalline solid forms of 17α-ethynylandrost-5-ene-3β,7β,17β-triol to treat inflammation conditions, with four inventive features centered on crystal form selection and the associated inflammation condition.
Crystalline form I treatment of an inflammation condition
Administering to the subject an effective amount of crystalline Form I 17α-ethynylandrost-5-ene-3β,7β,17β-triol to treat an inflammation condition.
Crystalline form ii for neuroinflammation-associated disease
Administering to the subject an effective amount of crystalline Form II 17α-ethynylandrost-5-ene-3β,7β,17β-triol, wherein the inflammation condition is a disease or condition associated with neuroinflammation selected from Alzheimer's Disease, Parkinson's Disease, amyotropic lateral sclerosis and age-related macular degeneration.
Crystalline form iii hydrate for neuroinflammation-associated disease
Administering to the subject an effective amount of a crystalline Form III 17α-ethynylandrost-5-ene-3β,7β,17β-triol hydrate, wherein the inflammation condition is a disease or condition associated with neuroinflammation, selected from Alzheimer's Disease, Parkinson's Disease, amyotropic lateral sclerosis and age-related macular degeneration.
Crystalline form iv solvate for neuroinflammation-associated disease
Administering to the subject an effective amount of a crystalline Form IV 17α-ethynylandrost-5-ene-3β,7β,17β-triol solvate, wherein the inflammation condition is a disease or condition associated with neuroinflammation, selected from Alzheimer's Disease, Parkinson's Disease, amyotropic lateral sclerosis and age-related macular degeneration.
Across the independent claims, the claim scope is centered on treating an inflammation condition by administering an effective amount of specifically defined crystalline solid forms (Form I, Form II, Form III hydrate, and Form IV solvate). For Forms II–IV, the inflammation condition is restricted to neuroinflammation-associated diseases selected from Alzheimer's Disease, Parkinson's Disease, amyotropic lateral sclerosis, and age-related macular degeneration.
Stated Advantages
Not explicitly described in patent.
Documented Applications
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