Methods and products for increasing the rate of healing of tissue wounds

摘要

Disclosed are methods for increasing the rate of healing of a tissue wound by administering a composition including a therapeutically effective amount of at least one cationic steroid antimicrobial (CSA). Also disclosed herein are methods of promoting wound healing 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 a tissue wound. Kits comprising such compositions and instructions on such methods are also contemplated herein.

主权项

1. A method for increasing the rate of healing of a tissue wound, comprising:
identifying a subject in need of accelerated healing of a tissue wound; and contacting the tissue wound with an effective amount of a tissue treatment composition to increase the rate of healing thereof, the tissue treatment composition comprising a cationic steroidal anti-microbial (CSA) compound of Formula V, or a pharmaceutically acceptable salt thereof, that promotes would healing and comprises a steroidal group and a plurality of cationic groups attached thereto: where,
rings A, B, C, and D are independently saturated, or are fully or partially unsaturated, provided that at least two of rings A, B, C, and D are 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 (C1-C6) alkyl; andR3, R7, and R12 are independently selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C1-C18) alkyl, substituted or unsubstituted (C1-C18) hydroxyalkyl, substituted or unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted (C1-C18) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) haloalkyl, substituted or unsubstituted (C2-C6) alkenyl, substituted or unsubstituted (C2-C6) alkynyl, oxo, linking group attached to a second CSA, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy, substituted or unsubstituted (C1-C18) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxamido, substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl, substituted or unsubstituted C-carboxy-(C1-C18) alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted (C1-C18) azidoalkyloxy, substituted or unsubstituted (C1-C18) cyanoalkyloxy, P.G.-HN—HC(Q5)-C(O)—O, substituted or unsubstituted (C1-C18) guanidinoalkyloxy, substituted or unsubstituted (C1-C18) quaternary ammonium alkyl carboxy, and substituted or unsubstituted (C1-C18) guanidinoalkylcarboxy, 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 not hydrogen; andR18 is selected from the group consisting of hydroxyl, substituted or unsubstituted (C1-C18) alkyl, substituted or unsubstituted (C1-C18) hydroxyalkyl, substituted or unsubstituted (C1-C18) alkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylcarboxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) alkylamino-(C1-C18) alkylamino, substituted or unsubstituted amido, substituted or unsubstituted (C1-C18) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) haloalkyl, substituted or unsubstituted (C2-C6) alkenyl, substituted or unsubstituted (C2-C6) alkynyl, linking group attached to a second CSA, substituted or unsubstituted (C1-C18) aminoalkyloxy, substituted or unsubstituted (C1-C18) aminoalkyloxy-(C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxy (C1-C18) alkyl, substituted or unsubstituted (C1-C18) aminoalkylaminocarbonyl, substituted or unsubstituted (C1-C18) aminoalkylcarboxamido, substituted or unsubstituted di(C1-C18 alkyl) aminoalkyl, substituted or unsubstituted C-carboxy-(C1-C18) alkyl, H2N—HC(Q5)-C(O)—O—, H2N—HC(Q5)-C(O)—N(H)—, substituted or unsubstituted (C1-C18) azidoalkyloxy, substituted or unsubstituted (C1-C18) cyanoalkyloxy, P.G.-HN—HC(Q5)-C(O)—O, substituted or unsubstituted (C1-C18) guanidinoalkyloxy, substituted or unsubstituted (C1-C18) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C1-C18) guanidinoalkylcarboxy, where Q5 is a side chain of an amino acid and P.G. is an amino protecting group.