Wound care compositions and articles thereof having antimicrobial properties

Abstract

Wound care compositions, wound care articles, and methods of treating a wound are described herein. Methods of preparing wound care compositions and wound care articles are also described.

Description

WOUND CARE COMPOSITIONS AND ARTICLES THEREOF HAVING ANTIMICROBIAL PROPERTIES BACKGROUND

[0001] A wide variety of compositions, materials, and devices are known in the art for use in treating a wound and tissue disruptions. Wounds may be the result of trauma, surgery, or disease and may require measures to control bleeding, absorb wound exudate, ease pain, assist in debridement, and protection from infection or escalating infection. Such measures aim to promote healing and offer protection from further damage.

[0002] Wound healing and tissue regeneration are a complicated series of biochemical processes involving four key phases: hemostasis, inflammation, proliferation, and remodeling. If the destructive processes that remove damaged tissues and the repair processes that form new tissue become imbalanced, a chronic non-healing wound may result. Proteases and growth factors regulate this balance. Chronic wounds, which have elevated levels of proteases present within the environment, most often stall in the inflammatory phase, or proceed through repair processes without establishing a sustained anatomic and functional result.

[0003] Oxidized celluloses “OCs” such as oxidized regenerated cellulose “ORC” and oxidized non-regenerated cellulose “OnRC” have been used in wound care as hemostatic agents and as healing promoters, especially for chronic wounds since OCs can inactivate matrix metalloproteases and bind growth factors. OCs initiate clotting via contact activation by turning to a gelatinous mass. OCs also lower the pH within a wound environment, which is beneficial against microbes, but may induce red cell lysis, interfere with osteogenesis, inactivate thrombin, and ultimately delay healing. pH interference is also a common problem associated with antimicrobial usage.

[0004] Infections can prevent wounds from healing and lead to chronic wounds and / or exacerbate existing chronic wounds. If untreated, wound infections can result in tissue loss, systemic infections, septic shock, and death. Bacterial biofilms may also form in a wound, whichpresent further challenges. A biofilm is an association of microorganisms of one or more species that can adhere to a surface forming three-dimensional microbial communities. The microbial communities can have coordinated multi-cellular behavior and produce extracellular polysaccharides that can embed bacteria in a protective matrix that can subvert a host’s defense mechanism and shield bacteria from biocides. Thus, many of the available treatments that are effective against free-living or planktonic bacteria are ineffective against the same bacteria when present in a biofilm.

[0005] Treating an infected chronic wound is particularly challenging, especially those that are inoculated with biofilms. What is needed are compositions and articles that aid in the balance of biological processes that support healing. SUMMARY

[0006] In one embodiment, a wound care composition is described. The wound care composition includes a collagen; an oxidized cellulose; a quaternary ammonium salt; a chelator compound; and a C8-12alkyl 1,2-diol.

[0007] In one embodiment, a wound care composition is described. The wound care composition includes a collagen; a quaternary ammonium salt; a chelator compound; and a C8-12alkyl 1,2-diol.

[0008] In one embodiment, a wound care composition is described. The wound care composition includes a collagen; an oxidized cellulose; a quaternary ammonium salt; and a chelator compound.

[0009] In one embodiment, a wound care article is described. The wound care article includes a wound care composition of the present disclosure, wherein the wound care composition is in the form of a free-standing construction.

[0010] In one embodiment, a method of preparing a wound care article is described. The method includes providing a wound care composition of the present disclosure and applying the wound care composition onto a substrate to form a layer and drying the layer to form a free- standing construction.

[0011] In one embodiment, a wound care article prepared by a method of the present disclosure is described. The wound care article includes a wound care composition of the present disclosure.The method includes applying the wound care composition onto a substrate to form a layer and drying the layer to form a free-standing construction.

[0012] In one embodiment, a method for treating a wound is described. The method includes contacting a wound with a wound care composition of the present disclosure.

[0013] In one embodiment, a method for treating a wound is described. The method includes contacting a wound with a wound care article of the present disclosure.

[0014] In one embodiment, a kit is described. The kit includes a wound care composition of the present disclosure and a set of instructions directing a user to contact the wound care composition to a wound.

[0015] In one embodiment, a kit is described. The kit includes a wound care article of the present disclosure and a set of instructions directing a user to contact the wound care article to a wound.

[0016] In one embodiment, a kit is described. The kit includes a wound care composition of the present disclosure, or components thereof, and a set of instructions directed a user to prepare a wound care article of the present disclosure. DETAILED DESCRIPTION

[0017] Described herein are wound care compositions and wound care articles that offer enhanced biofilm kill. The combination of a collagen, an oxidized cellulose, a quaternary ammonium salt, a chelator compound, and a C8-12alkyl 1,2-diol is shown to synergistically increase efficacy against biofilms of S. aureus and P.aeruginosa. Moreover, the present disclosure teaches that a heating step further increases the efficacy against biofilms. Although the reason for this heating observation is not yet clear, it is suspected that the collagen may undergo an intramolecular reaction or an intermolecular reaction with one or more the collagen, the oxidized cellulose, or the chelator compound. For example, collagens have amino groups that may undergo condensation reactions with carboxylic acids to form amides under elevated temperatures. Without wishing to be bound by theory, it may be the case that free amines, in some way, impede biofilm kill.

[0018] Collagens, oxidized celluloses, quaternary ammonium salts, chelator compounds, and C8-12alkyl 1,2-diols have each been individually incorporated into wound care compositions;however, the combination of collagens, oxidized celluloses, quaternary ammonium salts, chelator compounds, and C8-12alkyl 1,2-diols in a single medicament is not known, nor would have one expected the synergistic attributes of such combination. Currently, there is no concrete explanation as to why the said combination improves biofilm kill, but one may surmise that a supramolecular chemistry phenomenon is taking place.

[0019] The wound care compositions and wound care articles of the present disclosure allow for suitable treatment of wounds infected with biofilms and prevent wounds from becoming infected. Definitions

[0020] As used herein, “about” means ± 10 percent of a given value. For example, about 10 means 9 to 11.

[0021] As used herein, “alkonium salt” refers to a quaternary ammonium salt compound of formula (I): R1-N+(R2)3X- (I), wherein R1is a C6-22alkyl group, and each R2is independently selected from a C1-22alkyl group, and X is a pharmaceutically acceptable counterion (e.g., a halide, e.g., Cl, Br, I).

[0022] As used herein, “alkyl” refers to a straight or branched hydrocarbon chain. Example alkyl groups include methyl (-CH3), ethyl (-CH2CH3), propyl (-CH2CH2CH3), isopropyl (-CH(CH3)2), and the like.

[0023] As used herein, “aryl” refers to cyclic group characterized by aromaticity. Aromatic groups are defined by a conjugated planar ring with 4n+2π electrons. Aryl groups do not include heteroatoms within the ring, whereas as heteroaryl groups include at least one heteroatom within the ring, e.g., O, N, or S.

[0024] As used herein, “aralkyl” refers to an aryl group substituted with one or more alkyl group.

[0025] As used herein, “antiseptic” means an antimicrobial component that kills pathogenic and non-pathogenic microorganisms. Antiseptics generally interfere with cellular metabolism and / or interfere with the cell envelope. Antiseptics are sometimes called disinfectants. Example antiseptics include antimicrobial lipids, phenolic antiseptics, cationic antiseptics, iodine and / or iodophors, peroxide antiseptics, antimicrobial natural oils.

[0026] As used herein, “benzalkonium salt” refers to a quaternary ammonium salt compound of the formula (II): PhCH2N+(R3)3X- (II), wherein each R3is independently a C1-22alkyl group or a –(CH2)m-Y-C(O)-R4group, Y is -O- or -NH-, R4is a C1-22alkyl group, m is an integer of 1-6, and X is a pharmaceutically acceptable counterion (e.g., a halide, e.g., Cl, Br, I). “Ph” is

[0027] As used herein, “benzethonium salt” a quaternary ammonium salt compound of formula (III): PhCH2N+(R5)2-(CH2CH2O)n-R6X- (III), wherein each R5is independently a C1-22alkyl group, R6is a C1-22alkyl group, a C6-10aryl group, or a C7-22aralkyl group, n is an integer selected from 1-20, and X is a pharmaceutically acceptable counterion (e.g., a halide, e.g., Cl, Br, I). “Ph” is phenyl.

[0028] As used herein, “C8-12alkyl 1,2-diol” refers to an 8-12 carbon linear or branched alkyl group having two hydroxyl groups (i.e., -OH) – the first hydroxyl group bound to the first carbon and the second hydroxyl group bound the second carbon. A C8-12alkyl 1,2-diol is represented by formula (IV): HOCH2CR7(OH)-R8(IV), wherein R7is -H or alkyl and R8is alkyl, so long as R7and R8together contain 6-10 carbons. The term may also be referred to herein as “C8-12alkane 1,2-diol” or “1,2-C8-12alkanediol.”

[0029] As used herein, “chelator” refers to a compound having at least two carboxylic acid groups (i.e., -CO2H) wherein the oxygen atom of at least one oxygen of a carboxylic acid is 4-6 atoms (e.g., 4-5 atoms) away from an oxygen atom or a nitrogen atom. A “chelator salt” refers to a chelator which has been deprotonated (e.g., -CO2- Y+) and having a pharmaceutically acceptable counterion (e.g., Na+, Ca2+, or the like). A “chelator compound” refers to a chelator, a chelator salt, or a combination thereof.

[0030] As used herein, “collagen” refers to a structural protein found in, for example: (Type I): skin, tendon, vasculature, organs, bone (Type II): cartilage (Type III): reticulate (Type IV): basal lamina, epithelium-secreted layer of the basement membrane (Type V): cell surfaces, hair, and placenta

[0031] As used herein, “disinfecting” refers to a reduction in the number of active microorganisms present on a surface being disinfected. Disinfecting may kill or prevent microorganisms from growing or proliferating.

[0032] As used herein, “drying” refers to the removal of volatile or vaporizable compounds. When a substance herein is described as “dried,” it means that less than 1 wt.% of said compounds are present. Various methods of drying are known to a skilled artisan.

[0033] As used herein, “exclude” means that a component is absent (i.e., present in 0 wt.%).

[0034] As used herein, “free-standing construction” describes an article to which its shape is retained at temperatures less than 80 °C at 1 atm at relative humidity less than 50% for at least 3 months. In other words, the construction is physically stable and does not lose shape by way of melting, swelling, crystallization, phase separation, or the like. Dried wound care compositions and wound care articles including a dried wound care composition of the present disclosure are free-standing constructions.

[0035] As used herein, “microorganism” or “microbe” refers to bacteria, yeast, mold, fungi, protozoa, mycoplasma, and / or viruses including lipid-enveloped RNA and DNA viruses.

[0036] As used herein, “oxidized cellulose” or “oxidized celluloses,” abbreviated “OC” and “OCs” respectively, refer to a cellulose wherein at least a portion of its hydroxyl groups have been oxidized to carboxylic acids (i.e., -OH à -CO2H). Cellulose is a polymeric structural framework of plant cells, with repeating units of d-glucose. Due to the presence of strong hydrogen bonding between polymer chains, cellulose is insoluble in common solvents and in water. Oxidized cellulose is also insoluble in water. The term “oxidized cellulose” encompasses both oxidized non-regenerated cellulose and oxidized regenerated cellulose separately or in combination, unless otherwise specified. Percentages involving oxidized cellulose are intended to be the total amount of oxidized cellulose, whether ORC, OnRC, or the combination thereof.

[0037] As used herein, “oxidized non-regenerated cellulose” or “OnRC” refers to a non- regenerated cellulose wherein at least some portion of hydroxyl groups have been oxidized to carboxylic acids (i.e., -OH ^ -CO2H).

[0038] Asregenerated cellulose” or “ORC” refers to a regenerated cellulose wherein at least some portion of hydroxyl groups have been oxidized to carboxylic acids (i.e., -OH ^ -CO2H).

[0039] As used herein, “plasticizer” refers to a substance or combination of substances that lowers the glass transition temperature of another substance (e.g., a pressure-sensitive adhesive). Plasticizers effectively soften, increase flexibility, increase plasticity, decrease viscosity, and / or decrease friction of a substance to which it is added.

[0040] As used herein, “polymer” refers to a substance having one or more repeating monomer units. The chemical identities of the polymeric substances herein are at times described in terms of the monomers to which the polymer is derived. A skilled artisan would readily understand the reactivity profile of the recited monomers and how the monomers could synthetically be joined to form the polymer.

[0041] As used herein, “pressure-sensitive adhesive” refers to a non-reactive, self-stick adhesive that forms a bond when pressure is applied. No solvent, water, or heat is required to activate a pressure-sensitive adhesive.

[0042] As used herein, “preventing” refers to stopping or delaying the onset of a condition within a treated sample relative to an untreated control sample.

[0043] As used herein, “regenerated” as it is used in “regenerated cellulose” refers to a process in which natural cellulose (e.g., derived from a natural source such as wood and other agricultural products) undergoes a chemical manufacturing process that breaks down cellulose such that it may solubilized, functionalized, and ultimately “regenerated.” Regenerated celluloses are often called “rayon.” One of such chemical manufacturing processes is called “Viscose Method,” wherein the natural cellulose is treated with a strong base and carbon disulfide to form a xanthate derivative. The xanthate moieties are later removed, thereby “regenerating” the cellulose. Depending upon the selected process, resulting regenerated fibers may imitate the feel and texture of silk, wool, cotton, linen, or the like. As used herein, “non-regenerated” as it is used in “non-regenerated cellulose” refers to the absence of said regenerative processes described above. Regenerated cellulose and non-regenerated cellulose can differ in fiber organization and structure.

[0044] When referring to “solubility,” or “to solubilize,” the solubility of a component A in a component B refers to conditions in which only component A and component B are present, e.g., no added salts, compounds, or the like. Furthermore, any solubility values provided herein regard a temperature range of about 20 ⁰C to about 23 ⁰C at atmospheric pressure (i.e., 760 mm / Hg).

[0045] As used herein, the term “subject” refers to a mammal, e.g., humans, sheep, horses, cattle, pigs, dogs, cats, rats, mice, and the like.

[0046] As used herein, the term “treating” refers to alleviating clinical symptoms of a condition.

[0047] As used herein, the term “water-soluble” characterizes a material that dissolves in deionized water at a temperature of 23 °C in an amount of at least 7 wt.% (i.e., 7 g material per 100 g deionized water). A material is considered dissolved if the resulting solution is clear without visible cloudiness, phase separation, or precipitate at 23 °C for 24 h.

[0048] As used herein, “water-soluble polymer” refers to polymer that dissolves in deionized water at a temperature of 23 °C in an amount of at least 7 wt.% (i.e., 7 g material per 100 g deionized water). Likewise, a “water-soluble substrate” refers to a material consisting only of a compound(s) (e.g., polymer(s)) which are water-soluble.

[0049] As used herein, the term “wound” refers to broken skin, e.g., a cut, a puncture, an abrasion, a scratch, a rash, and the like. A “wound dressing” refers to an article that may control bleeding, absorb wound exudate, ease pain, assist in debriding, protect against infection, mediate infection, modulate proteases, or otherwise promote healing and protection from further damage. A “chronic wound” refers to a wound that does not progress through a normal, orderly, or timely sequence of repair, e.g., a wound that does not heal after 4 weeks of standard care.

[0050] As used herein, the term “pyridinium salt” refers to a quaternary ammonium salt of formula V:(V), wherein R9is a C4-22alkyl group and X is a pharmaceutically acceptable counterion (a halide, e.g., Cl, Br, I).

[0051] As used herein, the term “quaternary ammonium salt” refers to compound having one or more nitrogen atom substituted with four carbons (i.e., R-N+(R)3), or alternatively a nitrogen is substituted with three carbon groups wherein one carbon shares a double bond with nitrogen (i.e., R=N+(R)2), wherein R is a carbon, e.g., alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, or two R taken together to form a heteroaryl or heterocyclyl. The quaternary ammonium salts of the present disclosure possess antiseptic and / or disinfectantproperties. The quaternary ammonium salts of the present disclosure are not characterized by protonated amines, protonated imines, protonated guanidines, or the like, nor are they characterized by groups such as amine oxides. A review of quaternary ammonium salt compounds may be found at Vereshchagin, A. N. Int. J. Mol. Sci. 2021, 22, 6793, the contents of which are incorporated herein by reference in its entirety.

[0052] As used herein, the term “volatile” is used to characterize a compound that has a boiling point of no more than 260 °C at 1 atm. Accordingly, “non-volatile” is used to characterize a compound that has a boiling point of less than 260 °C at 1 atm. Wound care Compositions

[0053] In various embodiments, a wound care composition is described. The wound care composition may include, or consist essentially of, or consist only of a collagen, an oxidized cellulose, a quaternary ammonium salt, a chelator compound, and a C8-12alkyl 1,2-diol.

[0054] In various embodiments, a wound care composition is described. The wound care composition may include, or consist essentially of, or consist only of a collagen, a quaternary ammonium salt, a chelator compound, and a C8-12alkyl 1,2-diol. In other words, a wound care composition is described that may exclude the oxidized cellulose described herein. Such embodiments are captured within the comparative examples of the present disclosure, yet the antimicrobial activity showcased remains useful in treating wounds.

[0055] In various embodiments, a wound care composition is described. The wound care composition may include, or consist essentially of, or consist only of a collagen, an oxidized cellulose, a quaternary ammonium salt, and a chelator compound. In other words, a wound care composition is described that may exclude the C8-12alkyl 1,2-diol described herein. Such embodiments are captured within the comparative examples of the present disclosure, yet the antimicrobial activity showcased remains useful in treating wounds.

[0056] In many embodiments, the wound care compositions of the present disclosure may be a dried wound care composition, i.e., the wound care composition includes no greater than 1 wt.% volatile components (e.g., water), e.g., 1 wt.%, 0.8 wt.%, 0.5 wt.%, 0.2 wt.%, 0.1 wt.%, 0.05 wt.%, 0.01 wt.%, or 0 wt.%, or a value within a range between any of the preceding values. In many embodiments, a dried wound care composition may be a wound care article of the presentdisclosure. Dried wound care composition may be in the form of a free-standing construction and may themselves be a wound care article of the present disclosure. Dried wound care compositions may be further combined with other components (e.g., liners, adhesives, or the like) to form a wound care article. In some embodiments, the wound care composition may be in the form of a powder. Powdered compositions may be sprinkled onto and into wounds (independent of the articles described herein).

[0057] In many embodiments, the wound care compositions of the present disclosure may further include one or more volatile component present in an amount greater than 1 wt.%. Example volatile components may include water and organic solvents (e.g., ethanol, isopropanol, ethyl acetate, or the like). In some embodiments, a wound care composition may include no greater than 50 wt.% volatile components (e.g., water), e.g., 3 wt.%, 5 wt.%, 10 wt.%, 15 wt.%, 20 wt.%, 25 wt.%, 30 wt.%, 35 wt.%, 40 wt.%, 45 wt.%, or 50 wt.%, or a value within a range between any of the preceding values, e.g., between 20 wt.% and 35 wt.%. Wound care compositions including one or more volatile component may be referred to herein as wet wound care compositions. Wet wound care composition may be in the form of a solution, a dispersion, a colloid, or a suspension.

[0058] In many embodiments, the wound care compositions of the present disclosure may exclude one or more of: surfactants, water-soluble polymers, water-insoluble polymers, polysaccharides other than the oxidized cellulose, and proteins other than the collagen.

[0059] In many embodiments, the wound care compositions may exclude non-volatile liquid components (i.e., liquid at 20 °C and 1 atm) in amounts that would result in a dried wound care composition that is not a free-standing construction. Typically, this may mean that a dried wound care compositions may include < 15 wt.% total non-volatile liquid components, e.g., <15 wt.%, <10 wt.%, <5 wt.%, <2 wt.%, <1 wt.%, or the like. For example, non-volatile liquid components may include glycerol, polyols, triglyceride oils, or the like. As used in this context, a “liquid” is any free-flowing fluid that conforms to the shape of a container but retains a nearly constant volume independent of pressure. In many embodiments, the wound care composition may include non-volatile liquid components characterized by a viscosity of less than about 25 Pa•s at a temperature of 20 °C and a shear rate of 1 s-1(e.g., less than 25, 20, 15, 10, 5, 1, 0.5, 0.1, or the like) in amounts no more than 15 wt.%, e.g., <10 wt.%, <5 wt.%, <2 wt.%, <1 wt.%, or the like.

[0060] In many embodiments, dried wound care compositions may be characterized by a pH of about 2 to about 6, e.g., 2, 2.2, 2.5, 2.8, 3, 3.2, 3.5, 3.8, 4, 4.2, 4.5, 4.8, 5, 5.2, 5.5, 5.8, or 6, orrange between any of the preceding values, e.g., between 2.5 and 3.5, or the like. In some embodiments, the wound care compositions may further include a pH buffer to adjust the pH accordingly.

[0061] Dried wound care compositions or wound care articles including a dried wound care composition may be characterized by exhibiting a log reduction value against S. aureus or P. aeruginosa of at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8.

[0062] Further details are described below. Any further details and / or components may be combined. For embodiments not requiring a C8-12alkyl 1,2-diol or embodiments not requiring a oxidized cellulose, the following sections relating to such may be ignored. Collagen

[0063] Collagen is often used alongside ORC in wound care. Collagen attracts fibroblasts, thereby aiding angiogenesis and debridement. Collagen also supports granulation tissue formation and re-epithelization.

[0064] As used herein, “a collagen” or “the collagen” may include a collagenous material that is native, denatured, or a combination thereof. In some embodiments, a collagen may be selected from Type I, Type II, Type III, fragments thereof (e.g., denatured collagen, e.g., gelatin), and a combination thereof. In some embodiments, a collagen may be, or may include, collagen fragments having a molecular weight of about 5,000 to about 100,000 Daltons, e.g., 5,000, 10,000, 15,000, 20,000, 25,000, 30,000, 35,000, 40,000, 45,000, 50,000, 60,000, 70,000, 80,000, 90,000, 100,000 or a value between any of the preceding values, for example, between about 5,000 and about 50,000, or the like. In some embodiments, a collagen may be chemically modified, for example, an atelocollagen obtained by removing the immunogenic telopeptides from a natural collagen.

[0065] In many embodiments, a collagen that has been subjected to an elevated temperature may be characterized as a functionalized collagen. As used herein, a “functionalized collagen” means that a collagen is structurally different after being subjected to heat than it was prior to being subjected to heat. For example, a collagen subjected to heat may undergo an intramolecular condensation reaction wherein free amines in one portion of the protein may react with carboxylic acids in another portion of the protein to form an amide. Likewise, two or more collagen proteins may undergo intermolecular condensation reactions, i.e., two or more collagen proteins maycrosslink by way of amide bond formation. Further, for example, a collagen may undergo an intermolecular condensation reaction with other components that contain carboxylic acid groups, e.g., oxidized celluloses or chelator compounds. Thus, in many embodiments, a “functionalized collagen” means that at least a portion of the free amines within a protein terminus or side chain have undergone condensation with a carboxylic acid to form an amide bond.

[0066] In some embodiments, a collagen may be present in an amount of about 1 wt.% to about 95 wt.% with respect to the weight of the wound care composition (wet or dry). For example, a collagen may be present in an amount, in wt.%, of about 1, 5, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, or 95, or a value within a range between any of the preceding values, e.g., between about 1 and about 5, between about 20 and 90, or the like.

[0067] In some embodiments, a collagen may be present in a wt.% ratio (w / w) with respect to an amount of oxidized cellulose of about 60:1 to about 0.15:1. For example, the amount of a collagen present relative to an amount of oxidized cellulose present, in w / w, may be about 60:1, 55:1, 50:1, 45:1, 40:1, 35:1, 30:1, 25:1, 20:1, 15:1, 10:1, 5:1, 4:1, 3:1, 2:1, 1.5:1, 1:1, 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1, 0.3:1, 0.2:1, or 0.15:1, or a value between any of the preceding values, e.g., between about 1.5:1 to about 0.2:1, or the like.

[0068] In some embodiments, a collagen may be present in a wt.% ratio (w / w) with respect to an amount of quaternary ammonium salt (any quaternary ammonium salt described herein, e.g., benzalkonium salt) present in the wound care composition of about 6000:1 to about 3:1. For example, the amount of collagen present relative to the amount of quaternary ammonium salt present, in w / w, may be about 6000:1, 5000:1, 4000:1, 3000:1, 2000:1, 1000:1, 500:1, 100:1, 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 20:1, 10:1, 8:1, 5:1, or 3:1, or a value within a range between any of the preceding values, e.g., between about 50:1 and about 100:1, between about 30:1 and about 80:1, or the like.

[0069] In some embodiments, the collagen may be present in a wt.% ratio (w / w) with respect to the amount of the chelator compound (i.e., chelator, chelator salt, or a combination thereof, e.g., any chelator / salt described herein, e.g., citric acid, sodium citrate) of about 600:1 to 0.03:1. For example, a wt.% ratio of a collagen to chelator compound may be about 600:1, 400:1, 200:1, 100:1, 75:1, 50:1, 25:1, 20:1, 15:1, 10:1, 5:1, 4.8:1, 4.6:1, 4.4:1, 4.2:1, 4:1, 3.8:1, 3.6:1, 3.4:1, 3.2:1, 3:1, 2.8:1, 2.6:1, 2.4:1, 2.2:1, 2:1, 1.8:1, 1.6:1, 1.4:1, 1.2:1, 1:1, 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1,0.3:1, 0.2:1, 0.1:1, 0.09:1, 0.08:1, 0.07:1, 0.06:1, 0.05:1, 0.04:1, or 0.03:1, or a value within a range between any of the preceding values, e.g., between about 1.2:1 and 0.8;1, or the like.

[0070] In some embodiments, a collagen may be present in a wt.% ratio (w / w) with respect to an amount of a C8-12alkyl 1,2-diol (any C8-12alkyl 1,2-diol described herein, e.g., 1,2-octanediol) of about 1000:1 to 0.2:1. For example, a wt.% ratio of collagen to C8-12alkyl 1,2-diol may be about 1000:1, 900:1, 800:1, 700:1, 600:1, 400:1, 200:1, 100:1, 75:1, 50:1, 30:1, 25;1, 20:1, 15:1, 10:1, 8:1, 5:1, 4:1, 3:1, 2:1, 1:1, 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1, 0.3:1, or 0.2:1, or a value within a range between any of the preceding values, e.g., between about 4:1 and about 8:1, or the like. Oxidized Cellulose (“OC”)

[0071] Oxidized regenerated cellulose described herein is regenerated cellulose wherein at least a portion of the primary alcohol groups (C6) have been oxidized to carboxylic acid groups. In some embodiments, the regenerated cellulose may be prepared by the viscose or Bemberg process, e.g., rayon that has not been treated with titanium dioxide or similar heavy metal materials. In some embodiments, the regenerated cellulose may have a uniform filament diameter and a denier of about 1-9 (e.g., 1-3). In some embodiments, the regenerated cellulose may be characterized by a degree of polymerization of about 200 to about 500 units. The degree of polymerization (D.P.) of a cellulosic material may be determined by the method described by R. L. Mitchell, Industrial and Engineering Chemistry, vol.45, p.2520 (1953), the contents of which are incorporated herein by reference in its entirety. Oxidized non-regenerated cellulose described herein is also likewise oxidized but has not undergone regenerative processes. As used throughout, “oxidized cellulose” includes oxidized regenerated cellulose, oxidized non-regenerated cellulose, or a combination thereof.

[0072] In some embodiments, the oxidation of a regenerated cellulose may be characterized by a carboxyl content of about 5-50% (i.e., 5-50% of the hydroxyl groups have been oxidized to carboxylic acids), e.g., 5, 10, 15, 20, 25, 30, 35, 40, 45, or 50% carboxylated, or a value within a range between any of the preceding values. In some embodiments, the oxidation of a regenerated cellulose may have a carboxyl content of about 12-25 wt.% (e.g., 18-22 wt.%). Lower denier materials may be satisfactorily absorbable at a carboxyl content of only 12-13 wt.% whereas higher denier materials may be slowly absorbable at this level of oxidation. The carboxyl content may be measured according to United States Pharmacopeia (USP23-NF18), as exemplified in Wu, Y.et al Carbohydrate Polymers 2012, 88, 1023-1032, the contents of which are incorporated herein by reference in its entirety. In some embodiments, the oxidized regenerated cellulose of the present disclosure may be prepared according to a process described in U.S. Pat. No. 3,364,200 or U.S. Pat. No. 3,122,479, the contents of each of which are incorporated herein by reference in their entireties. The described oxidized regenerated cellulose at least partly disintegrates, degrades, or dissolves upon exposure to physiological fluids or process such that at least a portion of the material may be absorbed or assimilated at a wound site.

[0073] In some embodiments, the oxidized cellulose may be present in an amount of about 0.5 wt.% to about 80 wt.% with respect to the weight of the wound care composition (wet or dry). For example, the oxidized cellulose may be present in an amount, in wt.%, of about 0.5, 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, or 80, or a value within a range between any of the preceding values, e.g., between about 1 and about 5, between about 30 and about 50, or the like. Further for example, a wound care composition having 7 wt.% ORC prior to the removal of 30 wt.% volatile components (e.g., water) may have about 10 wt.% ORC in a dried wound care composition.

[0074] In some embodiments, the oxidized cellulose may be present in a wt.% ratio (w / w) with respect to an amount of quaternary ammonium salt (e.g., any quaternary ammonium salt described herein, e.g., benzalkonium salt) present in the wound care composition of about 1:1 to about 2000:1. For example, the amount of oxidized cellulose present relative to the amount of quaternary ammonium salt present, in w / w, may be about 1:1, 5:1, 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 70:1, 75:1, 80:1, 85:1, 90:1, 100:1, 110:1, 120:1, 130:1, 140:1, 150:1, 160:1, 170:1, 180:1, 190:1, 200:1, 220:1, 240:1, 260:1, 280:1, 300:1, 325:1, 350:1, 375:1, 400:1, 500:1, 750:1, 1000:1, 1250:1, 1500:1, 1750:1, or 2000:1 or a value within a range between any of the preceding values, e.g., between about 50:1 and about 120:1, between about 30:1 and about 80:1, or the like.

[0075] In some embodiments, the oxidized cellulose may be present in a wt.% ratio (w / w) with respect to an amount of the chelator compound (i.e., chelator, chelator salt, or a combination thereof (e.g., citric acid, sodium citrate)), of about 0.03:1 to about 200:1. For example, a wt.% ratio of the oxidized cellulose to chelator compound may be about 0.03:1, 0.05:1, 0.08:1, 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:11:1, 1.2:1, 1.4:1, 1.6:1, 1.8:1, 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, 10:1, 20:1, 30:1, 40:1,50:1, 75:1, 100:1, 125:1, 150:1, 175:1, or 200:1, or a value within a range between any of the preceding values, e.g., between about 0.8:1 and 1.2:1, or the like. In some embodiments, a chelator, a chelator salt, or a combination thereof may be present in a wt.% amount less than a wt.% amount of oxidized cellulose present.

[0076] In some embodiments, the oxidized cellulose may be present in a wt.% ratio (w / w) with respect to an amount of the C8-12alkyl 1,2-diol (e.g., 1,2-octanediol) of about 0.2:1 to about 1000:1. For example, a wt.% ratio of oxidized cellulose to C8-12alkyl 1,2-diol may be about 0.2:1, 0.5:1, 0.8:1, 1:1, 2:1, 3:1, 3.2:1, 3.5:1, 3.8:1, 4:1, 4.2:1, 4.5:1, 4.8:1, 5:1, 5.2:1, 5.5:1, 5.8:1, 6:1, 6.2:1, 6.5:1, 6.8:1, 7:1, 7.2:1, 7.5:1, 7.8:1, 8:1, 8.2:1, 8.5:1, 8.8:1, 9:1, 9.2:1, 9.5:1, 9.8:1, 10:1, 25:1, 50:1, 75:1, 100:1, 125:1, 150:1, 175:1, 200:1, 250:1, 300:1, 350:1, 400:1, 450:1, 500:1, 550:1, 600:1, 650:1, 700:1, 750:1, 800:1, 850:1, 900:1, 950:1, or 1000:1, or a value within a range between any of the preceding values, e.g., between about 4:1 and about 8:1, or the like.

[0077] In many embodiments, the oxidized cellulose may be oxidized regenerated cellulose.

[0078] In many embodiments, the oxidized cellulose may be oxidized non-regenerated cellulose.

[0079] In some embodiments, the oxidized cellulose may be a combination of oxidized regenerated cellulose and oxidized non-regenerated cellulose. Quaternary ammonium salts

[0080] In many embodiments, the quaternary ammonium salt may be selected from one or more alkonium salt, one or more benzalkonium salt, one or more benzethonium salt, one or more pyridinium salt, and a combination thereof.

[0081] In some embodiments, the quaternary ammonium salt may be an alkonium salt of formula Ia: R1-N+(CH3)2R2X- (Ia), wherein R1may be a C6-22alkyl, e.g., a C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, or C22alkyl, or a range between any of the preceding values, e.g., a C12-16alkyl, a C8-18alkyl, or the like; R2may be a C1-22alkyl, e.g., a C1, C2, C3, C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, or C22alkyl, or a range between any of the preceding values, e.g., a C1-6alkyl, a C1-4alkyl, or the like; and X is Cl, Br, or I.

[0082] In some embodiments, the quaternary ammonium salt may be an alkonium salt of formula (Ib): R1-N+(CH3)3X- (Ib), wherein R1may be a C6-22alkyl, e.g., a C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, or C22alkyl, or a range between any of the preceding values, e.g., a C12-16alkyl, a C8-18alkyl, or the like; and X is Cl, Br, or I.

[0083] In some embodiments, the quaternary ammonium salt may be an alkonium salt of the formula: .

[0084] In some embodiments, the quaternary ammonium salt may be an alkonium salt of the formula:.

[0085] In many embodiments, the quaternary ammonium salt may be a benzalkonium salt selected from one or more compound of the formula (IIa):(IIa), wherein n may be an integer from 1-22, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18, or a range between any of the preceding values, e.g., 8-18, 10-16, or the like; and X may be Cl, Br, or I. In some embodiments n may be selected from an integer of 8, 10, 12, 14, 16, or 18. In some embodiments the composition may include one or more benzalkonium chloride of formulaIIa. For example, the wound care composition may include a mixture of benzalkonium salts wherein n is 8, 10, 12, 14, 16, and 18.

[0086] In some embodiments, the quaternary ammonium salt may be a benzalkonium salt of formula IIb: PhCH2N+(CH3)2-(CH2)m-NH-C(O)-R4X- (IIb), wherein R4may be a C4-22alkyl group, e.g., C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, or C22alkyl, or a range between any of the preceding values, e.g., a C13-17alkyl, a C10-18alkyl, or the like; m may be an integer of 2-4; and X may be Cl, Br, or I. “Ph” is phenyl.

[0087] In some embodiments, the quaternary ammonium salt may be a benzalkonium salt of the formula: .

[0088] Ina benzethonium salt selected from one or more compound of formula (IIIa): PhCH2N+(CH3)2(CH2CH2O)n-R6X- (IIIa), wherein R6may be Ph or -Ph-R10, R10may be a C4-10alkyl, n may be an integer selected from 1- 6, and X may be Cl, Br, or I. “Ph” is phenyl or phenylene.

[0089] In some embodiments, the quaternary ammonium salt may be a benzethonium salt of the formula: .

[0090] In somebe a pyridinium salt of formula IVa:(IVa), wherein R9may be a C4-22alkyl, e.g., C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, or C22alkyl, or within a range of any of the preceding values, e.g., a C12-18alkyl, a C10-16alkyl, or the like; and X may be Cl or Br.

[0091] In some embodiments, the quaternary ammonium salt may be a pyridinium salt of formula:.

[0092] In some embodiments, the quaternary ammonium salt (e.g., benzalkonium chloride) may be present in an amount of about 0.01 wt.% to about 3 wt.% with respect to the weight of the wound care composition (wet or dry). For example, the quaternary ammonium salt may be present in an amount, in wt.%, of about 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.13, 0.15, 0.18, 0.2, 0.23, 0.25, 0.28, 0.3, 0.32, 0.35, 0.38, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.2, 1.5, 1.8, 2.0, 2.2, 2.5, 2.8, or 3.0 a value within a range between any of the preceding values, e.g., between about 0.05 and about 0.5, between about 0.7 and about 0.9, between about 1.5 and about 3.0 or the like. Further for example, a wound care composition having 0.13 wt.% quaternary ammonium salt prior to the removal of 30 wt.% volatile components (e.g., water) may have about 0.18 wt.% quaternary ammonium salt in a dried wound care composition.

[0093] In some embodiments, the quaternary ammonium salt (any quaternary ammonium salt described herein, e.g., benzalkonium salt) may be present in a wt.% ratio (w / w) with respect to an amount of chelator compound (i.e., chelator, a chelator salt, or a combination thereof (e.g., citric acid, sodium citrate)), of about 1:1000 to about 1:0.1. For example, a wt.% ratio of chelator, chelator salt, or a combination thereof to benzalkonium salt may be about 1:1000, 1:500, 1:250, 1:100, 1:50, 1:25, 1:10, 1:8, 1:6, 1:4, 1:2, 1:1, 1:0.9, 1:0.8, 1:0.7, 1:0.6, 1:0.5, 1:0.4, 1:0.3, 1:0.2,or 1:0.1, or value within a range between any of the preceding values, e.g., between about 1:2 and about 1:1, between about 1:10 and about 1:4, or the like.

[0094] In some embodiments, the quaternary ammonium salt (any quaternary ammonium salt described herein, e.g., benzalkonium salt) may be present in a wt.% ratio (w / w) with respect to an amount of C8-12alkyl 1,2-diol (e.g., 1,2-octanediol) of about 1:500 to about 1:0.1. For example, a wt.% ratio of quaternary ammonium salt to C8-12alkyl 1,2-diol may be about 1:500, 1:450, 1:400, 1:350, 1:300, 1:250, 1:200, 1:150, 1:100, 1:50, 1:40, 1:30, 1:20, 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 1:0.9, 1:0.8, 1:0.7, 1:0.6, 1:0.5, 1:0.4, 1:0.3, 1:0.2, or 1:0.1, or a value within a range between any of the preceding values, e.g., between about 1:5 and about 1:1, between about 1:0.5 to about 1:0.2, or the like.

[0095] In many embodiments, the wound care composition may exclude other antiseptic compounds, such as polyhexamethylene biguanide (“PHMB”), iodine, chlorhexidine, silver salts, or the like. Chelator Compound

[0096] In some embodiments, the chelator compound may be characterized by a molecular weight of less than about 500 g / mol. For example, the chelator compound may be characterized by a molecular weight about 90 g / mol to about 500 g / mol, e.g., 90, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, 500, or a value between any of the preceding values. A chelator salt will have a molecular weight greater than its corresponding non-salt form.

[0097] In some embodiments, a chelator salt may include a counterion selected from Na+, K+, Cs+, Mg2+, Ca2+, or a combination thereof.

[0098] In some embodiments, a chelator compound may be selected from citric acid, tartaric acid, succinic acid, ethylenediaminetetraacetic acid (“EDTA”), malic acid, oxalic acid, glutaric acid, glutamic acid, maleic acid, phthalic acid, pyromellitic acid, a salt thereof, and a combination thereof. In some embodiments, a chelator compound may be selected from citric acid, tartaric acid, succinic acid, ethylenediaminetetraacetic acid (“EDTA”), a salt thereof, and a combination thereof. In some embodiments, a chelator compound may consist essentially of citric acid, a citrate salt, or a combination thereof.

[0099] In some embodiments, a chelator salt may be selected from sodium citrate, sodium tartrate, sodium succinate, sodium calcium edetate, potassium ethylenediaminetetraacetic acid, or a combination thereof.

[0100] In some embodiments, the wound care composition may include citric acid and sodium citrate.

[0101] In some embodiments, a chelator compound (e.g., citric acid and / or sodium citrate) may be present in an amount of about 0.1 wt.% to about 50 wt.% with respect to the weight of the wound care composition (wet or dry). For example, a chelator compound may be present in an amount, in wt.%, of about 0.1, 0.2, 0.5, 0.8, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 24, 26, 28, 30, 32, 34, 36, 40, 42, 44, 48, or 50, or a value within a range between any of the preceding values, e.g., between about 3 and about 7, between about 10 and about 20, or the like. Further for example, a wound care composition having 4 wt.% chelator, chelator salt, or combination thereof prior to the removal of 30 wt.% volatile components (e.g., water) may have about 6 wt.% chelator, chelator salt, or combination thereof in a dried wound care composition.

[0102] In some embodiments, a chelator (e.g., citric acid) may be present in a wt.% ratio (w / w) with respect to an amount of chelator salt (e.g., sodium citrate) present of about 3:1 to about 0.3:1. For example, a chelator and a chelator may be present in a wt.% ratio (w / w) of about 3:1, 2.8:1, 2.6:1, 2.4:1, 2.2:1, 2:1, 1.8:1, 1.6:1, 1.4:1, 1.2:1, 1:1, 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1, or 0.3:1, or a value within a range between any of the preceding values, e.g., between about 0.8:1 and 0.7:1, or the like. When a chelator and a chelator salt are both present in a wound care composition, the total wt.% of chelator and chelator salt may be no greater than 20 wt.%. In many embodiments, a wt.% ratio (w / w) of chelator and chelator salt may be selected to achieve or maintain a pH of about 2 to about 6, e.g., 2, 2.2, 2.5, 2.8, 3, 3.2, 3.5, 3.8, 4, 4.2, 4.5, 4.8, 5, 5.2, 5.5, 5.8, or 6, or range between any of the preceding values, e.g., between 2.5 and 3.5, or the like.

[0103] In some embodiments, the chelator compound (i.e., chelator, a chelator salt, or a combination thereof (any chelator / salt described herein, e.g., citric acid and sodium citrate)) may be present in a wt.% ratio (w / w) with respect to an amount of a C8-12alkyl 1,2-diol (e.g., 1,2- octanediol) of about 0.02:1 to about 300:1. For example, a wt.% ratio of chelator compound to C8-12alkyl 1,2-diol may be about 0.02:1, 0.05:1, 0.08:1, 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, 5:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1, 30:1, 40:1, 50:1, 75:1, 100:1, 125:1, 150:1, 175:1, 200:1,225:1, 250:1, 275:1, or 300:1, or a value within a range between any of the preceding values, e.g., between about 15:1 and about 20:1, or the like. C8-12alkyl 1,2-diol

[0104] In some embodiments, the C8-12alkyl 1,2-diol may be 1,2-octanediol, (i.e., R7is H and R8is linear C6alkyl).

[0105] In some embodiments, the C8-12alkyl 1,2-diol (e.g., 1,2-octanediol) may be present in an amount of about 0.02 wt.% to about 20 wt.% with respect to the weight of the wound care composition (wet or dry). For example, the C8-12alkyl 1,2-diol may be present in an amount (wt.%) of about 0.02, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1,1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.2, 2.5, 2.8, 3.0, 3.2, 3.5, 3.8, 4.0, 4.2, 4.5, 4.8, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20, or a value within a range between any of the preceding values, e.g., between about 0.05 and about 1.0, between about 2.0 and about 5.0, or the like. Further for example, a wound care composition having 0.7 wt.% C8-12alkyl 1,2-diol prior to the removal of 30 wt.% volatile components (e.g., water) may have about 1 wt.% C8-12alkyl 1,2- diol in a dried wound care composition.

[0106] It is to be understood that any combination of components and the recited amounts cannot exceed 100 wt.%. A skilled artisan may readily adjust amounts within the recited ranges to adhere to this notion.

[0107] The following wound care compositions may be wet or dry. Wet wound care compositions may further include a volatile component (e.g., water) in an amount of at least 3 wt.%, e.g., 3, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 95, or 98, or a range within any of the preceding values, e.g., between 3 and 35 wt.%, or the like.

[0108] In some embodiments, a wound care composition may include, or consist essentially of, or consist only of: the collagen present in an amount of about 1 wt.% to about 95 wt.%, or a range described above; the oxidized cellulose present in an amount of about 0.5 wt.% to about 80 wt.%, or a range described above; the quaternary ammonium salt present in an amount of about 0.01 wt.% to about 3 wt.% (e.g., one or more benzalkonium chloride of Formula IIa above), or a range described above;the chelator compound present in an amount of about 0.1 wt.% to about 50 wt.% (e.g., citric acid, sodium citrate, or combination thereof), or a range described above; and the C8-12alkyl 1,2-diol present in an amount of about 0.02 wt.% to about 20 wt.% (e.g., 1,2- octane diol), or a range described above.

[0109] In some embodiments, a wound care composition may include, or consist essentially of, or consist only of: the collagen present in an amount of about 20 wt.% to about 90 wt.%; the oxidized cellulose present in an amount of about 5 wt.% to about 80 wt.%; the quaternary ammonium salt present in an amount of about 0.05 wt.% to about 1 wt.% (e.g., one or more benzalkonium chloride of Formula IIa above); the chelator compound present in an amount of about 3 wt.% and about 40 wt.% (e.g., citric acid, sodium citrate, malic acid, succinic acid, or combination thereof); and the C8-12alkyl 1,2-diol present in an amount of about 0.1 wt.% to about 10 wt.% (e.g., 1,2- octane diol).

[0110] In some embodiments, a wound care composition may include, or consist essentially of, or consist only of: the collagen present in an amount of about 1 wt.% to about 95 wt.%, or a range described above; the quaternary ammonium salt present in an amount of about 0.01 wt.% to about 3 wt.% (e.g., one or more benzalkonium chloride of Formula IIa above), or a range described above; the chelator compound present in an amount of about 0.1 wt.% to about 50 wt.% (e.g., citric acid, sodium citrate, or combination thereof), or a range described above; and the C8-12alkyl 1,2-diol present in an amount of about 0.02 wt.% to about 20 wt.% (e.g., 1,2- octane diol), or a range described above.

[0111] In some embodiments, a wound care composition may include, or consist essentially of, or consist only of: the collagen present in an amount of about 20 wt.% to about 90 wt.%; the quaternary ammonium salt present in an amount of about 0.05 wt.% to about 1 wt.% (e.g., one or more benzalkonium chloride of Formula IIa above); the chelator compound present in an amount of about 3 wt.% and about 40 wt.% (e.g., citric acid, sodium citrate, malic acid, succinic acid, or combination thereof); andthe C8-12alkyl 1,2-diol present in an amount of about 0.1 wt.% to about 10 wt.% (e.g., 1,2- octane diol).

[0112] In some embodiments, a wound care composition may include, or consist essentially of, or consist only of: the collagen present in an amount of about 1 wt.% to about 95 wt.%, or a range described above; the oxidized cellulose present in an amount of about 0.5 wt.% to about 80 wt.%, or a range described above; the quaternary ammonium salt present in an amount of about 0.01 wt.% to about 3 wt.% (e.g., one or more benzalkonium chloride of Formula IIa above), or a range described above; and the chelator compound present in an amount of about 0.1 wt.% to about 50 wt.% (e.g., citric acid, sodium citrate, or combination thereof), or a range described above.

[0113] In some embodiments, a wound care composition may include, or consist essentially of, or consist only of: the collagen present in an amount of about 20 wt.% to about 90 wt.%; the oxidized cellulose present in an amount of about 5 wt.% to about 80 wt.%; the quaternary ammonium salt present in an amount of about 0.05 wt.% to about 1 wt.% (e.g., one or more benzalkonium chloride of Formula IIa above); and the chelator compound present in an amount of about 3 wt.% and about 40 wt.% (e.g., citric acid, sodium citrate, malic acid, succinic acid, or combination thereof). Methods of Preparing Wound Care Compositions

[0114] In various embodiments, a method for preparing a wound care composition (i.e., wet) of the present disclosure is described. The method may include combining a collagen, an oxidized cellulose, a quaternary ammonium salt, a chelator compound, a C8-12alkyl 1,2-diol and one or more volatile component (e.g., water). Each component as described above.

[0115] In various embodiments, a method for preparing a wound care composition (i.e., wet) of the present disclosure is described. The method may include combining a collagen, an oxidized cellulose, a quaternary ammonium salt, a chelator compound, and one or more volatile component (e.g., water). Each component as described above.

[0116] In various embodiments, a method for preparing a wound care composition (i.e., wet) of the present disclosure is described. The method may include combining a collagen, a quaternary ammonium salt, a chelator compound, a C8-12alkyl 1,2-diol and one or more volatile component (e.g., water). Each component as described above.

[0117] In some embodiments, the method may further include mixing.

[0118] In some embodiments, the method may further include removing at least a portion of the one or more volatile component. Wound Care Articles

[0119] In various embodiments, a wound care article is described. The wound care article may include any dried wound care composition of the present disclosure.

[0120] In some embodiments, the wound care article may include a dried wound care composition as a free-standing construction characterized by a thickness (t) of about 3 mil to about 300 mil.

[0121] In some embodiments, the wound care article may include the collagen (e.g., functionalized collagen) present in an amount of about 1 gsm to about 450 gsm. For example, a collagen may be present in an amount (gsm) of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 18, 20, 22, 25, 50, 100, 150, 200, 250, 300, 400, 450, or 500 or a value within a range between any of the preceding values, e.g., between about 50 gsm and about 90 gsm, or the like. Further, a collagen may be present in a wt.% ratio relative to any component as described in the wound care compositions above.

[0122] In some embodiments, the wound care article may include the oxidized cellulose (e.g., oxidized regenerated cellulose) present in an amount of about 1 gsm to about 400 gsm. For example, the oxidized cellulose may be present in an amount (gsm) of 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, 32, 35, 38, 40, 42, 45, 48, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, or 400 or a value within a range between any of the preceding values, e.g., between about 30 gsm and about 50 gsm, or the like. Further, the oxidized cellulose may be present in a wt.% ratio relative to any other component as described in the wound care compositions above. For embodiments that do not require oxidized cellulose, the wound care article may include 0 gsm oxidized cellulose.

[0123] In some embodiments, the wound care article may include the quaternary ammonium salt (e.g., benzalkonium salt) present in an amount of about 0.01 gsm to about 5 gsm. For example, the quaternary ammonium salt may be present in an amount (gsm) of about 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.2, 1.5, 1.8, 2.0, 2.2, 2.5, 2.8, 3.0, 3.2, 3.5, 3.8, 4.0, 4.2, 4.5, 4.8, or 5.0, or a value within a range between any of the preceding values, e.g., between about 0.1 gsm and about 0.3 gsm, or the like. Further, the quaternary ammonium salt may be present in a wt.% ratio relative any other component as described in the wound care compositions above. For embodiments that do not require a C8-12alkyl 1,2-diol, the quaternary ammonium salt may be present in an amount of 0.2 gsm to 5 gsm (or any range therebetween, e.g., 0.5 gsm to 0.8 gsm).

[0124] In some embodiments, the wound care article may include the chelator compound (e.g., citric acid, sodium citrate) present in an amount of about 0.1 gsm to about 200 gsm. For example, a chelator, a chelator salt, or combination thereof may be present in an amount (gsm) of about 0.1, 0.2, 0.3, 0.4, 0.5, 1, 2, 3, 4, 5, 8, 12, 15, 18, 20, 22, 25, 28, 30, 32, 35, 38, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or 200, or a value within a range between any of the preceding values, e.g., between about 5 gsm and about 30 gsm, or the like. Further, a chelator, a chelator salt, or a combination thereof may be present in a wt.% ratio relative to any component as described in the wound care compositions above. For embodiments that do not require a C8-12alkyl 1,2-diol, the chelator compound may be present in an amount of about 10 gsm to about 200 gsm (or any range therebetween, e.g., 12 gsm to 25 gsm). In some embodiments that do not require a C8-12alkyl 1,2-diol, the chelator compound may be present in an amount of 10 gsm to about 200 gsm (or any range therebetween, e.g., 12 gsm to 25 gsm) and the quaternary ammonium salt may be present in an amount of 0.2 gsm to 5 gsm (or any range therebetween, e.g., 0.5 gsm to 0.8 gsm).

[0125] In some embodiments, the wound care article may include the C8-12alkyl 1,2-diol (e.g., 1,2-octanediol) present in an amount of about 0.01 gsm to about 50 gsm. For example, the C8-12alkyl 1,2-diol may be present in an amount (gsm) of about 0.01, 0.2, 0.4, 0.5, 1, 1.2, 1.5, 1.8, 2, 2.2, 2.5, 2.8, 3, 3.2, 3.5, 3.8, 4, 4.2, 4.5, 4.8, 5, 5.2, 5.5, 5.8, 6, 6.2, 6.5, 6.8, 7, 7.2, 7.5, 7.8, 8, 8.2, 8.5, 8.8, 9, 9.2, 9.5, 9.8, 10, 15, 20, 25, 30, 35, 40, 45, or 50, or a value within a range between any of the preceding values, e.g., between about 2 gsm and about 4 gsm, or the like. Further, the C8-12alkyl 1,2-diol may be present in a wt.% ratio relative to any component as described in the wound care compositions above.

[0126] In many embodiments, a wound care article may include the collagen, the oxidized cellulose, the quaternary ammonium salt (e.g., benzalkonium salt), the chelator compound (e.g., citric acid, sodium citrate), and the C8-12alkyl 1,2-diol (e.g., 1,2-octanediol) present in amounts such that the wound care article may be characterized by a total gsm of about 20 gsm to about 600 gsm. For example, the wound care article may characterized by a total gsm of about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, or 600, or a value within a range between any of the preceding values, e.g., between about 120 and about 200, or the like. In some embodiments, the total gsm may involve one or more of the gsm values disclosed above for the individual components. For example, the wound care article may be characterized by a total gsm of about 20 gsm to 600 gsm (or any range therebetween, e.g., 100 gsm to 200 gsm) derived from collagen being present in an amount of about 1 gsm to about 450 gsm (or any range therebetween, e.g., 80 gsm to 200 gsm), the oxidized cellulose being present in an amount of about 1 gsm to about 400 gsm (or any range therebetween, e.g., 30 gsm and 50 gsm), quaternary ammonium salt present in an amount of about 0.01 gsm to about 5 gsm (or any range therebetween, e.g., 0.5 gsm to 1 gsm), chelator compound present in an amount of about 0.1 gsm to about 200 gsm (or any range therebetween, e.g., 10 gsm to 25 gsm), and / or C8-12alkyl 1,2-diol present in an amount of about 0.01 gsm to about 50 gsm (or any range therebetween, e.g., 1 gsm to 10 gsm). In some embodiments, the total gsm may be calculated only based on the collagen, the oxidized cellulose, quaternary ammonium salt, the chelator compound, and the C8-12alkyl 1,2-diol present within the wound care article. In some embodiments, the wound care article may consist only of the collagen, oxidized cellulose, quaternary ammonium salt, the chelator compound, and the C8-12alkyl 1,2-diol and the total gsm based therefrom. Likewise, wound care articles that do not require the C8-12alkyl 1,2-diol may be characterized by a total gsm of about 20 gsm to about 600 gsm (or any range therebetween).

[0127] For embodiments not requiring oxidized cellulose, a wound care article may include the collagen, the quaternary ammonium salt (e.g., benzalkonium salt), the chelator compound (e.g., citric acid, sodium citrate), and the C8-12alkyl 1,2-diol (e.g., 1,2-octanediol) present inamounts such that the wound care article may be characterized by a total gsm of about 20 gsm to about 600 gsm. For example, the wound care article may characterized by a total gsm of about 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, 500, 510, 520, 530, 540, 550, 560, 570, 580, 590, or 600, or a value within a range between any of the preceding values, e.g., between about 120 and about 200, or the like. In some embodiments, the total gsm may involve one or more of the gsm values disclosed above for the individual components. For example, the wound care article may be characterized by a total gsm of about 20 gsm to 600 gsm (or any range therebetween, e.g., 100 gsm to 200 gsm) derived from collagen being present in an amount of about 1 gsm to about 450 gsm (or any range therebetween, e.g., 80 gsm to 200 gsm), quaternary ammonium salt present in an amount of about 0.01 gsm to about 5 gsm (or any range therebetween, e.g., 0.5 gsm to 1 gsm), chelator compound present in an amount of about 0.1 gsm to about 200 gsm (or any range therebetween, e.g., 10 gsm to 25 gsm), and / or C8-12alkyl 1,2-diol present in an amount of about 0.01 gsm to about 50 gsm (or any range therebetween, e.g., 1 gsm to 10 gsm). In some embodiments, the total gsm may be calculated only based on the collagen, quaternary ammonium salt, the chelator compound, and the C8-12alkyl 1,2-diol present within the wound care article. In some embodiments, the wound care article may consist only of the collagen, quaternary ammonium salt, the chelator compound, and the C8-12alkyl 1,2-diol and the total gsm based therefrom. Likewise, for wound care articles that do not require the C8-12alkyl 1,2-diol may be characterized by a total gsm of about 20 gsm to about 600 gsm (or any range therebetween).

[0128] In some embodiments, a wound care article may include, or consist essentially of, or consist only of: a collagen present in an amount of about 1 gsm to about 450 gsm (e.g., functionalized collagen), or a range described above; an oxidized cellulose present in an amount of about 1 gsm to 400 gsm (e.g., oxidized regenerated cellulose), or a range described above; a quaternary ammonium salt present in an amount of about 0.01 gsm to 5 gsm (e.g., one or more benzalkonium chloride of Formula IIa above), or a range stated above; a chelator compound present in an amount of about 0.1 gsm to about 200 gsm, (e.g., citric acid, sodium citrate, or a combination thereof), or a range described above; anda C8-12alkyl 1,2-diol present in an amount of about 0.01 gsm to 50 gsm (e.g., 1,2-octane diol), or a range described above.

[0129] In some embodiments, a wound care article may include, or consist essentially of, or consist only of: a collagen present in an amount of about 50 gsm to about 90 gsm (e.g., functionalized collagen); an oxidized cellulose present in an amount of about 30 gsm to 50 gsm (e.g., oxidized regenerated cellulose); a quaternary ammonium salt present in an amount of about 0.1 gsm to 0.3 gsm (e.g., one or more benzalkonium chloride of Formula IIa above); a chelator compound present in an amount of about 5 gsm to about 30 gsm, (e.g., citric acid, sodium citrate, or a combination thereof); and a C8-12alkyl 1,2-diol present in an amount of about 2 gsm to 4 gsm (e.g., 1,2-octane diol).

[0130] In some embodiments, a wound care article may include, or consist essentially of, or consist only of: a collagen present in an amount of about 1 gsm to about 450 gsm (e.g., functionalized collagen), or a range described above; a quaternary ammonium salt present in an amount of about 0.01 gsm to 5 gsm (e.g., one or more benzalkonium chloride of Formula IIa above), or a range stated above; a chelator compound present in an amount of about 0.1 gsm to about 200 gsm, (e.g., citric acid, sodium citrate, or a combination thereof), or a range described above; and a C8-12alkyl 1,2-diol present in an amount of about 0.01 gsm to 50 gsm (e.g., 1,2-octane diol), or a range described above.

[0131] In some embodiments, a wound care article may include, or consist essentially of, or consist only of: a collagen present in an amount of about 50 gsm to about 90 gsm (e.g., functionalized collagen); a quaternary ammonium salt present in an amount of about 0.1 gsm to 0.3 gsm (e.g., one or more benzalkonium chloride of Formula IIa above); a chelator compound present in an amount of about 5 gsm to about 30 gsm, (e.g., citric acid, sodium citrate, or a combination thereof); anda C8-12alkyl 1,2-diol present in an amount of about 2 gsm to 4 gsm (e.g., 1,2-octane diol).

[0132] In some embodiments, a wound care article may include, or consist essentially of, or consist only of: a collagen present in an amount of about 1 gsm to about 450 gsm (e.g., functionalized collagen), or a range described above; an oxidized cellulose present in an amount of about 30 gsm to 50 gsm (e.g., oxidized regenerated cellulose); a quaternary ammonium salt present in an amount of about 0.01 gsm to 5 gsm (e.g., one or more benzalkonium chloride of Formula IIa above), or a range stated above; and a chelator compound present in an amount of about 0.1 gsm to about 200 gsm, (e.g., citric acid, sodium citrate, or a combination thereof), or a range described above.

[0133] In some embodiments, a wound care article may include, or consist essentially of, or consist only of: a collagen present in an amount of about 50 gsm to about 90 gsm (e.g., functionalized collagen); an oxidized cellulose present in an amount of about 30 gsm to 50 gsm (e.g., oxidized regenerated cellulose); a quaternary ammonium salt present in an amount of about 0.1 gsm to 0.3 gsm (e.g., one or more benzalkonium chloride of Formula IIa above); and a chelator compound present in an amount of about 5 gsm to about 30 gsm, (e.g., citric acid, sodium citrate, or a combination thereof).

[0134] In many embodiments, the wound care article may be a wound dressing. Methods of Preparing Wound Care Articles

[0135] In various embodiments, a method for preparing a wound care article of the present disclosure is described. The method may include providing a wet wound care composition of the present disclosure and removing volatile component(s) (e.g., water), i.e., drying the wound care composition, to provide a free-standing construction (i.e., dried wound care composition). In some embodiments, the removing of volatile component(s) may include heating (dehydrating), freeze- drying, reduced pressure, or a combination thereof. In other embodiments, a method for preparinga wound care article of the present disclosure may include providing a dried wound care composition of the present disclosure and subsequently subjecting the dried wound care composition to an elevated temperature for a period.

[0136] In many embodiments, the method may at least include a heating step, i.e., subjecting the wound care composition to an elevated temperature, even if the wound care composition is dried by other means. As described above, the heating step is believed to alter the state of collagen to produce a “functionalized collagen.” In some embodiments, the method may include subjecting the wound care composition to a temperature of at least 50 °C, at least 60 °C, or at least 70 °C for a period. In some embodiments, the method may include subjecting the wound care composition to a temperature of at least 50 °C and no more than 100 °C, e.g., 50 °C, 55 °C, 60°C, 65 °C, 70 °C, 75 °C, 80 °C, 85 °C, 90 °C, 95 °C, or 100 °C, or a value within a range between any of the preceding values, e.g., between about 65 °C and about 75°C for a period. The period may be at least 1 h, at least 2 h, at least 5 h, at least 10 h, at least 15 h, at least 20 h, or at least 24 h, or a value within a range between any of the preceding values. In some embodiments, the heating step may be conducted under reduced pressure.

[0137] In some embodiments, the method may include freeze-drying the wet wound care composition to form a dried wound care composition, and subsequently heating the dried wound care composition to a temperature described above.

[0138] In various embodiments, a dried wound care composition or a wound care article of the present disclosure, prepared by a method of the present disclosure, is described. That is, a wet wound care composition or a dried wound care composition that has been subjected to a heating step. Dried wound care compositions or wound care articles including a dried wound care composition, prepared by said method, may be characterized by exhibiting a log reduction value against S. aureus or P. aeruginosa of at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8. Methods of Using Wound Care Compositions and Articles

[0139] In various embodiments, a method of treating a wound is described. The method may include contacting a wound with a wound care composition or a wound care article of the present disclosure.

[0140] In various embodiments, a method of promoting blood clotting is described. The method may include contacting a bleeding wound with a wound care composition or a wound care article of the present disclosure.

[0141] In various embodiments, a method of reducing the number of microbes in or around a wound is described. The method may include contacting a wound with a wound care composition or a wound care article of the present disclosure. In some embodiments, the microbes may include gram-positive bacteria, gram-negative bacteria, or a combination thereof. In some embodiments, the microbes may include Staphylococcus (e.g., Staphylococcus aureus), Pseudomonas (e.g., Pseudomonas aeruginosa), or a combination thereof. In many embodiments, microbes may be reduced within a biofilm environment. In some embodiments, the method may be effective in preventing the formation of a biofilm.

[0142] In many embodiments, a wound may be a chronic wound.

[0143] The wound care compositions of the present disclosure may be for use in the manufacture of a wound care article of the present disclosure; may be for use in the manufacture of a medicament for treating a wound; or a combination thereof.

[0144] The wound care articles of the present disclosure may be for use in the manufacture of a medicament for treating a wound. Kits

[0145] In various embodiments, a kit is described. The kit may include a collagen, an oxidized cellulose, a quaternary ammonium salt, a chelator compound, and a C8-12alkyl 1,2-diol. In some embodiments, the kit may further include one or more: volatile component(s). The kit may further include instructions directing a user to prepare a wound care composition according to the present disclosure.

[0146] In various embodiments, a kit is described. The kit may include a wound care composition of the disclosure. In many embodiments, the kit may further include a set of instructions directing a user to prepare a wound care article of the disclosure by way of any method set forth within the disclosure.

[0147] In various embodiments, a kit is described. The kit may include a wound care composition of the present disclosure. In many embodiments, the kit may further include a set of instructions directing a user to contact the wound care composition to a wound of subject.

[0148] In various embodiments a kit is described. The kit may include a wound care article of the present disclosure. In many embodiments, the kit may further include a set of instructions directing a user to contact the wound care article to a wound of a subject.EXAMPLES

[0149] Objects and advantages of this disclosure are further illustrated by the following examples, but the materials and amounts thereof recited in these examples, as well as other conditions and details, should not be construed to unduly limit this disclosure. These examples are merely for illustrative purposes only and are not meant to be limiting on the scope of the appended claims. Colony Biofilm Assay and Biofilm Survival Assay Method

[0150] Staphylococcus aureus, strain 15981 or Pseudomonas aeruginosa American Type Culture Collection strain 15442 was grown to stationary phase overnight in tryptic soy broth (Becton, Dickenson, and Company, Franklin Lakes, NJ) at 37 °C. The culture was diluted 1 to 10,000 in sterile phosphate-buffered saline and 10 microliters of the diluted suspension was placed in a single drop onto polycarbonate membranes (25 mm diameter, 0.2 micrometer pore size, polycarbonate filter membranes obtained from Sigma Millipore, location) placed on top of tryptic soy agar (TSA) containing 1.5 percent agar (Becton, Dickenson, and Company, Franklin Lakes, NJ). The bacteria were allowed to grow for 24 hours at 37 °C. After the growth period, the filters were aseptically transferred to TSA poured into sterile, polystyrene, 6-well plates.

[0151] The bacteria were covered with 20 mm circular disks of the articles described below and incubated for 24 hours at 37 °C. Each sample was tested in triplicate. The membranes covered in bacteria and any remaining wound care article were transferred into 10 mL of Dey / Englay (D / E) neutralizing broth (Becton, Dickenson, and Company, Franklin Lakes, NJ) in a 50 mL conical centrifuge tube. The samples were mixed on a vortex mixer at maximum speed for 1 min and then sonicated for 1 min in a sonicating water bath (Model 2150 from Branson Ultrasonics Corporation, Danbury, CT). The samples were serially diluted 10-fold in sterile phosphate buffered saline and were plated onto AC PetrifilmTMplates obtained from 3M, St. Paul, MN under trade designation “3M PETRIFILM Aerobic Count Plates”. The 3M PETRIFILM plates were incubated for 36 to 48 hours at 37 °C, the number of surviving colony forming units (CFU) were enumerated, and the average log reduction was calculated by subtracting the average log (CFU / sample) of the treated samples from the average log (CFU / sample) of the untreated samples in the same experiment.pH Measurement

[0152] All pH measurements were done using an Orion star™A214PH / ISE Meter from Thermo Scientific™ (Waltham, MA) using their standard procedure of calibration before each measurement.0.25 gram of each dried sample composition was placed into individual 20 mL glass vials. Sterile water (10 mL) was added to each vial and the pH of resulting mixture was measured after 5-10 minutes. Materials Table. Material Source Benzalkonium chloride (supplied as 50% solution in water), a combination of compounds of Formula Novo Nordisk, Bagsværd, Denmark IIa. Collagen Purified Bovine Dermis Fibrillar CollagenRegenity Biosciences, Oakland, NJCitric acid monohydrate Alfa Aesar, Ward Hill, MA Hydrolite 8 (1,2-octanediol) Symrise, Chaska, MN Malic acid Sigma-Aldrich, St Louis, MO Oxidized regenerated cellulose (powder)* Ethicon, Sommerville, NJ Sodium citrate dihydrate Spectrum Chemicals, Gardena, CA Succinic acid Sigma-Aldrich, St Louis, MO Examples 1-4 and Comparative Example 1.

[0153] Examples 1-4 differ in the type of chelator present. Comparative Example 1 differs from Example 1 in that Comparative Example 1 lacks a final heating process step.

[0154] Examples 1-4 and Comparative Example 1 were prepared by combining the components described in Table 1A in a glass jar and allowed to soak for one hour at room temperature before mixing with a Hamilton Beach 3-in-1 Hand Blender with Wisk 59768 for 15 – 30 seconds. The resulting mixtures were poured into dishes and were freeze dried immediately after mixing. Each of Examples 1-4 and Comparative Example 1 were freeze dried in a VirTis AdVantage Plus EL-85 lyophilizer (SP Industries, Warminster, Pennsylvania) using the following process steps: Samples were frozen for 150 minutes at -50 °C, dried at 10 °C for 120 minutes, anddried at 45 °C for 2250 minutes, with all drying steps occurring at 500 µbar of vacuum pressure. The resulting dried articles were removed from dishes and weighed to determine the basis weight. The weight percentages and basis weights for the dried articles are provided in Tables 1B and 1C, respectively.

[0155] The dried articles of Examples 1-4 were further heated in a convection oven at 72 °C for 24 hours. Comparative Example 1 did not undergo further heating. Example 1 and Comparative Example 1 are the same composition and a direct comparison to the effect of said heating step. Without wishing to be bound by theory, the heating step may crosslink the collagen, or otherwise encourage condensation reactions between the collagen and one or more components, i.e., a “functionalized” collagen. Even though Comparative Example 1 is denoted as a comparative example, it is intended to be encompassed by the scope of the present disclosure given that it shown to outperform Comparative Examples lacking one or more of the oxidized cellulose, chelator compound, and C8-12alkyl 1,2-diol, even when said Comparative Examples underwent heating step.

[0156] The Colony Biofilm Assay log reduction data for Examples 1-4 and Comparative Example 1 is provided in Table 1D below. The data teaches that each of the chelators within the composition affords excellent kill. It can further be seen that the final heating step substantially increases the effectiveness of the article(s), i.e., Example 1 compared to Comparative Example 1. Table 1A. Wound care compositions (“wet”) of Examples 1-4 and Comparative Example 1 ComponentEX 1 EX 2 EX 3 EX 4 CE 1gg g g gCollagen 1.070 1.069 1.069 1.069 1.070 ORC 0.876 0.875 0.875 0.875 0.876 BAC (1 wt.% aq.) 0.321 0.321 0.321 0.321 0.321 Hydrolite 8 0.063 0.063 0.063 0.063 0.063 Citric acid 0.389 0.500 0 0 0.389 Malic acid 0 0 0.500 0 0 Succinic acid 0 0 0 0.500 0 NaOH (10 wt.% aq.) 0.131 0 0 0 0.131 Acetic acid (0.05 M aq.) 97.15 97.17 97.17 97.17 97.15Total 100 100 100 100 100 Table 1B. Wound care compositions (“dry”) of Examples 1-4 and Comparative Example 1 ComponentEX 1 EX 2 EX 3 EX 4 CE 1wt.% wt.% wt.% wt.% wt.%Collagen 44.87 42.58 42.58 42.58 44.87 ORC 36.26 34.84 34.84 34.84 36.26 BAC 0.133 0.128 0.128 0.128 0.133 Hydrolite 8 2.62 2.52 2.52 2.52 2.62 Citric acid 14.96 19.94 0 0 14.96 Sodium citrate1.16 0 0 0 1.16Malic acid 0 0 19.94 0 0 Succinic acid 0 0 0 19.94 0 pH 3.16 2.7 2.72 2.82 2.7 Total 100 100 100 100 100 Table 1C. Wound care articles (basis weight) of Examples 1-4 and Comparative Example 1 ComponentEX 1 EX 2 EX 3 EX 4 CE 1gsm gsm gsm gsm gsmCollagen 52.00 46.84 45.14 51.53 52.00 ORC 42.03 38.33 36.93 42.16 42.03 BAC 0.15 0.14 0.14 0.15 0.15 Hydrolite 8 3.04 2.77 2.67 3.05 3.04 Citric acid 17.33 21.94 0.00 0.00 17.33 Sodium citrate1.34 0 0 0 1.34Malic acid 0.00 0.00 21.14 0.00 0.00 Succinic acid 0.00 0.00 0.00 24.13 0.00 Total 115.90 110.01 106.01 121.01 115.90 Table 1D. Colony Biofilm Assay for Examples 1-4 and Comparative Example 1 Example Log Reduction Value Stnd. Dev. (S. aureus) EX 1 5.94 0.81 EX 2 7.46 0.90 EX 3 > 8 0.05 EX 4 > 8 0.05 CE 1 2.40 0.15Examples 5 and Comparative Example 2

[0157] Example 5 and Comparative Example 2 differ in the presence of 1,2-octanediol.

[0158] Example 5 and Comparative Example 2 were made by combining the components described in Table 2A in a glass jar and allowing them to soak for 1 hour, after which they were mixed with a with a Hamilton Beach 3-in-1 Hand Blender with Wisk 59768 for 15 – 30 seconds. The resulting suspensions were poured into dishes and dried immediately after mixing. Example 5 and Comparative Example 2 were freeze dried in a VirTis Genesis Pilot Freeze Dryer (SP Industries, Warminster, Pennsylvania) using the following process: Samples were frozen for 150 minutes at -50 °C, dried at 10 °C for 120 minutes, dried at 45 °C for 360 minutes, and dried at 65 °C for 2579 minutes, with all drying steps occurring at 500 µbar of vacuum pressure. Note that the heating step (i.e., heated to a temperature of 65 °C was conducted in conjunction with the lyophilizing procedure. The weight percentages and basis weights for the dried articles are provided in Tables 2B and 2C, respectively.

[0159] The Colony Biofilm Assay log reduction data for Example 5 and Comparative Example 2 is provided in Table 2D below. The data teaches that the C8-12alkyl 1,2-diol (i.e., 1,2- octanediol) increases efficacy. Table 2A. Wound care compositions (“wet”) of Example 5 and Comparative Example 2 ComponentEX 5 CE 2ggCollagen 2.16 2.16 ORC 1.77 1.77 BAC (1 wt.% aq.) 0.56 0.56 Hydrolite 8 0.10 0 Citric acid 0.24 0.24 NaOH (10 wt.% aq.) 0.35 0.35 Acetic acid (0.05 M aq.) 194.81 194.91 Total 200 200Table 2B. Wound care compositions (“dry”) of Example 5 and Comparative Example 2 ComponentEX 5 CE 2wt.% wt.%Collagen 50.11 51.30 ORC 41.06 42.04 BAC 0.13 0.13 Hydrolite 8 2.32 0 Citric acid 3.83 3.96 Sodium Citrate 1.74 1.75 Total 100 100 Table 2C. Wound care articles (basis weight) of Example 5 and Comparative Example 2 ComponentEX 5 CE 2gsm gsmCollagen 68.34 69.96 ORC 56.00 57.33 BAC 0.18 0.18 Hydrolite 8 3.16 0 Citric acid 5.22 5.40 Sodium citrate 2.37 2.38 Total 136.39 136.37 Table 2D. Colony Biofilm Assay for Example 5 and Comparative Example 2 Example Log Reduction Value Stnd. Dev. (P. aerug.) EX 5 > 8 0.05 CE 2 2.46 0.28 Examples 6-7 and Comparative Examples 3-10

[0160] Example 6-7 differ in the amount of chelator compound present. Comparative Examples 3-10 differ in the presence or absence of one or more of: ORC, BAC, Hydrolite, and citric acid (or amount thereof).

[0161] Examples 6-7 and Comparative Examples 3-10 were made by combining the components described in Table 3A in a glass jar and allowing them to soak for 1 hour, after which they were mixed with a with a Hamilton Beach 3-in-1 Hand Blender with Wisk 59768 for 15 – 30 seconds. The resulting suspensions were poured into dishes and dried immediately after mixing.The weight percentages for wet wound care compositions are provided in Table 3A below. Examples 6-7 and Comparative Examples 3-10 were freeze dried in a VirTis Genesis Pilot Freeze Dryer (SP Industries, Warminster, Pennsylvania) using the following process: Samples were frozen for 150 minutes at -50 °C, dried at 10 °C for 120 minutes, dried at 45 °C for 360 minutes, and dried at 65 °C for 2579 minutes, with all drying steps occurring at 500 µbar of vacuum pressure. Each sample was further heated in a convection oven at 72 °C for 24 hours. The weight percentages for dried wound care composition / articles are provided in Table 3B below. The basis weights for the dried wound care articles are provided in Tables 3C below.

[0162] The Colony Biofilm Assay log reduction data for Examples 6-7 and Comparative Examples 3-10 is provided in Table 3D below. The data teaches that compositions including collagen, ORC, BAC, citric acid / citrate, and 1,2-octane-diol perform substantially better than compositions excluding any of the stated components. Table 3A. Wet wound care compositions (wt.%) Examples 6-7 and Comp. Examples 3-10 BAC Acetic ExampleCollagen ORCHydrolite Citric (1 wt.% aq.) 8 acid acid Total (0.05 M) wt.% wt.% wt.% wt.% wt.% wt.% wt.% CE 3 1.37 1.13 0.33 0 0 97.17 100 CE 4 1.34 1.10 0.32 0.06 0 97.18 100 EX 6 1.17 0.96 0.32 0.06 0.31 97.18 100 EX 7 1.07 0.87 0.33 0.06 0.50 97.17 100 CE 5 1.30 1.07 0.33 0 0.13 97.17 100 CE 6 1.21 0.98 0.33 0 0.31 97.17 100 CE 7 1.10 0.90 0.32 0 0.50 97.18 100 CE 8 2.32 0 0.33 0.06 0.13 97.16 100 CE 9 2.14 0 0.33 0.06 0.31 97.16 100 CE 10 1.95 0 0.33 0.06 0.50 97.16 100Table 3B. Dried wound care compositions (wt.%) Examples 6-7 and Comp. Examples 3-10 ExampleCollagen ORC BACHydrolite CitricpH8 acidTotalwt.% wt.% wt.% wt.% wt.% wt.% CE 3 54.93 44.94 0.13 0 0 3.27 100 CE 4 53.55 43.82 0.13 2.5 0 3.34 100 EX 6 46.65 38.20 0.13 2.5 12.5 2.69 100 EX 7 42.60 34.80 0.13 2.5 20 2.52 100 CE 5 52.18 42.69 0.13 0 5 2.92 100 CE 6 48.05 39.31 0.13 0 12.51 2.69 100 CE 7 43.91 35.95 0.13 0 20 2.46 100 CE 8 92.42 0 0.13 2.5 5 3.99 100 CE 9 84.86 0 0.13 2.5 12.50 3.21 100 CE 10 77.34 0 0.13 2.5 20.04 2.98 100 Table 3C. Wound care articles (gsm) Examples 6-7 and Comparative Examples 3-10 Hydroli mpleCollagen Ote Citric ExaRC BAC8acidTotalgsm gsm gsm gsm gsm gsm CE 3 81.30 66.51 0.19 0 0 148 CE 4 76.04 62.22 0.19 3.55 0 142 EX 6 66.27 54.24 0.19 3.55 17.75 142 EX 7 59.17 48.37 0.18 3.48 27.80 139 CE 5 73.58 60.19 0.18 0 7.05 141 CE 6 66.79 54.64 0.18 0 17.39 139 CE 7 56.21 46.02 0.17 0 25.6 128 CE 8 129.32 0 0.18 3.50 7.00 140 CE 9 111.17 0 0.17 3.28 16.38 131 CE 10 101.35 0 0.17 3.28 26.2 131 Table 3D. Colony Biofilm Assay for Examples 6-7 and Comparative Examples 3-10 Example Log Reduction Stnd Dev. Log Reduction Stnd Dev. Value Value (S. aureus) (P. aeruginosa) CE 3 0.25 0.05 -0.67 0.04 CE 4 0.89 0.24 -0.49 0.07 EX 6 -- -- 8.36 0.02 EX 7 6.19 0.34 8.28 0.03 CE 5 0.98 0.27 0.95 0.39 CE 6 0.93 0.21 -- -- CE 7 1.99 0.29 -- -- CE 8 1.06 0.1 0.29 0.14 CE 9 1.19 0.34 4.17 0.95 CE 10 2.36 0.24 -- --EQUIVALENTS

[0163] Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific embodiments described specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims.

Claims

CLAIMS What is claimed is:

1. A wound care composition comprising: a collagen; an oxidized cellulose; a quaternary ammonium salt; a chelator compound; and a C8-12alkyl 1,2-diol.

2. A wound care composition comprising: a collagen; a quaternary ammonium salt; a chelator compound; and a C8-12alkyl 1,2-diol.

3. The wound care composition of claim 1, wherein the oxidized cellulose is characterized by a carboxyl content of 5-50%.

4. The wound care composition of claim 1 or claim 3, wherein the oxidized cellulose is present in an amount of about 0.5 wt.% to about 20 wt.% with respect to the weight of the wound care composition.

5. The wound care composition of any one of claims 1, 3, 4, wherein the oxidized cellulose is present in a wt.% ratio of about 1:1 to about 2000:1 relative to an amount of quaternary ammonium salt present in the wound care composition.

6. The wound care composition of any one of claims 1, 3-5, wherein the oxidized cellulose is present in a wt.% amount of 1:0.75 to about 1:70 relative to an amount of the water-soluble polymer present in the wound care composition.

7. The wound care composition of any one of claims 1, 3-6, wherein the oxidized cellulose is oxidized regenerated cellulose.

8. The wound care composition of any one of claims 1, 3-7, wherein the oxidized cellulose is oxidized non-regenerated cellulose.

9. The wound care composition of any one of claims 1, 3-8, wherein the oxidized cellulose is a combination of oxidized regenerated cellulose and oxidized non-regenerated cellulose.

10. The wound care composition of any one of claims 1-9, wherein the quaternary ammonium salt is present in an amount of about 0.01 wt.% to about 3 wt.% with respect to the weight of the wound care composition.

11. The wound care composition of any one of claims 1-10, wherein the quaternary ammonium salt is present in a wt.% ratio of 1:15 to about 1:7000 relative to an amount of the water- soluble polymer present in the wound care composition.

12. The wound care composition of any one of claims 1-11, wherein the quaternary ammonium salt is a benzalkonium salt selected from one or more compound of formula IIa: (IIa),wherein n is selected from an or 13. The wound care composition of any one of claims 1-12, the chelator compound characterized by a molecular weight of 90 g / mol to 500 g / mol.

14. The wound care composition of any one of claims 1-13, the chelator compound selected from citric acid, tartaric acid, succinic acid, ethylenediaminetetraacetic acid (“EDTA”), malic acid,oxalic acid, glutaric acid, glutamic acid, maleic acid, phthalic acid, pyromellitic acid, a salt thereof, or a combination thereof.

15. The wound care composition of any one of claims 1-14, the chelator compound present in a total amount of about 0.1 wt.% to about 50 wt.% with respect to the weight of the wound care composition.

16. The wound care composition of any one of claims 1-15, comprising a chelator and a chelator salt present in a wt.% ratio of about 3:1 to about 0.3:

1.

17. The wound care composition of any one of claims 1, 3-16, the chelator compound present in a wt.% ratio of about 1:0.03 to about 1:200 relative to an amount of oxidized cellulose.

18. The wound care composition of any one of claims 1-17, the chelator compound present in a wt.% ratio of about 3000:1 to about 0.1:1 relative to an amount of the quaternary ammonium salt.

19. The wound care composition of any one of claims 1-18, wherein the C8-12alkyl 1,2-diol is 1,2-octane diol.

20. The wound care composition of any one of claims 1-19, wherein the C8-12alkyl 1,2-diol present in an amount of about 0.1 wt.% to about 20 wt.% with respect to the weight of the wound care composition.

21. The wound care composition of any one of claims 1, 3-20, wherein the C8-12alkyl 1,2-diol present in a wt.% ratio of about 1:0.2 to about 1:200 relative to an amount of oxidized cellulose.

22. The wound care composition of any one of claims 1-21, wherein the C8-12alkyl 1,2-diol present in a wt.% ratio of about 500:1 to about 0.1:1 relative to an amount of the quaternary ammonium salt.

23. The wound care composition of any one of claims 1-22, the C8-12alkyl 1,2-diol is present in a wt.% ratio of about 1:0.02 about 1:300 relative to an amount of the chelator compound.

24. The wound care composition of any one of claims 1-23, the collagen selected from Type I, Type II, Type III, fragments thereof, and a combination thereof.

25. The wound care composition of any one of claims 1-24, the collagen present in an amount of about 1 wt.% to about 60 wt.% with respect to the weight of the wound care composition.

26. The wound care composition of any one of claims 1, 3-25, the collagen present in a wt.% ratio of about 60:1 to about 0.15:1 relative to an amount of oxidized cellulose.

27. The wound care composition of any one of claims 1-26, the collagen present in a wt.% ratio of about 6000:1 to about 3:1 relative to an amount of the quaternary ammonium salt.

28. The wound care composition of any one of claims1-27, the collagen present in a wt.% ratio of about 600:1 to about 0.03:1 relative to an amount of the chelator compound.

29. The wound care composition of any one of claims 1-28, the collagen present in a wt.% ratio of about 600:1 to about 0.2:1 relative to an amount of the C8-12alkyl 1,2-diol.

30. The wound care composition of any one of claims 1-29, further comprising a pH buffer.

31. The wound care composition of any one of claims 1-30, characterized by a pH of 2-6.

32. The wound care composition of any one of claims 1-31, the collagen present in an amount of about 20 wt.% to about 90 wt.%; optionally the oxidized cellulose present in an amount of about 5 wt.% to about 80 wt.%; the quaternary ammonium salt present in an amount of about 0.05 wt.% to about 3 wt.%; the chelator compound present in an amount of about 3 wt.% to about 50 wt.%;the C8-12alkyl 1,2-diol present in an amount of about 0.1 wt.% to about 20 wt.%.

33. A wound care article comprising: a wound care composition of any one of claims 1-32, wherein the wound care composition is in the form of a free-standing construction.

34. The wound care article of claim 33, the collagen present in an amount from about from about 1 gsm to about 450 gsm.

35. The wound care article of any one of claims 33-34, the oxidized cellulose present in an amount from 1 gsm to 400 gsm.

36. The wound care article of any one of claims 33-35, the quaternary ammonium salt present in an amount from 0.01 gsm to 5 gsm.

37. The wound care article of any one of claims 33-36, the chelator compound present in an amount from about 0.1 gsm to about 200 gsm.

38. The wound care article of any one of claims 33-37, the C8-12alkyl 1,2-diol present in an amount from 0.01 gsm to 50 gsm.

39. The wound care article of any one of claims 33-38, the collagen present in an amount from about from about 50 gsm to about 90 gsm; optionally the oxidized cellulose present in an amount from 30 gsm to 50 gsm; the quaternary ammonium salt present in an amount from 0.1 gsm to 0.3 gsm; the chelator compound present in an amount from about 5 gsm to about 30 gsm; and the C8-12alkyl 1,2-diol present in an amount from 2 gsm to 4 gsm.

40. A method of preparing a wound care article, the method comprising: providing a wound care composition of any one of claims 1-32; and coating a substrate with the wound care composition to form a layer, anddrying the layer to form a free-standing construction.

41. The method of claim 40, the drying comprising freeze-drying the wound care composition.

42. The method of any one of claims 40-41, the drying comprising heating the wound care composition to a temperature of about 50 °C to about 100 °C for a period.

43. The method of claim 42, wherein the heating is effective to react the collagen with one or more of: the collagen, the oxidized cellulose, and the chelator compound.

44. The method of any one of claims 42-43, wherein upon heating the wound care composition, the collagen is transformed into a functionalized collagen.

45. The method of any one of claims 42-44, wherein upon heating the wound care composition, the collagen undergoes a condensation reaction.

46. A wound care article prepared by the method of any one of claims 41-45.

47. A wound care article of any one of claims 32-39 prepared by the method of any one of claims 41-45.

48. A method of treating a wound, the method comprising: contacting a wound with a wound care composition of any one of claims 1-32.

49. A method of treating a wound, the method comprising: contacting a wound with a wound care article of any one of claims 33-39.

50. A kit comprising: a wound care composition of any one of claims 1-32, and a set of instructions directing a user to contact a wound with the wound care composition.

51. A kit comprising: a wound care composition of any one of claims 1-32, and a set of instructions directing a user to prepare a wound care article according to any one of claims 40-45.

52. A kit comprising: a wound care article of any one of claims 33-39, and a set of instructions directing a user to contact a wound with the wound care article.

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