Antibacterial aqueous dispersion composition containing copper citrate as an active ingredient

Abstract

The present invention relates to an antibacterial aqueous dispersion composition containing copper citrate as an active ingredient, which has excellent aqueous dispersion stability, is added to personal care products, paints, etc., and exhibits a broad antibacterial spectrum against bacteria, molds, and viruses.

Description

[Technical Field]

[0001] This application claims the benefit of priority based on Korean Patent Application No. 10-2021-0037106, filed on March 23, 2021, and all contents disclosed in the documents of that Korean patent application are incorporated herein by reference.

[0002] The present invention relates to an antibacterial aqueous dispersion composition containing copper citrate as an active ingredient, and more specifically to an antibacterial aqueous dispersion composition containing copper citrate as an active ingredient, which has excellent aqueous dispersion stability, is added to personal care products, paints, etc., and exhibits a broad antibacterial spectrum against bacteria, fungi, and viruses. [Background technology]

[0003] Recently, in response to the global spread of the coronavirus disease (COVID-19), paint manufacturers around the world have been competing to release architectural paints that can kill the coronavirus. The active ingredients in these paints are elemental gold, silver, and copper, and the active substances that actually realize the antiviral properties are known to be the ionic components of these metals, which are produced in extremely small amounts when these metal elements come into contact with moisture in the air.

[0004] Antibacterial agents used in currently available antiviral paints can be broadly classified into ceramic forms, obtained by melting silver or copper with glass (silicate) at high temperatures, followed by cooling, crystallization, and pulverization, and zeolite-based compounds, such as zeolites substituted with silver or copper ions (i.e., Ag+ / zeolite or Cu2+ / zeolite) and cuprous oxide nanoparticle zeolites (Cu2O NPs / zeolite). However, these manufacturing processes are extremely difficult, requiring high-temperature melting and a metal substitution reaction of the zeolite. After manufacturing, they require a separate milling process to a few microns or smaller using an air jet mill. The powder (i.e., the milled powder) typically needs to be added to the paint at a concentration of 0.3% by weight (3,000 ppm) or more to achieve antibacterial effects, leading to price-performance limitations.

[0005] Meanwhile, zinc pyrithione has been used in architectural paints and personal care products (such as shampoos) containing levels of 1,000 to 5,000 ppm before antiviral properties were required. However, according to data from the European Chemicals Agency (ECHA), zinc pyrithione has a reported acute oral toxicity (LD50) of 269 mg / kg for rodents, which could pose a risk of falling under the toxic substance designation criteria of Article 16 of the ARECs (Act on the Registration and Evaluation of Chemicals) for substances with an acute oral toxicity of 300 mg / kg or less for rodents (i.e., a toxic substance).

[0006] According to literature, the minimum inhibitory concentration of copper ions against Staphylococcus epidermidis is known to be 9-90 ppm. This is a much lower concentration than the 1,000-5,000 ppm that is the optimum concentration for zinc pyrithione to exert its antibacterial properties, and for reference, the acute oral toxicity of copper citrate to rodents is 1,580 mg / kg, making it relatively safe.

[0007] Copper ion sources are generally in the form of simple salts such as cupric chloride (CuCl2) and copper sulfate (CuSO4). However, because these are highly soluble in water, they cannot be used in paints due to leaching issues. Therefore, there is a pressing need to develop antibacterial aqueous dispersion compositions for paints and personal care products that are insoluble in water and have excellent antibacterial effects even when used in small amounts, and that have the antiviral properties that zinc pyrithione lacks. Summary of the Invention [Problem to be solved by the invention]

[0008] While searching for a water-insoluble copper salt, the applicant focused on complex compounds of weak organic acids with copper. While these compounds can be a wide variety of combinations, including Cu-EDTA, copper oxalate, copper aspirinate, and copper citrate, the applicant selected copper citrate, which is relatively low in toxicity and easy to manufacture. Copper citrate is sometimes taken as a dietary supplement (copper ion supplement), and is also used as a processing aid in wine production to remove sulfide-based substances, which are by-products of the winemaking process, such as fermentation, and are responsible for unpleasant odors.

[0009] Therefore, an object of the present invention is to provide an antibacterial aqueous dispersion composition containing copper citrate as an active ingredient, which has excellent aqueous dispersion stability, can be added to personal care products, paints, etc., and exhibits a broad antibacterial spectrum against bacteria, fungi, and viruses. [Means for solving the problem]

[0010] To achieve the above object, the present invention provides an antibacterial aqueous dispersion composition containing copper citrate as an active ingredient. [Effects of the Invention]

[0011] The antibacterial aqueous dispersion composition according to the present invention, which contains copper citrate as an active ingredient, has excellent aqueous dispersion stability and is added to personal care products, paints, etc., and has the advantage of exhibiting a broad antibacterial spectrum against bacteria, fungi, and viruses. Furthermore, the antibacterial aqueous dispersion composition according to the present invention, which contains copper citrate as an active ingredient, is not only relatively safe for the human body, but also has the advantage of being able to ensure sufficient antibacterial activity even in small amounts. Furthermore, the antibacterial aqueous dispersion composition according to the present invention, which contains copper citrate as an active ingredient, has the advantage of being able to utilize copper citrate, which has been widely used mainly among the general public in Western Europe, industrially as well. [Brief explanation of the drawings]

[0012] [Figure 1] 1A shows an image of the control S. aureus strain used in the examples and comparative examples of the present invention after cultivation, and FIG. 1B shows an image of the S. aureus strain killed after contact with the sample according to the present invention. [Figure 2] 1A shows an image of the control E. coli strain used in the examples and comparative examples of the present invention after cultivation, and FIG. 1B shows an image of the E. coli strain killed after contact with the sample according to the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0013] The present invention will be described in detail below. The terms and words used in this specification and claims should not be interpreted in a limited way to their ordinary or dictionary meanings, but should be interpreted in a meaning and concept that corresponds to the technical idea of ​​the present invention, based on the principle that the inventor can appropriately define the concept of the term in order to best explain his / her invention.

[0014] The antibacterial aqueous dispersion composition according to the present invention contains a large amount of copper ions and can impart antibacterial or antiseptic properties to personal care products (e.g., shampoos, soaps, and cosmetics) and paints (especially, water-based architectural paints), etc., and although it contains copper citrate as an active ingredient, it may further contain one or more of metal oxides, dispersants, and auxiliary additives, if necessary.

[0015] Zinc pyrithione has typically been used in architectural paints and personal care products at levels of 1,000 to 2,500 ppm. However, while zinc pyrithione has excellent antifungal and antibacterial properties, there have been no reported cases of its antiviral properties. Therefore, despite the recent global pandemic of the coronavirus disease (COVID-19), which has created a demand for architectural paints and personal care products with antiviral properties, zinc pyrithione is considered to be limiting.

[0016] Therefore, the present applicant considered that the minimum inhibitory concentration of copper ions against Staphylococcus epidermidis is known to be 9-90 ppm, and that such copper ions exert effective antibacterial activity at much lower concentrations than the appropriate concentration (1,000-2,500 ppm) of zinc pyrithione required for antibacterial activity. Taking this into consideration, the applicant focused on copper complexes of weak organic acids with copper, such as Cu-EDTA, copper oxalate, copper aspirinate, and copper citrate, which are insoluble in water, as a source of copper ions. Among these, copper citrate, which has relatively low toxicity (acute oral toxicity to rodents: 1,580 mg / kg) and is easy to manufacture, was selected as the core component of the antibacterial aqueous dispersion composition. For reference, since there have been no reports of data on the acute oral toxicity of the above copper complex compounds except for copper citrate, data on the oral toxicity (LD50) of rodents for the "conjugate acid of copper ion" was used as reference and compiled as shown in Table 1 below.

[0017] [Table 1]

[0018] Copper citrate, which is contained as a core active ingredient in the antibacterial aqueous dispersion composition of the present invention, is produced according to the following reaction scheme 1. The produced copper citrate precipitates in the form of a hydrate insoluble in water, as shown in the following chemical formula 1, which is filtered and dried to obtain copper citrate anhydride, as shown in the following chemical formula 2. Meanwhile, copper citrate anhydride can be converted back to copper citrate hydrate upon contact with atmospheric moisture or water.

[0019] (Reaction Scheme 1) 3CuSO4(aq)+2Na3C6H5O7(aq)→Cu3(C6H5O7)2(s)+3Na2SO4(aq)

[0020] [ka]

[0021] [ka]

[0022] Meanwhile, the copper citrate contained in the antibacterial aqueous dispersion composition of the present invention may be contained in the form of a hydrate represented by the above chemical formula 1, or in the form of an anhydride represented by the above chemical formula 2, and is not particularly limited (that is, copper citrate may be contained in the antibacterial aqueous dispersion composition in the form of a hydrate or anhydride, because copper citrate is always present in the aqueous dispersion composition in the form of a hydrate).

[0023] However, when copper citrate anhydride is added in the form of a non-dried hydrate, the weight of copper citrate anhydride added after drying varies depending on the moisture content of the copper citrate hydrate filter cake, making it difficult to accurately control the copper ion content in the composition product as intended. Therefore, when considering this aspect, it may be more desirable to add copper citrate anhydride represented by Formula 2 to the composition.

[0024] Here, the copper citrate hydrate represented by Chemical Formula 1 is in the form of bluish-green copper citrate hemitrihydrate (Cu2C6H4O7).1.5H2O (having the properties of powder as a precipitate), and the copper citrate anhydrate represented by Chemical Formula 2 is Cu3(C6H5O7)2 in the form of sky blue powder.

[0025] The particle size of the copper citrate powder according to the present invention may be 0.1 to 100 μm, preferably 1 to 20 μm. If the particle size of the copper citrate powder is less than 0.1 μm, a separate grinding process may be required or fine dust may cause safety issues for workers during the process. If the particle size exceeds 100 μm, the powder may deviate from the particle size control standard for raw materials used in paints or personal care products (99.8% or more passing 300 Mesh (= 50 μm)). Or, due to the reduced surface area of ​​the particles, copper ion release may be reduced upon contact with moisture in the air, resulting in a decrease in antibacterial activity.

[0026] The copper citrate powder according to the present invention may have an average particle size (D50) of 0.5 to 10 μm, preferably 1 to 5 μm. If the average particle size (D50) of the copper citrate powder is less than 0.5 μm, problems may occur in the filtration and washing processes of the copper citrate powder prepared according to Reaction Scheme 1. If the average particle size (D50) of the copper citrate powder exceeds 10 μm, the layer stability of the aqueous dispersion composition, including precipitation, may decrease, potentially resulting in problems with the storage stability of the product.

[0027] The copper citrate may be contained in an amount of 0.1 to 50 wt %, preferably 15 to 45 wt %, based on the total weight of the antibacterial aqueous dispersion composition of the present invention. If the copper citrate is contained in an amount of less than 0.1 wt %, the concentration of copper citrate will be low, which may result in excessive logistics costs and insufficient antibacterial activity. If the copper citrate is contained in an amount of more than 50 wt %, the aqueous dispersion composition may have an excessive solids content, which may increase the viscosity and reduce flowability of the aqueous dispersion composition, resulting in reduced usability.

[0028] By including copper citrate in the composition, the antibacterial aqueous dispersion composition of the present invention can contain a large amount of copper ions. More specifically, the content of copper ions contained in the antibacterial aqueous dispersion composition may be 0.3 to 170 mg / mL, preferably 50 to 100 mg / mL. If the copper ion content in the antibacterial aqueous dispersion composition is less than 0.1 mg / mL, the antibacterial activity of the composition may be reduced, potentially resulting in a problem of not being able to exhibit a broad antibacterial spectrum against bacteria, fungi, and viruses. If the copper ion content exceeds 170 mg / mL, the aqueous dispersion composition may be less convenient to use.

[0029] Meanwhile, the antibacterial aqueous dispersion composition according to the present invention containing copper citrate as an active ingredient essentially contains pure water (DI water) in addition to copper citrate, and may further contain one or more of a metal oxide, a dispersant, and an auxiliary additive, as needed. Any of the metal oxide, dispersant, and auxiliary additive can serve to impart a synergistic antibacterial effect with the copper citrate.

[0030] Furthermore, the metal oxides are commonly used in the fields of personal care and paints, and may be included in the antibacterial aqueous dispersion composition of the present invention in order to minimize compositional heterogeneity in the formulations of personal care products and paints that have been used so far and to improve the formulation stability of the finished products.

[0031] Examples of such metal oxides include zinc oxide (ZnO), titanium dioxide (TiO2), silica (SiO2), alumina (Al2O3), and mixtures thereof. When the metal oxides are contained in the antibacterial aqueous dispersion composition of the present invention, they may be contained in an amount of 20 wt % or less, preferably 10 to 15 wt %, based on the total weight of the antibacterial aqueous dispersion composition.

[0032] The dispersant is preferably a surfactant, and any surfactant commonly used in the art may be used without limitation, and specific examples thereof include sodium lauryl sulfate, polyoxyethylene sorbitan monooleate (product name: Tween 80), polyethylene glycol tert-octylphenyl ether (product name: Triton X-100), sorbitan monopalmitate (product name: Span 40), and mixtures thereof. If the dispersant is included in the antibacterial aqueous dispersion composition of the present invention, it may be included in an amount of 0.1 to 1 wt %, preferably 0.5 to 0.8 wt %, based on the total weight of the antibacterial aqueous dispersion composition.

[0033] The auxiliary additive is preferably a thickener, and any thickener commonly used in the art may be used without limitation, and specific examples thereof include methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, xanthan gum, polyacrylic acid (product name: Carbopol), and mixtures thereof. If the auxiliary additive is included in the antibacterial aqueous dispersion composition of the present invention, it may be included in an amount of 0.1 to 3 wt %, preferably 0.7 to 1.5 wt %, based on the total weight of the antibacterial aqueous dispersion composition.

[0034] Another object of the present invention is to industrially utilize copper citrate, which has been widely used, mainly among the general public in Western Europe. The general method for producing copper citrate is generally electrochemical, specifically, by inserting a copper electrode into water containing dissolved citric acid and passing an electric current through it to obtain a low-concentration colloidal copper citrate aqueous solution. The concentration of the resulting colloidal copper citrate varies depending on the applied voltage, current amount, and time, but typically a small amount of copper citrate, around 10 ppm, is obtained in 6 hours. Therefore, this method does not allow for industrial use of copper citrate.

[0035] Therefore, the present invention provides a method for producing an antibacterial aqueous dispersion composition containing copper citrate as an active ingredient, by chemically synthesizing copper citrate in large quantities, so as to improve convenience of use and industrial applicability.

[0036] A method for preparing an antibacterial aqueous dispersion composition containing copper citrate as an active ingredient according to the present invention includes: a) reacting copper sulfate with sodium citrate to mass-produce copper citrate according to Reaction Scheme 1 below; and b) adding the synthesized copper citrate to purified water (DI water). If necessary, in step b), any one or more of a metal oxide, a dispersant, and an auxiliary additive may be added together with the copper citrate. If necessary, a milling process using a bead mill or the like may be performed after step b.

[0037] (Reaction Scheme 1) 3CuSO4(aq)+2Na3C6H5O7(aq)→Cu3(C6H5O7)2(s)+3Na2SO4(aq)

[0038] Meanwhile, copper citrate synthesized or produced by Reaction Scheme 1 precipitates in the form of copper citrate hydrate. To ensure quantitative determination of copper ion concentration, it may be desirable to filter the copper citrate hydrate and then completely dry it to convert it into copper citrate anhydrate.

[0039] The antibacterial aqueous dispersion composition of the present invention containing copper citrate as an active ingredient as described above can be used in a wide range of fields requiring antibacterial properties, such as personal care products and paints, and therefore can be included in products requiring antibacterial properties, such as personal care products and paints (particularly water-based paints), and can be manufactured into products using a bead mill or the like.

[0040] Preferred examples will be described below to aid in understanding the present invention. However, the following examples are merely illustrative of the present invention, and it will be apparent to those skilled in the art that various changes and modifications are possible within the scope of the scope and technical idea of ​​the present invention. Naturally, such changes and modifications also fall within the scope of the appended claims. [Example]

[0041] [Example 1] Preparation of an antibacterial aqueous dispersion composition containing copper citrate First, 413.7 g of DI water was placed in a 600 ml beaker, and 75.0 g of anhydrous copper citrate powder, which was prepared by reacting 374.5 g (1.5 mol) of copper sulfate pentahydrate with 294.1 g (1.0 mol) of sodium citrate dihydrate, 7.75 g of hydroxypropyl methyl cellulose (thickener), and 3.55 g of sodium lauryl sulfate (surfactant), were added thereto, followed by stirring and dispersing at a temperature of 30°C for 3 hours to prepare 500 g of an antibacterial aqueous dispersion composition.

[0042] [Example 2] Preparation of antibacterial aqueous dispersion composition containing copper citrate The same procedure as in Example 1 was carried out to prepare 500 g of an antibacterial aqueous dispersion composition, except that the amount of DI water was reduced by 50.0 g from 413.7 g to 363.7 g, and zinc oxide was added in an amount equivalent to the reduced amount.

[0043] [Example 3] Preparation of antibacterial aqueous dispersion composition containing copper citrate The same procedure as in Example 2 was carried out to prepare 500 g of an antibacterial aqueous dispersion composition, except that the amount of DI water was increased by 67.5 g from 363.7 g to 431.2 g, and the amount of copper citrate anhydrous powder was reduced by the increased amount.

[0044] Comparative Example 1: Preparation of a conventional structural adhesive composition An aqueous dispersion composition was prepared by mixing the same components as in Example 1, except that Cu2+ / zeolite was used instead of copper citrate. Meanwhile, the method for preparing Cu2+ / zeolite is a known technique, and the applicant independently prepared and used it. The compositions prepared in Examples 1 to 3 and Comparative Example 1 are shown in Table 2 below.

[0045] [Table 2] *Unit: grams (g)

[0046] [Test Example 1] Measurement of copper ion concentration in composition The concentrations (%) of copper ions (Cu2+) contained in the compositions prepared in Examples 1 to 3 and Comparative Example 1 were measured, and the results are shown in Table 3 below.

[0047] [Table 3]

[0048] [Test Example 2] Evaluation of antibacterial properties of the composition The antibacterial activity of each of the compositions prepared in Examples 1 to 3 and Comparative Example 1 against two types of bacteria (S. aureus and E. coli) was evaluated. The antibacterial evaluation method was carried out in accordance with ASTM E 2149. Bacteria pre-cultured for 18 hours were inoculated into 50 mL of phosphate buffer solution to a bacterial concentration of 1.5 to 3.0 x 10 CFU / mL. 0.1 g (0.2%) of each sample was added and shaken for 1 hour, after which the CFU (Colony Forming Unit) of the buffer was measured and the bacterial reduction rate was calculated according to Equation 1 below. The results are shown in Table 4 below. Meanwhile, as shown in Table 3, the copper ion concentration in the composition prepared in Comparative Example 1 was 1.1%, which is lower than the copper ion concentration (5.0%) of the composition prepared in Example 1. Therefore, to achieve the same copper ion concentration, the amount of the sample corresponding to Comparative Example 1 was increased to 0.5 g (1.0%).

[0049] (Formula 1) Bacterial reduction rate (%) = [(Number of bacteria after incubation in the control) - (Number of bacteria after incubation in the sample)] / (Number of bacteria after incubation in the control) x 100

[0050] [Table 4]

[0051] As a result of the evaluation, the antibacterial aqueous dispersion compositions of Examples 1 to 3 containing copper citrate showed a bacterial reduction rate of 98.1 to 99.9% after 1 hour of contact with bacteria, whereas Comparative Example 1, which used a common antibacterial agent, Cu2+ / zeolite, showed a bacterial reduction rate of 96.3 to 97.2%, confirming that its antibacterial performance was lower than that of Examples 1 to 3. Furthermore, through a comparison and control between Example 1, which contains only copper citrate, a thickener, and a surfactant, and Example 2, which also contains zinc oxide, it was confirmed that the addition of zinc oxide to the composition slightly improved the antibacterial performance against Staphylococcus aureus (S. aureus).

[0052] Meanwhile, Figure 1 shows an image (a) of the control S. aureus strain used in the examples and comparative examples of the present invention after cultivation and an image (b) of the S. aureus strain that died after contact with the sample of Example 1. Figure 2 shows an image (a) of the control E. coli strain used in the examples and comparative examples of the present invention after cultivation and an image (b) of the E. coli strain that died after contact with the sample of Example 1.

[0053] On the other hand, in the case of Cu2+ / zeolite contained in the composition of Comparative Example 1, the copper ion concentration in the aqueous dispersion composition was only 1.1%, and by increasing the amount of sample used in the antibacterial test by approximately five times, the same copper ion concentration was achieved as in Examples 1 and 2, but the bacterial reduction rate was 96.3 to 97.2%, which was inferior to the bacterial reduction rate of copper citrate.

[0054] Meanwhile, according to literature, the acute oral toxicity (LD50) of Cu2+ / zeolite containing 2.5% copper ions by weight is known to be 18,000 mg / kg in rodents. Considering that the acute oral toxicity (LD50) of pure copper citrate (copper ion concentration: 33.5%) is 1,580 mg / kg, it can be inferred that copper citrate is less harmful to the human body than Cu2+ / zeolite.

Claims

1. Contains the active ingredients copper citrate and metal oxides, The metal oxide may be zinc oxide (ZnO), silica (SiO ２ ), alumina (Al ２ O ３ ) and mixtures thereof; An antibacterial aqueous dispersion composition, characterized in that the copper citrate is insoluble in water.

2. The antibacterial aqueous dispersion composition according to claim 1, wherein the copper citrate is copper citrate hydrate represented by the following chemical formula 1 or copper citrate anhydride represented by the following chemical formula 2: 【Chemistry 1】 【Chemistry 2】

3. The antibacterial aqueous dispersion composition according to claim 2, wherein the copper citrate hydrate and the copper citrate anhydrous are in powder form.

4. The antibacterial aqueous dispersion composition according to claim 3, wherein the copper citrate powder has a particle size of 0.1 to 100 μm and an average particle size (D50) of 0.5 to 10 μm.

5. The antibacterial aqueous dispersion composition according to claim 1, wherein the copper citrate is contained in an amount of 0.1 to 50 wt % based on the total weight of the composition.

6. 2. The antibacterial aqueous dispersion composition according to claim 1, wherein the content of copper ions contained in the antibacterial aqueous dispersion composition is 0.3 to 170 mg / mL.

7. 2. The antibacterial aqueous dispersion composition according to claim 1, characterized in that the antibacterial aqueous dispersion composition consists of copper citrate and water.

8. The antibacterial aqueous dispersion composition according to claim 1, further comprising at least one of a dispersant and an auxiliary additive.

9. The dispersing agent is sodium lauryl sulfate, polyoxyethylene sorbitan monooleate, 9. The antibacterial aqueous dispersion composition according to claim 8, wherein the surfactant is selected from the group consisting of polyethylene glycol tert-octylphenyl ether, sorbitan monooleate, polyethylene glycol tert-octylphenyl ether, sorbitan monopalmitate, and mixtures thereof.

10. 9. The antibacterial aqueous dispersion composition according to claim 8, wherein the auxiliary additive is a thickener selected from the group consisting of methyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose, xanthan gum, polyacrylic acid, and mixtures thereof.

11. 2. The antibacterial aqueous dispersion composition according to claim 1, wherein the antibacterial aqueous dispersion composition is for use in personal care products or paints.

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