Organosilanes for the treatment of infections
Organosilicon quaternary ammonium compounds, their formulations, including lyophilized solid formulations, and methods of use to treat infections in humans and animals.
1. A quaternary ammonium compound of Formula:
wherein the quaternary amine has a balancing pharmaceutically acceptable anion;
wherein
m is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17;
n is 0, 1, or 2;
Q is —CR 4 R 4 —;
R 1 and R 2 are independently at each occurrence selected from the group consisting of hydrogen and ethyl;
R 4 is independently at each occurrence selected from the group consisting of hydrogen, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, halogen, and haloC 1-3 alkyl;
R 6 is independently at each occurrence selected from the group consisting of hydrogen, hydroxy, and C 1 -C 6 alkoxy;
B is independently at each occurrence selected from the group consisting of
and
and
M is hydrogen, sodium, potassium, cesium, or lithium.
2. The quaternary ammonium compound of claim 1 , wherein at least two R 4 substituents are hydrogen.
3. The quaternary ammonium compound of claim 1 , wherein the balancing anion is selected from the group consisting of chloride, fluoride, iodide, bromide, hydroxide, chlorite, chlorate, formate, acetate, lactate, benzoate, and salicylate anion.
4. The quaternary ammonium compound of claim 1 , wherein B is
5. The quaternary ammonium compound of claim 1 , wherein B is
6. The quaternary ammonium compound of claim 5 , wherein M is selected from the group consisting of sodium and potassium.
7. The quaternary ammonium compound of claim 1 of formula:
8. The quaternary ammonium compound of claim 1 that is a zwitterion.
9. The quaternary ammonium compound of claim 1 of formula:
10. The quaternary ammonium compound of claim 1 of formula:
11. The quaternary ammonium compound of claim 1 , wherein the compound is a lyophilized powder.
12. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.
13. The pharmaceutical composition of claim 12 , wherein the composition is suitable for topical delivery.
14. The pharmaceutical composition of claim 13 , wherein the composition is in the form of a liquid, cream, gel, spray, foam, wipe, powder, paste, or solid.
15. A method of treating a topical infection, wherein the treatment comprises administering an effective amount of a compound of claim 1 to a host in need thereof.
16. The method of claim 15 , wherein the host is human.
17. The method of claim 15 , wherein the host is a dog, cat, horse, or bovine.
18. The method of claim 15 , wherein the infection is bacterial, fungal, amoeba, or viral.
19. The method of claim 18 , wherein the infection is caused by Staphylococcus aureus, Pseudomonas aeruginosa, Fusarium, Aspergillus, Candida albicans, Curvularia spp., Haemophilus influenzae , or Acanthamoebic keratitis.
20. The method of claim 15 , wherein the infection is an ear infection; wherein the infection is an outer ear (otitis externa) infection, a middle ear (otitis media) infection, or an inner ear (otitis interna) infection; a nail infection, an infection in a chronic wound, or an infection that causes periodontal disease.