COMPOSITIONS AND METHODS FOR TREATING BONE DISEASES AND BROKEN BONES

摘要

Disclosed herein are methods of promoting osteogenesis in a subject, comprising administering a composition comprising a therapeutically effective amount of at least one cationic steroid antimicrobial (CSA). Also disclosed herein are methods of promoting osteogenesis in a subject in need of such promotion, comprising administering a composition comprising a therapeutically effective amount of at least one CSA. Additionally, disclosed herein are compounds and compositions comprising at least one CSA, or a pharmaceutically acceptable salt thereof, for use in the treatment of bone disease or the treatment of broken bones. Kits comprising such compositions and instructions on such methods are also contemplated herein.

主权项

1. A method of promoting osteogenesis in a subject in need of treatment for a bone disease or healing a broken bone, comprising:
identifying a subject in need of treatment for a bone disease or healing a broken bone; and administering to the subject an amount ranging from about 0.1 μg/g to about 50 μg/g of body weight and/or an amount ranging from about 0.001 mg to about 1000 mg of at least one cationic steroid antimicrobial (CSA) of Formula V, or a pharmaceutically acceptable salt thereof: wherein rings A, B, C, and D are independently saturated; m, n, p, and q are independently 0 or 1; R1, R2, R4, R5, R6, R8, R9, R10, R11, R13, R14, R15, R16, and R17 are independently selected from the group consisting of hydrogen and substituted or unsubstituted alkyl; R3, R7, R12, and R18 are independently selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted alkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkyloxyalkyl, substituted or unsubstituted alkylcarboxyalkyl, substituted or unsubstituted alkylaminoalkyl, substituted or unsubstituted alkylamino-alkylamino, substituted or unsubstituted alkylaminoalkylaminoalkylamino, substituted or unsubstituted aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylaminoalkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, oxo, linking group attached to a second CSA, substituted or unsubstituted aminoalkyloxy, substituted or unsubstituted aminoalkyloxyalkyl, substituted or unsubstituted aminoalkylcarboxy, substituted or unsubstituted aminoalkylaminocarbonyl, substituted or unsubstituted aminoalkylcarboxamido, substituted or unsubstituted dialkylaminoalkyl, substituted or unsubstituted C-carboxy alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted azidoalkyloxy, substituted or unsubstituted cyanoalkyloxy, P.G.-HN—HC(Q5)-C(O)—O, substituted or unsubstituted guanidinoalkyloxy, substituted or unsubstituted quaternary ammonium alkylcarboxy, and substituted or unsubstituted guanidinoalkyl carboxy, where Q5 is a side chain of an amino acid and P.G. is an amino protecting group; provided that at least two of R3, R7, and R12 are independently selected from the group consisting of aminoalkyloxy, aminoalkylcarboxy, alkylaminoalkyl, and di(alkyl)aminoalkyl.