Treatment and prevention of mastitis

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.

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 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 ) aminoalkylcarboxy, a substituted or unsubstituted (C 1 -C 18 ) aminoalkylaminocarbonyl, 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, and (C 1 -C 18 ) 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 or three 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 (C 1 -C 18 ) aminoalkyl, a substituted or unsubstituted (C 1 -C 18 ) aminoalkyloxy, 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 ) 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 ) aminoalkylcarboxy, a substituted or unsubstituted arylamino (C 1 -C 18 ) alkyl, a substituted or unsubstituted (C 1 -C 18 ) aminoalkyloxy (C 1 -C 18 ) aminoalkylaminocarbonyl, a substituted or unsubstituted (C 1 -C 18 ) aminoalkylaminocarbonyl, a substituted or unsubstituted (C 1 -C 18 ) aminoalkylcarboxyamido, a a substituted or unsubstituted (C 1 -C 18 ) quaternary ammonium alkylcarboxy, a substituted or unsubstituted (C 1 -C 18 ) 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, and a substituted or unsubstituted (C 1 -C 18 ) guanidinoalkylcarboxy.   
     
     
         10 . 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, an unsubstituted (C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) hydroxyalkyl, unsubstituted (C 1 -C 18 ) alkyloxy-(C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) alkylcarboxy-(C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 )alkyl, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, an unsubstituted (C 1 -C 18 ) aminoalkyl, an unsubstituted aryl, an unsubstituted arylamino-(C 1 -C 18 ) alkyl, oxo, an unsubstituted (C 1 -C 18 ) aminoalkyloxy, an unsubstituted (C 1 -C 18 ) amino alkyloxy-(C 1 -C 18 ) alkyl, an unsubstituted (C 1 -C 18 ) aminoalkylcarboxy, an unsubstituted (C 1 -C 18 ) aminoalkylaminocarbonyl, an unsubstituted (C 1 -C 18 ) aminoalkylcarboxamido, an unsubstituted di(C 1 -C 18  alkyl)aminoalkyl, unsubstituted C-carboxy(C 1 -C 18 )alkyl, unsubstituted (C 1 -C 18 ) guanidinoalkyloxy, unsubstituted (C 1 -C 18 ) quaternary ammonium alkylcarboxy, and unsubstituted (C 1 -C 18 ) guanidinoalkyl carboxy;   R 5 , R 8 , R 9 , R 10 , R 13 , and R 14  are independently selected from the group consisting of hydrogen, hydroxyl, an unsubstituted (C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) hydroxyalkyl, unsubstituted (C 1 -C 18 ) alkyloxy-(C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) alkylcarboxy-(C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 )alkyl, (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, an unsubstituted (C 1 -C 18 ) aminoalkyl, an unsubstituted aryl, an unsubstituted arylamino-(C 1 -C 18 ) alkyl, oxo, an unsubstituted (C 1 -C 18 ) aminoalkyloxy, an unsubstituted (C 1 -C 18 ) aminoalkyloxy-(C 1 -C 18 ) alkyl, an unsubstituted (C 1 -C 18 ) aminoalkylcarboxy, an unsubstituted (C 1 -C 18 ) aminoalkylaminocarbonyl, an unsubstituted (C 1 -C 18 ) aminoalkylcarboxamido, an unsubstituted di(C 1 -C 18  alkyl)aminoalkyl, unsubstituted C-carboxy(C 1 -C 18 )alkyl, unsubstituted (C 1 -C 18 ) guanidinoalkyloxy, unsubstituted (C 1 -C 18 ) quaternary ammonium alkylcarboxy, and unsubstituted (C 1 -C 18 ) guanidinoalkyl carboxy;   provided that at least two or three 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 of hydrogen, hydroxyl, an unsubstituted (C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) hydroxyalkyl, unsubstituted (C 1 -C 18 ) alkyloxy-(C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) alkylcarboxy-(C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 )alkyl, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, an unsubstituted (C 1 -C 18 ) aminoalkyl, an unsubstituted aryl, an unsubstituted arylamino-(C 1 -C 18 ) alkyl, oxo, an unsubstituted (C 1 -C 18 ) aminoalkyloxy, an unsubstituted (C 1 -C 18 ) aminoalkyloxy-(C 1 -C 18 ) alkyl, an unsubstituted (C 1 -C 18 ) aminoalkylcarboxy, an unsubstituted (C 1 -C 18 ) aminoalkylaminocarbonyl, an unsubstituted (C 1 -C 18 ) aminoalkylcarboxamido, an unsubstituted di(C 1 -C 18  alkyl)aminoalkyl, unsubstituted C-carboxy(C 1 -C 18 )alkyl, unsubstituted (C 1 -C 18 ) guanidinoalkyloxy, unsubstituted (C 1 -C 18 ) quaternary ammonium alkylcarboxy, and unsubstituted (C 1 -C 18 ) guanidinoalkyl carboxy.   
     
     
         11 . The method of  claim 1 , wherein the compound of Formula (I) or pharmaceutically acceptable salt thereof comprises a compound of Formula (IA): 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method of  claim 11 , wherein
 R 3 , R 7 , R 12 , and R 18  are independently selected from the group consisting of hydrogen, an unsubstituted (C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) hydroxyalkyl, unsubstituted (C 1 -C 18 ) alkyloxy-(C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) alkylcarboxy-(C 1 -C 18 ) alkyl, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 )alkyl, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, an unsubstituted (C 1 -C 18 ) aminoalkyl, an unsubstituted arylamino-(C 1 -C 18 ) alkyl, an unsubstituted (C 1 -C 18 ) aminoalkyloxy, an unsubstituted (C 1 -C 18 ) aminoalkyloxy-(C 1 -C 18 ) alkyl, an unsubstituted (C 1 -C 18 ) aminoalkylcarboxy, an unsubstituted (C 1 -C 18 ) aminoalkylaminocarbonyl, an unsubstituted (C 1 -C 18 ) aminoalkylcarboxamido, an unsubstituted di(C 1 -C 18  alkyl)amino alkyl, unsubstituted C-carboxy(C 1 -C 18 )alkyl, unsubstituted (C 1 -C 18 ) guanidinoalkyloxy, unsubstituted (C 1 -C 18 ) quaternary ammonium alkylcarboxy, and unsubstituted (C 1 -C 18 ) guanidinoalkyl carboxy; and   R 1 , R 2 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , and R 17  are independently selected from the group consisting of hydrogen and unsubstituted (C 1 -C 6 ) alkyl.   
     
     
         13 . The method of  claim 11 , wherein R 3 , R 7 , R 12 , and R 18  are independently selected from the group consisting of hydrogen, an unsubstituted (C 1 -C 6 ) alkyl, unsubstituted (C 1 -C 6 ) hydroxyalkyl, unsubstituted (C 1 -C 16 ) alkyloxy-(C 1 -C 5 ) alkyl, unsubstituted (C 1 -C 16 ) alkylcarboxy-(C 1 -C 5 ) alkyl, unsubstituted (C 1 -C 16 ) alkylamino-(C 1 -C 5 )alkyl, (C 1 -C 16 ) alkylamino-(C 1 -C 5 ) alkylamino, unsubstituted (C 1 -C 16 ) alkylamino-(C 1 -C 16 ) alkylamino-(C 1 -C 5 ) alkylamino, an unsubstituted (C 1 -C 16 ) aminoalkyl, an unsubstituted arylamino-(C 1 -C 5 ) alkyl, an unsubstituted (C 1 -C 5 ) aminoalkyloxy, an unsubstituted (C 1 -C 16 ) amino alkyloxy-(C 1 -C 5 ) alkyl, an unsubstituted (C 1 -C 5 ) aminoalkylcarboxy, an unsubstituted (C 1 -C 5 ) aminoalkylaminocarbonyl, an unsubstituted (C 1 -C 5 ) aminoalkylcarboxamido, an unsubstituted di(C 1 -C 5  alkyl)amino-(C 1 -C 5 ) alkyl, unsubstituted C-carboxy(C 1 -C 18 )alkyl, unsubstituted (C 1 -C 5 ) guanidinoalkyloxy, unsubstituted (C 1 -C 16 ) quaternary ammonium alkylcarboxy, and unsubstituted (C 1 -C 16 ) guanidinoalkylcarboxy; 
     
     
         14 . The method of  claim 11 , wherein R 1 , R 2 , R 4 , R 5 , R 6 , R 8 , R 10 , R 11 , R 14 , R 16 , and R 17  are each hydrogen; and R 9  and R 13  are each methyl. 
     
     
         15 . The method of  claim 11 , wherein R 3 , R 7 , R 12 , and R 18  are independently selected from the group consisting of aminoalkyloxy; aminoalkylcarboxy; alkylaminoalkyl; alkoxycarbonylalkyl; alkylcarbonylalkyl; di(alkyl)amino alkyl; C-carboxyalkyl; alkoxycarbonylalkyl; and alkylcarboxyalkyl. 
     
     
         16 . The method of  claims 11 , wherein
 R 3 , R 7 , and R 12  are independently selected from the group consisting of aminoalkyloxy and aminoalkylcarboxy; and   R 18  is selected from the group consisting of alkylaminoalkyl; alkoxycarbonylalkyl; alkylcarbonyloxyalkyl; di(alkyl)aminoalkyl; C-carboxyalkyl; alkylaminoalkyl; alkyoxycarbonylalkyl; and alkylcarboxyalkyl.   
     
     
         17 . The method of  claim 11 , wherein R 3 , R 7 , and R 12  are the same. 
     
     
         18 . The method of  claim 11 , wherein R 3 , R 7 , and R 12  are aminoalkyloxy or aminoalkylcarboxy. 
     
     
         19 . The method of  claim 11 , wherein R 18  is alkylaminoalkyl, alkoxycarbonylalkyl, di(alkyl)aminoalkyl, or alkylcarboxyalkyl. 
     
     
         20 . The method of  claim 11 , wherein R 3 , R 7 , R 12 , and R 18  are independently selected from the group consisting of amino-C 3 -alkyloxy; amino-C 3 -alkyl-carboxy; C 8 -alkylamino-C 5 -alkyl; C 8 -alkoxy-carbonyl-C 4 -alkyl; C 8 -alkyl-carbonyl-C 4 -alkyl; di-(C 5 -alkyl)amino-C 5 -alkyl; C-carboxy-C 4 -alkyl; C 13 -alkylamino-C 5 -alkyl; C 6 -alkoxy-carbonyl-C 4 -alkyl; and C 6 -alkyl-carboxy-C 4 -alkyl. 
     
     
         21 . The method of  claim 1 , wherein the compound of Formula (I) or pharmaceutically acceptable salt thereof comprises a compound of Formula (IB) or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 21 , wherein the compound of Formula (IB) is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         23 . The method of  claim 21 , wherein the compound of Formula (IB) or pharmaceutically acceptable salt thereof is 
       
         
           
           
               
               
           
         
       
     
     
         24 . The method of  claim 1 , wherein the pharmaceutically acceptable salt is a hydrochloride salt or a tri-hydrochloride salt. 
     
     
         25 . 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:   
       
         
           
           
               
               
           
         
       
       wherein
 rings A, B, C, and D are independently saturated; 
 m, n, p, and q are independently 0 or 1; 
 R 1 , R 2 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , and R 17  are independently selected from the group consisting of hydrogen and substituted or unsubstituted (C 1 -C 6 ) alkyl, provided that not all of R 1 , R 2 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 , R 11 , R 13 , R 14 , R 15 , R 16 , and R 17  are hydrogen; 
 R 3 , R 7 , R 12 , and R 18  are independently selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) hydroxyalkyl, substituted or unsubstituted (C 1 -C 18 ) alkyloxy-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) alkylcarboxy-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, substituted or unsubstituted (C 1 -C 18 ) alkylamino -(C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, substituted or unsubstituted (C 1 -C 18 ) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) haloalkyl, substituted or unsubstituted (C 2 -C 6 ) alkenyl, substituted or unsubstituted (C 2 -C 6 ) alkynyl, oxo, substituted or unsubstituted (C 1 -C 18 ) aminoalkyloxy, substituted or unsubstituted (C 1 -C 18 ) amino alkyloxy-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) aminoalkylcarboxy, substituted or unsubstituted (C 1 -C 18 ) amino alkylaminocarbonyl, substituted or unsubstituted (C 1 -C 18 ) amino alkylcarboxamido, substituted or unsubstituted di(C 1 -C 18  alkyl) aminoalkyl, 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)—, substituted or unsubstituted (C 1 -C 18 ) azidoalkyloxy, substituted or unsubstituted (C 1 -C 18 ) cyanoalkyloxy, substituted or unsubstituted (C 1 -C 18 ) guanidinoalkyloxy, substituted or unsubstituted (C 1 -C 18 ) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C 1 -C 18 ) guanidinoalkyl carboxy, where Q 5  is a side chain of an amino acid; 
 provided that at least two of R 3 , R 7 , R 12  and R 18  are independently selected from the group consisting of aminoalkyloxy, aminoalkylcarboxy, alkylaminoalkyl, and di(alkyl)aminoalkyl. 
 
     
     
         26 . A method for treating or preventing clinical mastitis in a lactating dairy cow, comprising:
 injecting an effective amount of 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 comprises:
 at least one solvent, co-solvent, adjuvant, excipient, or emulsifying agent selected from the group consisting of antioxidants, ascorbic acid, chelating agents, EDTA, carbohydrates, dextrin, hydroxyalkylcellulose, hydroxyalkylmethylcellulose, stearic acid, oils, water, saline, wetting agents, emulsifying agents, pH buffering substances, liposomes, compounds containing hydroxyl groups, alcohols, ethanol, isopropyl alcohol, glycols, propylene glycol, polyethyleneglycol, polypropylene glycol, glycol ether, glycerol, polyoxyethylene alcohols, polyoxyethylene fatty acid esters, soya lecithin, oleic acid, sorbitan esters, sorbitan trioleate, and polyvinylpyrrolidone; and 
   a compound having a sterol backbone of Formula (IB) or a pharmaceutically acceptable salt thereof:   
       
         
           
           
               
               
           
         
       
       where,
 R 3 , R 7 , and R 12  each include a cationic moiety attached to the sterol backbone via a hydrolysable linkage and R 18  is selected from the group consisting of hydrogen, hydroxyl, substituted or unsubstituted (C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) hydroxyalkyl, substituted or unsubstituted (C 1 -C 18 ) alkyloxy-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) alkylcarboxy-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, substituted or unsubstituted (C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino-(C 1 -C 18 ) alkylamino, substituted or unsubstituted (C 1 -C 18 ) aminoalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylamino-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) haloalkyl, substituted or unsubstituted (C 2 -C 6 ) alkenyl, substituted or unsubstituted (C 2 -C 6 ) alkynyl, oxo, substituted or unsubstituted (C 1 -C 18 ) aminoalkyloxy, substituted or unsubstituted (C 1 -C 18 ) aminoalkyloxy-(C 1 -C 18 ) alkyl, substituted or unsubstituted (C 1 -C 18 ) aminoalkylcarboxy, substituted or unsubstituted (C 1 -C 18 ) amino alkylaminocarbonyl, substituted or unsubstituted (C 1 -C 18 ) amino alkylcarboxamido, substituted or unsubstituted di(C 1 -C 18  alkyl) aminoalkyl, 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)—, substituted or unsubstituted (C 1 -C 18 ) azidoalkyloxy, substituted or unsubstituted (C 1 -C 18 ) cyanoalkyloxy, substituted or unsubstituted (C 1 -C 18 ) guanidinoalkyloxy, substituted or unsubstituted (C 1 -C 18 ) quaternary ammonium alkylcarboxy, and substituted or unsubstituted (C 1 -C 18 ) guanidinoalkyl carboxy, where Q 5  is a side chain of an amino acid. 
 
     
     
         27 . The method of  claim 26 , wherein the compound of Formula (IB) is selected from the group of: 
       
         
           
           
               
               
           
         
       
     
     
         28 . The method of  claim 25 , wherein the compound of Formula (IB) is