WO2023131855A1

WO2023131855A1 - Antimicrobial composition

Info

Publication number: WO2023131855A1
Application number: PCT/IB2022/062830
Authority: WO
Inventors: Churat Tiyapiboonchaiya; Sombat Tannarat; Anchalee WONGARIYAKAWEE
Original assignee: SCG Chemicals Public Company Limited
Priority date: 2022-01-05
Filing date: 2022-12-28
Publication date: 2023-07-13

Abstract

The present invention relates to an antimicrobial composition comprising silver, divalent metal salt of hydroxy carboxylic acid or carboxylic acid, and a compound which is selected from a group consisting of fatty acid ester of polyhydric alcohol, alkyl amido betaine having 16-26 carbon atoms, and a combination thereof.

Description

ANTIMICROBIAL COMPOSITION

TECHNICAL FIELD

Chemistry related to an antimicrobial composition.

BACKGROUND OF THE INVENTION

Illnesses caused by pathogens e.g., bacteria, fungi, and viruses are one of the causes of health problems and public health system issues which are now of much concern across the world, since microbes can quickly grow and proliferate, as well as can spread easily and through various channels, including airborne transmission, food and water contamination or direct contact. Furthermore, certain types of microbes are also capable of very fast mutation causing difficulties and delays in the development of vaccines for prevention and drugs for treatment of diseases caused by those mutated microbes.

Therefore, one of the common and extremely necessary approaches in preventing illnesses caused by the spread of pathogenic microorganisms at present is the development of different effective products or means that help eliminating or resisting the growth of microbes. Examples of the patent documents related to the development of products for removing and resisting microbes are as follows:

US patent no. US 7,582,418 B2 discloses a method of inhibiting the growth of microbes, including bacteria and fungi, by contacting them with an antimicrobial compound containing zinc chelate that can be selected from zinc lipoate and zinc bisglycinate. Examples of microbes that can be eliminated by this method are, for instance, Staphylococcus aureus, Streptococcus pyogenes, Salmonella typhimerium, Eschrichia coli and Candida albicans.

PCT patent publication no. WO 2007/076125 A2 discloses an antimicrobial composition comprising at least 0.05 wt% zinc compound. The zinc compound can be selected from a group consisting of zinc acetate, zinc butyrate, zinc chloride, zinc citrate, zinc gluconate, zinc glycerate, zinc glycolate, zinc formate, zinc lactate, zinc phthalocyanine, zinc picolinate, zinc propionate, zinc salicylate, zinc tartrate, and zinc undecylenate.

European patent publication no. EP 1 778010 A2 discloses an antimicrobial composition comprising a solvent, a silver compound, and a stabilizer. The stabilizer may be a polymer or a surfactant or a combination thereof. The silver compound may comprise salt which comprises cations and anions of silver, where anions may comprise saccharinate derivatives, long chain fatty acid, and alkyl dicarboxylate. Although the prior arts such as the patent documents above have already disclosed the development of antimicrobial compositions, there remains a need for the development of an antimicrobial composition that can eliminate or resist microbes more effectively and can control and prevent microbes from growing and proliferating again.

SUMMARY OF THE INVENTION

The first objective of the present invention is to develop an antimicrobial composition that can eliminate or resist pathogens more effectively, that is, to be able to eliminate or reduce all or almost all pathogens in a short period of time, and to be able to control and prevent microbes from growing and proliferating again after leaving it for a certain period of time.

Another objective of the present invention is to develop the antimicrobial composition suitable for coating a surface of substrate made of different materials, e.g., wood, cement, plastic, textile, woven fabric, non-woven fabric, natural fiber, synthetic fiber, metal, paper, etc., and to develop substrate coated with the antimicrobial composition, including the product related to air filtering and preventing the spread of microbes such as an air filter, an air filter pad, a face mask, a face shield or a personal protective equipment (PPE) comprising substrate coated with said antimicrobial composition.

According to a preferred embodiment of the present invention, the antimicrobial composition comprises: a) silver; b) divalent metal salt of hydroxy carboxylic acid or carboxylic acid; and c) a compound which is selected from a group consisting of fatty acid ester of polyhydric alcohol, alkyl amido betaine having 16-26 carbon atoms, and a combination thereof.

The components of the antimicrobial composition according to the present invention have synergistic effects in effectively eliminating and inhibiting the growth of microbes. The test result shows that it can eliminate over 99% of the bacteria, such as Bacillus cereus and Escherichia coli, and viruses with a very short period of contact. Furthermore, the composition also shows a great inhibiting effect on the growth of said microbes, where it can inhibit up to 100% microbes even after leaving it for a certain period of time, such as 24 hours. DETAILED DESCRIPTION

Any aspects shown herein shall encompass the application to other aspects of the present invention as well, unless stated otherwise.

Technical terms and scientific terms used herein have meanings as understood by a person of ordinary skill in the art, unless determined otherwise.

Throughout the present invention, the term “about” is used to indicate that any values appearing or shown herein may be varied or deviate Such variation or deviation may be caused by equipment error, or method used to determine the values.

The terms “comprise(s),” “contain(s),” “have/has”, and “include(s)” are open-end verbs. For example, any method or composition which “comprises,” “contains” or “includes” one component or multiple components or one step or multiple steps is not limited to only one component or one step or multiple steps or multiple components, but also encompasses components or steps that are not specified.

Tools, devices, methods, materials, or chemicals mentioned herein, unless specified otherwise, mean the tools, devices, methods, materials, or chemicals generally used or practiced by a person skilled in the art.

All components and/or methods disclosed and claimed in the present invention are intended to cover the aspects of the invention obtained from an action, a practice, a modification or a change of any factors which does not require any experiment that is substantially different from the present invention and gives properties and utility and provides the same effect as the aspects of the present invention according to the judgement of a person having ordinary skill in the art, although not specifically stated in the claims. Therefore, substitutions or analogues of the aspects of the present invention and any slight modifications or changes that is clearly apparent to a person of ordinary skill in the art, are considered to be within the spirit, the scope, and concept of the present invention as well.

The present invention will now be described in more detail by way of examples, but not intended to limit the scope of the invention.

The antimicrobial composition according to the present invention comprises: a) silver; b) divalent metal salt of hydroxy carboxylic acid or carboxylic acid; and c) a compound which is selected from a group consisting of fatty acid ester of polyhydric alcohol, alkyl amido betaine having 16-26 carbon atoms, and a combination thereof. In an embodiment, silver comprised in the antimicrobial composition may be in a form of metallic silver, that is, Ag° or ionic silver such as Ag⁺, Ag²⁺, Ag³⁺, etc. Preferably, silver comprised in the antimicrobial composition is in the form of metallic silver only.

In a preferred embodiment of the invention, the antimicrobial composition comprises silver that is in the form of metallic silver. Preferably, metallic silver coexists with a glass ceramic matrix. More preferably, metallic silver coexists with the glass ceramic matrix such that metallic silver is encapsulated within the glass ceramic matrix, or such that metallic silver is on a surface of the glass ceramic matrix, or a combination thereof. As a particularly preferred example, the glass ceramic matrix is phosphate glass matrix.

In a preferred embodiment of the invention, silver comprised in the antimicrobial composition consists of metallic silver encapsulated within the phosphate glass matrix, or metallic silver on the surface of the phosphate glass matrix, or a combination thereof.

In a specific embodiment, divalent metal salt may be selected from salt of divalent metal that can be selected from zinc, copper, nickel. Preferably, divalent metal salt of hydroxy carboxylic acid or carboxylic acid is zinc salt of hydroxy carboxylic acid or carboxylic acid.

Hydroxy carboxylic acid or carboxylic acid according to the present invention can be selected from a group consisting of gluconic acid, glycolic acid, salicylic acid, hydroxynaphthoic acid, acetic acid, butyric acid, glyceric acid, formic acid, propionic acid, tartaric acid, undecylenic acid, citric acid, and lactic acid, more preferably gluconic acid, citric acid, and lactic acid.

In a preferred emboddiment of the invention, divalent metal salt of hydroxy carboxylic acid or carboxylic acid is zinc gluconate, zinc glycolate, zinc salicylate, zinc hydroxynaphthoate, zinc acetate, zinc butyrate, zinc glycerate, zinc formate, zinc propionate, zinc tartarate, zinc undecylenate, zinc citrate, or zinc lactate, preferably zinc gluconate, zinc citrate, or zinc lactate. More preferably, divalent metal salt of hydroxy carboxylic acid or carboxylic acid is zinc gluconate.

Suitable fatty acid ester of polyhydric alcohol for using in the present invention has 11- 27 carbon atoms. Preferably, fatty acid ester of polyhydric alcohol comprises 2-10 hydroxyl groups, where a hydrogen atom of at least one hydroxyl group is substituted by an acyl group having 8-18 carbon atoms. More preferably, fatty acid ester of polyhydric alcohol comprises 3- 6 hydroxyl groups, where a hydrogen atom of at least one hydroxyl group is substituted by an acyl group having 8-18 carbon atoms. An example of fatty acid ester of polyhydric alcohol that may be used is selected from a group consisting of glycerol monocaprylate, glycerol monocaprate, and a combination thereof.

Suitable alkyl amido betaine for using in the present invention has carbon atoms in a range of 16-26, more preferably having carbon atoms in a range of 16-20. An example of alkyl amido betaine that may be used is, but not limited to, cocamidopropyl betaine.

According to a preferred embodiment of the present invention, the antimicrobial composition comprises divalent metal and silver at a weight ratio of divalent metal to silver in a range of 0.2-1144:1, preferably 0.84-168:1, more preferably 3-92:1, even more preferably 4-67:1, and most preferably 13-23:1, 13-17:1 or 16-23:1.

According to a preferred embodiment of the present invention, the antimicrobial composition comprises Zn²⁺ and Ag° at a weight ratio of Zn²⁺ to Ag° in a range of 0.2-1144:1, preferably 0.84-168:1, more preferably 3-92:1, even more preferably 4-67:1, and most preferably

13-23:1, 13-17:1, or 16-23:1.

In another preferred embodiment of the present invention, the antimicrobial composition comprises fatty acid ester of polyhydric alcohol and silver at a weight ratio of fatty acid ester of polyhydric alcohol to silver in a range of 0-5334:1, preferably 0-781:1, more preferably 15-427:1, even more preferably 19-313:1, and most preferably 61-107:1, 61-79:1, or 78-107:1.

In another preferred embodiment of the present invention, the antimicrobial composition comprises a mixture of glycerol monocaprylate and glycerol monocaprate, and metallic silver at a weight ratio of glycerol monocaprylate and glycerol monocaprate to Ag° in a range of 0-5334: 1 , preferably 0-781:1, more preferably 15-427:1, even more preferably 19-313:1, and most preferably 61-107:1, 61-79:1, or 78-107:1.

In another preferred embodiment of the present invention, the antimicrobial composition comprises alkyl amido betaine and silver at a weight ratio of alkyl amido betaine to silver in a range of 0-4000:1, preferably 0-586:1, more preferably 11-320:1, even more preferably

14-235:1, and most preferably 46-80:1, 46-59:1, or 58-80:1.

In another preferred embodiment of the present invention, the antimicrobial composition comprises cocamidopropyl betaine and Ag° at a weight ratio of cocamidopropyl betaine to Ag° in a range of 0-4000:1, preferably 0-586:1, more preferably 11-320:1, even more preferably 14-235:1, and most preferably 46-80:1, 46-59:1, or 58-80:1.

The antimicrobial composition according to the present invention may also comprise a binder that can be selected from a group consisting of polyvinyl alcohol, modified cellulose, long-chain fatty alcohol, modified polyurethane, water soluble polymer, and a combination thereof, preferably polyvinyl alcohol. The binder is present in an amount of 0-10 wt% of the antimicrobial composition, preferably 0.1-7 wt% of the antimicrobial composition.

In another embodiment, the antimicrobial composition according to the present invention may also comprise a solvent that can be selected from a group consisting of water, alcohol, ethyl acetate, white oil, white spirit, and a combination thereof, where a preferred solvent is water.

The composition according to the present invention can be in any preferred forms according to the application. It may be in a concentrated or diluted form, e.g., in the form of gel, solid, or coating layer on the substrates or specimens or finished products, etc.; or it may in the form of concentrated or diluted solution.

The antimicrobial composition according to the present invention is particularly preferred for coating the surface of substrates or specimens or products of which the microbial growth elimination and inhibition properties are required.

According to the present invention, also provided is a product comprising a substrate coated with the antimicrobial composition according to the invention. The substrate can be made of any material, for example, the substrate may be made of the material that can be selected from a group consisting of wood, cement, plastic, textile, woven fabric, non-woven fabric such as spunbond, melt blown, natural fiber, synthetic fiber, metal, or paper, etc.

Examples of the product according to the present invention are as follows: an air filter such as a cabin air filter for a car, an air filter pad such as a pre-filter pad for an air conditioner, a high efficiency particulate air (HEPA) filter pad, a face mask, a face shield or a personal protective equipment (PPE), etc.

The substrate as described above may be coated with any methods well-known in the art, for instance, wire rod coating, roll coating, curtain coating, rotogravure coating, spray coating, dip coating, casting, brush coating, printing, air knife coating, or other applicable coating methods.

Example

The present invention will now be described in more detail with reference to the examples of experiment. However, these examples are not meant to limit the scope of the invention.

1. Method of preparing the antimicrobial composition Prepare the composition examples according to the present invention (Examples 1-5) and the comparative composition examples (Comparative Examples 1-5) by mixing components in an amount as shown in Table 1 at room temperature (25°C) until a homogeneous solution is obtained. Table 1

Note: a Examples 1-5 have a pH of 5; Comparative Example 1 has a pH of 8 and contains zinc oxide (ZnO) in an amount of 2.4 wt% of the composition instead of zinc gluconate; Comparative Example 2 has a pH of 7.27; Comparative Example 3 has a pH of 5.62; Comparative Example 4 has a pH of 5.19; and Comparative Example 5 has a pH of 5.15. b Metallic silver is encapsulated within the phosphate glass matrix with the metallic silver amount of 1.5-2.6 wt% of the total weight of metallic silver and phosphate glass matrix. c There is zinc (Zn) in an amount of 14.3 wt% of zinc gluconate weight. d Cocamidopropyl betaine is in the form of aqueous solution with the concentration of

30 wt%.

From Table 1, it can be seen that the composition of Comparative Example 1, which uses zinc oxide instead of zinc gluconate, contains a quite high pH likely causing cytotoxicity. Therefore, it is not suitable for use. 2. Method of preparing the specimen coated with the antimicrobial composition

Prepare the specimen examples for testing the bactericidal and virucidal efficacy of the antimicrobial composition according to the present invention (Examples 1, 4, and 5) compared to the comparative composition examples (Comparative Examples 2-5) which are detailed as follows:

1) cutting a filter pad into the size of 10 x 10 cm²;

2) coating the prepared composition example on the surface of the filter pad using a wire bar coater No. 0 at the wet thickness of coating of 4 microns (the dry coat weight is about 6 g/m²);

3) heating the resulting filter pad coated with the composition example at 50°C for 5 minutes to obtain the specimen for testing the disinfectant efficacy in the next step.

3. Method of testing the bactericidal efficacy

Test the bactericidal efficacy on Bacillus Cereus (+), Escherichia Coli (-) for the specimen coated with the antimicrobial composition examples according to the present invention (Examples 1, 4, and 5) and the comparative composition examples (Comparative Example 2-5) which have components as shown in Table 1. The details are shown below:

1) cutting the specimen into the size of 1 cm²;

2) disinfecting the specimen with UV radiation for at least 30 minutes to sterilize it;

3) adding 10 pl of the gram-positive (Bacillus Cereus, +) or the gram-negative bacteria (Escherichia Coli, -) at the concentration of 10⁶ CFU/ml drop-wise onto the specimen;

4) swabbing the living bacteria off the specimen after it has been exposed to the bacteria for a specified period of time using 1 ml sterile distilled water. The time periods are specified as follows:

- TO: to swab immediately after the specimen comes into contacted with the bacteria,

- T24: to swab after the specimen comes into contacted with the bacteria for 24 hours.

Then, spreading a solution derived from swabbing the specimen over the entire agar surface in an agar plate (spread plate) then incubating it in a closed system incubator at 37°C for 24 hours;

5) counting the formed colonies and calculating in comparison between the quantity of bacteria from the control and the quantity of bacteria remaining from the experiment after contacting with the specimen for a different period of time according to the calculation method below. The test result is as shown in Table 2. Percentage reduction of bacteria at any time = [Quantity of bacteria from the control (CFU/ml) - Quantity of bacteria remaining from the experiment (CFU/ml) at the same incubation period] xlOO/Quantity of bacteria from the control (CFU/ml).

Note: The control was prepared by the same method as the experiment but with a filter pad that was not coated with the antimicrobial composition.

4. Method of testing the virucidal efficacy

Test the virucidal efficacy of the specimen coated with the antimicrobial composition, Example 1, which has components as shown in Table 1 according to the ISO 18184 standard which is adapted suitably for testing the SARS-CoV-2 virus. Then, calculate the virus titer from the control in comparison with that from the experiment after contacting with said specimen for 5, 15, and 30 minutes in plaque forming unit /ml (PFU/ml) according to the calculation method below. The test result is shown in Table 3.

Percentage reduction of viruses at any time = [Virus titer from the control (PFU/ml) - Virus titer from the experiment (PFU/ml) at the same condition] xlOO/Virus titer from the control (PFU/ml)

5. Test result

1) Bactericidal efficacy test result

Table 2 below shows the bactericidal efficacy test result derived from testing with the specimen examples 1, 4, and 5, which were coated with the antimicrobial composition according to the present invention, that is, the compositions, Examples 1, 4, and 5, respectively in Table 1, and the specimens, Comparatives 2, 3, 4, and 5, which were coated with the compositions, Comparative Examples 2, 3, 4, and 5, respectively in Table 1. Table 2

From the efficacy test result as shown in Table 2, it can be seen that the antimicrobial compositions with the type and amount of components according to the present invention are significantly more effective in disinfection including in inhibition of the growth of both types of bacteria than Comparative Examples. The antimicrobial composition according to the present invention can destroy and inhibit the growth of both types of bacteria up to 99-100% at TO, that is, when the bacteria was initially contacted with the specimen containing the antimicrobial composition. At T24 which means after leaving it for 24 hours, it can be seen that the disinfection and growth inhibition efficacy of the specimen with the composition according to the present invention is as high as 100%.

2) Virucidal efficacy test result

Table 3 below shows the (SARS-CoV-2) virucidal efficacy test result derived from testing with the specimen coated with the antimicrobial composition according to the present invention (Composition Example 1). Table 3

The test result in Table 3 shows that the antimicrobial composition according to the present invention has the high virucidal efficacy, can quickly kill the viruses and be active for a long time. It can kill the viruses up to 100% even with only 5 minutes of contact time with the virus. Furthermore, when extending the contact time (e.g., 15 and 30 minutes), it can be seen that the virucidal efficacy remains the same.

From all of the above test results, it shows that the antimicrobial composition according to the present invention can inhibit and kill microbes, e.g., the gram-positive (+) and gram-negative (-) bacteria as well as viruses more effectively than the compositions which are Comparative Examples and commonly available. BEST MODE OF THE INVENTION

Best mode of the invention is as described in the detailed description of the invention.

Claims

WHAT IS CLAIMED IS:

1. An antimicrobial composition comprising: a) silver; b) divalent metal salt of hydroxy carboxylic acid or carboxylic acid; and c) a compound which is selected from a group consisting of fatty acid ester of polyhydric alcohol, alkyl amido betaine having 16-26 carbon atoms, and a combination thereof.

2. The antimicrobial composition according to claim 1, wherein silver is in a form of metallic silver (Ag°).

3. The antimicrobial composition according to claim 2, wherein metallic silver coexists with a glass ceramic matrix.

4. The antimicrobial composition according to claim 3, wherein metallic silver coexists with the glass ceramic matrix such that metallic silver is encapsulated within the glass ceramic matrix, or on a surface of the glass ceramic matrix, or a combination thereof.

5. The antimicrobial composition according to claim 3 or 4, wherein the glass ceramic matrix is phosphate glass matrix.

6. The antimicrobial composition according to claim 1, wherein divalent metal salt of hydroxy carboxylic acid or carboxylic acid is zinc salt of hydroxy carboxylic acid or carboxylic acid.

7. The antimicrobial composition according to claim 1 or 6, wherein hydroxy carboxylic acid or carboxylic acid is selected from a group consisting of gluconic acid, glycolic acid, salicylic acid, hydroxynaphthoic acid, acetic acid, butyric acid, glyceric acid, formic acid, propionic acid, tartaric acid, undecylenic acid, lactic acid, and citric acid.

8. The antimicrobial composition according to claim 1 or 6, wherein divalent metal salt of hydroxy carboxylic acid is zinc gluconate.

9. The antimicrobial composition according to claim 1, wherein fatty acid ester of polyhydric alcohol has 11-27 carbon atoms. The antimicrobial composition according to claim 1 or 9, wherein fatty acid ester of polyhydric alcohol comprises 2-10 hydroxyl groups, where a hydrogen atom of at least one hydroxyl group is substituted by an acyl group having 8-18 carbon atoms. The antimicrobial composition according to any one of claims 1, 9 or 10, wherein fatty acid ester of polyhydric alcohol comprises 3-6 hydroxyl groups, where a hydrogen atom of at least one hydroxyl group is substituted by an acyl group having 8-18 carbon atoms. The antimicrobial composition according to any one of claims 1, 9-11, wherein fatty acid ester of polyhydric alcohol is selected from a group consisting of glycerol monocaprylate, glycerol monocaprate, and a combination thereof. The antimicrobial composition according to claim 1, wherein alkyl amido betaine has carbon atoms in a range of 16-20. The antimicrobial composition according to claim 1 or 13, wherein alkyl amido betaine is cocamidopropyl betaine. The antimicrobial composition according to claim 1, which comprises divalent metal and silver at a weight ratio of divalent metal to silver in a range of 0.2-1144:1. The antimicrobial composition according to claim 15, wherein the weight ratio of divalent metal to silver is in a range of 3-92:1. The antimicrobial composition according to claim 16, wherein the weight ratio of divalent metal to silver is in a range of 13-23:1. The antimicrobial composition according to claim 1, which comprises fatty acid ester of polyhydric alcohol and silver at a weight ratio of fatty acid ester of polyhydric alcohol to silver in a range of 0-5334:1. The antimicrobial composition according to claim 18, wherein the weight ratio of fatty acid ester of poly hydric alcohol to silver is in a range of 15-427:1. The antimicrobial composition according to claim 19, wherein the weight ratio of fatty acid ester of poly hydric alcohol to silver is in a range of 61-107:1. The antimicrobial composition according to claim 1, which comprises alkyl amido betaine and silver at a weight ratio of alkyl amido betaine to silver in a range of 0-4000: 1. 14 The antimicrobial composition according to claim 21, wherein the weight ratio of alkyl amido betaine to silver is in a range of 11-320: 1. The antimicrobial composition according to claim 22, wherein the weight ratio of alkyl amido betaine to silver is in a range of 46-80:1. The antimicrobial composition according to any one of claims 1-23, further comprising a binder which is selected from a group consisting of polyvinyl alcohol, modified cellulose, long-chain fatty alcohol, modified polyurethane, water soluble polymer, and a combination thereof. The antimicrobial composition according to claim 24, wherein the binder is present in an amount of 0-10 wt% of the antimicrobial composition. The antimicrobial composition according to claim 25, wherein the binder is present in an amount of 0.1-7 wt% of the antimicrobial composition. The antimicrobial composition according to any one of claims 1-26, further comprising a solvent which is selected from a group consisting of water, alcohol, ethyl acetate, white oil, white spirit, and a combination thereof. A product comprising a substrate coated with the antimicrobial composition according to any one of claims 1-27. The product according to claim 28, wherein the substrate is made of a material which is selected from a group consisting of wood, cement, plastic, textile, woven fabric, non-woven fabric, natural fiber, synthetic fiber, metal, paper, and a combination thereof. The product according to claim 28 or 29, which is an air filter, air filter pad, face mask, face shield, or personal protective equipment (PPE).