Antimicrobial gel composition

Abstract

Antimicrobial compositions for wound management and methods of producing the same are provided. The present invention relates to an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount of from 0.015 wt% to 0.15 wt%, hypochlorous acid (HOCl) in an amount of from 0.002 wt% to 0.1 wt%, a thickener based on synthetic silicate clay in an amount of from 1 wt% to 10 wt%, sodium chloride (NaCl) in an amount of from 0.03 wt% to 0.3 wt%, and purified water, wherein the purified water has a hardness, measured according to ISO 15923-2: 2017, of less than 5 ppm and a resistivity, measured according to ISO 3696: 1987, of greater than 15 M [omega] / cm before being added to the composition, and wherein the pH of the composition is in the range of 7.5 to 10.0, and wherein the buffer capacity [beta], measured at pH 8.0, is 0.15 or less.

Description

Technical Field

[0001] The present invention relates to an antimicrobial composition, a method for producing the antimicrobial composition, and a valve system device comprising the antimicrobial composition and a method for wound management. Background Art

[0002] Wounds are a hidden epidemic among the world's population, with significant social and economic consequences that impair the quality of life of millions of people. While acute wound management is relatively manageable in healthy patients, patients with chronic wounds can be difficult to assess and maintain. The number of cases of chronic wounds is increasing, yet existing standard-of-care solutions fail to meet treatment guidelines. While bandages and gauze are available to reduce bleeding, they have many drawbacks. They are non-biodegradable, prone to infection, and unsuitable for wounds with uneven shapes. They can cause secondary tissue damage and are ineffective in wound healing. Antibiotic resistance and a weak immune response pose challenges to the treatment of chronic infections. Due to this, the wound healing process and wound management devices have been extensively researched. Existing research recognizes the key role that hydrogels play in wound healing. They provide moisture to wounds, allowing painless debridement of necrotic and infected tissue, as well as granulation and complete healing. However, given their high water content, current hydrogels are not fully absorbable and are therefore best suited for wounds with mild to moderate exudate. Consistent with this, antimicrobial agents are needed to combat infection and aid the wound healing process. Therefore, in light of the foregoing discussion, a need exists to overcome the aforementioned shortcomings associated with currently available antimicrobial hydrogels.

[0003] US Patent Application 20200138953A1 discloses a stable hypohalous acid solution, particularly a stable solution or formulation comprising hypobromous acid and a stabilizing amount of dissolved inorganic carbon in the form of a bicarbonate or carbonate of an alkaline earth metal.

[0004] U.S. Patent Application 20200138953A1 discloses a bag-on-valve with a hypochlorous acid solution and a chlorine stabilizer, which is suitable for disinfecting food processing surfaces and sanitizing medical equipment in hospitals.

[0005] CN 113069413A discloses a hypochlorous acid gel that supports electron beam irradiation sterilization. The hypochlorous acid gel is prepared from the following raw materials in parts by weight: 50 to 70 parts of a gel base, 27.4 to 49.979 parts of a phosphate buffer solution, 0.001 to 0.6 parts of hypochlorous acid, and 0.02 to 2 parts of sodium hypochlorite, wherein the phosphate buffer solution is prepared from boric acid, potassium dihydrogen phosphate, sodium chloride, and pure water. The hypochlorous acid gel has a neutral pH and is believed to be non-irritating to wound surfaces. Preferably, the hypochlorous acid gel has a pH of 5.5 to 8.0. The only example has a pH of 6.8. The gel base powder is preferably any one or more of lithium magnesium silicate, magnesium aluminum silicate, and sodium magnesium fluorosilicate. It should also be noted that the phosphate buffer solution is required, and therefore the gel has a certain buffering capacity β for the pH value, which is quite high. According to the formula in the example of CN 113069413, the inventors calculated the buffer capacity to be β=0.189≈0.19≈0.2.

[0006] For prior art compositions comprising sodium hypochlorite and hypochlorous acid, the shelf life has generally proven to be unsatisfactory for convenient use.

[0007] Furthermore, it would be desirable to improve the treatment of wounds by providing additional delivery forms of antimicrobial agents.

[0008] One of the problems in the art is that antimicrobial compositions can be irritating to the skin. For hypochlorite and hypochlorous acid, the optimal pH for antimicrobial activity is at an acidic pH, such as pH 3 to 7. At the same time, an acidic pH is more irritating to the skin and can cause discomfort to the user. Summary of the Invention

[0009] It is an object of the present invention to obviate at least some of the disadvantages of the prior art and to provide an improved antimicrobial composition in gel form.

[0010] In a first aspect, an antimicrobial composition is provided comprising sodium hypochlorite (NaOCl) in an amount of 0.015 wt% to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.002 wt% to 0.1 wt%, a synthetic silicate clay-based thickener in an amount of 1 wt% to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 wt% to 0.3 wt%, and purified water, wherein the purified water has a hardness of less than 5 ppm measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm measured according to ISO 3696:1987 before being added to the composition, and wherein the pH of the composition is in the interval of 7.5 to 10.0.

[0011] In a second aspect, a method (400) for preparing an antimicrobial composition is provided, the method comprising the steps of:

[0012] a) Provide

[0013] i. Purified water, wherein the purified water, prior to being added to the composition, has a hardness of less than 5 ppm as measured in accordance with ISO 15923-2:2017 and a resistivity greater than 15 MΩ / cm as measured in accordance with ISO 3696:1987;

[0014] ii. thickeners based on synthetic silicate clays;

[0015] iii. sodium hypochlorite solution, and

[0016] iv. sodium chloride, and

[0017] b) mixing purified water, a thickener based on synthetic silicate clay, a sodium hypochlorite solution and sodium chloride to obtain an antimicrobial composition,

[0018] The pH of the composition is within the range of 7.5 to 10.0.

[0019] In a third aspect, a valve system device for wound management is provided, comprising a bag-on-valve (BoV) within a pressurized storage tank; and an antimicrobial composition for wound management contained in the bag, the antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 wt% to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.003 wt% to 0.03 wt%, a synthetic silicate clay-based thickener in an amount of 1 wt% to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 wt% to 0.3 wt%, and purified water, wherein the purified water has a hardness of less than 5 ppm measured according to ISO 15923-2:2017 and a resistivity greater than 15 MΩ / cm measured according to ISO 3696:1987 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less.

[0020] In a fourth aspect, there is provided a method for producing a valve system device for wound management, comprising the steps of:

[0021] a) Place the bag-on-valve (BoV) in the storage tank;

[0022] b) crimping the BoV onto a storage tank, which is then filled with propellant gas to obtain a pressurized storage container; and

[0023] c) Filling the bag of the BoV through the valve of the BoV with the antimicrobial composition as described above.

[0024] In a fifth aspect, there is provided a method for delivering an antimicrobial composition to a wound, the method comprising the step of applying to the wound an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 wt% to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.003 wt% to 0.03 wt%, a synthetic silicate clay-based thickener in an amount of 1 wt% to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 wt% to 0.3 wt%, and purified water, wherein the purified water has a hardness of less than 5 ppm measured according to ISO 15923-2:2017 and a resistivity greater than 15 MΩ / cm measured according to ISO 3696:1987 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less.

[0025] In a sixth aspect, a method for treating a wound is provided, wherein an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.002 to 0.1 wt%, a synthetic silicate clay-based thickener in an amount of 1 to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 to 0.3 wt%, and purified water is applied to the wound, wherein the purified water has a hardness of less than 5 ppm measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm measured according to ISO 3696:1987 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less.

[0026] In a seventh aspect, there is provided a composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.002 to 0.1 wt%, a synthetic silicate clay-based thickener in an amount of 1 to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 to 0.3 wt%, and purified water, wherein the purified water 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 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less, for use in preventing or treating infection in a wound.

[0027] Further embodiments of the invention are defined in the appended dependent claims.

[0028] When considered in conjunction with the description and drawings, these and other aspects of some embodiments herein will be better recognized and understood. However, it should be understood that the following description, although pointing out certain embodiments and many specific details therein, is given in an illustrative and non-restrictive manner only. Without departing from the spirit of this document, many changes and modifications can be made within the scope of some embodiments herein, and some embodiments herein include all such modifications.

[0029] One advantage of the present invention is that it can suppress pain sensation on the skin while simultaneously enhancing the antimicrobial effect locally in open wounds where it is needed. This is due to the low buffering capacity. The pH is slightly above neutral, i.e., above pH 7.5, and is therefore less irritating to the skin. In wounds, the pH is typically below 7.5, and due to the low buffering capacity of the antimicrobial gel, the pH of the antimicrobial gel will fall below 7.5 when mixed with the fluid in the wound. Due to the lower pH, the local antimicrobial effect in the wound is subsequently higher. Thus, the enhanced antimicrobial effect is localized where it is needed, i.e., in the wound. At the same time, the skin is not irritated by the low pH.

[0030] One advantage of the present invention is that the antimicrobial composition is provided in gel form, which enables additional treatment methods compared to non-gel aqueous solutions. The gel can be applied to a wound, for example, in the skin, and remain on the skin at a certain thickness while remaining moist for a period of time so that it can exert its antimicrobial effect for an extended period of time.

[0031] The shelf life is greatly improved, which is an advantage compared to many other compositions comprising sodium hypochlorite and hypochlorous acid, especially those in the form of a gel. For many similar compositions in the prior art, a short shelf life is a problem. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Other objects, features and advantages of the present invention will become apparent from the following description when read with reference to the accompanying drawings in which like reference numerals represent corresponding parts throughout the several views:

[0033] Figure 1 A table showing the composition of each ingredient of the antimicrobial composition of the present technology, according to one embodiment, is depicted. The active ingredient composition was determined by iodine titration in accordance with ISO 7393-3:1990(E) Water quality - Determination of free and total chlorine - Part 3: Iodineometric method for the determination of total chlorine.

[0034] Figure 2 Depicted are test results of preservative testing according to the USP Preservative Effectiveness Test according to exemplary cases. The method of USP 41 NF 36, Chapter 51 is referred to when conducting the antimicrobial effectiveness challenge test.

[0035] Figure 3 Depicted are test results for the biocompatibility of antimicrobial compositions of the present technology according to ISO 10993 Biological Evaluation of Medical Devices for in vivo and in vitro studies, according to exemplary scenarios. Biocompatibility testing was performed, including cytotoxicity, sensitization, intradermal reactivity, acute systemic toxicity, and material-mediated pyrogen testing.

[0036] Figure 4 is a flow chart depicting the steps involved in a method of producing an antimicrobial composition of the present technology, according to one embodiment.

[0037] Figure 5 An example of a process for packaging the antimicrobial composition of the present invention into a valve system device comprising a BoV is provided. DETAILED DESCRIPTION

[0038] Before the present invention is disclosed and described in detail, it should be understood that the present invention is not limited to the specific configurations, process steps and materials disclosed herein, as such configurations, process steps and materials may vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting, as the scope of the present invention is limited only by the appended claims and their equivalents.

[0039] It must be noted that, as used in this specification and the appended claims, unmodified nouns mean one or more unless the context clearly dictates otherwise.

[0040] The following terminology is used throughout the specification and claims.

[0041] As used herein, "antimicrobial" is the property of inhibiting or eliminating the growth of microorganisms. Microbial growth includes, but is not limited to, bacterial growth.

[0042] As used herein, buffer capacity is a quantitative measure of the resistance of a solution containing a buffer to changes in pH relative to changes in acid or base concentration. It can be defined as

[0043]

[0044] where d(C) is the minimal amount of added base or added acid, and where d(pH) is the minimal change in pH.

[0045] Buffer capacity depends on pH. For weak acids, buffer capacity is at pH = pK a The height of this peak depends on the pK a When the concentration of the buffer [HA] is very small, the buffer capacity is negligible and increases with the increase of the buffer concentration.

[0046] The buffering capacity β of the gel of the present invention should be less than 0.15. The buffering capacity is measured at pH 8.0. A lower buffering capacity is generally better because the pH in an open wound containing a liquid and having a pH lower than the pH of the gel will drop more. This, in turn, will result in more significant antimicrobial activity. Therefore, a lower buffering capacity is generally better than a higher buffering capacity. The upper limit of the buffering capacity β = 0.15 should be considered an upper limit, and therefore a lower buffering capacity is even better. Thus, in different embodiments, the buffering capacity may be lower 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. The buffering capacity is measured at pH 8.0. In one embodiment, the upper limit of the buffering capacity is the buffering capacity of the composition according to claim 1, i.e., without an added buffer. In an alternative embodiment, the restriction on buffer capacity is replaced by the restriction that no buffer is added in addition to the ingredients according to claim 1 .

[0047] The buffer capacity of 0.15 or less of the present invention is lower than the buffer capacity of CN 113069413 (which is about 0.19). Therefore, the pH of the gel of the present invention changes more in the wound, making the pH closer to the pH in the wound (which is generally less than pH 7.5). At a lower pH, the composition is more antimicrobial.

[0048] In the table below, the buffering capacity of CN 113069413 and the content of the formulation according to the invention are investigated. For the gel according to the invention, the minimum and maximum content of the ingredients are shown.

[0049]

[0050] Using the Henderson-Hasselbalch equation, the above numbers are redefined / theoretically calculated using the following formula.

[0051] pH = pKa + Log (A) / (HA)

[0052]

[0053] The buffer capacity of CN 113069413 was calculated using the molar concentration of boric acid as follows:

[0054]

[0055] It can be clearly seen that the buffer capacity of the gel according to the invention must be significantly lower than that of CN 113069413, since CN 113069413 comprises a phosphate buffer, whereas the gel according to the invention does not.

[0056] Based on the above calculations, the buffer capacity of D1 is estimated to be 0.189.

[0057] In the following detailed description, numerous specific details are set forth to provide a comprehensive 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 cases, well-known methods, procedures, and / or components are not described in detail in order to avoid obscuring the present invention.

[0058] In a first aspect, an antimicrobial composition is provided comprising sodium hypochlorite (NaOCl) in an amount of 0.015 wt% to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.002 wt% to 0.1 wt%, a synthetic silicate clay-based thickener in an amount of 1 wt% to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 wt% to 0.3 wt%, and purified water, wherein the purified water has a hardness of less than 5 ppm measured according to ISO 15923-2:2017 and a resistivity greater than 15 MΩ / cm measured according to ISO 3696:1987 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity measured at pH 8.0 is 0.15 or less.

[0059] One advantage of the present invention is that the composition increases moisture within the wound, which makes it effective in aiding the debridement and desloughing process in dry, necrotic wounds. The composition is intended for moistening and debridement of acute and chronic wounds, such as stage I to IV ulcers, venous stasis and diabetic ulcers, postoperative 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 promotes autolytic debridement. The composition has antimicrobial properties. Sodium hypochlorite provides antibacterial properties. The antimicrobial composition is a transparent composition that helps maintain a moist wound environment that aids wound healing.

[0060] Various additives have been shown to impair the shelf life of compositions containing sodium hypochlorite and hypochlorous acid. For example, various impurities and additives in the water used to prepare the compositions have been shown to accelerate the degradation of the active antimicrobial substance, resulting in reduced activity and an unacceptably short shelf life. While the detailed reaction mechanism is unknown at the molecular level, the inventors have discovered that high water hardness and the presence of metal ions accelerate the degradation of the active compound.

[0061] Water hardness is measured as total hardness according to 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.

[0062] The metal ion content is measured by measuring the resistivity of the water. This is a good approximation because the positive counterions are most often metal ions and because H + It is also believed to contribute to the degradation of the active ingredient. The electrical conductivity of the water (i.e., the reciprocal of the resistivity) is measured as outlined in ISO 3696:1987, and the resistivity is then calculated based on 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.

[0063] In particular, the present inventors believe that the combination of high water hardness and the presence of metal ions contributes to accelerated degradation of the active ingredient. Therefore, it is important to keep both the amount of metal ions and the water hardness low in the water used to prepare the composition. When the water hardness and resistivity are maintained within the above-mentioned ranges (i.e., resistivity greater than 15 MΩ / cm and hardness less than 5 ppm), the shelf life of the composition is improved.

[0064] Additionally, other quality standards apply to the water used in the preparation of the product, especially since the composition is a medicinal product and should meet high standards.

[0065] TOC is measured according to ISO 20236:2018 and recalculated to ppb by weight. In one embodiment, TOC does not exceed 50 ppb. In one embodiment, TOC is less than 10 ppb. All are calculated by weight.

[0066] In one embodiment, the TDS as measured according to ASTM D5907-10 is no more than 50 ppm by weight. In one embodiment, the TDS is no more than 15 ppm. In another embodiment, the TDS is no more than 5 ppm. All are calculated by weight. In addition, the level of heavy metals should be low. In one embodiment, the amount of the heavy metals arsenic, cadmium, and lead is less than 0.1 ppm by weight in total. In fact, it has been shown that the choice of thickener is not insignificant, because it should be acceptable from a medical point of view and should not accelerate the decomposition of the active antimicrobial component. All additives in the composition have the potential to accelerate the decomposition of the active ingredient, and therefore all additives must be carefully selected so that they do not accelerate the decomposition of the antimicrobial compound in the composition. It has been shown that the selected thickener based on synthetic silicate clay meets these requirements. In particular, when using a thickener based on synthetic silicate clay, and when the amount of metal ions and water hardness are within the required range, the antimicrobial component will not degrade.

[0067] The use of a synthetic silicate clay based thickener and the use of water having a resistivity higher than 15 MΩ / cm and a hardness lower than 5 ppm provides for an increased shelf life by not accelerating the decomposition of the antimicrobial agent.

[0068] All of the above limitations on water apply to purified water prior to adding it to the composition.

[0069] In one embodiment, the amount of sodium hypochlorite is from 0.04 wt% to 0.06 wt%.

[0070] In one embodiment, the amount of hypochlorous acid (HOCl) is 0.005 wt % to 0.02 wt %. This range of NaOCl and HOCl concentrations shows good biocompatibility and antimicrobial efficacy.

[0071] In one embodiment, the amount of sodium chloride is 0.05 wt% to 0.2 wt%. This range of NaCl is suitable for acting as a stabilizer and preservative ingredient.

[0072] In one embodiment, the synthetic silicate clay based thickener comprises lithium sodium magnesium silicate.

[0073] In one embodiment, a 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 polydimethylsiloxane, carboxymethylcellulose, xanthan gum, and carbomer are unable to retain the active ingredient and do not produce the desired gel.

[0074] In one embodiment, purified water constitutes the remainder of the composition other than sodium hypochlorite (NaOCl), hypochlorous acid (HOCl), a synthetic silicate clay-based thickener, and sodium chloride (NaCl). Purified water is required to ensure that no other ions are present in the gel that would destabilize the active ingredient.

[0075] The pH of the composition is higher than 7.5. In one embodiment, the pH of the composition is 7.5 to 10.0. The growth of wound healing cells (including fibroblasts and keratinocytes) is promoted by alkaline pH (Teshima et al, 2020). In an alternative embodiment, the pH of the composition is 7.5 to 9.5. In an alternative embodiment, the pH of the composition is 7.5 to 9.0. In an alternative embodiment, the pH of the composition is 8.0 to 9.0. In an alternative embodiment, the pH of the composition is 8.0 to 9.5. In an alternative embodiment, the pH of the composition is 8.0 to 10.0. For the present invention, including the specification, examples and claims, pH is measured following the method described in ASTM E70-19.

[0076] Compared to the prior art including CN 113069413A, the prior art of the present invention has a much lower buffer capacity. It is known that the intensity of pain sensation is much lower at high pH compared to lower pH. (Amiloride-blockable acid-sensing ion channels are leading acid sensors expressed in human nociceptors, Shinya Ugawa, J. Clin. Invest. 110: 1185-1190 (2002). doi: 10.1172 / JCI200215709.). Therefore, in terms of pain sensation, a pH higher than neutral is suitable. However, due to the low buffer capacity, the pH becomes lower in wounds with a lower pH. Wounds typically have a pH below 7.5. This produces a higher antimicrobial effect locally in the wound.

[0077] Hypochlorous acid (HOCl) exists in equilibrium so that at very low pH (below about 1.5), Cl2 is the predominant species; between about pH 1.5 and 7.5, HOCl is the predominant species; and above pH 7.5, (OC1) - Hypochlorous acid (HOCl) exists in different forms depending on the pH, although in the present invention, when the pH is above 7.5, it exists mainly in the form of (OC1) - exists, but it is still called hypochlorous acid (HOCl). It is also known as (OC1)- In contrast, the substance HOCl (which is the main substance at about pH 1.5 to 7.5) is the most antibacterial. In view of this, it is natural that the pH of many antibacterial compositions involving hypochlorous acid (HOCl) is in the pH range of 1.5 to 7.5. Due to the low buffering capacity of the gel, the gel will mix with the fluid in the wound, causing the pH to become lower, and HOCl becomes the main substance with a higher antimicrobial effect locally in the wound. The pH of the wound is usually lower than 7.5. Therefore, the composition is particularly suitable for treating wounds with neutral or acidic pH.

[0078] The present invention provides sufficient antimicrobial activity for wound treatment at a pH higher than 7.5. At the same time, there is also an additional effect of providing additional antimicrobial activity. Most wounds have a neutral pH, and for open wounds, the composition of the present invention will mix with the liquid in the open wound, and the pH of the mixture will then be lower than 7.5. This reduction in pH will improve the antimicrobial effect of the composition. It should be noted that this effect is present in the wound and very close to the wound where the composition mixes with the fluid from the wound. This provides the advantage of locally enhancing the antimicrobial effect in just the desired place, i.e., in the wound and / or near the wound. The farther away from the open wound, the less irritating the composition according to the present invention is to the skin due to the higher pH value. Therefore, the present invention combines lower irritation with antimicrobial effect when needed.

[0079] It should be noted that the buffering capacity in the composition according to the present invention is low, so that the pH value is affected by the fluid in the open wound. In this regard, it should be noted that CN 113069413 contains a phosphate buffer, so that the pH in the open wound does not change to a significant extent. Therefore, it is advantageous that the composition according to the present invention does not contain a buffer.

[0080] In one embodiment, the composition has a viscosity of 8,000 to 10,000 cp. This high viscosity allows the gel to remain in the wound cavity and provide more moisture. Viscosity was measured using a Brookfield viscometer according to ISO 2555:2018, Plastics—Resins in the liquid state or as emulsions or dispersions—Determination of apparent viscosity using a single cylinder type rotational viscometer method.

[0081] In a second aspect, a method (400) for preparing an antimicrobial composition is provided, the method comprising the steps of:

[0082] a) Provide

[0083] i. Purified water, wherein the purified water, prior to being added to the composition, has a hardness of less than 5 ppm as measured in accordance with ISO 15923-2:2017 and a resistivity greater than 15 MΩ / cm as measured in accordance with ISO 3696:1987;

[0084] ii. thickeners based on synthetic silicate clays;

[0085] iii. sodium hypochlorite solution, and

[0086] iv. sodium chloride, and

[0087] b) mixing purified water, a thickener based on synthetic silicate clay, a sodium hypochlorite solution and sodium chloride to obtain an antimicrobial composition,

[0088] wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffering capacity β measured at pH 8.0 is 0.15 or less.

[0089] In a specific embodiment of the second aspect, the method comprises the following steps:

[0090] a) filling (402) a container with purified water;

[0091] b) adding (406) lithium sodium magnesium silicate during mixing and stirring (408) for at least 90 seconds;

[0092] c) adding (410) sodium hypochlorite solution and stirring for at least 30 seconds; and

[0093] d) Sodium chloride (NaCl) is added (412) to the mixture and stirred for at least 120 seconds.

[0094] This specific implementation plan Figure 4 In one embodiment, Figure 4 Steps b) to d) are performed in sequential order.

[0095] In one embodiment, the concentration of the sodium hypochlorite solution in step c) is 4 wt % to 8 wt %.

[0096] In a third aspect, a valve system device for wound management is provided, the valve system device comprising: a bag-on-valve (BoV) within a pressurized storage tank; and an antimicrobial composition for wound management contained in the bag, the antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 wt% to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.003 wt% to 0.03 wt%, a synthetic silicate clay-based thickener in an amount of 1 wt% to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 wt% to 0.3 wt%, and purified water, wherein the purified water has a hardness of less than 5 ppm measured according to ISO 15923-2:2017 and a resistivity greater than 15 MΩ / cm measured according to ISO 3696:1987 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less.

[0097] In one embodiment, the pressurized storage tank contains a non-flammable propellant.

[0098] In one embodiment, the pressurized storage canister is an aerosol spray canister.

[0099] In a fourth aspect, there is provided a method for producing a valve system device for wound management, comprising the steps of:

[0100] a) Place the bag-on-valve (BoV) in the storage tank;

[0101] b) crimping the BoV onto a storage tank, which is then filled with propellant gas to obtain a pressurized storage container; and

[0102] c) Filling the bag of the BoV through the valve of the BoV with the antimicrobial composition as described above.

[0103] In one embodiment, said steps a) to c) of said method for producing a valve system device for wound management are performed in a sequential manner.

[0104] In a fifth aspect, there is provided a method for delivering an antimicrobial composition to a wound, the method comprising the step of applying to the wound an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 wt% to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.003 wt% to 0.03 wt%, a synthetic silicate clay-based thickener in an amount of 1 wt% to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 wt% to 0.3 wt%, and purified water, wherein the purified water has a hardness of less than 5 ppm measured according to ISO 15923-2:2017 and a resistivity greater than 15 MΩ / cm measured according to ISO 3696:1987 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less.

[0105] Various embodiments of the present invention provide an antimicrobial composition for wound management and a method for producing the same. The antimicrobial composition comprises sodium hypochlorite (NaOCl), hypochlorous acid (HOCl), a synthetic silicate clay-based thickener, sodium chloride (NaCl), and purified water, wherein the purified water must meet certain standards for hardness and resistivity.

[0106] In a sixth aspect, a method for treating a wound is provided, wherein an antimicrobial composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.002 to 0.1 wt%, a synthetic silicate clay-based thickener in an amount of 1 to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 to 0.3 wt%, and purified water is applied to the wound, wherein the purified water has a hardness of less than 5 ppm measured according to ISO 15923-2:2017 and a resistivity of greater than 15 MΩ / cm measured according to ISO 3696:1987 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less.

[0107] In a seventh aspect, there is provided a composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 to 0.15 wt%, hypochlorous acid (HOCl) in an amount of 0.002 to 0.1 wt%, a synthetic silicate clay-based thickener in an amount of 1 to 10 wt%, sodium chloride (NaCl) in an amount of 0.03 to 0.3 wt%, and purified water, wherein the purified water 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 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less, for use in preventing or treating infection in a wound.

[0108] Thus, the sixth and seventh aspects provide for the treatment of wounds, and in particular the prevention and / or treatment of infection in wounds.

[0109] The antimicrobial composition of the present invention has a pH higher than 7.5 and free available chlorine (30 ppm to 200 ppm), and is capable of killing a wide range of microorganisms, including bacteria and fungi. In one embodiment, the free available chlorine as measured according to ISO 7393-2:2017 is 30 to 200 ppm. The free available chlorine provides the composition with the ability to eliminate a wide range of microorganisms (including bacteria and fungi).

[0110] In one embodiment, the antimicrobial composition of the present invention is a hemostatic agent. In one embodiment, the antimicrobial composition of the present invention is a chemical hemostatic agent. The antimicrobial composition promotes hemostasis when applied, and can stop or slow bleeding from a wound.

[0111] In one 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 tank and an antimicrobial composition for wound management contained within the bag. The antimicrobial composition comprises sodium hypochlorite (NaOCl), hypochlorous acid (HOCl), a synthetic silicate clay-based thickener, sodium chloride (NaCl), and purified water. In one embodiment, when stored within the valve system device, the antimicrobial composition of the present invention is an aerosol spray composition. In another embodiment, when sprayed from the valve system device or applied to a wound via the valve system device, the antimicrobial composition of the present invention is an aerosol spray composition. In one embodiment, when applied to a wound from the valve system device, the antimicrobial composition of the present invention becomes aerated and forms a foam-like or froth-like spray composition on the wound. In one embodiment, the bag containing the antimicrobial composition for wound management does not contain a propellant, or does not contain a chemical propellant. The valve device of the present invention does not utilize chemical propellants that come into contact with the antimicrobial composition of the present invention.

[0112] In one embodiment, the pressurized storage tank of the valve system assembly of the present invention contains a chemical propellant. Specifically, the present invention does not utilize any flammable materials or any flammable propellants, which reduces the risk of operating the valve system assembly while exposed to high temperatures or fire. The absence of any flammable materials in the valve system assembly of the present invention also extends and maintains shelf life, as flammability is no longer an issue, particularly when storing the valve system assembly.

[0113] The chemical propellant contained in the pressurized storage tank provides pressure to the bag within the pressurized storage tank, which allows the composition within the bag to be indirectly pushed out of the valve system device when the composition is applied. Since the chemical propellant is contained outside the bag, the separation of the chemical propellant from the bag prevents any change in the quality or characteristics of the antimicrobial composition stored in the bag. In one embodiment, the chemical propellant is nitrogen. Using nitrogen as a propellant is not only non-flammable, inert, and has an extremely low boiling point (-195°C), but also helps maintain the flow of highly viscous liquids in the pipeline, which allows the distribution of nearly 99.9% by weight of the composition stored in the bag.

[0114] In one embodiment, the pressurized storage canister used in the valve system device of the present invention is an aerosol spray container suitable for dispensing a composition in foam or foam-like form. The use of a valve system in the device of the present invention allows the product to be dispensed in a pure form, i.e., without any additional mixing of unnecessary components, allowing the valve system to store and receive a greater volume of composition than conventional and pre-existing bag-on-valve product packaging. Furthermore, the valve system of the present invention allows for dispensing of the stored antimicrobial composition at 99.99% by weight, preventing any unused residual composition. The valve system device of the present invention can also be used for continuous and uninterrupted spray at any angle and with a uniform / controlled spray stream and pattern, unlike conventional aerosol spray systems that vary in spray volume when tilted. These characteristics of the valve system device enable it to be used to apply first aid solutions to unusual or difficult wound situations, such as incidents involving critically pinned persons or incidents requiring precise movement and handling. Thus, the valve system of the present invention provides overall improved efficiency in wound management over prior art techniques. Furthermore, the aerated composition generated by the valve system delivers a cooling effect to the wound, thereby providing further pain relief to the injured subject.

[0115] In one embodiment, the valve system used comprises a bag-on-valve (BoV) system. In one embodiment, wherein the valve system comprises a BoV system, the BoV comprises a bag connected to a valve. The bag connected to the valve is folded, curled, or compressed and does not contain material, which is configured to receive any liquid or fluid material that enters the bag through the valve.

[0116] In another embodiment of the present invention, a method for producing a valve system device for wound management is provided. The method comprises the steps of placing a bag-on-valve (BoV) within a storage canister, crimping the BoV onto the storage canister, subsequently filling the storage canister with a propellant gas to obtain a pressurized storage container, and filling the bag of the BoV through the valve of the BoV with an antimicrobial composition.

[0117] refer to Figure 1 , Figure 1 A table showing the composition of each component of an antimicrobial composition according to one embodiment is depicted. The antimicrobial composition of the present technology has antimicrobial properties. In one embodiment, as Figure 1As shown in the table in, in the antimicrobial composition, sodium hypochlorite is 0.05 wt%, hypochlorous acid (HOCl) is 0.01 wt%, sodium chloride is 0.10 wt%, and a synthetic silicate clay-based thickener is 4.0 wt%, and purified water is 95.85 wt%. In one embodiment, the synthetic silicate clay-based thickener comprises sodium magnesium lithium silicate. In one embodiment, the composition of sodium magnesium lithium silicate is 4.0 wt%.

[0118] Figure 2 Depicted are test results of preservative testing according to the USP (United States Pharmacopeia) preservative effectiveness test according to exemplary scenarios. The compositions of the antimicrobial compositions of the present technology were tested by an accredited laboratory for USP 51 and preservative effectiveness testing to demonstrate antibacterial effects. Figure 2 The table depicts the test results of the preservative test of the composition. Figure 2 As can be seen in the table, the antibacterial properties are imparted in particular by the addition of sodium hypochlorite, which leads to biosynthetic changes in cellular metabolism and inhibits bacterial growth by acting as an antiseptic. The effect of reducing the microbial population has been demonstrated in vitro for clinically relevant strains known to cause wound infections of both Gram-positive and Gram-negative bacteria, as well as fungi.

[0119] Figure 3 Depicted are test results of the biocompatibility of the antimicrobial compositions of the present technology according to International Organization for Standardization (ISO) 10993 for in vivo and in vitro studies, according to exemplary cases. Figure 3 As shown in , during the intradermal reactive irritation test of the antimicrobial composition of the present invention, there was no sign of erythema or edema. In addition, the antimicrobial composition of the present invention had no cytotoxic effect or oral toxicity.

[0120] Figure 44 is a flow chart depicting the steps involved in one embodiment of a method for preparing 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 sodium magnesium lithium silicate (a 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 dried 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 homogenized. In one embodiment, the sodium hypochlorite solution is 4% to 8% by weight.

[0121] Example

[0122] Example 1

[0123] Example 1 includes filling three liters of purified water into a container. This example also includes turning on a high shear mixer and setting the speed to 2000 rpm. This example also includes slowly adding 120 g ± 1 g of sodium magnesium lithium silicate (thickener) to the solution from the edge of the container. This example also includes continuously stirring the mixture at 2000 rpm for 30 minutes. This example also includes 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 also includes adding 3.0 g ± 0.1 g of PDV (NaCl) salt to the mixture. This example also includes stirring the mixture until the mixture is completely homogenized, wherein the mixture is stirred at 5500 rpm for 15 minutes. The sodium hypochlorite solution is 4% to 8% by weight.

[0124] Example 2

[0125] exist Figure 5 In the provided embodiment shown in , a semi-automatic crimping, inflating and filling machine (AM-04) is used to fill a pressurized storage tank with the form of an antimicrobial composition. First, a bag on valve (BoV) is placed in the storage tank. The valve of the BoV is crimped onto the storage tank, and then the storage tank is filled with nitrogen, a propellant gas, to obtain a pressurized storage tank containing the BoV. The antimicrobial composition is then filled into the connected bag (BOV) through the valve. This feature allows the product to be physically separated from the propellant gas used.

[0126] The following is a summary of the process parameter settings for small (50g) and large (100g) jars:

[0127]

[0128] *1 circle = 360 degrees

[0129] (BOV, non-aerosol) is classified as a non-flammable product according to EC Council Directive 75 / 324 / EEC (Annex 1 - Definition 1.9).

[0130] In one embodiment provided, the main components of the product, particularly the valve system device for wound management are:

[0131] - Antimicrobial wound composition: 0 wt% combustible components (based on water).

[0132] - Nitrogen: inert gas containing 0% by weight of flammable components. The term "aerosol" herein refers to a product property that depends on the force of pressure to expel the contents from the container (USFDA - Tamper Resistance Regulation - 21 CFR 700.25).

[0133] In one embodiment, the valve device for wound management of the bag-on-valve technology of the present invention is a compartmentalized aerosol dispenser comprising a metal / plastic bag connected to a valve or valve body. No mixing of the propellant gas and the product occurs (NIST Aerosol and Bag-on-Valve Definition Guide (DDF 1 / 28 / 12) - February 2012).

[0134] Various embodiments of the present invention provide antimicrobial compositions developed for the moisturization and debridement of acute and chronic wounds, such as stage I to IV ulcers, venous stasis and diabetic ulcers, post-operative wounds, first and second degree burns, and pressure sores, to help maintain a moist wound environment, promote granulation and epithelialization, and promote autolytic debridement.

[0135] Example 3

[0136] exist Figure 2 In the provided examples shown in , the Preservative Effectiveness Test USP 51 was used to evaluate the antimicrobial properties of the gels when tested against selected bacteria, fungi and yeasts, respectively.

[0137] In this method, a gel is inoculated with a controlled amount of a specific microorganism. The test then compares the initial microbial levels to a test sample at a specific temperature at multiple time intervals over a 28-day period. The log reduction of the organisms is evaluated at specified time intervals to quantitatively assess the effectiveness of the gel's antimicrobial properties in preventing microbial proliferation and / or killing or reducing the organism population.

[0138] For surface-based products, the preservative is effective in the product being inspected if:

[0139] Bacteria - For bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia), a log reduction of at least 2.0 compared to the initial counts was observed on day 14, and no improvement was observed on day 28 compared to the counts on day 14. Yeast and molds - For yeast and molds (Candida albicans and Aspergillus brasiliensis), no improvement was observed on days 14 and 28 compared to the initial calculated counts.

[0140] Example 4

[0141] In one example provided, iodometric titration was performed to determine the hypochlorous acid and sodium hypochlorite in the raw materials used to prepare the hydrogel compositions of the present invention.

[0142] The reagents used were initially prepared according to the following procedure:

[0143]

[0144] The samples prepared were sodium hypochlorite, antimicrobial aqueous solution ( aqua, which wound care solution) and an antimicrobial gel composition ( aqua gel, which The wound care gel is the same, and its contents are based on Figure 1 and falling within claim 1):

[0145]

[0146] Titrate the sample. Rinse the burette with a small amount of sodium thiosulfate solution and then fill it with sodium thiosulfate to just above the zero mark. Pour a small amount of solution through the burette tip to release trapped bubbles. Add approximately 25 ml of 10% potassium iodide solution to the sample solution. Add approximately 10 ml of acetic acid to create acidic conditions. The addition of acetic acid and potassium iodide causes the color of the sample solution to change from colorless to amber-brown. The sample solution is then titrated with 0.2N / 0.05N sodium thiosulfate to a straw yellow color. Since iodine is released rapidly, the titration needs to be performed quickly. Add approximately 5 ml of starch indicator and continue titrating until the blue color disappears. The added starch indicator reacts with the iodine to form a very intense blue / purple complex. Stop the titration once a clear solution is obtained. Then, record the volume of sodium solution titrated for further calculations.

[0147] Calculate the number of moles of sodium thiosulfate per titration using the following equation:

[0148]

[0149] And by calculating the moles of sodium thiosulfate, use the stoichiometric reaction to calculate the moles of hypochlorite

[0150]

[0151] The stoichiometry of the equation indicates that there are 2 moles of thiosulfate ions per mole of hypochlorous acid:

[0152] Moles of HOCl = 1 / 2S2O3 2- Moore

[0153] Moles of HOCl = moles of NaOCl.

[0154] The concentration of NaOCl in the feedstock (in wt %) was calculated using the following calculation:

[0155]

[0156] V is the volume of the titrant (in ml), N represents the normality of the sodium thiosulfate used (N), and M represents the mass of the sample. The calculated mw of NaOCl is 74.44 g / mol.

[0157] Antimicrobial aqueous solution ( aqua, which comes from The concentrations of NaOCl and HOCl (in wt %) in the wound care solution (the wound care solution) were calculated using the following calculation:

[0158]

[0159] In the calculations provided, the normality of sodium thiosulfate used was 0.05 N, the mw of NaOCl was 74.44 g / mol, and the mw of HOCl was 52.46 g / mol.

[0160] It is obvious to those skilled in the art that the present invention can be easily produced in other specific forms without departing from its essential characteristics. The present embodiments are therefore to be considered as illustrative only and not restrictive, the scope of the invention being indicated by the claims rather than the foregoing description, and all variations falling therein are therefore intended to be embraced therein.

[0161] Example 5

[0162] Since the quality of the water used to prepare the composition is very important, examples of water purification of the water used in preparing the composition are given.

[0163] First, tap water is fed into the first stage of the RO / DI system, which consists of a sediment filter (primarily composed of sand of various sizes) and a carbon filter. The sediment filter is used to capture large, free-floating particles or contaminants. The carbon filter, on the other hand, consists of granular carbon and absorbs organic matter and other dissolved contaminants such as chlorine and chloramines.

[0164] After the carbon filtration stage, the water enters the softener column and the hard mineral ions in the water (such as magnesium Mg 2+ and calcium Ca 2+ ) are removed. When hard water enters the mineral tank, it flows through a bed of spherical resin beads. These beads are charged with sodium ions. The resin beads are negatively charged anions. Calcium and magnesium minerals are positively charged, making them cations. As the hard water passes through the resin, the beads grab the mineral ions and remove them from the water. As the beads capture the mineral ions, sodium ions are released.

[0165] The water is then fed into a reverse osmosis (RO) system and filtered through multiple layers of membranes, which removes most contaminants such as salt, bacteria, heavy metals, and other organic matter. From there, the water is divided into two distinct water lines: wastewater and product water. The product water is nearly pure and flows into a storage tank that acts as a storage tank for the DI (deionization) system. A certain percentage of the wastewater is recirculated into the RO system, and the remainder is discharged to the drain line.

[0166] Before being fed into the DI system, the RO water is cooled by a chiller to a temperature range of 20 to 25°C. The cooled water then passes through an ultraviolet (UV) purifier for disinfection. UV purifiers expose living organisms, such as bacteria, viruses, or cysts (such as Cryptosporidium and Giardia), to germicidal ultraviolet radiation to destroy the DNA in the pathogenic microorganisms so that they cannot, at least not reproduce.

[0167] After UV disinfection, the water passes through three identical deionization columns containing resin. During the deionization stage, an ion exchange process is used to attract mineral impurities such as sodium and other metal elements. The negatively charged cation resin attracts the positively charged ions in the water, while the positively charged anion resin attracts the negative ions. Finally, the DI water passes through ultrafine filter cartridges (i.e., 0.45 μm and 0.2 μm), and the water is then fed into the pipeline to the point of use in the production plant. Unused purified water is recycled back to the storage tank and fed back into the DI system to continuously repeat the same deionization process.

Claims

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

2. The antimicrobial composition according to claim 1, wherein the amount of sodium hypochlorite is 0.04 wt% to 0.06 wt%.

3. The antimicrobial composition according to any one of claims 1 to 2, wherein the amount of hypochlorous acid (HOCl) is 0.005 wt% to 0.02 wt%.

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

5. An antimicrobial composition according to any one of claims 1 to 4, wherein the synthetic silicate clay based thickener comprises lithium sodium magnesium silicate.

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

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

8. The antimicrobial composition of any one of claims 1 to 7, wherein the composition has 30 to 200 ppm of free available chlorine.

9. A method (400) for preparing an antimicrobial composition, comprising the steps of: a) Provide i. Purified water, wherein the purified water 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 before being added to the composition; ii. thickeners based on synthetic silicate clays; iii. sodium hypochlorite solution, and iv. sodium chloride, and b) mixing said purified water, said synthetic silicate clay based thickener, said sodium hypochlorite solution and said sodium chloride to obtain said antimicrobial composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less.

10. The method according to claim 9, wherein the concentration of the sodium hypochlorite solution is 4 wt% to 8 wt%.

11. The method of any one of claims 9 to 10, wherein the synthetic silicate clay based thickener comprises lithium sodium magnesium silicate.

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

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

14. A valve system device for wound management according to any one of claims 12 to 13, wherein the pressurized storage canister is an aerosol spray canister.

15. A method for producing a valve system device for wound management, comprising the steps of: a) Place the bag-on-valve (BoV) in the storage tank; b) crimping the BoV onto the storage tank and subsequently filling the storage tank with propellant gas to obtain a pressurized storage container; as well as c) Filling the bag of the BoV through the valve of the BoV The antimicrobial composition according to any one of claims 1 to 9.

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

17. The method of claim 16, wherein applying the antimicrobial composition to the wound is performed via a valve system device comprising a bag within a pressurized storage tank and the antimicrobial composition for wound management contained in the bag.

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

19. A composition comprising sodium hypochlorite (NaOCl) in an amount of 0.015 to 0.15 wt. %, hypochlorous acid (HOCl) in an amount of 0.002 to 0.1 wt. %, a synthetic silicate clay-based thickener in an amount of 1 to 10 wt. %, sodium chloride (NaCl) in an amount of 0.03 to 0.3 wt. %, and purified water, wherein the purified water 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 before being added to the composition, wherein the pH of the composition is in the interval of 7.5 to 10.0, and wherein the buffer capacity β measured at pH 8.0 is 0.15 or less, for use in preventing or treating infection in a wound.

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