KR102650456B1 - Antimicrobial composition containing plasma radical solution and manufacturing method thereof - Google Patents

Abstract

The present invention relates to an antibacterial composition containing a plasma radical solution with excellent antibacterial effect and a method for producing the same. A composition that can be mixed stably while maintaining antibacterial properties by adding a plasma radical solution with very high reactivity and other additives. It is about manufacturing method. Antibacterial compositions containing such radical solutions can not only be used in the cosmetics industry through pH adjustment, but can also be used in various industrial fields such as household environmental products, quasi-drugs, and pharmaceuticals.

Description

Antimicrobial composition containing plasma radical solution and manufacturing method thereof}

The present invention relates to an antibacterial composition containing a plasma radical solution with excellent antibacterial effect and a method for producing the same. The present invention relates to a composition that can be mixed stably while maintaining antibacterial effect by adding a plasma radical solution with very high reactivity and other additives. It's about method. Antibacterial compositions containing such radical solutions can not only be used in the cosmetics industry through pH adjustment, but can also be used in various industrial fields such as household environment products, quasi-drugs, and pharmaceuticals.

Starting with the SARS virus in 2011, the importance of personal hygiene management is increasing due to the continuous and powerful outbreak of infectious diseases such as Ebola and MERS viruses. In particular, the 2019 coronavirus (COVID-19) has become a global pandemic and has continued for over a year. As the outbreak cycle of infectious diseases prevalent around the world becomes shorter and the types of infectious diseases become more diverse, the importance of maintaining personal hygiene and cleanliness is increasingly emphasized. As a result, the use of hygiene management products such as hand sanitizers and hand cleaners (hand cleaners) is actively recommended in cases where it is difficult to wash hands immediately or when there is a risk of infection by external pathogens, and the demand for disinfection and antibacterial products is increasing. It is expected to increase.

Hygiene management products such as hand sanitizers and hand cleaners are generally classified into gel type and liquid type, and are managed as quasi-drugs and basic cosmetics, and most of them are manufactured based on alcohol and hypochlorous acid. It is becoming. However, alcohol and hypochlorous acid contained in conventional disinfection and antibacterial products are harmful to the human body, causing dermatitis, burns, etc., causing various risks and accidents to occur one after another. For this reason, demand for and interest in products that can safely manage personal hygiene is increasing.

The present invention relates to a method for producing a composition that can be mixed stably while maintaining antibacterial properties by adding a highly reactive plasma radical solution and other additives. A plasma radical solution is a solution in which various active species are dissolved in water by reacting active species containing ions and radicals generated in plasma with water. These active species are artificially created by plasma and are quite unstable and have very high reactivity. For this reason, the active species react with other added substances to return to a stable form and lose their unique efficacy. However, the present invention provides a composition formulation and manufacturing method that can further maximize the efficacy of the unique plasma radical solution (antibacterial) without losing it even when mixed with a plasma radical solution having a very high reactivity.

That is, the purpose of the present invention is to provide an antibacterial agent composition containing a plasma radical solution that can exhibit high antibacterial efficacy and has high stability, and a method for producing the same.

The antibacterial composition according to an embodiment of the present invention may include a plasma radical solution with very high reactivity as an active ingredient.

In one embodiment, the antibacterial composition may further include HEPES (Hydroxyethyl piperazine Ethane Sulfonicacid).

In one embodiment, the antibacterial composition may further include mandarin extract.

In one embodiment, the antibacterial composition may further include hyaluronic acid.

In one embodiment, it may include 85 to 97% by weight of the plasma radical solution, 0.1 to 1.5% by weight of HEPES, 0.5 to 2.0% by weight of mandarin extract, and 0.0001 to 0.1% by weight of hyaluronic acid, based on the total weight.

In one embodiment, the pH of the antibacterial composition may be 3.0 to 4.0.

In one embodiment, the antibacterial composition may further include 0.4 to 2.0% by weight of glycerin, 1.0 to 3.0% by weight of 1,3-butylene glycol, and 0.5 to 3.0% by weight of propanediol, based on the total weight.

In one embodiment, the antibacterial composition may be in the form of a hand sanitizer (quasi-drug), disinfectant, household disinfectant (home environment product), and hand cleaner (cosmetics, hand cleaner).

Meanwhile, the method for producing an antibacterial composition according to another embodiment of the present invention is an agent that mixes a highly reactive plasma radical solution, HEPES (Hydroxyethyl piperazine Ethane Sulfonicacid), glycerin, 1,3-butylene glycol, and propanediol. Level 1; It may include a second step of cooling the mixed solution after the first step, adding hyaluronic acid and stirring, and a third step of adding mandarin extract to the mixed solution after the second step.

In one embodiment, in the first step, the temperature of the mixed solution may be maintained at 40 to 60°C.

In one embodiment, in the second step, the mixed solution after the first step is cooled to 20 to 40° C., and then hyaluronic acid may be added.

In one embodiment, in the third step, the mixed solution after the second step may be cooled to 20 to 30° C. and then the mandarin extract may be added.

The antibacterial composition according to the present invention exhibits strong antibacterial properties and harmlessness to the human body by appropriately adjusting the pH of the highly reactive plasma radical solution, and at the same time prevents precipitation of the mandarin extract, which exhibits fungal efficacy, from occurring, making it highly safe for the hands. It can be used in the formulation of disinfectants (quasi-drugs), disinfectants, household disinfectants, etc. (living environment products).

In addition, moisturizers of polyhydric alcohols such as glycerin, 1,3-butylene glycol, and propanediol, which are added for moisturizing action in human skin, are added to the antibacterial composition containing this plasma radical solution to produce highly stable hand cleaners (cosmetics, It can be used as a formulation for hand cleaner.

Figures 1a - 1b show the evaluation results of sterilization and antibacterial tests against S.Aureus and C.Albicans of the antibacterial composition, ethanol (Comparative Example 1), and hypochlorous acid water (Comparative Example 2) according to an embodiment of the present invention, respectively. .
Figures 2a - 2b show the results of bactericidal and antibacterial tests for bacteria (S. Aureus) and fungi (C. Albicans) of samples with different contents of mandarin extract, respectively.
Figure 3 shows the results of stability evaluation according to the HEPES content of the antibacterial composition according to an example of the present invention.
Figures 4a - 4b show the results of sterilization and antibacterial test evaluations for S. Aureus and C. Albicans of samples with different HEPES contents, respectively.

The terms used in this application are only used to describe specific embodiments and are not intended to limit the present invention. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this application, terms such as “comprise” or “have” are intended to designate the presence of features, steps, operations, components, parts, or combinations thereof described in the specification, but are not intended to indicate the presence of one or more other features or steps. , it should be understood that it does not exclude in advance the possibility of the existence or addition of operations, components, parts, or combinations thereof.

Unless otherwise defined, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by a person of ordinary skill in the technical field to which the present invention pertains. Terms defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related technology, and unless explicitly defined in the present application, should not be interpreted in an ideal or excessively formal sense. No.

The antibacterial composition according to an embodiment of the present invention contains a plasma radical solution with very high reactivity as an active ingredient.

The plasma radical solution is a component that has sterilizing power against microorganisms and thus exhibits antibacterial efficacy. This plasma radical solution becomes acidic, and the dissolved active species may include one or more of nitrogen active species and oxygen active species.

In one embodiment, the plasma radical solution may be prepared through the following steps.

(a) Plasma can be generated to generate active species including nitrogen oxides. In one embodiment, a microwave plasma generator may be used to generate plasma, and as the plasma is generated, active species including nitrogen oxides may be generated.

(b) The active species can be oxidized using one or more of corona discharge and a catalyst. Among the nitrogen oxides produced in step (a), the solubility of NO at room temperature is very low at about 56 mg/L, so it is difficult to dissolve it in liquid, so it must be oxidized to NO ₂ and dissolved in a solvent. At this time, one or more of corona discharge and catalyst can be used to oxidize NO to NO ₂ . Active species oxidized to NO ₂ can be hydrolyzed in liquid and are easy to dissolve in a solvent. When NO ₂ is dissolved, a large amount of NO ₂ ^- , NO ₃ ^- , and ONOO ^- can be generated.

(c) A plasma radical solution can be prepared by dissolving the oxidized active species in a solvent. At this time, either distilled water or purified water may be selected as the solvent so that the active species can be dissolved in the solvent. At this time, the active species can be dissolved in the solvent through bubbling. When bubbling is performed, fine bubbles are formed in the solvent, so the reaction area between the active species and the solvent increases, and thus the active species can be better dissolved in the solvent.

In one embodiment, the antibacterial composition of the present invention may further include HEPES (Hydroxyethyl piperazine Ethane Sulfonicacid), mandarin extract, and hyaluronic acid.

The HEPES (Hydroxyethyl piperazine Ethane Sulfonicacid) is an ingredient for adjusting the pH of the plasma radical solution to 3.0 to 4.0. The plasma radical solution is acidic with a pH of 0 to 3.0, but if the pH is too low (less than 3), precipitation of the mandarin extract occurs. On the other hand, if the pH of the plasma radical solution becomes higher than 4.0, the antibacterial, or sterilizing, effect disappears.

Therefore, the present invention can prepare an antibacterial composition containing 0.1 to 1.5% by weight of HEPES, which has excellent antibacterial efficacy without generating precipitates.

The mandarin extract is an ingredient for imparting fungal activity to the composition of the present invention. Mandarin is a mandarin tangerine ( Citrus Nobilis ) from the Rutaceae family. It contains antibacterial flavonoids and organic acids (Citirc Acid, Ascorbic Acid, Lactic Acid) and can exhibit antifungal activity. In the present invention, for example, a mandarin extract obtained by solvent (e.g. purified water) extraction and fractionation methods can be used.

When the above-mentioned mandarin extract is mixed with a plasma radical solution, a precipitate is formed under acidic conditions of pH less than 3. Therefore, in order to maintain the antibacterial effect of the plasma radical solution without generating precipitates due to the plasma radical solution and the mandarin extract, the plasma radical solution is contained in an amount of 85 to 97% by weight, based on the total weight of the composition of the present invention. It is preferable to include HEPES in an amount of 0.1 to 1.5% by weight, and the mandarin extract in an amount of 0.5 to 2.0% by weight.

When the plasma radical solution is contained in an amount of less than 85% by weight, the antibacterial effect is minimal, and when it is contained in an amount exceeding 97% by weight, there is a problem in that the solution reacts with the mandarin extract and generates precipitates as the pH decreases.

If the HEPES is included in less than 0.1% by weight, the pH of the plasma radical solution is low, causing precipitation of the mandarin extract, and if it is more than 1.5% by weight, the antibacterial properties of the plasma radical solution, which is an active ingredient, decreases as the pH increases. There is a problem.

On the other hand, when the mandarin extract is included in less than 0.5% by weight, the sterilizing effect against fungi is minimal, and when it is added in excess of 2.0% by weight, there is a problem in that the sterilizing effect against bacteria is reduced as it is added in excess.

That is, the present invention contains 85 to 97% by weight of a plasma radical solution, 0.1 to 1.5% by weight of HEPES, and 0.5 to 2.0% by weight of mandarin extract, so that the pH is adjusted to 3.0 to 4.0 to exhibit strong antibacterial properties and at the same time, the mandarin extract Since precipitation does not occur, it can be used as a formulation for highly stable hand sanitizers (quasi-drugs), disinfectants, household disinfectants, etc. (living environment products).

Meanwhile, the present invention may further include hyaluronic acid in the above ingredients.

The hyaluronic acid is an ingredient that provides the composition of the present invention with a moisturizing effect on human skin. Hyaluronic acid is a polysaccharide and a natural moisturizing factor (NMF) that exists in large quantities in human skin, and plays a moisturizing role in human skin. .

In one embodiment, the hyaluronic acid is preferably included in an amount of 0.0001 to 0.1% by weight based on the total weight. If it is outside the above range, precipitation may occur as crystals are formed by combining with the pectin component of the mandarin extract.

Meanwhile, the antibacterial composition may further include a moisturizing ingredient to enhance the moisturizing function. For example, the moisturizing ingredient may include glycerin, 1,3-butylene glycol, and propanediol. Preferably, it may contain 0.4 to 2.0% by weight of glycerin, 1.0 to 3.0% by weight of 1,3-butylene glycol, and 0.5 to 3.0% by weight of propanediol.

Additionally, the antibacterial composition of the present invention may additionally contain ingredients such as surfactants, fragrances, oils, thickeners, and extracts, as needed. In one embodiment, the antibacterial composition may be in the form of a hand sanitizer (quasi-drug), disinfectant, household disinfectant, etc. (living environment product).

The antibacterial composition according to the present invention exhibits strong antibacterial properties and harmlessness to the human body by appropriately adjusting the pH of the highly reactive plasma radical solution, and at the same time prevents precipitation of the mandarin extract, which exhibits fungal efficacy, from occurring, making it highly safe for the hands. It can be used in the formulation of disinfectants (quasi-drugs), disinfectants, household disinfectants, etc. (living environment products).

Meanwhile, the method for producing an antibacterial composition according to another embodiment of the present invention includes the first step of mixing a plasma radical solution, HEPES (Hydroxyethyl piperazine Ethane Sulfonicacid), glycerin, 1,3-butylene glycol, and propanediol. It may include a second step of adding hyaluronic acid to the mixed solution and stirring, and a third step of adding mandarin extract to the mixed solution after the second step.

First, the first step of mixing the plasma radical solution, HEPES (Hydroxyethyl piperazine Ethane Sulfonicacid), glycerin, 1,3-butylene glycol, and propanediol is performed.

In one embodiment, in the first step, in order to increase the miscibility and solubility of HEPES, glycerin, 1,3-butylene glycol, and propanediol, the temperature of the mixed solution is maintained at 40 to 60 ° C. for about 10 minutes. It is desirable to dissolve it by sufficiently stirring it for 30 minutes.

Next, a second step is performed in which hyaluronic acid is added to the mixed solution after the first step and stirred.

In one embodiment, in the second step, it is preferable to cool the mixed solution after the first step to 20 to 40° C. and then add hyaluronic acid. After adding hyaluronic acid, a mixed solution can be prepared by sufficiently stirring for about 10 to 30 minutes.

Next, a third step is performed in which mandarin extract is added to the mixed solution after the second step.

The ingredient pectin contained in the mandarin extract of the present invention can form lumps when mixed with hyaluronic acid, a strong acid and viscous substance. Additionally, when mandarin extract is added to a mixed solution at high temperature (40°C or higher), precipitation may occur.

Therefore, in the present invention, after sufficiently stirring the hyaluronic acid in the second step, in the third step, the temperature of the mixed solution is sufficiently cooled to 20 to 30 ° C. and then the mandarin extract is added while maintaining this temperature to form a stable formulation. An antibacterial composition can be prepared.

Hereinafter, the disinfection and antibacterial effects will be examined in detail by comparing the antibacterial composition according to an embodiment of the present invention with the comparative example composition.

<Example 1: Preparation of an antibacterial composition containing plasma radical solution>

A PHASE A solution was prepared including 94.7999% by weight of plasma radical solution, 0.800% by weight of HEPES, and 0.700% by weight of humectants glycerin, 2.000% by weight of 1,3-butylene glycol, and 0.800% by weight of propanediol.

Afterwards, 0.0001% by weight of hyaluronic acid was added to the PHASE A solution and stirred at a speed of 40 RPM for 10 minutes while maintaining the temperature at 20 to 40°C. After sufficient stirring, the plasma radical solution to which hyaluronic acid was added was cooled to a temperature of 25° C. while stirring at a speed of 10 RPM.

If the cooling process is omitted, since the natural cooling process takes some time, problems such as precipitation of extracts, discoloration of the formulation, and off-odor may occur during the natural cooling process. Therefore, the formulation must be stably cooled through the cooling process. It is desirable to give.

Next, 0.800% by weight of mandarin extract was added to the cooled hyaluronic acid-added PHASE A solution and stirred at a speed of 40 RPM for 10 minutes at room temperature to obtain antibacterial composition sample 1 according to Example 1 of the present invention.

<Comparative Example 1>

Ethanol was prepared as comparative sample 1.

<Comparative Example 2>

Hypochlorous acid water was prepared as comparative sample 2.

<Sterilization and antibacterial test>

In order to confirm the sterilization and antibacterial tests of ethanol, hypochlorous acid water, and plasma radical solution, the sterilization and antibacterial activity of Example 1 and Comparative Examples 1 and 2 were evaluated, and the results are shown in Figures 1a-1b and Tables 1 and 2.

(1) Sterilization and antibacterial evaluation

The bactericidal power was evaluated for two strains to be tested (Staphylococcus aureus (ATCC 6538) and Candida Albicans (ATCC 10231) according to the following method.

First, the initial cultures of the two strains to be tested were serially diluted 10 times with TSB (Tryptoic Soy Broth) medium (refrigerated at 4°C) to prepare 1x10 ⁵ CFU per mL of bacterial solution. Next, the test group added 0.1 mL of bacterial solution to Sample 1 and Comparative Samples 1 and 2 (1 mL), suspended them well, and left them at room temperature for 5 minutes. For the control group, 0.1 mL of bacterial solution was added to PBS buffer (1 mL), suspended well, and left at room temperature for 5 minutes.

Afterwards, the test group and the control group were left for 5 minutes, centrifuged (9,900 RPM, 1 minute), the supernatant was removed, 1 mL of TSB medium or PBS buffer was added to suspend the precipitate well, and centrifuged again. The washing process to remove the supernatant was repeated twice, and finally, 1 mL of TSB medium or PBS buffer was added to the precipitate to suspend it well.

Next, 0.1 mL of the 1 mL suspension was spread on three or more TSA (Tryptoic Soy Agar) or YM (Yeast Malt) media, and cultured at 37°C for 20 to 24 hours. The inhibition rate against bacteria was calculated according to the formula below, and the results are shown in Tables 1 and 2. (Table 1: S.Aureus sterilization and antibacterial test results, Table 2: C.Albicans sterilization and antibacterial test results)

[Formula] Inhibition rate (%) = [Control group bacterial count (CFU) - Test group bacterial count (CFU)] / Control group bacterial count (CFU) × 100

division Viable bacteria count (CFU/ml) Inhibition rate (%) Example 1 ⁰ 100% Comparative Example 1 ⁰ 100% Comparative Example 2 ⁰ 100%

(※ Control group bacterial count (CFU): ^1.4

division Viable bacteria count (CFU/ml) Inhibition rate (%) Example 1 ⁰ 100% Comparative Example 1 ⁰ 100% Comparative Example 2 ⁰ 100%

(※ Control group bacterial count (CFU): ²

Looking at Figures 1a-1b, which are the results of the sterilizing power evaluation, it can be seen that in the case of Sample 1, both Staphylococcus aureus and Candida, which are bacteria that must be killed, were killed, showing excellent antibacterial efficacy.

Meanwhile, looking at Figures 1a-1b and Tables 1 and 2, Example 1 showed similar sterilizing power to Comparative Examples 1 and 2. This shows that the antibacterial composition containing the plasma radical solution has a similar effect compared to ethanol and hypochlorous acid, which are conventionally used for disinfection and sterilization.

<Efficacy evaluation according to mandarin extract content>

In order to evaluate the efficacy of the antibacterial composition according to the mandarin extract content, 0.4% by weight and 2.1% by weight of the mandarin extract were used, respectively, and the same process as Example 1 was used, except that a change in the weight% of the mandarin extract was used. Comparative examples 3 and 4 were obtained.

Thereafter, the sterilization and antibacterial activity of bacteria (S. Aureus) and fungi (C. Albicans) of Example 1 and Comparative Examples 3 and 4 were evaluated, and the results are shown in Figures 2a-2b and Tables 3-4. Here, Figures 2a - 2b and Tables 3 - 4 show the results of sterilization and antibacterial evaluation of bacteria (S.Aureus) and fungi (C.Albicans) in that order.

division Viable count (CFU) Inhibition rate (%) Example 1 ⁰ 100% Comparative Example 3 ⁰ 100% Comparative Example 4 ^1.1 45%

(※ Control group bacterial count (CFU): ^1.4

division Viable count (CFU) Inhibition rate (%) Example 1 ⁰ 100% Comparative Example 3 ^1.85 7.5% Comparative Example 4 ⁰ 100%

(※ Control group bacterial count (CFU): ²

Referring to Figures 2a-2b and Tables 3-4, Comparative Example 3, which contained 0.4% by weight of mandarin extract, showed a decrease in the sterilizing power of fungi (C. Albicans) compared to Example 1. This is because the content of mandarin extract, which sterilizes fungi, is low.

Meanwhile, as shown in Figure 2b and Table 4, Comparative Example 4, which contained a mandarin extract content of 2.1% by weight, showed similar results in sterilizing power of fungi (C. Albicans) as Example 1. However, as shown in Figure 2a and Table 3, in Comparative Example 4, it can be confirmed that the sterilization and antibacterial activity of bacteria (S. Aureus) is reduced compared to Example 1. This is believed to reduce the antibacterial activity of the plasma radical solution due to excessive reaction between various active species in the plasma radical solution and the mandarin extract. In addition, as the weight percent of the basic mandarin extract increases, the plasma radical solution becomes more basic and the antibacterial activity of the plasma radical solution is inhibited.

Therefore, it is most preferable that the mandarin extract is included in an amount of 0.5 to 2.0% by weight based on the total weight of the antibacterial composition containing the plasma radical solution of the present invention.

<Efficacy evaluation according to HEPES content>

In order to evaluate the efficacy of the antibacterial composition according to the HEPES content, Comparative Example 5 was prepared through the same process as Example 1, except that 0.05% by weight and 1.6% by weight of HEPES were used, respectively, and a change in the weight% of HEPES was used. , got 6.

Thereafter, the stability, sterilization, and antibacterial activity of Example 1 and Comparative Examples 5 and 6 were evaluated, and the results are shown in Figures 3 and 4a-4b and Tables 5 and 6. Here, Figures 4a - 4b and Tables -5 and 6 show the results of antibacterial evaluation of bacteria (S.Aureus) and fungi (C.Albicans) in that order.

division Viable count (CFU) Inhibition rate (%) Example 1 ⁰ 100% Comparative Example 5 ⁰ 100% Comparative Example 6 ^1.3 5%

(※ Control group bacterial count (CFU): ^1.4

division Viable count (CFU) Inhibition rate (%) Example 1 ⁰ 100% Comparative Example 5 ⁰ 100% Comparative Example 6 ⁰ 100%

(※ Control group bacterial count (CFU): ²

Referring to Figure 3, it can be seen that the mandarin extract was precipitated in Comparative Example 5, which contained a HEPES content of 0.05% by weight. This is because the content of HEPES is low and the pH of the plasma radical solution is less than 3, so the components of the mandarin extract precipitate and a precipitation phenomenon occurs. In general, the stability of the mandarin extract itself tends to decrease at pH levels below 3 due to a component called pectin in the mandarin extract.

On the other hand, Comparative Example 6, which contained 1.6% by weight of HEPES, had a high pH, resulting in a decrease in the antibacterial and sterilizing power of the plasma radical solution. Referring to Figures 4a and 4b and Tables 5 and 6, Comparative Example 6, which contained a HEPES content of 1.6% by weight, showed a decrease in the sterilizing power of bacteria (S. Aureus) compared to Comparative Example 5 and Example 1.

Therefore, it is most preferable that HEPES is included in an amount of 0.1 to 1.5% by weight, based on the total weight of the antibacterial composition of the present invention.

Although the present invention has been described above with reference to preferred embodiments, those skilled in the art may make various modifications and changes to the present invention without departing from the spirit and scope of the present invention as set forth in the following patent claims. You will understand that it is possible.

Claims (12)

An antibacterial composition comprising 85 to 97% by weight of a plasma radical solution, 0.1 to 1.5% by weight of HEPES (Hydroxyethyl piperazine Ethane Sulfonicacid), 0.5 to 2.0% by weight of mandarin extract, and 0.0001 to 0.1% by weight of hyaluronic acid. delete delete delete delete According to paragraph 1,
The antibacterial agent composition has a pH of 3.0 to 4.0. According to paragraph 1,
The antibacterial agent composition further includes 0.4 to 2.0% by weight of glycerin, 1.0 to 3.0% by weight of 1,3-butylene glycol, and 0.5 to 3.0% by weight of propanediol, based on the total weight. According to paragraph 1,
The antibacterial agent composition is a hand sanitizer, disinfectant, or household disinfectant formulation. A first step of mixing a plasma radical solution, HEPES (Hydroxyethyl piperazine Ethane Sulfonicacid), glycerin, 1,3-butylene glycol, and propanediol;
A second step of adding hyaluronic acid to the mixed solution after the first step and stirring it; and
A third step of adding mandarin extract after cooling the mixed solution after the second step to 20 to 30°C.
Method for producing an antibacterial composition. According to clause 9,
In the first step, the temperature of the mixed liquid is maintained at 40 to 60 ° C.
Method for producing an antibacterial composition. According to clause 9,
In the second step, the mixed solution after the first step is cooled to 20 to 40 ° C, and then hyaluronic acid is added.
Method for producing an antibacterial composition. delete