Compositions and methods for wound care

Abstract

A wound dressing and method for making the same is provided, which includes an absorbable polyelectrolyte material and ionic crystals. The weight percentage of the ionic crystals in the polyelectrolyte material can be adjusted for the desired use of the wound dressing.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims priority and the benefit thereof to U.S. Provisional Patent Application No. 62 / 797,576, filed on January 28, 2019, which is incorporated herein by reference in its entirety.

Background Art

[0002] All references, patents, and patent applications cited herein are incorporated by reference in their entirety.

Summary of the Invention

Problems to be Solved by the Invention

[0003] Hemostats can be broadly classified into two types of hemorrhage control products: bioabsorbable hemostats and non - resorbable hemostats. Most of the soluble hemostats are based on oxidized cellulose - based structures (e.g., oxidized (regenerated) cellulose). A bioabsorbable cellulose - based hemostat composed of non - oxidized carboxymethyl cellulose (CMC) has been described for non - compressive use for hemorrhage control, but lacks control of specific end - product properties. See, for example, International Publication No. WO 2016 / 067266, International Publication No. WO 2016 / 067250, U.S. Patent Application Publication No. 2017 / 0335017, and U.S. Patent Application Publication No. 2016 / 0121019. What is needed are combination hemostatic products and methods for controlling the properties of the end - product by combining two or more components together.

Means for Solving the Problems

[0004] Aspects described herein provide hybrid wound care articles (e.g., hemostats) that include a bioabsorbable polyelectrolyte material embedded with ionic crystals (e.g., salts) and their clinical benefits.

[0005] In yet another aspect, generally and particularly in the clinical setting of hemorrhagic wounds, there is provided a hybrid wound care article comprising a bioabsorbable polyelectrolyte material embedded with an ionic crystal (e.g., a salt) that is utilized to control and vary the polymer component properties. Controllable properties include, for example, the hydrophilic / hydrophobic nature of the product, its interaction with the body, adhesiveness, percent absorbance, biodegradation rate, clotting strength, charge, and acidity.

[0006] A polyelectrolyte is a polymer whose repeating units contain electrolyte (ionic) groups. These groups dissociate in aqueous solution, charging the polymer.

[0007] In another aspect, the wound care article includes a non-oxidizing CMC / NaCl wick (referring to gauze, thin fabric, yarn, etc.) product. Further aspects described herein characterize the degree of substitution (DS) and salt level within the hybrid hemostat as a means to control the component ratio and, as a result, the overall behavior of the product and its use. BRIEF DESCRIPTION OF THE DRAWINGS

[0008]

Figure 1

Figure 2

[0009] Detailed Description I. Salt-Embedded WoundClot The aspects described herein provide an exemplary manufacturing process that utilizes a saturated solution (described in section IV below). In this aspect, a high constant concentration and, for example, the presence of inorganic salt precipitation during manufacture result in the production of a salt-embedded hemostat.

[0010] A further aspect describes, for example, a method of making a wound care article that uses three different salts: sodium monochloroacetate (ClCH2COONa) (CAANa) reactant, sodium glycolate (OHCH2COONa), and sodium chloride (NaCl) as by-products (Figure 1). [Reference 1]. Since the reaction occurs in an organic solvent, the NaCl inorganic salt retains its solid form in a crystalline shape with low solubility. The inorganic salt crystals are dispersed in the reaction medium and trapped by the porous structure of the treated fabric, while the organic salts are washed away by the organic medium.

[0011] Alternatively, one can produce a CMC substance according to conventional methods (an unsaturated solution with the formation of the lower organic salt CAANa), and intentionally add the required amount of salt onto the CMC product to embed the salt in the wound care article, and can provide specific properties as described herein.

[0012] In one aspect, the chemical structure of the salt is monovalent. Without being bound by theory, it is believed that salts with a higher electrovalent value may result in cross-linking and elimination of the bioabsorbable properties of the wound care article.

[0013] HPLC-LCMS analysis was used to determine the residual organic salts in the form of CAA derivatives in an exemplary hybrid hemostat. The hybrid hemostat product was found to contain, on average, 0.29 wt% residual CAA derivative. The CAA derivative is considered to have no significant effect at this concentration on the exemplary hybrid hemostat. II. Salts for Controlling Hemostatic Action Properties

[0014] The aspects provided herein utilize different amounts of salts to control the behavior properties of an exemplary bioabsorbable hybrid hemostat.

[0015] Although not bound by theory, the basic hemostat-body interaction is thought to be governed by the nature of polyelectrolyte-aqueous liquid physical interactions. It is a well-known physical principle that the more polar a molecule is, the more rapidly it dissolves in an aqueous environment. The polar nature of a polyelectrolyte is affected, for example, by: A) the amount of charge along the polymer chain B) the degree of ionic dissociation (ID) of those charges.

[0016] With respect to CMC, ionic groups can be defined by measuring the degree of substitution (DS) (e.g., by titration or Fourier-transform infrared spectroscopy (FTIR)) as each ionic group is added to the cellulose structure. The relevant range of DS for this CMC hemostat is, for example, between 0.6 - 1.4 and most often between 0.7 - 1.2.

[0017] The embodiments described herein can be directed to controlling the hemostat-body interaction based on the degree of ionic dissociation.

[0018] Several theories can explain the charge-solution interactions that give rise to the properties described herein. For example, the Poisson-Boltzmann equation can take many forms throughout various scientific fields. In biophysics and certain interfacial chemistry applications, it is simply known as the Poisson-Boltzmann equation. In electrochemistry, it is known as the Gouy-Chapman theory; in solution chemistry, it is known as the Debye-Huckel theory; and in colloid chemistry, it is also known as the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. All of these theories relate to how the existing charge interactions and their interactions with the environment are affected by the presence of other charges. Generally speaking, a higher concentration of the existing ions results in screening of a particular charge and a reduction of its potential interactions in the environment.

[0019] In one aspect, the embedded solid salt crystals within an exemplary dry CMC hemostat have an important role once the product is exposed to a liquid (blood / exudate). As the product begins to absorb the liquid, the monovalent crystals locally dissolve around the region in contact with the liquid and release free ions of the polyelectrolyte (also referred to as free ions) into the local surrounding region. The greater the amount of salt embedded in the CMC product, the higher the local concentration of free ions when exposed to the liquid. The even higher free ion concentration affects the dissociation ratio of the bound ion groups of the CMC with a decreasing number, and the polymer chains become even less charged.

[0020] Although not bound by theory, it is believed that the absorption rate of the polymer is decreased and the associated properties are modified. This effect can cause a temporary change in the behavior of the CMC hemostat due to the dynamic behavior of the overall system. When the chemical potential is evenly distributed across the polymer chains, the system returns to its standard behavior. The benefit of the temporary effect is that it occurs and can then dissipate back to the standard behavior within the time frame of treating a bleeding wound and stopping the blood flow. By increasing the amount of salt, one can enhance gel formation, which aids in effective hemorrhage control by slowing or stopping the blood flow from the wound through occlusion of the flow with the gelatinous form of the product, and slows the dissolution rate for the gelatinous form of the product. Therefore, severe bleeding can be treated with ease while the bioabsorbable properties of the CMC product are preserved for later treatment processes.

[0021] The aspects described herein provide a wound dressing comprising an absorbent polyelectrolyte material and an ionic crystal, wherein the weight percent of the ionic crystal in the absorbent polyelectrolyte material is at least about 5% w / w of the total weight.

[0022] The term "wound dressing" (also referred to as a wound dressing material, wound covering material, etc.) refers to a device, material, or substance that is applied to or adapted to be associated with an internal or external body wound or injury to assist in treating or improving the wound or injury and is typically sterilized prior to use. A wound dressing can include a support structure and other active or inert ingredients to assist in treating or improving the wound or injury.

[0023] The term "polyelectrolyte" refers to a polymer with repeating units having an electrolyte group.

[0024] In another aspect, ionic crystals (e.g., NaCl, NaBr, NaI, NaF, KCl, KBr, KI, and KF) are embedded in the absorbent polyelectrolyte material. In a further aspect, the weight percentage of the ionic crystal is about 20 to 70% w / w of the total weight. The ionic crystal can be, for example, a divalent or trivalent salt crystal.

[0025] The polyelectrolyte material can be bioabsorbable (e.g., non-oxidized carboxymethyl cellulose). In this aspect, the degree of substitution of non-oxidized carboxymethyl cellulose is about 0.3 - 1.8 or can be about 0.75 - 1.2.

[0026] In this aspect, the degree of polymerization of non-oxidized carboxymethyl cellulose is about 20 - 3500 or can be about 100 - 1500.

[0027] In another aspect, the polyelectrolyte material is selected from the group consisting of bioresorbable, biodegradable, and bioabsorbable polyelectrolyte materials. In yet another aspect, the polyelectrolyte material is selected from the group consisting of non-oxidized polysaccharides, oxidized polysaccharides, regenerated polysaccharides, non-regenerated polysaccharides, bleached polysaccharides, unbleached polysaccharides, mercerized polysaccharides, non-mercerized polysaccharides, scoured polysaccharides, natural polysaccharides, or combinations thereof.

[0028] In a further aspect, the polyelectrolyte material contains a polyelectrolyte ionic group selected from the group consisting of monovalent cations, monovalent anions, divalent cations, divalent anions, trivalent cations, and trivalent anions. In another aspect, the polyelectrolyte material can contain one or more polyelectrolyte ionic groups selected from the group consisting of monovalent cations, monovalent anions, divalent cations, divalent anions, trivalent cations, and trivalent anions.

[0029] In yet another aspect, the ionic crystal includes an ionic group selected from the group consisting of monovalent cations, monovalent anions, divalent cations, divalent anions, trivalent cations, and trivalent anions.

[0030] In one aspect, the valence of the polyelectrolyte ionic group and the ionic crystal is the same. In another aspect, the valence is selected from the group consisting of 1, 2, and 3.

[0031] The wound care article can be formed from a material selected from the group consisting of powder (also referred to as powder), film, fabric (also referred to as woven, knitted, cloth, fabric, etc.), foam (such as foam material, foam), thread, fibrous material (such as fiber), coating (such as film), solution, gel, or a combination thereof. The wound care article can be in the form of a hemostat (such as a hemostat, hemostatic agent, hemostatic forceps, etc.) or a bandage (such as a bandage, dressing, bandage, bandage, etc.). In another aspect, the fabric can be selected from the group consisting of woven, non-woven, and knitted fabrics.

[0032] In yet another aspect, the wound care article further comprises an active ingredient (also referred to as an active component) (e.g., an antibiotic (also sometimes referred to as an antibacterial agent), an antimicrobial (also sometimes referred to as an antibacterial agent), an analgesic (also sometimes referred to as an analgesic drug), a clotting agent, a steroid, a wound healing agent, a cooling agent, and an electric potential agent). The antibiotic can be selected from the group consisting of cefazolin, erythromycin, and cefoxitin. The antimicrobial can be selected from the group consisting of disinfectants and anti-microbial peptides (also referred to as antibacterial peptides). The analgesic can be selected from the group consisting of acetaminophen, ibuprofen, naproxen, celecoxib, rofecoxib, etoricoxib, codeine, oxycodone, hydrocodone, dihydromorphine, pethidine, tramadol, buprenorphine, alcohol, and cannabis. The steroid can be selected from the group consisting of androgens, anabolic steroids (also referred to as anabolic steroids, protein anabolic steroids), anti-androgens, estrogens, progestogens, corticosteroids, and neurosteroids. The wound healing agent can be selected from the group consisting of silver sulphadiazene, silver nitrate, povidone iodine (also referred to as povidone iodine), chlorohexidine, and polyhexamethylene biguanide.

[0033] In another aspect, the absorption percentage of the wound care article is from about 2000 to about 4000 percent over about 24 hours. III. Method for manufacturing a wound care article

[0034] The embodiments described herein provide a method of making a wound dressing article, including treating cellulose with an alkaline solution; mixing the alkaline solution with a chloroacetic acid (CAA) solution to form a saturated sodium chloroacetate (NaCAA) solution, wherein ionic crystals are formed in the NaCAA solution; and treating the cellulose with the NaCAA solution to form carboxymethyl cellulose (CMC) having embedded ionic crystals, wherein the weight percentage of ionic crystals in the absorbent polyelectrolyte material is at least about 5% w / w of the total weight. In this embodiment, the CMC can be washed with ethanol. In another embodiment, the CMC can be neutralized with an acid.

[0035] In another embodiment, the weight percentage of ionic crystals is about 20 to 70% w / w of the total weight.

[0036] In a further embodiment, the polyelectrolyte material is non-oxidized carboxymethyl cellulose. In yet another embodiment, the degree of substitution of the non-oxidized carboxymethyl cellulose is about 0.3 - 1.8. The degree of substitution of the non-oxidized carboxymethyl cellulose can be about 0.75 - 1.2. In a further embodiment, the degree of polymerization of the non-oxidized carboxymethyl cellulose is about 20 - 3500 or 100 - 1500.

[0037] In another embodiment, the alkaline solution includes sodium hydroxide and a solvent. The solvent can be selected from the group consisting of H2O and ethanol. In another embodiment, the CAA solution can include CAA and a solvent. The solvent can be selected from the group consisting of H2O, ethanol, and others.

[0038] In one embodiment, mixing the alkaline solution with a chloroacetic acid (CAA) solution is performed at around 50°C.

[0039] In another embodiment, the cellulose is treated with a NaCAA solution at about 50 to about 60 °C for about 12 to 14 hours.

[0040] To produce a wound care article, it involves associating an absorbent polyelectrolyte material with an ionic crystal, and provided is a method in which the weight percentage of the ionic crystal bound to the absorbent polyelectrolyte material is at least about 5% w / w of the total weight.

[0041] In this embodiment, the ionic salt crystals are substantially associated with the absorbent polyelectrolyte material. The term "substantially associated" means that at least about 50%, 60%, 70%, 80%, or 90% of the salt crystals are in the vicinity of the absorbent polyelectrolyte material or are physically or chemically connected to the absorbent polyelectrolyte material (e.g., by mechanical force, coating, impregnating, deposition, or embedding).

[0042] In another embodiment, the weight percentage of the ionic crystal is about 20 to 70% w / w of the total weight. In a further embodiment, the ionic crystal is selected from the group consisting of NaCl, NaBr, NaI, NaF, KCl, KBr, KI, and KF. The ionic crystal can be selected from divalent or trivalent salt crystals.

[0043] In another embodiment, the polyelectrolyte material is non-oxidized carboxymethyl cellulose. The degree of substitution of the non-oxidized carboxymethyl cellulose can be about 0.3 - 1.8 or 0.75 - 1.2.

[0044] In another embodiment, the degree of polymerization of the non-oxidized carboxymethyl cellulose is about 20 - 3500 or 100 - 1500.

[0045] The polyelectrolyte substance can be selected from the group consisting of bioreadsorbability, biodegradability, and biocompatibility. The polyelectrolyte substance can be selected from the group consisting of non-oxidized polysaccharides, oxidized polysaccharides, regenerated polysaccharides, non-regenerated polysaccharides, decolorized polysaccharides, non-decolorized polysaccharides, mercerized polysaccharides, non-mercerized polysaccharides, refined polysaccharides, natural polysaccharides, or combinations thereof.

[0046] The polyelectrolyte substance can contain a polyelectrolyte ion group selected from the group consisting of monovalent cations, monovalent anions, divalent cations, divalent anions, trivalent cations, and trivalent anions.

[0047] In another aspect, the ionic crystal can contain an ion group selected from the group consisting of monovalent cations, monovalent anions, divalent cations, divalent anions, trivalent cations, and trivalent anions.

[0048] The valences of the polyelectrolyte ion group and the ionic crystal can be the same. The valence can be selected from the group consisting of 1, 2, and 3.

[0049] In another aspect, the wound dressing can be formed from a material selected from the group consisting of powders, films, foams, fabrics, threads, fibrous materials, coatings, solutions, gels, or combinations thereof.

[0050] The wound dressing can be in the form of a hemostat or a bandage. The fabric can be selected from the group consisting of woven, non-woven, and knitted fabrics.

[0051] In this aspect, the wound dressing can further contain active ingredients (e.g., antibiotics, antimicrobial agents, analgesics, coagulants, steroids, wound healing agents, coolants, and potentiating agents).

[0052] The embodiments described herein provide a method for increasing the hydrophilicity of the wound dressings described herein by reducing the weight percentage of the ionic crystal in the absorbent polyelectrolyte substance to approximately 5% w / w of the total weight.

[0053] A further aspect provides a method of increasing the absorption of body fluids by the wound care articles described herein by reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte material to approximately 5% w / w of the total weight.

[0054] Yet a further aspect provides a method of increasing the gel stability of the wound care articles described herein by increasing the weight percentage of ionic crystals in the absorbent polyelectrolyte material to about 90% w / w of the total weight.

[0055] A further aspect provides a method of increasing the topographic adjustment potential of the wound care articles described herein by reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte material to approximately 5% w / w of the total weight.

[0056] The aspects described herein provide a method of increasing the adhesion of the wound care articles described herein to a wound by reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte material to approximately 5% w / w of the total weight.

[0057] The aspects described herein provide a method of increasing the clot activation time (sometimes referred to as coagulation activation time) for a wound covered by the wound care articles described herein by increasing the weight percentage of ionic crystals in the absorbent polyelectrolyte material to about 90% w / w of the total weight.

[0058] The aspects described herein provide a method of reducing swelling associated with a wound covered by the wound care articles described herein by reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte material to approximately 5% w / w of the total weight. IV. Results and Discussion

[0059] To evaluate the influence of salt concentration in the local ambient region near the polyelectrolyte material, exemplary laboratory experiments were conducted.

[0060] Figure 2 shows the influence of NaCl concentration on water adsorption by the product, where a higher salt concentration reduces the adsorption capacity of the sample. The influence of the salt was evaluated by two methods - (1) measuring the amount of salt in the embedded product (reduced by sonication), and (2) measuring the median salt concentration to which the product was exposed.

[0061] According to Figure 2, the non-sonicated samples with a higher salt concentration gave a lower water absorption profile. The decrease in water absorption could be compared to samples absorbed from saline solutions containing 0.9 wt% and 2 wt% NaCl. These results indicate that a higher salt concentration in the sample or in the absorption solution reduces the water adsorption capacity of the product.

[0062] Free chloride tests performed on the dissolved samples before and after sonication showed that the CMC / NaCl product was composed of NaCl crystals in two forms within the thin end, namely, a 5 - 15 wt% cover layer that could be washed away by sonication and a 5 - 50 wt% internal embedded layer that could dissolve during thin end dissolution. The NaCl content in the product affects and controls the properties of the product when applied for wound healing purposes and applications.

[0063] When a polyelectrolyte chain is immersed in an aqueous solution of an electrolyte, the electrostatic field around the chain increases the local concentration of diffusible counterions and decreases one of the co-ions. The difference between the two concentrations is maximum at the chain surface and decreases quasi-exponentially to zero in the bulk.

[0064] The distribution of the local concentration of free ions can be determined by the ratio between electrostatic and thermal energies. In this regime, when this ratio increases beyond a critical value, a fraction of the counterions are electrostatically adsorbed onto the chain, forming temporary ion pairs with the polymer charges. This phenomenon is known as counterion condensation. [Reference 2]

[0065] This behavior typically demonstrates the Debye-Hückel theory of the non-ideality of electrolyte solutions. [Reference 3]. According to the Debye-Hückel theory, non-ideality mainly arises from ions of opposite charges attracting each other, while ions of the same charge repel each other due to electrostatic forces. As a result, an electrical double layer (EDL) is created near the sample surface and has an important influence on its water absorption capacity: a higher ionic (salt) concentration in the absorbed solution shields the CMC hydrophilic properties, and decreases the water absorption rate and dissolution rate of the product, and is also manifested in a stronger gel.

[0066] In this example, the concentration of chloride ions (Cl - ) has the greatest influence on the clot structure. Under physiological conditions, the presence of Cl - can promote aggregation by affecting the thickness of fibrin (fibrous) fibers during the coagulation process. Chloride varies the dissociation rate of certain side chains of the protein chains, and reacts and varies their tendency to clump together. Therefore, manipulating the salt around a wound can significantly vary the structure, thickness, and strength of the clot. [Reference 4].

[0067] By controlling NaCl in the product, the product can be modified for specific application targets. For example, higher NaCl leveled products can maintain lower absorbance rates and can extend the biodegradation process. This property can be applied to severe bleeding injuries where harder and more stable products are required. The gradual dissociation of ions provides a long activation time for Hageman factors and promotes the natural coagulation cascade. Lower NaCl leveled products can be used for high absorption rates with short-term stability. V. Exemplary Manufacturing Process for Salt-Impregnated CMC

[0068] Tank 1: Reaction vessel Tank 2: Mixing vessel (for solution preparation)

[0069] Roll the fabric gauze and place it in Tank 1. The fabric gauze can also be placed by any suitable method (e.g., folded, stepwise arranged). The gauze is a cellulose raw material modified by a chemical reaction. The same reaction can also be used for other carbohydrate substrates (e.g., starch or chitin) that can undergo an etherification reaction to form carboxy-methyl substituents on the substrate.

[0070] In Tank 2, mix an alkali solution (NaOH (aq) ) in an ethanol solvent for 30 minutes.

[0071] Transfer the content of Tank 2 together with the fabric to Tank 1 and mix for 4 hours to form alkali cellulose (i.e., the activation step to subject cellulose crystals to the reaction stage).

[0072] In the mixing vessel (Tank 2), mix chloroacetic acid (CAA) with water and ethanol to produce a homogeneous CAA solution.

[0073] The medium (a mixture of a solvent and an alkali solution) from tank 1 is gradually transferred to tank 2 under stirring conditions. The mixing between CAA and the alkali substance (NaOH) results in the conversion of CAA to its salt form, sodium chloroacetate - NaCAA. Since NaCAA has limited solubility in the medium (i.e., a mixture of ethanol and water from the alkali solution), NaCAA dissolves up to its maximum capacity, the medium becomes saturated, and the remaining formed salt of NaCAA becomes solid as a precipitate in the medium. This stage is exothermic and is maintained at 50°C.

[0074] Once a saturated solution of NaCAA is formed in tank 2, all the substances (medium + precipitate) are transferred to tank 1 - to alkali cellulose. In this reaction (etherification) stage, NaCAA molecules chemically bond to the cellulose substrate and form carboxymethyl cellulose (CMC). For each substitution (i.e., the bonding of one NaCAA molecule to cellulose), one NaCl molecule is formed. In this manner, the solubility of NaCl in the medium is very limited (e.g., the solubility of NaCl in ethanol is 0.65 / kg), so the salts are formed as solid crystals and they are trapped between the fabric fibers. The reaction can be maintained at 50 - 60°C for 12 - 14 hours.

[0075] Regarding the reaction, the medium is rinsed with ethanol to remove the alkali residue and neutralized with an HCl solution for 12 hours at the ambient temperature. In this manner, the neutralization reaction can be NaOH + HCl ⇒ NaCl + H2O, and as a result, additional NaCl is provided during the neutralization of CMC.

[0076] Once the fabric is neutralized, the ethanol is transferred to waste, and the fabric is transferred to the drying stage outside the reactor (e.g., evaporating the ethanol with air).

[0077] The product is then cut, folded, packaged, and sterilized.

[0078] The aspects described herein are disclosed with reference to certain embodiments, but many modifications, alterations, and variations to the described embodiments are possible without departing from the field and scope of the invention as defined in the appended claims. Accordingly, the invention is not intended to be limited to the described embodiments, but rather it is intended to have the full scope defined by the language of the following claims. References

[0079] 1. Saputra et al., Int. J. Chem. Eng. Appl., 2014, 5(1), 36 - 40. 2. A - M. Zhivkov (2013). Electric Properties of Carboxymethyl Cellulose, Cellulose - Fundamental Aspects, Dr. Theo G. M. Van De Ven (Ed.). 3. P. Debye and E. Huckel, Physikalische Zeitschrift., 1923, 24, 185 - 206. 4. Di Stasio et al., Biophysical J., 1998, 75, 1973 - 1979.

Claims

1. An absorbent polyelectrolyte material and an ionic crystal are included, and the weight percentage of the ionic crystal in the absorbent polyelectrolyte material is at least 5% w / w of the total weight. The ionic crystal is embedded in the absorbent polyelectrolyte material. The ionic crystal is selected from the group consisting of NaCl and KCl. The polyelectrolyte material is non-oxidized carboxymethyl cellulose, a wound dressing article.

2. The weight percentage of the ionic crystal is 20 to 70% w / w of the total weight. The wound dressing article according to Claim 1.

3. The polyelectrolyte material is biocompatible. The wound dressing article according to Claim 1.

4. The degree of substitution of the non-oxidized carboxymethyl cellulose is 0.3 - 1.

8. The wound dressing article according to Claim 1.

5. The degree of substitution of the non-oxidized carboxymethyl cellulose is 0.75 - 1.

2. The wound dressing article according to Claim 4.

6. The degree of polymerization of the non-oxidized carboxymethyl cellulose is 20 - 3500. The wound dressing article according to Claim 1.

7. The degree of polymerization of the non-oxidized carboxymethyl cellulose is 100 - 1500. The wound dressing article according to Claim 6.

8. The polyelectrolyte material includes a polyelectrolyte ionic group selected from the group consisting of monovalent cations, monovalent anions, divalent cations, divalent anions, trivalent cations, and trivalent anions. The wound dressing article according to Claim 1.

9. The ionic crystal includes an ionic group selected from the group consisting of monovalent cations and monovalent anions. The wound dressing article according to Claim 1.

10. The valences of the polyelectrolyte ionic group and the ionic crystal are the same. The wound dressing article according to Claim 8 or 11.

11. The valence is 1. The wound dressing article according to Claim 10.

12. The wound dressing article is formed from a material selected from the group consisting of powders, films, fabrics, foams, threads, fibrous materials, coatings, solutions, gels, or combinations thereof. The wound dressing article according to Claim 1.

13. The ionic crystal is trapped in the fabric. The wound dressing article according to Claim 12.

14. The wound dressing article is in the form of a hemostat or a bandage. The wound dressing article according to Claim 12.

15. The wound dressing article according to claim 12, wherein the fabric is selected from the group consisting of woven, non-woven, and knitted fabrics.

16. The wound dressing article according to claim 1, further comprising an active ingredient.

17. The wound dressing article according to claim 16, wherein the active ingredient is selected from the group consisting of antibiotics, antimicrobial agents, analgesics, coagulants, steroids, wound healing agents, cooling agents, and potentiating agents.

18. The wound dressing article according to claim 17, wherein the antibiotic is selected from the group consisting of cefazolin, erythromycin, and cefoxitin.

19. The wound dressing article according to claim 17, wherein the antimicrobial agent is selected from the group consisting of disinfectants and antimicrobial peptides.

20. The wound dressing article according to claim 17, wherein the analgesic is selected from the group consisting of acetaminophen, ibuprofen, naproxen, celecoxib, rofecoxib, etoricoxib, codeine, oxycodone, hydrocodone, dihydromorphine, pethidine, tramadol, buprenorphine, alcohol, and cannabis.

21. The wound dressing article according to claim 17, wherein the steroid is selected from the group consisting of androgens, anabolic steroids, antiandrogens, estrogens, progestogens, corticosteroids, and neurosteroids.

22. The wound dressing article according to claim 17, wherein the wound healing agent is selected from the group consisting of silver sulfadiazine, silver nitrate, povidone iodine, chlorhexidine, and polyhexamethylene biguanide.

23. The wound dressing article according to claim 1, wherein the absorption percentage of the wound dressing article is from 2000 to 4000 percent over 24 hours.

24. A method for producing the wound dressing article according to any one of claims 1 to 23, treating cellulose with an alkaline solution; mixing the alkaline solution with a chloroacetic acid (CAA) solution to form a saturated sodium chloroacetate (NaCAA) solution, wherein ionic crystals are formed in the NaCAA solution; and treating the cellulose with the NaCAA solution to form non-oxidized carboxymethyl cellulose (CMC) having embedded ionic crystals comprising the method.

25. The method according to claim 24, further comprising washing the CMC with ethanol.

26. The method according to claim 25, further comprising neutralizing the CMC with an acid. **Claim 27** The method according to claim 24, wherein the alkaline solution contains sodium hydroxide and a solvent. **Claim 28** The solvent is selected from the group consisting of H ２ O and ethanol, the method according to claim 27. **Claim 29** The method according to claim 24, wherein the CAA solution contains CAA and a solvent. **Claim 30** The solvent is selected from the group consisting of H ２ O and ethanol, the method according to claim 29. **Claim 31** The method according to claim 24, wherein mixing the alkaline solution with the chloroacetic acid (CAA) solution is carried out at around 50°C. **Claim 32** The method according to claim 24, wherein the cellulose is treated with the NaCAA solution at 50 to 60°C for 12 to 14 hours. **Claim 33** A method for increasing the water affinity of the wound dressing article according to claim 1, comprising reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte substance so as not to be lower than 5% w / w of the total weight. **Claim 34** A method for increasing the absorption of body fluids by the wound dressing article according to claim 1, comprising reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte substance to approximately 5% w / w of the total weight. **Claim 35** A method for increasing the gel stability of the wound dressing article according to claim 1, comprising increasing the weight percentage of ionic crystals in the absorbent polyelectrolyte substance to approximately 90% w / w of the total weight of the ionic crystals contained in the wound dressing article. **Claim 36** A method for increasing the topographic adjustment potential of the wound dressing article according to claim 1, comprising reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte substance to approximately 5% w / w of the total weight. **Claim 37** A method for increasing the adhesion to the wound of the wound dressing article according to claim 1, comprising reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte substance to approximately 5% w / w of the total weight. **Claim 38** A method for increasing the coagulation activation time for a wound covered by the wound dressing article according to claim 1, comprising increasing the weight percentage of ionic crystals in the absorbent polyelectrolyte substance to approximately 90% w / w of the total weight of the ionic crystals contained in the wound dressing article. **Claim 39** A method of reducing an increase related to a wound covered by the wound dressing article according to claim 1, the method comprising reducing the weight percentage of ionic crystals in the absorbent polyelectrolyte material to approximately 5% w / w of the total weight.

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