Hydrophobic ceragenin compounds and devices incorporating same

1. A hydrophobic cationic steroidal anti-microbial (CSA) compound comprising:

a sterol structure comprising four fused carbon rings;

at least one cationic substituent attached to each of at least three of the four fused carbon rings so as to form an amphiphilic compound having a hydrophobic sterol face and a hydrophilic cationic face;

at least one hydrophobic substituent attached to at least one of the fused carbon rings;

wherein the CSA compound has a CLogP value of at least 6.5 and a structure as in Formula (1):

wherein

q=0 and p=1;

R 3 , R 7 and R 12 independently include a cationic group;

R 17 is a hydrophobic substituent selected from a trimethylsilane and a hydrophobic substituent which includes a heteroatom and a hydrocarbon group of at least 9 carbon atoms and fewer than 16 carbon atoms distal to the heteroatom; and

R 1 , R 2 , R 4 -R 6 , R 8 -R 16 are any substituent, with the proviso that R 16 does not form a fused ring with R 17 .

2. A hydrophobic CSA compound as in claim 1 , wherein the CLogP value is at least 7.5.

3. A hydrophobic CSA compound as in claim 1 , wherein the ClogP value is at least 8.5.

4. A hydrophobic CSA compound as in claim 1 , wherein the hydrophobic substituent includes a trimethylsilane.

5. A hydrophobic CSA compound as in claim 1 , wherein the hydrophobic substituent is attached at the C17 position of the steroid structure.

6. A hydrophobic CSA compound as in claim 1 , wherein the hydrophobic substituent includes a heteroatom and a hydrocarbon group of at least 9 carbon atoms and fewer than 16 carbon atoms distal to the heteroatom.

7. A hydrophobic CSA compound as in claim 6 , wherein the hydrocarbon group is a straight chain hydrocarbon.

8. A hydrophobic CSA compound as in claim 7 , wherein the hydrocarbon group includes from 11 to 15 carbon atoms.

9. A hydrophobic CSA as in claim 1 , wherein the CSA compound is selected from the group consisting of:

10. A device comprising a polymer structure and the hydrophobic CSA compound of claim 1 incorporated into the polymer structure with non-covalent interactions.

11. The device of claim 10 , wherein the polymer structure includes polyvinyl alcohol, sodium polyacrylate, an acrylate polymer, polyethylene oxide, polyAMPS, polyvinylpyrrolidone, polyacrylamide, silicone, agarose, methylcellulose, hyaluronan, or a combination thereof.

12. The device of claim 10 , wherein the device comprises a medical device selected from the group consisting of bone implant, bone pin, bone screw, tissue graft, endotracheal tube, coronary stent, peripheral stent, catheter, arterio-venous graft, by-pass graft, pacemaker or defibrillator lead, anastomotic clip, arterial closure device, patent foramen ovale closure device, and drug delivery balloon.

13. The device of claim 10 , wherein the polymer is coated on a substrate.

14. The device of claim 10 , wherein the hydrophobic CSA compound elutes from the polymer in excess saline water at a rate of 0.1-100 μg/ml, 0.5-50 μg/ml, or 1-10 μg/ml at 3 days, one week, or one month and/or over a period of 3 days, one week and/or one month.

15. A hydrophobic cationic steroidal anti-microbial (CSA) compound comprising:

a sterol structure comprising four fused carbon rings;

at least one cationic substituent attached to each of at least three of the four fused carbon rings so as to form an amphiphilic compound having a hydrophobic sterol face and a hydrophilic cationic face;

at least one hydrophobic substituent attached to at least one of the fused carbon rings;

wherein the CSA compound has a CLogP value of at least 6.5 and a structure selected from the group consisting of:

16. A device comprising a polymer structure and the hydrophobic CSA compound of claim 15 incorporated into the polymer structure with non-covalent interactions.

17. The device of claim 16 , wherein the device comprises a medical device selected from the group consisting of bone implant, bone pin, bone screw, tissue graft, endotracheal tube, coronary stent, peripheral stent, catheter, arterio-venous graft, by-pass graft, pacemaker or defibrillator lead, anastomotic clip, arterial closure device, patent foramen ovale closure device, and drug delivery balloon.

18. A medical device comprising a polymer structure and a hydrophobic cationic steroidal anti-microbial (CSA) compound incorporated into the polymer with non-covalent interactions, the CSA compound comprising:

a sterol structure comprising four fused carbon rings;

at least one cationic substituent attached to each of at least three of the four fused carbon rings so as to form an amphiphilic compound having a hydrophobic sterol face and a hydrophilic cationic face;

at least one hydrophobic substituent attached to at least one of the fused carbon rings;

wherein the CSA compound has a CLogP value of at least 6.5 and a structure as in Formula (1):

wherein

q=0 and p=1;

R 3 , R 7 , and R 12 independently include a cationic group;

R 17 is a hydrophobic substituent; and

R 1 , R 2 , R 4 -R 6 , R 8 -R 16 are any substituent, with the proviso that R 16 does not form a fused ring with R 17 .

19. The medical device of claim 18 , wherein the polymer structure includes polyvinyl alcohol, sodium polyacrylate, an acrylate polymer, polyethylene oxide, polyAMPS, polyvinylpyrrolidone, polyacrylamide, silicone, agarose, methylcellulose, hyaluronan, or a combination thereof.

20. The medical device of claim 18 , wherein the medical device is selected from the group consisting of bone implant, bone pin, bone screw, tissue graft, endotracheal tube, coronary stent, peripheral stent, catheter, arterio-venous graft, by-pass graft, pacemaker or defibrillator lead, anastomotic clip, arterial closure device, patent foramen ovale closure device, and drug delivery balloon.