US-12616716-B2 - Wound healing dressings and formulations and methods of use thereof

US12616716B2US 12616716 B2US12616716 B2US 12616716B2US-12616716-B2

Abstract

Described herein are wound dressings and methods of their use, wherein the wound dressings comprise a polymeric component. The polymeric component is a polyethyleneimine intermediate selected from the group consisting of: at least one R 60 is —(CH 2 ) 3 OH but less than 50% of all R 60 are —(CH 2 ) 3 OH; and the polyethyleneimine intermediate has a ratio of total quaternary amines to total hydroxyl groups of at least 1:1.

Inventors

Stephen Robert Herchen
Rong-Chang Liang
Christian Ewald JANSSEN
Ran Avraham Frenkel

Assignees

POLAROID IP B.V.

Dates

Publication Date: 20260505
Application Date: 20241211

Claims (12)

1 . A wound dressing comprising a polymeric component, wherein the polymeric component is a polyethyleneimine intermediate selected from the group consisting of wherein each R 60 is independently selected from —(CH 2 ) 3 OH and —C 6 H 13 ; at least one R 60 is —(CH 2 ) 3 OH but less than 50% of all R 60 is —(CH 2 ) 3 OH; each n is an integer independently selected from 1 to 3000; each X − is independently selected from the group consisting of acetate, halide, sulfate, sulfonate, phosphate, phosphonate, carbonate, silicate, hexafluorophosphate, hexafluoroantimonate, triflate, and borate; and the polyethyleneimine intermediate has a ratio of total quaternary amines to total hydroxyl groups of at least 1:1.
2 . The wound dressing of claim 1 , wherein —(CH 2 ) 3 OH is present in the polyethyleneimine intermediate in an amount of 5 mol % to 20 mol %; and —C 6 H 13 is present in the polyethyleneimine intermediate in an amount of 80 mol % to 95 mol %.
3 . The wound dressing of claim 2 , wherein the polyethyleneimine intermediate is and —(CH 2 ) 3 OH is present in the polyethyleneimine intermediate as R 60 in an amount of 10 mol %, and —C 6 H 13 is present in the polyethyleneimine intermediate as R 60 in an amount of 90 mol %; or —(CH 2 ) 3 OH is present in the polyethyleneimine intermediate as R 60 in an amount of 12 mol %, and —C 6 H 13 is present in the polyethyleneimine intermediate as R 60 in an amount of 88 mol %.
4 . The wound dressing of claim 3 , wherein at least 20% of the nitrogen atoms of the polyethyleneimine intermediate are quaternized.
5 . The wound dressing of claim 4 , wherein the polymeric component is antibacterial against one of or both gram negative strain bacteria and gram positive strain bacteria.
6 . The wound dressing of claim 5 , wherein an outer layer of the wound dressing contains the polymeric component.
7 . The wound dressing of claim 5 , wherein the polymeric component is impregnated into the wound dressing.
8 . The wound dressing of claim 5 , wherein the wound dressing is selected from the group consisting of a wrap, a packing, a gauze, a plaster, a bandage, a lint, a film, and any combination of the foregoing.
9 . The wound dressing of claim 1 , wherein —(CH 2 ) 3 OH is present in the polyethyleneimine intermediate in an amount of 10 mol % to 15 mol %; and —C 6 H 13 is present in the polyethyleneimine intermediate in an amount of 85 mol % to 90 mol %.
10 . The wound dressing of claim 8 , wherein the wound dressing is a foam, a hydrogel, or a hydrocolloid.
11 . The wound dressing of claim 1 , wherein each n is an integer independently selected from 10 to 1000.
12 . A method of promoting healing of a wound or a surgical site in a subject in need thereof, the method comprising applying, to the wound or the surgical site, the wound dressing of claim 1 .

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of International Application No. PCT/IB2024/053809, filed on Apr. 18, 2024, which claims the benefit of priority to U.S. Provisional Patent Application No. 63/460,399, filed Apr. 19, 2023, both of which are hereby incorporated by reference herein in their entireties. FIELD The embodiments of the present disclosure relate to wound healing dressings and formulations comprising compositions of quaternary ammonium polymer structures with broad spectrum antimicrobial properties, and methods of their use. BACKGROUND Wound healing is a natural physiological reaction to tissue injury. Wounds generally heal in four to six weeks. Chronic wounds are those that fail to heal within this time frame. One factor that can lead to impaired healing is bacterial colonization. Wound dressings and/or topical formulations with antimicrobial properties can control and reduce or prevent infection, thereby promoting wound healing. SUMMARY In one aspect, described herein is a wound dressing comprising a polymeric component selected from a group consisting of: (1) a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite comprising: (i) a first adduct of a first multifunctional crosslinker and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinker;(ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate and a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises optionally substituted hydroxyalkylene functionality that reacts with the first adduct, and nitrogen atoms present in the polyethyleneimine intermediate are at least partially quaternized;(iii) optionally a polyol;(iv) optionally a water-soluble polymer; and(v) optionally a third multifunctional crosslinker; (2) a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite comprising the first adduct, the polyol, the water-soluble polymer, and optionally the third multifunctional crosslinker;(3) the polyethyleneimine intermediate;(4) the second adduct; and(5) a combination of two or more thereof. In some embodiments, (i) the first adduct and (ii) the polyethyleneimine intermediate or the second adduct are prepared separately and mixed thereafter to form the polymer, the copolymer, the interpenetrating polymer network, the polyelectrolyte complex, the blend, or the composite. In some embodiments, the polymeric component is antibacterial against one of or both gram negative strain bacteria and gram positive strain bacteria. In some embodiments, the polyethyleneimine intermediate has a ratio of total quaternary amines to total hydroxyl groups of at least 1:1. In some embodiments, an 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 a wrap, a covering, a barrier, a layer, a packing, a gauze, a plaster, a bandage, a lint, a suture, a film, a foamed product, a hydrogel, a hydrocolloid, an alginate product, a bioactive product, a tissue-engineered skin substitute, a medicated product, a liquid bandage, a smart dressing, and a composite, or any combination of the foregoing. In some embodiments, the wound dressing is configured to provide an indication of one or more parameters relating to a status of the wound site. In another aspect, described herein is a topical formulation comprising a polymeric component selected from a group consisting of: (1) a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite comprising: (i) a first adduct of a first multifunctional crosslinker and a first quaternary ammonium salt, wherein the first quaternary ammonium salt has a reactive linking group to react with the first multifunctional crosslinker;(ii) a polyethyleneimine intermediate, or a second adduct of the polyethyleneimine intermediate and a second multifunctional crosslinker; wherein the polyethyleneimine intermediate comprises optionally substituted hydroxyalkylene functionality that reacts with the first adduct, and nitrogen atoms present in the polyethyleneimine intermediate are at least partially quaternized;(iii) optionally a polyol;(iv) optionally a water-soluble polymer; and(v) optionally a third multifunctional crosslinker; or (2) a polymer, copolymer, interpenetrating polymer network, polyelectrolyte complex, blend or composite comprising the first adduct, the polyol, the water-soluble polymer, and optionally the third multifunctional crosslinker;(3) the polyethyleneimine intermediate;(4) the second adduct; and(5) a combination of two or more thereof;and at least one pharmaceutically acceptable excipient;