Vitamin D3 and analogs thereof for treating alopecia

Inventors

Jimenez, Joaquin J. • Narain, Niven Rajin • McCook, John Patrick

Assignees

BPGbio Inc

Abstract

The invention provides methods and pharmaceutical compositions for preventing or treating alopecia, such as chemotherapy-induced alopecia (CIA). The pharmaceutical compositions of the invention comprises an effective amount of a vitamin D compound in a formulation that topically delivers the vitamin D compound to the epidermis layer but substantially avoids the dermis layer. In chemotherapy patients, the pharmaceutical compositions of the invention can be administered either before or concurrent with the chemotherapy medication.

Core Innovation

The document discloses pharmaceutical compositions for preventing or treating alopecia, including chemotherapy-induced alopecia, using a vitamin D compound. The vitamin D compound is represented by Formula (I) and includes vitamin D3, calcitriol (1,25-dihydroxyvitamin D3), vitamin D analogs, metabolites, derivatives, mimics, stereoisomers, isotopically labeled vitamin D compounds, prodrugs, salts, and solvates. The compositions are topical and are formulated with carriers to deliver or accumulate in the epidermis while substantially avoiding dermis delivery.

The carrier consists of propylene glycol and ethanol at specified % (w/w) ratios selected from 35:65 through 45:55, or propylene glycol, ethanol, and ethoxydiglycol or 2-(2-ethoxyethoxy)ethanol at about 30%, about 60%, and about 10% (w/w), respectively. The pharmaceutical composition comprises 3-100 μg/mL of the vitamin D compound. The disclosure also includes topical vitamin D formulation concepts and a vitamin D/calcitriol topical vehicle approach.

The document further describes modulation of gene and protein targets in normal keratinocytes, including HSPA2/HSF4 mRNA and protein/gene modulation involving SLC1A1, KCNB2, KCNN4, SLC1A3, GST, Keratin 1, Keratin 17, Galectin 1, S100A9, and S100A13. The compositions are described as reducing toxicity and are supported by diffusion and absorption discussion using topical delivery concepts.

Claims Coverage

The independent claims in the provided set cover vitamin D compound-containing pharmaceutical compositions with specified carriers and concentration constraints, and cellular modulation in normal keratinocytes. Across the independent claims, the inventive features center on carrier composition and ratiometric constraints, the identity and amount of the vitamin D compound, and biomarker directionality for defined protein and gene panels.

The independent claims define vitamin D compound compositions either by Formula (I) or by 1,25-dihydroxyvitamin D3, formulated with propylene glycol/ethanol carriers at defined % (w/w) ratios or with a three-component carrier including ethoxydiglycol or 2-(2-ethoxyethoxy)ethanol at defined percentages. Additional claim coverage specifies biological modulation in normal keratinocytes, including reducing expression of a defined protein set and inducing overexpression of defined keratinocyte marker proteins.

Stated Advantages

Documented Applications

No documented applications found