PHOSPHONATE-CONTAINING POLYMERS FOR VIRULENCE SUPPRESSION
Medical compositions and methods of suppressing microbial virulence are provided. By suppressing virulence, administration and/or application of the medical compositions can be used to prevent, mitigate, or treat a microbial infection. More specifically, the medical compositions include a phosphonate-containing polymer. The phosphonate-containing polymers can suppress the expression of various virulence factors without destroying all microbes that may be present.
1 . A medical composition comprising:
a phosphonate-containing polymer having at least 0.8 mmoles phosphonate per gram of the phosphonate-containing polymer, wherein the phosphonate-containing polymer is a polymerized reaction product of a monomer composition comprising a first monomer of Formula (I) or a salt thereof
wherein
each R 1 is independently hydrogen, aryl, aralkyl, or alkaryl;
R 2 is hydrogen or methyl;
X is oxy or —NH—;
R 3 is an alkylene or a heteroalkylene with one or more oxygen heteroatoms;
R 4 is alkylene;
Q is —(CO)—O—, —NR 5 —(CO)—NR 5 —, —(CO)—NR 5 —, or —O—(CO)—NR 5 —;
R 5 is hydrogen or alkyl,
m is equal to 0 or 1; and
wherein the medical composition is suitable for administration for preventing, mitigating, or treating a microbial infection.
2 . (canceled)
3 . The medical composition of claim 1 , wherein the first monomer of Formula (I) is a monomer of Formula (I-C) or a salt thereof
wherein X
1 is oxy or —NR 5 —.
4 . The medical composition of claim 1 , wherein the first monomer of Formula (I) is a monomer of Formula (I-D) or a salt thereof
wherein X
1 is oxy or —NR 5 —.
5 . The medical composition of claim 1 , wherein the monomer composition further comprises a second monomer that is hydrophilic and that comprises a) an ethylenically unsaturated group and b) a polar group that is an acidic group or salt thereof, a hydroxyl group, an ether, or a nitrogen-containing group.
6 . The medical composition of claim 1 , wherein the monomer composition further comprises a second monomer that comprises a) ethylenically unsaturated group and 2) a zwitterionic group.
7 . The medical composition of claim 6 , wherein the second monomer is of Formula (III)
wherein
R 6 is hydrogen or methyl;
X 2 is oxy or —NH—;
R 7 is an alkylene or a heteroalkylene having an oxygen heteroatom; and
R 8 and R 9 are a) each independently an alkyl, aryl, aralkyl, or alkaryl, or b) R 8 and R 9 both combine with the nitrogen to which they are both attached to form a heterocyclic ring having 3 to 7 ring members; and
Z - is carboxylate or sulfonate.
8 . The medical composition of claim 5 , wherein the phosphonate-containing polymer comprises greater than 25 mole percent of the first monomer.
9 . The medical composition of claim 5 , wherein the phosphonate-containing polymer comprises greater than 50 mole percent of the first monomer.
10 . The medical composition of claim 1 , wherein the medical composition is a spray, lotion, ointment, gel, solution, emulsion, dispersion, foam, coating, paste, powder, tablet, adhesive, or capsule.
11 . A method of suppressing microbial virulence, the method comprising administrating and/or applying a medical composition of claim 1 .
12 . The method of claim 11 , wherein the first monomer of Formula (I) is a monomer of Formula (I-C), Formula (I-D) or a salt thereof
wherein X
1 is oxy or —NR 5 —.
13 . The method of claim 11 , wherein administering the medical composition suppresses at least one type of virulence factor.
14 . The method of claim 13 , wherein the virulence factor is pyocyanin, pyoverdine, collagenase, or a biofilm.
15 . The method of claim 14 , wherein the biofilm is on a mammalian tissue or on a permanent or degradable implant.
16 . The method of claim 11 , wherein the log reduction of microbes is less than 1.
17 . The method of claim 11 , wherein administrating and/or applying the medical composition prevents, mitigates, or treats a microbial infection.
18 . The method of claim 11 , wherein administrating and/or applying the medical composition comprises applying the medical composition to skin, mucosa, tissue, a wound site, a surgical site, an implant, catheter, suture, or a bone.
19 . The method of claim 11 , wherein administrating and/or applying the medical composition reduces or inhibits virulence of at least one of gram negative Pseudomonas aeruginosa, gram positive Enterococcus faecalis, or gram positive Staphylococcus aureus.