Wound healing dressings and formulations and methods of use thereof

Abstract

Described herein are dressings, compositions, and formulations for wound healing. These dressings, compositions and formulations contain at least one quaternary ammonium polymer, quaternary ammonium copolymer, quaternary ammonium interpenetrating polymer network, quaternary ammonium polyelectrolyte complex, quaternary ammonium blend or quaternary ammonium composite having broad spectrum antimicrobial properties.

Description

[0001] Inter-references to related applications

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 460399, filed April 19, 2023, which is incorporated herein by reference in its entirety. Technical Field

[0003] Embodiments of this disclosure relate to wound healing dressings and formulations comprising compositions having a quaternary ammonium polymer structure with broad-spectrum antimicrobial properties, and methods of using thereof. Background Technology

[0004] Wound healing is a natural physiological response to tissue damage. Wounds typically heal within four to six weeks. Chronic wounds are those that fail to heal within this timeframe. One factor that can impair healing is bacterial colonization. Wound dressings and / or topical preparations with antimicrobial properties can control, reduce, or prevent infection, thereby promoting wound healing. Summary of the Invention

[0005] In one aspect, this document describes wound dressings comprising polymeric components selected from the group consisting of:

[0006] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0007] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0008] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0009] (iii) Optional polyols;

[0010] (iv) optional water-soluble polymers; and,

[0011] (v) An optional third multifunctional crosslinking agent;

[0012] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0013] (3) Polyethyleneimine intermediates;

[0014] (4) Second adduct; and,

[0015] (5) A combination of the two or more of the above.

[0016] In some embodiments, (i) the first adduct and (ii) the polyethyleneimine intermediate or the second adduct are prepared separately and subsequently mixed to form a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend, or composite material. In some embodiments, the polymeric component has antibacterial activity against one or both of Gram-negative and Gram-positive bacterial strains. In some embodiments, the ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:1. In some embodiments, the outer layer of the wound dressing contains the polymeric component. In some embodiments, the polymeric component is impregnated into the wound dressing. In some embodiments, the wound dressing is selected from the group consisting of: wraps, coverings, barriers, layers, packings, gauze, plasters, bandages, cotton lint, sutures, films, foamed products, hydrogels, hydrocolloids, alginate products, bioactive products, tissue-engineered skin substitutes, pharmaceutical products, liquid bandages, smart dressings, and composite materials, or any combination thereof. In some embodiments, the wound dressing is configured to provide an indication of one or more parameters related to the state of the wound site.

[0017] In another aspect, this article describes a topical formulation comprising a polymeric component selected from the group consisting of:

[0018] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0019] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0020] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0021] (iii) Optional polyols;

[0022] (iv) optional water-soluble polymers; and,

[0023] (v) An optional third multifunctional crosslinking agent; or,

[0024] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0025] (3) Polyethyleneimine intermediates;

[0026] (4) Second adduct; and,

[0027] (5) A combination of the two or more of the above;

[0028] and at least one pharmaceutically acceptable excipient;

[0029] The ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:1.

[0030] In some embodiments, the topical formulation is in the form of a cream, gel, paste, foam, spray, powder, emulsion, liquid, or ointment. In some embodiments, the polymeric component has antibacterial activity against one or both of Gram-negative and Gram-positive bacterial strains.

[0031] In another aspect, this document describes a method for preventing or reducing bacterial growth or infection in a subject's wound, surgical site, or implant, the method comprising applying or coating to the wound, surgical site, or implant a composition comprising a polymeric component selected from the group consisting of:

[0032] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0033] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0034] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0035] (iii) Optional polyols;

[0036] (iv) optional water-soluble polymers; and,

[0037] (v) An optional third multifunctional crosslinking agent; or,

[0038] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0039] (3) Polyethyleneimine intermediates;

[0040] (4) Second adduct; and,

[0041] (5) A combination of the two or more of the above;

[0042] And at least one pharmaceutically acceptable excipient.

[0043] In another aspect, this document describes a method for treating a wound or surgical site in a subject in need, the method comprising applying to the wound or surgical site a composition comprising a polymeric component selected from the group consisting of:

[0044] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0045] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0046] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0047] (iii) Optional polyols;

[0048] (iv) optional water-soluble polymers; and,

[0049] (v) An optional third multifunctional crosslinking agent; or,

[0050] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0051] (3) Polyethyleneimine intermediates;

[0052] (4) Second adduct; and,

[0053] (5) A combination of the two or more of the above;

[0054] And at least one pharmaceutically acceptable excipient.

[0055] In another respect, this article describes a method for promoting wound or surgical site healing in a subject in need, the method comprising applying to the wound or surgical site a composition comprising a polymeric component selected from the group consisting of:

[0056] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0057] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0058] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0059] (iii) Optional polyols;

[0060] (iv) optional water-soluble polymers; and,

[0061] (v) An optional third multifunctional crosslinking agent; or,

[0062] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0063] (3) Polyethyleneimine intermediates;

[0064] (4) Second adduct; and,

[0065] (5) A combination of the two or more of the above;

[0066] And at least one pharmaceutically acceptable excipient.

[0067] In some embodiments, the wound is an external wound. In some embodiments, the wound is an internal wound. In some embodiments, the method is part of an acute wound care protocol. In some embodiments, the method is part of a chronic wound care protocol. In some embodiments, the wound is infected. In some embodiments, the wound is not infected.

[0068] In another aspect, this document describes a method for protecting a wound site of a subject in need, the method comprising surrounding at least a portion of the wound site with a dressing, and contacting the wound site with a composition comprising a polymeric component selected from the group consisting of:

[0069] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0070] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0071] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0072] (iii) Optional polyols;

[0073] (iv) optional water-soluble polymers; and,

[0074] (v) An optional third multifunctional crosslinking agent; or,

[0075] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0076] (3) Polyethyleneimine intermediates;

[0077] (4) Second adduct; and,

[0078] (5) A combination of the two or more of the above;

[0079] And at least one pharmaceutically acceptable excipient.

[0080] In another respect, this document describes a method for preventing or reducing infection in a subject in need, the method comprising administering to the subject a composition comprising a polymeric component selected from the group consisting of:

[0081] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0082] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0083] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0084] (iii) Optional polyols;

[0085] (iv) optional water-soluble polymers; and,

[0086] (v) An optional third multifunctional crosslinking agent; or,

[0087] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0088] (3) Polyethyleneimine intermediates;

[0089] (4) Second adduct; and,

[0090] (5) A combination of the two or more of the above;

[0091] And at least one pharmaceutically acceptable excipient.

[0092] In another aspect, this document describes a method for treating an infection in a subject in need, the method comprising administering to the subject a composition comprising a polymeric component selected from the group consisting of:

[0093] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0094] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0095] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0096] (iii) Optional polyols;

[0097] (iv) optional water-soluble polymers; and,

[0098] (v) An optional third multifunctional crosslinking agent; or,

[0099] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0100] (3) Polyethyleneimine intermediates;

[0101] (4) Second adduct; and,

[0102] (5) A combination of the two or more of the above;

[0103] And at least one pharmaceutically acceptable excipient.

[0104] In some embodiments, the infection is a localized infection. In some embodiments, the infection is a systemic infection.

[0105] In another respect, this document describes a method for treating sepsis in a subject in need, the method comprising administering to the subject a composition comprising a polymeric component selected from the group consisting of:

[0106] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0107] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0108] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0109] (iii) Optional polyols;

[0110] (iv) optional water-soluble polymers; and,

[0111] (v) An optional third multifunctional crosslinking agent; or,

[0112] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0113] (3) Polyethyleneimine intermediates;

[0114] (4) Second adduct; and,

[0115] (5) A combination of the two or more of the above;

[0116] And at least one pharmaceutically acceptable excipient.

[0117] In another aspect, this document describes a method for preventing or reducing necrosis in a subject in need, the method comprising administering to the subject a composition comprising a polymeric component selected from the group consisting of:

[0118] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising:

[0119] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0120] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0121] (iii) Optional polyols;

[0122] (iv) optional water-soluble polymers; and,

[0123] (v) An optional third multifunctional crosslinking agent; or,

[0124] (2) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising a first adduct, a polyol, a water-soluble polymer and an optional third multifunctional crosslinker;

[0125] (3) Polyethyleneimine intermediates;

[0126] (4) Second adduct; and,

[0127] (5) A combination of the two or more of the above;

[0128] And at least one pharmaceutically acceptable excipient.

[0129] In some embodiments, the subject is a human or animal subject. In some embodiments, the composition has antibacterial activity against one or both of Gram-negative and Gram-positive bacterial strains. In some embodiments, the ratio of total quaternary amines to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:1.

[0130] In some embodiments, the polyethyleneimine intermediate comprises the reaction product of a reagent comprising polyethyleneimine and an alkylating agent. In some embodiments, the reagent further comprises a monoepoxide or lactone. In some embodiments, the monoepoxide or lactone is optionally substituted with a C1-C6 alkyl group, wherein the C1-C6 alkyl group is optionally substituted with a substituent selected from the group consisting of: -(C6-C 10 aryl); and optionally substituted with hydroxyl -(C1-C6 alkoxy); C1-C6 alkoxy; optionally substituted with C1-C6 alkyl C6-C 10 Aryl; and carboxyl. In some embodiments, the monoepoxide is a C1-C6 alkyl ethylene oxide. In some embodiments, the C1-C6 alkyl ethylene oxide is selected from the group consisting of methyl ethylene oxide, ethyl ethylene oxide, propyl ethylene oxide, and butyl ethylene oxide. In some embodiments, the polyethyleneimine intermediate comprises the reaction product of a reagent comprising polyethyleneimine, the monoepoxide, and optionally an alkylating agent; the monoepoxide is -(C1-C6 alkylene)-N + (R 20 )3X - Replace; each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl; and each X - The alkylating agent is independently selected from the group consisting of: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives. In some embodiments, the alkylating agent comprises one or more R... 21 -LG, where each R 21 Independently selected from C1-C6 alkyl groups optionally substituted with substituents selected from the following: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 The alkylating agent is an aryl group and optionally a -(C1-C6 alkoxy) group substituted with -OH; and each LG is a leaving group. In some embodiments, the alkylating agent is a benzoylmethyl halide, a benzyl halide, or a hexyl halide.

[0131] In some embodiments, the reagent for the reaction product contained in the polyethyleneimine intermediate further comprises a monoisocyanate. In some embodiments, the monoisocyanate comprises one or more R... 30 -NCO, where each R 30 Independently selected from (1) C6-C 20 Alkyl group, optionally substituted with one to three independent substituents selected from: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (Aryl); and (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c ); where each R a Independently C1-C6 alkyl; and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3. In some embodiments, the monoisocyanate comprises octyl isocyanate, octadecyl isocyanate, or a combination thereof.

[0132] In some embodiments, the molecular weight of polyethyleneimine is from about 300 to about 270,000 Daltons. In some embodiments, the molecular weight of polyethyleneimine is from about 10,000 to about 200,000 Daltons. In some embodiments, the molecular weight of polyethyleneimine is from about 25,000 to about 120,000 Daltons. In some embodiments, the polyethyleneimine is branched. In some embodiments, the polyethyleneimine is hyperbranched. In some embodiments, the ratio of primary amine to secondary amine to tertiary amine in the polyethyleneimine is from about 1:2:1 to about 1:1:1. In some embodiments, the ratio of primary amine to secondary amine to tertiary amine in the polyethyleneimine is from about 1:1:0.7. In some embodiments, the polyethyleneimine intermediate is selected from one or more of the following: ,

[0133] , , ,

[0134] , , and copolymers or blends of any two or more thereof, wherein:

[0135] Each Y 3 Independently H or -OY 2 ;

[0136] Each Y2 Independently H or -C(O)-NHR 30 ;

[0137] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000;

[0138] Z stands for -(C2-C6 alkylene)-;

[0139] Each R 10 Independently selected from hydrogen; C1-C6 alkyl groups optionally substituted with substituents selected from the following: -N + (R 20 )3X - -(C6-C 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 aryl) and carboxyl; and each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl;

[0140] Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH;

[0141] Each R 30 Independently selected from (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (Aryl); and (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR.a (OR b (OR) c ); where each R a Independently C1-C6 alkyl; and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3; and

[0142] Each X - Independently selected from the group consisting of: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate and borate, and their organic substituted derivatives;

[0143] The premise is:

[0144] When R 10 To be optionally selected from -(C6-C) 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 When the C1-C6 alkyl group is substituted with aryl and carboxyl substituents, the polyethyleneimine intermediate is independently selected from... , and In some embodiments, the polyethyleneimine intermediate is... or ;

[0145] Each R 60 Independently selected from -Y groups optionally substituted by 1-3 substituents selected from the following 4 -(C1-C 18 Alkyl groups: -OH, -N + (R 20 )3X - -(C1-C6 alkoxy), carboxyl, -(C6-C 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH; and at least one R 60 All R-substituted with -OH, but less than 50% 60 Replaced by -OH;

[0146] Y 4 It does not exist or is -C(O)-;

[0147] And each R 20 Choose independently the following groups: C1-C 18Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary substituted N. 18 Heteroalkyl groups; and C6-C groups optionally substituted with the following: 10 Aryl groups: -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl);

[0148] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000; and

[0149] Each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0150] In some embodiments, the polyethyleneimine intermediate is or ;

[0151] Each R 60 Independently selected from -Y groups optionally substituted by 1-3 substituents selected from the following 4 -(C1-C 18 Alkyl groups: -OH, -N + (R 20 )3X - -(C6-C 10 Aryl), -C(O)O (C1-C6 alkyl) and -C(O)- (C6-C 10 (aryl); and at least one R 60 All R-substituted with -OH, but less than 50% 60 Replaced by -OH;

[0152] Y 4 It does not exist or is -C(O)-;

[0153] And each R 20 Independently selected from the group consisting of C1-C6 alkyl groups;

[0154] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000; and

[0155] Each X -The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0156] In some embodiments, each R 60 Independently selected from -(C1-C) groups optionally substituted with -OH. 18 Alkyl); and at least one R 60 All R-substituted with -OH, but less than 50% 60 It is replaced by -OH.

[0157] In some embodiments, the polyethyleneimine intermediate is selected from the group consisting of:

[0158]

[0159] Where A is B is And each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 100. In some embodiments, one or more bromide anions are independently selected from the group consisting of X. - Substitution: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organic substituted derivatives.

[0160] In some embodiments, the polyethyleneimine intermediate is selected from the group consisting of:

[0161]

[0162] Where A is B is Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 100; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0163] In some embodiments, at least 20% of the nitrogen atoms in the polyethyleneimine intermediate are quaternized.

[0164] In some embodiments, the polymer component is a polyethyleneimine intermediate.

[0165] In some embodiments, the first quaternary ammonium salt has the following chemical structure: ,in

[0166] R 1 Choose from the following groups: -(C8-C 30 alkyl), -(C8-C 30 (heteroalkyl), -(C8-C) 30 (heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl), -(C6-C 10 aryl)-(C8-C 30 alkyl), -(C6-C 10 aryl)-(C8-C 30 heteroalkyl), -(CR m R n ) x10 -W 10 -(CR p R q ) y10 -H and -(CR) m R n ) x11 -W 11 -(CR p R q ) y11 H-; where -(C8-C 30 (heteroalkyl), -(C8-C) 30 (heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl)-(C8-C 30 (Heteroalkyl) has 1 to 4 heteroatoms independently selected from O, S and Si;

[0167] R 2 Choose from the following groups: -(C1-C4 alkyl), -(C1-C4 heteroalkyl), -(C1-C4 heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl), -(C6-C 10 aryl)-(C1-C4 alkyl), -(C6-C 10 aryl)-(C1-C4 heteroalkyl);-(CR) m R n ) x20 -W 20 -(CR p R q ) y20 -H and -(CR) m R n ) x21-W 21 -(CR p R q ) y21 -H; where -(C1-C4 heteroalkyl), -(C1-C4 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 Aryl)-(C1-C4 heteroalkyl) has 1 to 4 heteroatoms independently selected from O, S and Si;

[0168] R 3 Choose from the following groups: -(C1-C 30 alkyl), -(C1-C 30 (heteroalkyl), -(C1-C) 30 (heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl), -(C6-C 10 aryl)-(C1-C 30 alkyl), -(C6-C 10 aryl)-(C1-C 30 heteroalkyl), -(CR m R n ) x30 -W 30 -(CR p R q ) y30 -H and -(CR) m R n ) x31 -W 31 -(CR p R q ) y31 -H; where -(C1-C 30 (heteroalkyl), -(C1-C) 30 (heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl)-(C1-C 30 (Heteroalkyl) has 1 to 4 heteroatoms independently selected from O, S and Si;

[0169] A is a linking group selected from the group consisting of: -(C3-C 20 alkylene)-, -(C3-C 20 (heteroalkyl)-, -(C6-C 10 (Asaryl)-(C3-C 20 alkylene)-, -(CR m R n ) x40 -W 40 -(CR p Rq ) y40 - and -(CR m R n ) x41 -W 41 -(CR p R q ) y41 -, where -(C3-C 20 (heteroalkyl) - having 1 to 4 heteroatoms independently selected from O, S and Si; and -(C3-C 20 alkylene)- and -(C3-C 20 (heteroalkyl) - optionally substituted by 1 to 6 independent substituents selected from the following: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 (Aromatic);

[0170] Each R m R n R p and R q Independently selected from H and C1-C4 alkyl groups;

[0171] W 10 W 20 W 30 and W 40 Independently selected from -C(O)-, -C(O)O-, -OC(O)-, -C(O)NH- and -NHC(O)-;

[0172] W 11 W 21 W 31 and W 41 Independently selected from 5- to 6-membered cycloalkyl groups, C6-C 10 Aryl, 5- to 6-membered heterocyclic alkyl and 5- to 6-membered heteroaryl, wherein the heterocyclic alkyl contains 1-2 cyclic heteroatoms selected from O, N, S and Si; and the heteroaryl contains 1-3 cyclic heteroatoms selected from O, N, S and Si;

[0173] x10 is an integer from 1 to 30 and y10 is an integer from 0 to 29, where 8 ≤ (x10 + y10) ≤ 30;

[0174] x11 is an integer from 1 to 30 and y11 is an integer from 0 to 29, where 8 ≤ (x11 + y11) ≤ 30;

[0175] x20 is an integer from 1 to 4, and y20 is an integer from 0 to 3, where x20 + y20 ≤ 4;

[0176] x21 is an integer from 1 to 4, and y21 is an integer from 0 to 3, where x21 + y21 ≤ 4;

[0177] x30 is an integer from 1 to 30, and y30 is an integer from 0 to 29, where x30 + y30 ≤ 30;

[0178] x31 is an integer from 1 to 30, and y31 is an integer from 0 to 29, where x31 + y31 ≤ 30;

[0179] x40 is an integer from 1 to 19, and y40 is an integer from 1 to 19, where 3 ≤ (x40 + y40) ≤ 20;

[0180] x41 is an integer from 1 to 20, and y41 is an integer from 0 to 19, where 3 ≤ (x41 + y41) ≤ 20;

[0181] Y is selected from the following groups: -OH, -NHR 4 -SH, -CO2H, -C(O)NHR 4 -C(S)NHR 4 , and ;

[0182] Each R 4 Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 (Aryl) has 1 to 4 heteroatoms independently selected from O, S, and Si; and

[0183] X - It is independently an organic substituted derivative of acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, borate, or any of the foregoing.

[0184] In some embodiments, R1 Choose from the following groups: -(C 12 -C 30 alkyl), -(C 12 -C 30 heteroalkyl), -(C 12 -C 30 alkyl)-(C6-C 10 aryl), -(C 12 -C 30 (heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl)-(C 12 -C 30 alkyl) and -(C6-C 10 aryl)-(C 12 -C 30 (heteroalkyl); wherein -(C 12 -C 30 heteroalkyl), -(C 12 -C 30 (heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl)-(C 12 -C 30 The heteroalkyl group has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, R 3 Choose from the following groups: -(C1-C4 alkyl), -(C1-C4 heteroalkyl), -(C1-C4 alkyl)-(C6 ... 10 aryl), -(C1-C4 heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl)-(C1-C4 alkyl) and -(C6-C 10 aryl)-(C1-C4 heteroalkyl); wherein -(C1-C4 heteroalkyl), -(C1-C4 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 Aryl)-(C1-C4 heteroalkyl) has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, R 2 and R 3 At least one of them is -(C1-C4 alkyl). In some embodiments, R 2 and R 3 It is a methyl group. In some embodiments, A is -(CH2). m -or-(CH2CHR) 5 -O-) n -CH2CHR 5-, where m is an integer from 2 to 20; n is 0, 1, 2, 3, 4 or 5; and each R 5 Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 The aryl group has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, R 5 It is H or methyl. In some embodiments, the first quaternary ammonium salt is , , , , , , , Or a combination of the two or more thereof. In some embodiments, the first quaternary ammonium salt is present in the polymer, copolymer or interpenetrating polymer network of the polymerizing component (1) or (2) in an amount of about 1% to about 50% by weight.

[0185] In some embodiments, the first multifunctional crosslinker is a bifunctional crosslinker. In some embodiments, the bifunctional crosslinker is a diisocyanate. In some embodiments, the diisocyanate is selected from the group consisting of hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), xylene diisocyanate (XDI), methylene-bis-(4-cyclohexyl isocyanate) (H12MDI), m-tetramethylxylene diisocyanate (TMXDI), and trimethylhexamethylene diisocyanate (TMDI). In some embodiments, the second multifunctional crosslinker (if present) is a second polyisocyanate; the third multifunctional crosslinker (if present) is a third polyisocyanate; and the second polyisocyanate is different from the third polyisocyanate. In some embodiments, the second multifunctional crosslinker (if present) is a second polyisocyanate; the third multifunctional crosslinker (if present) is a third polyisocyanate; and the second polyisocyanate and the third polyisocyanate are the same. In some embodiments, the first polyfunctional crosslinker is a first polyisocyanate; the second polyfunctional crosslinker (if present) is a second polyisocyanate; and the third polyfunctional crosslinker (if present) is a third polyisocyanate; and the first, second, and third polyisocyanates are different. In some embodiments, the first polyfunctional crosslinker is a first polyisocyanate; the second polyfunctional crosslinker (if present) is a second polyisocyanate; and the third polyfunctional crosslinker (if present) is a third polyisocyanate; and the first, second, and third polyisocyanates are the same. In some embodiments, the average isocyanate functionality of each of the first, second, and third polyisocyanates is 2 to 5. In some embodiments, the average isocyanate functionality of each of the first, second, and third polyisocyanates is 3 to 4. In some embodiments, each of the first, second, and third polyisocyanates is prepared from a diisocyanate independently selected from the group consisting of: hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), xylene diisocyanate (XDI), methylene-bis-(4-cyclohexyl isocyanate) (H12MDI), m-tetramethylxylene diisocyanate (TMXDI), and trimethylhexamethylene diisocyanate (TMDI). In some embodiments, each of the first, second, and third polyisocyanates is independently selected from the group consisting of: DESMODUR® N-3300, DESMODUR® N-100, DESMODUR® Z4470SN, WANNATE® T-series polyisocyanates, and LUPRANATE® M-series polyisocyanates. In some embodiments, the average isocyanate functionality of the first adduct is 2 to 3.In some embodiments, the average isocyanate functionality of the first adduct is from about 2.05 to about 2.3. In some embodiments, the first multifunctional crosslinker is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (2) in an amount from about 2% to about 25% by weight. In some embodiments, the second multifunctional crosslinker is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or in the polymerizing component (4) in an amount from about 0.1% to about 10% by weight. In some embodiments, the third multifunctional crosslinker is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (2) in an amount from about 0.1% to about 20% by weight.

[0186] In some embodiments, the polyol is selected from the group consisting of: polyether polyols, polyester polyols, polyacrylic acid polyols, polymethacrylic acid polyols, polycaprolactone polyols, polybutadiene polyols, poly(acrylonitrile-co-butadiene) polyols, polysiloxane polyols, copolymers of any two or more thereof, and combinations of any two or more thereof. In some embodiments, the polyol is selected from the group consisting of: poly(tetramethylene glycol), polyethylene glycol, polypropylene glycol, poly(ethylene glycol-b-propylene glycol-b-ethylene glycol), and poly(propylene glycol-b-polyethylene glycol-b-propylene glycol). In some embodiments, the polyol has a weight-average molecular weight of about 300 to about 3000. In some embodiments, the polyol has a weight-average molecular weight of about 400 to about 2000. In some embodiments, the polyol has a weight-average molecular weight of about 600 to about 1500. In some embodiments, the polyol is present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2) in an amount of about 1% to about 40% by weight.

[0187] In some embodiments, the polymeric component (1) further comprises (vi) a first multifunctional crosslinking agent and a third adduct of a second quaternary ammonium salt. ,in

[0188] R 1a R 2a and R 3a Each independently is -(C1-C 20 alkyl), -(C1-C 20 alkyl)-(C6-C 10 aryl) or -(C6-C 10 aryl)-(C1-C 20 alkyl);

[0189] A 1 The linking group is selected from the group consisting of: -(C3-C 20 alkylene)-, -(C3-C 20 (heteroalkyl)-, -(C6-C10 (Asaryl)-(C3-C 20 alkylene)-, -(CR m1 R n1 ) x42 -W 42 -(CR p1 R q1 ) y42 - and -(CR m1 R n1 ) x43 -W 43 -(CR p1 R q1 ) y43 -, where -(C3-C 20 (heteroalkyl) - having 1 to 4 heteroatoms independently selected from O, S and Si; and -(C3-C 20 alkylene)- and -(C3-C 20 (heteroalkyl) - optionally substituted by 1 to 6 independent substituents selected from the following: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 (Aromatic);

[0190] Each R m1 R n1 R p1 and R q1 Independently selected from H and C1-C4 alkyl groups;

[0191] W 42 Selected from -C(O)-; -C(O)O-; -OC(O)-; -C(O)NH-; and -NHC(O)-;

[0192] W 43 Selected from 5- to 6-membered cycloalkyl groups, C6-C 10 Aryl, 5- to 6-membered heterocyclic alkyl and 5- to 6-membered heteroaryl, wherein the heterocyclic alkyl contains 1-2 cyclic heteroatoms selected from O, N, S and Si; and the heteroaryl contains 1-3 cyclic heteroatoms selected from O, N, S and Si;

[0193] x42 is an integer from 1 to 19, and y42 is an integer from 1 to 19, where 3 ≤ (x42 + y42) ≤ 20;

[0194] x43 is an integer from 1 to 20, and y43 is an integer from 0 to 19, where 3 ≤ (x43 + y43) ≤ 20;

[0195] Y 1 Choose from the following groups: -OH, -NHR 4a -SH, -CO2H, -C(O)NHR 4a -C(S)NHR 4a , and ;

[0196] Each R 4a Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 (Aryl) has 1 to 4 heteroatoms independently selected from O, S, and Si; and

[0197] X - It is independently an organic substituted derivative of acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, borate, or any of the foregoing.

[0198] In some embodiments, R 1a R 2a and R 3a At least one of them is -(C1-C4 alkyl). In some embodiments, R 1a R 2a and R 3a Both of them are -(C1-C4 alkyl).

[0199] In some embodiments, the polymeric component (1) further comprises (vi) a fourth multifunctional crosslinking agent and a third adduct of a second quaternary ammonium salt. ,in,

[0200] R 1a R 2a and R 3a Each independently is -(C1-C 20 alkyl), -(C1-C 20 alkyl)-(C6-C10 aryl) or -(C6-C 10 aryl)-(C1-C 20 alkyl);

[0201] A 1 The linking group is selected from the group consisting of: -(C3-C 20 alkylene)-, -(C3-C 20 (heteroalkyl)-, -(C6-C 10 (Asaryl)-(C3-C 20 alkylene)-, -(CR m1 R n1 ) x42 -W 42 -(CR p1 R q1 ) y42 - and -(CR m1 R n1 ) x43 -W 43 -(CR p1 R q1 ) y43 -, where -(C3-C 20 (heteroalkyl) - having 1 to 4 heteroatoms independently selected from O, S and Si; and -(C3-C 20 alkylene)- and -(C3-C 20 (heteroalkyl) - optionally substituted by 1 to 6 independent substituents selected from the following: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 (Aromatic);

[0202] Each R m1 R n1 R p1 and R q1 Independently selected from H and C1-C4 alkyl groups;

[0203] W 42 Selected from -C(O)-; -C(O)O-; -OC(O)-; -C(O)NH-; and -NHC(O)-;

[0204] W 43 Selected from 5- to 6-membered cycloalkyl groups, C6-C 10Aryl, 5- to 6-membered heterocyclic alkyl and 5- to 6-membered heteroaryl, wherein the heterocyclic alkyl contains 1-2 cyclic heteroatoms selected from O, N, S and Si; and the heteroaryl contains 1-3 cyclic heteroatoms selected from O, N, S and Si;

[0205] x42 is an integer from 1 to 19, and y42 is an integer from 1 to 19, where 3 ≤ (x42 + y42) ≤ 20;

[0206] x43 is an integer from 1 to 20, and y43 is an integer from 0 to 19, where 3 ≤ (x43 + y43) ≤ 20;

[0207] Y 1 Choose from the following groups: -OH, -NHR 4a -SH, -CO2H, -C(O)NHR 4a -C(S)NHR 4a , and ;

[0208] Each R 4a Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 (Aryl) has 1 to 4 heteroatoms independently selected from O, S, and Si; and

[0209] X - It is independently an organic substituted derivative of acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, borate, or any of the foregoing.

[0210] In some embodiments, R 1a R 2a and R 3a At least one of them is -(C1-C4 alkyl). In some embodiments, R 1a R 2a and R 3a Both of them are -(C1-C4 alkyl).

[0211] In some embodiments, a fourth multifunctional crosslinker is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 0.1% by weight to about 15% by weight. In some embodiments, the fourth multifunctional crosslinker is different from the first multifunctional crosslinker and different from the second multifunctional crosslinker (if present) and different from the third multifunctional crosslinker (if present). In some embodiments, the fourth multifunctional crosslinker is a fourth polyisocyanate. In some embodiments, the fourth polyisocyanate is prepared from a diisocyanate selected from the group consisting of: hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), xylene diisocyanate (XDI), methylene-bis-(4-cyclohexyl isocyanate) (H12MDI), m-tetramethylxylene diisocyanate (TMXDI), and trimethylhexamethylene diisocyanate (TMDI). In some embodiments, the fourth polyisocyanate is selected from the group consisting of: DESMODUR® N-3300, DESMODUR® N-100, DESMODUR® Z4470SN, WANNATE® T series polyisocyanates and LUPRANATE® M series polyisocyanates.

[0212] In some embodiments, the second quaternary ammonium salt is (C18DMDEG-Br) or (C2DMDEG-Br). In some embodiments, the second quaternary ammonium salt is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 1% to about 15% by weight. In some embodiments, the average isocyanate functionality of the third adduct is 2 to 3. In some embodiments, the average isocyanate functionality of the third adduct is about 2.05 to about 2.3. In some embodiments, the third adduct is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 2% to about 30% by weight.

[0213] In some embodiments, the polyethyleneimine intermediate is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1), (3), or (4) in an amount of about 0.1% to about 50% by weight. In some embodiments, the second adduct is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (4) in an amount of about 1% to about 30% by weight.

[0214] In some embodiments, the water-soluble polymer is crosslinked with each of the following: (a) a first multifunctional crosslinker incorporated into the first adduct; (b) a second multifunctional crosslinker incorporated into the second adduct (if present); (c) a third multifunctional crosslinker (if present); or (d) any combination of two or more thereof. In some embodiments, the water-soluble polymer is selected from the group consisting of: hydroxyethyl cellulose (HEC), hydroxypropyl cellulose, polyvinyl alcohol, poly(hydroxyethyl methacrylate-co-alkyl methacrylate), poly(hydroxyethyl methacrylate-co-alkyl methacrylate), poly(hydroxyethyl acrylate-co-alkyl methacrylate), poly(hydroxyethyl acrylate-co-alkyl methacrylate), polyacrylamide, polyethyleneimine intermediates, copolymers of two or more thereof, copolymers of one or more thereof with polyvinylpyrrolidone poly(glycidyl acrylate) or poly(glycidyl methacrylate), and combinations or blends of two or more thereof. In some embodiments, the water-soluble polymer is hydroxyethyl cellulose or a hydrophobically modified derivative thereof. In some embodiments, the water-soluble polymer is another polyethyleneimine intermediate. In some embodiments, the water-soluble polymer is present in the polymer, copolymer, or interpenetrating polymer network of polymeric component (1) or (2) in an amount of about 0.5% to about 15% by weight. In some embodiments, polymeric components (1) and (2) further comprise a chain extender selected from the group consisting of: HO-(C n H 2n )-OH and HO-(C n H 2n-2 )-OH or combinations thereof, where n is an integer between 2 and 8. In some embodiments, the chain extender is propylene glycol, 1,4-butanediol, neopentyl glycol, hexanediol, cyclohexanediol, or a combination of two or more thereof. In some embodiments, the chain extender is present in the polymerization component in an amount from about 0.5% by weight to about 10% by weight.

[0215] In some embodiments, the polymer component further comprises a third quaternary ammonium salt. ,in

[0216] R 1a R 2a and R 3a Each can be independently methyl or ethyl;

[0217] A 2 Choose from the following groups: -(C3-C 20 alkylene)-, -(C3-C 20 (heteroalkyl)-, -(C6-C 10 (Asaryl)-(C3-C 20 alkylene)-, -(CR m1 R n1 )x42 -W 42 -(CR p1 R q1 ) y42 - and -(CR m1 R n1 ) x43 -W 43 -(CR p1 R q1 ) y43 -, where -(C3-C 20 (heteroalkyl) - having 1 to 4 heteroatoms independently selected from O, S and Si; and -(C3-C 20 alkylene)- and -(C3-C 20 (heteroalkyl) - optionally substituted by 1 to 6 independent substituents selected from the following: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 (Aromatic);

[0218] Each R m1 R n1 R p1 and R q1 Independently selected from H and C1-C4 alkyl groups;

[0219] W 42 Selected from -C(O)-; -C(O)O-; -OC(O)-; -C(O)NH-; and -NHC(O)-;

[0220] W 43 Selected from 5- to 6-membered cycloalkyl groups, C6-C 10 Aryl, 5- to 6-membered heterocyclic alkyl and 5- to 6-membered heteroaryl, wherein the heterocyclic alkyl contains 1-2 cyclic heteroatoms selected from O, N, S and Si; and the heteroaryl contains 1-3 cyclic heteroatoms selected from O, N, S and Si;

[0221] x42 is an integer from 1 to 19, and y42 is an integer from 1 to 19, where 3 ≤ (x42 + y42) ≤ 20;

[0222] x43 is an integer from 1 to 20, and y43 is an integer from 0 to 19, where 3 ≤ (x43 + y43) ≤ 20;

[0223] Y 1a For H;

[0224] Each R 4a Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 (Aryl) has 1 to 4 heteroatoms independently selected from O, S, and Si; and

[0225] X - It is independently an organic substituted derivative of acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, borate, or any of the foregoing.

[0226] In another aspect, this document describes a method for manufacturing the wound dressing described herein, comprising incorporating a composition including polymeric components into a fibrous material by one of the following:

[0227] (i) Spraying the fiber material with the composition.

[0228] (ii) Immersing the fiber material in a fluid containing the composition.

[0229] (iii) Impregnating the fibers of the fibrous material with a fluid containing the composition.

[0230] (iv) Applying a coating containing the composition to the surface of the fibrous material.

[0231] (v) Adhere a backing containing the composition to the fibrous material.

[0232] (vi) Applying microneedles containing the composition to the fibrous material.

[0233] (vii) Embedding the layer containing the composition into the fibrous material;

[0234] (viii) Constructing fibers of the fibrous material using the composition by electrospinning; or

[0235] (ix) Interweaving the fibers containing the composition with the fibers of the fiber material.

[0236] In another aspect, this document provides a method for preparing the polyurethane foam wound dressing described herein, comprising incorporating the composition into the polyurethane foam wound dressing by mixing a composition including a polymeric component with a polyurethane prior to curing, to provide the polyurethane foam wound dressing.

[0237] In another aspect, this document describes a polymer with wound-healing properties comprising a polyethyleneimine intermediate, wherein the ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:1. In some embodiments, the polymer is selected from the group consisting of:

[0238] ,

[0239] Where A is B is And each n is an integer independently selected from 2 to 3000, preferably an integer independently selected from 10 to 100. In some embodiments, one or more bromide anions are independently selected from the group consisting of X. - Substitution: Acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives. In some embodiments, the polymer is selected from the group consisting of:

[0240] ,

[0241] Where A is B is Each n is an integer independently selected from 2 to 3000, preferably an integer independently selected from 10 to 100; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives. Attached Figure Description

[0242] Figure 1A SEM images depicting control Staphylococcus aureus biofilms, and Figure 1B SEM images depicting Staphylococcus aureus biofilms treated with the compound disclosed herein (100 μM) are shown in Example 4.

[0243] Figure 2A and Figure 2BThe activity of the disclosed compound (25 μM) on Staphylococcus aureus biofilm over time was depicted using SYTO 9 staining or propidium iodide staining, respectively. All time points were compared with the control (0 h) using one-way ANOVA and Bonferroni's multiple comparison test. * p = 0.01, ** p = 0.001, *** p = 0.0001, **** p = <0.0001. Data are presented as mean (± SEM), n = 3.

[0244] Figure 3A and Figure 3B The activities of the compounds disclosed herein at different concentrations (6.25, 12.5, 25, 50, 100 μM) on Staphylococcus aureus biofilms were quantified using SYTO 9 staining or propidium iodide staining. All concentrations were compared with a control (0 μM) using one-way ANOVA and Bonfrony's multiple comparison test. *p = 0.01, **p = 0.001, ***p = 0.0001, ****p = <0.0001. Data are presented as mean (±SEM), n = 3.

[0245] Figure 4A and Figure 4B Describe non-limiting instances of bandages, and Figure 4C Describe non-limiting examples of foamed products in the form of cushions.

[0246] Figure 5 Research design for efficacy studies in a mouse model of Staphylococcus aureus-induced wound infection.

[0247] Figure 6A and Figure 6B The in vivo antimicrobial efficacy of the two compounds disclosed herein in a rodent wound infection model was described at 72 and 96 hours post-inoculation. Staphylococcus aureus NRS 384 at 1×10⁻⁶ 5CFU / wound inoculation. Treatment was administered in a total volume of 10 μL. Concentrations used are indicated on the x-axis. Total bacteria in the wound were counted on a TSA plate. Individual symbols represent biological replicates (mice, n=3). Bar graphs show the mean ± sem for each group. For the plating method, the limit of detection (LOD) for CFU was set at 1 Log CFU(1, Log). For statistical comparisons, the treatment group was compared with the control bacteria or antibiotic control (vancomycin) group using ordinary one-way ANOVA and Dunnett's multiple comparisons test. **** p<0.0001.

[0248] Figure 7A and Figure 7B The in vivo antimicrobial efficacy of the two compounds disclosed herein in a rodent wound infection model was described at 24 and 72 hours post-inoculation. Staphylococcus aureus NRS 384 at 1×10⁻⁶ 5 CFU / wound inoculation. Treatment was administered in total volumes of 10 μL, with the concentration indicated on the x-axis. Total bacterial counts were performed on wounds on TSA plates at (A) 24 hours and (B) 72 hours post-treatment. Individual symbols represent biological replicates (mice, n=5). Bar graphs and lines represent the mean ± sem for each group. For the plating method, the limit of detection (LOD) for CFU was set at 1 Log CFU(1, Log). For statistical comparisons, all treatment groups were compared to the control bacterial group using ordinary one-way ANOVA and Dunnett's multiple comparisons test. **p<0.005, ***p<0.001, ****p<0.0001.

[0249] Figure 8A and Figure 8B This study describes the in vivo antimicrobial efficacy of the two compounds disclosed herein in a rodent wound infection model 72 hours post-inoculation. Staphylococcus aureus NRS 384 at 1×10⁻⁶ 5 CFU / wound inoculation. Treatment was administered in total volumes of 10 μL, with the concentration indicated on the x-axis. Total bacteria were counted on the wounds on TSA plates 72 hours post-treatment. Individual symbols represent biological replicates (mice, n=5). Bar graphs and lines represent the mean ± sem for each group. For the plating method, the limit of detection (LOD) for CFU was set at 1 Log CFU(1, Log). For statistical comparisons, all treatment groups were compared to the control bacterial group using ordinary one-way ANOVA and Dunnett's multiple comparisons test. ns = not significant. *p<0.01, **p<0.005, ***p<0.001, ****p<0.0001.

[0250] Figure 9 The in vivo antimicrobial efficacy of the two compounds disclosed herein was characterized in a rodent wound infection model 7 days after inoculation and treatment. Staphylococcus aureus NRS 384 at 1×10⁻⁶ 5 CFU / wound inoculation. Treatment was administered in total volumes of 10 μL, with the concentration indicated on the x-axis. Total bacteria were counted on the wounds on TSA plates 7 days post-treatment. Individual symbols represent biological replicates (mice, n=5). Bars and lines represent the mean ± sem for each group. For the plating method, the limit of detection (LOD) for CFU was set at 1 Log CFU(1, Log). For statistical comparisons, all treatment groups were compared to the control bacterial group using ordinary one-way ANOVA and Dunnett's multiple comparisons test. ****p<0.0001. ns = not significant.

[0251] Figure 10 This study describes the in vivo antimicrobial efficacy of the two compounds disclosed herein in a rodent wound infection model 24 hours after inoculation and treatment. Staphylococcus aureus NRS 384 at 1×10⁻⁶ 5 CFU / wound inoculation. Treatment was administered in total volumes of 10 μL, with the concentration used indicated on the x-axis. Total bacterial counts were performed on the wound on a TSA plate 24 hours post-treatment. Individual symbols represent biological replicates (mice, n=3). Bars and lines represent the mean ± sem for each group. Dashed lines indicate that the limit of detection (LOD) for CFU was set at 1 Log CFU (1, Log). Figure 7A Female BALB / c mice from the same group described in the preliminary study were used to compare the efficacy of the same test compound with male BALB / c mice. For statistical comparisons, two-way analysis of variance and Tukey's multiple comparisons test were used to compare the two groups in all groups. ns = not significant. ****p<0.0001. There was no statistically significant difference in the antimicrobial efficacy of the two compounds between male and female BALB / c mice.

[0252] Figure 11A and Figure 11B This study describes the antimicrobial efficacy of the compounds disclosed herein in HYDROFIBER®-loaded dressings. Staphylococcus aureus NRS 384 was inhibited at a concentration of 1 × 10⁻⁶. 5CFU / wound inoculation. Treatment was administered in total volumes of 10 μL, with the concentration used indicated on the x-axis. (A) Total bacterial counts on TSA and (B) CHROMagar™ Staphylococcus aureus (CHROMO). Individual symbols indicate biological replicates (n=3 mice). Mean ± SEM for each group. The limit of detection (LOD) for TSA was set at 10 CFU (1, Log) and the LOD for CHROMO was set at 100 CFU (2, Log), as shown by the red dashed line. Control group = no bacteria. For statistical comparisons, ordinary one-way ANOVA and Dunnett's multiple comparison test were used to compare all treatment groups with the "bacteria only" group. *p<0.01, **p<0.005, ****p<0.0001.

[0253] Figure 12 The percentage of the wound area remaining up to 9 days after injury is depicted after treatment with different concentrations of the compounds disclosed herein or with a mordant.

[0254] Figure 13 The percentage of the wound area remaining up to 9 days after injury is depicted after treatment with different concentrations of the compounds disclosed herein or with a mordant.

[0255] Figure 14 The percentage of wounds closed by contraction up to 9 days after injury following treatment with different concentrations of the compounds disclosed herein or with mordants is depicted.

[0256] Figure 15 The percentage of wound closure via epithelial reformation after treatment with different concentrations of the compounds disclosed herein or with mordants is depicted.

[0257] Figure 16 The percentage of wounds closed by contraction up to 9 days after injury following treatment with different concentrations of the compounds disclosed herein or with mordants is depicted.

[0258] Figure 17 The percentage of wound closure via epithelial reformation after treatment with different concentrations of the compounds disclosed herein or with mordants is depicted.

[0259] Figure 18 The MICs of the selected compounds disclosed herein are depicted against a range of wound bacteria (Gram-positive or Gram-negative). For every three bars, compound 32-1 is represented by the left bar, compound 32-1A by the center bar, and compound 32-1B by the right bar. *p<0.01, **p<0.005, ***p<0.001, ****p<0.0001.

[0260] Figure 19A and Figure 19B The MICs of the selected compounds disclosed herein are depicted against a range of wound bacteria (Gram-positive or Gram-negative). For each group, A = compound 32-2, B = compound 32-2A, C = compound 32-2B, D = compound 32-2C, E = compound 32-2D, F = compound 32-2E. *p<0.01, **p<0.005, ***p<0.001, ****p<0.0001.

[0261] Figure 20 and Figure 21 Depicting the dose-dependent inhibition region of compound-impregnated wound dressings against methicillin-resistant Gram-positive (NRS 384 / MRSA) bacteria. ****p<0.0001. Detailed Implementation

[0262] In the following description, numerous specific details are set forth for illustrative purposes to provide a thorough understanding of the present technology. However, it will be apparent that the present technology can be practiced without these specific details. It should be understood that certain aspects, methods, embodiments, variations, and features of the present technology are described below at different levels of detail in order to provide a general understanding of the present technology.

[0263] definition

[0264] For convenience, the meanings of some terms and phrases used in this specification, examples, and appended claims are provided below. Unless otherwise stated or implied from the context, the following terms and phrases have the meanings provided below. Definitions are provided to aid in describing particular embodiments and are not intended to limit the claimed subject matter. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this art pertains. If the use of terminology in the art deviates significantly from the definitions provided herein, the definitions provided in this specification shall prevail.

[0265] Unless the context clearly indicates otherwise, as used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include multiple indicators. For example, reference to “a cell” includes a combination of two or more types of cells, etc.

[0266] As used herein, the term "about" or "approximately" with respect to a value or parameter is generally considered to include a value within a range of 5%, 10%, 15%, or 20% in either direction (greater than or less than) of the stated value, unless otherwise stated or otherwise obvious from the context (unless the stated value would be less than 0% or more than 100% of a possible value). As used herein, references to "about" or "approximately" to a value or parameter include (and describe) an embodiment of the stated value or parameter. For example, a description referring to "about X" includes a description of "X".

[0267] As used herein, the term “or” means “and / or”. The term “and / or” as used herein, such as in phrases like “A and / or B”, is intended to include A and B; A or B; A (alone); and B (alone). Similarly, the term “and / or” as used herein, such as in phrases like “A, B, and / or C”, is intended to cover each of the following embodiments: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0268] As used herein, the term "includes" means that other elements may exist in addition to the elements defined herein. The use of "includes" indicates inclusion rather than limitation.

[0269] The term "consisting of" refers to the compositions, methods, and their respective components described herein, excluding any elements not listed in the description of the embodiments.

[0270] As used herein, the term "consistently of" refers to those elements required for a given embodiment. This term allows for the presence of additional elements that do not substantially affect the basic and novel or functional features of the embodiment of the invention.

[0271] As used herein, “aryl” refers to a fully aromatic carbon ring (all-carbon) ring. An “aryl” can consist of two or more fused rings (rings sharing two adjacent carbon atoms). When an aryl is a fused ring system, the ring attached to the rest of the molecule is fully aromatic. The other rings in a fused ring system may or may not be fully aromatic. Examples of aryl groups include, but are not limited to, groups of benzene, naphthalene, and azurite.

[0272] As used herein, "alkyl" refers to a straight-chain or branched hydrocarbon chain containing a fully saturated (without double or triple bonds) hydrocarbon group. The alkyl groups in the compounds disclosed herein may contain 1 to 15 carbon atoms. Alkyl groups as used herein may have 1 to 4 carbon atoms, 1 to 5 carbon atoms, 1 to 6 carbon atoms, 1 to 7 carbon atoms, 1 to 8 carbon atoms, 1 to 9 carbon atoms, 1 to 10 carbon atoms, 1 to 11 carbon atoms, 1 to 12 carbon atoms, 1 to 13 carbon atoms, 1 to 14 carbon atoms, or 1 to 15 carbon atoms. As used herein, C1-C6 alkyl represents an alkyl group having 1 to 6 carbon atoms, C1-C4 alkyl represents an alkyl group having 1 to 4 carbon atoms, and C1-C3 alkyl represents an alkyl group having 1 to 3 carbon atoms, etc. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, tert-pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, and dodecyl.

[0273] As used herein, “alkoxy” refers to an alkyl group as defined above, which is attached to the parent molecule via an oxygen-O- atom. As used herein, C1-C6 alkoxy groups represent alkoxy groups containing 1 to 6 carbon atoms, and C1-C3 alkoxy groups represent alkoxy groups containing 1 to 3 carbon atoms. Representative examples of alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, tert-butoxy, pentoxy, and hexoxy.

[0274] As used herein, “cycloalkyl” refers to a ring of 3 to 14 carbon atoms (i.e., C3-C4) in some embodiments. 14 cycloalkyl groups), or 3 to 10 cyclic carbon atoms (i.e., C3-C4). 10 Cycloalkyl groups are monocyclic, bicyclic, or polycyclic hydrocarbon ring systems consisting of cycloalkyl groups, or 3 to 8 cyclic carbon atoms (i.e., C3-C8 cycloalkyl), 3 to 6 cyclic carbon atoms (i.e., C3-C6 cycloalkyl), or 5 to 6 cyclic carbon atoms (i.e., C5-C6 cycloalkyl). The cycloalkyl group may be saturated or characterized by one or more unsaturated sites (i.e., carbon-carbon double and / or triple bonds), provided that the unsaturated sites do not produce an aromatic system. Examples of monocyclic cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cyclohexynyl, cycloheptyl, cycloheptadienyl, cyclooctyl, cyclooctenyl, cyclooctadienyl, and similar groups. The rings of bicyclic and polycyclic cycloalkyl groups may be fused, bridged, or spirocyclic.

[0275] As used herein, unless otherwise stated, "heteroalkyl" means an alkyl group as defined herein, wherein one or more of the constitutive carbon atoms have been substituted with nitrogen, oxygen, sulfur, or silicon. A representative example of a heteroalkyl group is an alkoxy group. Heteroalkylene groups are divalent heteroalkyl groups.

[0276] As used herein, unless otherwise stated, the term "heteroaryl" refers in some embodiments to a monocyclic or fused bicyclic aromatic group (or ring) having 5 to 14 members (i.e., quinary to 14-membered heteroaryl), 5 to 10 members (i.e., quinary to 10-membered heteroaryl), or 5 to 6 members (i.e., quinary to 6-membered heteroaryl) (i.e., ring apex), and containing one to five, one to four, one to three, one to two, or one heteroatom selected from nitrogen (N), oxygen (O), and sulfur (S). When chemically permissible, the heteroaryl group may be attached to the remainder of the molecule via a carbon atom or heteroatom of the heteroaryl group. Non-limiting examples of heteroaryl groups include pyridinyl, pyrazinyl, pyrazinyl, pyrimidinyl, triazinyl, purineyl, thienopyridinyl, thienopyrimidinyl, pyrazolopyrimidinyl, pyrazolopyridinyl, imidazopyridine, isothiazolyl, pyrazolyl, indazoleyl, pteridinyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiadiazolyl, pyrroleyl, thiazolyl, furanyl, thiopheneyl, and similar groups.

[0277] The term "heterocyclic alkyl" refers, in some embodiments, to a non-aromatic monocyclic, bicyclic, or polycyclic alkyl ring having 3 to 14 members (e.g., 3- to 14-membered heterocycles), 3 to 10 members (e.g., 3- to 10-membered heterocycles), 3 to 8 members (e.g., 3- to 8-membered heterocycles), 3 to 6 members (e.g., 3- to 6-membered heterocycles), or 5 to 6 members (e.g., 5- to 6-membered heterocycles), and having one to five, one to four, one to three, one to two, or one heteroatom selected from nitrogen (N), oxygen (O), sulfur (S), and silicon (Si). Heterocyclic alkyl rings are saturated or characterized by one or more unsaturated sites (e.g., one or more carbon-carbon double bonds, carbon-carbon triple bonds, carbon-nitrogen double bonds, and / or nitrogen-nitrogen double bonds), provided that the unsaturated sites do not produce an aromatic system. The rings of bicyclic and polycyclic heterocyclic alkyl rings can be fused, bridged, or spirocyclic. Non-limiting examples of heterocyclic alkyl groups include aziridine, ethylene oxide, cyclothioethane, pyrrolidine, imidazoline, pyrazolidine, dioxacyclopentane, phthalimide, piperidine, 1,4-dioxane, morpholine, thiomorpholine, thiomorpholine-S-oxide, thiomorpholine-S,S-oxide, piperazine, 3,4,5,6-tetrahydropyridazine, tetrahydropyran, pyran, decahydroisoquinoline, 3-pyrrolidine, thiopyran, tetrahydrofuran, tetrahydrothiophene, quinine ring, and the like. When chemically permissible, heterocyclic alkyl groups may be attached to the remainder of the molecule via a cyclic carbon atom or a cyclic heteroatom.

[0278] As used herein, unless otherwise stated, “independent selection” means that each specified group is selected independently from the subsequent list of species.

[0279] The term “statistically significant” or “significant” refers to statistical significance and usually means a difference of two standard deviations (2SD) or greater.

[0280] The terms “decrease,” “reduced,” “reduction,” or “inhibit” are used herein to mean a reduction in statistical significance. In some embodiments, “reduce,” “reduction,” or “reduction” or “inhibit” generally means a reduction of at least 10% compared to a reference level (e.g., in the absence of a given treatment or agent), and may include, for example, a reduction of at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or more. As used herein, “decrease” or “inhibit” does not cover complete inhibition or reduction compared to a reference level. “Complete inhibition” is 100% inhibition compared to a reference level. The reduction may preferably be reduced to a level acceptable within the normal range for subjects without a pre-existing condition.

[0281] The terms “increased,” “increase,” “enhance,” or “activate” are used herein to mean a statistically significant increase. In some embodiments, “increased,” “increase,” “enhance,” or “activate” may mean an increase of at least 10% compared to a reference level, such as at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90%, or at most and including 100% increase or any increase between 10% and 100%, or an increase of at least about 2 times, or at least about 3 times, or at least about 4 times, or at least about 5 times, or at least about 10 times compared to a reference level, or any increase or greater between 2 times and 10 times. In the context of a marker or symptom, “increase” means a statistically significant increase in such a level.

[0282] As used herein, the term "polyisocyanate" generally refers to a family of polyisocyanates containing more than one isocyanate reactive group, such as, but not limited to, DESMODUR® N3300 and N100 (manufactured by Covestro Deutschland AG, Leverkusen, Germany), which are aliphatic polyisocyanates based on hexamethylene diisocyanate (HDI) trimers; DESMODUR® Z4470SN (manufactured by Covestro Deutschland AG, Leverkusen, Germany), which are multifunctional polyisocyanates based on isophorone diisocyanate (IPDI); WANNATE® T-series polyisocyanates, which are aromatic polyisocyanates based on toluene diisocyanate (TDI); and LUPRANATE® M-series polyisocyanates, which are aromatic polyisocyanates based on 4,4-diphenylmethane diisocyanate (MDI).

[0283] As used herein, the term "antimicrobial" is generally used to indicate that a composition or coating kills at least some degree of microorganisms on a portion of a surface (e.g., a wound). For example, antimicrobial can be used to indicate biostatic efficacy, a reduction in the level of disinfection of at least one organism (3-log, or 99.9%), a reduction in the level of disinfection of at least one organism (5-log, or 99.999%), or sterilization (no detectable organisms). Microorganisms or microorganisms can include any bacterial, viral, fungal (including molds and yeasts), or spore species. Therefore, antimicrobial as used herein encompasses antiviral, antibacterial, and antifungal properties.

[0284] The term polymer in this document includes random polymers, alternating polymers, block polymers, and graft polymers. The term copolymer in this document includes random copolymers, block copolymers, graft copolymers, interpolymer complexes, interpenetrating networks, and their blends.

[0285] As used herein, and unless otherwise specified, the term "weight %" has the common meaning of the percentage (%) of the ingredients in a chemical composition by weight, based on the total weight of the composition "as made". For example, "based on the total weight of the composition", an aqueous composition containing 1% by weight of amine is equivalent to a composition containing 99.0 g of water and 1.0 g of amine. Unless otherwise specified, weight % in a composition indicates the weight % of the active material. "As made" means that the written composition shows what is added to the mixing container, and not what may end up in the mixture after some components have reacted (e.g., hydrolyzed or polymerized).

[0286] As used herein, “subject” means an animal, such as a mammal (including humans), that has been or will be the subject of treatment, observation, or experimentation. Unless otherwise indicated, “subject” and “patient” are used interchangeably. Mammals include, but are not limited to, mice, rodents, rats, apes, humans, livestock, dogs, cats, loitering animals, and pets. The methods described herein are applicable to human therapeutics and / or veterinary applications. In some embodiments, the subject is a mammal. In some embodiments, the subject is a human.

[0287] The term "therapeutic effective amount" refers to the amount of a compound that, when administered in one or more doses to a patient (e.g., a human) requiring such treatment, is sufficient to achieve the treatment as defined below. Therapeutic effective amounts will vary depending on the patient, the disease being treated, the patient's weight and / or age, the severity of the disease or condition, or the method of administration determined by a qualified prescriber or caregiver.

[0288] The terms “treatment” or “treating” mean the application of the preparations disclosed herein for the purpose of: (i) delaying the onset of a disease / symptom, i.e., preventing or delaying the development of clinical symptoms of the disease / symptom; (ii) inhibiting a disease / symptom, i.e., suppressing the development of clinical symptoms; and / or (iii) alleviating a disease / symptom, i.e., reducing or eliminating clinical symptoms or their severity.

[0289] As used herein, the term "dressing" or "wound dressing" includes any type of wrapping, covering, barrier, layer, packing, gauze, plaster, bandage, lint, suture, film, foam product, hydrogel, hydrocolloid, alginate product, bioactive product, tissue-engineered skin substitute, pharmaceutical product, liquid bandage, or composite product (which may include any of the foregoing or substitutes) designed to be placed on or applied to a portion of tissue. For example, such dressings may be used on or near the stratum corneum or other parts of the skin, or for internal wound healing. In some embodiments, the dressing may be provided as an overskin bandage ( Figure 1A ) or foam pad ( Figure 1B ).

[0290] Unless otherwise defined herein, the scientific and technical terms used in connection with this application should have the meanings commonly understood by one of ordinary skill in the art to which this disclosure pertains. It should be understood that the technology is not limited to the specific methods, schemes, and reagents described herein and therefore can vary. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the technology as defined solely by the claims. Definitions of commonly used terms in immunology and molecular biology can be found in each of the following: The Merck Manual of Diagnosis and Therapy (2011), 19th edition, published by Merck Sharp & Dohme Corp. (ISBN 978-0-911910-19-3); The Encyclopedia of Molecular Cell Biology and Molecular Medicine, edited by Robert S. Porter et al., published by Blackwell Science Ltd., 1999–2012 (ISBN 9783527600908); Molecular Biology and Biotechnology: a Comprehensive Desk Reference (1995), edited by Robert A. Meyers, published by VCH Publishers, Inc. (ISBN 1-56081-569-8); Immunology (2006), by Werner Luttmann, published by Elsevier; Janeway's Immunobiology (2014). Kenneth Murphy, Allan Mowat, Casey Weaver (eds.), Taylor & Francis Limited (ISBN 0815345305, 9780815345305); Lewin's Genes XI, (2014), Jones & Bartlett Publishers (ISBN 1449659055); Molecular Cloning: A Laboratory Manual, 4th edition, 2012, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA (ISBN 1936113414); Basic Methods in Molecular Biology, 2012, Elsevier SciencePublishing, Inc., New York, USA (ISBN 044460149X); Laboratory Methods in Enzymology: DNA, (2013). Jon Lorsch (Ed.) Elsevier (ISBN 0124199542); Current Protocols in ProteinScience (CPPS) (2005). Frederick M. Ausubel (ed.), John Wiley and Sons (ISBN 047150338X, 9780471503385); Sons, Inc.; and Current Protocols in Immunology (CPI) (2003). Coligan, JE et al. (eds.) JohnWiley and Sons, Inc. (ISBN 0471142735, 9780471142737).

[0291] Other terms are defined in the description of various aspects of the invention herein.

[0292] The polymeric components of the wound dressings, compositions, and formulations of the present invention

[0293] The polymeric components described herein are anti-infective. In some embodiments, the polymeric components have antibacterial activity against one or both of Gram-negative and Gram-positive bacterial strains.

[0294] In one aspect, this document provides polymeric components selected from the group consisting of:

[0295] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0296] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0297] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0298] (iii) Optional polyols;

[0299] (iv) optional water-soluble polymers; and,

[0300] (v) An optional third multifunctional crosslinking agent;

[0301] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0302] (3) Polyethyleneimine intermediates;

[0303] (4) Second adduct; and,

[0304] (5) A combination of the two or more of the above.

[0305] As used in this context, "a combination of the two or more of the foregoing" encompasses blends of two or more polymeric components. For example, the polymeric component may be a blend of polymer of polymeric component (1) and polymer of polymeric component (2). In another example, the polymeric component may be a blend of interpenetrating polymer networks of polymeric component (1) and interpenetrating polymer networks of polymeric component (2). The term "blend" refers to a physical mixture within a blend in which no further chemical reaction occurs between the components.

[0306] In some embodiments, the polymeric component is a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend, or composite material, wherein the polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend, and composite material comprises, is substantially composed of, or is composed of the following:

[0307] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0308] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0309] (iii) Optional polyols;

[0310] (iv) optional water-soluble polymers; and,

[0311] (v) An optional third multifunctional crosslinker.

[0312] In some embodiments, the polymeric component is a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend, or composite material, wherein the polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend, or composite material comprises, is substantially composed of, or is composed of: a first adduct, a polyol, a water-soluble polymer, and optionally a third multifunctional crosslinking agent.

[0313] In some embodiments, the polymer component is a polyethyleneimine intermediate.

[0314] In some embodiments, the polymer component is a second adduct.

[0315] In some embodiments, the polymeric component is a polymer, an interpenetrating polymer network, a polyelectrolyte complex, a blend, or a composite material, each comprising or substantially consisting of a random polymerization / crosslinking product of a reagent comprising, substantially consisting of, or consisting of: (i) a first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt; (ii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate and a second multifunctional crosslinking agent; and (iii) a water-soluble polymer. In some embodiments, the polymer is composed of a random polymerization / crosslinking product of a reagent comprising, substantially consisting of, or consisting of: (i) a first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt; (ii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate and a second multifunctional crosslinking agent; and (iii) a water-soluble polymer.

[0316] In some embodiments, the polymeric component is a polymer, an interpenetrating polymer network, a polyelectrolyte complex, a blend, or a composite material, each comprising or substantially consisting of a random polymerization / crosslinking product of a reagent comprising, substantially consisting of, or consisting of: (i) a first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt; and (ii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate and a second multifunctional crosslinking agent. In some embodiments, the polymer is composed of a random polymerization / crosslinking product of a reagent comprising, substantially consisting of, or consisting of: (i) a first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt; and (ii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate and a second multifunctional crosslinking agent.

[0317] In some embodiments, the polymeric component is a polymer, an interpenetrating polymer network, a polyelectrolyte complex, a blend, or a composite material, each comprising or substantially consisting of a random polymerization / crosslinking product of a reagent comprising, substantially consisting of, or consisting of: (i) a first adduct of a first polyfunctional crosslinking agent and a first quaternary ammonium salt; (ii) an optional polyol; (iii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate and a second polyfunctional crosslinking agent; (iv) an optional third polyfunctional crosslinking agent; and (v) a water-soluble polymer. In some embodiments, the polymer is composed of a random polymerization / crosslinking product of a reagent comprising, substantially consisting of, or consisting of: (i) a first adduct of a first polyfunctional crosslinking agent and a first quaternary ammonium salt; (ii) an optional polyol; (iii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate and a second polyfunctional crosslinking agent; (iv) an optional third polyfunctional crosslinking agent; and (v) a water-soluble polymer.

[0318] In some embodiments, (i) the first adduct and (ii) the polyethyleneimine intermediate or the second adduct are prepared and subsequently mixed to form a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material.

[0319] Water-soluble polymers comprise, are substantially composed of, or consist of the following: hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydrophobically modified cellulose, polyvinyl alcohol, poly(hydroxyethyl methacrylate-co-alkyl methacrylate), poly(hydroxyethyl methacrylate-co-alkyl methacrylate), poly(hydroxyethyl acrylate-co-alkyl methacrylate), poly(hydroxyethyl acrylate-co-alkyl methacrylate), polyethyleneimine, polyacrylamide, or modified polymers or copolymers thereof (e.g., providing reactive functional groups, hydrophobicity, and / or surface activity), or combinations or blends of two or more thereof, or copolymers of two or more thereof, or copolymers of one or more thereof with polyvinylpyrrolidone, poly(glycidyl acrylate), or poly(glycidyl methacrylate).

[0320] The water-soluble polymer may be present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2) in an amount from about 0.5% by weight to about 15% by weight. This includes any value between about 0.5%, 0.75%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5%, or 15% by weight. In some embodiments, the water-soluble polymer is present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2) in an amount from about 0.5% by weight to about 15% by weight, from about 3% by weight to about 12% by weight, or from about 5% by weight to about 10% by weight.

[0321] In some embodiments, the polymeric component is a polymer, an interpenetrating polymer network, a polyelectrolyte complex, a blend, or a composite material, each comprising or substantially comprising a random polymerization / crosslinking product of a reagent comprising, substantially comprising, or comprising: (i) a first adduct of a first polyfunctional crosslinking agent with a first quaternary ammonium salt; (ii) an optional polyol; (iii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate with a second polyfunctional crosslinking agent; and (iv) an optional third polyfunctional crosslinking agent.

[0322] First-quaternary ammonium salts can have the following chemical structures:

[0323] ,

[0324] in:

[0325] R 1 Choose the group consisting of each of the following: -(C8-C 30 alkyl), -(C8-C 30 (heteroalkyl), -(C8-C)30 (heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl), -(C6-C 10 aryl)-(C8-C 30 alkyl), -(C6-C 10 aryl)-(C8-C 30 heteroalkyl), -(CR m R n ) x10 -W 10 -(CR p R q ) y10 -H and -(CR) m R n ) x11 -W 11 -(CR p R q ) y11 H-; where -(C8-C 30 (heteroalkyl), -(C8-C) 30 (heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl)-(C8-C 30 (Heteroalkyl) has 1 to 4 heteroatoms independently selected from O, S and Si;

[0326] R 2 Choose from the following groups: -(C1-C4 alkyl), -(C1-C4 heteroalkyl), -(C1-C4 heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl), -(C6-C 10 aryl)-(C1-C4 alkyl), -(C6-C 10 aryl)-(C1-C4 heteroalkyl);-(CR) m R n ) x20 -W 20 -(CR p R q ) y20 -H and -(CR) m R n ) x21 -W 21 -(CR p R q ) y21 -H; where -(C1-C4 heteroalkyl), -(C1-C4 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10Aryl)-(C1-C4 heteroalkyl) has one to two heteroatoms independently selected from O, S and Si;

[0327] R 3 Choose the group consisting of each of the following: -(C1-C 30 alkyl), -(C1-C 30 (heteroalkyl), -(C1-C) 30 (heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl), -(C6-C 10 aryl)-(C1-C 30 alkyl), -(C6-C 10 aryl)-(C1-C 30 heteroalkyl), -(CR m R n ) x30 -W 30 -(CR p R q ) y30 -H and -(CR) m R n ) x31 -W 31 -(CR p R q ) y31 -H; where -(C1-C 30 (heteroalkyl), -(C1-C) 30 (heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl)-(C1-C 30 (Heteroalkyl) has 1 to 4 heteroatoms independently selected from O, S and Si;

[0328] A is a linking group selected from the group consisting of: -(C3-C 20 alkylene)-, -(C3-C 20 (heteroalkyl)-, -(C6-C 10 (Asaryl)-(C3-C 20 alkylene), -(CR m R n ) x40 -W 40 -(CR p R q ) y40 - and -(CR m R n ) x41 -W 41 -(CR p R q )y41 -, where -(C3-C 20 (heteroalkyl) - having 1 to 4 heteroatoms independently selected from O, S and Si; and -(C3-C 20 alkylene)- and -(C3-C 20 (heteroalkyl) - optionally substituted by 1 to 6 independent substituents selected from the following: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 (Aromatic);

[0329] Each R m R n R p and R q Independently selected from H and C1-C4 alkyl groups;

[0330] W 10 W 20 W 30 and W 40 Independently selected from -C(O)-, -C(O)O-, -OC(O)-, -C(O)NH- and -NHC(O)-;

[0331] W 11 W 21 W 31 and W 41 Independently selected from 5- to 6-membered cycloalkyl groups, C6-C 10 Aryl, 5- to 6-membered heterocyclic alkyl and 5- to 6-membered heteroaryl, wherein the heterocyclic alkyl contains 1-2 cyclic heteroatoms selected from O, N, S and Si; and the heteroaryl contains 1-3 cyclic heteroatoms selected from O, N, S and Si;

[0332] x10 is an integer from 1 to 30 and y10 is an integer from 0 to 29, where 8 ≤ (x10 + y10) ≤ 30;

[0333] x11 is an integer from 1 to 30 and y11 is an integer from 0 to 29, where 8 ≤ (x11 + y11) ≤ 30;

[0334] x20 is an integer from 1 to 4, and y20 is an integer from 0 to 3, where x20 + y20 ≤ 4;

[0335] x21 is an integer from 1 to 4, and y21 is an integer from 0 to 3, where x21 + y21 ≤ 4;

[0336] x30 is an integer from 1 to 30, and y30 is an integer from 0 to 29, where x30 + y30 ≤ 30;

[0337] x31 is an integer from 1 to 30, and y31 is an integer from 0 to 29, where x31 + y31 ≤ 30;

[0338] x40 is an integer from 1 to 19, and y40 is an integer from 1 to 19, where 3 ≤ (x40 + y40) ≤ 20;

[0339] x41 is an integer from 1 to 20, and y41 is an integer from 0 to 19, where 3 ≤ (x41 + y41) ≤ 20;

[0340] Y is selected from the following groups: -OH, -NHR 4 -SH, -CO2H, -C(O)NHR 4 -C(S)NHR 4 , and ;

[0341] Each R 4 Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 (Aryl) has 1 to 4 heteroatoms independently selected from O, S, and Si; and

[0342] X - It is independently an organic substituted derivative of acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, borate, or any of the foregoing.

[0343] In some embodiments, R 1 Choose from the following groups: -(C 12 -C 30 alkyl), -(C 12 -C 30 heteroalkyl), -(C 12 -C 30alkyl)-(C6-C 10 aryl), -(C 12 -C 30 (heteroalkyl)-(C6-C 10 aryl), -(C6-C 10 aryl)-(C 12 -C 30 alkyl) and -(C6-C 10 aryl)-(C 12 -C 30 (heteroalkyl); wherein -(C 12 -C 30 heteroalkyl), -(C 12 -C 30 (heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl)-(C 12 -C 30 The heteroalkyl group has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, R 1 For -(C 12 -C 30 Alkyl). In some embodiments, R 1 -(C8-C) having 1 to 4 heteroatoms independently selected from O, S, and Si 30 (Heteroalkyl). In some embodiments, R 1 -(C6-C 10 aryl)-(C 12 -C 30 Alkyl). In some embodiments, R 1 For (C) 12 -C 30 alkyl)-(C6-C 10 Aryl). In some embodiments, R 1 -(C6-C) having 1 to 4 heteroatoms independently selected from O, S, and Si 10 aryl)-(C 12 -C 30 (Heteroalkyl). In some embodiments, R 1 -(C) having 1 to 4 heteroatoms independently selected from O, S, and Si 12 -C 30 (heteroalkyl)-(C6-C 10 Aryl). In some embodiments, R 1 -(CR) m R n ) x10 -W 10 -(CR p R q ) y10-H. In some embodiments, R 1 -(CR) m R n ) x11 -W 11 -(CR p R q ) y11 -H.

[0344] In some embodiments, R 2 It is -(C1-C4 alkyl). In some embodiments, R 2 It is a -(C1-C4 heteroalkyl) having 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, R 2 -(C6-C 10 Aryl)-(C1-C4 alkyl). In some embodiments, R 2 -(C1-C4 alkyl)-(C6-C 10 Aryl). In some embodiments, R 2 -(C6-C 10 Aryl). In some embodiments, R 2 -(C6-C) having 1 to 4 heteroatoms independently selected from O, S, and Si 10 Aryl)-(C1-C4 heteroalkyl). In some embodiments, R 2 -(C1-C4 heteroalkyl)-(C6-C4 heteroalkyl) having 1 to 4 heteroatoms independently selected from O, S and Si 10 Aryl). In some embodiments, R 2 -(CR) m R n ) x20 -W 20 -(CR p R q ) y20 -H. In some embodiments, R 2 -(CR) m R n ) x21 -W 21 -(CR p R q ) y21 -H.

[0345] In some embodiments, R 3 Choose from the following groups: -(C1-C4 alkyl), -(C1-C4 heteroalkyl), -(C1-C4 alkyl)-(C6 ... 10 aryl), -(C1-C4 heteroalkyl)-(C6-C 10 aryl), -(C6-C 10aryl)-(C1-C4 alkyl) and -(C6-C 10 aryl)-(C1-C4 heteroalkyl); wherein -(C1-C4 heteroalkyl), -(C1-C4 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 Aryl)-(C1-C4 heteroalkyl) has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, R 3 It is -(C1-C4 alkyl). In some embodiments, R 3 It is a -(C1-C4 heteroalkyl) having 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, R 3 -(C6-C 10 Aryl)-(C1-C4 alkyl). In some embodiments, R 3 -(C1-C4 alkyl)-(C6-C 10 Aryl). In some embodiments, R 3 -(C6-C) having 1 to 4 heteroatoms independently selected from O, S, and Si 10 Aryl)-(C1-C4 heteroalkyl). In some embodiments, R 3 -(C1-C4 heteroalkyl)-(C6-C4 heteroalkyl) having 1 to 4 heteroatoms independently selected from O, S and Si 10 Aryl). In some embodiments, R 3 -(CR) m R n ) x30 -W 30 -(CR p R q ) y30 -H. In some embodiments, R 3 -(CR) m R n ) x31 -W 31 -(CR p R q ) y31 -H.

[0346] In some embodiments, R 2 and R 3 At least one of them is -(C1-C4 alkyl). In some embodiments, R 2 and R 3 methyl. In some embodiments, R 1 C 12 -C 30 Alkyl, and R 2 and R 3 It is a methyl group.

[0347] In some embodiments, A is -(C3-C 20 (alkylene)-, which is optionally substituted by 1 to 6 independent substituents selected from the following: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 Aryl). In some embodiments, A is -(C3-C 20 (heteroalkyl)-, having 1 to 4 heteroatoms independently selected from O, S and Si and optionally substituted by 1 to 6 substituents independently selected from: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 Aryl). In some embodiments, A is -(C6-C 10 (Asaryl)-(C3-C 20 Alkylene)-. In some embodiments, A is -(C3-C 20 alkylene)-(C6-C 10 (Aspartic)-.

[0348] In some embodiments, A is -(CR) m R n ) x40 -W 40 -(CR p R q ) y40 - In some embodiments, A is -(CR m R n ) x41 -W 41 -(CR p R q ) y41 -

[0349] In some embodiments, A is -(CH2). m -or-(CH2CHR) 5 -O-) n CH2CHR 5 -, where m is an integer from 2 to 20; n is 0, 1, 2, 3, 4 or 5; and each R 5Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 The aryl group has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, R 5 It is H or methyl.

[0350] In some embodiments, Y is -OH. In some embodiments, Y is -NHR. 4 In some embodiments, Y is -SH. In some embodiments, Y is -CO2H. In some embodiments, Y is -C(O)NHR 4 , where R 4 Choose from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 The aryl group has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, Y is -C(S)NHR. 4 , where R 4 Choose from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10The aryl group has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, Y is... , where each R 4 Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 The aryl group has 1 to 4 heteroatoms independently selected from O, S, and Si. In some embodiments, Y is... , where each R 4 Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 Aryl groups have 1 to 4 heteroatoms independently selected from O, S and Si.

[0351] X - The group consisting independently of acetate, halide (e.g., chloride, bromide, or iodide), sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives, may be selected independently. As used herein, and unless otherwise stated, "organically substituted derivative" means an anion in which the sulfur, phosphorus, boron, silicon, or carbonyl atom is substituted by an alkyl or aryl group. Non-limiting examples include methyl sulfate, methanesulfonate, p-toluenesulfonate, trifluoromethanesulfonate, and trifluoroacetate.

[0352] In some embodiments, the first quaternary ammonium salt is , , , , , , , , or a combination of the two or more of the above.

[0353] The first quaternary ammonium salt may be present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2) in an amount of about 1% by weight to about 50% by weight. This includes about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50% by weight, or any value between these values. In some embodiments, the first quaternary ammonium salt is present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2) in an amount of about 5% by weight to about 25% by weight. More precisely, the amount of the quaternary ammonium salt can be expressed in milliequivalents per gram (mN / g) rather than as a percentage by weight of the total weight of the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2). The first quaternary ammonium salt may be present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2) in an amount of about 0.1 mN / g to about 1.0 mN / g. This includes any value between 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1.0 mN / g. In some embodiments, the first quaternary ammonium salt is present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2) in an amount of about 0.4 mN / g to about 0.9 mN / g. In some embodiments, the first quaternary ammonium salt is present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (2) in an amount of about 0.5 mN / g to about 0.8 mN / g.

[0354] The first multifunctional crosslinking agent may be a bifunctional crosslinking agent. In some embodiments, the bifunctional crosslinking agent is a diisocyanate. In some embodiments, the diisocyanate is selected from the group consisting of: hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), xylene diisocyanate (XDI), methylene-bis-(4-cyclohexyl isocyanate) (H12MDI), m-tetramethylxylene diisocyanate (TMXDI), and trimethylhexamethylene diisocyanate (TMDI).

[0355] The first multifunctional crosslinking agent may be a first polyisocyanate. In some embodiments, the average isocyanate functionality of the first polyisocyanate is 2 to 5. This includes an average isocyanate functionality of 2, 3, 4, or 5. In some embodiments, the average isocyanate functionality of the first polyisocyanate is 3 to 4.

[0356] The second multifunctional crosslinking agent may be a second polyisocyanate. In some embodiments, the average isocyanate functionality of the second polyisocyanate is 2 to 5. This includes an average isocyanate functionality of 2, 3, 4, or 5. In some embodiments, the average isocyanate functionality of the second polyisocyanate is 3 to 4.

[0357] The third multifunctional crosslinking agent may be a third polyisocyanate. In some embodiments, the average isocyanate functionality of the third polyisocyanate is 2 to 5. This includes an average isocyanate functionality of 2, 3, 4, or 5. In some embodiments, the average isocyanate functionality of the third polyisocyanate is 3 to 4.

[0358] In some embodiments, the first polyfunctional crosslinker is a first polyisocyanate; the second polyfunctional crosslinker (if present) is a second polyisocyanate; and the third polyfunctional crosslinker (if present) is a third polyisocyanate; wherein the first polyisocyanate, the second polyisocyanate, and the third polyisocyanate are different. In some embodiments, the first polyfunctional crosslinker is a first polyisocyanate; the second polyfunctional crosslinker (if present) is a second polyisocyanate; and the third polyfunctional crosslinker (if present) is a third polyisocyanate; wherein the first polyisocyanate, the second polyisocyanate, and the third polyisocyanate are the same.

[0359] Each of the first, second, and third polyisocyanates may be prepared independently from diisocyanates selected from the group consisting of: hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), xylene diisocyanate (XDI), methylene-bis-(4-cyclohexyl isocyanate) (H12MDI), m-tetramethylxylene diisocyanate (TMXDI), and trimethylhexamethylene diisocyanate (TMDI).

[0360] In some embodiments, each of the first, second, and third polyisocyanates is independently selected from the group consisting of: DESMODUR® N-3300, DESMODUR® N-100, DESMODUR® Z4470SN, WANNATE® T-series polyisocyanates, and LUPRANATE® M-series polyisocyanates. DESMODUR® N-3300 and DESMODUR® N-100 are aliphatic polyisocyanates based on HDI (hexamethylene diisocyanate) trimers. DESMODUR® Z4470SN is a multifunctional polyisocyanate based on IPDI (isophorone diisocyanate). WANNATE® T-series polyisocyanates are aromatic polyisocyanates based on toluene diisocyanate (TDI). LUPRANATE® M-series polyisocyanates are aromatic polyisocyanates based on 4,4-diphenylmethane diisocyanate (MDI).

[0361] The first multifunctional crosslinking agent may be present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (2) in an amount of about 2% by weight to about 25% by weight. This includes 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25% by weight, or any value between these values. In some embodiments, the first multifunctional crosslinking agent is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (2) in an amount of about 7% by weight to about 15% by weight, or about 5% by weight to about 20% by weight.

[0362] The second multifunctional crosslinker may be present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or in the polymerizing component (4) in an amount of about 0.1% by weight to about 10% by weight. This includes any value between 0.1%, 0.25%, 0.5%, 0.75%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% by weight. In some embodiments, the second multifunctional crosslinker is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or in the polymerizing component (4) in an amount of about 1% by weight to about 10% by weight, about 2% by about 8% by weight, or about 3% by about 6% by weight.

[0363] The third multifunctional crosslinking agent may be present in an amount of about 0.1% by weight to about 20% by weight in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (2). This includes 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5 or 20% by weight, or any value between these values. In some embodiments, a third multifunctional crosslinking agent is present in the polymer, copolymer or interpenetrating polymer network of the polymerizing component (1) or (2) in an amount of about 1% to about 20% by weight or about 2% to about 15% by weight.

[0364] In some embodiments, the average isocyanate functionality of the first adduct is 2 to 3. In some embodiments, the average isocyanate functionality of the first adduct is about 2.05 to about 2.3.

[0365] The first adduct may be present in an amount of about 5% by weight to about 70% by weight in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (2). This includes about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69 or 70% by weight, or any value between these values. In some embodiments, the first adduct is present in the polymer, copolymer or interpenetrating polymer network of the polymerizing component (1) or (2) in amounts of about 10% to about 50% by weight, about 15% to about 65% by weight, about 15% to about 60% by weight, about 15% to about 50% by weight, about 20% to about 70% by weight, about 20% to about 60% by weight or about 20% to about 50% by weight.

[0366] The polyol may be present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (2) in an amount from about 1% by weight to about 40% by weight. This includes any value between 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40% by weight. In some embodiments, the polyol is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) or (2) in an amount from about 5% by weight to about 25% by weight.

[0367] The polyol may be selected from the group consisting of: polyether polyols, polyester polyols, polyacrylic acid polyols, polymethacrylic acid polyols, polycaprolactone polyols, polybutadiene polyols, poly(acrylonitrile-co-butadiene) polyols, polysiloxane polyols, copolymers of any two or more thereof, and combinations of any two or more thereof.

[0368] In some embodiments, the polyol comprises, is substantially composed of, or is composed of: polybutanediol (PTMG), polyethylene glycol (PEG), polypropylene glycol (PPG), or combinations thereof, or copolymers thereof with polyester, polycaprolactone, polybutadiene, poly(acrylonitrile-butadiene), polysiloxane, or polyacrylate. In some embodiments, the polyol is selected from the group consisting of: poly(tetramethylene glycol), polyethylene glycol, polypropylene glycol, poly(ethylene glycol-b-propylene glycol-b-ethylene glycol), and poly(propylene glycol-b-polyethylene glycol-b-propylene glycol).

[0369] In some embodiments, the polyol comprises, is substantially composed of, or is composed of polyether polyols, polyester polyols, or combinations thereof.

[0370] The average molecular weight of the polyol can be from about 300 to about 3000 Daltons. This includes any value between about 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1050, 1100, 1150, 1200, 1250, 1300, 1350, 1400, 1450, 1500, 1550, 1600, 1650, 1700, 1750, 1800, 1850, 1900, 1950, or 2000 Daltons. In some embodiments, the average molecular weight of the polyol is from about 400 to about 2000, or from about 600 to about 1500 Daltons.

[0371] In some embodiments, the polyol is pre-reacted with a first polyisocyanate to form an isocyanate-terminated prepolymer. In some embodiments, the polyol is pre-reacted with a third polyisocyanate to form an isocyanate-terminated prepolymer.

[0372] In some embodiments, the ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:1. This includes ratios such as: 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.2:1, 2.4:1, 2.6:1, 2.8:1, 3:1, 3.2:1, 3.4:1, 3.6:1, 3.8:1, 4:1, 4.2:1, 4.4:1, 4.6:1, 4.8:1, 5:1, 5.2:1, 5.4:1, 5.6:1, 5.8:1, 6:1, 6.2:1, 6.4:1, 6.6. :1, 6.8:1, 7:1, 7.2:1, 7.4:1, 7.6:1, 7.8:1, 8:1, 8.2:1, 8.4:1, 8.6:1, 8.8:1, 9:1, 9.2:1, 9.4:1, 9.6:1, 9.8:1, 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1, 99:1 or higher, or any value in between.

[0373] In some embodiments, the polyethyleneimine intermediate comprises optionally substituted hydroxyalkylene functional groups, which react with a first adduct and a second polyfunctional crosslinker (if present). In some embodiments, the polyethyleneimine intermediate comprises optionally substituted hydroxyalkylene functional groups, which react with a first adduct and a second polyfunctional crosslinker (if present) and a third polyfunctional crosslinker (if present).

[0374] In some embodiments, the hydroxyalkylene functional group is optionally substituted with a C1-C6 alkyl group, which is optionally substituted with a substituent selected from the group consisting of: -N + (R 20 )3X - -(C6-C 10 Aryl) and optionally -(C1-C6 alkoxy) substituted with -OH, optionally -(C1-C6 alkyl) substituted with -(C6-C) 10 aryl) and carboxyl; each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary substituted N. 18Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl; and each X - The group is independently selected from the group consisting of: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives. In some embodiments, the hydroxyalkylene functional group is substituted with a C1-C6 alkyl group, wherein the C1-C6 alkyl group is -N + (R 20 )3X - Replace, each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl; and each X - Independently selected from the group consisting of: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives. In some embodiments, the hydroxyalkylene functional group is replaced by -(CH2)-N + (Me)3Cl - Substitution. In some embodiments, the hydroxyalkylene functional group is hydroxyethylidene, hydroxypropylidene, hydroxybutylidene, or an oligomer thereof.

[0375] In some embodiments, the polyethyleneimine intermediate comprises the reaction product of a reagent comprising polyethyleneimine and an alkylating agent. In some embodiments, the reagent further comprises a monoepoxide or lactone. In some embodiments, the monoepoxide or lactone is optionally substituted with a C1-C6 alkyl group, wherein the C1-C6 alkyl group is optionally substituted with a substituent selected from the group consisting of: -(C6-C 10 aryl); and optionally substituted with hydroxyl -(C1-C6 alkoxy); C1-C6 alkoxy; optionally substituted with C1-C6 alkyl C6-C 10 Aryl; and carboxyl.

[0376] In some embodiments, the polyethyleneimine intermediate comprises a reaction product of a reagent comprising polyethyleneimine, a monoepoxide, or an alkylating agent, wherein the monoepoxide is optionally substituted with a C1-C6 alkyl group, and the C1-C6 alkyl group is optionally substituted with a substituent selected from the group consisting of: -(C6-C 10 aryl); and optionally substituted with hydroxyl -(C1-C6 alkoxy); C1-C6 alkoxy; optionally substituted with C1-C6 alkyl C6-C 10 Aryl; and carboxyl.

[0377] In some embodiments, the monoepoxide is a C1-C6 alkyl ethylene oxide. In some embodiments, the C1-C6 alkyl ethylene oxide is selected from the group consisting of: methyl ethylene oxide (propylene oxide), ethyl ethylene oxide (1-epoxybutane or 1,2-epoxybutane), propyl ethylene oxide (1-epoxypentane), butyl ethylene oxide (1-epoxyhexane), and hexyl ethylene oxide (1-epoxyoctane). In some embodiments, the C1-C6 alkyl ethylene oxide is methyl ethylene oxide or propylene oxide. In some embodiments, the C1-C6 alkyl ethylene oxide is butyl ethylene oxide or 1-epoxyhexane. In some embodiments, the C1-C6 alkyl ethylene oxide is hexyl ethylene oxide or epioxide.

[0378] In some embodiments, the polyethyleneimine intermediate comprises the reaction product of a reagent comprising polyethyleneimine, a monoepoxide, and optionally an alkylating agent; the monoepoxide is -(C1-C6 alkylene)-N + (R 20 )3X - Replace; each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0379] In some embodiments, the polyethyleneimine intermediate comprises a reaction product containing a reagent comprising polyethyleneimine and a monoepoxide; the monoepoxide is coated with -(C1-C6 alkylene)-N +(R 20 )3X - Replace; each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0380] In some embodiments, the alkylating agent comprises one or more R 21 -LG, where each R 21 Independently selected from C1-C6 alkyl groups optionally substituted with substituents selected from the following: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 The alkylating agent is an aryl group and optionally a -(C1-C6 alkoxy) group substituted with -OH; and each LG is a leaving group. As used herein, and unless otherwise indicated, the leaving group may be a halogen group, a sulfonate group, or the like. In some embodiments, the alkylating agent is a benzoylmethyl halide, a benzyl halide, or a hexyl halide.

[0381] In some embodiments, the reagent for the reaction product contained in the polyethyleneimine intermediate further comprises a monoisocyanate. In some embodiments, the monoisocyanate comprises one or more R... 30 -NCO, where each R 30 Independently selected from (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (Aryl); and (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c); where each R a Independently C1-C6 alkyl; and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3. In some embodiments, the monoisocyanate comprises octyl isocyanate, octadecyl isocyanate, or a combination thereof.

[0382] The polyethyleneimine intermediate may be present in the polymer, copolymer, or interpenetrating polymer network of polymerizing components (1), (3), or (4) in an amount from about 0.1% by weight to about 50% by weight. This includes amounts of 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16. 5, 17, 17.5, 18, 18.5, 19, 19.5, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50% by weight, or any value between these values. In some embodiments, the polyethyleneimine intermediate is present in the polymer, copolymer or interpenetrating polymer network of the polymerizing component (1), (3) or (4) in an amount of about 3% by weight to about 30% by weight.

[0383] In some embodiments, at least 20% of the nitrogen atoms in the polyethyleneimine intermediate are quaternized. In some embodiments, at least 30% of the nitrogen atoms in the polyethyleneimine intermediate are quaternized.

[0384] The molecular weight of polyethyleneimine can be from about 300 to about 270,000 Daltons. This includes about 300, 400, 500, 600, 700, 800, 900, 1000, 2500, 5000, 10,000, 25,000, 50,000, 75,000, 100,000, 125,000, 150,000, 175,000, 200,000, 225,000, 250,000, or 270,000 Daltons, or any value between these values. In some embodiments, the molecular weight of polyethyleneimine is from about 10,000 to about 200,000 Daltons or from about 25,000 to about 120,000 Daltons.

[0385] In some embodiments, polyethyleneimine is branched. In some embodiments, polyethyleneimine is hyperbranched.

[0386] In some embodiments, the ratio of primary amine to secondary amine to tertiary amine in polyethyleneimine is about 1:2:1 to about 1:1:1. In some embodiments, the ratio of primary amine to secondary amine to tertiary amine in polyethyleneimine is about 1:1:0.7.

[0387] In some embodiments, the polyethyleneimine intermediate is selected from... , , , , , , and copolymers or blends of any two or more thereof, wherein:

[0388] Each Y 3 Independently H or -OY 2 ;

[0389] Each Y 2 Independently H or -C(O)-NHR 30 ;

[0390] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000;

[0391] Z stands for -(C2-C6 alkylene)-;

[0392] Each R 10 Independently selected from hydrogen; optionally substituted with a C1-C6 alkyl group selected from the following substituents: -N(R 20 )3、-(C6-C 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 aryl) and carboxyl; and each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl;

[0393] Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH;

[0394] Each R 30 Independently selected from (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (Aryl); and (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c ); where each R a Independently C1-C6 alkyl; and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3; and

[0395] Each X - Independently selected from the group consisting of: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate and borate, and their organic substituted derivatives;

[0396] The premise is:

[0397] When R 10 To be optionally selected from -(C6-C) 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 When the C1-C6 alkyl group is substituted with aryl and carboxyl substituents, the polyethyleneimine intermediate is independently selected from... , and .

[0398] In some embodiments, the polyethyleneimine intermediate is:

[0399] or ;

[0400] Each R 60 Independently selected from -Y groups optionally substituted by 1-3 substituents selected from the following 4-(C1-C 18 Alkyl groups: -OH, -N + (R 20 )3X - -(C1-C6 alkoxy), carboxyl, -(C6-C 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH; and at least one R 60 All R-substituted with -OH, but less than 50% 60 Replaced by -OH;

[0401] Y 4 It does not exist or is -C(O)-;

[0402] And each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary substituted N. 18 Heteroalkyl groups; and C6-C groups optionally substituted with the following: 10 Aryl groups: -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl);

[0403] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000; and

[0404] Each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0405] In some embodiments, the polyethyleneimine intermediate is:

[0406] or ;in

[0407] Each R 60 Independently selected from -Y groups optionally substituted by 1-3 substituents selected from the following 4 -(C1-C 18 Alkyl groups: -OH, -N + (R 20 )3X - -(C6-C 10Aryl), -C(O)O (C1-C6 alkyl) and -C(O)- (C6-C 10 (aryl); and at least one R 60 All R-substituted with -OH, but less than 50% 60 Replaced by -OH;

[0408] Y 4 It does not exist or is -C(O)-;

[0409] And each R 20 Independently selected from the group consisting of C1-C6 alkyl groups;

[0410] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000; and

[0411] Each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0412] In some embodiments, each R 60 Independently selected from -(C1-C) groups optionally substituted with -OH. 18 Alkyl); and at least one R 60 All R-substituted with -OH, but less than 50% 60 It is replaced by -OH.

[0413] In some embodiments, each R 60 Independently select from the following groups: -CH3, -C4H9, -C6H 13 -C8H 17 -C 18 H 37 , -CH2Ph, -CH2C(O)OCH2CH3, -CH2C(O)Ph, -(CH2)3OH, -CH2CH(CH3)OH, -CH2CH(OH)CH2N + (CH3)3 and -C(O)(CH2)5OH. In some embodiments, each R 60 Independently select from the following groups: -CH3, -C4H9, -C6H 13 -C8H 17 -C 18 H 37 , -CH2Ph, -CH2C(O)OCH2CH3, -CH2C(O)Ph, -(CH2)3OH, -CH2CH(CH3)OH, -CH2CH(OH)CH2N +(CH3)3 and -C(O)(CH2)5OH; and at least one R 60 All R-substituted with -OH, but less than 50% 60 It is replaced by -OH.

[0414] In some embodiments, at least one R 60 All R groups replaced by -OH, but less than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, or 49%. 60 Replaced by -OH. In some embodiments, about 1% to about 49% of all R 60 Replaced by -OH. This includes about 1% to about 40%, about 1% to about 30%, about 1% to about 20%, about 1% to about 18%, about 1% to about 15%, about 1% to about 10%, about 5% to about 40%, about 5% to about 30%, about 5% to about 20%, about 5% to about 18%, about 5% to about 15%, about 5% to about 10%, and any range therein.

[0415] In some embodiments, the polyethyleneimine intermediate is selected from the group consisting of:

[0416]

[0417] Where A is B is And each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 100. In some embodiments, one or more bromide anions are independently selected from the group consisting of X. - Substitution: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organic substituted derivatives.

[0418] In some embodiments, the polyethyleneimine intermediate is selected from the group consisting of:

[0419] ,

[0420] Where A is B is Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 100; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0421] In some embodiments, the second adduct has formula (I):

[0422] Formula (I)

[0423] in:

[0424] Each A is selected independently. , , , , , , or copolymers or blends of any two or more thereof; and the connection of each A forms a urethane bond;

[0425] Each Y 3 Independently H or -OY 2 , where each Y 3 Cannot be H;

[0426] Each Y 2 Independently H or -C(O)-NHR 30 , where each Y 2 Cannot be C(O)-NHR 30 ;

[0427] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000;

[0428] Z stands for -(C2-C6 alkylene)-;

[0429] Each R 10 Independently selected from hydrogen; optionally substituted with a C1-C6 alkyl group selected from the following substituents: -N(R 20 )3、-(C6-C 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 aryl) and carboxyl; and each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl;

[0430] Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH;

[0431] Each R 30 Independently selected from: (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c () and (3) ; where each R a Independently -(C1-C6 alkyl); and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3;

[0432] Each R 40 Independently, -(C1-C) substituted with phenyl groups 10 (alkylene)-, or 3- to 8-membered cycloalkyl ring; and,

[0433] Each X - Independently selected from the group consisting of: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate and borate, and their organic substituted derivatives;

[0434] The premise is:

[0435] When R 10 To be optionally selected from -(C6-C)10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 When a C1-C6 alkyl group is substituted with aryl and carboxyl substituents, then each A is independently selected from... , and .

[0436] In some embodiments, the second adduct has formula (II):

[0437] Equation (II)

[0438] in:

[0439] Each A is selected independently. , , , , , , or copolymers or blends of any two or more thereof; and the connection of each A forms a urethane bond;

[0440] Each Y 3 Independently H or -OY 2 , where each Y 3 Cannot be H;

[0441] Each Y 2 Independently H or -C(O)-NHR 30 , where each Y 2 Cannot be C(O)-NHR 30 ;

[0442] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000;

[0443] Z stands for -(C2-C6 alkylene)-;

[0444] Each R 10 Independently selected from hydrogen; optionally substituted with a C1-C6 alkyl group selected from the following substituents: -N(R 20 )3、-(C6-C 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 aryl) and carboxyl; and each R 20 Choose independently the following groups: C1-C 18Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl;

[0445] Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH;

[0446] Each R 30 Independently selected from: (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c () and (3) ; where each R a Independently -(C1-C6 alkyl); and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3;

[0447] Each R 40 Independently, -(C1-C) substituted with phenyl groups 10 (alkylene)-, or 3- to 8-membered cycloalkyl ring; and

[0448] Each X - Independently selected from the group consisting of: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate and borate, and their organic substituted derivatives;

[0449] The premise is:

[0450] When R 10 To be optionally selected from -(C6-C) 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 When a C1-C6 alkyl group is substituted with aryl and carboxyl substituents, then each A is independently selected from... , and .

[0451] In some embodiments, the second adduct is present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (4) in an amount of about 1% by weight to about 30% by weight. This includes any value between about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30% by weight. In some embodiments, the second adduct is present in the polymer, copolymer, or interpenetrating polymer network of polymerizing component (1) or (4) in an amount of about 3% by weight to about 15% by weight.

[0452] The reagent used for random polymerization / crosslinking products may further comprise (i) a first or fourth polyfunctional crosslinking agent and (ii) a third adduct of a second quaternary ammonium salt. ,in

[0453] R 1a R 2a and R 3a Each independently is -(C1-C 20 alkyl), -(C1-C 20 alkyl)-(C6-C 10 aryl) or -(C6-C 10 aryl)-(C1-C 20 alkyl);

[0454] A 1 The linking group is selected from the group consisting of: -(C3-C 20 alkylene)-, -(C3-C 20 (heteroalkyl)-, -(C6-C 10 (Asaryl)-(C3-C 20 alkylene), -(CR m1 R n1 ) x42 -W 42 -(CR p1 R q1 ) y42- and -(CR m1 R n1 ) x43 -W 43 -(CR p1 R q1 ) y43 -, where -(C3-C 20 (heteroalkyl) - having 1 to 4 heteroatoms independently selected from O, S and Si; and -(C3-C 20 alkylene)- and -(C3-C 20 (heteroalkyl) - optionally substituted by 1 to 6 independent substituents selected from the following: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 (Aromatic);

[0455] Each R m1 R n1 R p1 and R q1 Independently selected from H and C1-C4 alkyl groups;

[0456] W 42 Selected from -C(O)-; -C(O)O-; -OC(O)-; -C(O)NH-; and -NHC(O)-;

[0457] W 43 Selected from 5- to 6-membered cycloalkyl groups, C6-C 10 Aryl, 5- to 6-membered heterocyclic alkyl and 5- to 6-membered heteroaryl, wherein the heterocyclic alkyl contains 1-2 cyclic heteroatoms selected from O, N, S and Si; and the heteroaryl contains 1-3 cyclic heteroatoms selected from O, N, S and Si;

[0458] x42 is an integer from 1 to 19, and y42 is an integer from 1 to 19, where 3 ≤ (x42 + y42) ≤ 20;

[0459] x43 is an integer from 1 to 20, and y43 is an integer from 0 to 19, where 3 ≤ (x43 + y43) ≤ 20;

[0460] Y 1 Choose from the following groups: -OH, -NHR 4a -SH, -CO2H, -C(O)NHR 4a -C(S)NHR 4a , and ;

[0461] Each R 4a Independently select from the following groups: H, (C-(C6-C) 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 (Aryl) has 1 to 4 heteroatoms independently selected from O, S, and Si; and

[0462] X - It is independently an organic substituted derivative of acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, borate, or any of the foregoing.

[0463] The fourth multifunctional crosslinking agent may be present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 0.1% by weight to about 15% by weight. This includes 0.1, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, or 15% by weight, or any value between these values. In some embodiments, the fourth multifunctional crosslinking agent is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 2% by weight to about 8% by weight.

[0464] The fourth multifunctional crosslinker may be different from the first multifunctional crosslinker, different from the second multifunctional crosslinker (if present), and different from the third multifunctional crosslinker (if present).

[0465] In some embodiments, the fourth multifunctional crosslinking agent is a fourth polyisocyanate. In some embodiments, the fourth polyisocyanate is prepared from a diisocyanate selected from the group consisting of: hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), xylene diisocyanate (XDI), methylene-bis-(4-cyclohexyl isocyanate) (H12MDI), m-tetramethylxylene diisocyanate (TMXDI), and trimethylhexamethylene diisocyanate (TMDI). In some embodiments, the fourth polyisocyanate is selected from the group consisting of: DESMODUR® N-3300, DESMODUR® N-100, DESMODUR® Z4470SN, WANNATE® T-series polyisocyanates, and LUPRANATE® M-series polyisocyanates.

[0466] In some embodiments of the second quaternary ammonium salt, R 1a R 2a and R 3a At least one of them is -(C1-C4 alkyl). In some embodiments of the second quaternary ammonium salt, R 1a R 2a and R 3a Both of them are -(C1-C4 alkyl). In some embodiments, the second quaternary ammonium salt is (C18DMDEG-Br) or (C2DMDEG-Br).

[0467] The second quaternary ammonium salt may be present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 1% by weight to about 15% by weight. This includes any value between about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% by weight. In some embodiments, the second quaternary ammonium salt is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 3% by weight to about 10% by weight.

[0468] In some embodiments, the average isocyanate functionality of the third adduct is 2 to 3. In some embodiments, the average isocyanate functionality of the third adduct is 2.05 to about 2.3.

[0469] The third adduct may be present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 2% by weight to about 30% by weight. This includes about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30% by weight or any value between these values. In some embodiments, the second quaternary ammonium salt is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1) in an amount of about 3% by weight to about 20% by weight.

[0470] The reagent used for random polymerization / crosslinking products may further include a chain extender selected from the group consisting of: HO-(C n H 2n )-OH and HO-(C n H 2n-2 )-OH or combinations thereof, where n is an integer between 2 and 8. In some embodiments, the chain extender is propylene glycol, 1,4-butanediol, neopentyl glycol, hexanediol, cyclohexanediol, or a combination of two or more thereof. The chain extender may be present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing components (1) and (2) in an amount of about 0.5% by weight to about 10% by weight. This includes any value between about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% by weight. In some embodiments, the chain extender may be present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing components (1) and (2) in an amount of about 1% by weight to about 5% by weight.

[0471] In some embodiments, the polymeric component is a polymer, an interpenetrating polymer network, a polyelectrolyte complex, a blend, or a composite material, each comprising a random polymerization / crosslinking product of a reagent or substantially composed of: (i) a first adduct of a first polyfunctional crosslinker with a first quaternary ammonium salt; (ii) an optional polyol; (iii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate with a second polyfunctional crosslinker; (iv) an optional third polyfunctional crosslinker; (v) an optional third adduct of (a) a first or fourth polyfunctional crosslinker with (b) a second quaternary ammonium salt; (vi) an optional chain extender; and (vii) a water-soluble polymer.

[0472] In some embodiments, the polymeric component is a polymer, an interpenetrating polymer network, a polyelectrolyte complex, a blend, or a composite material, each comprising a random polymerization / crosslinking product of a reagent or substantially composed of: (i) a first adduct of a first polyfunctional crosslinker with a first quaternary ammonium salt; (ii) an optional polyol; (iii) a polyethyleneimine intermediate, or a second adduct of a polyethyleneimine intermediate with a second polyfunctional crosslinker; (iv) an optional third polyfunctional crosslinker; (v) an optional third adduct of (a) a first or fourth polyfunctional crosslinker with (b) a second quaternary ammonium salt; and (vi) an optional chain extender.

[0473] In some embodiments, the polymer component further comprises a third quaternary ammonium salt. ,in,

[0474] R 1a R 2a and R 3a Each can be independently methyl or ethyl;

[0475] A 2 Choose from the following groups: -(C3-C 20 alkylene)-, -(C3-C 20 (heteroalkyl)-, -(C6-C 10 (Asaryl)-(C3-C 20 alkylene)-, -(CR m1 R n1 ) x42 -W 42 -(CR p1 R q1 ) y42 - and -(CR m1 R n1 ) x43 -W 43 -(CR p1 R q1 ) y43 -, where -(C3-C 20 (heteroalkyl) - having 1 to 4 heteroatoms independently selected from O, S and Si; and -(C3-C 20 alkylene)- and -(C3-C 20 (heteroalkyl) - optionally substituted by 1 to 6 independent substituents selected from the following: -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10aryl) and -(C6-C 10 (Aromatic);

[0476] Each R m1 R n1 R p1 and R q1 Independently selected from H and C1-C4 alkyl groups;

[0477] W 42 Selected from -C(O)-; -C(O)O-; -OC(O)-; -C(O)NH-; and -NHC(O)-;

[0478] W 43 Selected from 5- to 6-membered cycloalkyl groups, C6-C 10 Aryl, 5- to 6-membered heterocyclic alkyl and 5- to 6-membered heteroaryl, wherein the heterocyclic alkyl contains 1-2 cyclic heteroatoms selected from O, N, S and Si; and the heteroaryl contains 1-3 cyclic heteroatoms selected from O, N, S and Si;

[0479] x42 is an integer from 1 to 19, and y42 is an integer from 1 to 19, where 3 ≤ (x42 + y42) ≤ 20;

[0480] x43 is an integer from 1 to 20, and y43 is an integer from 0 to 19, where 3 ≤ (x43 + y43) ≤ 20;

[0481] Y 1a For H;

[0482] Each R 4a Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 (Aryl) has 1 to 4 heteroatoms independently selected from O, S, and Si; and

[0483] X - It is independently an organic substituted derivative of acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, borate, or any of the foregoing.

[0484] In some embodiments, a first quaternary ammonium salt reacts with a first polyisocyanate to form a first adduct, wherein the first adduct retains unreacted isocyanate functional groups in the first polyisocyanate. In some embodiments, about 10% to about 40%, preferably about 25% to about 33%, of the isocyanate functional groups on the first polyisocyanate are converted to, for example, urethane or urea, by reacting with the first quaternary ammonium salt. The unreacted isocyanate functional groups are then reacted with one or more of a polyol (if present), a chain extender (if present), a polyethyleneimine intermediate or a second adduct, water, and a water-soluble polymer (if reactive). Similarly, in some embodiments, a second quaternary ammonium salt reacts with a first or fourth polyisocyanate to form a third adduct, wherein the third adduct retains unreacted isocyanate functional groups in the first or fourth polyisocyanate. In some embodiments, about 10% to about 40%, preferably about 25% to 33%, of the isocyanate functional groups on the first or fourth polyisocyanate are converted to, for example, urethane or urea, by reacting with the second quaternary ammonium salt. The third multifunctional crosslinking agent (if present) and / or the third adduct may also react with one or more of the following: a polyol (if present), a chain extender (if present), a polyethyleneimine intermediate or the second adduct, water, and a water-soluble polymer (if reactive). The first and third adducts are pre-formed prior to interaction with the polyol (if present), the chain extender (if present), the polyethyleneimine intermediate or the second adduct, and the water-soluble polymer (if reactive).

[0485] In another aspect, the polymer or interpenetrating polymer network is prepared by the following:

[0486] (a) Reacting the first multifunctional crosslinking agent with the first quaternary ammonium salt to form the first adduct;

[0487] (b) Optionally, react the polyethyleneimine intermediate with a second multifunctional crosslinking agent to form a second adduct;

[0488] (c) Optionally, react the first or fourth multifunctional crosslinking agent with the second quaternary ammonium salt to form a third adduct;

[0489] (d) Combining (i) the first adduct, (ii) the polyethyleneimine intermediate or the second adduct and (iii) the third adduct (if present) with an optional polyol and an optional third multifunctional crosslinking agent to form an oil phase;

[0490] (e) Dissolving the water-soluble polymer in water to form an aqueous phase;

[0491] (f) Combining the oil phase with the aqueous phase to form an oil-in-water emulsion; and,

[0492] (g) The emulsion is coated onto a surface and the emulsion is dried and cured on the surface to form the polymer or interpenetrating polymer network on the surface.

[0493] In some embodiments, a capping agent is added to the oil phase after step (d) but before step (f).

[0494] In some embodiments, step (d) further comprises combining (i) the first adduct, (ii) the polyethyleneimine intermediate or the second adduct and (iii) the third adduct (if present) with an optional polyol and an optional second multifunctional crosslinker in an organic solvent or diluent to form an oil phase.

[0495] In some embodiments, step (d) further comprises adding a chain extender to the oil phase. In some embodiments, step I further comprises adding a chain extender to the aqueous phase.

[0496] In some embodiments, step I further comprises adding a surfactant to the aqueous phase. In some embodiments, step I further comprises adding a defoamer or antifoaming agent to the aqueous phase. In some embodiments, step I further comprises adding a surfactant and a defoamer or antifoaming agent to the aqueous phase.

[0497] In some embodiments, step (f) further comprises performing a direct emulsification process, wherein an emulsion is formed by vigorous shearing and mixing. In some embodiments, step (f) further comprises performing a direct emulsification process, wherein an emulsion is formed by ultrasonic treatment.

[0498] In some embodiments, step (f) further comprises performing a phase inversion emulsification process, wherein an oil-in-water emulsion is first prepared, followed by phase inversion to form an oil-in-water emulsion. Phase inversion can be performed, for example, by changing the phase ratio, temperature, surfactant, solvent, or any combination of both or more thereof.

[0499] In some embodiments, the multiphase water-in-oil-in-water emulsion is formed prior to conversion into an oil-in-water emulsion in step (f).

[0500] In some embodiments, in step (f), the oil phase and the aqueous phase are combined to form a combination of an oil-in-water emulsion and a multiphase oil-in-water emulsion.

[0501] In another aspect, the reagents used to prepare the polymer or interpenetrating polymer network described herein are included in the composition.

[0502] Therefore, in another aspect, this document provides a composition comprising an oil-in-water emulsion, wherein the oil-in-water emulsion comprises

[0503] (i) The oil phase, which comprises:

[0504] A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0505] Optional polyols;

[0506] Polyethyleneimine intermediate, or a second adduct of said polyethyleneimine intermediate with a second polyfunctional crosslinking agent; and,

[0507] Optional third multifunctional crosslinking agent; and,

[0508] (ii) an aqueous phase containing water-soluble polymers.

[0509] This composition can be applied to a surface and allowed to dry and cure, thereby forming a polymer or interpenetrating polymer network according to the present invention.

[0510] The reactive linking group of the first quaternary ammonium salt can be selected from the group consisting of: -OH, -NHR 4 -SH, -CO2H, -C(O)NHR 4 -C(S)NHR 4 , and , where each R 4 Independently select from the following groups: H, -(C6-C 10 aryl)-(C1-C3 alkyl), -(C6-C 10 aryl)-(C1-C3 heteroalkyl), -(C1-C3 alkyl)-(C6-C 10 aryl), -(C1-C3 heteroalkyl)-(C6-C 10 aryl) and -(C6-C 10 aryl), wherein -(C6-C 10 aryl)-(C1-C3 heteroalkyl) and -(C1-C3 heteroalkyl)-(C6-C 10 Aryl groups have 1 to 4 heteroatoms independently selected from O, S and Si.

[0511] Based on the dry weight of the oil phase, the first quaternary ammonium salt described herein and incorporated in the first adduct may be present in the oil phase in an amount from about 1% by weight to about 50% by weight. As used herein, and unless otherwise specified, "dry weight of the oil phase" means the weight of the oil phase in the absence of any organic solvent and any water. This includes about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50% or any value between these values. In some embodiments, the first quaternary ammonium salt incorporated into the first adduct exists in the oil phase in an amount of about 1% to about 25% by weight, or about 5% to about 25% by weight, based on the dry weight of the oil phase.

[0512] Based on the dry weight of the oil phase, the first polyfunctional crosslinking agent (e.g., the first polyisocyanate) described herein and incorporated into the first adduct may be present in the oil phase in an amount from about 2% by weight to about 25% by weight. This includes about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25%, or any value between these values. In some embodiments, based on the dry weight of the oil phase, the first polyfunctional crosslinking agent (e.g., the first polyisocyanate) incorporated into the first adduct is present in the oil phase in an amount from about 5% by weight to about 20% by weight.

[0513] The first adduct described herein may be present in the oil phase in an amount from about 5% by weight to about 70% by weight, based on the dry weight of the oil phase. This includes about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, or 70%, or any value between these values. In some embodiments, the first adduct is present, on a dry weight basis of the oil phase, in an amount of about 10% to about 50% by weight, about 15% to about 65% by weight, about 15% to about 60% by weight, about 15% to about 50% by weight, about 20% to about 70% by weight, about 20% to about 60% by weight, or about 20% to about 50% by weight.

[0514] The polyethyleneimine intermediates described herein may be present in the oil phase in amounts from about 0.1% by weight to about 50% by weight, based on the dry weight of the oil phase. This includes 0.1%, 0.25%, 0.5%, 0.75%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 10.5%, 11%, 11.5%, 12%, 12.5%, 13%, 13.5%, 14%, 14.5%, 15%, 15.5%, 16%, 16%. 5%, 17%, 17.5%, 18%, 18.5%, 19%, 19.5%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, or 50%, or any value between these values. In some embodiments, the polyethyleneimine intermediate is present in the oil phase in an amount of about 3% to about 30% by weight, based on the dry weight of the oil phase.

[0515] The second polyfunctional crosslinking agent (e.g., the second polyisocyanate) described herein and incorporated into the second adduct may be present in the oil phase in an amount from about 0.1% to about 10% by weight, based on the dry weight of the oil phase. This includes any value between about 0.1%, 0.25%, 0.5%, 0.75%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10%. In some embodiments, the second polyfunctional crosslinking agent (e.g., the second polyisocyanate) is present in the oil phase in an amount from about 2% to about 8% by weight, or from about 3% to about 6% by weight, based on the dry weight of the oil phase.

[0516] The second adduct described herein may be present in the oil phase in an amount from about 1% to about 30% by weight, based on the dry weight of the oil phase. This includes about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% or any value between these values. In some embodiments, the second adduct is present in the oil phase in an amount from about 3% to about 15% by weight, based on the dry weight of the oil phase.

[0517] In some embodiments, the oil phase further comprises a third polyfunctional crosslinker as described herein. The third polyfunctional crosslinker (e.g., a third polyisocyanate) may be present in the oil phase in an amount from about 5% by weight to about 25% by weight, based on the dry weight of the oil phase. This includes any value between about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, or 25%. In some embodiments, the third polyfunctional crosslinker (e.g., a third polyisocyanate) is present in the oil phase in an amount from about 5% by weight to about 20% by weight, based on the dry weight of the oil phase.

[0518] In some embodiments, the oil phase further comprises the third adduct described herein. The third adduct may be present in the oil phase in an amount from about 2% by weight to about 30% by weight, based on the dry weight of the oil phase. This includes about 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, or 30% or any value between these. In some embodiments, the third adduct is present in the oil phase in an amount from about 3% by weight to about 20% by weight, based on the dry weight of the oil phase.

[0519] In some embodiments, the second quaternary ammonium salt described herein and incorporated into the third adduct is present in the oil phase in an amount of about 1% to about 15% by weight, based on the dry weight of the oil phase. This includes any value between about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15%. In some embodiments, the second quaternary ammonium salt described herein and incorporated into the third adduct is present in the oil phase in an amount of about 3% to about 10% by weight, based on the dry weight of the oil phase.

[0520] Based on the dry weight of the oil phase, the fourth polyfunctional crosslinking agent (e.g., the fourth polyisocyanate) described herein and incorporated into the third adduct may be present in the oil phase in an amount from about 0.1% by weight to about 15% by weight. This includes any value between about 0.1%, 0.25%, 0.5%, 0.75%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 4.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10%, 11%, 12%, 13%, 14%, or 15%. In some embodiments, based on the dry weight of the oil phase, the fourth polyfunctional crosslinking agent (e.g., the fourth polyisocyanate) described herein and incorporated into the third adduct is present in the oil phase in an amount from about 2% by weight to about 8% by weight.

[0521] In some embodiments, the reactive isocyanate functional groups on the first and / or third adducts are protected by a capping agent. Reaction with the capping agent converts the reactive isocyanate functional groups into capped isocyanates (i.e., the isocyanate groups are reversibly protected from immediate reaction with nucleophiles). This reduces the reaction rate of the polyisocyanate with water and / or the crosslinking rate with, for example, any polyols in the oil phase and / or water-soluble polymers (e.g., hydroxyethyl cellulose) in the aqueous phase during subsequent emulsification steps. In some embodiments, rheological properties, particle size, and reproducibility of the resulting emulsion distribution are significantly improved. In some embodiments, the coatability and processing range of the coating process are also significantly improved. In some embodiments, the defect rate of the resulting surface coating is reduced, and the yield of the coated product is also improved. In some embodiments, a capping agent is not used to provide a faster-curing coating.

[0522] In some embodiments, the capping agent is selected from the group consisting of: oximes, phenols, malonates, alcohols, lactams, dicarbonyl compounds, isohydroxyoxime acids, bisulfite addition compounds, hydroxylamines, parabens, and salicylates. In some embodiments, the capping agent is selected from the group consisting of: acetone oximes, methyl ethyl ketone oximes, sodium bisulfite, diethyl malonate, and 3,5-dimethylpyrazole.

[0523] In some embodiments, the composition further comprises a deblocking agent. Deblocking agents include, but are not limited to, organotin compounds, organobismuth compounds, and tertiary amines. Non-limiting examples include triethanolamine; N,N,N'N'-tetra(2-hydroxyethyl)ethylenediamine; and K-KATXK-651 (bismuth carboxylate catalyst).

[0524] In some embodiments, the oil phase further comprises a chain extender selected from the group consisting of: HO-(C n H 2n )-OH and HO-(C n H 2n-2 The chain extender is propylene glycol, 1,4-butanediol, neopentyl glycol, hexanediol, cyclohexanediol, or a combination of two or more thereof. The chain extender may be present in the oil phase at a maximum of about 10% by weight, based on the dry weight of the oil phase. This includes any value between about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or the like. In some embodiments, the chain extender is present in the oil phase at about 0.5% by weight to about 10% by weight, or about 1% by weight to about 5% by weight, based on the dry weight of the oil phase.

[0525] In some embodiments, the oil phase further comprises an organic solvent or diluent. In some embodiments, the organic solvent or diluent in the oil phase is water-miscible. In some embodiments, the organic solvent or diluent is acetone. In some embodiments, the organic solvent or diluent is present in the oil phase in an amount of about 5% to about 35% by weight, based on the weight of the oil phase. This includes about 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, or 35%, or any value between these values. In some embodiments, the organic solvent or diluent is present in the oil phase in an amount of about 10% to about 30% by weight, based on the weight of the oil phase.

[0526] Based on the dry weight of the oil phase, the polyol may be present in the oil phase in an amount from about 1% by weight to about 40% by weight. This includes about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, or 40%, or any value between these values. In some embodiments, based on the dry weight of the oil phase, the polyol is present in the oil phase in an amount from about 5% by weight to about 25% by weight.

[0527] The weight percentage of the water-soluble polymer in the aqueous phase is calculated by the amount present in the oil phase that interacts with the oil phase itself and / or oil phase components (e.g., the first adduct, optionally the second multifunctional crosslinker). The water-soluble polymer described herein may be present in the aqueous phase in an amount from about 0.5% by weight to about 15% by weight of the dry weight of the oil phase. This includes about 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15% or any value between these values. In some embodiments, the water-soluble polymer described herein is present in the aqueous phase in an amount from about 3% by weight to about 12% by weight, or from about 5% by weight to about 10% by weight of the dry weight of the oil phase.

[0528] The water-soluble polymer may be a reactive water-soluble polymer and crosslinked with one or more of a first adduct and a third multifunctional crosslinking agent (if present). In some embodiments, the water-soluble polymer is a reactive water-soluble polymer and crosslinked with the first adduct, the third multifunctional crosslinking agent (if present), the third adduct (if present), or any combination of both or more of the foregoing.

[0529] In some embodiments, the water-soluble polymer is a non-reactive water-soluble polymer and is not covalently bonded to any component in the oil or aqueous phase (e.g., a first adduct, a third multifunctional crosslinker (if present)), a third adduct (if present, or any combination of the two or more thereof).

[0530] In some embodiments, the aqueous phase further comprises a water-soluble low molecular weight chain extender or crosslinker. The inclusion of a water-soluble low molecular weight chain extender or crosslinker can increase the degree of crosslinking of the random polymerization product. Examples of water-soluble low molecular weight chain extenders or crosslinkers include, but are not limited to, polyfunctional amines, such as ethylenediamine, diethylenetriamine, and triethylenetetramine.

[0531] In some embodiments, the aqueous phase further comprises a surfactant. In some embodiments, the surfactant is a nonionic surfactant. In some embodiments, the average hydrophilicity-lipophilicity balance (HLB) value of the nonionic surfactant is preferably about 12 to about 15. Nonionic surfactants include, but are not limited to, TRITON. TM X-114 ((1,1,3,3-tetramethylbutyl)phenyl-polyethylene glycol), SILWET TM L-7604 (siloxane polyether copolymer) and combinations thereof.

[0532] The weight percentage of surfactant in the aqueous phase is calculated by the amount present in the oil phase that interacts with or adsorbs onto the oil phase. Based on the dry weight of the oil phase, the surfactant may be present in the aqueous phase in an amount from about 0.01% by weight to about 2% by weight. This includes about 0.05%, 0.075%, 0.1%, 0.25%, 0.5%, 0.75%, 1%, 1.25%, 1.5%, 1.75%, or 2% or any value between these values. In some embodiments, based on the dry weight of the oil phase, the surfactant is present in the aqueous phase in an amount from about 0.05% by weight to about 2% by weight, or from about 0.1% by weight to about 1% by weight.

[0533] In some embodiments, the aqueous phase further comprises a defoamer or antifoaming agent. In some embodiments, the defoamer is FOAMSTAR. ® ST 2410 (a star-shaped polymer-based defoamer).

[0534] Polyethyleneimine intermediates can be used as antimicrobial compounds. In some embodiments, quaternization does not occur on the polyethyleneimine backbone, but rather on the side chain substitution. Therefore, in another aspect, this document provides an antimicrobial compound selected from:

[0535] , , , , , , or copolymers or blends of any two or more thereof, wherein:

[0536] Each Y 3 Independently H or -OY 2 ;

[0537] Each Y 2 Independently H or -C(O)-NHR 30 ;

[0538] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000;

[0539] Z stands for -(C2-C6 alkylene)-;

[0540] Each R 10 For -N + (R 20 )3X - Substituted C1-C6 alkyl groups, and each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary substituted N. 18 Heteroalkyl groups; and C6-C groups optionally substituted with the following: 10 Aryl groups: -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl);

[0541] Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH;

[0542] Each R 30 Independently selected from (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (Aryl); and (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c ); where each R a Independently C1-C6 alkyl; and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3; and

[0543] Each X -The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0544] In some embodiments, each Y 2 For H.

[0545] In some embodiments, the compound is selected from:

[0546] ,

[0547] Where A is B is And each n is an integer independently selected from 1 to 3000 or 2 to 3000, preferably an integer independently selected from 10 to 100. In some embodiments, one or more bromide anions are independently selected from the group consisting of X. - Substitution: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organic substituted derivatives.

[0548] In some embodiments, the compound is selected from:

[0549] ,

[0550] Where A is B is Each n is an integer independently selected from 1 to 3000 or 2 to 3000, preferably an integer independently selected from 10 to 100; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0551] The second adduct, a random polymerization product of the polyethyleneimine intermediate disclosed herein and a (multifunctional) crosslinking agent, can be used as an antimicrobial compound. Therefore, in another aspect, a random polymerization product of a polyethyleneimine intermediate and a crosslinking agent is provided, wherein the polyethyleneimine intermediate is selected from:

[0552] , , , , , , or copolymers or blends of any two or more thereof, wherein:

[0553] Each Y 3 Independently H or -OY 2 , where each Y 3 Cannot be H;

[0554] Each Y 2 Independently H or -C(O)-NHR 30 , where each Y 2 Cannot be -C(O)-NHR 30 ;

[0555] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000;

[0556] Z stands for -(C2-C6 alkylene)-;

[0557] Each R 10 For -N + (R 20 )3X - Substituted C1-C6 alkyl groups, and each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and optionally C6-C substituted with the following: 10 Aryl groups: -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl);

[0558] Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH;

[0559] Each R 30 Independently selected from (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10(Aryl); and (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c ); where each R a Independently C1-C6 alkyl; and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3; and

[0560] Each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0561] In some embodiments, the crosslinking agent is a polyisocyanate. In some embodiments, the polyisocyanate is prepared from diisocyanates independently selected from the group consisting of: hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), xylene diisocyanate (XDI), methylene-bis-(4-cyclohexyl isocyanate) (H12MDI), m-tetramethylxylene diisocyanate (TMXDI), and trimethylhexamethylene diisocyanate (TMDI). In some embodiments, the polyisocyanate is independently selected from the group consisting of: DESMODUR® N-3300, DESMODUR® N-100, DESMODUR® Z4470SN, WANNATE® T series polyisocyanates, and LUPRANATE® M series polyisocyanates.

[0562] In some embodiments, the random polymerization product has formula (I):

[0563] Formula (I),

[0564] in:

[0565] Each A is selected independently. , , , , , , or copolymers or blends of any two or more thereof; and the connection of each A forms a urethane bond;

[0566] Each Y 3 Independently H or -OY2 , where each Y 3 Cannot be H;

[0567] Each Y 2 Independently H or -C(O)-NHR 30 , where each Y 2 Cannot be -C(O)-NHR 30 ;

[0568] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000;

[0569] Z stands for -(C2-C6 alkylene)-;

[0570] Each R 10 For -N + (R 20 )3X - Substituted C1-C6 alkyl groups, and each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and optionally C6-C substituted with the following: 10 Aryl groups: -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl);

[0571] Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH;

[0572] Each R 30 Independently selected from: (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR.a (OR b (OR) c () and (3) ; where each R a Independently -(C1-C6 alkyl); and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3;

[0573] Each R 40 Independently, -(C1-C) substituted with phenyl groups 10 (alkylene)-, or 3- to 8-membered cycloalkyl ring; and,

[0574] Each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0575] In some embodiments, the random polymerization product has formula (II):

[0576] Equation (II),

[0577] in:

[0578] Each A is selected independently. , , , , and , or copolymers or blends of any two or more thereof; and the connection of each A forms a urethane bond;

[0579] Each Y 3 Independently H or -OY 2 , where each Y 3 Cannot be H;

[0580] Each Y 2 Independently H or -C(O)-NHR 30 , where each Y 2 Cannot be -C(O)-NHR 30 ;

[0581] Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000;

[0582] Z stands for -(C2-C6 alkylene)-;

[0583] Each R 10For -N + (R 20 )3X - Substituted C1-C6 alkyl groups, and each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and optionally C6-C substituted with the following: 10 Aryl groups: -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl);

[0584] Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH;

[0585] Each R 30 Independently selected from: (1) C6-C 20 Alkyl group, optionally substituted by 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c () and (3) ; where each R a Independently -(C1-C6 alkyl); and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3;

[0586] Each R 40 Independently, -(C1-C) substituted with phenyl groups 10 (alkylene)-, or 3- to 8-membered cycloalkyl ring; and

[0587] Each X -The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0588] In another respect, this article provides a polymer with wound-healing properties comprising, substantially comprising, or comprising a polyethyleneimine intermediate, wherein the ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:1.

[0589] In some embodiments, the polymer is selected from the group consisting of:

[0590] ,

[0591] Where A is B is And each n is an integer independently selected from 2 to 3000, preferably an integer independently selected from 10 to 100.

[0592] In some embodiments, the polymer is selected from the group consisting of:

[0593] ,

[0594] Where A is B is And each n is an integer independently selected from 2 to 3000, preferably an integer independently selected from 10 to 100. In some embodiments, one or more bromide anions are independently selected from the group consisting of X. - Substitution: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organic substituted derivatives.

[0595] In some embodiments, the polymer is selected from the group consisting of:

[0596] ,

[0597] Where A is B is Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 100; and each X -The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

[0598] It should be understood that the polymers described herein and their general preparation methods offer considerable flexibility to tailor and fine-tune their physical and chemical properties, as well as their antimicrobial properties, for a wide range of different surfaces, substrates, and applications. Examples of variables that can be used for this fine-tuning include, but are not limited to, the structure and amount of each of the following: a first quaternary ammonium salt, optional polyol, optional chain extender, water-soluble polymer, a first polyfunctional crosslinker (e.g., a first polyisocyanate), a polyethyleneimine intermediate or a second adduct (an adduct of its second polyfunctional crosslinker, such as a second polyisocyanate), optional a third polyfunctional crosslinker (e.g., a third polyisocyanate), optional a second quaternary ammonium salt, optional a fourth polyfunctional crosslinker (e.g., a fourth polyisocyanate); and the degree of crosslinking. It should also be understood that polyfunctional crosslinkers other than polyisocyanates can be used, such as, but not limited to, polyfunctional epoxides, imides, carbodiimides, and aldehydes.

[0599] Compositions and Formulations

[0600] In another aspect, this document provides a composition comprising, substantially consisting of, or consisting of the polymeric components described herein.

[0601] In another respect, this document provides a composition comprising, substantially consisting of, or consisting of the following polymeric components selected from the group consisting of:

[0602] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0603] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0604] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0605] (iii) Optional polyols;

[0606] (iv) optional water-soluble polymers; and,

[0607] (v) An optional third multifunctional crosslinking agent;

[0608] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0609] (3) Polyethyleneimine intermediates;

[0610] (4) Second adduct; and,

[0611] (5) A combination of the two or more of the above;

[0612] And at least one pharmaceutically acceptable excipient.

[0613] In some embodiments, the composition comprises, is substantially composed of, or consists of the following: polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or consist of the following:

[0614] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0615] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0616] (iii) Optional polyols;

[0617] (iv) optional water-soluble polymers; and,

[0618] (v) An optional third multifunctional crosslinker.

[0619] In some embodiments, the composition comprises, is substantially composed of, or is composed of: a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend, and composite material, wherein the polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend, and composite material comprises, is substantially composed of, or is composed of: a first adduct, a polyol, a water-soluble polymer, and optionally a third multifunctional crosslinker.

[0620] In some embodiments, the composition comprises, is substantially composed of, or is composed of the polyethyleneimine intermediate described herein.

[0621] In some embodiments, the composition comprises, is substantially composed of, or is composed of the second adduct described herein.

[0622] In some embodiments, the polymeric component comprises, is substantially composed of, or is composed of the following: a polymer or interpenetrating polymer network as described in U.S. Provisional Application No. 63 / 410,714 or U.S. Provisional Application No. 63 / 410,722, the contents of which are hereby incorporated herein by reference.

[0623] In some embodiments, the polymeric component is present in the composition when applied to a subject or to a wound site of a subject. In some embodiments, precursors to the polymeric component are present in the composition when applied to a subject or to a wound site of a subject, and the precursors react with each other to provide the polymeric component. In non-limiting examples, the composition comprises, is substantially composed of, or is composed of the oil-in-water emulsion described herein. In some embodiments, the oil-in-water emulsion is as described in U.S. Provisional Application No. 63 / 410,714 or U.S. Provisional Application No. 63 / 410,722.

[0624] The compositions described herein may include at least one pharmaceutically acceptable excipient.

[0625] The compositions described herein are formulated for topical application. Topical formulations include, but are not limited to, creams, gels, pastes, foams, sprays, powders, emulsions, liquids, or ointments. In some embodiments, the liquid is a solution. In some embodiments, the liquid is a suspension. In some embodiments, the liquid is an oil.

[0626] Pharmaceutically acceptable excipients include solvents, thickeners, preservatives, emulsifiers and / or surfactants, pH adjusters and buffers, penetration enhancers, antioxidants, chelating agents, solubilizers, viscosity enhancers, emollients, etc. "Pharmaceutically acceptable" means a material that is not biologically or otherwise undesirable; for example, the material can be incorporated into a pharmaceutical composition administered to a patient without causing any undesirable biological effects or interacting in a harmful manner with any other component of the composition containing it. When the term "pharmaceutically acceptable" is used to refer to a pharmaceutical carrier or excipient, it implies that the carrier or excipient has met the standards required for toxicological and manufacturing testing or is included in the Inactive Ingredient Guide prepared by the US Food and Drug Administration.

[0627] Examples of solvents include, but are not limited to, sterile water, glycerol, medium-chain triglycerides, isopropyl myristate, diisopropyl adipate, isopropyl palmitate, propylene glycol, olive oil, castor oil, coconut oil, light mineral oil, diethylene glycol monoethyl ether (TRANSCUTOL® P), diethyl sebacate, benzyl alcohol, cyclomethicone, PEG 400, anhydrous ethanol, and dimethyl isosorbide dimethyl ester.

[0628] Thickeners may be selected from crosslinked polyacrylic acid polymers (e.g., carbomer); cellulose derivatives (e.g., hydroxyethyl cellulose, ethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, sodium carboxymethyl cellulose); alginate, locust bean gum, guar gum, or their derivatives; inorganic polymers (e.g., Weegum, an aluminum and magnesium silicate); PEMULEN™ (a copolymer of acrylic acid and C10-C30 alkyl acrylates crosslinked with allyl pentaerythritol); or any combination thereof. Examples of thickeners include, but are not limited to, alginate, cetearyl alcohol, PROMULGEN® D, CARBOPOL® 974P NF polymer, PEMULEN® TR-2, PEMULEN® TR-1, KLUCEL® HG Pharm, CARBOPOL® 980 NF polymer, and SEPINEO® P 600. Commercial carbomers include, but are not limited to, CARBOPOL® polymers such as CARBOPOL® Ultrez 10 NF, CARBOPOL® Ultrez 20, CARBOPOL® ETD 2020 NF, CARBOPOL® 71G NF, CARBOPOL® 971P NF, CARBOPOL® 974P NF, CARBOPOL® 980 NF, CARBOPOL® 981 NF, and CARBOPOL® 5984 EP. CARBOPOL® Ultrez 10 NF and CARBOPOL® ETD 2020 NF are carbomer homopolymers or copolymers containing block copolymers of polyethylene glycol and long-chain alkyl esters.

[0629] Examples of preservatives include, but are not limited to, phenoxyethanol, urea derivatives (such as, but not limited to, diazoalkylurea and imidazoalkylurea), ethylhexylglycerin, hydantoin, benzoic acid, sorbic acid, anisic acid, methylparaben, and propylparaben.

[0630] Examples of emulsifiers include, but are not limited to, BRIJ® L4, ARLACEL® 165, TWEEN® 20, BRIJ® S721, BRIJ® S2, PROMULGEN® D, stearyl chloride dimethylbenzylamine, PEMULEN® TR-2, PEMULEN® TR-1, sodium monostearate, SEPINEO® P 600, lauryl ether-4, polysorbate 20, dehydrated sorbitan monostearate, and PEG-35 castor oil. Nonionic emulsifiers include, but are not limited to, BRIJ® L4, ARLACEL® 165, sodium monostearate, lauryl ether-4, polysorbate 20, and PEG-35 castor oil. Cationic surfactants include, but are not limited to, stearyl chloride dimethylbenzylamine.

[0631] Examples of pH adjusters and buffers include, but are not limited to, triethanolamine, hydrogen chloride, sodium hydroxide, potassium hydroxide, and cocamidodiethylamine.

[0632] Examples of penetration enhancers include, but are not limited to, sulfoxides, such as dimethyl sulfoxide (DMSO) and decylmethyl sulfoxide (C2SO). 10 MSO); ethers, such as diethylene glycol monoethyl ether (commercially available as TRANSCUTOL® P) and diethylene glycol monomethyl ether; 1-substituted azaheptan-2-ones, such as 1-n-dodecyl-cycloazaheptan-2-one; alcohols, such as propanol, octanol, benzyl alcohol, etc.; fatty acids, such as lauric acid, oleic acid and valeric acid; fatty acid esters, such as isopropyl myristate, isopropyl palmitate, methyl propionate and ethyl oleate; polyol esters, such as butanediol and polyethylene glycol monolaurate; amides and other nitrogen-containing compounds, such as urea, N,N-dimethylacetamide (DMA), N,N-dimethylformamide (DMF), 2-pyrrolidone, 1-methyl-2-pyrrolidone, ethanolamine, diethanolamine and triethanolamine; terpenes and terpenoids; ketones; organic acids, such as salicylic acid and salicylates, citric acid and succinic acid, etc.; and any mixtures thereof. Suitable penetration enhancers also include, but are not limited to, medium-chain triglycerides, isopropyl myristate, diisopropyl adipate, isopropyl palmitate, propylene glycol, diethylene glycol monoethyl ether (TRANSCUTOL® P), oleyl alcohol, anhydrous ethanol, benzyl alcohol, lauryl ether-4, diethyl sebacate, and dimethyl isosorbide.

[0633] Examples of antioxidants include, but are not limited to, citric acid, butylated hydroxytoluene, ascorbic acid, glutathione, retinol, α-tocopherol, β-carotene, α-carotene, ubiquinone, butylated hydroxyanisole, EDTA, selenium, zinc, lignans, uric acid, lipoic acid, and N-acetylcysteine.

[0634] Examples of chelating agents include, but are not limited to, EDTA or its salts and / or solvates citric acid; and tartaric acid.

[0635] Examples of solubilizers include, but are not limited to, lauryl alcohol polyether-4.

[0636] Examples of viscosity enhancers include, but are not limited to, PEG 3350.

[0637] Examples of emollients include, but are not limited to, olive oil, medium-chain triglycerides, isopropyl myristate, diisopropyl adipate, isopropyl palmitate, castor oil, light mineral oil, cyclomethicone, diethyl sebacate, benzyl alcohol, PEG-35 castor oil, and coconut oil.

[0638] wound dressing

[0639] In another respect, wound dressings comprising the polymeric components described herein are provided herein.

[0640] In another respect, this article provides wound dressings comprising polymeric components selected from the group consisting of:

[0641] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0642] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0643] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0644] (iii) Optional polyols;

[0645] (iv) optional water-soluble polymers; and,

[0646] (v) An optional third multifunctional crosslinking agent;

[0647] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0648] (3) Polyethyleneimine intermediates;

[0649] (4) Second adduct; and,

[0650] (5) A combination of the two or more of the above.

[0651] In some embodiments, the outer layer of the wound dressing contains a polymeric component. In some embodiments, the polymeric component is impregnated into the wound dressing.

[0652] The dressings described herein include or are equipped with a coating, coating fluid, or spray fluid comprising, substantially comprising, or composed of the compositions described herein. The dressings are advantageously configured to absorb exudates, retain moisture, allow gas exchange, provide thermal insulation, act as an anti-infective agent (e.g., between the wound site and the environment), be easily removable, and be biocompatible. In some embodiments, the dressings are configured for single use and / or sterile. In some embodiments, the dressings are configured for use in local negative pressure therapy.

[0653] For example, such dressings may include wraps, coverings, barriers, layers, packings, gauze, plasters, bandages, cotton wool, sutures, films, foam products, hydrogels, hydrocolloids, alginate products, bioactive products, tissue-engineered skin substitutes, pharmaceutical products, liquid bandages, smart dressings or composite products (which may include any of the foregoing or substitutes, or any combination of the foregoing).

[0654] Specifically, dressings may be composed of one or more natural polymers, one or more synthetic polymers, or blends thereof. Natural polymers include (a) polysaccharides, including (i) cellulose and its compounds, which can be used in dressings for ulcers, for example, to improve pain relief and recovery time; (ii) alginate, which consists of polysaccharide chains and contributes to the clotting process and drug release in wound healing; (ii) polydextrose, a complex branched glucan including additional polysaccharides composed of glucose molecules; (iii) chitosan, a linear polysaccharide, and chitin, an amide derivative of glucose; and (iv) hyaluronic acid, an injectable glycosaminoglycan, for example in gel form; (b) polysaccharide sulfates, including (i) heparin, which has a clotting effect, and (ii) chondroitin; and (c) proteins, including (i) collagen and (ii) fibrin, a coagulant. Synthetic polymers include, for example, (a) polycaprolactone, (b) polyglycolic acid, a biodegradable polystyrene, (c) polylactic acid, which is also a biodegradable polystyrene, (c) polylactic-coglycolic acid, a polymer of polylactic acid and glycolic acid, (d) polyvinyl alcohol, I polyurethane, (f) polyorthoester, and (g) polytetrafluoroethylene.

[0655] In another aspect, by providing the compositions described herein (e.g., in the form of a coating, coating fluid, or spray fluid) to a dressing as described above, an antimicrobial barrier can thus be applied to the wound site, allowing control of antimicrobial activity while promoting cell and tissue proliferation and regeneration. Furthermore, by preventing infection or reducing the likelihood of infection, the compositions according to the technology disclosed herein prevent damage and / or loss of function that might otherwise result from infection. The compositions disclosed herein have antimicrobial activity against both Gram-negative and Gram-positive bacterial strains, including, for example, methicillin-resistant Staphylococcus aureus (MRSA), without inducing bacterial resistance. In some embodiments, the compositions described herein may be used alone or in combination with one or more drugs and / or one or more medical devices for a variety of indications, including, for example, acute wound care, chronic wound care, burn care, local infections, systemic infections, sepsis and necrosis, and other indications, for human and veterinary use.

[0656] In some embodiments, dressings provided with the compositions described herein further include at least one indicator. The at least one indicator may be, for example, an internal or external indicator. The at least one indicator is configured to provide indication of one or more parameters, such as temperature, pH, humidity, or oxygenation. For example, in some embodiments, the dressing may change color in response to contact with a bacterial infection microenvironment. The selection of specific types of dressings, compositions, and optional indicators allows for personalized treatment. Furthermore, by providing indicators, such “smart dressings” communicate efficacy levels (e.g., wound condition and / or recovery status) to, for example, a care provider.

[0657] In some embodiments, the dressing provided with the composition described herein is a pharmaceutical product. As used herein, a "pharmaceutical product" dressing contains at least one additional pharmaceutical agent. Suitable additional pharmaceutical agents include, but are not limited to, anti-inflammatory agents, anesthetic agents, additional anti-infective agents, or combinations thereof.

[0658] In one aspect, the dressing consists of, contains, or is substantially composed of the composition according to embodiments of the present disclosure. In another aspect, an existing dressing is prepared by modifying it to include (e.g., by combining or adding) the composition according to embodiments of the present disclosure.

[0659] In another aspect, a method for preparing an antimicrobial dressing includes providing a dressing containing one or more of the aforementioned natural or synthetic polymers, and applying a coating, coating fluid, or spray fluid to the dressing, the coating or coating fluid being substantially composed of the compositions described herein, or composed of the compositions described herein. For example, the method may include contacting the natural and / or synthetic polymers with the coating, coating fluid, or spray fluid, for example (i) by spraying the dressing with the spray fluid, (ii) by immersing the dressing in a fluid, thereby soaking the dressing in the fluid, (iii) by impregnating the fibers of the dressing with the fluid, (iv) by applying a coating layer to the surface of the dressing, (v) by adhering a backing containing the coating to the dressing, (vi) by applying microneedles containing the compositions to the natural or synthetic polymer of the dressing, or (vii) by constructing fibers of the dressing having polymeric components therein, for example by using electrospinning to produce nanofibers containing the polymers, copolymers, or interpenetrating polymer networks described herein, or by alternative techniques.

[0660] Therefore, in another aspect, this document describes a method for preparing the wound dressing described herein, comprising incorporating a composition including a polymeric component into a fibrous material by one of the following:

[0661] (i) Spraying the fiber material with the composition.

[0662] (ii) Immersing the fiber material in a fluid containing the composition.

[0663] (iii) Impregnating the fibers of the fibrous material with a fluid containing the composition.

[0664] (iv) Applying a coating containing the composition to the surface of the fibrous material.

[0665] (v) Adhere a backing containing the composition to the fibrous material.

[0666] (vi) Applying microneedles containing the composition to the fibrous material.

[0667] (vii) Embedding the layer containing the composition into the fibrous material;

[0668] (viii) Constructing fibers of the fibrous material using the composition by electrospinning; or

[0669] (ix) Interweaving the fibers containing the composition with the fibers of the fiber material.

[0670] In another aspect, this document provides a method for preparing the polyurethane foam wound dressing described herein, comprising incorporating the composition into the polyurethane foam wound dressing by mixing a composition including a polymeric component with a polyurethane prior to curing, to provide the polyurethane foam wound dressing.

[0671] How to use

[0672] In another respect, this article provides a method for preventing or reducing bacterial growth or infection in a subject's wound, surgical site, or implant, the method comprising applying or coating to the wound, surgical site, or implant a composition, substantially composed of, or consisting of, the composition comprising, substantially composed of, or consisting of a polymeric component selected from the group consisting of:

[0673] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0674] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0675] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0676] (iii) Optional polyols;

[0677] (iv) optional water-soluble polymers; and,

[0678] (v) An optional third multifunctional crosslinking agent;

[0679] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0680] (3) Polyethyleneimine intermediates;

[0681] (4) Second adduct; and,

[0682] (5) A combination of the two or more of the above;

[0683] And at least one pharmaceutically acceptable excipient.

[0684] In another respect, this article provides a method for treating a wound or surgical site in a subject in need, the method comprising applying to the wound or surgical site a composition, substantially composed of, or consisting of, a polymeric component selected from the group consisting of:

[0685] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0686] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0687] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0688] (iii) Optional polyols;

[0689] (iv) optional water-soluble polymers; and,

[0690] (v) An optional third multifunctional crosslinking agent;

[0691] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0692] (3) Polyethyleneimine intermediates;

[0693] (4) Second adduct; and,

[0694] (5) A combination of the two or more of the above;

[0695] And at least one pharmaceutically acceptable excipient.

[0696] In another respect, this article provides a method for promoting wound or surgical site healing in a subject in need, the method comprising applying to the wound or surgical site a composition, substantially composed of, or consisting of, a polymeric component selected from the group consisting of:

[0697] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0698] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0699] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0700] (iii) Optional polyols;

[0701] (iv) optional water-soluble polymers; and,

[0702] (v) An optional third multifunctional crosslinking agent;

[0703] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0704] (3) Polyethyleneimine intermediates;

[0705] (4) Second adduct; and,

[0706] (5) A combination of the two or more of the above;

[0707] And at least one pharmaceutically acceptable excipient.

[0708] In some embodiments, the wound is infected. In some embodiments, the wound is not infected.

[0709] In another respect, this article provides a method for protecting a wound site of a subject in need, the method comprising, substantially comprising, or comprising: surrounding at least a portion of the wound site with a dressing, and bringing the wound site into contact with a composition comprising, substantially comprising, or comprising of the following polymeric components selected from the group consisting of:

[0710] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0711] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0712] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0713] (iii) Optional polyols;

[0714] (iv) optional water-soluble polymers; and,

[0715] (v) An optional third multifunctional crosslinking agent;

[0716] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0717] (3) Polyethyleneimine intermediates;

[0718] (4) Second adduct; and,

[0719] (5) A combination of the two or more of the above;

[0720] And at least one pharmaceutically acceptable excipient.

[0721] In some embodiments, the composition is placed on a dressing before contact with the wound site. In some embodiments, the composition is applied to the wound site before contact with the dressing.

[0722] In another respect, this article provides a method for preventing or reducing infection in a subject in need, the method comprising administering to the subject a composition, substantially composed of, or consisting of, a polymeric component selected from the group consisting of:

[0723] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0724] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0725] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0726] (iii) Optional polyols;

[0727] (iv) Optional water-soluble polymers; and

[0728] (v) An optional third multifunctional crosslinking agent;

[0729] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0730] (3) Polyethyleneimine intermediates;

[0731] (4) Second adduct; and

[0732] (5) A combination of the two or more of the above;

[0733] And at least one pharmaceutically acceptable excipient.

[0734] In another respect, this article provides a method for treating an infection in a subject in need, the method comprising administering to the subject a composition, substantially composed of, or consisting of, a composition comprising, substantially composed of, or consisting of, a polymeric component selected from the group consisting of:

[0735] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0736] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0737] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0738] (iii) Optional polyols;

[0739] (iv) Optional water-soluble polymers; and

[0740] (v) An optional third multifunctional crosslinking agent;

[0741] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0742] (3) Polyethyleneimine intermediates;

[0743] (4) Second adduct; and

[0744] (5) A combination of the two or more of the above;

[0745] And at least one pharmaceutically acceptable excipient.

[0746] In some embodiments, the infection is a localized infection. In some embodiments, the infection is a systemic infection.

[0747] In another respect, this article provides a method for treating sepsis in a subject in need, the method comprising administering to the subject a composition, substantially composed of, or consisting of, a composition comprising, substantially composed of, or consisting of, a polymeric component selected from the group consisting of:

[0748] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0749] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0750] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0751] (iii) Optional polyols;

[0752] (iv) optional water-soluble polymers; and,

[0753] (v) An optional third multifunctional crosslinking agent;

[0754] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0755] (3) Polyethyleneimine intermediates;

[0756] (4) Second adduct; and,

[0757] (5) A combination of the two or more of the above;

[0758] And at least one pharmaceutically acceptable excipient.

[0759] In another respect, this article provides a method for preventing or reducing necrosis in a subject in need, the method comprising administering to the subject a composition, substantially composed of, or consisting of, a polymeric component selected from the group consisting of:

[0760] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0761] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0762] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0763] (iii) Optional polyols;

[0764] (iv) optional water-soluble polymers; and,

[0765] (v) An optional third multifunctional crosslinking agent;

[0766] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0767] (3) Polyethyleneimine intermediates;

[0768] (4) Second adduct; and,

[0769] (5) A combination of the two or more of the above;

[0770] And at least one pharmaceutically acceptable excipient.

[0771] In another respect, this article provides a method for preventing or reducing bacterial growth or infection in wounds, surgical sites, or implants of subjects in need, the method comprising applying or coating a composition, substantially composed of, or consisting of the wound, surgical site, or implant, the composition comprising, substantially composed of, or consisting of a polymeric component selected from the group consisting of:

[0772] (1) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, and composites comprise, are substantially composed of, or are composed of the following:

[0773] (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent;

[0774] (ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate with a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized.

[0775] (iii) Optional polyols;

[0776] (iv) optional water-soluble polymers; and,

[0777] (v) An optional third multifunctional crosslinking agent;

[0778] (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites, wherein the polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends and composites comprise, are substantially composed of or consist of: a first adduct, a polyol, a water-soluble polymer and an optional third polyfunctional crosslinker;

[0779] (3) Polyethyleneimine intermediates;

[0780] (4) Second adduct; and,

[0781] (5) A combination of the two or more of the above;

[0782] And at least one pharmaceutically acceptable excipient.

[0783] In some embodiments, the subjects are human or animal subjects.

[0784] In some embodiments, the wound is an external wound. External wounds include, but are not limited to, abrasions, lacerations, punctures, avulsions, skin tears, and burns. In some embodiments, the wound is an internal wound. In some embodiments, the wound arises from a complication of a disease or condition. Non-limiting examples include diabetic ulcers, venous ulcers, and arterial ulcers.

[0785] The compositions disclosed herein are administered to a subject in an effective or therapeutically effective amount. An "effective amount" means an amount of compound sufficient to provide the desired effect (e.g., prevention of bacterial growth, prevention of necrosis, and / or prevention of infection).

[0786] The description of embodiments of this disclosure is not intended to be exhaustive or to limit this disclosure to the precise forms disclosed. Although specific embodiments and examples of this disclosure have been described herein for illustrative purposes, various equivalent modifications can be made within the scope of this disclosure, as will be recognized by those skilled in the art. For example, while method steps or functions are presented in a given order, alternative embodiments may perform functions in a different order or may perform functions substantially simultaneously. The teachings of this disclosure provided herein can be suitably applied to other procedures or methods. The various embodiments described herein may be combined to provide other embodiments. Modifications may be made to aspects of this disclosure as necessary to provide other embodiments of this disclosure by employing the compositions, functions, and concepts in the foregoing references and applications. Furthermore, due to considerations of biological functional equivalence, some changes may be made to the protein structure without affecting the type or amount of biological action. These and other changes may be made to this disclosure in accordance with the detailed description. All such modifications are intended to be included within the scope of the appended claims.

[0787] Specific elements of any of the above embodiments may be combined or substituted with elements in other embodiments. Furthermore, while advantages relating to certain embodiments of the invention have been described in the context of those embodiments, other embodiments may also present such advantages, and not all embodiments are necessarily required to present such advantages that fall within the scope of this disclosure.

[0788] The techniques described herein are further illustrated by the following examples, which should not be construed as further limitations. Although similar or equivalent methods and materials described herein can be used to practice or test the invention, suitable methods and materials are described below.

[0789] Example

[0790] The present invention has now been generally described, and the following examples will make the invention more readily understood. These examples are included only for the purpose of illustrating certain aspects and embodiments of the invention and are not intended to limit the invention.

[0791] Synthesis Example

[0792] Examples 1-4. Water-based compositions with or without water-soluble polyethyleneimine intermediates

[0793]

[0794] Preparation of the aqueous phase:

[0795] 3.1 parts of HEC 380K (2-hydroxyethyl cellulose, average Mw = 380,000, from Aldrich) were fully dissolved in 96.9 parts of DI water. The pH of the solution was adjusted to 4.5 with 5% H3PO4 solution.

[0796] Example 1: Preparation of polymers without polyethyleneimine intermediates

[0797] Preparation of the oil phase:

[0798] 5.0 g (10.7 mmol) of thoroughly dried C18DMDEG was added to a solution of 7.67 g (16.03 mmol, 48 mmol reactive NCO) of DESMODUR® N100 in 5 g of anhydrous toluene under nitrogen atmosphere and at 90 °C, and allowed to react for 15 hours. After removing the toluene under reduced pressure, a clear, viscous liquid (first adduct) was obtained.

[0799] 4.144 parts of the first adduct (N100-C18DMDEG(Br-)), 0.356 parts of PTMG 1000 (poly(tetramethylene glycol), average Mn=1000, from Aldrich), and 1.5 parts of MEK (methyl ethyl ketone) were pre-reacted at 70°C for 1 hour. The mixture was cooled to room temperature and vacuum dried until the solids content reached approximately 90% by weight. 0.828 parts of polyisocyanate N100 (DESMODUR N100, from Convestro) and 1.276 parts of dry acetone were added to the solution and mixed thoroughly.

[0800] Preparation of oil-in-water emulsions

[0801] The aqueous solution prepared above was added to the oil phase at room temperature and emulsified five times by ultrasonic treatment (100 watts) for 10 seconds each time, with a 10-second pulse between each ultrasonic treatment. The total emulsification time was approximately 90 to 120 seconds. The polymer product was obtained by heating at 60°C for 15 hours.

[0802] Example 2-4

[0803] Preparation of QPEI 37169

[0804]

[0805] QPEI 37169 was prepared as shown in the reaction scheme above.

[0806] For the purposes of the chemical methods described herein, it is assumed that the ratio of primary, secondary, and tertiary amines in the branched PEI is 1:2:1, as reported in the literature. See, for example, Klibanov, A. et al., (2006). “One-Step Painting-Like Coating Procedures to make Surfaces Highly and Permanently Bactericidal.” Biotechnol. Prog., 22(2): 584-589; and Gao, B. et al., (2007). “Studies on the Preparation and Antibacterial Properties of Quaternized Polyethyleneimine.” J. Biomaterials Science, Polymer Edition, 18(5): 531-544.

[0807] The procedure used is essentially as described by Gao et al. (2007). The structure of QPEI 37169 is intended to be an approximation, which indicates that most primary and secondary amines have reacted with epoxides, and most tertiary amines are quaternized by alkylation with benzyl chloride.

[0808] Under nitrogen atmosphere, 3.33 g of 70 kDa PEI solution (30% in water / 1 g PEI, assuming mw = 43.1 g / mol, 23.2 mmol) was added to a 25 mL two-necked flask and cooled to 0 °C. 5.4 g (92.8 mmol) of propylene oxide was added dropwise to this mixture at 0–3 °C. After the addition was complete, the reaction mixture was stirred at 0–3 °C for seven hours. The temperature of the reaction mixture was then raised to 35 °C, and unreacted propylene oxide (approximately 3.60 mL) was distilled off. 11.75 g (10.6 mL, 92.8 mmol) of benzyl chloride was added to the resulting solution, and the reaction mixture was heated to 50 °C and maintained for 30 hours. The reaction mixture was extracted with diethyl ether (3 × 20 mL) to remove unreacted benzyl chloride, residual propylene oxide, and lipophilic byproducts or impurities (if present). The aqueous phase was separated, vacuum evaporated, and then lyophilized to leave QPEI 37169 (2.85 g) as a transparent solid. The product was characterized by proton NMR and infrared (IR) spectroscopy. QPEI 37169 contains nitrogen functionalization via benzyl chloride and propylene oxide in an approximately 1:1 ratio (i.e., the number of benzyl groups on the nitrogen atom is approximately equal to the number of 2-hydroxypropyl groups).

[0809] Preparation of QPEI HB37169

[0810] QPEI HB37169 was prepared using the same reactants as in the preparation of QPEI 37169, except that it used superbranched polyethyleneimine with the same molecular weight.

[0811] Preparation of QPEI HB37478

[0812] Except for replacing the quaternizing agent benzyl bromide with hexyl bromide and using hyperbranched polyethyleneimine with the same molecular weight, QPEI HB37478 was prepared using the same reactants as in the preparation of QPEI 37169.

[0813] Example 5-9. QPEI 37169 as a polyethyleneimine intermediate in the aqueous phase.

[0814] Table 3.

[0815]

[0816] Except for the compositional changes shown in Table 3, the compositions of Examples 5-9 were prepared using the same procedures as in Examples 1-4.

[0817] Examples 10-20 describe further examples of polyethyleneimine intermediates or second adducts that can be used in the techniques of this invention.

[0818] Example 10. Synthesis of polyethyleneimine intermediate 40840

[0819]

[0820] The 500 mL three-necked round-bottom flask is equipped with a thermometer, a condenser, and a magnetic stirrer. The reaction flask is purged with nitrogen and the reaction is carried out under a nitrogen flow.

[0821] 10 g of PEI (70 kDa branched, 30% by weight aqueous solution, a solid polymer with an amine content of 18 mmol / g, a primary, secondary, and tertiary amine ratio of 1:2:1), potassium carbonate (37.07 g, 0.232 mol), and 150 mL of tert-amyl alcohol were added to a round-bottom flask. The mixture was stirred under nitrogen for 30 minutes, and then 3-bromo-1-propanol (64.5 g, 0.464 mol, 1.3 equivalents, for complete quaternization) was added dropwise at room temperature. The resulting mixture was heated and stirred at 95 °C for 96 hours.

[0822] After 96 hours, the mixture was cooled to room temperature and filtered to remove insoluble solids. The filtered solids were washed with 150 mL of methanol. The combined filtrates were treated with 250 mL of diethyl ether, resulting in a white precipitate. The organic phase was decanted, and the white solids were dissolved in 200 mL of methanol and precipitated with 200 mL of diethyl ether. This dissolution / precipitation process was repeated twice, and the resulting white paste-like solids were dried in a rotary evaporator and then further dried under high vacuum for 5 hours. The yield of the dried product was 17.4 g. 1 The product was characterized by 1H NMR, and the degree of quaternization was analyzed by molar silver titration to measure the amount of bromide.

[0823] Example 11. Synthesis of polyethyleneimine intermediate 40660

[0824]

[0825] The 2L, 3-necked round-bottom flask is equipped with a dropping funnel, a condenser, and a magnetic stirrer. The reaction flask is purged with nitrogen, and the reaction is carried out under a nitrogen flow.

[0826] 10 g of PEI (70 kDa branched, 30% by weight aqueous solution, solid polymer with an amine content of 18 mmol / g, primary, secondary, and tertiary amine ratio of 1:2:1) was added to a reaction flask, followed by 835 mL of water. 114.3 g of glycidyltrimethylammonium chloride (0.754 mol, theoretically about 4 equivalents for complete conversion) was dissolved in 130 mL of water and added dropwise to the reaction mixture. 153 g (210 mL, 1.5 mol) of triethylamine was added dropwise to the reaction mixture at room temperature. The resulting two-phase reaction mixture was vigorously stirred at room temperature for 4 days, after which the reaction mixture was a clear mixture. All solvents were removed in a rotary evaporator at 55 °C. The paste-like liquid residue was dissolved in 200 mL of methanol, and the polymer product was precipitated with 400 mL of diethyl ether. This methanol / diethyl ether dissolution and precipitation was repeated six times. The final precipitate was dried in a rotary evaporator, followed by drying under high vacuum to obtain 46.5 g of the final product. 1 The product was characterized by 1H NMR, and the degree of quaternization was analyzed by molar silver titration to measure the amount of chloride.

[0827] Example 12. Synthesis of polyethyleneimine intermediate 40818

[0828]

[0829] The 100 mL one-necked round-bottom flask is equipped with a condenser, a heating cup, and a magnetic stirrer. The reaction flask is purged with nitrogen and the reaction is carried out under a nitrogen flow.

[0830] 2 g of glycidyl-functionalized PEI (3.3 mmol + 13.3 mmol reactive N), 7 g of hexane (40 mmol, 3 equivalents), and 4.4 mL of tert-amyl alcohol were added to a flask, and the reaction mixture was heated at 96 °C for 96 hours. The color of the reaction mixture changed from colorless to pale orange. The reaction mixture was cooled to room temperature, and the resulting solution was poured into tert-butyl methyl ether (TBME) while stirring vigorously to form a precipitate. The liquid was decanted from the precipitated solid, and the solid was dissolved in methanol and reprecipitated with TBME. This process was repeated three times, and the product was dried using a rotary evaporator and then under high vacuum to give 4.06 g of product. 1 The product was characterized by 1H NMR, and the degree of quaternization was analyzed by molar silver titration to measure the amount of halide.

[0831] Example 13. Synthesis of a polyethyleneimine intermediate terminated with monoisocyanate (approximately 85% free OH groups).

[0832] As shown below, the structure of the polymer product is intended to approximate that most of the hydroxyl groups (approximately 85% molar equivalent) have reacted with the monoisocyanate blend to form a carbamate, with some remaining hydroxyl groups unreacted.

[0833]

[0834] The concentration of reactive hydroxyl groups (mmol / g of dry polymer) was determined by titrating a known amount (g) of dry hydroxyalkyl quaternary ammonium polyethyleneimine (HA-Q-PEI) with a known excess (g, mmol) of octadecyl isocyanate. Infrared (IR) spectroscopy was used to monitor the concentration at 2263 cm⁻¹. -1 The reaction progress is monitored by observing the decrease in the isocyanate peak, thereby determining the percentage of monoisocyanate consumed in the reaction. Based on the percentage decrease in this peak, the number of millimoles of isocyanate consumed is estimated. This value corresponds to the number of millimoles of polymer hydroxyl groups reacting with the isocyanate. In this way, the hydroxyl concentration of the polymer (millimoles of reactive hydroxyl groups / gram of dry polymer) is calculated and then used in subsequent reactions to determine the amount of monoisocyanate required to functionalize a specific percentage of reactive hydroxyl groups in the polymer, thereby fine-tuning the hydrophilic / hydrophobic properties of the polymer.

[0835] Using the procedure described in Example 2, 2.0 g (2.27 mmol, assuming a molecular weight of 881 g / mol for the polymer unit cell) of hydroxypropyl quaternary ammonium PEI, QPEI 37169, was prepared, dried under vacuum at 60 °C for two hours, and then stored overnight in a desiccator at room temperature. 13.8 g of tert-butanol and 9.2 g of dimethylacetamide were added to the dried polymer. The resulting mixture was stirred under nitrogen until the polymer was completely dissolved. Both solvents were thoroughly dried with a molecular sieve at 4 Å before use. A mixture of 1.6 g (5.41 mmol) of octadecyl isocyanate and 0.36 g (2.32 mmol) of octyl isocyanate was added dropwise to the polymer solution. This mixture contained a total of 7.73 mmol of monoisocyanate, which represented approximately 85% of the available hydroxyl groups. The reaction mixture became slightly turbid. The resulting reaction mixture was stirred under nitrogen at room temperature for twelve hours. The reaction mixture was filtered through a PTFE filter (1 µm pore size) to give 20.83 g of a 12.19% solid solution capped with QPEI 37169. IR spectroscopy revealed the expected new peaks corresponding to the urethane carbonyl group, with no residual isocyanate peaks.

[0836] In some embodiments, after the reaction with one or more monoisocyanates is complete, the reaction mixture is added to water to precipitate the capped product. This product is separated and washed with water to remove any water-soluble impurities, and then dried for use in subsequent steps. This water precipitation step can be used to remove any water-soluble impurities that could cause toxicity.

[0837] Example 14. The process of crosslinking reaction of octadecyl / octylcarbamate quaternary ammonium PEI (an example of second adduct formation)

[0838] As shown below, the structure of polymer compound (A) is intended to approximate that some unreacted hydroxyl groups at the end of QPEI 37169 have reacted with polyisocyanate to form urethane crosslinks.

[0839]

[0840] Using the procedure described in Example 13, 20 g of octadecyl / octylcarbamate quaternary ammonium PEI was prepared by adding 1.25 g of Desmodur N3300 (50% anhydrous acetone solution) and 0.18 g of dibutyltin dilaurate (1% anhydrous toluene solution). The resulting mixture was thoroughly mixed and subjected to a reaction at 60°C for 30 minutes to form compound (A) to give the second adduct.

[0841] It should be noted that the above crosslinking process was also carried out without the presence of dibutyltin dilaurate catalyst.

[0842] Example 15. Aqueous solutions of HA-Q-PEI polymers with different PEI molecular weights, nitrogen quaternization groups, and anionic relative ions.

[0843] Various HA-Q-PEIs (hydroxyalkyl quaternary ammonium PEIs) with the following formulas:

[0844]

[0845] The preparation was carried out using a procedure similar to that described in Example 2 (Preparation of QPEI 37169). See Table 5 (R1 = methyl for each polymer).

[0846] Table 5.

[0847]

[0848] Example 16. Aqueous solutions of HA-Q-PEI polymers with different PEI molecular weights

[0849] Additional HA-Q-PEI polymers in the following formula (R1 = methyl, R2 = hexyl, X = bromide ion):

[0850]

[0851] Different molecular weights were prepared using a procedure similar to that described in Example 2 (Preparation of QPEI 37169). See Table 6.

[0852] Table 6.

[0853]

[0854] Example 17. Preparation of the second adduct

[0855] The second adduct of the following formula:

[0856]

[0857] Using a procedure similar to that described in Example 14, the octadecyl / octylcarbamate quaternary ammonium PEI was replaced with HA-Q-PEI (prepared from PEI: molecular weight = 70,000 (branched), R1 = methyl, R2 = hexyl, X = bromide) and the amount of crosslinking agent Z (DESMODUR® N100) was varied to prepare the product (see Table 7):

[0858] (DESMODUR® N100).

[0859] Table 7.

[0860]

[0861] Example 18. Polyethyleneimine intermediates with or without monoisocyanate substitution

[0862] Polyethyleneimine intermediates with monoisocyanate substitution (MUA-Q-PEI-A polymer, where R3=C) 18 Alkyl or C8 alkyl)

[0863]

[0864] The polymer was prepared from HA-Q-PEI (prepared from PEI: molecular weight = 70,000 (branched), R1 = methyl, R2 = benzyl) and a mixture of monoisocyanates (octadecyl isocyanate to octyl isocyanate in a ratio of 7:3), wherein approximately 90% of the HA-Q-PEI hydroxyl groups reacted with the monoisocyanate mixture (see similar scheme in Example 13). The MUA-Q-PEI-A100 polymer was also prepared similarly, wherein approximately 100% of the HA-Q-PEI hydroxyl groups reacted with the monoisocyanate mixture. See Table 8.

[0865] Table 8.

[0866]

[0867] Example 19. Second adduct using N3300 polyisocyanate crosslinking agent

[0868] The second adduct of the following formula (PUA-Q-PEI-B polymer, where R3 = C) 18 Alkyl or C8 alkyl):

[0869]

[0870] The preparation was performed using a procedure similar to that described in Example 14. Specifically, HA-Q-PEI (prepared from PEI: molecular weight = 25,000 (superbranched), R1 = methyl, R2 = hexyl, X = bromide) was reacted with a mixture of monoisocyanates (octadecyl isocyanate to octyl isocyanate in a ratio of 7:3), wherein approximately 90% of the HA-Q-PEI hydroxyl groups reacted with the monoisocyanate mixture, and the remaining hydroxyl groups were subsequently reacted with varying amounts of crosslinking agent Z (DESMODUR® N3300):

[0871] (DESMODUR® N3300).

[0872] Table 9.

[0873]

[0874] Example 20. Compound 20-1

[0875] Compound 20-1 is similar to QPEI samples 3-8 and 3-9 of Example 16 and was prepared from PEI with a MW = 270 kDa. Compound 20-1 (lot 105159) contains a nitrogen functionalization ratio of hexyl halide to propylene oxide greater than 1:1 (i.e., more hexyl groups than 2-hydroxypropyl groups on the nitrogen atom). Compound 20-1 (lot 99367) contains approximately a 1:1 ratio of nitrogen functionalization via hexyl halide to nitrogen functionalization via propylene oxide (i.e., the number of hexyl groups on the nitrogen atom is approximately equal to the number of 2-hydroxypropyl groups).

[0876] Example 21. Compound 21-1

[0877] Compound 21-1 is similar to compound HB37478, but is prepared by PEI with MW = 25 kDa. Compound 21-1 contains a ratio of nitrogen functionalization via hexyl halide to nitrogen functionalization via propylene oxide of approximately 1:1 (i.e., the number of hexyl groups on the nitrogen atom is approximately equal to the number of 2-hydroxypropyl groups).

[0878] Example 22. Compound 22-1

[0879] Compound 22-1 (lot 109590) is similar to HB37478 of Example 4, but uses a branched 70 kDa PEI instead of a superbranched 70 kDa PEI. Compound 22-1 (lot 109590) contains approximately a 1:1 ratio of hexyl halide-based nitrogen functionalization to propylene oxide-based nitrogen functionalization (i.e., the number of hexyl groups on the nitrogen atom is approximately equal to the number of 2-hydroxypropyl groups).

[0880] Example 23. Compound 23-1

[0881] Compound 23-1 (lots 105402 and 109634) is similar to QPEI sample 2-9 of Example 15 (prepared from PEI with MW = 70 kDa). Compound 23-1 (lots 105402 and 109634) contains nitrogen functionalization via benzoylmethyl halide and nitrogen functionalization via propylene oxide in an approximately 1:1 ratio (i.e., the number of benzoylmethyl groups on the nitrogen atom is approximately equal to the number of 2-hydroxypropyl groups).

[0882] Example 24. Compound 24-1

[0883] Compound 24-1 (batch 109781) is similar to QPEI 37169 of Example 2 (prepared from PEI with MW=70 kDa). Compound 24-1 (batch 109781) contains approximately a 1:1 ratio of nitrogen functionalization via benzyl halide and nitrogen functionalization via propylene oxide (i.e., the number of benzyl groups on the nitrogen atom is approximately equal to the number of 2-hydroxypropyl groups).

[0884] Example 25. Compound 25-1

[0885] Compound 25-1 (batch 110417) is similar to compound 23-1, but is prepared by PEI with MW = 750 kDA.

[0886] Example 26. Compound 26-1

[0887] Compound 26-1 (batch 109831) is similar to polyethyleneimine intermediate 40660 of Example 11 (prepared from PEI at MW = 70 kDa).

[0888] Example 27. Compound 27-1

[0889] Compound 27-1 (batch 110420) is similar to polyethyleneimine intermediate 40818 of Example 12 (prepared from PEI with MW = 70 kDa).

[0890] Example 28. Compound 28-1

[0891] Compound 28-1 corresponds to the intermediate compound in the synthesis of QPEI 37169 in Example 2, which is obtained by reacting PEI (MW = 70 kDa) with propylene oxide. Therefore, quaternary amines are not present in compound 28-1.

[0892] Example 29. Compound 29-1

[0893]

[0894] The 1-L three-necked round-bottom flask is equipped with a dropping funnel, condenser, water bath, and mechanical stirrer. The flask is rinsed with nitrogen and the reaction is carried out under a nitrogen flow.

[0895] A 50% aqueous solution of 20 g of 70 kDa branched PEI (10 g PEI polymer, 0.180 mol amine content, wherein the ratio of primary, secondary, and tertiary amines is approximately 1:2:1) was added to a flask and stirred at approximately 200 RPM. It should be noted that, theoretically, 0.180 mol nitrogen content at this primary, secondary, and tertiary amine ratio can react with 0.36 mol of an alkyl halide. For this example, it is defined as "1 equivalent alkyl halide".

[0896] At ambient temperature, 150 ml of tert-amyl alcohol was added to the flask, followed by K2CO3 (32.1 g, 0.232 mol). A mixture of bromopropanol (1.29 g, 0.0093 mol) and 1-bromohexane (151.86 g, 0.92 mol) was added dropwise over 1–2 hours at ambient temperature (total halogenated alkane = 0.93 mol, 2.6 equivalents, mol% content of each halogenated alkane = 1% bromopropanol / 99% 1-bromohexane).

[0897] The reaction temperature was increased to 96°C, and the reactants were stirred at 96°C for 98 hours. The reactants were cooled to 25-30°C, filtered, and washed with methanol (50 ml). The filtrate was evaporated under vacuum until dry, maintaining a temperature below 50°C. Diethyl ether (200 ml) was added to the residue, and the mixture was stirred at room temperature for 30-60 minutes, resulting in a light brown slurry. This mixture was allowed to settle, and the supernatant was decanted. This diethyl ether grinding and decanting process was repeated 3-4 times until the residual haloalkane content in the decantation layer was less than 0.5%, as determined by GC analysis.

[0898] After the grinding / decantation process, the mixture was evaporated under reduced pressure to dryness while maintaining a temperature below 40°C, yielding a grayish-white viscous solid. This solid was dissolved in methyl ethyl ketone (100 ml) at 25-30°C, filtered through diatomaceous earth, and the filtrate was evaporated under reduced pressure to dryness at 45°C. The resulting solid was dried at a temperature below 45°C for 4-6 hours to obtain a grayish-white solid product (37.8 g). The water content was determined to be 0.24% by Karl Fischer analysis. The bromine content was determined to be 23.6% by AgNO3 titration. Assuming similar alkylation rates between the two haloalkanes, the theoretical molar percentages of the reaction of PEI with 1-bromopropanol and 1-bromohexane were 1% and 99%, respectively.

[0899] Example 30. Compound 30-1

[0900]

[0901] The 1-L four-necked round-bottom flask is equipped with a dropping funnel, condenser, water bath, and mechanical stirrer. The flask is rinsed with nitrogen and the reaction is carried out under a nitrogen flow.

[0902] 10 g of 25 kDa superbranched PEI (0.180 moles of amine content, wherein the ratio of primary, secondary, and tertiary amines is approximately 1:1:1) was added to a flask along with water (10 ml). It should be noted that, theoretically, 0.180 moles of nitrogen content at this primary, secondary, and tertiary amine ratio can react with 0.36 moles of alkyl halide. For this example, it is defined as “1 equivalent alkyl halide”.

[0903] Add 50 ml of tert-amyl alcohol to a flask at ambient temperature and stir the suspension at 160–180 rpm. After stirring for 15–30 minutes, cool the mixture to 0–5 °C and add bromopropanol (3.2 g, 0.023 mol, 0.064 equivalents) dropwise over 15–30 minutes at 0–5 °C. Stir the reaction mixture at 0–5 °C for 4–5 hours, then raise the temperature to ambient temperature. Stir the reaction mixture at ambient temperature for 14–15 hours, after which the reaction mixture will be a turbid solution.

[0904] Reduce the water content of the reactants by azeotropic distillation of the solvent (approximately 10 mL). Add this volume of tert-amyl alcohol to the reactants, and repeat the distillation process three times. Add tert-amyl alcohol to make up the original reaction volume, and stir the resulting mixture at 50–60 °C for 60–90 minutes to obtain a clear solution.

[0905] A mixture of 1-bromooctadecane (232.1 g, 0.696 mol) and 1-bromooctane (44.8 g, 0.232 mol) (0.928 mol, 2.6 equivalent alkyl halides) was added at 50-60 °C. The temperature was raised to 94-98 °C, and the reaction mixture was stirred at this temperature for 48 hours to obtain a clear brown solution. The solvent was removed under reduced pressure below 60 °C, and the resulting residue was cooled to 25-30 °C, and 500 mL of acetone was added. The resulting suspension was stirred at 25-30 °C for 30-60 minutes. Stirring was stopped, and the suspension was allowed to stand for 1 hour. The supernatant was decanted from the solids, and acetone (500 mL) was added to the solid residue. This suspension was stirred at 25-30 °C for 30-60 minutes, then stirring was stopped, and the suspension was allowed to settle for more than 30-60 minutes, and the supernatant was decanted from the settled solids. Repeat the process of stirring, settling, and decanting the suspension several times until the 1-bromohexane and 1-bromooctane content in the supernatant is less than 0.5% as measured by GC analysis.

[0906] The remaining solvent was removed under reduced pressure at below 35°C. The solid product was further dried at below 35°C for 8–10 hours to obtain 40.6 g of QPEI product as a light brown solid. The bromine content was determined to be approximately 23% by AgNO3 titration. The theoretical molar percentages of the reaction with 1-bromopropanol and a 75 / 25 mixture of 1-bromooctadecane and 1-bromooctane were 6.4% and 93.6%, respectively.

[0907] Example 31. Compound 31-1

[0908]

[0909] The 0.5-L four-necked round-bottom flask is equipped with a dropping funnel, condenser, water bath, and mechanical stirrer. The flask is rinsed with nitrogen and the reaction is carried out under a nitrogen stream.

[0910] Add 10 g of 25 kDa superbranched PEI (0.180 mol amine content, wherein the ratio of primary, secondary, and tertiary amines is approximately 1:1:1) to a flask and stir at 160–180 RPM. Note that, theoretically, 0.180 mol amine content of nitrogen can react with 0.120 mol caprolactone ("1 equivalent of caprolactone" in this example) and 0.360 mol 1-bromohexane ("1 equivalent of 1-caprolactone" in this example) at the primary, secondary, and tertiary amine ratio.

[0911] Add water (10 g) and tert-amyl alcohol (50 ml) together to a flask and cool the resulting solid suspension to 0-5°C.

[0912] Caprolactone (2.65 g, 0.0238 mol, 0.2 equivalent) was added dropwise over 15-30 minutes at 0-5°C. The resulting mixture was stirred at 0-5°C for 4-5 hours. The temperature was then raised to 25-30°C, and the reactants were stirred at this temperature for 14-15 hours to obtain a turbid solution.

[0913] Distill off tert-amyl alcohol to remove water via azeotropic extraction from the reaction mixture, and add fresh tert-amyl alcohol to replace the distilled solvent. Raise the reaction temperature to 50-60°C and stir the reaction mixture for 60-90 minutes to obtain a clear solution. Add 1-bromohexane (153.2 g, 0.928 mol, 2.6 equivalents). Stir the resulting reaction mixture at 50-60°C for 15-30 minutes, then raise the temperature to 94-98°C. Stir the reaction mixture at this temperature for 48 hours to obtain a solid suspension.

[0914] Cool the reactants to 25-30°C. Add diethyl ether dropwise (100 ml) and stir the resulting suspension at 25-30°C for 30-60 minutes. Stop stirring and allow the suspension to stand for 1 hour. Decant the supernatant from the settled solids and add fresh diethyl ether (100 ml). Repeat this stirring, settling, and decantation process several times until the 1-bromohexane content in the decantate is less than 0.5% as measured by GC analysis.

[0915] The remaining solvent was removed under reduced pressure at below 35°C. The crude solid product was further dried at below 35°C for 10–12 hours to obtain a beige solid QPEI product (32 g). The water content was measured to be 1200 PPM by Karl Fischer analysis. The bromine content was determined to be approximately 35% by AgNO3 titration.

[0916] Assuming that caprolactone mainly reacts with primary amines, the theoretical molar percentages of PEI reacting with caprolactone and 1-bromohexane are approximately 7% and 93%, respectively.

[0917] Example 32. Additional Compounds

[0918] The following compounds were prepared using a procedure similar to that in the examples above. A = B = .

[0919]

[0920] Compounds 32-1 and 32-2 were prepared in a manner similar to that described in Example 29. The general steps for synthesizing compounds 32-1 and 32-2 are as follows.

[0921] (1) A mixture of 70 kDa PEI, bromopropanol, bromohexane and K2CO3 aqueous solution with tert-amyl alcohol was heated at 96-98 °C for 4 days and then cooled to room temperature.

[0922] (2) The resulting mixture was filtered to remove inorganic salts and the filtered solids were washed with tert-amyl alcohol.

[0923] (3) Evaporate the filtrate under reduced pressure.

[0924] (4) Grind the residue with diethyl ether 5-6 times.

[0925] (5) Dissolve the crude product in methyl ethyl ketone, filter and evaporate under reduced pressure until dry.

[0926] Unless otherwise specified, the respective R of the following compounds (32-1A, 32-1B and 32-2A to 32-2I) is... 60 The stoichiometric ratio of the groups is a theoretical value calculated based on the amount of reactants used in the synthesis scheme.

[0927] Compound 32-1A [General formula B; 70 kDa PEI (branch); R] 60 : -(CH2)3OH (10%), -C6H 13 [(90%)] was synthesized in a similar manner to compound 32-1, but the crude product dissolved in methyl ethyl ketone was treated with an aqueous sodium bicarbonate solution before filtration and evaporation to dryness to raise the pH of the QPEI product to closer to neutral.

[0928] Compound 32-1B [General formula B; 70 kDa PEI (branch); R] 60 : -(CH2)3OH (10%), -C6H 13[90%] was synthesized in a similar manner to compound 32-1, but the residue from step (3) was dissolved in dichloromethane and washed with an aqueous sodium bicarbonate solution, followed by separation of the dichloromethane layer from the aqueous layer and evaporation under reduced pressure until dry. The crude product was then used in steps (4) and (5).

[0929] Compound 32-2A [General formula B; 70 kDa PEI (branch); R] 60 :-(CH2)3OH (5%),-C6H 13 [(95%)] was synthesized in a similar manner to compound 32-2, but the crude product dissolved in methyl ethyl ketone was treated with an aqueous sodium bicarbonate solution before filtration and evaporation to dryness to raise the pH of the QPEI product to closer to neutral.

[0930] Compound 32-2B [General formula B; 70 kDa PEI (branch); R] 60 :-(CH2)3OH (5%),-C6H 13 [95%] was synthesized in a similar manner to compound 32-2, but the residue from step (3) was dissolved in dichloromethane and washed with an aqueous sodium bicarbonate solution, followed by separation of the dichloromethane layer from the aqueous layer and evaporation under reduced pressure until dry. The crude product was then used in steps (4) and (5).

[0931] Compound 32-2C [General formula B; 70 kDa PEI (branch); R] 60 -(CH2)3OH (15%), -C6H 13 [(85%) - determined by NMR analysis] was synthesized in a similar manner to compound 32-2, but the residue from step (3) was dissolved in an aqueous KOH / ethanol solution, filtered, and concentrated under reduced pressure. The crude product was then used in steps (4) and (5). The crude product from step (5) was dissolved in ethanol for bioassays.

[0932] Compound 32-2D [General formula B; 70 kDa PEI (branch); R] 60 :-(CH2)3OH (5%),-C6H 13 [(95%)] was synthesized in a similar manner to compound 32-2, but with additional water added to the initial reaction mixture of step (1). The crude product from step (5) was dissolved in ethanol for bioassay.

[0933] Compound 32-2E [General formula B; 70 kDa PEI (branch); R] 60 : -(CH2)3OH (12%), -C6H 13[(88%) - determined by NMR analysis] was synthesized in a manner similar to that of compound 32-2C, wherein the residue from step (3) was dissolved in an aqueous KOH / ethanol solution, filtered, and concentrated under reduced pressure. The crude product was then used in steps (4) and (5). The crude product from step (5) was dissolved in ethanol for bioassays.

[0934] Compound 32-2F [General formula B; 70 kDa PEI (branch); R] 60 :-(CH2)3OH (5%),-C6H 13 [(95%)] was synthesized in a similar manner to compound 32-2, but the mixture in step (1) was heated to 80°C instead of 96-98°C. The crude product from step (5) was dissolved in ethanol for bioassay.

[0935] Compound 32-2G [General formula B; 70 kDa PEI (branch); R] 60 :-(CH2)3OH (5%),-C6H 13 [95%] was synthesized in a similar manner to compound 32-2, but the mixture in step (1) was heated to 80°C instead of 96-98°C, and the grinding in step (4) was performed using methyl tert-butyl ether (MTBE) instead of diethyl ether. The crude product from step (5) was dissolved in ethanol for bioassay.

[0936] Compound 32-2H [General formula B; 70 kDa PEI (branch); R] 60 :-(CH2)3OH (5%),-C6H 13 [(95%)] was synthesized in a manner similar to that of compound 32-2, but the mixture in step (1) contained isopropanol instead of tert-amyl alcohol, the mixture in step (1) was heated to 80°C instead of 96-98°C, and the grinding in step (4) was performed using methyl tert-butyl ether (MTBE) instead of diethyl ether. The crude product from step (5) was dissolved in isopropanol for bioassay.

[0937] Compound 32-2I [General formula B; 70 kDa PEI (branch); R] 60 :-(CH2)3OH (5%),-C6H 13 [(95%)] was synthesized in a similar manner to compound 32-2, but the mixture in step (1) contained isopropanol instead of tert-amyl alcohol, and the mixture in step (1) was heated to 80°C instead of 96-98°C. The crude product from step (5) was dissolved in isopropanol for bioassay.

[0938] Biological examples

[0939] Example 1. Efficacy study of polymers in a mouse model of Staphylococcus aureus-induced wound infection.

[0940] Grouping

[0941] This project involves five separate efficacy studies, which typically include a wound control group, an infection control group, a vancomycin group, and several test samples (e.g., polymers of the present invention).

[0942] Preparation of inoculum

[0943] i. Define the date of infection as day 0 or hour 0.

[0944] ii. On day -1, streak the bacteria in the -80°C glycerol stock solution onto a TSA. Incubate the plate overnight (20-24 h) at 35±2°C.

[0945] iii. On day 0, pick a single colony from the TSA plate and suspend it in sterile saline, monitoring OD600 (Biochrom-ultrospec-10). Adjust the bacterial concentration to the desired level by adding more colonies or more saline. (For Biochrom-ultrospec-10, the CFU / OD600 ratio is approximately 2.50E+08CFU / ml, OD600 = 0.30). This is the inoculum.

[0946] iv. Calculate the actual CFU level of the inoculum: Place 200 μL of inoculum into a 96-well plate, followed by a series of 10-fold dilutions to obtain 10-10 CFU levels. 0 Up to 10 -5 Six dilutions were prepared. For each dilution, 10 µL was taken onto a TSA plate and incubated overnight at 35±2℃. The next day, the CFU count for each dilution was counted, and the actual CFU level of the inoculum was calculated. The calculation formula is as follows:

[0947] .

[0948] Apply the inoculum topically. A total of 20 µl of inoculum was used per mouse.

[0949] Establishment of a wound infection model

[0950] i. On day 0, i.e. the day of injury and vaccination, mice were anesthetized by injection of 50 mg / kg zoletil and 10 mg / kg xylazine.

[0951] ii. Trim the hair from the cervical spine to the mid-lumbar spine, wash the skin with iodine solution, and then rinse with ethanol. Create a full-thickness skin wound on the dorsal side of each mouse using a 10.0 mm disposable skin biopsy piercing device.

[0952] iii. Transfer 20 μL of inoculum containing approximately 5.0E+06 NRS384 cells in saline suspension into the wound and allow it to be absorbed over 3–5 minutes. Then apply TEGADEM... TM Apply a bandage to the wound to prevent cross-infection.

[0953] treat

[0954] Preparation of vancomycin solution

[0955] Vancomycin solution: Weigh vancomycin and add it to the appropriate volume of physiological saline to prepare a solution with a concentration of 1 mg / mL or 0.2 mg / mL. The dosage volume is 10 μL or 50 μL per wound site.

[0956] Preparation of test solution

[0957] Compound 20-1 solution: Weigh compound 20-1 (batch 105159) and add it to the corresponding volume of dd water to prepare a solution with a concentration of 300 μM or 30 μM. The dosage volume is 10 μL or 50 μL per wound site.

[0958] A solution of compound 21-1 was also prepared in a similar manner.

[0959] A solution of control compound 39637 was also prepared similarly.

[0960] (Compound 39637)

[0961] Vancomycin treatment

[0962] Treatment was initiated 5 minutes after infection, according to the study design. See also Figure 5 The formulation was prepared based on the target concentration. 10 μL / 50 μL of vancomycin was inhaled into the wound site and allowed to absorb for 5 minutes. Then, TEGADERM was... TM Apply a bandage to the wound to prevent cross-infection. Remove TEGADEM 12 hours after infection. TM Apply a bandage; the wound should be dry at this point. Inhale 10 μL / 50 μL of vancomycin into the wound and allow it to absorb for 5 minutes. Then apply the original TEGADERM. TM Apply a bandage to the wound to prevent cross-infection. Remove TEGADEM 24 hours after infection. TMApply a bandage; the wound should be dry at this point. Inhale 10 μL / 50 μL of vancomycin into the wound and allow it to absorb for 5 minutes. Then apply new TEGADERM. TM Apply a bandage to the wound to prevent cross-infection. Remove TEGADEM 36 hours after infection. TM Bandage. There is a small amount of exudate at the wound site. Use a dry swab to absorb the exudate around the wound edges without touching the wound surface. Aspirate 10 μL / 50 μL of vancomycin into the wound site and allow it to absorb for 5 minutes. Then apply TEGADERM. TM Apply a bandage (not a new bandage) to the wound to prevent cross-infection. Follow the above procedure for the next few days. Change the TEGADERS daily. TM Bandage. Remove TEGADEM 72 hours after infection. TM Bandage applied. A small amount of exudate remains at the wound site. Use a dry swab to absorb the exudate around the wound edges without touching the wound surface. Then collect a sample from the wound area to test for bacterial load.

[0963] Treatment of test products

[0964] Treatment was initiated 5 minutes after infection, according to the study design. The formulation was prepared based on the target concentration. 50 μL of the test sample was aspirated into the wound site and allowed to absorb for 5 minutes. Then, TEGADEM was administered. TM Apply a bandage to the wound to prevent cross-infection. Remove TEGADEM 24 hours after infection. TM Apply a bandage; the wound should be dry at this point. Aspirate 50 μL of the test sample into the wound and allow it to absorb for 5 minutes. Then apply new TEGADERM. TM Apply a bandage to the wound to prevent cross-infection. Remove TEGADEM 48 hours after infection. TM Bandage. A small amount of exudate is present at the wound site. Absorb the exudate around the wound edges using a dry swab, without touching the wound surface. Aspirate 50 μL of the test sample into the wound site and allow it to absorb for 5 minutes. Then apply new TEGADERM. TM Apply a bandage to the wound to prevent cross-infection. Remove TEGADEM 72 hours after infection. TM Bandage applied. A small amount of exudate remains at the wound site. Use a dry swab to absorb the exudate around the wound edges without touching the wound surface. Then collect a sample from the wound area to test for bacterial load.

[0965] Measurement of bacterial load at the wound site

[0966] At some point after infection, animals were euthanized using CO2. Samples were excised from each wound and collected in 5 ml of sterile saline for homogenization. An IKA T10 homogenizer equipped with an S10N-10G dispersant was used at maximum speed. The homogenized tissue was serially diluted 10-fold in 96-well plates, with 10 μL of each dilution spotted onto a TSA agar plate. The plates were incubated overnight at 35±2°C or until colonies reached a countable size. CFU were counted visually.

[0967] Statistical analysis

[0968] The data was analyzed using GraphPad Prism 7 and expressed as mean ± SEM.

[0969] Results summary:

[0970] Research I

[0971] At 12 and 24 hours post-Staphylococcal infection, the bacterial load at the wound site was similar, increasing to 8.59 lg CFU / wound site and 8.78 lg CFU / wound site, respectively. Following intervention with compound 20-1 (batch 105159), the bacterial load at 12 and 24 hours post-infection was significantly reduced to 4.07 lg CFU / wound site and 4.06 lg CFU / wound site, respectively, compared to the corresponding infection control group (P<0.05, P<0.05). Meanwhile, in the vancomycin group, a single 10 μg dose had no significant effect at 12 hours post-infection, but after two administrations, the bacterial load was reduced by 1.12 lg CFU / wound site compared to the 24-hour infection control group (P<0.05). See Table 10.

[0972] Table 10. Design and Results of Study I

[0973]

[0974] Research II

[0975] At 12 and 24 hours post-Staphylococcal infection, the bacterial load at the wound site was similar, increasing to 8.59 lg CFU / wound site and 8.86 lg CFU / wound site, respectively. After intervention with compound 20-1 (batch 105159) at a concentration of 300 μM, the bacterial load at 12 and 24 hours was significantly reduced to 3.05 lg CFU / wound site and 4.97 lg CFU / wound site, respectively, compared to the corresponding infection control group (P<0.05, P<0.05).

[0976] At 12 and 24 hours post-Staphylococcal infection, the bacterial load at the wound site was similar, increasing to 8.59 lg CFU / wound site and 8.86 lg CFU / wound site, respectively. After intervention with 100 μM compound 20-1 (batch 105159), the bacterial load at 12 and 24 hours was significantly reduced to 3.36 lg CFU / wound site and 4.21 lg CFU / wound site, respectively, compared to the corresponding infection control group (P<0.05, P<0.05).

[0977] At 12 and 24 hours post-Staphylococcal infection, the bacterial load at the wound site was similar, increasing to 8.59 lg CFU / wound site and 8.86 lg CFU / wound site, respectively. After intervention with compound 20-1 (batch 105159) at a concentration of 30 μM, the bacterial load at 12 and 24 hours was significantly reduced to 5.69 lg CFU / wound site and 5.70 lg CFU / wound site, respectively, compared to the corresponding infection control group (P<0.05, P<0.05).

[0978] At 12 and 24 hours post-Staphylococcal infection, the bacterial load at the wound site was similar, increasing to 8.59 lg CFU / wound site and 8.86 lg CFU / wound site, respectively. After intervention with 10 μM compound 20-1 (batch 105159), the bacterial load at 12 and 24 hours was significantly reduced to 5.83 lg CFU / wound site and 6.54 lg CFU / wound site, respectively, compared to the corresponding infection control group (P<0.05, P<0.05).

[0979] Compared with the corresponding infection control group, compound 20-1 (batch 105159) showed significant antibacterial activity at four different test concentrations of 300 μM and 100 μM, and 30 μM and 10 μM, exhibiting a dose-response relationship. The concentrations at 300 μM and 100 μM showed the best efficacy. See Table 11.

[0980] Table 11. Design and Results of Study II

[0981]

[0982] Research III

[0983] At 24, 48, and 72 hours post-Staphylococcal infection, the bacterial load at the wound site reached 8.77 lg CFU / wound site, 8.57 lg CFU / wound site, and 7.96 lg CFU / wound site, respectively. After intervention with compound 20-1 (batch 105159), the bacterial load was significantly reduced compared to the corresponding infection group. The bacterial load at 24, 48, and 72 hours was significantly reduced to 5.15 Ig, 5.39 Ig, and 4.22 Ig, respectively (P < 0.001).

[0984] The efficacy of compound 20-1 (batch 105159) appears to become more stable with increasing treatment duration. See Table 12.

[0985] Table 12. Study III: Design and results of the antibacterial activity of compound 20-1 in a series of mouse wound infection models at different doses.

[0986]

[0987] Study IV

[0988] At 12 and 24 hours post-Staphylococcal infection, the bacterial load at the wound site reached 8.59 1g CFU / wound site and 8.72 1g CFU / wound site, respectively. After intervention with compound 21-1 at a concentration of 300 μM, the bacterial load at 24 and 48 hours significantly decreased to 5.21 Ig CFU / wound site and 5.58 Ig CFU / wound site, respectively (P < 0.005).

[0989] At 12 and 24 hours post-Staphylococcal infection, the bacterial load at the wound site reached 8.59 1g CFU / wound site and 8.72 1g CFU / wound site, respectively. After intervention with 100 μM compound 21-1, the bacterial load at 24 and 48 hours significantly decreased to 6.37 Ig CFU / wound site and 6.80 Ig CFU / wound site, respectively (P < 0.005).

[0990] At 12 and 24 hours post-Staphylococcal infection, the bacterial load at the wound site reached 8.59 1g CFU / wound site and 8.72 1g CFU / wound site, respectively. After intervention with compound 21-1 at a concentration of 25 μM, the bacterial load at 24 and 48 hours significantly decreased to 7.81 Ig CFU / wound site and 8.01 Ig CFU / wound site, respectively (P < 0.05).

[0991] Compared with the corresponding infection group, compound 21-1 showed significant antibacterial activity at all three different test concentrations, and this activity exhibited a dose-response relationship. See Table 13.

[0992] Research V

[0993] At 12, 24, and 72 hours post-Staphylococcal infection, the bacterial load at the wound site was 8.46 lg CFU / wound site, 8.54 lg CFU / wound site, and 8.26 lg CFU / wound site, respectively. A single application of compound 20-1 (batch 105159) reduced the bacterial load at 24, 48, and 72 hours post-infection by 4.54 lg CFU / wound site, 2.88 lg CFU / wound site, and 0.43 lg CFU / wound site, respectively. This indicates that its effect gradually weakens from 24 to 72 hours post-infection. See Table 14.

[0994] At a concentration of 100 μM applied once daily, compound 20-1 (batch 105159) showed a 2.56 lg CFU / wound site reduction in bacterial load compared to the 72-hour infection control group (p<0.005).

[0995] Table 13. Design and results of Study IV: Activity of compound 21-1 at three different concentrations

[0996]

[0997] Table 14. Design and results of Study V, duration of antibacterial activity of compound 20-1 after a single application.

[0998]

[0999] Example 2. Cytotoxicity studies of mammalian cells

[1000] Primary human dermal fibroblasts (HDF) and human keratinocytes (HaCaT) were selected for cytotoxicity and proliferation assays. HDF cells were cultured in Dalberg's modified Eagle Medium (DMEM) (GIBCO™) that was high in glucose, glutamine-free, and phenol red-free. The HDF medium was further supplemented with 10% heat-inactivated fetal bovine serum (GIBCO™), 1% L-glutamine (GIBCO™), and 1% penicillin-streptomycin (GIBCO™). HaCaT cells were cultured in high in glucose, glutamine-free, and calcium-free DMEM (GIBCO™) that was supplemented throughout the culture with 10% heat-inactivated fetal bovine serum, 1% L-glutamine, 1% penicillin-streptomycin, and 1mM calcium chloride (Sigma).

[1001] Mammalian cell populations were maintained under standard culture conditions of 37°C, 5% CO2, and >95% relative humidity. After reaching 80% confluence, cells were removed from the incubator, the culture medium was aspirated, and the monolayer was washed with Dalberg's modified Eagle's saline (DPBS). Following washing, 10 mL of 1% trypsin (GIBCO™) was added to each flask and the cells were incubated to promote cell detachment from the culture vessel. After detachment, 10 mL of culture medium was added to each flask to neutralize trypsin activity. A total 20-mL volume was transferred to a universal tube and centrifuged at 400 rcf for 5 minutes. Afterward, the cell aggregates were resuspended in 10 mL of warm culture medium, and the cell count per mL was determined using a hemocytometer. The HDF cell suspension was then adjusted to 5 × 10⁻⁶ cells / mL. 4 Cells / mL, and the HaCaT cell suspension was adjusted to 1×10⁻⁶. 5 Cells / mL. Add 100 μL of cell suspension to each well of a sterile, cell culture-treated 96-well microtiter plate. Incubate the plate under standard conditions for 16–24 hours to allow cell adhesion to the culture vessel. After adhesion, thaw the stock compounds and prepare a series of 2-fold dilutions for each compound in warm medium in a flat 96-well plate, ranging from 100 μM to 0.8 μM (compounds 20-1 and 25-1: 2.5 μM to 0.02 μM). Remove the culture plate from the incubator, remove the medium, and wash the monolayer with 100 μL of warm DPBS. Transfer the contents of the test substance dilution plate to the culture plate. This applies to the average of three biological replicates for each dilution of each compound, with three technical replicates per replicate (n=9). Return the plate to the incubator and incubate under standard conditions for 24 hours.

[1002] Cytotoxicity test

[1003] Lactate dehydrogenase (LDH) secretion is used to quantitatively measure cell damage and cytotoxicity. Since LDH is released into the cell culture medium due to damage to the plasma membrane, extracellular LDH in the medium can be quantified via a coupled enzymatic reaction in which LDH is reduced from NAD+ to NADH, catalyzing the conversion of lactate to pyruvate. The oxidative oxidation of NADH by flavoproteins leads to the reduction of resazurine, forming highly fluorescent halogen. The halogen level, proportional to the amount of LDH released into the medium, can therefore be used to measure cytotoxicity.

[1004] After incubation with the selected compound, 50 μL of culture medium from each well was transferred to the corresponding well of a new 96-well culture plate. The presence of lactate dehydrogenase (LDH) was then quantified using the INVITROGEN™ CyQUANT™ LDH Cytotoxicity Assay Fluorescence Kit. Total fluorescence was measured by reading the plate at 560 nm excitation and 590 nm emission on a plate reader.

[1005] Cell proliferation test

[1006] After collecting the culture medium used for LDH quantification, the remaining cell culture medium was aspirated, and the cell monolayer was washed with 100 μL of warm DPBS and fresh culture medium was added. The cell proliferation assay, CELLTITER 96® Aqueous One Solution, was then used to determine the number of cells remaining in the culture vessel. This assay utilizes the tetrazolium compound [3-(4,5-dimethylthiazolyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, an inner salt, which is bioreduced by NADPH or NADH in metabolically active cells to a colored formazan product.

[1007] Add 20 μL of MTS (CELLTITER 96® Aqueous One Solution CellProliferation Assay) solution to each well and incubate the plate in the incubator for 4 hours. Collect the cell plates and measure the colorimetric change in absorbance at 490 nm using a plate reader. Use calibration curves to determine the number of viable cells present under each treatment condition.

[1008] Microbiological methods: bacterial strains and culture conditions

[1009] All microbiological work was performed in a Class II biosafety enclosure. Clinically isolated Klebsiella pneumoniae KL1 strain (isolated from a leg wound swab) and Staphylococcus aureus MR1 ​​(methicillin-resistant Staphylococcus aureus (MRSA) isolated from a leg ulcer) were provided from our hospital's clinical isolate bank. All other strains were obtained from ATCC. Table 15 describes all strains used in this study. Mueller-Hinton (MH) medium was used as the culture medium in all subsequent experiments. Overnight cultures (ONCs) were prepared as follows: single colonies of bacteria maintained on MH agar were inoculated into 5 mL of MH medium and incubated overnight at 37°C with continuous shaking (200 rpm) for 14–15 hours.

[1010] Table 15. Bacterial strains used in this study

[1011]

[1012] Results summary:

[1013] Table 16. Overview of the cytotoxicity values ​​of the tested compounds.

[1014]

[1015] A strong concordance was found between cell viability (MTS) and overall cytotoxicity (LDH). Overall cytotoxicity appeared to be slightly higher in the HDF population. No positive effects on mammalian cell proliferation were observed for any of the screened compounds. For most compounds, a negative impact on cell viability was observed at treatment concentrations comparable to those that inhibited bacterial growth. Most compounds induced cytotoxicity at higher treatment concentrations (50 μM, 100 μM). A dose-dependent decrease in cytotoxicity and cell death was observed for almost all compounds.

[1016] Compound 20-1 (lots 105159 and 99367) showed a dose-dependent increase in LDH secretion at 0.31 μM.

[1017] For compound 39637 (batches 105543 and 109466), LDH secretion in both HDF and HaCaT populations began to rapidly exceed control levels at 3.12 μM. Batchette 105543 appeared to exhibit a slightly higher cytotoxic effect. However, for both batches, almost no viable cells were observed in each cell population at 6.3 μM.

[1018] Compound 22-1 (batch 109590) and compound 21-1 (batch 109770) exhibited highly similar cytotoxic concentrations, with almost no HDF and HaCaT live cells at 3.12 μM.

[1019] Compound 24-1 (batch 109781) had a slightly reduced cytotoxic effect on mammalian cells, with a surge in LDH secretion and a lack of viable cells observed at 6.25 μM.

[1020] Compounds 40840 and 40598 showed minimal cytotoxicity against mammalian cells: overall HDF cytotoxicity increased by 13.8% compared to the control.

[1021] Compounds 40840, 40598, 28-1 (batch 109666) and 40597 (batch 10944) exhibited minimal cytotoxicity. These compounds also showed limited antimicrobial activity.

[1022] Compounds 20-1 (batch 105159) and 20-1 (batch 99367) exhibited broad antimicrobial activity at relatively low concentrations. Compounds 20-1 (batch 105159) and 20-1 (batch 99367) also showed high mammalian cytotoxicity and broad antimicrobial activity at relatively low concentrations.

[1023] Compounds 26-1 and 27-1 were cytotoxic to mammalian cells at all tested concentrations. Compound 26-1 exhibited selective antimicrobial activity against Staphylococcus aureus strain ATCC 29213 and clinical isolate MR1.

[1024] Compound 25-1 was most active against all Gram-positive species at a relatively low μM concentration (6.25 μM), including one Gram-negative species, Klebsiella pneumoniae KL1.

[1025] Example 3. Antimicrobial activity study

[1026] Minimum Inhibitory Concentration (MIC)

[1027] The antimicrobial efficacy of the tested compounds was studied using a standard culture microdilution method. Each compound was serially diluted twofold in sterile MH medium in a flat-bottomed 96-well plate, ranging from 100 μM to 0.8 μM. The ONC of each bacterial strain was adjusted to obtain a standard bacterial concentration (5 × 10⁻⁶). 5CFU / mL was added to each dilution to determine the MIC in a total volume of 100 μL MH medium. All plates were statically incubated at 37°C for 24 h. Sterile dH2O was used as a mediator-only control, including a positive control (bacteria only) and a negative control (MH medium only) for each bacterial strain. To determine the MIC breakpoint, the plates were stained with 10 μL of 0.02% respazine and incubated at 37°C for 30 min. After incubation, all plates were imaged and absorbance was measured at 570 nm (plate reader). The MIC was defined as the lowest concentration of the compound that inhibited growth. For all compounds tested, MH medium was used as a negative control on each plate, and bacteria only as a positive control. Serial 2-fold dilutions were performed by mixing 50 μL of the highest concentration (×2) of sterile MH medium containing 50 μL of sterile MH medium from columns A to H.

[1028] MIC Data Analysis

[1029] Data were exported to Microsoft Excel and background normalized by subtracting the OD570nm values ​​from the wells containing only culture medium (negative control). MIC values ​​were determined by plotting the OD570nm values ​​(Y) against the logarithmic concentration (X) of each compound. A modified Gompertz model was used to fit the data for more accurate MICs. The mean OD570nm of each test compound concentration was fitted to an S-shaped curve using a modified Gompertz function (y = A + Ce - e(B(x - M))), and the minimum inhibitory concentration (MIC) was determined from the inflection point of the lower asymptote (GraphPad Prism 9.0). This was applied as the average of three biological replicates for each dilution of each compound, with four technical replicates per replicate (n=12).

[1030] Minimum Bacterial Concentration (MBC) Procedure

[1031] To determine the concentration of the MBC compound, the cutoff point was estimated from the MIC curve. For all bacterial strains, overnight cultures were set up as described above. The next day, the overnight culture was adjusted to 5 × 10⁻⁶. 5Cell density per cell per milliliter. In short, the culture was adjusted and diluted (1:150) according to the McFarland standard (0.08–0.12). The adjusted culture was inoculated into 96-well plates containing 50 μL of sterile Muller-Hinton medium (MHB) and two concentrations of each compound. The MBC plates were incubated statically at 37°C for 24 hours. Sterile dH2O was used as a mediator control, and the assay also included a positive control (bacteria only) and a negative control (medium only). MBC cultures were quantified by serial dilution in 96-well plates and spot-spotting onto Muller-Hinton agar (MHA). The MHA plates were incubated at 37°C for 24 hours and counted. Results are expressed as CFU per milliliter.

[1032] Results summary:

[1033] Table 17. Overview of MIC values ​​for the compounds tested against the listed bacteria. All values ​​are in µM.

[1034]

[1035] Table 18. Overview of MBC values ​​for the compounds tested against the listed bacteria. All values ​​are in µM.

[1036]

[1037] Compounds 23-1 (lots 105402 and 109634), 39637 (lots 105543 and 109466), 22-1 (lot 109590), 21-1 (lot 109770) and 24-1 (lot 109781) exhibited strong antimicrobial activity against the Gram-positive species Enterococcus faecalis and Staphylococcus aureus.

[1038] In Gram-negative bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa), three compounds showed inhibitory effects within the studied concentration range: compounds 20-1 (batch 105159), 20-1 (batch 99367), and 22-1 (batch 109590).

[1039] Compounds 39637 (lots 105543 and 109466), 22-1 (lot 109590), and 21-1 (lot 109770) inhibited Staphylococcus aureus at concentrations ranging from 1.57 μM to 6.25 μM.

[1040] Of all the compounds tested, the most potent MIC and MBC were lower in Gram-positive bacteria; however, at higher concentrations, they did appear to have broad-spectrum activity in Gram-negative bacteria.

[1041] Compound 20-1 (lots 105159 and 99367) exhibited the most potent MBC inhibition profile across all bacterial strains. The MBC values ​​clearly demonstrate the inhibitory effect on all strains at relatively low concentrations.

[1042] Of all the compounds tested above, the following exhibited the lowest antimicrobial activity: compounds 40840 (batch 110435), 40598 (batch 109448), 28-1 (batch 109666), 26-1 (batch 109831), and 40597 (batch 109444). Compound 25-1 (batch 110417) showed low antimicrobial efficacy via MIC, but inhibited five of the seven strains at 6.25 μM in the MBC.

[1043] Test additional compounds to obtain MIC values ​​for the same bacteria shown in Tables 17 and 18 (see Table 19). ****: MIC of QPEI ≤ 12.5 μM for all tested bacteria; ***: MIC of QPEI > 12.5 μM and MIC ≤ 50 μM for >50% of tested bacteria; **: MIC of QPEI > 12.5 μM and MIC ≤ 50 μM for <50% of tested bacteria; *: MIC of QPEI > 100 μM for all tested bacteria.

[1044] Table 19.

[1045]

[1046] Example 4. Biomembrane Inhibition Efficacy - Microscopic Results

[1047] General bacterial cell culture

[1048] All culture techniques were performed aseptically in a Class II microbiological safety cabinet (Microflow, Bioquell, Hampshire, UK). All surfaces and items within the Class II cabinet were sprayed with 70% ethanol to establish aseptic working conditions. Stock plates were produced as needed by streaking individual Microbank beads onto Mueller Hinton agar plates (MHA; Oxoid, UK) and then incubating the plates at 37°C for 24 hours. The stock plates were then sealed with sealing film to minimize moisture loss and stored at 4°C for up to two months.

[1049] Biomembrane preparation

[1050] Overnight (O / N) cultures of Staphylococcus aureus were produced by inoculating 10 mL of Mueller Hinton Broth (MHB; Oxoid, UK) with a single colony and then incubating at 37°C with shaking at 140 rpm (Labnet 211DS shaking incubator, Labnet International, USA) for 16 hours. The stable-phase O / N cultures were diluted to obtain a cell density of 10⁷ CFU / mL, which was validated by spot plating and colony counting. Biofilms were prepared by inoculating a sterile filter membrane (0.22 μm, GE Healthcare, USA) onto a Mueller Hinton Agar (MHA; Oxoid, UK) plate with 4 μL of the adjusted inoculum. After drying, the plate was incubated upright at 37°C for 4 hours. After incubation, the biofilm was removed from the incubator and treated with 4 μL of different concentrations (100, 50, 25, 12.5, or 6.25 μM) of the compounds selected in Table 19. During the specific treatment culture period, the biofilm was again cultured upright at 37°C.

[1051] Scanning electron microscopy

[1052] After treatment with the selected compound, the biofilm-containing filter membrane was aseptically removed from the agar surface and transferred to a 6-well plate. In each well, the biofilm was covered with 3–4 mL of pure water containing 1% (v / v) glutaraldehyde (Sigma-Aldrich; Poole, UK). The glutaraldehyde solution was then incubated at RT (room temperature) for at least one hour. After one hour, the 1% glutaraldehyde was removed and replaced with pure water. This step was repeated two or three times to ensure complete removal of the glutaraldehyde solution. In each well, 3–4 mL of pure water containing 10% (v / v) ethanol was added to the biofilm and incubated for 30 minutes. This process was then repeated with successive solutions of 30%, 50%, 70%, and 90% (v / v) ethanol in pure water. After incubation with ethanol solutions of gradually increasing concentrations, the biofilm was immersed in 100% EtOH for 30 minutes. This process was repeated a second time with fresh 100% EtOH. After washing with ethanol, the biofilm was critically dried using an E3100 critical point dryer (Quorum, Houston, US). This process replaced the remaining ethanol in the sample with liquid carbon dioxide, resulting in a dried sample. After drying, a 5 nm layer of gold was coated onto the biofilm using a Polaron T-100 coater / thickness monitor (Ladd, Williston, US). The sample was then imaged using a Zeiss EVO-60 microscope with scanning electron microscopy. Imaging was performed using a LaB6 emitter at an EHT of 20 kV and a probe current of 100 pA. All biofilm treatment conditions were performed in triplicate (n=3).

[1053] SEM images of the control biofilm and the biofilm treated with the selected compound (100 μM) are shown in [the image]. Figure 1A and Figure 1B middle.

[1054] Confocal microscopy

[1055] After treatment with the selected compound, the biofilm-containing filter membranes were stained using the FILMTRACER™ LIVE / DEAD® Biofilm Viability Kit prepared according to the manufacturer's instructions. LIVE / DEAD® Biofilm Viability Staining includes SYTO 9 (a LIVE cell-permeable stain) and propidium iodide (PI) (a DEAD cell-impermeable stain). The staining solution (4 µL) was applied directly to the biofilm surface and incubated in the dark at room temperature for 20 minutes. The biofilm-containing filter membrane was then inverted onto a clean coverslip.

[1056] Confocal laser microscopy imaging was performed using a Zeiss LSM710 laser scanning confocal microscope. For signal acquisition, a 488 nm laser was used for SYTO 9 and a 561 nm laser for PI. For 3D images, all samples were z-stacked at 45 µM for more than 10 slices. Representative images were taken from the maximum intensity projection for each sample. To quantify the LIVE / DEAD® signal, the relative intensities of the two trajectories (SYTO9 and PI) in the corresponding regions were measured for each sample. All biofilm treatment conditions were performed with three biological replicates (n=3).

[1057] The quantitative demonstration of the activity of the selected compound (25 μM) against Staphylococcus aureus colony biofilm over a 3-hour period was presented in... Figure 2A (SYTO 9) and Figure 2B (Propidium iodide). Quantitative analysis of the activity of the same compound at different concentrations against Staphylococcus aureus colony biofilms is presented in [the table / document / etc.]. Figure 3A (SYTO 9) and Figure 3B In (propidium iodide). Compared with the untreated control, the selected compound rapidly inhibited biofilm viability, with dead cell levels measurable at 15 minutes, indicating a real-time mode of action that is likely contact-dependent via membrane disruption and / or membrane permeation.

[1058] Example 5. In vitro efficacy of the compound against Gram-positive and Gram-negative bacteria.

[1059] The bacterial strains tested included CLSI and NCTC reference and quality control (QC) strains from the following organism groups: *Acinetobacter baumannii*, *Enterococcus faecalis*, *Escherichia coli*, *Klebsiella pneumoniae*, *Pseudomonas aeruginosa*, and *Staphylococcus aureus*. Some strains contained molecularly characteristic β-lactamase genes, including carbapenemase (KPC-2) and extended-spectrum β-lactamase (SHV-18) genes.

[1060] Following CLSI guidelines M07 (2018) and M100 (2023), antimicrobial susceptibility of isolates was tested using a microdilution method. Frozen 96-well MIC plates were produced. The test medium was cationic-regulated Mueller-Hinton medium (CAMHB). Individual MIC values ​​for eight test compounds were measured for each of the nine test strains. Additional MIC values ​​for levofloxacin (a comparator) were generated for several QC strains.

[1061] Prepare compound stock solutions and mix them overnight as needed. Check the pH of each stock solution and adjust as needed until a minimum pH of 5.0 is achieved (pH range 5.0–7.0). Some compound stock solutions may require heating to aid dissolution.

[1062] When performing microdilution susceptibility testing of culture media, current CLSI quality assurance practices were followed. MIC values ​​were validated by simultaneously testing a control (levofloxacin) against CLSI-recommended QC strains, including Staphylococcus aureus ATCC 29213 (methicillin sensitive), Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, and Pseudomonas aeruginosa ATCC 27853. Initial inoculum density (target, 5 × 10⁵ CFU / mL) was monitored during susceptibility testing by bacterial colony counting.

[1063] The MIC values ​​of the eight test compounds and levofloxacin for the nine QC and reference strains are shown in Table 20.

[1064] Table 20.

[1065]

[1066] Compound 32-10 exhibited broad-spectrum antibacterial activity, with Gram-positive MIC values ​​against Staphylococcus aureus and Enterococcus faecalis ranging from 3.125 μM to 6.25 μM, and Gram-negative activity against Enterobacteriaceae and non-fermenting bacteria (Acinetobacter baumannii and Pseudomonas aeruginosa) ranging from 12.5 μM to 50 μM.

[1067] Compound 21-1 was observed to have Gram-positive activity against Staphylococcus aureus and Enterococcus faecalis isolates, with a MIC of 0.2 μM. Due to solubility issues in CAMHB, the highest concentration of compound 21-1 with a measurable MIC was 0.8 μM. Against Gram-negative bacteria, the MIC of compound 21-1 ranged from 0.8 μM to >8 μM.

[1068] Compound 29-1 exhibited broad-spectrum activity, with a Gram-positive MIC of 0.8 μM against Staphylococcus aureus and a Gram-positive MIC of 1.6 μM–3.125 μM against Enterococcus faecalis. Gram-negative activity against the tested Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae) and non-fermenting bacteria (Acinetobacter baumannii and Pseudomonas aeruginosa) isolates ranged from 6.25 μM to 25 μM.

[1069] Compound 32-2 was observed to exhibit Gram-positive activity against Staphylococcus aureus and Enterococcus faecalis isolates, with MIC values ​​of 0.4 μM and 1.6 μM, respectively. Due to solubility limitations in CAMHB, the highest concentration of compound 32-2 with measurable MIC values ​​was 6.25 μM. Against Gram-negative bacteria, the MIC values ​​of compound 32-2 ranged from 6.25 μM to >6.25 μM.

[1070] Compound 32-1 exhibits broad-spectrum activity, with a Gram-positive MIC of ≤...

Claims

1. A wound dressing comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above.

2. The wound dressing according to claim 1, wherein the polymeric component has antibacterial activity against one or both of Gram-negative strain bacteria and Gram-positive strain bacteria.

3. The wound dressing according to claim 1 or claim 2, wherein the ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:

1.

4. The wound dressing according to any one of claims 1 to 3, wherein the outer layer of the wound dressing contains the polymeric component.

5. The wound dressing according to any one of claims 1 to 3, wherein the polymeric component is impregnated into the wound dressing.

6. The wound dressing according to any one of claims 1 to 5, wherein the wound dressing is selected from the group consisting of: wraps, coverings, barriers, layers, packings, gauze, plasters, bandages, cotton wool, sutures, films, foamed products, hydrogels, hydrocolloids, alginate products, bioactive products, tissue-engineered skin substitutes, pharmaceutical products, liquid bandages, smart dressings, and composite materials, or any combination thereof.

7. The wound dressing according to any one of claims 1 to 5, wherein the wound dressing is configured to provide an indication of one or more parameters related to the state of the wound site.

8. A topical formulation comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) Optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; and at least one pharmaceutically acceptable excipient; The ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:

1.

9. The topical formulation according to claim 8, wherein it is in the form of cream, gel, paste, foam, spray, powder, emulsion, liquid or ointment.

10. The topical formulation according to claim 8 or claim 9, wherein the polymeric component has antibacterial activity against one or both of Gram-negative and Gram-positive bacterial strains.

11. A method for preventing or reducing bacterial growth or infection in a wound, surgical site, or implant of a subject, the method comprising applying or coating to the wound, surgical site, or implant a composition comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; And at least one pharmaceutically acceptable excipient.

12. A method of treating a wound or surgical site of a subject in need, the method comprising applying to the wound or surgical site a composition comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; And at least one pharmaceutically acceptable excipient.

13. A method for promoting wound or surgical site healing in a subject in need, the method comprising applying to the wound or surgical site a composition comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; And at least one pharmaceutically acceptable excipient.

14. The method according to any one of claims 11 to 13, wherein the wound is an external wound.

15. The method according to any one of claims 11 to 13, wherein the wound is an internal wound.

16. The method according to any one of claims 11 to 15, wherein the method is part of an acute wound care protocol.

17. The method according to any one of claims 11 to 15, wherein the method is part of a chronic wound care regimen.

18. The method according to any one of claims 11 to 17, wherein the wound is infected.

19. The method according to any one of claims 11 to 17, wherein the wound is not infected.

20. A method for protecting a wound site of a subject in need, the method comprising surrounding at least a portion of the wound site with a dressing, and contacting the wound site with a composition comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; And at least one pharmaceutically acceptable excipient.

21. A method for preventing or reducing infection in a subject in need, the method comprising administering to the subject a composition comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; And at least one pharmaceutically acceptable excipient.

22. A method of treating an infection in a subject in need, the method comprising administering to the subject a composition comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; And at least one pharmaceutically acceptable excipient.

23. The method of claim 21 or claim 22, wherein the infection is a local infection.

24. The method of claim 21 or claim 22, wherein the infection is a systemic infection.

25. A method of treating sepsis in a subject in need, the method comprising administering to the subject a composition comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; And at least one pharmaceutically acceptable excipient.

26. A method for preventing or reducing necrosis in a subject in need, the method comprising administering to the subject a composition comprising a polymeric component selected from the group consisting of: (1) Polyethyleneimine intermediates; (2) Polymers, copolymers, interpenetrating polymer networks, polyelectrolyte complexes, blends, or composites, comprising: (i) A first adduct of a first multifunctional crosslinking agent and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinking agent; (ii) the polyethyleneimine intermediate, or the polyethyleneimine intermediate and the second adduct of the second polyfunctional crosslinker; wherein the polyethyleneimine intermediate comprises an optionally substituted hydroxyalkylene functional group that reacts with the first adduct, and the nitrogen atom present in the polyethyleneimine intermediate is at least partially quaternized. (iii) Optional polyols; (iv) optional water-soluble polymers; and, (v) An optional third multifunctional crosslinking agent; or, (3) A polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite material comprising the first adduct, the polyol, the water-soluble polymer and optionally the third multifunctional crosslinking agent; (4) The second adduct; and, (5) A combination of the two or more of the above; And at least one pharmaceutically acceptable excipient.

27. The method according to any one of claims 11 to 26, wherein the subject is a human or animal subject.

28. The method according to any one of claims 11 to 27, wherein the composition has antibacterial activity against one or both of Gram-negative and Gram-positive bacterial strains.

29. The method according to any one of claims 11 to 28, wherein the ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:

1.

30. The wound dressing, topical formulation, or method according to any one of claims 1 to 29, wherein the polyethyleneimine intermediate comprises a reaction product of a reagent, the reagent comprising polyethyleneimine and an alkylating agent.

31. The wound dressing, topical preparation, or method of claim 30, wherein the reagent further comprises a monoepoxide or lactone.

32. The wound dressing, topical formulation, or method according to claim 31, wherein the monoepoxide or the lactone is optionally substituted with a C1-C6 alkyl group, wherein the C1-C6 alkyl group is optionally substituted with a substituent selected from: -(C6-C 10 aryl); and optionally substituted with hydroxyl -(C1-C6 alkoxy); C1-C6 alkoxy; optionally substituted with C1-C6 alkyl C6-C 10 Aryl; and carboxyl.

33. The wound dressing, topical formulation, or method according to claim 31, wherein the monoepoxide is a C1-C6 alkyl ethylene oxide.

34. The wound dressing, topical formulation, or method according to claim 33, wherein the C1-C6 alkyl epoxide is selected from the group consisting of methyl ethylene oxide, ethyl ethylene oxide, propyl ethylene oxide, and butyl ethylene oxide.

35. The wound dressing, topical formulation, or method according to any one of claims 1 to 29, wherein the polyethyleneimine intermediate comprises a reaction product of a reagent comprising polyethyleneimine, a monoepoxide, and optionally an alkylating agent; the monoepoxide being -(C1-C6 alkylene)-N + (R 20 )3X - Replace; each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

36. The wound dressing, topical formulation, or method according to any one of claims 30 to 35, wherein the alkylating agent comprises one or more R 21 -LG, where each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 Aryl) and optionally -(C1-C6 alkoxy) substituted with -OH; and each LG is a leaving group.

37. The wound dressing, topical preparation, or method according to claim 36, wherein the alkylating agent is a benzoyl methyl halide, a benzyl halide, or a hexyl halide.

38. The wound dressing, topical formulation, or method according to any one of claims 30 to 37, wherein the reagent for the reaction product contained in the polyethyleneimine intermediate further comprises a monoisocyanate.

39. The wound dressing, topical formulation, or method of claim 38, wherein the monoisocyanate comprises one or more R... 30 -NCO, where each R 30 Independently selected from (1) C6-C 20 Alkyl group, optionally substituted with 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (Aryl); and (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c ); where each R a Independently C1-C6 alkyl; and each R b and each R c It is independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3.

40. The wound dressing, topical formulation, or method according to claim 38 or claim 39, wherein the monoisocyanate comprises octyl isocyanate, octadecyl isocyanate, or a combination thereof.

41. The wound dressing, topical preparation or method according to any one of claims 30 to 40, wherein the molecular weight of the polyethyleneimine is about 300 to about 270,000 Daltons.

42. The wound dressing, topical preparation or method according to any one of claims 30 to 41, wherein the molecular weight of the polyethyleneimine is about 10,000 to about 200,000 Daltons.

43. The wound dressing, topical preparation or method according to any one of claims 30 to 42, wherein the polyethyleneimine has a molecular weight of about 25,000 to about 120,000 Daltons.

44. The wound dressing, topical preparation, or method according to any one of claims 30 to 43, wherein the polyethyleneimine is branched.

45. The wound dressing, topical preparation, or method according to any one of claims 30 to 43, wherein the polyethyleneimine is hyperbranched.

46. ​​The wound dressing, topical preparation or method according to any one of claims 30 to 45, wherein the ratio of the primary amine to the secondary amine to the tertiary amine of the polyethyleneimine is about 1:2:1 to about 1:1:

1.

47. The wound dressing, topical preparation or method according to any one of claims 30 to 45, wherein the ratio of the primary amine to the secondary amine to the tertiary amine of the polyethyleneimine is about 1:1:0.

7.

48. The wound dressing, topical preparation, or method according to any one of claims 1 to 29, wherein the polyethyleneimine intermediate is selected from one or more of the following: , , , , , , and copolymers or blends of any two or more thereof, wherein: Each Y 3 Independently H or -OY 2 ; Each Y 2 Independently H or -C(O)-NHR 30 ; Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000; Z stands for -(C2-C6 alkylene)-; Each R 10 Independently selected from hydrogen; C1-C6 alkyl groups optionally substituted with substituents selected from the following: -N + (R 20 )3X - -(C6-C 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 aryl) and carboxyl; and each R 20 Choose independently the following groups: C1-C 18 Alkyl; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary-substituted N. 18 Heteroalkyl; and C6-C alkyl groups optionally substituted with -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl). 10 Aryl; Each R 21 Independently selected from C1-C6 alkyl groups, optionally substituted by substituents selected from: -OH, -(C1-C6 alkoxy), carboxyl, -(C6-C6 alkoxy), ... 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH; Each R 30 Independently selected from (1) C6-C 20 Alkyl group, optionally substituted with 1 to 3 substituents independently selected from the following: halogen, -SiR a (OR b (OR) c ) and -(C6-C 10 (Aryl); and (2) C6-C 10 Aryl group, optionally substituted by 1 to 3 substituents independently selected from: halogen, -(C1-C6 alkyl), and -SiR. a (OR b (OR) c ); where each R a Independently C1-C6 alkyl; and each R b and each R c Independently selected from -(C1-C6 alkyl) and -Si(C1-C6 alkyl)3; and, Each X - Independently selected from the group consisting of: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate and borate, and their organic substituted derivatives; The premise is: When R 10 To be optionally selected from -(C6-C) 10 aryl) and optionally substituted with -OH -(C1-C6 alkoxy), -(C1-C6 alkoxy), optionally substituted with -(C1-C6 alkyl) -(C6-C 10 When the C1-C6 alkyl group is substituted with aryl and carboxyl groups, then the polyethyleneimine intermediate is independently selected from... , and .

49. The wound dressing, topical formulation, or method according to any one of claims 1 to 29, wherein the polyethyleneimine intermediate is... or ; Each R 60 Independently selected from -Y groups optionally substituted by 1-3 substituents selected from the following 4 -(C1-C 18 Alkyl groups: -OH, -N + (R 20 )3X - -(C1-C6 alkoxy), carboxyl, -(C6-C 10 aryl), -C(O)O (C1-C6 alkyl), -C(O)- (C6-C 10 aryl) and optionally -(C1-C6 alkoxy) substituted with -OH; and at least one R 60 All R-substituted with -OH, but less than 50% 60 Replaced by -OH; Y 4 It does not exist or is -C(O)-; And each R 20 Choose independently the following groups: C1-C 18 Alkyl group; C1-C having 1 to 4 heteroatoms independently selected from O, S, Si and tertiary substituted N. 18 Heteroalkyl groups; and C6-C groups optionally substituted with the following: 10 Aryl groups: -(C1-C6 alkyl), -(C1-C6 alkoxy), -C(O)O-(C1-C6 alkyl), -C(O)NH(C1-C6 alkyl), -C(O)N(C1-C6 alkyl)2 or -OC(O)-(C1-C6 alkyl); Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000; and, Each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

50. The wound dressing, topical formulation, or method according to any one of claims 1 to 29, wherein the polyethyleneimine intermediate is... or ; Each R 60 Independently selected from -Y groups optionally substituted by 1-3 substituents selected from the following 4 -(C1-C 18 Alkyl groups: -OH, -N + (R 20 )3X - -(C6-C 10 Aryl), -C(O)O (C1-C6 alkyl) and -C(O)- (C6-C 10 (aryl); and at least one R 60 All R-substituted with -OH, but less than 50% 60 Replaced by -OH; Y 4 It does not exist or is -C(O)-; And each R 20 Independently selected from the group consisting of C1-C6 alkyl groups; Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 1000; and, Each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

51. The wound dressing, topical preparation, or method according to claim 50, wherein each R 60 Independently selected from -(C1-C) groups optionally substituted with -OH. 18 Alkyl); and at least one R 60 All R-substituted with -OH, but less than 50% 60 It is replaced by -OH.

52. The wound dressing, topical formulation, or method according to any one of claims 1 to 29, wherein the polyethyleneimine intermediate is selected from the group consisting of: Where A is B is And each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 100.

53. The wound dressing, topical preparation, or method according to claim 52, wherein the one or more bromide anions are independently selected from the group consisting of X. - Substitution: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organic substituted derivatives.

54. The wound dressing, topical formulation, or method according to any one of claims 1 to 29, wherein the polyethyleneimine intermediate is selected from the group consisting of: ， Where A is B is Each n is an integer independently selected from 1 to 3000, preferably an integer independently selected from 10 to 100; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

55. The wound dressing, topical formulation, or method according to any one of claims 1 to 54, wherein at least 20% of the nitrogen atoms of the polyethyleneimine intermediate are quaternized.

56. The wound dressing, topical formulation, or method according to any one of claims 1 to 55, wherein the polyethyleneimine intermediate is present in the polymer, copolymer, or interpenetrating polymer network of the polymerizing component (1), (3), or (4) in an amount of about 0.1% by weight to about 50% by weight.

57. The wound dressing, topical preparation, or method according to any one of claims 1 to 56, wherein the polymeric component is the polyethyleneimine intermediate.

58. A method of preparing a wound dressing according to any one of claims 1 to 8 and 30 to 57, comprising incorporating a composition including the polymeric component into a fibrous material by one of the following: (i) Spraying the fiber material with the composition. (ii) Immersing the fiber material in a fluid containing the composition. (iii) Impregnating the fibers of the fibrous material with a fluid containing the composition. (iv) Applying a coating containing the composition to the surface of the fibrous material. (v) Adhere a backing containing the composition to the fibrous material. (vi) Applying microneedles containing the composition to the fibrous material. (vii) Embedding the layer containing the composition into the fibrous material; (viii) Constructing fibers of the fibrous material from the composition by electrospinning; or... (ix) Interweaving the fibers containing the composition with the fibers of the fiber material.

59. A polymer having wound-healing properties, comprising a polyethyleneimine intermediate, wherein the ratio of total quaternary ammonium to total hydroxyl groups in the polyethyleneimine intermediate is at least 1:

1.

60. The polymer according to claim 59, wherein the polymer is selected from the group consisting of: ， Where A is B is And each n is an integer independently selected from 2 to 3000, preferably an integer independently selected from 10 to 100.

61. The polymer of claim 60, wherein the one or more bromide anions are independently selected from the group consisting of X. - Substitution: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organic substituted derivatives.

62. The polymer according to claim 59, wherein the polymer is selected from the group consisting of: ， Where A is B is Each n is an integer independently selected from 2 to 3000, preferably an integer independently selected from 10 to 100; and each X - The group consisting independently of the following: acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, trifluoromethanesulfonate, and borate, and their organically substituted derivatives.

Images