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

PA200202W002WOUND CARE COMPOSITIONS AND ARTICLES THEREOF HAVING ANTIMICROBIAL PROPERTIESBACKGROUND

[0001] A wide variety of compositions, materials, and devices are known in the art for use in treating wounds 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] 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, which present 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.

[0004] 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

[0005] 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 Cs-i2 alkyl 1,2-diol.

[0006] 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.

[0007] 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.

[0008] 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.

[0009] 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.

[0010] 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.

[0011] 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.

[0012] 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.

[0013] 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

[0014] Described herein are wound care compositions and wound care articles that offer enhanced biofilm kill. The combination of a collagen, a quaternary ammonium salt, a chelator compound, and a Cs-i2 alkyl 1,2-diol is shown to synergistically increase efficacy against biofilms of S. aureus and P. aeruginosa. 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.

[0015] Collagens, quaternary ammonium salts, chelator compounds, and Cs-i2 alkyl 1,2-diols have each been individually incorporated into wound care compositions; however, the combination of collagens, quaternary ammonium salts, chelator compounds, and Cs-i2 alkyl 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.

[0016] 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

[0017] As used herein, “about” means ± 10 percent of a given value. For example, about 10 means 9 to 11.

[0018] 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).

[0019] 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.

[0020] 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.

[0021] As used herein, “aralkyl” refers to an aryl group substituted with one or more alkyl group.

[0022] 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.

[0023] 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 C1.22 alkyl group or a -(CH2)m-Y-C(O)-R4group, Y is -O- or -NH-, R4is a C1.22 alkyl 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 phenyl.

[0024] As used herein, “benzethonium salt” refers to a quaternary ammonium salt compound of formula (III):PhCH2N+(R5)2-(CH2CH2O)n-R6X’ (III),wherein each R5is independently a C1-22 alkyl group, R6is a C1-22 alkyl group, a Ce-io aryl group, or a C7-22 aralkyl 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.

[0025] As used herein, “Cs-i2 alkyl 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 Cs-i2 alkyl 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 “Cs-i2 alkane 1,2-diol” or “l,2-Cs-i2 alkanediol.”

[0026] As used herein, “chelator” refers to a compound having at least one carboxylic acid group (i.e., -CO2H) wherein the oxygen atom of the at least one carboxylic acid is 2-4 atoms away from an oxygen atom or a nitrogen atom. A “chelator salt” refers to a chelator which has been deprotonated (e.g., -CC 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.

[0027] 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

[0028] 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.

[0029] 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.

[0030] As used herein, “exclude” means that a component is absent (i.e., present in 0 wt.%).

[0031] 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.

[0032] As used herein, “gsm” means grams per square meter. “Total gsm” refers to the total grams of all materials, or regarding all materials recited, within one square meter.

[0033] As used herein, “microorganism” or “microbe” refers to bacteria, yeast, mold, fungi, protozoa, mycoplasma, and / or viruses including lipid-enveloped RNA and DNA viruses.

[0034] 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.

[0035] 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 themonomers 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.

[0036] 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 pressuresensitive adhesive.

[0037] As used herein, “preventing” refers to stopping or delaying the onset of a condition within a treated sample relative to an untreated control sample.

[0038] 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.

[0039] 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 °C to about 23 °C at atmospheric pressure (i.e., 760 mm / Hg).

[0040] As used herein, the term “subject” refers to a mammal, e.g., humans, sheep, horses, cattle, pigs, dogs, cats, rats, mice, and the like.

[0041] As used herein, the term “treating” refers to alleviating clinical symptoms of a condition.

[0042] 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.

[0043] 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.

[0044] 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, absorbwound 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.

[0045] As used herein, the term “pyridinium salt” refers to a quaternary ammonium salt of formula V:sj v- bf AR9(V),wherein R9is a C4-22 alkyl group and X is a pharmaceutically acceptable counterion (a halide, e.g., Cl, Br, I).

[0046] 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 disinfectant properties. 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. Set. 2021, 22. 6793, the contents of which are incorporated herein by reference in its entirety.

[0047] 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

[0048] 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 Cs-i2 alkyl 1,2-diol.

[0049] 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, and a chelator compound. In other words, a wound care composition may exclude the Cs-i2 alkyl 1,2-diol described herein.

[0050] 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, and a Cs-i2 alkyl 1,2-diol. In other words, a wound care composition may exclude the chelator compound described herein.

[0051] 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 present disclosure. 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 characterized as a powder. Powdered compositions may be sprinkled onto and into wounds (independent of the articles described herein).

[0052] 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 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.

[0053] 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, and proteins other than the collagen.

[0054] 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 shearrate 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.

[0055] 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, or range 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.

[0056] 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.

[0057] Further details are described below. Any further details and / or components may be combined. For embodiments not requiring a Cs-i2 alkyl 1,2-diol or embodiments not requiring a chelator compound, the following sections relating to such may be ignored.Collagen

[0058] 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.

[0059] 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.

[0060] 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 may crosslink 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., chelator compounds. Thus, in many embodiments, a “functionalized collagen” means that at least a portion of the free amines within aprotein terminus or side chain have undergone condensation with a carboxylic acid to form an amide bond.

[0061] 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.

[0062] 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.

[0063] 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.

[0064] In some embodiments, a collagen may be present in a wt.% ratio (w / w) with respect to an amount of a Cs-i2 alkyl 1,2-diol (any Cs-i2 alkyl 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 Cs-i2 alkyl 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, orthe like.Quaternary ammonium salts

[0065] 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.

[0066] In some embodiments, the quaternary ammonium salt may be an alkonium salt of formula la:R1-N+(CH3)2R2X- (la),wherein R1may be a Ce-22 alkyl, e.g., a Ce, C7, Cs, C9, C10, Cn, C12, C13, C14, C15, Ci6, C17, Cis, C19, C20, C21, or C22 alkyl, or a range between any of the preceding values, e.g., a C12-16 alkyl, a Cs-is alkyl, or the like; R2may be a C1-22 alkyl, e.g., a Ci, C2, C3, C4, C5, C6, C7, Cs, C9, C10, Cn, C12, C13, C14, Ci5, Ci6, C17, Cis, C19, C20, C21, or C22 alkyl, or a range between any of the preceding values, e.g., a C1-6 alkyl, a C1.4 alkyl, or the like; and X is Cl, Br, or I.

[0067] In some embodiments, the quaternary ammonium salt may be an alkonium salt of formula (lb):R1-N+(CH3)3X- (lb),wherein R1may be a C6-22alkyl. e.g., a Ce, C7, Cs, Cs, C10, Cn, C12, Cn, C14, C15, Ci6, C17, Cis, C19, C20, C21, or C22 alkyl, or a range between any of the preceding values, e.g., a C12-16 alkyl, a Cs-is alkyl, or the like; and X is Cl, Br, or I.

[0068] In some embodiments, the quaternary ammonium salt may be an alkonium salt of the formula:

[0069] In some embodiments, the quaternary ammonium salt may be an alkonium salt of the formula:> RCl"

[0070] In many embodiments, the quaternary ammonium salt may be a benzalkonium salt selected from one or more compound of the formula (Ila):(Ila),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 formula Ila. Forexample, the wound care composition may include a mixture of benzalkonium salts wherein n is 8, 10, 12, 14, 16, and 18.

[0071] In some embodiments, the quaternary ammonium salt may be a benzalkonium salt of formula lib:PhCH2N+(CH3)2-(CH2)m-NH-C(O)-R4X’ (lib), wherein R4may be a C4-22 alkyl group, e.g., C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, or C22 alkyl, or a range between any of the preceding values, e.g., a C13-17 alkyl, a C10-18 alkyl, or the like; m may be an integer of 2-4; and X may be Cl, Br, or I. “Ph” is phenyl.

[0072] In some embodiments, the quaternary ammonium salt may be a benzalkonium salt of the formula:

[0073] In some embodiments, the quaternary ammonium salt may be a benzethonium salt selected from one or more compound of formula (Illa):PhCH2N+(CH3)2(CH2CH2O)n-R6X’ (Illa),wherein R6may be Ph or -Ph-R10, R10may be a C4-10 alkyl, n may be an integer selected from 1-6, and X may be Cl, Br, or I. “Ph” is phenyl or phenylene.

[0074] In some embodiments, the quaternary ammonium salt may be a benzethonium salt of the formula:Cl

[0075] In some embodiments, the quaternary ammonium salt may be a pyridinium salt of formula IVa:(IVa),wherein R9may be a C4-22 alkyl, e.g., C4, C5, C6, C7, C8, C9, C10, C11, C12, C13, C14, C15, C16, C17, C18, C19, C20, C21, or C22 alkyl, or within a range of any of the preceding values, e.g., a C12-18 alkyl, a C10-16 alkyl, or the like; and X may be Cl or Br.

[0076] In some embodiments, the quaternary ammonium salt may be a pyridinium salt of formula:

[0077] 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.

[0078] 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.

[0079] 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 C8-12 alkyl 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 C8-12 alkyl 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.

[0080] 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

[0081] Compounds with heteroatoms distanced 2, 3, or 4 atoms (e.g., carbon atoms) apart can form 5, 6, or 7-membered metallacycles with multivalent ions, such as calcium.

[0082] 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.

[0083] In some embodiments, the chelator compound may include at least two carboxylic acid groups.

[0084] In some embodiments, the chelator compound may include at least one carboxylic acid group and at least one hydroxyl group.

[0085] In some embodiments, a chelator salt may include a counterion selected from Na+, K+, Cs+, Mg2+, Ca2+, or a combination thereof.

[0086] In some embodiments, a chelator compound may be selected from citric acid, tartaric acid, succinic acid, ethylenediaminetetraacetic acid (“EDTA”), lactic acid, 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.

[0087] 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.

[0088] In some embodiments, the wound care composition may include citric acid and sodium citrate.

[0089] 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.

[0090] 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.

[0091] 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 C8-12 alkyl 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 C8-12 alkyl 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.Cs-i2 alkyl 1,2-diol

[0092] In some embodiments, the Cs-i2 alkyl 1,2-diol may be 1,2-octanediol, (i.e., R7is H and R8is linear C6 alkyl).

[0093] In some embodiments, the Cs-i2 alkyl 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 Cs-i2 alkyl 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.% C8-12 alkyl 1,2-diol prior to the removal of 30 wt.% volatile components (e.g., water) may have about 1 wt.% C8-12 alkyl 1,2-diol in a dried wound care composition.

[0094] 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.

[0095] 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.

[0096] 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 Ila 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; andthe C8-12 alkyl 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.

[0097] 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 Ila 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 C8-12 alkyl 1,2-diol present in an amount of about 0.1 wt.% to about 10 wt.% (e.g., 1,2-octane diol).Methods of Preparing Wound Care Compositions

[0098] 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 Cs-i2 alkyl 1,2-diol and one or more volatile component (e.g., water). Each component as described above.

[0099] 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, and one or more volatile component (e.g., water). Each component as described above.

[0100] 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 C8-12 alkyl 1,2-diol and one or more volatile component (e.g., water). Each component as described above.

[0101] In some embodiments, the method may further include mixing.

[0102] In some embodiments, the method may further include removing at least a portion of the one or more volatile component.Wound Care Articles

[0103] In various embodiments, a wound care article is described. The wound care article may include any dried wound care composition of the present disclosure.

[0104] 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.

[0105] 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 (gsm = grams per square meter). 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.

[0106] 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 C8-12 alkyl 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).

[0107] 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 C8-12 alkyl 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); and in some embodiments that do not require a C8-12 alkyl 1,2-diol, the chelator compound may be present in an amount of 10 gsm to about 200 gsm (or any rangetherebetween, 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).

[0108] In some embodiments, the wound care article may include the C8-12 alkyl 1,2-diol (e.g., 1,2-octanediol) present in an amount of about 0.01 gsm to about 50 gsm. For example, the C8-12 alkyl 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 C8-12 alkyl 1,2-diol may be present in a wt.% ratio relative to any component as described in the wound care compositions above.

[0109] In many embodiments, 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 C8-12 alkyl 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), 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 C8-12 alkyl 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 C8-12 alkyl 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 C8-12 alkyl 1,2-diol and the total gsm based therefrom. Likewise, for wound care articles that do not require the C8-12 alkyl 1,2-diol may be characterized by a total gsm of about 20 gsm to about 600 gsm (or any range therebetween).

[0110] 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 Ila 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 Cs-i2 alkyl 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.

[0111] 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 Ila 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 C8-12 alkyl 1,2-diol present in an amount of about 2 gsm to 4 gsm (e.g., 1,2-octane diol).

[0112] In many embodiments, the wound care article may be a wound dressing.Methods of Preparing Wound Care Articles

[0113] 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 preparing a 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.

[0114] 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 10h, 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.

[0115] 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.

[0116] 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

[0117] 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.

[0118] 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.

[0119] 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 grampositive 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.

[0120] In many embodiments, a wound may be a chronic wound.

[0121] 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.

[0122] The wound care articles of the present disclosure may be for use in the manufacture of a medicament for treating a wound.Kits

[0123] In various embodiments, a kit is described. The kit may include a collagen, a quaternary ammonium salt, a chelator compound, and a C8-12 alkyl 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.

[0124] 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.

[0125] 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.

[0126] 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

[0127] 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 Bio film Assay and Bio film Survival Assay Method

[0128] 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.

[0129] 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 conicalcentrifuge 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 Petrifilm™ plates 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

[0130] 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 SourceBenzalkonium chloride (supplied as 50% solution inNovo Nordisk, Bagsvaerd, Denmark water), a combination of compounds of Formula Ila.Purified Bovine Dermis Fibrillar Collagen Regenity Biosciences, Oakland, NJ Purified Bovine Tendon Fibrillar Collagen Regenity Biosciences, Oakland, NJ Citric acid monohydrate Alfa Aesar, Ward Hill, MAHydrolite 8 (1,2-octanediol) Symrise, Chaska, MNExamples 1-5 and Comparative Examples 1-4.

[0131] Examples 1-5 and Comparative Examples 1-4 were prepared by combining the components described in Table 1 A in a glass jar and allowed to soak for one hour at room temperature before mixing with a Hamilton Beach 3-in-l 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 1-5 and Comparative Examples 1-4 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, and dried at 45 °C for 2250 minutes, with all drying steps occurring at 500 pbar 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 IB and 1C, respectively.

[0132] The dried articles of Examples 1-5 and Comparative Examples 1-4 were further heated in a convection oven at 72 °C for 24 hours. 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.

[0133] The Colony Biofilm Assay log reduction data for Examples 1-5 and Comparative Examples 1-4 is provided in Table ID below.

[0134] Examples 1-3 differ in the amount of citric acid present.

[0135] Examples 1-3 were made using Purified Bovine Dermis Fibrillar Collagen and all other examples and comparative examples were made using Purified Bovine Tendon Fibrillar Collagen.

[0136] Example 1 and Example 4 differ in total basis weight and the basis weights of BAC and diol. The amount of citric acid is comparable. Example 4, having greater basis weight BAC, lesser basis weight diol, and overall lesser total basis weight, outperforms Example 1.

[0137] Example 4 and Comparative Examples 1-3 differ in the presence or absence of components, i.e., without diol and citric acid, without citric acid, without diol, respectively. The results show that BAC, diol, and citric acid synergistically influence antimicrobial activity.

[0138] Examples 2 and Example 5 differ in the basis weight of BAC, but have comparable total basis weight and basis weights of diol and citric acid. Example 5 outperforms Example 2 by an unexpected margin.

[0139] Example 5 and Comparative Example 4 illustrate that the unexpected activity of Example 5 is not merely due to higher basis weight of BAC, which further supports that BAC, diol, and citric acid are behaving synergistically.Table 1A. Wet wound care compositions (wt.%) Examples 1-5 and Comp. Examples 1-4AceticBAC Hydrolite CitricCollagen acid Total Example (1 wt.% aq.) 8 acid(0.05 M)wt.% wt.% wt.% wt.% wt.% wt.% EX 1 2.32 0.33 0.06 0.13 97.16 100 EX 2 2.14 0.33 0.06 0.31 97.16 100 EX 3 1.95 0.33 0.06 0.50 97.16 100EX 4 1.026 0.628 0.031 0.188 98.127 100 CE 1 1.244 0.629 0 0 98.126 100 CE 2 1.216 0.625 0.031 0 98.128 100 CE 3 1.060 0.638 0 0.188 98.122 100EX 5 1.026 0.628 0.031 0.188 98.127 100 CE 4 1.244 0.629 0 0 98.126 100Table IB. Dried wound care compositions (wt.%) Examples 1-5 and Comp. Examples 1-4Hydrolite CitricCollagen BAC pH Total Example 8 acidwt.% wt.% wt.% wt.% wt.% EX 1 92.42 0.13 2.5 5 3.99 100 EX 2 84.86 0.13 2.5 12.50 3.21 100 EX 3 77.34 0.13 2.5 20.04 2.98 100EX 4 82 0.5 2.5 15 3.27 100 CE 1 99.5 0.5 0 0 4.61 100 CE 2 97 0.5 2.5 0 4.71 100 CE 3 84.5 0.5 0 15 3.31 100EX 5 82 0.5 2.5 15 3.27 100 CE 4 99.5 0.5 0 0 4.61 100Table 1C. Wound care articles (gsm) Examples 1-5 and Comparative Examples 1-4 Hydrolite CitricCollagen BAC Total Example 8 acidgsm gsm gsm gsm gsm EX 1 129.32 0.18 3.50 7.00 140 EX 2 111.17 0.17 3.28 16.38 131 EX 3 101.35 0.17 3.28 26.2 131EX 4 48.72 0.30 1.49 8.91 59.4 CE 1 61.69 0.31 0 0 62.0 CE 2 62.78 0.32 1.62 0 64.7 CE 3 52.39 0.31 0 9.3 62.0EX 5 103.60 0.63 3.15 18.93 126.18 CE 4 134.60 0.68 0 0 135.28Table 3D. Colony Biofilm Assay for Examples 1-5 and Comparative Examples 1-4 Example Log Reduction Stnd Dev. Log Reduction Stnd Dev.Value Value(N. aureus) (P. aeruginosa)EX 1 1.06 0.1 0.29 0.14 EX 2 1.19 0.34 4.17 0.95 EX 3 2.36 0.24 — —EX 4 3.51 0.03 — — CE 1 1.49 0.07 — — CE 2 2.64 0.34 — — CE 3 2.80 0.34 — —EX 5 8.41 0.08 — — CE 4 4.62 0.39 — —EQUIVALENTS

[0140] 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

CLAIMSWhat is claimed is:

1. A wound care composition comprising:a collagen;a quaternary ammonium salt;a chelator compound; anda Cs-i2 alkyl 1,2-diol.

2. The wound care composition of claim 1, 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.

3. The wound care composition of any one of claims 1-2, 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.

4. The wound care composition of any one of claims 1-3, wherein the quaternary ammonium salt is a benzalkonium salt selected from one or more compound of formula Ila:(Ila),wherein n is selected from an integer of 8, 10, 12, 14, 16, or 18.

5. The wound care composition of any one of claims 1-4, the chelator compound characterized by a molecular weight of 90 g / mol to 500 g / mol.

6. The wound care composition of any one of claims 1-5, the chelator compound selected from lactic acid, 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.

7. The wound care composition of any one of claims 1-6, 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.

8. The wound care composition of any one of claims 1-7, comprising a chelator and a chelator salt present in a wt.% ratio of about 3: 1 to about 0.3:1.

9. The wound care composition of any one of claims 1-8, 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.

10. The wound care composition of any one of claims 1-9, wherein the Cs-i2 alkyl 1,2-diol is 1,2- octane diol.

11. The wound care composition of any one of claims 1-10, wherein the Cs-i2 alkyl 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.

12. The wound care composition of any one of claims 1-11, wherein the Cs-i2 alkyl 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.

13. The wound care composition of any one of claims 1-12, the Cs-i2 alkyl 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.

14. The wound care composition of any one of claims 1-13, the collagen selected from Type I, Type II, Type III, fragments thereof, and a combination thereof.

15. The wound care composition of any one of claims 1-14, the collagen present in an amount of about 1 wt.% to about 95 wt.% with respect to the weight of the wound care composition.

16. The wound care composition of any one of claims 1-15, the collagen present in a wt.% ratio of about 6000: 1 to about 3:1 relative to an amount of the quaternary ammonium salt.

17. The wound care composition of any one of claims 1-16, the collagen present in a wt.% ratio of about 600:1 to about 0.03:1 relative to an amount of the chelator compound.

18. The wound care composition of any one of claims 1-17, the collagen present in a wt.% ratio of about 600:1 to about 0.2: 1 relative to an amount of the Cs-i2 alkyl 1,2-diol.

19. The wound care composition of any one of claims 1-18, further comprising a pH buffer.

20. The wound care composition of any one of claims 1-19, characterized by a pH of 2-6.

21. The wound care composition of any one of claims 1-20,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 3 wt.%; the chelator compound present in an amount of about 3 wt.% to about 50 wt.%;the Cs-i2 alkyl 1,2-diol present in an amount of about 0.1 wt.% to about 20 wt.%.

22. The wound care composition of any one of claims 1-21, characterized as being in the form of a powder.

23. A wound care article comprising:a wound care composition of any one of claims 1-22,wherein the wound care composition is in the form of a free-standing construction.

24. The wound care article of any one of claims 23, the collagen present in an amount from about from about 10 gsm to about 450 gsm.

25. The wound care article of any one of claims 23-24, the quaternary ammonium salt present in an amount from 0.01 gsm to 5 gsm.

26. The wound care article of any one of claims 23-25, the chelator compound present in an amount from about 0.1 gsm to about 200 gsm.

27. The wound care article of any one of claims 23-26, the Cs-i2 alkyl 1,2-diol present in an amount from 0.01 gsm to 50 gsm.

28. The wound care article of any one of claims 23-27,the collagen present in an amount from about from about 50 gsm to about 90 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 Cs-i2 alkyl 1,2-diol present in an amount from 2 gsm to 4 gsm.

29. The wound care article of any one of claims 23-28, characterized by a total basis weight from about 20 gsm to about 600 gsm.

30. A method of preparing a wound care article, the method comprising:providing a wound care composition of any one of claims 1-22; andcoating a substrate with the wound care composition to form a layer, anddrying the layer to form a free-standing construction.

31. The method of claim 30, the drying comprising freeze-drying the wound care composition.

32. The method of any one of claims 30-31, the drying comprising heating the wound care composition to a temperature of about 50 °C to about 100 °C for a period.

33. The method of claim 32, wherein upon heating the wound care composition, the collagen is transformed into a functionalized collagen.

34. The method of any one of claims 32-33, wherein upon heating the wound care composition, the collagen undergoes a condensation reaction.

35. A wound care article prepared by the method of any one of claims 30-34.

36. A method of treating a wound, the method comprising:contacting a wound with a wound care composition of any one of claims 1-22.

37. A method of treating a wound, the method comprising:contacting a wound with a wound care article of any one of claims 23-29.

38. A kit comprising:a wound care composition of any one of claims 1-22, anda set of instructions directing a user to contact a wound with the wound care composition.

39. A kit comprising:a wound care composition of any one of claims 1-22, anda set of instructions directing a user to prepare a wound care article according to any one of claims 28-32.

40. A kit comprising:a wound care article of any one of claims 23-29, anda set of instructions directing a user to contact a wound with the wound care article.

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