HEMOSTATIC WOUND DRESSING
Hemostatic wound dressings that include cationic polymers and related hydrogels, methods for making and using the wound dressings.
1 . A wound dressing, comprising a cationic polymer comprising:
(a) polymer backbone;
(b) a plurality of cationic centers, each cationic center covalently coupled to the polymer backbone by a first linker;
(c) a counter ion associated with each cationic center; and
(d) a hydrolyzable group covalently coupled to each cationic center through a second linker, wherein the hydrolyzable group is hydrolyzable to an anionic center to provide a zwitterionic polymer having the anionic center covalently coupled to the cationic center through the second linker.
2 . The wound dressing of claim 1 , wherein the polymer has the formula:
PB-(L 1 -N + (R a )(R b )-L 2 -A(=O)—OR c ) n (X − ) n
wherein
PB is the polymer backbone having n pendant groups L 1 -N + (R a )(R b )-L 2 -A(=O)—OR c );
N + is the cationic center;
R a and R b are independently selected from hydrogen, alkyl, and aryl;
A(=O)—OR c is the hydrolyzable group, wherein A is selected from the group consisting of C, S, SO, P, or PO, and R c is an alkyl, aryl, acyl, or silyl group that may be further substituted with one or more substituents;
L 1 is a linker that covalently couples the cationic center to the polymer backbone;
L 2 is a linker that covalently couples the cationic center to the hydrolyzable group;
X − is the counter ion associated with the cationic center; and
n is an integer from about 10 to about 10,000.
3 . The wound dressing of claim 1 , wherein the counter ion is a hydrophobic organic counter ion.
4 . The wound dressing of claim 1 , wherein the counter ion is selected from the group consisting of C1-C20 carboxylates and C1-C20 alkylsulfonates.
5 . The wound dressing of claim 1 , wherein the counter ion is a therapeutic agent.
6 . The wound dressing of claim 1 , wherein the counter ion is selected from the group consisting of an antimicrobial, an antibacterial, and an antifungal agent.
7 . The wound dressing of claim 1 , wherein the counter ion is selected from the group consisting of amino acids, proteins, and peptides.
8 . The wound dressing of claim 1 , wherein the hydrolyzable group releases a hydrophobic organic group on hydrolysis.
9 . The wound dressing of claim 1 , wherein the hydrolyzable group releases a C1-C20 carboxylate on hydrolysis.
10 . The wound dressing of claim 1 , wherein the hydrolyzable group releases a therapeutic agent on hydrolysis.
11 . The wound dressing of claim 1 , wherein the hydrolyzable group releases an antimicrobial, an antibacterial, or an antifungal agent on hydrolysis.
12 . The wound dressing of claim 1 , wherein the cationic center is selected from the group consisting of ammonium, imidazolium, triazaolium, pyridinium, morpholinium, oxazolidinium, pyrazinium, pyridazinium, pyrimidinium, piperazinium, and pyrrolidinium.
13 . The wound dressing of claim 2 , wherein R a and R b are independently selected from the group consisting of C1-C10 straight chain and branched alkyl groups.
14 . The wound dressing of claim 2 , wherein L 1 is selected from the group consisting of —C(═O)O—(CH 2 ) n — and —C(═O)NH—(CH 2 ) n —, wherein n is an integer from 1 to 20.
15 . The wound dressing of claim 2 , wherein L 2 is —(CH 2 ) n —, where n is an integer from 1 to 20.
16 . The wound dressing of claim 2 , wherein A is selected from the group consisting of C, SO, and PO.
17 . The wound dressing of claim 2 , wherein R c is C1-C20 alkyl.
18 . The wound dressing of claim 2 , wherein R c is an amino acid.
19 . The wound dressing of claim 2 , wherein X − is selected from the group consisting of halide, carboxylate, alkylsulfonate, sulfate; nitrate, perchlorate, tetrafluoroborate, hexafluorophosphate, trifluoromethylsulfonate, bis(trifluoromethylsulfonyl)amide, lactate, and salicylate.
20 . The wound dressing of claim 1 , wherein the cationic polymer is a hydrogel.
21 . The wound dressing of claim 20 , wherein the hydrogel is a chemical hydrogel.
22 . The wound dressing of claim 20 , wherein the hydrogel is an interpenetrating network hydrogel.
23 . The wound dressing of claim 20 , wherein the hydrogel comprises first and second polymers, wherein the first polymer is a cationic polymer hydrolyzable to provide a zwitterionic polymer, and wherein the second polymer is a zwitterionic polymer.
24 . The wound dressing of claim 23 , wherein the first and second polymers are crosslinked.
25 . The wound dressing of claim 23 , wherein the hydrogel is prepared by copolymerizing a first cationic monomer having a hydrolyzable group and second zwitterionic monomer.
26 . The wound dressing of claim 24 , wherein the hydrogel is prepared by copolymerizing a first cationic monomer having a hydrolyzable group and second zwitterionic monomer.
27 . The wound dressing of claim 25 , wherein the hydrogel is prepared by polymerizing the first monomer to provide a cationic polymer having hydrolyzable groups, adding the second monomer to the cationic polymer, and polymerizing the second monomer in the presence of the cationic polymer.
28 . The wound dressing of claim 25 , wherein the hydrogel is prepared by polymerizing the second monomer to provide a zwitterionic polymer, adding the first monomer having a hydrolyzable group to the zwitterionic polymer, and polymerizing the first monomer in the presence of the zwitterionic polymer.
29 . The wound dressing of claim 20 , wherein the hydrogel is prepared by polymerizing a first cationic monomer having a hydrolyzable group to provide a cationic polymer having hydrolyzable groups, and hydrolyzing at least a portion of the hydrolyzable groups of the cationic polymer.
30 . A method for treating a wound, comprising applying the wound dressing of claim 1 to a wound.