Biocidal polymers
Pharmaceutical compositions containing biocidal co-polymers of poly(styrenes), poly(acrylates), poly(acrylamides), and poly(C 1 -C 6 )alkylene glycols are disclosed, along with methods of using the compositions to treat microbial infections in mammals.
1. A pharmaceutical composition for treating microbial infection in a subject in need thereof, the composition comprising an antimicrobial-effective amount of a compound selected from the group consisting of a polymer of formula -(A) n -, wherein each A is a residue independently selected from the group consisting of:
wherein each R is independently selected from the group consisting of hydrogen; linear or branched C 1 -C 30 -alkyl, alkenyl, or alkynyl; unsubstituted amino-C 1 -C 6 -alkyl; mono-substituted amino-C 1 -C 6 -alkyl; disubstituted amino-C 1 -C 6 -alkyl; mono- or bicyclic aryl; mono- or bicyclic heteroaryl having up to 5 heteroatoms selected from N, O, and S; mono- or bicyclic aryl-C 1 -C 6 -alkyl; and mono- or bicyclic hetero aryl-C 1 -C 6 -alkyl;
wherein each R′ is independently selected from same group recited above for R, provided that one R′ is hydrogen;
wherein n is an integer ≧3; and
wherein at least one A is a residue containing a nitrogen atom, the nitrogen atom being capable of being quaternized, or a pharmaceutically suitable salt thereof.
2. The pharmaceutical composition of claim 1 , further comprising, in combination, a pharmaceutically suitable carrier.
3. The pharmaceutical composition of claim 2 , wherein the pharmaceutically suitable carrier is suitable for oral, rectal, parenteral, nasal or bronchial administration.
4. The pharmaceutical composition of claim 1 , wherein the compound has a molecular weight of between about 4.5 kDa and 11.5 kDa as determined by gel permeation chromatography.
5. The pharmaceutical composition of claim 1 , wherein each R is independently selected from the group consisting of hydrogen; linear or branched C 1 -C 30 -alkyl, alkenyl, or alkynyl; unsubstituted amino-C 1 -C 6 -alkyl; mono-substituted amino-C 1 -C 6 -alkyl; disubstituted amino-C 1 -C 6 -alkyl; mono- or bicyclic aryl; and mono- or bicyclic heteroaryl having up to 5 heteroatoms selected from N, O, and S.
6. The pharmaceutical composition of claim 1 , wherein n is an integer ≧6.
7. A method of preventing and treating microbial infections in a subject in need thereof, the method comprising administering to the subject an effective anti-microbial amount of a compound selected from the group consisting of formula -(A) n -, wherein each “A” is a residue independently selected from the group consisting of:
wherein each R is independently selected from the group consisting of hydrogen; linear or branched C 1 -C 30 -alkyl, alkenyl, or alkynyl; unsubstituted amino-C 1 -C 6 -alkyl; mono-substituted amino-C 1 -C 6 -alkyl; disubstituted amino-C 1 -C 6 -alkyl; mono- or bicyclic aryl; mono- or bicyclic heteroaryl having up to 5 heteroatoms selected from N, O, and S; mono- or bicyclic aryl-C 1 -C 6 -alkyl; and mono- or bicyclic hetero aryl-C 1 -C 6 -alkyl;
wherein each R′ is independently selected from same group recited above for R, provided that one R′ is hydrogen;
wherein n is an integer ≧3; and
wherein at least one A is a residue containing a nitrogen atom, the nitrogen atom being capable of being quaternized, or a pharmaceutically suitable salt thereof.
8. The method of claim 7 , wherein the compound is administered to a mammalian subject.
9. The method of claim 7 , wherein the compound is administered to a human subject.
10. The method of claim 7 , wherein the compound is administered in combination with a pharmaceutically suitable carrier.
11. The method of claim 7 , wherein the compound is administered in combination with a pharmaceutically suitable carrier suitable for oral, rectal, parenteral, nasal or bronchial administration.
12. The method of claim 7 , wherein a compound having a molecular weight of between about 4.5 kDa and 11.5 kDa as determined by gel permeation chromatography is administered to the subject.
13. The method of claim 7 , wherein a compound where each R is independently selected from the group consisting of hydrogen; linear or branched C 1 -C 30 -alkyl, alkenyl, or alkynyl; unsubstituted amino-C 1 -C 6 -alkyl; mono-substituted amino-C 1 -C 6 -alkyl; disubstituted amino-C 1 -C 6 -alkyl; mono- or bicyclic aryl; and mono- or bicyclic heteroaryl having up to 5 heteroatoms selected from N, O, and S is administered to the subject.
14. The method of claim 7 , wherein a compound wherein n is an integer ≧6 is administered to the subject.
15. The method of claim 7 , wherein the amount of compound administered to the subject is sufficient to provide a concentration of the compound, at point of contact with a microbial cell, of from about 1 μM to about 100 μM.
16. The method of claim 7 , wherein the amount of compound administered to the subject is sufficient to provide a concentration of the compound, at point of contact with a microbial cell, of from about 1 μM to about 10 μM.