Wound care compositions with antimicrobial properties and articles thereof

Abstract

Described herein are wound care compositions, wound care articles, and methods of making them. Also described are methods of treating a wound with the wound care compositions and wound care articles.

Description

Background Technology

[0001] Various compositions, materials, and devices for treating wounds and tissue damage are known in the art. Wounds may be caused by trauma, surgery, or disease, and may require measures to control bleeding, absorb wound exudates, alleviate pain, aid in debridement, and protect against infection or exacerbation of infection. Such measures are designed to promote healing and provide protection against further damage.

[0002] Wound healing and tissue regeneration are a series of complex biochemical processes involving four key phases: hemostasis, inflammation, proliferation, and remodeling. An imbalance between the destructive process of removing damaged tissue and the repair process of forming new tissue can lead to chronic non-healing wounds. Proteases and growth factors regulate this balance. Chronic wounds with elevated levels of proteases in the environment most often stall in the inflammatory phase or continue into the repair process without resulting in lasting anatomical and functional outcomes.

[0003] Oxidized cellulose "OCs" (such as oxidized regenerated cellulose "ORC" and oxidized non-regenerated cellulose "OnRC") have been used in wound care as hemostatic agents and healing promoters, especially for chronic wounds, because OCs can inactivate matrix metalloproteinases and bind growth factors. OCs initiate clotting by transforming into gel-like clumps upon contact activation. OCs also lower the pH within the wound environment, which is beneficial for combating microorganisms, but may induce erythrocyte lysis, interfere with bone formation, inactivate thrombin, and ultimately delay healing. pH disturbance is also a common problem associated with antimicrobial use.

[0004] Infection can prevent wound healing and lead to chronic wounds and / or worsen existing chronic wounds. If left untreated, wound infections can result in tissue loss, systemic infection, septic shock, and death. Bacterial biofilms can also form in wounds, posing further challenges. Biofilms are communities of one or more types of microorganisms that attach to surfaces, forming three-dimensional microbial communities. These communities can exhibit coordinated multicellular behavior and produce extracellular polysaccharides that embed bacteria within a protective matrix that can disrupt the host's defense mechanisms and shield the bacteria from biocides. Therefore, many treatments effective against free bacteria are ineffective when the same bacteria are present in a biofilm.

[0005] Treating infected chronic wounds is particularly challenging, especially those infiltrated by biofilms. What is needed are compositions and products that help balance the biological processes that support healing. Summary of the Invention

[0006] In one embodiment, a wound care composition is described. The wound care composition comprises oxidized cellulose; a quaternary ammonium salt; a chelating agent, a chelating agent salt, or a combination thereof; and a water-soluble polymer.

[0007] In one embodiment, a wound care article is described. The wound care article comprises the wound care composition of this disclosure, wherein the wound care composition is in the form of a self-supporting membrane or a self-supporting membrane stack.

[0008] In one embodiment, an article is described. The wound care article comprises: Oxidized cellulose; quaternary ammonium salt; chelating agent, chelating agent salt or combination thereof; and water-soluble polymer, wherein at least the quaternary ammonium salt; the chelating agent, the chelating agent salt or combination thereof; and the water-soluble polymer is in the form of a self-standing membrane or a self-standing membrane stack.

[0009] In one embodiment, a method for 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 to a substrate to form a layer and drying the layer to form a self-supporting membrane. The method optionally further includes forming one or more additional self-supporting membranes and pressing a plurality of self-supporting membranes together to form a self-supporting membrane stack.

[0010] In one embodiment, a method for preparing a wound care article is described. The method includes: mixing a water-soluble polymer with one or more of a quaternary ammonium salt and a chelating agent, a chelating agent salt, or a combination thereof to form a composition; coating a substrate with the composition to form a layer; and drying the layer to form a self-supporting membrane stack. The method optionally further includes forming one or more additional self-supporting membranes and pressing a plurality of self-supporting membranes together to form a self-supporting membrane stack. The self-supporting membrane or the self-supporting membrane stack contains the quaternary ammonium salt and the chelating agent, the chelating agent salt, or a combination thereof; and the method further includes applying the oxidized cellulose to the surface of the self-supporting membrane or the self-supporting membrane stack when the self-supporting membrane or the self-supporting membrane stack excludes the oxidized cellulose.

[0011] In one embodiment, a method for treating a wound is described. The method includes contacting the wound with a wound care composition of this disclosure.

[0012] In one embodiment, a method for treating a wound is described. The method includes bringing the wound into contact with a wound care product of this disclosure.

[0013] In one embodiment, a kit is described. The kit includes the wound care composition of this disclosure and a set of instructions for the user to apply the wound care composition to a wound.

[0014] In one embodiment, a kit is described. The kit includes the wound care product of this disclosure and a set of instructions for the user to apply the wound care product to a wound.

[0015] In one embodiment, a kit is described. The kit includes the wound care composition or components thereof disclosed herein, and a set of instructions guiding a user in preparing the wound care product of this disclosure. Attached Figure Description

[0016] Figure 1 This is an example wound care product disclosed herein.

[0017] Figure 2 This is an example wound care product disclosed herein.

[0018] Figure 3 This is an example wound care product disclosed herein.

[0019] Figure 4 This is an example wound care product disclosed herein.

[0020] Figure 5 This is an example wound care product disclosed herein.

[0021] Figure 6 This is an example wound care product disclosed herein. Detailed Implementation

[0022] This article describes wound care compositions and wound care products that provide enhanced biofilm killing. Oxidized cellulose, quaternary ammonium salts, and chelating agents, chelating agent salts, or combinations thereof, mixed in a film-forming water-soluble polymer matrix, have been shown to synergistically increase protection against Staphylococcus aureus (Staphylococcus aureus). S. aureus ) and Pseudomonas aeruginosa ( P. aeruginosa The efficacy of biofilms.

[0023] Oxidized cellulose, quaternary ammonium salts, and chelating compounds have each been individually incorporated into wound care compositions; however, mixing oxidized cellulose, quaternary ammonium salts, and chelating compounds in a single agent is unknown, and synergistic properties of such mixtures have not been anticipated. Furthermore, this disclosure states that the presence of C is not required. 8-12 Alkyl 1,2-diols are used to enhance biofilm killing, as previously desired for compositions containing quaternary ammonium salts and chelating compounds as defined herein. In other words, oxidized cellulose appears to have a similar effect, although structurally similar to C... 8-12 Alkyl 1,2-diols are irrelevant. Currently, oxidized cellulose or C... 8-12 How alkyl 1,2-diols mechanistically help disrupt biofilms associated with quaternary ammonium salts and chelating compounds.

[0024] The wound care compositions and wound care products disclosed herein allow for proper treatment of wounds infected with biofilms and prevent wound infection.

[0025] definition

[0026] As used in this article, “about” means ±10% of a given value. For example, about 10 means 9 to 11.

[0027] As used herein, "alkonium salt" refers to the quaternary ammonium salt compound of formula (I): R 1 -N + (R 2 )3X - (I), Where R 1 C 6-22 Alkyl groups, and each R 2 Selected independently from C 1-22 An alkyl group, and X is a pharmaceutically acceptable counterion (e.g., a halogen, such as Cl, Br, I).

[0028] As used herein, "alkyl" refers to a straight-chain or branched hydrocarbon chain. Examples of alkyl groups include methyl (-CH3), ethyl (-CH2CH3), propyl (-CH2CH2CH3), isopropyl (-CH(CH3)2), etc.

[0029] As used herein, “aryl” refers to a cyclic group characterized by aromaticity. An aromatic group is defined by a conjugated planar ring having 4n+2 π electrons. An aryl group does not contain a heteroatom within the ring, while a heteroaryl group includes at least one heteroatom within the ring, such as O, N, or S.

[0030] As used in this article, "aralkyl" refers to an aryl group that has been replaced by one or more alkyl groups.

[0031] As used herein, "preservative" refers to an antimicrobial component that kills both pathogenic and non-pathogenic microorganisms. Preservatives typically interfere with cell metabolism and / or cell membranes. Preservatives are sometimes referred to as disinfectants. Examples of preservatives include antimicrobial lipids, phenolic preservatives, cationic preservatives, iodine and / or povidone-iodine, peroxide preservatives, and antimicrobial natural oils.

[0032] As used herein, “benzalkonium salt” refers to the quaternary ammonium salt compound of formula (II): PhCH2N + (R 3 )3 X - (II), Each R 3Independently for C 1-22 Alkyl groups or –(CH2) m -YC(O)-R 4 Group, Y is -O- or -NH-, R 4 C 1-22 Alkyl group, m is an integer from 1 to 6, and X is a pharmaceutically acceptable counterion (e.g., halogen, such as Cl, Br, I). “Ph” stands for phenyl.

[0033] As used herein, “benzethonium salt” refers to the quaternary ammonium salt compound of formula (III): PhCH2N + (R 5 )2-(CH2CH2O) n -R 6 X - (III), Each R 5 Independently for C 1-22 alkyl group, R 6 C 1-22 alkyl groups, C6- 10 aryl group or C 7-22 An aralkyl group, where n is an integer selected from 1 to 20, and X is a pharmaceutically acceptable counterion (e.g., a halogen, such as Cl, Br, I). “Ph” stands for phenyl.

[0034] As used in this article, "C" 8-12 "Alkyl 1,2-diol" refers to an 8- to 12-carbon straight-chain or branched alkyl group having two hydroxyl groups (i.e., -OH), with the first hydroxyl group bonded to the first carbon and the second hydroxyl group bonded to the second carbon. 8-12 Alkyl 1,2-diols are represented by formula (IV): HOCH2CR 7 (OH)-R 8 (IV), Where R 7 It is -H or alkyl and R 8 For alkyl groups, as long as R 7 and R 8 Together they contain 6 to 10 carbon atoms. This term may also be referred to as "C" in this text. 8-12 "Alkane 1,2-diol" or "1,2-C" 8-12 Alkanediols.

[0035] As used herein, a "chelating agent" refers to a compound having at least two carboxylic acid groups (i.e., -CO2H), wherein the oxygen atom of at least one oxygen atom in the carboxylic acid is spaced 4 to 6 atoms (e.g., 4 to 5 atoms) from an oxygen atom or a nitrogen atom. A "chelating agent salt" refers to a deprotonated (e.g., -CO2) salt. - Y + ), and has pharmaceutically acceptable counterions (e.g., Na+). + Ca 2 + Chelating agents (e.g., chelating agents, chelating salts, or combinations thereof). "Chlorinating compound" refers to a chelating agent, chelating salt, or a combination thereof.

[0036] As used in this article, "collagen" refers to structural proteins that exist, for example, in the following: (Type I): Skin, tendons, vascular system, organs, bones (Type II): Cartilage (Type III): Reticulate (Type IV): Basement membrane, epithelial secretory layer (Type V): Cell surface, hair, and placenta.

[0037] As used in this article, "disinfection" refers to reducing the number of live microorganisms present on the surface being disinfected. Disinfection can kill or prevent the growth or proliferation of microorganisms.

[0038] As used herein, “drying” means the removal of volatile or evaporable compounds. When a substance is described herein as “dry,” it means that less than 1% by weight of the compound is present. Various drying methods are known to those skilled in the art.

[0039] As used in this article, “exclusion” means that the component is not present (i.e., present at 0% by weight).

[0040] As used herein, "self-supporting structure," "self-supporting membrane," or "self-supporting membrane stack" describes an article whose shape is maintained for at least 3 months at a temperature below 80°C, at 1 atm, and at a relative humidity below 50%. In other words, the structure is physically stable and does not lose its shape through melting, swelling, crystallization, phase separation, or the like. The wound care article of this disclosure has a self-supporting structure. The wound care article comprises the dried wound care composition of this disclosure, wherein the dried wound care composition is a self-supporting membrane or a self-supporting membrane stack.

[0041] As used herein, “microorganism” or “microbe” refers to bacteria, yeast, mold, fungi, protozoa, mycoplasma and / or viruses (including lipid-enveloped RNA and DNA viruses).

[0042] As used herein, “oxidized cellulose” or “various oxidized celluloses” is abbreviated as “OC” and “OCs”, respectively, referring to cellulose in which at least a portion of its hydroxyl groups have been oxidized to carboxylic acids (i.e., -OH → -CO2H). Cellulose is the polymeric structural framework of plant cells, containing repeating units of d-glucose. Due to the strong hydrogen bonds between the polymer chains, cellulose is insoluble in common solvents and water. Oxidized cellulose is also insoluble in water. Unless otherwise specified, the term “oxidized cellulose” alone or in combination covers both oxidized non-regenerated cellulose and oxidized regenerated cellulose. Percentages involving oxidized cellulose are intended to refer to the total amount of oxidized cellulose, whether ORC, OnRC, or a combination thereof.

[0043] As used herein, “oxidized non-regenerated cellulose” or “OnRC” refers to cellulose in which at least a portion of the hydroxyl groups have been oxidized to carboxylic acids (i.e., -OH). Non-regenerated cellulose (-CO2H).

[0044] As used herein, “oxidized regenerated cellulose” or “ORC” refers to cellulose in which at least a portion of the hydroxyl groups have been oxidized to carboxylic acids (i.e., -OH). Regenerated cellulose (-CO2H).

[0045] As used herein, "plasticizer" refers to a substance or combination of substances that lowers the glass transition temperature of another substance (e.g., pressure-sensitive adhesive). Plasticizers effectively soften, increase flexibility, increase plasticity, reduce viscosity, and / or reduce friction of the substance in which the plasticizer is added.

[0046] As used herein, "polymer" refers to a substance having one or more repeating monomer units. The chemical properties of polymeric substances described herein are sometimes based on the monomers from which the polymer is derived. Those skilled in the art will readily understand the reactivity characteristics of the monomers and how the monomers can be synthetically joined to form a polymer.

[0047] As used in this article, “stop” means to halt or delay the onset of a condition in a treated sample relative to an untreated control sample.

[0048] As used herein, “regenerated” in the context of “regenerated cellulose” refers to a process in which natural cellulose (e.g., derived from natural sources such as wood and other agricultural products) undergoes a chemical manufacturing process that breaks down the cellulose so that it can be dissolved, functionalized, and ultimately “regenerated.” Regenerated cellulose is commonly referred to as “rayon.” One such chemical manufacturing process is called the “viscose process,” in which natural cellulose is treated with a strong alkali and carbon disulfide to form xanthate derivatives. The xanthate portion is then removed, thus “regenerating” the cellulose. Depending on the process chosen, the resulting regenerated fibers can mimic the feel and texture of silk, wool, cotton, linen, etc. As used herein, “non-regenerated” in the context of “non-regenerated cellulose” refers to the absence of the aforementioned regeneration process. Regenerated and non-regenerated cellulose can differ in fiber structure and organization.

[0049] When referring to “solubility” or “dissolution”, the solubility of component A in component B refers to conditions in which only component A and component B are present, for example, without the addition of salts, compounds, etc. Furthermore, any solubility values ​​provided herein refer to a temperature range of approximately 20°C to approximately 23°C at atmospheric pressure (i.e., 760 mm / Hg).

[0050] As used in this article, the term "subject" refers to a mammal, such as a human, sheep, horse, cow, pig, dog, cat, rat, mouse, etc.

[0051] As used in this article, the term "treatment" refers to alleviating the clinical symptoms of a disease.

[0052] As used herein, the term "water solubility" refers to the dissolution of a material in deionized water at a temperature of 23°C in an amount of at least 7% by weight (i.e., 7g of material per 100g of deionized water). The material is considered dissolved if the resulting solution remains clear without visible turbidity, phase separation, or precipitation for 24 hours at 23°C.

[0053] As used herein, the term "water-soluble polymer" refers to a polymer that dissolves in deionized water at a temperature of 23°C in an amount of at least 7% by weight (i.e., 7g of material per 100g of deionized water). Similarly, "water-soluble matrix" refers to a material consisting solely of water-soluble compounds (e.g., polymers).

[0054] As used herein, the term "wound" refers to broken skin, such as cuts, punctures, abrasions, scratches, rashes, etc. "Wound dressing" refers to a product that controls bleeding, absorbs wound exudate, relieves pain, aids in debridement, protects against infection, improves infection, regulates proteases, or otherwise promotes healing and protects against further damage. "Chronic wound" refers to a wound that does not progress through a normal, orderly, or timely healing sequence, such as a wound that fails to heal after 4 weeks of standard care.

[0055] As used herein, the term "pyridinium salt" refers to the quaternary ammonium salt of formula V: (V), Where R 9 C 4-22 An alkyl group, and X is a pharmaceutically acceptable counterion (halogen, e.g., Cl, Br, I).

[0056] As used herein, the term "quaternary ammonium salt" refers to a compound having one or more nitrogen atoms substituted with four carbon atoms (i.e., RN). + (R)3), or alternatively, nitrogen is replaced by three carbon groups, one of which shares a double bond with nitrogen (i.e., R=N). + (R)2), where R is carbon, for example, alkyl, alkenyl, alkoxy, cycloalkyl, cycloalkenyl, heterocyclic, aryl, heteroaryl, or two Rs together forming a heteroaryl or heterocyclic group. The quaternary ammonium salts of this disclosure have antiseptic and / or disinfectant properties. The quaternary ammonium salts of this disclosure are not characterized by protonated amines, protonated imines, protonated guanidines, etc., nor by groups such as amine oxides. A review of quaternary ammonium salt compounds can be found in Vereshchagin, AN, *International Journal of Molecular Sciences* (…). Int. J. Mol.Sci. )》2021, 22 The full text of document 6793 is incorporated herein by reference.

[0057] As used herein, the term "volatile" is used to characterize compounds having a boiling point of no more than 260 °C at 1 atm. Therefore, "non-volatile" is used to characterize compounds having a boiling point of less than 260 °C at 1 atm.

[0058] Figure 1 A diagram illustrating an example wound care article 100 (or a layer thereof) of this disclosure is provided. The wound care article 100 is shown as a self-supporting structure (e.g., a monolayer membrane) having oxidized cellulose 102, a quaternary ammonium salt 104, and a chelating compound 105 dissolved in a water-soluble polymer 106 (matrix). The selection, arrangement, and amount of the components are for illustrative purposes.

[0059] Figure 2 A diagram illustrating an example wound care article 200 (or a layer thereof) of this disclosure. The wound care article 200 is shown as a self-supporting structure (e.g., a monolayer membrane), containing a dissolved quaternary ammonium salt 204 and a chelating agent compound 205 within a water-soluble polymer 206 (matrix), and a discontinuous oxidized cellulose coating 208 on the surface. The selection, arrangement, and amount of the components are for illustrative purposes.

[0060] Figure 3A diagram illustrating an example wound care article 300 (or a layer thereof) of this disclosure is provided. The wound care article 300 is shown as a self-supporting structure (e.g., a monolayer membrane) having oxidized cellulose 302, a quaternary ammonium salt 304, and a chelating compound 305 dissolved in a water-soluble polymer 306 (matrix). The wound care article 300 is also shown having a discontinuous oxidized cellulose coating 308 on its surface. The selection, arrangement, and amount of the components are for illustrative purposes.

[0061] Figure 4 The diagram illustrates an example wound care article 400 of this disclosure. The wound care article 400 is shown as a self-supporting structure (e.g., a three-layer membrane), wherein a first layer 412 has oxidized cellulose 402 and a quaternary ammonium salt 404 dissolved in a water-soluble polymer 406 (matrix); a second layer 614 has a quaternary ammonium salt 604 and a chelating agent compound 405 dissolved in the water-soluble polymer 406 (matrix); and a third layer 416 has a quaternary ammonium salt 404 dissolved in the water-soluble polymer 406 (matrix). The wound care article 400 is also shown having a discontinuous oxidized cellulose coating 408 on its surface. Each layer is shown characterized by a thickness t, and the aggregate layer is shown characterized by a total thickness T. The number of layers and the selection, arrangement, and amount of the components in each layer are for illustrative purposes.

[0062] Figure 5 A diagram illustrating an example wound care article 500 of this disclosure is provided. The wound care article 500 is shown as a self-supporting structure (e.g., a bilayer membrane) having a first layer 512 and a second layer 514, each shown having a quaternary ammonium salt 504 and a chelating agent compound 505 dissolved in a water-soluble polymer 506 (matrix). The wound care article 500 is also shown as having a water-soluble substrate 518 having a discontinuous oxidized cellulose coating 508 on its surface, wherein the discontinuous oxidized cellulose coating 508 contacts the first layer 512. Each layer may be characterized by a thickness t, and all layers in the stack may be characterized by a total thickness T (not shown). Similarly, the water-soluble substrate 518 is characterized by a thickness th. The number of layers and the selection, arrangement, and amount of the components of each layer are for illustrative purposes.

[0063] Figure 6A diagram illustrating an example wound care article 600 of this disclosure is provided. The wound care article 600 is shown as a self-contained structure (e.g., a three-layer membrane), wherein a first layer 612 has a quaternary ammonium salt 604 and a chelating agent compound 605 dissolved in a water-soluble polymer 606 (matrix); a second layer 614 has oxidized cellulose 602 and a quaternary ammonium salt 604 dissolved in the water-soluble polymer 606 (matrix); and a third layer 616 has a quaternary ammonium salt 604 dissolved in the water-soluble polymer 606 (matrix). The wound care article 600 is also shown as having a water-soluble substrate 618 having a discontinuous oxidized cellulose coating 608 on its surface, wherein the discontinuous oxidized cellulose coating 608 is in contact with both the first layer 612 and the third layer 616. Each layer may be characterized by a thickness t, and the aggregated layers may be characterized by a total thickness T (not shown). Similarly, each water-soluble substrate 618 may be characterized by a thickness th (not shown). The number of layers, as well as the selection, arrangement, and quantity of components in each layer, are for illustrative purposes.

[0064] Wound care composition

[0065] In various embodiments, a wound care composition is described. This wound care composition may comprise or consist essentially of: oxidized cellulose; a quaternary ammonium salt; a chelating agent, a chelating agent salt, or a combination thereof; and a water-soluble polymer.

[0066] In many embodiments, the wound care composition may comprise or consist essentially of: oxidized cellulose; quaternary ammonium salt; chelating agent, chelating agent salt, or a combination thereof; water-soluble polymer; and plasticizer.

[0067] In many embodiments, the wound care composition may comprise or consist essentially of: oxidized cellulose; quaternary ammonium salt; chelating agent, chelating agent salt, or a combination thereof; water-soluble polymer; and collagen.

[0068] In many embodiments, the wound care composition may comprise or consist essentially of: oxidized cellulose; quaternary ammonium salt; chelating agent, chelating agent salt, or a combination thereof; water-soluble polymer; plasticizer; and collagen.

[0069] In many embodiments, the wound care composition of this disclosure may be a dry wound care composition, i.e., the wound care composition contains no more than 1% by weight of a volatile component (e.g., water), for example, 1% by weight, 0.8% by weight, 0.5% by weight, 0.2% by weight, 0.1% by weight, 0.05% by weight, 0.01% by weight, or 0% by weight, or values ​​within any of the foregoing values. In many embodiments, the dry wound care composition may be a wound care article of this disclosure. The dry wound care composition may be in a self-supporting form.

[0070] In many embodiments, the wound care compositions of this disclosure may further comprise one or more volatile components present in an amount greater than 1% by weight. Example volatile components may include water and organic solvents (e.g., ethanol, isopropanol, ethyl acetate, etc.). In some embodiments, the wound care composition may comprise no more than 50% by weight of a volatile component (e.g., water), for example, 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight, or values ​​within the range of any of the foregoing values ​​(e.g., between 20% and 35% by weight). Wound care compositions comprising one or more volatile components may herein be referred to as moist wound care compositions. Moist wound care compositions may be in the form of solutions, dispersions, colloids, or suspensions. Dry wound care compositions may be in a self-contained form and may be either wound care articles of this disclosure on their own or combined with other components (e.g., pads, adhesives, etc.) to form wound care articles.

[0071] In many embodiments, the wound care compositions of this disclosure exclude one or more of the following: surfactants, water-insoluble polymers, polysaccharides other than oxidized cellulose, and proteins other than collagen. In many embodiments, the wound care compositions of this disclosure exclude C 8-12 Alkyl 1,2-diols (e.g., 1,2-octanediol).

[0072] dry The wound care composition or wound care article containing a dry wound care composition is characterized by exhibiting a log reduction value of at least 3, at least 4, at least 5, or at least 6, at least 7 against Staphylococcus aureus or Pseudomonas aeruginosa.

[0073] Further details are described below. Any further details and / or components may be combined.

[0074] Oxidized cellulose ("OC")

[0075] The oxidized regenerated cellulose described herein is regenerated cellulose in which at least a portion of the primary alcohol groups (C6) have been oxidized to carboxylic acid groups. In some embodiments, the regenerated cellulose can be prepared by viscose or the Bemberg process, for example, rayon untreated 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 to 9 (e.g., 1 to 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 (DP) of the cellulose material can be determined by the method described in RL Mitchell, Industrial and Engineering Chemistry, Vol. 45, p. 2520 (1953), the entire contents of which are incorporated herein by reference. The oxidized non-regenerated cellulose described herein is also oxidized but has not undergone a regeneration process. As used throughout, “oxidized cellulose” includes oxidized regenerated cellulose, oxidized non-regenerated cellulose, or combinations thereof.

[0076] In some embodiments, the oxidation of regenerated cellulose is characterized by a carboxyl content of about 5% to 50% (i.e., 5% to 50% of the hydroxyl groups have been oxidized to carboxylic acids), for example, carboxylations of 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, or values ​​within any of the foregoing ranges. In some embodiments, the oxidation of regenerated cellulose may have a carboxyl content of about 12% to 25% by weight (e.g., 18% to 22% by weight). Lower denier materials may exhibit satisfactory absorbability at only 12% to 13% by weight carboxyl content, while higher denier materials may be slowly absorbed at this oxidation level. The carboxyl content may be measured according to the United States Pharmacopeia (USP23-NF18), such as Wu, Y. et al., carbohydrate polymers ( Carbohydrate Polymers The examples in [reference needed], 2012, 88, 1023-1032, are cited in which the entire contents of that document are incorporated herein by reference. In some embodiments, the oxidized regenerated cellulose of this disclosure may be prepared according to the process described in U.S. Patent No. 3,364,200 or U.S. Patent No. 3,122,479, the entire contents of each of which are incorporated herein by reference. The described oxidized regenerated cellulose at least partially disintegrates, degrades, or dissolves upon exposure to physiological fluids or processes so that at least a portion of the material may be absorbed or assimilated at the wound site.

[0077] In many embodiments, oxidized cellulose exists within the composition as a dispersed powder / granules, rather than in the form of a fibrous sheet structure formed by knitting, weaving, or other methods. In some embodiments, dispersed oxidized cellulose may involve dispersion throughout the composition (see, for example, Figure 1 ) and / or may involve powder / particles dispersed on the surface of other composition components (see, for example, Figure 2 ).

[0078] In some embodiments, oxidized cellulose may be present in an amount from about 0.5% by weight to about 20% by weight relative to the weight of the wound care composition (wet or dry). For example, oxidized cellulose may be present in an amount (in weight percent) of about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20, or in a range between any of the foregoing values ​​(e.g., between about 5 and about 8, between about 2 and 6, etc.). Further, for example, a wound care composition having 7% by weight of ORC before removing 30% by weight of volatile components (e.g., water) may have about 10% by weight of ORC in the dried wound care composition. In some embodiments, oxidized cellulose may be present in the dried wound care composition in an amount of at least 8% by weight.

[0079] In some embodiments, oxidized cellulose may be present in a weight % (w / w) ratio of about 1:1 to about 2000:1 relative to the amount of quaternary ammonium salt (e.g., any quaternary ammonium salt described herein, such as benzalkonium salt) present in the wound care composition. For example, the amount of oxidized cellulose present (w / w) relative to the amount of quaternary ammonium salt present 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, etc. 1. Values ​​in the range of 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 any of the foregoing values ​​(e.g., between approximately 50:1 and approximately 120:1, between approximately 30:1 and approximately 80:1, etc.).

[0080] In some embodiments, oxidized cellulose may be present in a weight % (w / w) ratio of about 1:0.75 to about 1:70 relative to the amount of water-soluble polymer (any water-soluble polymer described herein, such as polyvinylpyrrolidone) present in the wound care composition. For example, the amount of oxidized cellulose present (in w / w) relative to the amount of water-soluble polymer present may be about 1:0.75, 1:0.8, 1:0.9, 1:1, 1:2, 1:5, 1:7, 1:10, 1:15, 1:18, 1:20, 1:22, 1:25, 1:28, 1:30, 1:32, 1:35, 1:38, 1:40, 1:42, 1:45, 1:48, 1:50, 1:52, 1:55, 1:58, 1:60, 1:62, 1:65, 1:68 or 1:70 or a value within any of the foregoing values ​​(e.g., between about 1:20 and about 1:30, between about 1:25 and about 1:40, etc.).

[0081] In many implementations, oxidized cellulose can be oxidized regenerated cellulose.

[0082] In many implementations, oxidized cellulose can be oxidized non-regenerated cellulose.

[0083] In some implementations, oxidized cellulose can be a combination of oxidized regenerated cellulose and oxidized non-regenerated cellulose.

[0084] Quaternary ammonium salts

[0085] In many embodiments, the quaternary ammonium salt may be selected from one or more alkylammonium salts, one or more benzalkonium salts, one or more benzyl ammonium salts, one or more pyridinium salts, and combinations thereof.

[0086] In some implementations, the quaternary ammonium salt can be an alkylammonium salt of formula Ia: R 1 -N + (CH3)2R 2 X - (Ia), Where R 1 It can be C 6-22 Alkyl groups, such as C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl, C 10 Alkyl, C 11 Alkyl, C 12 Alkyl, C 13 Alkyl, C 14 Alkyl, C 15 Alkyl, C 16 Alkyl, C 17 Alkyl, C 18 Alkyl, C 19 Alkyl, C20 Alkyl, C 21 Alkyl or C 22 Alkyl, or any range between the aforementioned values, for example, C 12-16 Alkyl, C 8-18 Alkyl groups, etc.; R 2 It can be C 1-22 Alkyl groups, for example, C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl, C 10 Alkyl, C 11 Alkyl, C 12 Alkyl, C 13 Alkyl, C 14 Alkyl, C 15 Alkyl, C 16 Alkyl, C 17 Alkyl, C 18 Alkyl, C 19 Alkyl, C 20 Alkyl, C 21 Alkyl or C 22 Alkyl, or any range between the aforementioned values, for example, C 1-6 Alkyl, C 1-4 Alkyl groups, etc.; and X is Cl, Br, or I.

[0087] In some implementations, the quaternary ammonium salt can be an alkylammonium salt of formula (Ib): R 1 -N + (CH3)3X - (Ib), Where R 1 It can be C 6-22 Alkyl groups, such as C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl, C 10 Alkyl, C 11 Alkyl, C 12 Alkyl, C 13 Alkyl, C 14 Alkyl, C 15 Alkyl, C 16 Alkyl, C 17 Alkyl, C 18 Alkyl, C 19 Alkyl, C 20 Alkyl, C 21 Alkyl or C 22 Alkyl, or any range between the aforementioned values, for example, C 12-16 Alkyl, C 8-18 Alkyl groups, etc.; and X is Cl, Br, or I.

[0088] In some implementations, the quaternary ammonium salt can be an alkylammonium salt of the following formula: .

[0089] In some implementations, the quaternary ammonium salt can be an alkylammonium salt of the following formula: .

[0090] In many embodiments, the quaternary ammonium salt may be a benzalkonium salt selected from one or more compounds of formula (IIa): (IIa), Where n can be an integer from 1 to 22, for example, 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 foregoing values, for example, 8 to 18, 10 to 16, etc.; and X can be Cl, Br, or I. In some embodiments, n can be selected from an integer of 8, 10, 12, 14, 16, or 18. In some embodiments, the composition may comprise one or more of formula IIa benzalkonium chloride. For example, a wound care composition may comprise a mixture of benzalkonium salts, wherein n is 8, 10, 12, 14, 16, and 18.

[0091] In some implementations, the quaternary ammonium salt can be a benzalkonium salt of formula IIb: PhCH2N + (CH3)2-(CH2) m -NH-C(O)-R 4 X - (IIb), Where R 4 It can be C 4-22 Alkyl groups, for example, C4 alkyl, C5 alkyl, C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl, C 10 Alkyl, C 11 Alkyl, C 12 Alkyl, C 13 Alkyl, C 14 Alkyl, C 15 Alkyl, C 16 Alkyl, C 17 Alkyl, C 18 Alkyl, C 19 Alkyl, C 20 Alkyl, C 21 Alkyl or C 22 Alkyl, or any range between the aforementioned values, for example, C 13-17 Alkyl, C 10-18 Alkyl groups, etc.; m can be an integer from 2 to 4; and X can be Cl, Br, or I. "Ph" stands for phenyl.

[0092] In some implementations, the quaternary ammonium salt can be a benzalkonium salt of the following formula: .

[0093] In some embodiments, the quaternary ammonium salt may be a benzyl ammonium salt selected from one or more compounds of formula (IIIa): PhCH2N + (CH3)2(CH2CH2O) n -R 6 X - (IIIa), Where R 6 It can be Ph or -Ph-R 10 R 10 It can be C 4-10 Alkyl group, n can be an integer selected from 1 to 6, and X can be Cl, Br, or I. "Ph" means phenyl or phenylene.

[0094] In some implementations, the quaternary ammonium salt can be a benzyl ammonium salt of the following formula: .

[0095] In some implementations, the quaternary ammonium salt can be a pyridinium salt of formula IVa: (IVa), Where R 9 It can be C 4-22 Alkyl groups, such as C4 alkyl, C5 alkyl, C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl, C 10 Alkyl, C 11 Alkyl, C 12 Alkyl, C 13 Alkyl, C 14 Alkyl, C 15 Alkyl, C 16 Alkyl, C 17 Alkyl, C 18 Alkyl, C 19 Alkyl, C 20 Alkyl, C 21 Alkyl or C 22 Alkyl, or within any of the foregoing values, for example, C 12-18 Alkyl, C 10-16 Alkyl groups, etc.; and X can be Cl or Br.

[0096] In some implementations, the quaternary ammonium salt can be a pyridinium salt of the following formula: .

[0097] In some embodiments, the quaternary ammonium salt (e.g., benzalkonium chloride) may be present in an amount from about 0.01% by weight to about 1% by weight relative to the weight of the wound care composition (wetting or drying). For example, the quaternary ammonium salt may be present in an amount (in weight%) 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, or 1.0, or in any of the foregoing values ​​(e.g., between about 0.05 and about 0.5, between about 0.7 and about 0.9, etc.). For example, a wound care composition having 0.13% by weight of quaternary ammonium salt before removing 30% by weight of volatile components (e.g., water) may have about 0.18% by weight of quaternary ammonium salt in the dried wound care composition.

[0098] In some embodiments, a quaternary ammonium salt (e.g., benzalkonium salt) may be present in a weight % (w / w) ratio of about 1:15 to about 1:7000 relative to the amount of water-soluble polymer (any water-soluble polymer described herein, e.g., polyvinylpyrrolidone) present in the wound care composition. For example, the amount of quaternary ammonium salt present (w / w) relative to the amount of water-soluble polymer present may be about 1:15, 1:25, 1:50, 1:75, 1:100, 1:150, 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, etc. Values ​​in the range of 1:850, 1:900, 1:950, 1:1000, 1:1250, 1:3000, 1:3500, 1:4000, 1:4500, 1:5000, 1:5500, 1:6000, 1:6500, or 1:7000, or between any of the foregoing values ​​(e.g., between approximately 1:200 and approximately 1:400, between approximately 1:500 and approximately 1:750, etc.).

[0099] In many implementations, the wound care composition may exclude other antiseptic compounds such as polyhexamethylene biguanide (“PHMB”), iodine, chlorhexidine, silver salts, etc.

[0100] Water-soluble polymers

[0101] In many embodiments, the water-soluble polymer may be characterized by its glass transition temperature (“T”). g The temperature is at least 20°C. In some embodiments, the water-soluble polymer may be characterized by T... gNo higher than 180°C. For example, water-soluble polymers may be characterized by T... g (°C) is a value within the range of 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, 170, 175, or 180, or between any of the aforementioned values ​​(e.g., between 50 and 90, between 30 and 120, etc.).

[0102] In many embodiments, the water-soluble polymer may be characterized as being electrically neutral, i.e., free of salts.

[0103] In many embodiments, the water-soluble polymer may be selected from polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, polyacrylic acid, polyacrylamide, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, guar gum, hydroxypropyl guar gum, and butene glycol, as well as combinations thereof. In some embodiments, the water-soluble polymer may consist essentially of polyvinylpyrrolidone. In other embodiments, the water-soluble polymer may consist essentially of polyvinyl alcohol.

[0104] In some embodiments, the water-soluble polymer (e.g., polyvinylpyrrolidone) may be present in an amount from about 15% by weight to about 70% by weight relative to the weight of the wound care composition (wetted or dried). For example, the water-soluble polymer may be present in an amount (in weight percent) of about 15, 18, 20, 22, 25, 28, 30, 32, 35, 38, 40, 42, 45, 48, 50, 52, 55, 58, 60, 62, 64, 65, 68, or 70, or in a range between any of the foregoing values ​​(e.g., between about 20 and about 40, between about 30 and about 55, etc.). Further, for example, a wound care composition having 40% by weight of the water-soluble polymer before removing 30% by weight of the volatile component (e.g., water) may have about 57% by weight of the water-soluble polymer in the dried wound care composition.

[0105] In some implementations, the water-soluble polymer may exclude polysaccharides other than oxidized cellulose.

[0106] Chelating compounds

[0107] In some embodiments, the wound care composition may contain a chelating agent. In some embodiments, the wound care composition may contain a chelating agent salt. In some embodiments, the wound care composition may contain both a chelating agent and a chelating agent salt.

[0108] In some embodiments, the chelating agent is characterized by a molecular weight of less than about 500 g / mol. For example, the chelating agent is characterized by a molecular weight of about 90 g / mol to about 500 g / mol, such as 90, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400, 420, 440, 460, 480, 500, or any value between the foregoing. Its chelating salt will have a molecular weight greater than that of its corresponding non-salt form.

[0109] In some embodiments, the chelating salt may contain a component selected from Na. + K + Cs + Mg 2+ Ca 2+ Or their combination of counterions.

[0110] In some embodiments, the chelating agent 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, and combinations thereof. In some embodiments, the chelating agent may consist essentially of citric acid.

[0111] In some implementations, the chelating salt may be selected from sodium citrate, sodium tartrate, sodium succinate, sodium calcium edetate, potassium ethylenediaminetetraacetate, or combinations thereof.

[0112] In some embodiments, the wound care composition may contain citric acid and sodium citrate.

[0113] In some embodiments, the chelating agent, chelating salt, or combination thereof (e.g., citric acid, sodium citrate) may be present in an amount from about 0.1% by weight to about 30% by weight relative to the weight of the wound care composition (wetting or drying). For example, the chelating agent may be present in an amount (in weight percent) 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, or 30 or in a range between any of the foregoing values ​​(e.g., between about 3 and about 7, between about 4 and about 10, etc.). For example, a wound care composition having 4% by weight of a chelating agent, chelating salt, or combination thereof before removing 30% by weight of the volatile component (e.g., water) may have about 6% by weight of a chelating agent, chelating salt, or combination thereof in the dried wound care composition.

[0114] In some embodiments, the chelating agent (e.g., citric acid) may be present in a weight % (w / w) ratio of about 3:1 to about 0.3:1 relative to the amount of the chelating agent salt (e.g., sodium citrate). For example, the chelating agent and the chelating salt may be present in a weight % (w / w) ratio 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 values ​​within any of the foregoing values ​​(e.g., between about 0.8:1 and 0.7:1, etc.). When both the chelating agent and the chelating salt are present in the wound care composition, the total weight % of the chelating agent and the chelating salt may not exceed 20% by weight. In many embodiments, the weight % ratio (w / w) of the chelating agent and the chelating agent salt can be selected to achieve or maintain a pH of about 2 to about 6, for example, 2, 3, 4, 5 or 6 or a value in the range between any of the foregoing values ​​(e.g., between about 2 and about 4).

[0115] In some embodiments, the chelating agent, chelating agent salt, or combination thereof (e.g., citric acid, sodium citrate) may be present in a weight % (w / w) ratio of about 1:0.03 to about 1:200 relative to the amount of oxidized cellulose. For example, the weight % ratio of the chelating agent, chelating agent salt, or combination thereof to oxidized cellulose may be about 1:0.03, 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, 1:1, 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 0.8, 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, or 1:200, or values ​​within a range of any of the foregoing values ​​(e.g., between about 1:0.8 and about 1:1.2, etc.). In some embodiments, the chelating agent, chelating agent salt, or combination thereof may be present in a weight percentage less than the weight percentage of the oxidized cellulose present.

[0116] In some embodiments, the chelating agent, chelating salt, or combination thereof (e.g., citric acid, sodium citrate) may be present in a weight % ratio (w / w) of about 3000:1 to about 0.1:1 relative to the amount of the quaternary ammonium salt (any quaternary ammonium salt described herein, such as benzalkonium salt). For example, the weight % ratio of the chelating agent, chelating agent salt, or combination thereof to benzalkonium salt can be about 3000:1, 2500:1, 2000:1, 1500:1, 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, 0.2:1, or 0.1:1, or a value within the range of any of the foregoing values ​​(e.g., between about 2:1 and about 1:1, between about 10:1 and about 4:1, etc.).

[0117] In some embodiments, the chelating agent, chelating salt, or combination thereof (e.g., citric acid, sodium citrate) may be present in a weight % (w / w) ratio of about 1:0.5 to about 1:700 relative to the amount of the water-soluble polymer (any water-soluble polymer described herein, e.g., polyvinylpyrrolidone). For example, the weight % ratio of the chelating agent, chelating salt, or combination thereof to the water-soluble polymer may be: about 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 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 0.6, 1:4.8, 1:5, 1:10, 1:25, 1:50, 1:75, 1:100, 1:150, 1:200, 1:250, 1:300, 1:350, 1:400, 1:450, 1:500, 1:550, 1:600, 1:650 or 1:700 or values ​​within a range of any of the foregoing values ​​(e.g., between approximately 1:2 and approximately 1:3, etc.).

[0118] plasticizer

[0119] In many embodiments, the wound care composition may also contain a plasticizer. The plasticizer is characterized by a boiling point greater than 105°C and a molecular weight less than 5000 g / mol. For example, the plasticizer is characterized by a boiling point (in °C) of 110, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 320, 340, 360, 380, 400 or greater, or within a range of any of the foregoing values ​​(e.g., between about 280 and about 320, etc.). For example, a plasticizer may be characterized by a molecular weight (g / mol) of 80, 90, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, 300, 350, 400, 450, 500, 550, 600 or greater, or within any of the foregoing values ​​(e.g., between about 80 and about 100, etc.).

[0120] In some embodiments, the plasticizer may be selected from glycerol, polyglycerol having 2 to 20 glycerol units, esterified polyglycerol (e.g., having a group -OC(O)-R, wherein R is a C that is substituted with at least two -OH groups). 1-18 Alkyl groups), polyethylene oxide, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, 2-methyl-1,3-propanediol, sorbitol, pentaerythritol, trimethylolpropane, bis(trimethylolpropane), ethylene oxide / propylene oxide copolymers, and combinations thereof. In some embodiments, the plasticizer may consist essentially of glycerol.

[0121] In some embodiments, the plasticizer (e.g., glycerin) may be present in an amount from about 15% to about 60% by weight relative to the weight of the wound care composition (wetted or dried). For example, the plasticizer may be present in an amount (in weight percent) of about 15, 18, 20, 22, 25, 28, 30, 32, 35, 38, 40, 42, 45, 48, 50, 52, 55, 58, or 60, or in any of the foregoing values ​​(e.g., between about 15 and about 30, between about 20 and about 40, etc.). Further, for example, a wound care composition having 30% by weight of plasticizer before removing 30% by weight of volatile components (e.g., water) may have about 43% by weight of chelating agent, chelating agent salt, or combinations thereof in the dried wound care composition.

[0122] In some embodiments, the plasticizer (e.g., glycerol) may be present in a weight % (w / w) ratio of about 60:1 to about 0.75:1 relative to the amount of oxidized cellulose. For example, the weight % ratio of plasticizer to oxidized cellulose may be about 60:1, 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, or 0.75:1, or a value within a range of any of the foregoing values ​​(e.g., between about 10:1 and about 1:1, etc.).

[0123] In some embodiments, the plasticizer (e.g., glycerol) may be present in a weight % ratio (w / w) of about 6000:1 to about 15:1 relative to the amount of the quaternary ammonium salt (any quaternary ammonium salt described herein, e.g., benzalkonium salt). For example, the weight % ratio of plasticizer to quaternary ammonium salt may be about 6000:1, 5500:1, 5000:1, 4500:1, 4000:1, 3500:1, 3000:1, 2500:1, 2000:1, 1500:1, 1000:1, 900:1, 800:1, 700:1, 600:1, 500:1, 400:1, 3000:1, etc. Values ​​in the range of :1, 200:1, 100:1, 95:1, 90:1, 85:1, 80:1, 75:1, 70:1, 65:1, 60:1, 55:1, 50:1, 45:1, 40:1, 35:1, 30:1, 25:1, 20:1, or 15:1, or any of the foregoing values ​​(e.g., between approximately 40:1 and approximately 20:1).

[0124] In some embodiments, the plasticizer (e.g., glycerol) may be present in a weight % (w / w) ratio of about 4:1 to about 0.2:1 relative to the amount of the water-soluble polymer (any water-soluble polymer described herein, e.g., polyvinylpyrrolidone). For example, the weight % ratio of plasticizer to water-soluble polymer may be about 4:1, 3.8:1, 3.6:1, 3.2:1, 3:1, 2.8:1, 2.6:1, 2.4:1, 2.2:1, 2:1, 1.8:1, 1.5:1, 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, or 0.2:1, or a value within a range of any of the foregoing values ​​(e.g., between about 1:1 and about 0.6:1, etc.).

[0125] In some embodiments, the plasticizer (e.g., glycerol) may be present in a weight % (w / w) ratio of about 600:1 to about 0.05:1 relative to the amount of the chelating agent, chelating agent salt, or combination thereof (any chelating agent / salt described herein, e.g., citric acid, sodium citrate). For example, the weight % ratio of the plasticizer to the chelating agent, chelating agent salt, or combination thereof may be about 600:1, 500:1, 400:1, 300:1, 200:1, 100:1, 75:1, 50:1, 25:1, 20:1, 15:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:1, or 0.5:1, or a value within a range of any of the foregoing values ​​(e.g., between about 10:1 and about 1:1, etc.).

[0126] Collagen

[0127] Collagen is often used in conjunction with ORC (oral recombinant collagen) for wound care. Collagen attracts fibroblasts, thereby aiding in angiogenesis and wound debridement. Collagen also supports granulation tissue formation and re-epithelialization.

[0128] As used herein, "collagen" or "the / said collagen" may include natural, denatured, or combinations thereof collagen raw materials. In some embodiments, the wound care composition may also contain collagen. In some embodiments, the collagen may be selected from type I, type II, type III, fragments thereof (e.g., denatured collagen, such as gelatin), and combinations thereof. In some embodiments, the collagen may be or may comprise collagen fragments having a molecular weight of about 5,000 Daltons to about 100,000 Daltons, for example, 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 any of the foregoing values ​​(e.g., about 5,000 to about 50,000, etc.). In some embodiments, the collagen may be chemically modified, such as telopeptide-free collagen obtained by removing immunogenic telopeptides from natural collagen.

[0129] In some embodiments, collagen may be present in an amount from about 1% by weight to about 60% by weight relative to the weight of the wound care composition (wetted or dried). For example, collagen may be present in an amount (in weight percent) of about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 25, 28, 30, 35, 40, 45, 50, or 60 or in a range between any of the foregoing values ​​(e.g., between about 5 and about 8, between about 2 and 6, etc.). In other embodiments, the wound care composition may exclude collagen.

[0130] In some embodiments, collagen may be present in a weight % (w / w) ratio of about 60:1 to about 0.15:1 relative to the amount of oxidized cellulose. For example, the amount of collagen present (w / w) relative to the amount of oxidized cellulose present 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 within the range of any of the foregoing values ​​(e.g., between about 1.5:1 and about 0.2:1, etc.).

[0131] In some embodiments, collagen may be present in a weight % (w / w) ratio of about 6000:1 to about 3:1 relative to the amount of quaternary ammonium salt (any quaternary ammonium salt described herein, e.g., benzalkonium salt) present in the wound care composition. For example, the amount of collagen present (w / w) relative to the amount of quaternary ammonium salt present may be a value in the range of 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 between any of the foregoing values ​​(e.g., between about 50:1 and about 100:1, between about 30:1 and about 80:1, etc.).

[0132] In some embodiments, collagen may be present in a weight percentage (w / w) of about 1:1.3 to about 1:23.3 relative to the amount of water-soluble polymer (any water-soluble polymer described herein, e.g., polyvinylpyrrolidone) present in the wound care composition. For example, the amount of collagen present (w / w) relative to the amount of water-soluble polymer present may be a value in the range of about 1:1.3, 1:1.5, 1:1.8, 1:2, 1:5, 1:10, 1:12, 1:15, 1:18, 1:20, 1:22, 1:23.3 or any of the foregoing values ​​(e.g., between about 1:15 and about 1:20, between about 1:1.5 and about 1:5, etc.).

[0133] In some embodiments, collagen may be present in a weight % (w / w) ratio of about 600:1 to 0.03:1 relative to the amount of chelating agent, chelating agent salt, or combination thereof (any chelating agent / salt described herein, e.g., citric acid, sodium citrate). For example, the weight % ratio of collagen to chelating agent, chelating agent salt, or combination thereof 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. Values ​​in the range of 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, 0.7:1, 0.06:1, 0.05:1, 0.04:1, or 0.03:1, or any of the foregoing values ​​(e.g., between approximately 1.2:1 and 0.8:1, etc.).

[0134] In some embodiments, collagen may be present in a weight % (w / w) ratio of about 1:0.25 to 1:60 relative to the amount of plasticizer (any plasticizer described herein, e.g., glycerol). For example, the weight % ratio of collagen to plasticizer may be about 1:0.25, 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2, 1:2.2, 1:2.5, 1:2.8, 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, or 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, 1:15, 1:20, 1:25, 1:30, 1:35, 1:40, 1:45, 1:50, 1:55 or 1:60 or values ​​within a range of any of the foregoing values ​​(e.g., between about 1:3 and about 1:7).

[0135] In some implementations, if protein materials are present, the wound care composition may exclude protein materials other than collagen.

[0136] It should be understood that no combination of components and described amounts may exceed 100% by weight. Those skilled in the art can readily adjust the amounts within the described range to comply with this concept.

[0137] The following wound care compositions may be moist or dry. Moist wound care compositions may also contain a volatile component (e.g., water) in an amount of at least 3% by weight, for example, 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or any range within the foregoing values ​​(e.g., between 3% and 35% by weight).

[0138] In some embodiments, the wound care composition may comprise or consist essentially of the following: The oxidized cellulose is present in an amount of about 1% to about 20% by weight; Quaternary ammonium salts (e.g., one or more of the above formula II benzalkonium chloride), which are present in an amount of about 0.01% by weight to about 1% by weight; A water-soluble polymer (e.g., polyvinylpyrrolidone), present in an amount of about 15% by weight to about 70% by weight; and The chelating agent, chelating salt, or combination thereof (e.g., a combination of citric acid and sodium citrate) is present in an amount of about 0.1% by weight to about 30% by weight.

[0139] In some embodiments, oxidized cellulose and quaternary ammonium salt can be present in a weight ratio of 2000:1 to 1:1; oxidized cellulose and chelating agent and / or chelating agent salt can be present in a weight ratio of 200:1 to 0.03:1; and quaternary ammonium salt and chelating agent and / or chelating agent salt can be present in a weight ratio of 1:0.1 to 1:3000.

[0140] In some embodiments, the wound care composition may comprise or consist essentially of the following: The oxidized cellulose is present in an amount of about 1% to 20% by weight; The quaternary ammonium salt is present in an amount of about 0.01% by weight to 1% by weight; (e.g., one or more benzalkonium chlorides of formula II above). A water-soluble polymer (e.g., polyvinylpyrrolidone), present in an amount of about 15% to 70% by weight; and The chelating agent, chelating salt, or combination thereof (e.g., a combination of citric acid and sodium citrate) is present in an amount of about 0.1% to 30% by weight.

[0141] In some embodiments, oxidized cellulose and quaternary ammonium salt can be present in a weight ratio of 1:1 to 2000:1; the oxidized cellulose and the chelating agent and / or chelating agent salt can be present in a weight ratio of 0.03:1 to 2000:1; and the quaternary ammonium salt and chelating agent and / or chelating agent salt can be present in a weight ratio of 1:300 to 1:0.1.

[0142] Method for preparing wound care compositions

[0143] In various embodiments, a method for preparing the wound care composition (i.e., wetting) of this disclosure is described. This method may include mixing oxidized cellulose, a quaternary ammonium salt, a chelating agent, a chelating agent salt, or a combination thereof, a water-soluble polymer, and a volatile component (e.g., water).

[0144] In some embodiments, the method may further include mixing oxidized cellulose, quaternary ammonium salt, chelating agent, chelating agent salt or combination thereof; water-soluble polymer, and volatile component with one or more of the following: plasticizer and collagen.

[0145] In some implementations, the method may also include mixing.

[0146] In some embodiments, the method may further include removing volatile components (e.g., water) from the moist wound care composition to form a dry wound care composition. Removal of volatile components may include heating (dehydration), freeze-drying, depressurization, or a combination thereof.

[0147] In various embodiments, a method for preparing the wound care composition of this disclosure (i.e., dried) is described. This method may include providing the moist wound care composition of this disclosure, and removing volatile components (e.g., water) from the moist wound care composition to form a dried wound care composition. Removal of the volatile components may include heating (dehydration), freeze-drying, depressurization, or a combination thereof.

[0148] wound care products

[0149] In various embodiments, a wound care product is described. The wound care product may include any dry wound care composition disclosed herein.

[0150] In many embodiments, the wound care product may be a self-standing construction. A self-standing construction may involve a dried wound care composition in the form of a self-standing membrane or a stack of self-standing membranes. Typically, a single self-standing membrane is characterized by a thickness (t) of about 3 mils to about 30 mils. Typically, a stack of self-standing membranes (i.e., more than one self-standing membrane pressed together) is characterized by a thickness (T) of about 6 mils to about 300 mils.

[0151] This disclosure covers self-standing structures produced by non-membrane counterparts, such as blocks of 6 to 300 mils prepared, for example, by dispensing a moist wound care composition into a mold and then drying; however, membrane structures are generally easier to manufacture and offer a variety of possibilities throughout the self-standing structure.

[0152] In some embodiments, the wound care article may comprise a single self-standing membrane or a stack of self-standing membranes (i.e., multiple self-standing membranes pressed together). The wound care composition may be contained within a single self-standing membrane, within each self-standing membrane in a stack of self-standing membranes, or distributed in any number of ways throughout the stack of self-standing membranes. For example, each self-standing membrane in a stack of self-standing membranes may comprise a water-soluble polymer and one or more of the following: oxidized cellulose; quaternary ammonium salts; chelating agents, chelating salts, or combinations thereof; plasticizers; and collagen, provided that the stack of self-standing membranes collectively contains the wound care composition (e.g., see illustration). Figures 1 to 6The selection, amount, and arrangement of components within a self-supporting membrane stack can be based on desired characteristics of the article, such as increased or decreased clotting, the availability of surface-applied antimicrobial agents, a greater need for inactivated matrix metalloproteinases and bound growth factors, and delayed or accelerated wound contact (e.g., timed contact) of selected components. For example, it may be advantageous to have oxidized cellulose on the surface of a wound care article, allowing the oxidized cellulose to contact the wound first and thus promote clotting more quickly.

[0153] In some embodiments, wound care products may include self-supporting membranes or self-supporting membrane stacks having a concentration of about 5 grams per square meter (g / m²). 2 Oxidized cellulose (or gsm) may be present in amounts of approximately 5 gsm, 6 gsm, 7 gsm, 8 gsm, 9 gsm, 10 gsm, 11 gsm, 12 gsm, 13 gsm, 14 gsm, 15 gsm, 16 gsm, 17 gsm, 18 gsm, 19 gsm, 20 gsm, 21 gsm, 22 gsm, 23 gsm, 24 gsm, 25 gsm, 26 gsm, 27 gsm, 28 gsm, 29 gsm, 30 gsm, 32 gsm, 35 gsm, 38 gsm, 40 gsm, 42 gsm, etc. The amount (gsm) is present in the range of 45 gsm, 48 gsm, 50 gsm, 55 gsm, 60 gsm, 65 gsm, 70 gsm, 75 gsm, 80 gsm, 85 gsm, 90 gsm, 95 gsm, 100 gsm, 110 gsm, 120 gsm, 130 gsm, 140 gsm, 150 gsm, 160 gsm, 170 gsm, 180 gsm, 190 gsm, or 200 gsm, or values ​​within any of the foregoing values ​​(e.g., between about 6 gsm and about 35 gsm). In some embodiments, the self-supporting membrane or self-supporting membrane stack may contain at least 6 gsm of oxidized cellulose. In other embodiments, the wound care product may contain up to 100 gsm of oxidized cellulose, including oxidized cellulose that can be coated onto a self-supporting membrane or a self-supporting membrane stack. For example, the wound care product may contain values ​​of 5 gsm, 10 gsm, 15 gsm, 20 gsm, 25 gsm, 30 gsm, 35 gsm, 40 gsm, 45 gsm, 50 gsm, 55 gsm, 60 gsm, 65 gsm, 70 gsm, 75 gsm, 80 gsm, 85 gsm, 90 gsm, 95 gsm, or 100 gsm, or values ​​within any of the foregoing values ​​(e.g., between about 35 gsm and about 80 gsm, etc.). Furthermore, oxidized cellulose may be present in a weight percentage relative to any other component as described above in the wound care composition.

[0154] In some embodiments, wound care articles may include a self-standing membrane or a self-standing membrane stack having a quaternary ammonium salt (any quaternary ammonium salt of this disclosure, such as benzalkonium salt) present in an amount of about 0.05 gsm to about 1 gsm. For example, the quaternary ammonium salt may be present in amounts (gsm) of about 0.05 gsm, 0.1 gsm, 0.15 gsm, 0.2 gsm, 0.25 gsm, 0.3 gsm, 0.35 gsm, 0.4 gsm, 0.45 gsm, 0.5 gsm, 0.55 gsm, 0.6 gsm, 0.65 gsm, 0.7 gsm, 0.75 gsm, 0.8 gsm, 0.85 gsm, 0.9 gsm, 0.95 gsm, or 1 gsm, or values ​​within any of the foregoing values ​​(e.g., between about 0.3 gsm and about 0.4 gsm, etc.). Furthermore, the quaternary ammonium salt may be present in weight percentages relative to any other component as described above in the wound care composition.

[0155] In some embodiments, wound care articles may include a self-standing membrane or a self-standing membrane stack having a water-soluble polymer (any water-soluble polymer disclosed herein, for example, polyvinylpyrrolidone) present in an amount of about 100 gsm to about 200 gsm. For example, the water-soluble polymer may be present in amounts (gsm) of about 100 gsm, 105 gsm, 110 gsm, 115 gsm, 120 gsm, 125 gsm, 130 gsm, 135 gsm, 140 gsm, 145 gsm, 150 gsm, 155 gsm, 160 gsm, 165 gsm, 170 gsm, 175 gsm, 180 gsm, 185 gsm, 190 gsm, 195 gsm, or 200 gsm, or values ​​within any of the foregoing values ​​(e.g., between about 110 gsm and about 155 gsm, etc.). Furthermore, the water-soluble polymer may be present in weight percentages relative to any component as described above in the wound care composition.

[0156] In some embodiments, the wound care article may include a self-standing membrane or a self-standing membrane stack having a chelating agent, chelating salt, or combination thereof (any chelating agent / salt of this disclosure, e.g., citric acid, sodium citrate) present in an amount from about 5 gsm to about 40 gsm. For example, the chelating agent, chelating salt, or combination thereof may be present in an amount (gsm) of about 5 gsm, 12 gsm, 15 gsm, 18 gsm, 20 gsm, 22 gsm, 25 gsm, 28 gsm, 30 gsm, 32 gsm, 35 gsm, 38 gsm, or 40 gsm, or in a range between any of the foregoing values ​​(e.g., between about 15 gsm and about 25 gsm, etc.). Furthermore, the chelating agent, chelating salt, or combination thereof may be present in a weight percentage relative to any component as described above in the wound care composition.

[0157] In some embodiments, the wound care article may include a self-standing membrane or a self-standing membrane stack, which also has a plasticizer (any plasticizer disclosed herein, such as glycerin) present in an amount of about 50 gsm to about 150 gsm. For example, the plasticizer may be present in amounts (gsm) of about 50 gsm, 55 gsm, 60 gsm, 65 gsm, 70 gsm, 75 gsm, 80 gsm, 85 gsm, 90 gsm, 95 gsm, 100 gsm, 105 gsm, 110 gsm, 115 gsm, 120 gsm, 125 gsm, 130 gsm, 135 gsm, 140 gsm, 145 gsm, or 150 gsm, or in a range between any of the foregoing values ​​(e.g., between about 110 gsm and about 130 gsm, etc.). Furthermore, the plasticizer may be present in a weight percentage relative to any component as described above in the wound care composition.

[0158] In some embodiments, the wound care article may include a self-standing membrane or a self-standing membrane stack, which further comprises collagen present in an amount of about 1 gsm to about 25 gsm. For example, the collagen may be present in an amount (gsm) of about 1 gsm, 2 gsm, 3 gsm, 4 gsm, 5 gsm, 6 gsm, 7 gsm, 8 gsm, 9 gsm, 10 gsm, 12 gsm, 15 gsm, 18 gsm, 20 gsm, 22 gsm, or 25 gsm, or in a range between any of the foregoing values ​​(e.g., between about 3 gsm and about 5 gsm, etc.). Furthermore, the collagen may be present in a weight percentage relative to any of the components described above in the wound care composition.

[0159] In some embodiments, the wound care article may include a self-supporting membrane or a self-supporting membrane stack, which has or is substantially composed of the following: Oxidized cellulose, which is present in an amount of about 5 gsm to 100 gsm or in the range above; Quaternary ammonium salts (e.g., one or more of the above formula IIa benzalkonium chloride), which are present in amounts from about 0.05 gsm to 1 gsm or in the range described above; Chelating agents, chelating salts, or combinations thereof (e.g., citric acid, sodium citrate), wherein the chelating agent, chelating salt, or combination thereof is present in an amount from about 5 gsm to 40 gsm or within the range described above; and A water-soluble polymer (e.g., polyvinylpyrrolidone) is present in an amount of about 100 gsm to 200 gsm or within the range described above.

[0160] In some embodiments, the wound care article may include a self-supporting membrane or a self-supporting membrane stack, which has or is substantially composed of the following: Oxidized cellulose, which is present in an amount of about 5 gsm to 50 gsm or in the range above; Quaternary ammonium salts (e.g., one or more of the above formula IIa benzalkonium chloride), which are present in amounts from about 0.05 gsm to 1 gsm or in the range described above; Chelating agents, chelating salts, or combinations thereof (e.g., citric acid, sodium citrate), wherein the chelating agent, chelating salt, or combination thereof is present in an amount from about 5 gsm to 40 gsm or within the range described above. A water-soluble polymer (e.g., polyvinylpyrrolidone), present in an amount of about 100 gsm to 200 gsm or within the range described above, and One or more of the following: Plasticizers (e.g., glycerin), present in amounts from about 50 gsm to 150 gsm, and Collagen, which exists in amounts ranging from approximately 1 gsm to 25 gsm.

[0161] In some embodiments, a wound care article may include a single self-standing membrane or two to ten self-standing membranes within a stack of self-standing membranes. For example, a wound care article may include one, two, three, four, five, six, seven, eight, nine, or ten self-standing membranes, or values ​​within any of the aforementioned ranges (e.g., between four and six, between three and seven, etc.) (see, for example, an illustration of three self-standing membranes within a stack of self-standing membranes). Figure 4 and Figure 6 ; This shows two self-standing membranes in a self-standing membrane stack. Figure 5 ).

[0162] In many embodiments, the wound care product may also include a water-soluble base. The water-soluble base may comprise or consist essentially of materials as described above for water-soluble polymers, such as polyvinylpyrrolidone, polyvinyl alcohol, etc. In some embodiments, the water-soluble base may consist essentially of polyvinylpyrrolidone, polyvinyl alcohol, or combinations thereof. In some embodiments, the water-soluble base may consist essentially of a polyvinylpyrrolidone nonwoven fabric, a polyvinylpyrrolidone film, or combinations thereof. In some embodiments, the water-soluble base may consist essentially of a polyvinyl alcohol nonwoven fabric, a polyvinyl alcohol film, or combinations thereof. In many embodiments, the water-soluble base may be in contact with one or more surfaces of a self-supporting membrane or self-supporting membrane stack. The water-soluble base may typically be included in wound care products comprising an oxidized cellulose coating (e.g., discontinuous or continuous) in contact with a surface of a self-supporting membrane or self-supporting membrane stack. In some embodiments, the water-soluble base may be characterized by a thickness (th) of about 3 mils to about 150 mils, for example, 3 mils, 5 mils, 10 mils, 20 mils, 30 mils, 40 mils, 50 mils, 60 mils, 70 mils, 80 mils, 90 mils, 100 mils, 120 mils, or 150 mils, or values ​​within any of the foregoing values ​​(e.g., between about 30 mils and about 50 mils, etc.). In some embodiments, the wound care product may comprise a thickness of about 50 g / m³. 2 Approximately 400g / m 2 For example, 50g / m 2 60g / m 2 70g / m 2 80g / m 2 90g / m 2 100g / m 2 120g / m 2 150g / m 2 180g / m 2 200g / m 2 220g / m 2 250g / m 2 280g / m 2 300g / m 2 320g / m 2 350g / m 2 380g / m 2 Or 400g / m 2 Or between any of the aforementioned values ​​(e.g., approximately 100 g / m³). 2 With approximately 200g / m 2 The amount of water-soluble substrate exists within a range of values ​​between (between).

[0163] In many implementations, wound care products can be wound dressings.

[0164] Methods for preparing wound care products

[0165] In various embodiments, a method for preparing the wound care article of this disclosure is described. The method may include providing the wound care composition of this disclosure, coating a substrate with the wound care composition to form a layer, and drying the layer to form a single self-standing membrane. Optionally, the method may also include forming one or more additional self-standing membranes according to prior steps, and pressing the single self-standing membrane and one or more additional self-standing membranes to form a self-standing membrane stack. The single self-standing membrane or the self-standing membrane stack is a wound care article or at least a portion of a wound care article.

[0166] In some embodiments, a single self-standing membrane containing a wound care composition may be pressed together with one or more additional self-standing membranes containing one or more components of a wound care composition to form a self-standing membrane stack. In some embodiments, each self-standing membrane within the self-standing membrane stack contains a wound care composition.

[0167] In various embodiments, a method for preparing the wound care article of this disclosure is described. The method may include: providing oxidized cellulose, a quaternary ammonium salt, a chelating agent compound, and a water-soluble polymer; mixing the water-soluble polymer with one or more of the oxidized cellulose, the quaternary ammonium salt, and the chelating agent compound to form a composition; coating a substrate with the composition to form a layer; and drying the layer to form a single self-standing membrane. The method may optionally further include: forming one or more additional self-standing membranes according to the preceding steps; and pressing the single self-standing membrane and one or more additional self-standing membranes together to form a self-standing membrane stack. The single self-standing membrane or the self-standing membrane stack must contain the quaternary ammonium salt and the chelating agent compound. In other words, when a wound care product comprises only a single self-standing membrane, the single self-standing membrane must contain both a quaternary ammonium salt and a chelating agent compound; however, any given "single" self-standing membrane does not need to contain both a quaternary ammonium salt and a chelating agent compound when combined with one or more additional self-standing membranes to form a self-standing membrane stack, as long as the quaternary ammonium salt and the chelating agent compound are present within at least one self-standing membrane of the self-standing membrane stack. When the single self-standing membrane or self-standing membrane stack excludes oxidized cellulose, the method may further include applying oxidized cellulose to the surface of the single self-standing membrane or the surface of the self-standing membrane stack. The single self-standing membrane or self-standing membrane stack is a wound care product or at least a portion thereof. The method achieves a configuration in which the components of any wound care composition described herein can be distributed in various ways throughout the self-standing membrane stack. In other words, it may be advantageous for some regions of the self-standing membrane stack to contain higher or lower concentrations of any given component compared to other regions within the self-standing membrane stack.

[0168] In some embodiments, the method may include forming a single self-standing membrane using a composition comprising a quaternary ammonium salt, a chelating compound, and a water-soluble polymer, wherein oxidized cellulose may be coated on the surface of the single self-standing membrane. In other embodiments, the method may include forming a single self-standing membrane using a composition comprising oxidized cellulose, a quaternary ammonium salt, a chelating compound, and a water-soluble polymer; optionally, the surface of the single self-standing membrane may be coated with oxidized cellulose. In some embodiments, the composition for forming the single self-standing membrane may also comprise one or more of the following: a plasticizer; and collagen.

[0169] In some embodiments, the method may include preparing a plurality of self-standing membranes and pressing the plurality of self-standing membranes together to form a self-standing membrane stack. Each self-standing membrane may be formed using a composition comprising a quaternary ammonium salt, a chelating compound, and a water-soluble polymer, wherein oxidized cellulose may be coated on the surface of the self-standing membrane stack. In other embodiments, each self-standing membrane may be formed using a composition comprising oxidized cellulose, a quaternary ammonium salt, a chelating compound, and a water-soluble polymer (i.e., a wound care composition); optionally, the surface of the self-standing membrane stack may be coated with oxidized cellulose. In some embodiments, the composition may also comprise one or more of the following: a plasticizer; and collagen.

[0170] In some embodiments, a single self-standing membrane may comprise a quaternary ammonium salt, a chelating compound, a water-soluble polymer, and oxidized cellulose. In some embodiments, each self-standing membrane within a self-standing membrane stack may comprise a quaternary ammonium salt, a chelating compound, a water-soluble polymer, and oxidized cellulose.

[0171] In some embodiments, drying of the composition layer may include heating, freeze-drying, depressurization, or a combination thereof. Drying can effectively remove volatile components (e.g., water).

[0172] In some embodiments, applying oxidized cellulose to the surface of a single self-standing membrane or a stack of self-standing membranes may involve the powder coating techniques described herein. Powder coating techniques can provide discontinuous oxidized cellulose coatings. If desired, discontinuous oxidized cellulose coatings can allow for faster decomposition in wound environments. In other embodiments, applying oxidized cellulose to the surface of a single self-standing membrane or a stack of self-standing membranes may involve the slurry coating techniques described herein. Slurry coating techniques can provide continuous oxidized cellulose coatings.

[0173] In other embodiments, the method may further include providing a water-soluble substrate (e.g., the water-soluble polymer described herein) and applying oxidized cellulose to a surface of the water-soluble substrate to provide an oxidized cellulose coating on the water-soluble substrate. In some embodiments, applying oxidized cellulose to the surface of the water-soluble substrate may involve a powder coating technique. Powder coating techniques can provide a discontinuous oxidized cellulose coating. The water-soluble substrate with the oxidized cellulose coating may subsequently be pressed onto the surface of a single self-standing membrane or self-standing membrane stack. The use of a water-soluble substrate with an oxidized cellulose coating thereon is intended to be covered by, but not required by, the method steps of applying oxidized cellulose to the surface of a single self-standing membrane or self-standing membrane stack.

[0174] Methods of using wound care compositions and products

[0175] In various embodiments, a method for treating a wound is described. This method may include contacting the wound with a wound care composition or wound care product of this disclosure.

[0176] In various embodiments, a method for promoting blood clotting is described. This method may include contacting a bleeding wound with a wound care composition or wound care product of this disclosure.

[0177] In various embodiments, a method for reducing the number of microorganisms in or around a wound is described. This method may include contacting the wound with a wound care composition or wound care product of this disclosure. In some embodiments, the microorganisms may include Gram-positive bacteria, Gram-negative bacteria, or a combination thereof. In some embodiments, the microorganisms may include Staphylococcus aureus (…). Staphylococcus (For example, Staphylococcus aureus) Staphylococcus aureus ), Pseudomonas ( Pseudomonas (For example, Pseudomonas aeruginosa) Pseudomonas aeruginosa () or combinations thereof. In many embodiments, this method can reduce the number of microorganisms within the biofilm environment. In some embodiments, this method can effectively prevent biofilm formation.

[0178] In many implementations, the wound can be a chronic wound.

[0179] The wound care compositions disclosed herein may be used in the manufacture of wound care articles of the present disclosure; in the manufacture of agents for treating wounds; or combinations thereof.

[0180] The wound care product disclosed herein can be used in the manufacture of pharmaceuticals for treating wounds.

[0181] kit

[0182] In various embodiments, a kit is described. The kit may comprise oxidized cellulose, a quaternary ammonium salt, a chelating compound, and a water-soluble polymer. In some embodiments, the kit may also comprise one or more of the following: a volatile component; a plasticizer; and collagen. The kit may also include instructions for users to prepare wound care compositions according to this disclosure.

[0183] In various embodiments, a kit is described. The kit may include the wound care compositions of this disclosure. In many embodiments, the kit may also include a set of instructions instructing a user to prepare the wound care products of this disclosure using any of the methods listed herein.

[0184] In various embodiments, a kit is described. The kit may include the wound care composition disclosed herein. In many embodiments, the kit may also include a set of instructions instructing the user to apply the wound care composition to the subject's wound.

[0185] In various embodiments, a kit is described. The kit may include the wound care products of this disclosure. In many embodiments, the kit may also include a set of instructions instructing the user to apply the wound care products to the subject's wound.

[0186] Example

[0187] The following embodiments further illustrate the purpose and advantages of this disclosure, but the materials and quantities described in these embodiments, as well as other conditions and details, should not be construed as unduly limiting this disclosure. These embodiments are for illustrative purposes only and are not intended to limit the scope of the appended claims.

[0188] Methods for colony biofilm assay and biofilm viability assay

[0189] Staphylococcus aureus strain 15981 or Pseudomonas aeruginosa strain 15442 from the USC Type Culture Collection were grown overnight at 37°C to the stationary phase in trypsin-soybean liquid medium (Becton, Dickenson, and Company, Franklin Lakes, NJ). The cultures were diluted 1:10,000 in sterile phosphate-buffered saline, and 10 μL of the diluted suspension was dropped dropwise onto a polycarbonate membrane (25 mm diameter, 0.2 μm pore size, polycarbonate filter membrane from Sigma Millipore, location), which was placed on top of trypsin-soybean agar (TSA) containing 1.5% agar (Becton, Dickenson, and Company, Franklin Lakes, NJ). The bacteria were allowed to grow at 37°C for 24 hours. After the growth period, the filter was aseptically transferred to TSA poured into a sterile 6-well polystyrene plate.

[0190] Cover the bacteria in a 20 mm round dish containing the following wound care product and incubate at 37°C for 24 hours. Test each sample in triplicate. Transfer the bacterial-covered membrane and any residual wound care product to 10 mL of Dey / Englay (D / E) neutralization medium (Becton Dickinson, Franklin Lake, NJ) in a 50 mL conical centrifuge tube. Vortex the sample at maximum speed for 1 min and then sonicate it in an ultrasonic bath (Model 2150, from Branson Ultrasonics Corporation, Danbury, Connecticut) for 1 min. Serially dilute the sample 10-fold in sterile phosphate-buffered saline and plate it onto an AC plate purchased from 3M Inc., St. Paul, Minnesota, under the trade name “3M PETRIFILMAerobic Count Plates”. Petrifilm ™ On the slide. Incubate 3MPETRIFILM slides at 37°C for 36 to 48 hours, count the number of surviving colony-forming units (CFU), and calculate the mean log reduction by subtracting the mean log of the treated samples (CFU / sample) from the mean log of the untreated samples in the same experiment.

[0191]

[0192] Example 1 and Comparative Examples 1 to 3: Antimicrobial Agent Solubility

[0193] The antimicrobial agents listed in Table 1 were added dropwise to four separate vials containing a mixture of oxidized regenerated cellulose (0.25 g) in water (4 g). White precipitates were observed with all reagents except benzalkonium chloride. Chlorhexidine digluconate, polyhexamethylene biguanide, and oteninidine dihydrochloride were not suitable active agents with oxidized regenerated cellulose because, theoretically, these active agents would complex with the oxidized regenerated cellulose and precipitate from the solution.

[0194]

[0195] Example 2 and Comparative Examples 4 and 5

[0196] Examples 2 and Comparative Examples 4 and 5 were prepared using the amounts provided in Table 2A: Glycerin, BAC (supplied as a 50% aqueous solution), citric acid / sodium citrate (if present), and water were added to a MAX 100 cup (Flacktec Inc.; Landrum, SC) and mixed at 3500 rpm for 1 min using a 34 a DAC 400 FVZ SpeedMixer™ (Flacktec Inc.; Landrum, SC). Subsequently, PVP K60 (47%, in water) (Ashland) was added to the MAX 100 cup, and the resulting mixture was further mixed at 3500 rpm for 1 min. The composition was then scraped onto a release liner with a gap of 254 microns (i.e., 10 mils; wetted thickness approximately 1 / 2 of the gap; dry thickness approximately 4 mils, and basis weight 100 g / m²). 2 The composition was dried in a convection oven at 80°C for 20 min. The resulting self-supporting membrane was flexible and could be removed from the release liner. Two self-supporting membrane layers were joined together by hand pressure to prepare a 200 g / m² membrane. 2 Self-standing membrane stack (i.e., each of the two membranes is 100 g / m³) 2 ).

[0197] Example 2: Self-standing membrane stacks were powder coated with oxidized regenerated cellulose (“ORC”) by the following direct powder coating method to obtain 14.7%, 13.64%, and 15.82% w / w ORC, respectively.

[0198] Direct coating method. Powdered ORC in the form of extremely small fibers (e.g., fragments smaller than 1 mm) can be dispersed by hand on top of a self-standing membrane stack and gently pressed onto the slightly sticky membrane. Excess ORC powder can be removed by flipping the membrane to allow it to detach. The membrane can be flipped, and powdered ORC can be applied in the same manner.

[0199] Comparative Example 4 was not powder coated using ORC.

[0200] Comparative Example 5 does not contain citric acid, sodium citrate, or BAC.

[0201]

[0202] Other suitable coating methods

[0203] The following powder coating techniques are alternative methods for constructing the articles disclosed herein.

[0204] Indirect-1 Powder Coating: OC can be deposited onto one or more substrates (e.g., polyvinyl alcohol nonwoven fabrics or films) at a rate (e.g., 1 m per min) using a vibratory feeder (e.g., Eriez Magnetics, model 20A) to provide an OC coating thereon. Deionized water can be sprayed onto the OC powder substrate to bind the OC powder to the substrate. The sprayed water may partially dissolve a portion of the substrate. The OC powder substrate can be dried at room temperature (approximately 21°C at 1 atm) for a period of time (e.g., 24 h) and subsequently pressed together to form a self-supporting film stack.

[0205] Indirect-2 Powder Coating: OC can be deposited onto a membrane liner (e.g., polyethylene terephthalate) using a sieve. An aqueous solution of a water-soluble polymer (e.g., 10 wt% PVP K30) can be sprayed onto the deposited OC powder, and the resulting structure is dried at an elevated temperature (e.g., 60°C) for a period of time (e.g., 24 h). The water-soluble polymer can be used to bind the OC powder. The dried structures can then be pressed together to form a self-supporting membrane stack.

[0206] Indirect-3 Powder Coating: A film liner (e.g., polyethylene terephthalate) can be placed on top of a substrate (e.g., polyvinyl alcohol nonwoven substrate, polyvinyl alcohol film, etc.) having an OC powder coating thereon. The resulting structure can be calendered under pressure (e.g., 100 Psi, approximately 690 kPa) and at a speed of, for example, 3 ft per min, through two heated (e.g., 200℉, approximately 93°C) flat rollers. Calendering presses the OC powder into the substrate, and the film liner can then be removed. The OC powder substrate can then be laminated to the self-supporting film stack by hand.

[0207] Indirect-4 Powder Coating: A nonwoven substrate (e.g., polyvinyl alcohol) can be placed on top of a nonwoven substrate (e.g., polyvinyl alcohol) having an OC powder coating. The resulting structure can be calendered by passing it through two heated (e.g., 200℉, approximately 93°C) flat rollers at a pressure (e.g., 100 Psi, approximately 690 kPa) and a speed (e.g., 3 ft per min). The nonwoven fabric can become a layer encapsulating the OC powder. The OC powder substrates can then be pressed together to form a self-supporting film stack.

[0208] Indirect-5 Powder Coating: A film substrate (e.g., polyvinyl alcohol) can be placed on top of a nonwoven substrate (e.g., polyvinyl alcohol) having an OC powder coating thereon. The resulting structure can be calendered under pressure (e.g., 100 Psi, approximately 690 kPa) and at a speed (e.g., 3 ft per min) through two heated (e.g., 200℉, approximately 93°C) flat rollers. The film and nonwoven fabric can become a layer encapsulating the OC powder. The OC powder substrate can then be pressed together to form a self-supporting film stack.

[0209] Equivalent scheme

[0210] Using only conventional experiments, those skilled in the art will recognize or be able to identify many equivalents of the specific embodiments described herein. Such equivalents are intended to be covered within the scope of the appended claims.

Claims

1. A wound care composition, the wound care composition comprising: Oxidized cellulose; Quaternary ammonium salts; Chelating agents, chelating salts, or combinations thereof; and Water-soluble polymer.

2. The wound care composition according to claim 1, wherein the oxidized cellulose is characterized in that the carboxyl content is 5% to 50%.

3. The wound care composition according to any one of claims 1 to 2, wherein the oxidized cellulose is present in an amount of about 0.5% to about 20% by weight relative to the weight of the wound care composition.

4. The wound care composition according to any one of claims 1 to 3, wherein the oxidized cellulose is present in a weight percentage of about 1:1 to about 2000:1 relative to the amount of quaternary ammonium salt present in the wound care composition.

5. The wound care composition according to any one of claims 1 to 4, wherein the oxidized cellulose is present in an amount of about 1:70 by weight, relative to the amount of the water-soluble polymer present in the wound care composition.

6. The wound care composition according to any one of claims 1 to 5, wherein the oxidized cellulose is oxidized regenerated cellulose.

7. The wound care composition according to any one of claims 1 to 5, wherein the oxidized cellulose is oxidized non-regenerated cellulose.

8. The wound care composition according to any one of claims 1 to 5, wherein the oxidized cellulose is a combination of oxidized regenerated cellulose and oxidized non-regenerated cellulose.

9. The wound care composition according to any one of claims 1 to 8, wherein the quaternary ammonium salt is present in an amount of about 0.01% by weight to about 1% by weight relative to the weight of the wound care composition.

10. The wound care composition according to any one of claims 1 to 9, wherein the quaternary ammonium salt is present in a weight percentage of about 1:15 to 1:7000 relative to the amount of the water-soluble polymer present in the wound care composition.

11. The wound care composition according to any one of claims 1 to 10, wherein the quaternary ammonium salt is a benzalkonium salt selected from one or more compounds of formula IIa: (IIa), Where n is an integer selected from 8, 10, 12, 14, 16 or 18.

12. The wound care composition according to any one of claims 1 to 11, wherein the water-soluble polymer is selected from polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, polyacrylic acid, polyacrylamide, hydroxypropyl methylcellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, guar gum, hydroxypropyl guar gum, butene vinyl alcohol, and combinations thereof.

13. The wound care composition according to any one of claims 1 to 12, wherein the water-soluble polymer is present in an amount of about 15% to about 70% by weight relative to the weight of the wound care composition.

14. The wound care composition according to any one of claims 1 to 13, wherein the wound care composition further comprises a chelating agent, a chelating agent salt, or a combination thereof.

15. The wound care composition according to any one of claims 1 to 14, wherein the chelating agent or the chelating agent salt is characterized in that the molecular weight is from 90 g / mol to 500 g / mol.

16. The wound care composition according to any one of claims 1 to 15, wherein the chelating agent is 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, or combinations thereof.

17. The wound care composition according to any one of claims 1 to 16, wherein the chelating agent, the chelating agent salt, or a combination thereof is present in a total amount of about 0.1% to about 30% by weight relative to the weight of the wound care composition.

18. The wound care composition according to any one of claims 1 to 17, wherein the wound care composition comprises a chelating agent and a chelating agent salt present in a weight percentage ratio of about 3:1 to about 0.3:

1.

19. The wound care composition according to any one of claims 1 to 18, wherein the chelating agent, the chelating agent salt, or a combination thereof is present in a weight % ratio of about 1:0.03 to about 1:200 relative to the amount of oxidized cellulose.

20. The wound care composition according to any one of claims 1 to 19, wherein the chelating agent, the chelating agent salt, or a combination thereof is present in a weight % ratio of about 3000:1 to about 1:0.1 relative to the amount of the quaternary ammonium salt.

21. The wound care composition according to any one of claims 1 to 20, wherein the chelating agent, the chelating agent salt, or a combination thereof is present in a weight percentage of about 1:0.5 to about 1:700 relative to the amount of the water-soluble polymer.

22. The wound care composition according to any one of claims 1 to 21, wherein the wound care composition further comprises a plasticizer.

23. The wound care composition according to any one of claims 1 to 22, wherein the wound care composition further comprises a plasticizer characterized by a boiling point greater than 105°C and a molecular weight less than 5000 g / mol.

24. The wound care composition according to any one of claims 1 to 23, wherein the wound care composition further comprises a plasticizer selected from the group consisting of glycerol, polyglycerol having 2 to 20 glycerol units, esterified polyglycerol, polyethylene oxide, polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, 2-methyl-1,3-propanediol, sorbitol, pentaerythritol, trimethylolpropane, bis(trimethylolpropane), ethylene oxide / propylene oxide copolymer, and combinations thereof.

25. The wound care composition according to any one of claims 1 to 24, wherein the wound care composition further comprises a plasticizer present in an amount of about 15% to about 60% by weight relative to the weight of the wound care composition.

26. The wound care composition according to any one of claims 1 to 25, wherein the wound care composition further comprises a plasticizer present in a weight percentage of about 60:1 to about 0.75:1 relative to the amount of oxidized cellulose.

27. The wound care composition according to any one of claims 1 to 26, wherein the wound care composition further comprises a plasticizer present in a weight % ratio of about 6000:1 to about 15:1 relative to the amount of the quaternary ammonium salt.

28. The wound care composition according to any one of claims 1 to 27, wherein the wound care composition further comprises a plasticizer present in a weight percentage ratio of about 4:1 to about 0.2:1 relative to the amount of the water-soluble polymer.

29. The wound care composition according to any one of claims 1 to 28, wherein the wound care composition further comprises collagen.

30. The wound care composition according to any one of claims 1 to 29, wherein the wound care composition further comprises collagen selected from type I, type II, type III, fragments thereof, and combinations thereof.

31. The wound care composition according to any one of claims 1 to 30, wherein the wound care composition further comprises collagen in an amount of about 1% to about 60% by weight relative to the weight of the wound care composition.

32. The wound care composition according to any one of claims 1 to 31, wherein the wound care composition further comprises collagen present in a weight percentage ratio of about 60:1 to about 0.15:1 relative to the amount of oxidized cellulose.

33. The wound care composition according to any one of claims 1 to 32, wherein the wound care composition further comprises collagen present in a weight % ratio of about 6000:1 to about 3:1 relative to the amount of the quaternary ammonium salt.

34. The wound care composition according to any one of claims 1 to 33, wherein the wound care composition further comprises collagen present in a weight percentage of about 1:0.75 to about 1:23.3 relative to the amount of the water-soluble polymer.

35. The wound care composition according to any one of claims 1 to 34, wherein the wound care composition further comprises a pH buffer solution.

36. The wound care composition according to any one of claims 1 to 35, wherein the wound care composition is characterized by a pH of 2 to 6.

37. The wound care composition according to any one of claims 1 to 36, The oxidized cellulose is present in an amount of about 1% to about 20% by weight; The quaternary ammonium salt is present in an amount of about 0.01% by weight to about 1% by weight; The water-soluble polymer is present in an amount of about 15% to about 70% by weight; and The chelating agent, the chelating agent salt, or a combination thereof are present in an amount of about 0.1% by weight to about 30% by weight.

38. The wound care composition according to any one of claims 1 to 37, The oxidized cellulose and the quaternary ammonium salt exist in a weight ratio of 2000:1 to 1:1; The oxidized cellulose and the chelating agent and / or chelating agent salt are present in a weight ratio of 200:1 to 0.03:1; and The quaternary ammonium salt and chelating agent and / or chelating agent salt are present in a weight ratio of 1:0.1 to 1:3000.

39. The wound care composition according to any one of claims 1 to 38, The oxidized cellulose is present in an amount of about 1% to 20% by weight; The quaternary ammonium salt is present in an amount of about 0.01% by weight to 1% by weight; The water-soluble polymer is present in an amount of about 15% to 70% by weight; and The chelating agent, chelating agent salt, or combination thereof is present in an amount of about 0.1% to 30% by weight.

40. The wound care composition according to any one of claims 1 to 39, The oxidized cellulose and the quaternary ammonium salt can be present in a weight ratio of 1:1 to 2000:1; The oxidized cellulose and the chelating agent and / or chelating agent salt can be present in a weight ratio of 0.03:1 to 2000:1; and The quaternary ammonium salt and the chelating agent and / or chelating agent salt can be present in a weight ratio of 1:300 to 1:0.

1.

41. A wound care product, the wound care product comprising: The wound care composition according to any one of claims 1 to 40.

42. A wound care product, the wound care product comprising: The wound care composition according to any one of claims 1 to 40, The wound care composition is in the form of a self-standing membrane or a self-standing membrane stack, the self-standing membrane stack comprising a plurality of self-standing membranes pressed together.

43. A wound care product, said wound care product comprising: Oxidized cellulose; Quaternary ammonium salts; Chelating agents, chelating salts, or combinations thereof; and Water-soluble polymers Wherein at least the quaternary ammonium salt, the chelating agent, the chelating agent salt, or a combination thereof, and the water-soluble polymer are in the form of a self-standing membrane or a self-standing membrane stack comprising a plurality of self-standing membranes pressed together.

44. The wound care article according to any one of claims 41 to 43, wherein the wound care article further comprises one or more of the following: Plasticizers, and Collagen.

45. The wound care article according to any one of claims 41 to 44, wherein at least a portion of the oxidized cellulose forms a discontinuous coating in contact with the surface of the self-supporting membrane or the self-supporting membrane stack.

46. ​​The wound care article according to any one of claims 41 to 45, wherein the self-standing membrane stack comprises 2 to 10 self-standing membranes pressed together. Each self-supporting membrane contains the water-soluble polymer. At least one self-supporting membrane contains the quaternary ammonium salt, and At least one self-supporting membrane contains the chelating agent, the chelating agent salt, or a combination thereof.

47. The wound care article according to any one of claims 41 to 46, wherein at least one self-supporting membrane comprises the oxidized cellulose.

48. The wound care article according to any one of claims 41 to 47, wherein the self-supporting membrane or self-supporting membrane stack is characterized by a thickness of about 3 mils to about 30 mils.

49. The wound care article according to any one of claims 41 to 48, wherein the oxidized cellulose is present in an amount of 5 gsm to 200 gsm.

50. The wound care product according to any one of claims 41 to 49, wherein the quaternary ammonium salt is present in an amount of 0.05 gsm to 1 gsm.

51. The wound care article according to any one of claims 41 to 50, wherein the water-soluble polymer is present in an amount of 100 gsm to 200 gsm.

52. The wound care product according to any one of claims 41 to 51, wherein the chelating agent, the chelating agent salt, or a combination thereof is present in an amount of 5 gsm to 40 gsm.

53. The wound care article according to any one of claims 41 to 52, wherein the wound care article further comprises a plasticizer present in an amount of 50 gsm to 150 gsm.

54. The wound care product according to any one of claims 51 to 53, wherein the wound care product further comprises collagen present in an amount of 1 gsm to 25 gsm.

55. A method for preparing a wound care product, the method comprising: Provide a wound care composition according to any one of claims 1 to 40; as well as The wound care composition is applied to a base to form a layer, and The layer is dried to form a single self-supporting film. The method may optionally further include: One or more additional self-supporting membranes are formed according to the previous steps, and The single self-supporting membrane and one or more additional self-supporting membranes are pressed together to form a self-supporting membrane stack.

56. A method for preparing a wound care article according to any one of claims 41 to 54, the method comprising: Provides oxidized cellulose; Quaternary ammonium salts; Chelating agents, chelating salts, or combinations thereof; And water-soluble polymers, The water-soluble polymer is mixed with one or more of the oxidized cellulose, the quaternary ammonium salt, and the chelating agent, the chelating agent salt, or combinations thereof to form a composition. The composition is used to coat the substrate to form a layer, and The layer is dried to form a single self-supporting film. The method may optionally further include: One or more additional self-supporting membranes are formed according to the previous steps, and The single self-supporting membrane and the one or more additional self-supporting membranes are pressed together to form a self-supporting membrane stack. The prerequisite is that the single self-standing membrane or the self-standing membrane stack comprises the quaternary ammonium salt and the chelating agent, the chelating agent salt, or a combination thereof, and The method further includes the following condition: when the single self-supporting membrane or the self-supporting stack excludes the oxidized cellulose: The oxidized cellulose is applied to the surface of the single self-supporting membrane or the surface of the self-supporting membrane stack.

57. The method of claim 56, wherein the quaternary ammonium salt, the chelating agent, the chelating agent salt or a combination thereof, the water-soluble polymer, and the oxidized cellulose are mixed to form the composition.

58. The method according to any one of claims 56 to 57, the method further comprising applying oxidized cellulose to the surface of the single self-supporting membrane or the surface of the self-supporting membrane stack.

59. The method according to any one of claims 56 to 58, wherein drying the layer comprises heating, depressurization, freeze drying, or a combination thereof.

60. The method according to any one of claims 56 to 59, the method further comprising: Provides a water-soluble base. The water-soluble substrate is coated with oxidized cellulose to form a water-soluble substrate having an oxidized cellulose coating thereon, and The water-soluble substrate having the oxidized cellulose coating is pressed onto the surface of the single self-standing membrane or the self-standing membrane stack.

61. A method for treating a wound, the method comprising: Bring the wound into contact with the wound care composition according to any one of claims 1 to 40.

62. A method for treating a wound, the method comprising: Bring the wound into contact with the wound care product according to any one of claims 41 to 54.

63. A kit, the kit comprising: The wound care composition according to any one of claims 1 to 40, and A set of instructions that guides the user to apply the wound care composition to the wound.

64. A kit comprising: The wound care composition according to any one of claims 1 to 40, and A set of instructions that guides the user in preparing the wound care product according to any one of claims 55 to 60.

65. A kit comprising: The wound care product according to any one of claims 41 to 54, and A set of instructions that guides the user to apply the wound care product to the wound.

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