Treatment and prevention of mastitis

Patent metadata

Field	Value
Publication number	US-2016193232-A1
Application number	US-201615070845-A
Country	US
Kind code	A1
Filing date	Mar 15, 2016
Priority date	Oct 17, 2012
Publication date	Jul 7, 2016
Grant date	—

Abstract

Treating and/or preventing clinical mastitis includes administering a cationic steroidal anti-microbial (CSA) formulation to the intra-mammary organ of a mammal (e.g., a dairy cow), such as by injection into the mammary organ and/or topical application. The CSA formulation can be effective in treating and/or preventing mastitis caused by gram positive bacteria, gram negative bacteria, fungus, and/or prototheca. The dairy cow can be lactating and have a somatic cell count (SCC) less than or equal to 500,000 cells/mL at the time of administering the CSA formulation. Alternatively, the dairy cow can be lactating and have a somatic cell count (SCC) greater than 500,000 cells/mL at the time of administering the CSA formulation. The dairy cow can be taken out of production during the administration of the CSA formulation for a period of time of about 3 days or less, 2 days or less, or 1 day or less.

First claim

What is claimed is:

1 . A method for treating or preventing clinical mastitis in a mammal, comprising:
administering a cationic steroidal anti-microbial (CSA) formulation to the intra-mammary organ of the mammal to treat or prevent clinical mastitis, wherein the CSA formulation is effective in treating and/or preventing clinical mastitis in a mammal caused by at least one of gram positive bacteria, gram negative bacteria, fungus, or prototheca, and includes a compound of Formula (I) or a pharmaceutically acceptable salt thereof:

where,
each of rings A, B, C, and D is independently saturated;
m, n, p, and q are independently 0 or 1; and
at least two of R 1-4 , R 6 , R 7 , R 11 , R 12 , R 15 , R 16 , R 17 , and R 18 include amine or cationic groups.

2 . The method of claim 1 , wherein the CSA formulation is administered by injection into the mammary organ or injection through the teat of the mammary organ.

3 . The method of claim 1 , wherein the CSA formulation is administered by injection into the teat of the mammary organ.

4 . The method of claim 1 , wherein the subject is a human.

5 . The method of claim 1 , wherein the subject is a dairy cow.

6 . The method of claim 5 , wherein the dairy cow is lactating and has a somatic cell count (SCC) greater than 500,000 cells/mL at the time of administering the CSA.

7 . The method of claim 6 , wherein the dairy cow is taken out of production for a period of time of 3 days or less while administering the CSA formulation.

8 . The method of claim 1 , wherein
R 1 through R 4 , R 6 , R 7 , R 11 , R 12 , R 15 , R 16 , and R 18 are independently selected from the group consisting of hydrogen, hydroxyl, a substituted or unsubstituted alkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted alkyloxyalkyl, a substituted or unsubstituted alkylcarboxyalkyl, a substituted or unsubstituted alkylaminoalkyl, a substituted or unsubstituted alkylaminoalkylamino, a substituted or unsubstituted alkylaminoalkylaminoalkylamino, a substituted or unsubstituted aminoalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted arylaminoalkyl, a substituted or unsubstituted haloalkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, oxo, a linking group attached to a second steroid, a substituted or unsubstituted aminoalkyloxy, a substituted or unsubstituted aminoalkyloxyalkyl, a substituted or unsubstituted aminoalkylcarboxy, a substituted or unsubstituted aminoalkylaminocarbonyl, a substituted or unsubstituted aminoalkylcarboxamido, a substituted or unsubstituted di(alkyl)aminoalkyl, a substituted or unsubstituted C-carboxyalkyl, H 2 N—HC(Q 5 )-C(O)—O—, H 2 N—HC(Q 5 )-C(O)—N(H)—, a substituted or unsubstituted azidoalkyloxy, a substituted or unsubstituted cyanoalkyloxy, P.G.-HN—HC(Q 5 )-C(O)—O—, a substituted or unsubstituted guanidinoalkyloxy, a substituted or unsubstituted quaternary ammonium alkylcarboxy, and a substituted or unsubstituted guanidinoalkyl carboxy, where Q 5 is a side chain of an amino acid, and P.G. is an amino protecting group; and R 5 , R 8 , R 9 , R 10 , R 13 , and R 14 are independently selected from the group consisting of hydrogen, hydroxyl, a substituted or unsubstituted alkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted alkyloxyalkyl, a substituted or unsubstituted aminoalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted haloalkyl, a substituted or unsubstituted alkenyl, a substituted or unsubstituted alkynyl, oxo, a linking group attached to a second steroid, a substituted or unsubstituted aminoalkyloxy, a substituted or unsubstituted aminoalkylcarboxy, a substituted or unsubstituted aminoalkylaminocarbonyl, a substituted or unsubstituted di(alkyl)aminoalkyl, a substituted or unsubstituted C-carboxyalkyl, H 2 N—HC(Q 5 )-C(O)—O—, H 2 N—HC(Q 5 )-C(O)—N(H)—, azidoalkyloxy, cyanoalkyloxy, P.G.-HN—HC(Q 5 )-C(O)—O—, guanidinoalkyloxy, and guanidinoalkylcarboxy, where Q 5 is a side chain of an amino acid, and P.G. is an amino protecting group, provided that at least two of R 1-4 , R 6 , R 7 , R 11 , R 12 , R 15 , R 16 , R 17 , and R 18 are independently selected from the group consisting of a substituted or unsubstituted aminoalkyl, a substituted or unsubstituted aminoalkyloxy, a substituted or unsubstituted alkylcarboxyalkyl, a substituted or unsubstituted alkylaminoalkylamino, a substituted or unsubstituted alkylaminoalkylaminoalkylamino, a substituted or unsubstituted aminoalkylcarboxy, a substituted or unsubstituted arylaminoalkyl, a substituted or unsubstituted aminoalkyloxyaminoalkylaminocarbonyl, a substituted or unsubstituted aminoalkylaminocarbonyl, a substituted or unsubstituted aminoalkylcarboxyamido, a quaternary ammonium alkylcarboxy, a substituted or unsubstituted di(alkyl)aminoalkyl, a substituted or unsubstituted C-carboxyalkyl, H 2 N—HC(Q 5 )-C(O)—O—, H 2 N—HC(Q 5 )-C(O)—N(H)—, azidoalkyloxy, cyanoalkyloxy, P.G.-HN—HC(Q 5 )-C(O)—O—, a substituted or unsubstituted guanidinoalkyloxy, and a substituted or unsubstituted guanidinoalkylcarboxy.

9 . The method of claim 8 , wherein
R 1 through R 4 , R 6 , R 7 , R 11 , R 12 , R 15 , R 16 , and R 18 are independently selected from the group consisting of hydrogen, hydroxyl, a substituted or unsubstituted (C 1 -C 18 ) alkyl, a substituted or unsubstituted (C 1 -C 18 ) hydroxyalkyl, a substituted or unsubstituted (C 1 -C 18 ) alkyloxy-(C 1 -C 18 ) alkyl, a substituted or unsubstituted (C 1 -C 18 ) alkylcarboxy-(C 1 -C 18 ) alkyl, a substituted or unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 )alkyl, a substituted or unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, a substituted or unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, a substituted or unsubstituted (C 1 -C 18 ) aminoalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted arylamino-(C 1 -C 18 ) alkyl, a substituted or unsubstituted (C 1 -C 18 ) haloalkyl, a substituted or unsubstituted C 2 -C 6 alkenyl, a substituted or unsubstituted C 2 -C 6 alkynyl, oxo, a linking group attached to a second steroid, a substituted or unsubstituted (C 1 -C 18 ) aminoalkyloxy, a substituted or unsubstituted (C 1 -C 18 ) aminoalkyloxy-(C 1 -C 18 ) alkyl, a substituted or unsubstituted (C 1 -C 18 ) aminoalkylcarboxy, a substituted or unsubstituted (C 1 -C 18 ) aminoalkylaminocarbonyl, a substituted or unsubstituted (C 1 -C 18 ) aminoalkylcarboxamido, a substituted or unsubstituted di(C 1 -C 18 alkyl)aminoalkyl, a substituted or unsubstituted C-carboxy(C 1 -C 18 )alkyl, H 2 N—HC(Q 5 )-C(O)—O—, H 2 N—HC(Q 5 )-C(O)—N(H)—, a substituted or unsubstituted (C 1 -C 18 ) azidoalkyloxy, a substituted or unsubstituted (C 1 -C 18 ) cyanoalkyloxy, P.G.-HN—HC(Q 5 )-C(O)—O—, a substituted or unsubstituted (C 1 -C 18 ) guanidinoalkyloxy, a substituted or unsubstituted (C 1 -C 18 ) quaternary ammonium alkylcarboxy, and a substituted or unsubstituted (C 1 -C 18 ) guanidinoalkyl carboxy, where Q 5 is a side chain of an amino acid and P.G. is an amino protecting group; R 5 , R 8 , R 9 , R 10 , R 13 , and R 14 are independently selected from the group consisting of hydrogen, hydroxyl, a substituted or unsubstituted (C 1 -C 18 ) alkyl, a substituted or unsubstituted (C 1 -C 18 ) hydroxyalkyl, a substituted or unsubstituted (C 1 -C 18 ) alkyloxy-(C 1 -C 18 ) alkyl, a substituted or unsubstituted (C 1 -C 18 ) aminoalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted (C 1 C 18 ) haloalkyl, a substituted or unsubstituted (C 2 -C 6 ) alkenyl, a substituted

Assignees

• Beus Chad S
• Savage Paul B
• Univ Brigham Young

Inventors

• Beus Chad S
• Savage Paul B

Classifications

• A61K9/0041

  Mammary glands, e.g. breasts, udder; Intramammary administration · CPC title

• A61K31/575 Primary

  substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title