Antibacterial gel composition

Abstract

Provided are antimicrobial compositions for wound management and methods of producing the antimicrobial compositions, comprising sodium hypochlorite (NaOCl) in an amount ranging from 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount ranging from 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount ranging from 1 to 10% by weight, sodium chloride (NaCl) in an amount ranging from 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and the composition has a pH in the range of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of 0.15 or less.

Description

[Technical Field]

[0001] The present invention relates to antimicrobial compositions, methods for producing said antimicrobial compositions, and valve system devices, as well as methods for wound management comprising said antimicrobial compositions. [Background technology]

[0002] In general, wounds are a hidden epidemic among populations worldwide, with significant social and economic consequences that impair the quality of life of millions of people. While acute wound management in healthy patients is relatively manageable, assessing and maintaining patients with chronic wounds can be difficult. Although the incidence of chronic wounds is increasing, existing standard therapeutic solutions cannot meet the treatment criteria. Although bandages and gauze are useful for reducing bleeding, they have several drawbacks. They are not biodegradable, prone to infection, and not suitable for wounds with uneven shapes. They have the potential to cause secondary tissue destruction and are not effective for wound healing.

[0003] Antibiotic resistance and weak immune responses create challenges in treating chronic infections. This has led to extensive research on the topic of wound healing and wound management devices. Existing research has recognized the important role played by hydrogels in wound healing. The supply of moisture to the wound allows for painless debridement of necrotic and infected tissue, as well as granulation and complete healing. However, given the high water content of current hydrogels, they are not completely absorbent, and therefore, current hydrogels are best suited for wounds with mild to moderate exudation. Consistent with this, there is a need for antibacterial properties to combat infection and aid in the wound healing process. Therefore, in light of the above discussion, there is a need to overcome the aforementioned shortcomings associated with currently available antibacterial hydrogels.

[0004] U.S. Patent Application No. 20200138953(A1) discloses a stabilized hypohalous acid solution, particularly a stabilized solution or formulation comprising hypobromous acid and a stabilizing amount of dissolved inorganic carbon in the form of an alkaline earth metal bicarbonate or carbonate.

[0005] U.S. Patent Application No. 20200138953(A1) discloses a bag-on-valve canister containing a hypochlorous acid solution and a chlorine stabilizer suitable for use in sanitizing food processing surfaces and disinfecting medical equipment in hospitals.

[0006] CN113069413(A) discloses a hypochlorous acid gel that aids in electron beam sterilization. The hypochlorous acid gel is prepared from the following parts by weight of raw materials: 50-70 parts gel matrix, 27.4-49.979 parts phosphate buffer solution, 0.001-0.6 parts hypochlorous acid, and 0.02-2 parts sodium hypochlorite, where the phosphate buffer solution is prepared from boric acid, potassium dihydrogen phosphate, sodium chloride, and purified water. The hypochlorous acid gel has a neutral pH and is said to be non-irritating to the wound surface. Preferably, the pH of the hypochlorous acid gel is 5.5-8.0. The only example has a pH of 6.8. The gel matrix powder is preferably one or more of magnesium lithium silicate, magnesium aluminum silicate, and magnesium sodium fluorosilicate. It should be noted that a phosphate buffer solution is required, and therefore the gel has a certain buffering capacity β with respect to the pH value, which is quite high. The buffering capacity of the formulation in the example of CN113069413 was calculated by the inventors to be β = 0.189 ≒ 0.19 ≒ 0.2. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] U.S. Patent Application No. 20200138953(A1) [Patent Document 2] CN113069413(A) [Non-patent literature]

[0008] [Non-Patent Document 1] Shinya Ugawa, J. Clin. Invest. 110:1185-1190 (2002). doi:10.1172 / JCI200215709 Summary of the Invention [Problem to be solved by the invention]

[0009] In the case of prior art compositions containing sodium hypochlorite and hypochlorous acid, the shelf life has often been found to be unsatisfactory for convenient use.

[0010] Furthermore, it would be desirable to improve wound treatment by providing additional delivery forms of antimicrobial agents.

[0011] A problem in the art is that antibacterial compositions are irritating to the skin. For hypochlorite and hypochlorous acid, the optimum pH value for antibacterial effect is an acidic pH, such as pH 3 to 7. Acidic pH is also more irritating to the skin, which may cause an unpleasant sensation to the user.

[0012] One of the aims of the present invention is to provide an improved antibacterial composition in gel form that avoids at least some of the drawbacks of the prior art. [Means for solving the problem]

[0013] In a first aspect, there is provided an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount ranging from 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount ranging from 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount ranging from 1 to 10% by weight, sodium chloride (NaCl) in an amount ranging from 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0.

[0014] In a second aspect, there is provided a method (400) for producing an antimicrobial composition, the method comprising: a) i. purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured in accordance with ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured in accordance with ISO 3696:1987; ii. Synthetic silicate clay-based thickeners; iii. Sodium hypochlorite solution, and iv. Sodium chloride preparing a b) mixing the purified water, the synthetic silicate clay-based thickener, the sodium hypochlorite solution, and the sodium chloride to obtain the antimicrobial composition. Including, A method is provided wherein the composition has a pH in the interval of 7.5 to 10.0.

[0015] In a third aspect, there is provided a valve system device for wound management comprising a bag-on-valve (BoV) within a pressurized storage canister and an antimicrobial composition for wound management contained in the bag, the antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount in the range of 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount in the range of 0.003 to 0.03% by weight, a synthetic silicate clay-based thickener in an amount in the range of 1 to 10% by weight, sodium chloride (NaCl) in an amount in the range of 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of 0.15 or less.

[0016] In a fourth aspect, there is provided a method of producing a valve system device for wound management, comprising: a) placing a bag-on-valve (BoV) inside a storage canister; b) crimping the BoV into the storage canister and then filling the storage canister with a propellant gas to obtain a pressurized storage vessel; and c) filling the bag of the BoV with the antimicrobial composition through the valve of the BoV; A method is provided, comprising:

[0017] In a fifth aspect, there is provided a method of delivering an antimicrobial composition to a wound, the method comprising the step of applying the antimicrobial composition to the wound, the antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount in the range of 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount in the range of 0.003 to 0.03% by weight, a synthetic silicate clay-based thickener in an amount in the range of 1 to 10% by weight, sodium chloride (NaCl) in an amount in the range of 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of less than or equal to 0.15.

[0018] In a sixth aspect, there is provided a method of treating a wound comprising applying to the wound an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount in the range of 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount in the range of 0.002 to 0.1% by weight, a synthetic silicate clay based thickener in an amount in the range of 1 to 10% by weight, sodium chloride (NaCl) in an amount in the range of 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of less than or equal to 0.15.

[0019] In a seventh aspect, there is provided a composition for the prevention or treatment of infection in a wound, comprising sodium hypochlorite (NaOCl) in an amount in the range of 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount in the range of 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount in the range of 1 to 10% by weight, sodium chloride (NaCl) in an amount in the range of 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of more than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of less than or equal to 0.15.

[0020] Further embodiments of the invention are defined in the accompanying independent claims.

[0021] These and other aspects of the embodiments herein will be better appreciated and understood in view of the description and the accompanying drawings. It should be understood, however, that the following description, while indicating certain specific embodiments and numerous specific details thereof, is given by way of illustration and not by way of limitation. Many changes and modifications may be made within the scope of the embodiments herein without departing from the spirit thereof, and the embodiments herein include all such modifications.

[0022] The advantage of the present invention is that pain sensation to the skin can be suppressed while, when needed, the local antibacterial effect in open wounds is enhanced. This is due to the low buffering capacity. The pH is slightly higher than neutral, i.e., above pH 7.5, which reduces skin irritation. In wounds, the pH is usually lower than 7.5, and due to the low buffering capacity of the antibacterial gel, the pH of the antibacterial gel will be lower than 7.5 when mixed with the fluid in the wound. Because the pH is lower, the antibacterial effect will therefore be higher locally in the wound. Therefore, the enhanced antibacterial effect is seen where it is needed, i.e., in the wound. At the same time, the skin is not irritated by the low pH.

[0023] It is an advantage of the present invention that the antimicrobial composition is provided in gel form, which allows for additional treatment methods compared to aqueous solutions that are not in gel form. The gel can, for example, be applied to a skin wound and remain on the skin at a certain thickness while remaining moist for a period of time, so that the gel can exert its antimicrobial effect for an extended period of time.

[0024] The greatly improved shelf life is an advantage over many other compositions containing sodium hypochlorite and hypochlorous acid, particularly in gel form, which suffer from the short shelf life of many similar prior art compositions.

[0025] Other objects, features and advantages of the present invention will become apparent from the following description when read in conjunction with the accompanying drawings, in which like reference numerals indicate corresponding parts throughout the several views. [Brief explanation of the drawings]

[0026] [Figure 1] 1 illustrates a table illustrating the composition of each component of the antimicrobial composition of the present technology, according to an embodiment. The composition of the active ingredients is determined by iodometric titration according to ISO 7393-3:1990(E) Water quality - Determination of free and total chlorine - Part 3: Iodometric method for the determination of total chlorine. [Figure 2]Illustrates test results for a preservative test according to the USP, Preservative Effectiveness Test, with an exemplary scenario. The method of USP 41NF36, Chapter 51 is cited for conducting the antimicrobial effectiveness challenge test. [Figure 3] 1 illustrates the biocompatibility test results of the antimicrobial composition of the present technology according to ISO 10993, Biological Evaluation of Medical Devices for In Vivo and In Vitro Studies, according to an exemplary scenario. Biocompatibility tests were performed, including cytotoxicity, sensitization, endothelial reactivity, acute systemic toxicity, and substance-mediated fever tests. [Figure 4] FIG. 1 is a flow diagram illustrating steps involved in a method of producing an antimicrobial composition of the present technology, according to an embodiment. [Figure 5] An example process for packaging the antimicrobial composition of the present invention in a valve system device with a BoV is provided. DETAILED DESCRIPTION OF THE INVENTION

[0027] Before the present invention is disclosed and described in detail, it is to be understood that the invention is not limited to the particular configurations, process steps, and materials disclosed herein, as such configurations, process steps, and materials may vary somewhat. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims and equivalents thereof.

[0028] It must be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0029] The following terms are used throughout the description and claims.

[0030] "Antimicrobial," as used herein, refers to the property of inhibiting or eliminating microbial growth, including but not limited to bacterial growth.

[0031] Buffer capacity, as used herein, is a quantitative measure of the resistance of a solution containing a buffering agent to changes in pH in response to changes in acid or alkali concentration. Buffer capacity is defined as:

[0032]

number

[0033] where d(C) is the infinitesimal amount of added base or added acid, and d(pH) is the infinitesimal change in pH.

[0034] Buffering capacity depends on pH. For weak acids, the buffering capacity is pH = pK a The height of this peak is determined by the pK a The buffering capacity is negligible when the concentration of the buffering agent [HA] is very small and increases as the concentration of the buffering agent increases.

[0035] The buffering capacity β of the gel should be less than 0.15. Buffering capacity is measured at pH 8.0. A lower buffering capacity is generally better, since an open wound containing fluid and having a lower pH than the gel's pH will have a lower pH. This, in turn, results in more pronounced antibacterial activity. Therefore, a lower buffering capacity is generally better than a higher buffering capacity. The upper limit of buffering capacity β=0.15 should be recognized as an upper limit, and therefore lower buffering capacities are even better. Thus, in various embodiments, the buffering capacity can be less than β=0.15, 0.14, 0.13, 0.12, 0.11, 0.10, 0.090, 0.080, 0.070, 0.060, 0.050, 0.040, 0.030, 0.020, and 0.010. Buffering capacity is measured at pH 8.0. In one embodiment, the upper limit of the buffer capacity is such that, i.e., the buffer capacity consists of the ingredients according to claim 1 without the addition of a buffer. In an alternative embodiment, the buffer capacity limit is replaced by a limit without the addition of a buffer in addition to the ingredients according to claim 1.

[0036] The buffering capacity of 0.15 or less is lower than the buffering capacity of CN113069413, which is about 0.19. This allows the pH of the gel to change more in the wound, resulting in a higher pH, similar to wounds that typically have a pH below 7.5. At lower pH, the composition is more antimicrobial.

[0037] The following table considers the buffering capacity of CN113069413 and the contents of the formulation. In the case of the gel, the contents are given in terms of minimum and maximum amounts of the ingredients.

[0038] [Table 1]

[0039] Using the Henderson-Hasselbalch equation, the above values ​​were redefined / theoretically calculated using the following formula: pH = pKa + Log(A) / (HA)

[0040] [Table 2]

[0041] The buffering capacity of CN113069413 is calculated using the boric acid molarity as follows:

[0042] [Table 3]

[0043] It can clearly be seen that the buffering capacity of the present gel must be significantly lower than that of CN113069413, since CN113069413 contains a phosphate buffer which the present gel does not.

[0044] Based on the above calculations, the buffer capacity of DI is estimated to be 0.189.

[0045] In the following detailed description, numerous specific details are set forth to provide a thorough understanding of the present invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and / or components have not been described in detail so as not to obscure the present invention.

[0046] In a first aspect, there is provided an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount ranging from 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount ranging from 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount ranging from 1 to 10% by weight, sodium chloride (NaCl) in an amount ranging from 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity measured at pH 8.0 of 0.15 or less.

[0047] One advantage of the present invention is that the composition improves moisture inside the wound, making it effective in assisting the debridement and de-sloughing process in dry, necrotic wounds. The composition is intended for moistening and debridement of acute and chronic wounds, such as stage I-IV ulcers, venous stasis and diabetic ulcerations, post-surgical wounds, first- and second-degree burns, and bedsores. The antimicrobial composition of the present technology helps maintain a moist wound environment, promotes granulation and epithelialization, and facilitates autolytic debridement. The composition has antimicrobial properties. Sodium hypochlorite provides bacteriostatic properties. The antimicrobial composition is a cleansing composition that helps maintain a moist wound environment conducive to wound healing.

[0048] It has been found that various additives reduce the shelf life of compositions containing sodium hypochlorite and hypochlorous acid.For example, it has been found that various impurities and additives in the water used to prepare the composition can accelerate the decomposition of the active antibacterial substance, resulting in a decrease in the activity of the composition and an unacceptably short shelf life.Although the detailed reaction mechanism at the molecular level is unknown, the inventors have found that high water hardness and the presence of metal ions accelerate the decomposition of the active compound.

[0049] Water hardness is measured as total hardness in accordance with ISO 15923-2:2017 and is expressed in ppm. In one embodiment, the hardness does not exceed 5 ppm. In one embodiment, the hardness does not exceed 4 ppm. In one embodiment, the hardness does not exceed 3 ppm. In one embodiment, the hardness does not exceed 2 ppm. In one embodiment, the hardness does not exceed 1 ppm.

[0050] The metal ion content is determined by measuring the resistivity of the water. The positive counterions are most often metal ions, H +is also considered to contribute to the degradation of the active ingredient, so the above is a good approximation. The conductivity of water (i.e., the reciprocal of resistivity) is measured as outlined in ISO 3696:1987, and then the resistivity is calculated as the reciprocal. In one embodiment, the resistivity is greater than 15 MΩ / cm. In one embodiment, the resistivity is greater than 16 MΩ / cm. In one embodiment, the resistivity is greater than 17 MΩ / cm. In one embodiment, the resistivity is greater than 17.2 MΩ / cm. In one embodiment, the resistivity is greater than 17.5 MΩ / cm.

[0051] In particular, the inventors believe that high water hardness combined with the presence of metal ions contributes to the accelerated decomposition of active ingredients. Therefore, it is important to maintain both the amount of metal ions and the water hardness low for the water used to prepare the present composition. When the water hardness and resistivity are maintained within the above-mentioned boundary values ​​(i.e., resistivity higher than 15 MΩ / cm and hardness less than 5 ppm), the shelf life of the present composition is improved.

[0052] Additionally, other quality standards for the water used in preparing the product are also suitable, especially since the composition is a medical product and should meet high standards.

[0053] TOC is measured in accordance with ISO20236:2018 and recalculated to ppb by mass. In one embodiment, TOC does not exceed 50 ppb. In one embodiment, TOC is less than 10 ppb. All calculations are by mass.

[0054] In one embodiment, the TDS, as measured in accordance with ASTM D5907-10, does not exceed 50 ppm by weight. In one embodiment, the TDS does not exceed 15 ppm. In another embodiment, the TDS does not exceed 5 ppm. All calculations are by weight.

[0055] Additionally, the level of heavy metals should be low: in one embodiment, the amount of heavy metals arsenic, cadmium and lead combined is less than 0.1 ppm by mass.

[0056] In fact, it has been found that the choice of thickener is not without importance, both because it must be medically acceptable and also because it should not accelerate the degradation of the active antibacterial ingredient. All additives to the composition have the potential to accelerate the degradation of the active ingredient, and therefore all additives must be carefully selected so that they do not accelerate the degradation of the antibacterial compound in the composition. It has been found that selected synthetic silicate clay-based thickeners meet these requirements. In particular, the antibacterial ingredient does not decompose when a synthetic silicate clay-based thickener is used and when the amount of metal ions and water hardness are within the required boundaries.

[0057] The use of synthetic silicate clay-based thickeners, along with the use of water with a resistivity greater than 15 MΩ / cm and a hardness less than 5 ppm, provides improved shelf life by not accelerating the degradation of the antimicrobial agent.

[0058] All of the above limits for water apply to purified water before it is added to the composition.

[0059] In one embodiment, the amount of sodium hypochlorite is in the range of 0.04 to 0.06% by weight.

[0060] In one embodiment, the amount of hypochlorous acid (HOCl) is in the range of 0.005 to 0.02% by weight. This range of NaOCl and HOCl concentrations exhibits good biocompatibility and antimicrobial efficacy.

[0061] In one embodiment, the amount of sodium chloride is in the range of 0.05 to 0.2% by weight, which is suitable for acting as a stabilizer and preservative component.

[0062] In one embodiment, the synthetic silicate clay-based thickener comprises lithium magnesium sodium silicate.

[0063] In one embodiment, the synthetic silicate clay-based thickener is present in an amount ranging from 3 to 5% by weight. This synthetic silicate clay has been found to be suitable for retaining the active ingredient in a semi-liquid form. Other thickeners, such as dimethicone, carboxymethylcellulose, xanthan gum, and carbomer, were unable to retain the active ingredient and did not produce the desired gel.

[0064] In one embodiment, purified water makes up the remainder of the composition, in addition to sodium hypochlorite (NaOCl), hypochlorous acid (HOCl), a synthetic silicate clay-based thickener, and sodium chloride (NaCl), and is necessary to ensure the absence of other ions in the gel that may compromise the stability of the active ingredients.

[0065] The composition has a pH greater than 7.5. In one embodiment, the composition has a pH in the range of 7.5 to 10.0. The growth of wound healing cells, including fibroblasts and keratinocytes, is promoted by an alkaline pH (Teshima et al., 2020). In an alternative embodiment, the composition has a pH in the range of 7.5 to 9.5. In an alternative embodiment, the composition has a pH in the range of 7.5 to 9.0. In an alternative embodiment, the composition has a pH in the range of 8.0 to 9.0. In an alternative embodiment, the composition has a pH in the range of 8.0 to 9.5. In an alternative embodiment, the composition has a pH in the range of 8.0 to 10.0. For the present invention, including generally the present description, examples, and claims, pH is measured according to the method set forth in ASTM E70-19.

[0066] Compared to the prior art, including prior art CN113069413(A), the present invention has a significantly lower buffering capacity. It is known that the intensity of pain sensation is significantly lower at high pH compared to lower pH (amiloride-blockable acid-sensing ion channels are the primary acid sensors expressed in human nociceptors. Shinya Ugawa, J. Clin. Invest. 110:1185-1190 (2002). doi:10.1172 / JCI200215709). Therefore, with respect to pain sensation, a pH higher than neutral is preferred.

[0067] However, due to the low buffering capacity, the pH will be lower in wounds with lower pH, which typically have a pH below 7.5, which results in a higher localized antimicrobial effect in the wound.

[0068] Hypochlorous acid (HOCl) exists in equilibrium, so at very low pH below about 1.5, Cl2 is the predominant species, between pH about 1.5 and 7.5, HOCl is the predominant species, and above pH 7.5, (OCl) - Hypochlorous acid (HOCl) exists in different forms depending on the pH, but above pH 7.5, in the present invention, it is (OCl) - It exists primarily as hypochlorous acid (HOCl), which is still called hypochlorous acid (HOCl). The HOCl species, which is the predominant species at pH levels between about 1.5 and 7.5, is (OCl) - It is further known that hypochlorous acid (HOCl) has the highest antibacterial activity compared to other substances. With this in mind, it is not surprising that many antibacterial compositions containing hypochlorous acid (HOCl) have a pH in the range of 1.5 to 7.5. Due to the low buffering capacity of the gel, the gel mixes with the fluid in the wound, resulting in a lower pH, and HOCl becomes the predominant chemical species that has a higher local antibacterial effect in the wound. Typically, wounds have a pH lower than 7.5. Therefore, the present composition is particularly suitable for treating wounds with a neutral or acidic pH.

[0069] The pH of the present invention, above 7.5, provides sufficient antibacterial activity for wound treatment. At the same time, there is an additional benefit of providing further antibacterial activity. Most wounds have a neutral pH, and in the case of an open wound, the composition of the present invention will mix with the fluid in the open wound, and the pH of this mixture will then be lower than 7.5. This lowering of the pH improves the antibacterial effect of the composition. It should be noted that this effect is present at the wound and in the immediate vicinity of the wound where the composition mixes with the fluid derived from the wound. This provides the advantage of locally enhancing the antibacterial effect when desired, i.e., right at and / or near the wound. The composition according to the present invention is less irritating to the skin further away from the open wound due to the higher pH value. Thus, the present invention combines antibacterial effect with less irritation when needed.

[0070] It should be noted that the buffer capacity of the composition according to the present invention is low, and therefore the pH value is affected by the fluid in open wounds.In this regard, it should be noted that CN113069413 contains a phosphate buffer, and therefore the pH in open wounds does not change appreciably.Therefore, it is advantageous that the composition according to the present invention does not contain a buffer.

[0071] In one embodiment, the viscosity of the composition is in the range of 8000-10000 cP. Such a high viscosity allows the gel to remain in the wound cavity, providing more moisture.

[0072] Viscosity is measured using a Brookfield viscometer in accordance with ISO 2555:2018, Plastics - Liquid, or emulsion or dispersion resins - Determination of apparent viscosity using the single cylinder rotational viscometer method.

[0073] In a second aspect, there is provided a method (400) for producing an antimicrobial composition, the method comprising: a) i. purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured in accordance with ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured in accordance with ISO 3696:1987; ii. Synthetic silicate clay-based thickeners; iii. Sodium hypochlorite solution, and iv. Sodium chloride preparing a b) mixing purified water, a synthetic silicate clay-based thickener, sodium hypochlorite solution, and sodium chloride to obtain an antimicrobial composition; Including, A method is provided wherein the composition has a pH in the interval of 7.5 to 10.0 and a buffer capacity β measured at pH 8.0 of 0.15 or less.

[0074] In one particular embodiment of the second aspect, the method comprises: a) filling a container with purified water (402); b) adding lithium magnesium sodium silicate (406) during the mixing and stirring for at least 90 seconds (408); c) adding sodium hypochlorite solution and stirring for at least 30 seconds (410); and d) adding sodium chloride (NaCl) to the mixture and stirring for at least 120 seconds (412); Includes.

[0075] This particular embodiment is illustrated in Figure 4. In one embodiment, steps b) to d) in Figure 4 are performed in sequential order.

[0076] In one embodiment, the sodium hypochlorite solution in step c) has a concentration in the range of 4 to 8% by weight.

[0077] In a third aspect, there is provided a valve system device for wound management comprising a bag-on-valve (BoV) within a pressurized storage canister and an antimicrobial composition for wound management contained in the bag, the antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount in the range of 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount in the range of 0.003 to 0.03% by weight, a synthetic silicate clay-based thickener in an amount in the range of 1 to 10% by weight, sodium chloride (NaCl) in an amount in the range of 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of 0.15 or less.

[0078] In one embodiment, the pressurized storage canister contains a non-flammable propellant.

[0079] In one embodiment, the pressurized storage canister is an aerosol spray canister.

[0080] In a fourth aspect, there is provided a method of producing a valve system device for wound management, comprising: a) placing a bag-on-valve (BoV) inside a storage canister; b) crimping the BoV into a storage canister and then filling the storage canister with a propellant gas to obtain a pressurized storage vessel; and c) filling the bag of the BoV with the antibacterial composition through the valve of the BoV; A method is provided, comprising:

[0081] In one embodiment, steps a) to c) of the method for producing a valve system device for wound management are performed sequentially.

[0082] In a fifth aspect, there is provided a method of delivering an antimicrobial composition to a wound, the method comprising the step of applying an antimicrobial composition to the wound, the antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount in the range of 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount in the range of 0.003 to 0.03% by weight, a synthetic silicate clay-based thickener in an amount in the range of 1 to 10% by weight, sodium chloride (NaCl) in an amount in the range of 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of less than or equal to 0.15.

[0083] Various embodiments of the present invention provide antimicrobial compositions for wound management and methods of producing the antimicrobial compositions, which include sodium hypochlorite (NaOCl), hypochlorous acid (HOCl), a synthetic silicate clay-based thickener, sodium chloride (NaCl), and purified water, where the purified water must meet certain standards for hardness and resistivity.

[0084] In a sixth aspect, there is provided a method of treating a wound, comprising applying to the wound an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount in the range of 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount in the range of 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount in the range of 1 to 10% by weight, sodium chloride (NaCl) in an amount in the range of 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of less than or equal to 0.15.

[0085] In a seventh aspect, there is provided a composition for the prevention or treatment of infection in a wound, comprising sodium hypochlorite (NaOCl) in an amount in the range of 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount in the range of 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount in the range of 1 to 10% by weight, sodium chloride (NaCl) in an amount in the range of 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of more than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of 0.15 or less.

[0086] Thus, the sixth and seventh aspects provide for the treatment of wounds, in particular the prevention and / or treatment of infection in wounds.

[0087] The antimicrobial compositions of the present technology have a pH greater than 7.5 and free chlorine (30 ppm to 200 ppm) that can kill a broad range of microorganisms, including bacteria and fungi. In one embodiment, the free chlorine, as measured in accordance with ISO 7393-2:2017, is in the range of 30 to 200 ppm. The free chlorine gives the compositions the ability to eliminate a broad range of microorganisms, including bacteria and fungi.

[0088] In embodiments, the antimicrobial compositions of the present invention are hemostatic agents. In embodiments, the antimicrobial compositions of the present invention are chemical hemostatic agents. When applied, the antimicrobial compositions can promote hemostasis and stop or slow bleeding in a wound.

[0089] In an embodiment of the present invention, a valve system for wound management is provided. The valve system comprises or consists of a bag within a pressurized storage canister and an antimicrobial composition for wound management contained in the bag. The antimicrobial composition includes sodium hypochlorite (NaOCl), hypochlorous acid (HOCl), a synthetic silicate clay-based thickener, sodium chloride (NaCl), and purified water. In an embodiment, the antimicrobial composition of the present invention is within the valve system device when stored. In another embodiment, the antimicrobial composition of the present invention is an aerosolized spray composition when sprayed from the valve system device or when applied to a wound from the valve system device. In one embodiment, when the antimicrobial composition of the present invention is applied to a wound from the valve system device, the antimicrobial composition becomes aerosolized and forms a foam or froth spray composition on the wound. In an embodiment, the bag containing the antimicrobial composition for wound management is propellant-free or chemical propellant-free. The valve device of the present invention does not utilize a chemical propellant that comes into contact with the antimicrobial composition of the present invention.

[0090] In one embodiment, the pressurized storage canister of the valve system device of the present invention includes a chemical propellant. In particular, the present invention does not use any flammable materials or any flammable propellants, which also reduces the risk of exposure to high temperatures or fire when handling the valve system device. The valve system device of the present invention, which does not use any flammable materials, also allows for an extended and sustained shelf life, especially since there is no concern of combustion when the valve system device is stored.

[0091] The chemical propellant contained in the pressurized storage canister applies pressure to the bag inside the pressurized storage canister, thereby indirectly propelling the composition inside the bag out of the valve system device when the composition is applied. Because the chemical propellant is contained outside the bag, the chemical propellant is isolated from the bag, preventing any change in the quality or characteristics of the antimicrobial composition stored in the bag. In one embodiment, the chemical propellant is nitrogen gas. The use of nitrogen gas as a propellant not only provides a non-flammable, inert, and extremely low boiling point (-195°C), but also helps maintain the flow of most viscous liquids in piping, thereby enabling dispensing of approximately 99.9% by mass of the composition stored in the bag.

[0092] In embodiments, the pressurized storage canister used in the valve system device of the present invention is an aerosol spray container suitable for use in spraying a foam or foam-like form of the composition. The use of a valve system in the device of the present invention allows for the product to be dispensed in pure form, i.e., without any additional mixing of unnecessary ingredients, allowing for the storage and storage of larger amounts of the composition via the valve system compared to traditional and existing bag-on-valve product packaging. Furthermore, the valve system of the present invention allows for the dispensing of 99.99% by weight of the stored antimicrobial composition, preventing any unused residue of the composition. The valve system device can also be used for continuous and intermittent spraying at any angle and with a uniform / controlled spray flow and pattern, unlike traditional aerosol spray systems that vary spray volume with tilt. The above characteristics of the valve system device allow for its use in first aid applications for unusual or difficult wound cases, such as accidents involving severely injured individuals or accidents requiring precise maneuvers and responses. Thus, the valve system of the present invention provides improved overall wound management efficiency over that of the prior art. Additionally, the aerosolized composition produced from the valve system provides a cooling effect to the wound, thereby further reducing the pain experienced by the subject suffering from the wound.

[0093] In one embodiment, the valve system used comprises a bag-on-valve system (BoV). In embodiments where the valve system comprises a BoV system, the BoV comprises a bag attached to a valve. The bag attached to the valve, without any substance therein, is folded, rolled or compressed, and is configured to receive any liquid or fluid substance that is to be placed into the bag through the valve.

[0094] In another embodiment of the present invention, there is provided a method of producing a valve system device for wound management, said method comprising the steps of placing a bag-on-valve (BoV) inside a storage canister, crimping the BoV to the storage canister and then filling the storage canister with a propellant gas to obtain a pressurized storage container, and filling a bag of the BoV with an antimicrobial composition via a valve on the BoV.

[0095] Referring to FIG. 1, FIG. 1 illustrates a table illustrating the composition of each component of an antimicrobial composition according to one particular embodiment. The antimicrobial composition of the present technology has antimicrobial properties. In an embodiment, the antimicrobial composition contains 0.05% by weight of sodium hypochlorite, 0.01% by weight of hypochlorous acid (HOCl), 0.10% by weight of sodium chloride, 4.0% by weight of a synthetic silicate clay-based thickener, and 95.85% by weight of purified water, as shown in the table in FIG. 1. In an embodiment, the synthetic silicate clay-based thickener includes lithium magnesium sodium silicate. In an embodiment, the lithium magnesium sodium silicate has a composition of 4.0% by weight.

[0096] FIG. 2 illustrates test results of a preservative test according to the USP (United States Pharmacopoeia), Preservative Effectiveness Test, according to an exemplary scenario. To demonstrate bacteriostatic activity, the antimicrobial composition of the present technology was tested by a certified laboratory using USP 51 and Preservative Effectiveness Tests. The table in FIG. 2 illustrates the test results of the preservative test of the composition. As can be observed from the table in FIG. 2, bacteriostatic properties are conferred, inter alia, by the addition of sodium hypochlorite, which causes biosynthetic alterations in cellular metabolism and inhibits bacterial growth when acting as a preservative. The microbial population reduction effect was demonstrated in vitro against clinically relevant strains of fungi known to cause both Gram-positive and Gram-negative wound infections.

[0097] Figure 3 illustrates the biocompatibility test results of the antimicrobial composition of the present technology according to International Organization for Standardization (ISO) 10993 for in vivo and in vitro studies according to an exemplary scenario. As shown in Figure 3, there is no evidence of erythema or edema during the endothelial reactivity stimulation test for the antimicrobial composition of the present technology. Furthermore, there is no cytotoxic effect or oral toxicity caused by the antimicrobial composition of the present technology.

[0098] FIG. 4 is a flow diagram illustrating the steps involved in a specific embodiment of a method for manufacturing an antimicrobial composition of the present technology. The method produces approximately 3 liters of composition. In step 402, the method includes filling a container with 3 liters of purified water. In step 404, the method includes turning on a high-shear mixer and setting the speed to 2000 rpm. In step 406, the method includes slowly adding 120 g ± 1 g of lithium magnesium sodium silicate (thickener) to the solution from the edge of the container. In step 408, the method includes continuously stirring the mixture at 2000 rpm for 30 minutes. In step 410, the method includes slowly adding 30 mL ± 0.05 mL of sodium hypochlorite solution (4% to 8% by weight) to the mixture from the edge and stirring at 5500 rpm for 5 minutes. In step 412, the method includes adding 3.0 g±0.1 g of pure dry vacuum (PDV) salt (NaCl) to the mixture. In step 414, the method includes stirring the mixture at 5500 rpm for 15 minutes until the mixture is completely homogenous. In embodiments, the sodium hypochlorite solution is 4% to 8% by weight. [Example]

[0099] Example 1 Example 1 included filling a container with 3 liters of purified water. This example further included turning on a high-shear mixer and setting the speed to 2000 rpm. This example further included slowly adding 120 g ± 1 g of lithium magnesium sodium silicate (thickener) to the solution from the edge of the container. This example further included continuously stirring the mixture at 2000 rpm for 30 minutes. This example further included slowly adding 30 mL ± 0.05 mL of sodium hypochlorite solution to the mixture from the edge and stirring at 5500 rpm for 5 minutes. This example further included adding 3.0 g ± 0.1 g of PDV (NaCl) salt to the mixture. This example further included stirring the mixture until it was completely homogenous, and the mixture was stirred at 5500 rpm for 15 minutes. The sodium hypochlorite solution was in the range of 4-8% by weight.

[0100] Example 2 In the example presented and illustrated in FIG. 5, a semi-automatic crimping, degassing, and filling machine (AM-04) was used to fill a pressurized storage canister with a form of antimicrobial composition. First, a bag-on-valve (BoV) was placed inside the storage canister. The valve of the BoV was crimped onto the storage canister, and then the storage canister was filled with nitrogen, a propellant gas, to obtain a pressurized storage canister equipped with a BoV. Next, the antimicrobial composition was filled into the attached bag through the valve (BOV) into the bag of the BoV. This mechanism allows the product to be physically isolated from the propellant gas used.

[0101] Below is a summary of the process parameter settings for the small (50 g) and large (100 g) canisters.

[0102] [Table 4]

[0103] (BOV, non-aerosol) is classified as a non-flammable product according to European Council Directive 75 / 324 / EEC (Annex 1 - Regulation 1.9).

[0104] In the example provided, the main components of this product, specifically a valve system device for wound management, are: - Antimicrobial wound composition: 0% by weight of flammable components (based on water). - Nitrogen gas: an inert gas containing 0% by weight of flammable components. The term "aerosol" here refers to the property of a product that relies on the force of pressure to propel the contents from a container (US FDA - Tamper Evident Regulations - 21CFR700.25).

[0105] In one embodiment, the valve device for bag-on-valve technology wound management of the present invention is a compartmentalized aerosol dispenser with a metal / plastic bag attached to the valve or valve body, and no mixing of the propellant gas and the product occurs (NIST Guidelines for the Definition of Aerosols and Bag-on-Valves (DDF1 / 28 / 12) - February 2012).

[0106] Various embodiments of the present invention provide antimicrobial compositions developed for the moistening and debridement of acute and chronic wounds, such as stage I-IV ulcers, venous stasis and diabetic ulcerations, post-surgical wounds, first and second degree burns, and pressure sores, to help maintain a moist wound environment, promote granulation and epithelialization, and facilitate autolytic debridement.

[0107] Example 3 In the examples presented and illustrated in Figure 2, the preservative efficacy test USP51 was used to evaluate the antimicrobial properties of the gel when tested against selected bacteria, fungi and yeasts, respectively.

[0108] In this method, a gel is inoculated with a controlled amount of a specific microorganism. The test then compares the initial levels of the microorganism to test samples at various time intervals over a 28-day period at a specified temperature. The log reduction of the organisms is assessed at the specified time intervals to quantitatively assess the effectiveness of the antimicrobial properties of the gel in preventing microbial growth and / or killing or reducing the organism population.

[0109] For topical products, a preservative is effective if, in the test product: Bacteria - A 2.0 log reduction in bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia) from the initial count on Day 14 and no increase from Day 14 counts at Day 28 are observed. Yeasts and Molds - For yeasts and molds (Candida albicans and Aspergillus brasiliensis), no increase from the initial calculations is observed at 14 and 28 days.

[0110] Example 4 In the examples provided, iodometric titrations were performed to determine hypochlorous acid and sodium hypochlorite in the raw materials used to prepare the hydrogel compositions of the present invention.

[0111] First, the reagents used were prepared according to the following procedure:

[0112] [Table 5]

[0113] The samples prepared were sodium hypochlorite of the present invention, namely an antimicrobial aqueous solution (Hydrocyn® aqua, which is the same as Bactiguard® wound care solution) and an antimicrobial gel composition (Hydrocyn® aqua gel, which has the ingredients according to the table in Figure 1 and is the same as Bactiguard® wound care gel according to claim 1) prepared as follows:

[0114] [Table 6]

[0115] The sample was titrated. The buret was rinsed with a small amount of sodium thiosulfate solution and then filled to just above the zero mark with sodium thiosulfate. A small amount of solution was poured from the tip of the buret to release any trapped air bubbles. Approximately 25 ml of 10% potassium iodide solution was added to the sample solution. Approximately 10 ml of acetic acid was added to achieve a nearly acidic state. The addition of acetic acid and potassium iodide caused the sample solution to change color from colorless to amber-brown. The sample solution was then titrated with 0.2 N / 0.05 N sodium thiosulfate until it turned straw-colored. The titration was rapid, as iodine was rapidly released. Approximately 5 ml of starch indicator was added, and titration continued until the blue color disappeared. The added starch indicator reacted with iodine to form a very intense blue / purple complex. The titration was stopped as soon as a clear solution was obtained. The amount of sodium solution titrated was then recorded for further calculations.

[0116] The number of moles of sodium thiosulfate for each titration is calculated using the following formula:

[0117]

number

[0118] The stoichiometric reaction was used to calculate the moles of hypochlorite, with the calculated moles of sodium thiosulfate. H + (aq) + HOCl(aq) + 2S2O3 2- (aq) → S4O6 2- (aq)+Cl - (aq)+H2O(aq)

[0119] The stoichiometry of the formula indicates that there are 2 moles of thiosulfate ions per mole of hypochlorous acid: Number of moles of HOCl = S2O3 2- 1 / 2 mole of Moles of HOCl = Moles of NaOCl

[0120] The concentration (wt%) of NaOCl in the feedstock was calculated using the following calculation:

[0121]

number

[0122] V is the amount of titrant (in ml), N represents the normality (N) of the sodium thiosulfate used, and M represents the mass of the sample. The calculated mw of NaOCl is 74.44 g / mol.

[0123] The concentrations (wt%) of NaOCl and HOCl in the antimicrobial aqueous solution (Hydrocyn® aqua, a wound care solution derived from Bactiguard®) were calculated using the following calculation:

[0124]

number

[0125] In the calculations presented, the normality of the sodium thiosulfate used is 0.05N, the mw of NaOCl is 74.44 g / mol, and the mw of HOCl is 52.46 g / mol.

[0126] As will be readily apparent to those skilled in the art, the present invention may be readily produced in other specific forms without departing from its essential characteristics. Accordingly, the present embodiments are to be considered merely illustrative and not limiting, the scope of the present invention being indicated by the claims rather than the foregoing description, and all changes within that scope are therefore intended to be embraced by the claims.

[0127] Example 5 Since the quality of the water used in producing the present composition is very important, examples of water purification are provided below for the water used in making the present composition.

[0128] First, tap water was fed into the first stage of the RO / DI system, which consisted of a sediment filter (primarily containing sand of various sizes) and a carbon filter. The sediment filter was used to capture large free-floating particles or contaminants. The carbon filter consisted of granular carbon, while it absorbed organic matter and other dissolved contaminants (such as chlorine and chloramines).

[0129] After the carbon filtration stage, the water is put into a softener column to remove hard inorganic ions (magnesium, Mg 2+ and calcium, Ca 2+ When hard water enters the mineral tank, it flows through a bed of spherical resin beads. These beads are loaded with sodium ions. The resin beads are anionic, with a negative charge. Calcium and magnesium minerals have a positive charge, making them cationic. As the hard water passes through the resin, the beads grab hold of the inorganic ions, removing them from the water. As the beads capture the inorganic ions, sodium ions are released.

[0130] The water was then fed into a reverse osmosis (RO) system where it was filtered through multiple layers of thin films that removed most of the contaminants, such as salts, bacteria, heavy metals, and other organic matter. From here, the water was split into two different water lines: a waste line and a product line. The product water was almost pure and went to a storage tank that served as a reservoir for the DI (deionization) system. A percentage of the waste water was recycled to the RO system, while the remaining portion was discharged into a drain line.

[0131] Before being fed into the DI system, the RO water was cooled to a temperature range of 20-25°C by a chiller. The cooled water then passed through an ultraviolet (UV) purifier for the disinfection process. The UV purifier exposes viable organisms, such as bacteria, viruses, or fungi (such as Cryptosporidium and Giardia), to germicidal ultraviolet radiation, destroying the DNA in pathogenic microorganisms so they are at least unable to reproduce.

[0132] After UV disinfection, the water was passed through three identical deionization columns containing resins. The deionization stage was used as an ion exchange process to attract inorganic impurities such as sodium and other metallic elements. The negatively charged cation resin attracts positively charged ions in the water, while the positively charged anion resin attracts anions. Finally, the DI water was passed through ultrafine filter cartridges (i.e., 0.45 μm and 0.2 μm), and then piped to the manufacturing site's point of use. The unused purified water was circulated back to the reservoir and re-fed to the DI system, continuously repeating the same deionization process. [Explanation of symbols]

[0133] 400 Method for Producing an Antibacterial Composition 402 Fill a container with 3 liters of purified water 404 Turn on the high shear mixer and set the speed to 2000 rpm 406 Slowly add 120g ± 1g of lithium magnesium sodium silicate (thickener) to the solution around the edge of the container. 408 The mixture is continuously stirred at 2000 rpm for 30 minutes. 410 Slowly add 30 mL ± 0.05 mL of sodium hypochlorite solution (4% to 8% by weight) to the mixture from the edge and stir at 5500 rpm for 5 minutes. 412 Add 3.0g ± 0.1g of pure dry vacuum (PDV) salt (NaCl) to the mixture. 414 Stir the mixture at 5500 rpm for 15 minutes until the mixture is completely homogenous.

Claims

1. 1. An antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount ranging from 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount ranging from 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount ranging from 1 to 10% by weight, sodium chloride (NaCl) in an amount ranging from 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of 0.15 or less.

2. 2. The antimicrobial composition of claim 1, wherein the amount of sodium hypochlorite is in the range of 0.04 to 0.06% by weight.

3. 3. The antibacterial composition according to claim 1, wherein the amount of hypochlorous acid (HOCl) is in the range of 0.005 to 0.02% by weight.

4. 4. The antimicrobial composition according to any one of claims 1 to 3, wherein the amount of sodium chloride is in the range of 0.05 to 0.2% by weight.

5. 5. The antimicrobial composition of claim 1, wherein the synthetic silicate clay-based thickener comprises lithium magnesium sodium silicate.

6. 6. The antimicrobial composition of any one of claims 1 to 5, wherein the synthetic silicate clay-based thickener is present in an amount in the interval 3 to 5% by weight.

7. 7. The antimicrobial composition of any one of claims 1 to 6, wherein the purified water constitutes the remainder of the composition, in addition to sodium hypochlorite (NaOCl), hypochlorous acid (HOCl), a synthetic silicate clay-based thickener, and sodium chloride (NaCl).

8. 8. The antimicrobial composition of any one of claims 1 to 7, having free chlorine in the range of 30 to 200 ppm.

9. 1. A method (400) for producing an antimicrobial composition, the method comprising: a) i. purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured in accordance with ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured in accordance with ISO 3696:1987; ii. Synthetic silicate clay-based thickeners; iii. Sodium hypochlorite solution, and iv. Sodium chloride preparing a b) mixing the purified water, the synthetic silicate clay-based thickener, the sodium hypochlorite solution, and the sodium chloride to obtain the antimicrobial composition. Including, The composition has a pH in the range of 7.5 to 10.0 and a buffering capacity β measured at pH 8.0 of 0.15 or less.

10. 10. The method of claim 9, wherein the sodium hypochlorite solution has a concentration in the range of 4 to 8% by weight.

11. 11. The method of claim 9 or 10, wherein the synthetic silicate clay-based thickener comprises lithium magnesium sodium silicate.

12. Bag-on-valve (BoV) and an antimicrobial composition for wound management contained in the bag, the antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount ranging from 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount ranging from 0.003 to 0.03% by weight, a synthetic silicate clay-based thickener in an amount ranging from 1 to 10% by weight, sodium chloride (NaCl) in an amount ranging from 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of 0.15 or less.

1. A valve system device for wound management comprising:

13. 13. The valve system apparatus for wound management of claim 12, wherein the pressurized storage canister contains a non-flammable propellant.

14. 14. A valve system device for wound management according to claim 12 or 13, wherein the pressurised storage canister is an aerosol spray canister.

15. 1. A method of producing a valve system device for wound management, comprising: a) placing a bag-on-valve (BoV) inside a storage canister; b) crimping the BoV into the storage canister and then filling the storage canister with a propellant gas to obtain a pressurized storage vessel; and c) filling the bag of the BoV with the antimicrobial composition of any one of claims 1 to 9 through the valve of the BoV; A method comprising:

16. 1. A method of delivering an antimicrobial composition to a wound, the method comprising applying the antimicrobial composition to the wound, the antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount ranging from 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount ranging from 0.003 to 0.03% by weight, a synthetic silicate clay-based thickener in an amount ranging from 1 to 10% by weight, sodium chloride (NaCl) in an amount ranging from 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of 0.15 or less.

17. 17. The method of claim 16, wherein application of the antimicrobial composition to the wound is performed from a valve system device, the valve system device including a bag within a pressurized storage canister and the antimicrobial composition for wound management contained in the bag.

18. 1. A method of treating a wound, comprising applying to the wound an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount ranging from 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount ranging from 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount ranging from 1 to 10% by weight, sodium chloride (NaCl) in an amount ranging from 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured according to ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0 and a buffer capacity β measured at pH 8.0 of 0.15 or less.

19. 1. A composition for the prevention or treatment of infection in a wound, comprising sodium hypochlorite (NaOCl) in an amount ranging from 0.015 to 0.15% by weight, hypochlorous acid (HOCl) in an amount ranging from 0.002 to 0.1% by weight, a synthetic silicate clay-based thickener in an amount ranging from 1 to 10% by weight, sodium chloride (NaCl) in an amount ranging from 0.03 to 0.3% by weight, and purified water, wherein the purified water prior to addition to the composition has a hardness of less than 5 ppm as measured in accordance with ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm as measured in accordance with ISO 3696:1987, and wherein the composition has a pH in the interval of 7.5 to 10.0, and a buffer capacity β measured at pH 8.0 of 0.15 or less.

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