Antimicrobial and Antiviral Compounds and Methods for Their Use
The present invention provides protonated compounds having antiviral and antimicrobial activity. The invention also provides antimicrobial compositions comprising protonated compounds of the invention. The protonated compounds of the invention provide efficacious antimicrobial activity against resistant strains of bacteria and opportunistic fungi. The invention also provides antiviral compositions comprising compounds of the invention. Viruses that may be treated by compositions of the invention include, but are not limited to, HIV, HSV, CMV, HBV, HCV and influenza virus.
1 . A liposomal composition comprising the compound of Formula 1
Wherein X and Y are independently
CH 3 CH 2 CH 2 CH 2 —,
CH 3 CH 2 CH 2 —,
CH 3 CH 2 —,
HO—CH 2 CH 2 CH 2 CH 2 —,
XO—CH 2 CH 2 CH 2 CH 2 —, or
YO—CH 2 CH 2 CH 2 CH 2 —;
wherein Z is H, purine, modified purine, pyrimidine, or modified pyrimidine;
wherein A is H, alkyl, alkoxy, alkyl(O-alkyl), aryl, alkenyl, alkanol, phenol, or enol; and a lipid.
2 . The liposomal composition of claim 1 further comprising one or more excipients.
3 . The liposomal composition of claim 1 wherein said compound is a protonated compound.
4 . The liposomal composition of claim 1 wherein X and Y are independently selected from the group consisting of CH 3 CH 2 CH 2 CH 2 — and HO—CH 2 CH 2 CH 2 CH 2 —; Z is selected from the group consisting of thymidine and H; and A is selected from the group consisting of H and OCH 3 .
5 . The liposomal composition of claim 1 , wherein X and Y are CH 3 CH 2 CH 2 CH 2 —; Z is thymidine; and A is H.
6 . The liposomal composition of claim 1 , wherein said lipid comprises neutral lipids, cholesterol, and methoxy-terminated polyethylene glycol.
7 . The liposomal composition of claim 1 , wherein the ratio of said lipid to said compound of Formula 1 is about 9:1 w/w % to about 3:1 w/w %.
8 . The liposomal composition of claim 1 , comprising liposomes having a particle size is from about 60 nm to about 110 nm.
9 . The liposomal composition of claim 1 , wherein the ratio of said lipid to said compound of Formula 1 is about 1:5 w/w % to about 1:3 w/w %; and further comprises liposomes having a particle size of about 80 nm to about 100 nm.
10 . The liposomal composition of claim 1 , wherein said lipid comprises partially hydrogenated soy phosphatidylcholine, cholesterol, and methoxy-terminated polyethylene glycol.
11 . The liposomal composition of claim 9 wherein said liposome composition comprises partially hydrogenated soy phosphatidylcholine, cholesterol, and methoxy-terminated polyethylene glycol in a ratio of about 50 to about 60 w/w %: about 30 to about 40 w/w %: about 5 to about 10 w/w %.
12 . The liposomal composition of claim 1 , wherein said lipid comprises partially hydrogenated soy phosphatidylcholine, cholesterol, methoxy-terminated polyethylene glycol in a ratio of about 56:38:6 w/w %; and
said liposomal composition has a lipid to drug ratio of about 4 to about 1 w/w % and has a liposomal particle size of about 80 nm to about 100 nm.
13 . A compound of Formula 2
14 . A compound of Formula 3
15 . A compound of Formula 4
16 . A method of treating a mammal suffering from a bacterial infection consisting of administering to said mammal an effective amount of a liposomal composition comprising a compound of Formula 1
Wherein X and Y are independently
CH 3 CH 2 CH 2 CH 2 —,
CH 3 CH 2 CH 2 —,
CH 3 CH 2 —,
HO—CH 2 CH 2 CH 2 CH 2 —,
XO—CH 2 CH 2 CH 2 CH 2 —, or
YO—CH 2 CH 2 CH 2 CH 2 —;
wherein Z is H, purine, modified purine, pyrimidine, or modified pyrimidine;
wherein A is H, alkyl, alkoxy, alkyl(O-alkyl), aryl, alkenyl, alkanol, phenol, or enol; and,
a lipid.
17 . The method of claim 16 wherein the liposomal composition further comprises one or more excipients.
18 . The method of claim 16 wherein said bacterial infection is caused by Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Mycobacterium and Escherichia coli, Aerococcus, Listeria, Streptomyces, Chlamydia, Lactobacillus, Eubacterium, Arachnid, Mycobacterium, Peptostreptococcus, Corynebacterium, Erysipelothrix, Dermatophilus, Rhodococcus, Pseudomonas, Streptococcus, Bacillus, Peptococcus, Pneumococcus, Micrococcus, Neisseria, Klebsiella, Kurthia, Nocardia, Serratia, Rothia, Escherichia, Propionibacterium, Actinomyces, Helicobacter, Enterococcus, Shigella, Vibrio, Clostridium, Salmonella, Yersinia , or Haemophilus.
19 . The method of claim 16 wherein the liposomal composition is administered topically.
20 . The method of claim 16 wherein the liposomal composition is administered orally.
21 . The method of claim 16 wherein the liposomal composition is administered via aerosol.
22 . A method of treating a mammal suffering from a fungal infection consisting of administering an effective amount of a liposomal composition comprising a compound of Formula 1
Wherein X and Y are independently
CH 3 CH 2 CH 2 CH 2 —,
CH 3 CH 2 CH 2 —,
CH 3 CH 2 —,
HO—CH 2 CH 2 CH 2 CH 2 —,
XO—CH 2 CH 2 CH 2 CH 2 —, or
YO—CH 2 CH 2 CH 2 CH 2 —;
wherein Z is H, purine, modified purine, pyrimidine, or modified pyrimidine;
wherein A is H, alkyl, alkoxy, alkyl(O-alkyl), aryl, alkenyl, alkanol, phenol, or enol; and,
a lipid.
23 . The method of claim 22 wherein the liposomal composition further comprises one or more excipients.
24 . The method of claim 22 wherein said fungal infection is caused by Trichophyton, Epidermophyton, Microsporum, Candida, Pityrosporum, Trichophyton , or Epidermophyton.
25 . The method of claim 22 wherein the liposomal composition is administered topically.
26 . The method of claim 22 wherein the liposomal composition is administered orally.
27 . The method of claim 22 wherein the liposomal composition is administered via aerosol.
28 . A method of treating a mammal suffering from a viral infection consisting of administering an effective amount of a liposomal composition comprising a compound of Formula 1
Wherein X and Y are independently
CH 3 CH 2 CH 2 CH 2 —,
CH 3 CH 2 CH 2 —,
CH 3 CH 2 —,
HO—CH 2 CH 2 CH 2 CH 2 —,
XO—CH 2 CH 2 CH 2 CH 2 , or
YO—CH 2 CH 2 CH 2 CH 2 —;
wherein Z is H, purine, modified purine, pyrimidine, or modified pyrimidine;
wherein A is H, alkyl, alkoxy, alkyl(O-alkyl), aryl, alkenyl, alkanol, phenol, or enol; and
a lipid.
29 . The method of claim 28 wherein the liposomal composition further comprises one or more excipients.
30 . The method of claim 28 wherein said viral infection is caused by HIV, HSV, CMV, HBV, HCV or influenza virus.
31 . The method of claim 28 wherein the pharmaceutical composition is administered topically.
32 . The method of claim 28 wherein the pharmaceutical composition is administered orally.
33 . The method of claim 28 wherein the pharmaceutical composition is administered via aerosol.