SURFACE DISINFECTANT AND COATING

Abstract

The invention relates to the film-forming antimicrobial, antibacterial, antiviral, antiparasitic, and antifungal composition comprises a) a film-forming materials, b) one or more antimicrobial, antibacterial, antiviral, antiparasitic, and antifungal compound(s), c) one or more solubilizing agents, and optionally, d) one or more plasticizer, and e), one or more surfactants or detergents. The invention also relates to a use in prevention or treatment of a disorder in a mammal, such as a human and use of treating animated and non-animated surfaces.

Claims

1. A water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition, comprising, a) a film forming material selected from the group consisting of methacrylic acid-ethyl acrylate copolymer and methacrylic acid-acrylic ester copolymer, b) one or more antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compounds selected from the group consisting of thymol, benzethonium chloride, benzalkonium chloride, citric acid, lactic acid, carvacrol, 2-phenylphenol, chloroxylenol, 1,2-hexanediol, 1,2-octanediol, terpineol and 1,2-decanediol, c) one or more solubilizing agents, which is a solvent, or a mixture of solvents selected from the group consisting of water and a low molecular weight alcohol, and d) optionally, one or more plasticizer, e) optionally, one or more surfactants or detergents.

2. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, comprising a) a film forming materials selected from the group consisting of ethyl cellulose, polyvinyl alcohol, or an acrylate polymers or co-polymers, b) one or more antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compounds selected from the group consisting of thymol, benzethonium chloride, benzalkonium chloride, citric acid, lactic acid and 1,2-hexanediol, c) one or more solubilizing agents, which is a solvent, or a mixture of solvents selected from the group comprising consisting of water and a low molecular weight alcohol, such as ethanol and propanol, d) optionally, one or more plasticizer, and e) optionally, one or more surfactants or detergents.

3. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, wherein the acrylate polymers or co-polymers is selected from the group consisting of methacrylic acid-ethyl acrylate copolymer and methacrylic acid-acrylic ester copolymer.

4. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, wherein the the methacrylic acid-ethyl acrylate copolymer is Kollicoat MAE 30 DP™.

5. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claims 1, wherein the pH of the liquid is below 6.

6. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, whereby the film forming materials is methacrylic acid-ethyl acrylate copolymer at a ratio for methacrylic acid to ethyl acrylate of 5:1 to 1:5 .

7. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, comprising a) a film forming materials selected from methacrylic acid-ethyl acrylate copolymer at a ratio of 1:2 to 2:1, b) one or more antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compounds selected from the group consisting of thymol, 1,2-hexanediol and 1,2-octanediol, c) one or more solubilizing agents, which is a solvent, or a mixture of solvents selected from the group consisting of water and ethanol, d) optionally, one or more plasticizer, and e) optionally, one or more surfactants or detergents.

8. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, comprising a) a film forming materials selected from methacrylic acid-ethyl acrylate copolymer at a ratio of 1:1 to 1:1, b) one or more antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compounds selected from the group consisting of thymol and 1,2-hexanediol, c) one or more solubilizing agents, selected from water and ethanol, d) optionally, one or more plasticizer, and e) optionally, one or more surfactants or detergents selected from polysorbate 80 and/or sodium laurate sulfate.

9. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, whereby the concentrations of the antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compound is 0.01-0.8 v/v % of 1,2-hexanediol and 0.01-0.8 w/v % of thymol, or 0.1-0.5 v/v % of 1,2-hexanediol and 0.1-0.5 w/v % of thymol, or 0.1-0.3 v/v % of 1,2-hexanediol and 0.1-0.3w/v % of thymol, or 0.25-3.2 v/v % 1,2-hexanediol and 0.15-0.25 w/v % thymol, whereby the percentages of the concetrations are relative to the total weight or volume of the composition.

10. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, whereby the concentrations of the antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compound is 0.30 w/v % 1,2-hexanediol and 0.24 w/v % thymol.

11. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, wherein the surfactant or detergents or a mixture of surfactants or detergents is selected from the group consisting of glyceryl trioctanoate, dibutyl sebacate, triethyl citrate, triacetin, acetylated monoglycerides and diethyl phthalate or 1,2-hexanediol, glycerol, caprylic/capric triglycerides, glycerol monolaurate, anionic detergent and surfactant, carboxylates, carboxylate-based fluorosurfactants, or selected from the group consisting of nonionic and zwitter ionic surfactants and detergens, or cationinc detergents and surfactants.

12. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1 any one of the preceding claims, wherein the surfactant or detergents or a mixture of surfactants or detergents is selected from sodium lauryl sulfate and Polysorbate 80.

13. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, further comprising one or more odour masking agent, selected from the group consisting of menthol, citronellal, citrus, lemon, and fragrances.

14. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, further comprising one or more anti itching agent.

15. The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition according to claim 1, further comprising one or more anti-inflammatory agent.

16. (canceled)

17. (canceled)

18. (canceled)

19. (canceled)

20. (canceled)

21. (canceled)

22. (canceled)

23. (canceled)

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0144] FIG. 1 is a schematic demonstrating the step by step procedure of the culture method used for the evaluation and quantification of the antibacterial activity from the devised formulation. The steps comprising (1) Dip a swab in bacteria suspension; (2) Introduce bacteria to the surface; (3) Collect the bacteria from the surface; (4) Suspend the bacteria in phosphate-buffered saline (PBS) and (5) culture the bacteria, then count the colonies.

[0145] FIG. 2 Demonstrates some selected examples photos of the colony counting on agar plates from diluted bacteria suspensions, where the Escherichia coli (E. coli) was added at day 28 onto the coating and uncoated surface (control) and subsequently, the antibacterial activity was measured. The devised coating demonstrated login bacteria density (in CFU/cm.sup.2) of 1.36 ±0.18, whilst the control (without any coating) showed 3.42±0.09, which corresponds to log reduction of 2.06±0.21 (99.1% killed bacteria).

[0146] FIG. 3A A table demonstrating the long-term antibacterial activity of the devised coating formulation against Escherichia coli (E. coli). Each time point and log reduction data corresponds to the measured bacteria killing within 5 min after the bacteria have been introduced to the coating surface. *Log =1 means 1/10 survived (90% killed), 2 means 1/100 survived (99% killed), 3 means 1/1000 survived (99.9% killed) etc.

[0147] FIG. 3B is a graph demonstrating the long-term antibacterial activity of the devised coating formulation against Escherichia coli (E. coli). Each time point and log reduction data correspond to the measured bacteria killing within 5 min after the bacteria have been introduced to the coating surface.

[0148] FIG. 4 Photos demonstrating the stability of our coating formulation (ethyl cellulose (1.0 g, 300 cP), benzethonium chloride (0.2 g), benzalkonium chloride (0.1 g), and thymol (0.1 g) was dissolved in 100 ml of ethanol SDA 3C (95.2% ethanol, 4.8% isopropanol v/v), formulated as described in Example 1), and some commercial products (Complete Home™, Detrapel®, Microban®, and MonoFoil®) after manipulating the coated surface (polystyrene plastics) by 50 times finger swipes and 20 seconds rinsing with water.

[0149] FIG. 5 Photo demonstrating the friction stability of our coating formulation after manipulating the coated polystyrene plastic surface (1 ml solution of the coating formulation was sprayed by a commercial airbrush from an about 15 cm distance, as described in Example 2) by tape peeling (showed severe damage), fingernail scratch 240 times (showed severe damage), 1,200 times cloth wipes (showed slight damage), 1,200 times finger wipes (showed slight damage).

[0150] FIG. 6A Photo demonstrating the temperature stability of the coating formulation after coating a polystyrene plastic surface and then storing the coated materials at 60° C. for 24 h. Demonstrating a temperature stable coating with no damage.

[0151] FIG. 6B Photo demonstrating the temperature stability of the coating formulation after coating a polystyrene plastic surface and then storing the coated materials at —20° C. for 24 h. Demonstrating a temperature stable coating with no damage.

[0152] FIG. 7A Photo demonstrating the temperature storage stability of the coating solution after mixing the ingredients and then storing the solution at 60° C. for 24 h. Demonstrating a temperature stable solution without any precipitation or heterogeneity.

[0153] FIG. 7B Photo demonstrating the temperature storage stability of the coating solution after mixing the ingredients and then storing the solution at −20° C. for 24 h. Demonstrating a temperature stable solution without any precipitation or heterogeneity.

[0154] FIG. 8 Photo demonstrating the long-term storage stability of the coating solution after mixing the ingredients and then storing the solution at room temperature (r.t.) for 33 days. The solution remains colorless and without any precipitation or heterogeneity.

[0155] FIG. 9A Photo demonstrating the coating solution's stability against centrifugation. After centrifugation of the solution at 20,000 rcf for 1 h, the solution remained colorless and without any precipitation.

[0156] FIG. 9B Photo demonstrating the Ultraviolet (UV)-light stability of the coating formulation after coating a polystyrene plastic surface and then storing under UV-irradiation in a biosafety cabinet for 1 h. The experiments demonstrated UV-stable coating surfaces.

[0157] FIG. 9C Photo demonstrating the stability of the coating formulation after coating a polystyrene plastic surface and spitting on and wiping the surface. No damage to the surface was observed after the experiment.

[0158] FIG. 9D Photo demonstrating the stability of the coating formulation after coating a polystyrene plastic surface and spraying the commercial Lysol® All Purpose Cleaner onto the surface, followed by wiping the surface. Some damage to the surface was observed after the experiment.

[0159] FIG. 10 Photo demonstrating the transparency of the coated surface by visualizing the text completely when covered with the coated material. For example, “Coronavirus Disease 2019”, “CDC is responding to the novel coronavirus outb . . . ”, and “Learn More About COVID-19” are beneath the coated material and can be seen almost as clearly as the part uncovered/uncoated, such as “Is it COVID-19 or” and “Sepsis”.

[0160] FIG. 11 The first photo shows the finger rub. The other photos show the impact of finger rubs on the coating, with the number at the top left corner being the number of rubs. The surface was made of polystyrene and sprayed with an amount of 1 L per 50 m.sup.2. The coating was intact until at least 500 rubs.

[0161] FIG. 12. The first photo shows the wiping with water. The other photos show the impact of such wiping on the coating, with the number at the top left corner being the number of wipes. The surface was made of polystyrene and sprayed with an amount of 1 L per 50 m.sup.2. The coating was intact until at least 60 wipes.

[0162] FIG. 13. The first photo shows the wiping with water. The other photos show the impact of such wiping on the coating, with the number at the top left corner being the number of wipes.

[0163] The surface was made of polystyrene and sprayed with an amount of 1 L per 10.91 m.sup.2. The coating was intact until at least 60 wipes.

[0164] FIG. 14. The photo shows the solution not centrifuged and after being centrifuged for 10 min at different speeds (100, 500, 10000, and 20000 rcf). No precipitate was observed for the 100 rcf one, and precipitates were observed for the 500, 10000, and 20000 rcf ones.

[0165] FIG. 15. The photos show the E. coli cultured after exposure to the coating formulation described in Example 1 (coated 0 days, 7 days, 15 days, and 31 days before the antibacterial experiment, formed by spraying 1 L per 50 m.sup.2) for 10 min (the “Our coating” row), and exposure to uncoated polystyrene surfaces (the “Control” row). Both experiments were repeated three times. On the Petri dishes, the numbers (0, −1, . . . , −5) at the tips of the pies indicate serial dilution to different bacteria concentrations relative to the original concentration (10°, 10.sup.−4, . . . , 10.sup.−5. The numbers on the edge of the pies indicate the number of colonies. Using the 0 day(s) (d) one as an example: For our coating, there were 0, 3, and 0 colonies at the original concentration. For controls, there were 5, 3, and 17 colonies at 100×dilution. Therefore, the percent of bacteria killed was 1−(0+3+0)/((5+3+17)*100)=99.88%. The percent of E. coli killed was 98.5%, 97.5%, and 60% for 7 days, 15 days, and 31 days, respectively.

Procedure:

[0166] 1. The bacteria were introduced to the coating as a suspension in water.
2. After collecting the bacteria by swabbing, the swabs were dipped into Dey-Engley Neutralizing Broth, and the serial dilutions were also using Dey-Engley Neutralizing Broth as the diluent.

[0167] FIG. 16. The same volume of E. coli suspension was introduced onto the surface by swabbing as in FIG. 15. Then, the same amount of the coating formulation solution as described in Example 1 (liquid) was sprayed onto the surface as in FIG. 15. After 30 seconds, the bacteria were collected by swabbing, serially diluted, and cultured in the same way as in FIG. 15. The results show that all E. coli was killed, indicating efficacy of >99.97%.

[0168] FIG. 17. The photos show coatings with different sprayed amounts (50 m2/L and 10.91 m.sup.2/L) before and right after being placed at 60° C. or −20° C. for 24 h, and when they were back to room temperature (R.T.).

[0169] FIG. 18. The the coating formulation solution as described in Example 1 displayed no visual changes after sitting at room temperature for 28 days.

[0170] FIG. 190. The coating formulation solution described in Example 1 displayed no visual changes after sitting at 4° C. for 16 days.

[0171] FIG. 20. Left: The the coating solution formulation described in Example 1 froze at −20° C.

[0172] Right: No phase separation was observed after it melts.

[0173] FIG. 21. Coagulation occurred after freezing the solution at −20 ° C., thawing, repeating this freeze-thaw cycle twice, freezing at −80° C., thawing. The melting point was measured to be −11° C. during the last thawing.

[0174] FIG. 22. The coating solution formulation described in Example 1 was contained in a vial, after sitting at 60° C. for 24 h. A slight number of solid pieces was formed (highlighted in the circle).

[0175] FIG. 23. The photos show water on a fabric surface coated (the two photos on the left) and not coated (the two photos on the right) with the coating formulation described in Example 1. The coated one had water absorbed into the fabric, and the uncoated one repelled the water. Therefore, the coated fabric was more hydrophilic than the uncoated one.

[0176] FIG. 24. Left: The coated substrates were placed at the center of a Labconco Purifier Biological Safety Cabinet for 1 h UV irradiation. One of the coatings was sprayed at an amount of 1 L per 50 m.sup.2, the other 1 L per 10.91 m.sup.2. Right: Neither of them displayed any visual changes after the UV irradiation.

[0177] FIG. 25. Optical microscope photos of the coatings (formulation described in Example 1). Top two photos: Sprayed by Master Airbrush (Multi-purpose Gravity Feed Dual-action Airbrush Kit with 6 Foot Hose and a Powerful ⅕ hp Single Piston Quiet Air Compressor) with an amount of 50 m.sup.2/L. Bottom two photos: Sprayed by Graco TC Pro Cordless Airless Paint Sprayer with a TC Pro 208 0.008 in. Tip at the pressure level 4 from a distance of about 1.5 m.

[0178] FIG. 26 Photo demonstrating the effect from the number of layers coated. The transparent surface turned opaquer with more layers of coating applied. The numbers at the top left corners of the photos are the number of layers coated. The spraying coverage was 50 m.sup.2/L for each layer.

[0179] FIG. 27 Graph demonstrating the viscosity the coating solution at 25° C. and 6.5° C. as a function of shear rate.

[0180] FIG. 28 Photo demonstrating the SEM images of the coated formulations on glass, plastic (polystyrene) and metal (aluminum) with 600×, 1200× and 2000× magnification.

[0181] FIG. 29. Temperature program in table 8.

[0182] FIG. 30. Demonstrate the time it takes for the Graco TC Pro SPRAYER to coat 1 m.sup.2 of surface at 50 m.sup.2/L at different pressure levels.

[0183] FIG. 31 Photo demonstrating the optical microscope photos of the coatings. Top two photos: Sprayed by Master Airbrush (Multi-purpose Gravity Feed Dual-action Airbrush Kit with 6 Foot Hose and a Powerful ⅕ hp Single Piston Quiet Air Compressor) with an amount of 50 m.sup.2/L. Bottom two photos: Sprayed by Graco TC Pro Cordless Airless Paint Sprayer with a TC Pro 208 0.008 in. Tip at the pressure level 4 from a distance of about 1.5 m.

[0184] FIG. 32 Photo demonstrating the transmission electron microscopy (TEM) image of coating solution formulation showing that it contains nanoparticles.

[0185] FIG. 33 Graph demonstrating the particle size distribution by number of the coating solution made in the lab (lower line) and the one made by the Mexican manufacturer (large scale production, higher line) determined by dynamic light scattering (DLS). The former has a Z-average diameter of 148.9±0.9 nm and a PDI of 0.050±0.014. The latter has a Z-average diameter of 134.7±1.0 nm and a PDI of 0.016±0.011. The two were very close, indicating that the manufacturer was producing a product consistent with what we made in the lab.

[0186] FIG. 34 The first photo shows the coated ceramic surface prior finger rub. The other photos show the impact of finger rubs on the coating, with the numbers of rubs are shown at the top left corner of the photos. The black circle highlights the damage done to the coating at the end.

[0187] FIG. 35 The first photo shows the coated wood surface prior finger rub. The other photos show the impact of finger rubs on the coating, with the numbers of rubs are shown at the top left corner of the photos. The red circle highlights the damage done to the coating at the end.

[0188] FIG. 36 The first photo shows the uncoated and coated apple at day 1. The second photo after day 92.

[0189] FIG. 37 The first photo shows the uncoated apple sliced in the middle at day 92. The second photo the coated apple sliced in the middle at day 92.

DETAILED DESCRIPTION

Definitions

[0190] As used herein “antimicrobial” means an agent or compound having the ability to kill or defect one or more bacteria, viruses, fungi and/or parasites. The antimicrobial may have antibacterial, antiviral, antifungal and antiparasitic disinfectant effects. The expression “one or more antimicrobial compounds” includes polymers thereof.

[0191] As used herein “disorder” includes any disease or illness or syndrome.

[0192] Kollicoat MAE 30 DP, CAS Number: CAS nr 25212-88-8, is a copolymer derived from methacrylic acid/ethyl acryliate, The ratio of the components in the copolymer are 1:1 and the average molecular weight is 250000 M/g. Kollicoat MAE 30 DP contains 0.7 wt % sodium lauryl sulfate and 2.3 wt % polysorbate 80 as surfactant/emylsifier/detergent.

[0193] Benzethonium chloride has structural formula

##STR00002##

and systematic IUPAC name, Benzyldimethyl(2-{2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy}ethyl)azanium chloride, and CAS Number 121-54-0.

##STR00003##

[0194] Benzalkonium chloride has structural formula n=8, 10, 12, 14, 16, 18 and IUPAC name N-Alkyl-N-benzyl-N,N-dimethylammonium chloride, and CAS Number 8001-54-5.

[0195] Thymol has structural formula

##STR00004##

and systematic IUPAC name 5-Methyl-2-(propan-2-yl)benzenol and CAS Number 89-83-8.

[0196] The invention relates to a water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition, comprising or consisting of,

[0197] a) 0.1 to 10.0 wt %, or 1 to 6 wt % or 1 to 4 wt % of a film forming materials selected from the group comprising or consisting of ethyl cellulose, polyvinyl alcohol, polyvinyl acetate, polyvinyl alcohol-polyethylene glycol graft-copolymer, and/or an acrylate polymers, poly(methacrylic acid)polymer or co-polymers,

[0198] b) 0.15 to 0.80 wt %, or 0.20 to 0.60 wt % 0.40 to 0.60 wt % of one or more antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compounds selected from the group comprising or consisting of thymol, benzethonium chloride, benzalkonium chloride, citric acid, lactic acid, carvacrol, 2-phenylphenol, chloroxylenol, 1,2-hexanediol, 1,2-octanediol, terpineol and 1,2-decanediol,

[0199] c) up to 100 wt % of one or more solubilizing agents, which is a solvent, or a mixture of solvents selected from the group comprising or consisting of water and a low molecular weight alcohol, such as ethanol and propanol, and

[0200] d) 0 wt % to 5 wt %, or 0.1 wt % to 1 wt %, one or more plasticizer,

[0201] e) optionally, one or more surfactants or detergents,

[0202] f) optionally, one or more agent selected from antivirals, antibacterial, antiparasitic, antifungal drug, mineral, vitamin, fatty acid, protein, odour masking agent, anti-itching agent, anti-inflammatory agent, and insecticidal compounds.

[0203] The invention relates to a water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition, comprising or consisting of,

[0204] a) 0.1 to 10.0 wt %, or 1 to 6 wt %, or 2 to 4 wt % of a film forming materials selected from the group comprising or consisting of an acrylate polymers or poly(methacrylic acid)polymer or co-polymers,

[0205] b) 0.15 to 0.80 wt %, or 0.20 to 0.60 wt %, or 0.40 to 0.60 wt % of one or more antimicrobial, 5 antibacterial, antiviral, antiparasitic and antifungal compounds selected from the group comprising or consisting of thymol, benzethonium chloride, benzalkonium chloride, 1,2-hexanediol, 1,2-octanediol, terpineol and 1,2-decanediol,

[0206] c) up to 100wt % of one or more solubilizing agents, which is a solvent, or a mixture of solvents selected from the group comprising or consisting of water and a low molecular weight alcohol, such as ethanol and propanol, and

[0207] d) 0 wt % to 5 wt %, or 0.1 wt % to 1 wt %, one or more plasticizer,

[0208] e) optionally, one or more surfactants or detergents,

[0209] f) optionally, 0 wt % to 25 wt %, or 10 wt % to 10 wt %, 0 wt % to 5 wt % of one or more agent selected from antivirals, antibacterial, antiparasitic, antifungal drug, mineral, vitamin, fatty acid, protein, odour masking agent, anti-itching agent, anti-inflammatory agent, and insecticidal compounds.

[0210] The acrylate polymers or co-polymers may be selected from the group comprising or consisting of methacrylic acid-ethyl acrylate copolymer and methacrylic acid-acrylic ester copolymer. The acrylate polymers or co-polymers may be methacrylic acid-ethyl acrylate copolymer or Kollicoat MAE 30 DP™.

[0211] The amount of film forming materials, or methacrylic acid-ethyl acrylate copolymer or Kollicoat MAE 30 DP™ in the final composition may be 0.5 to 20 wt %, or 1 to 15 wt %, or 1 to 5 wt %, 1.5 to 5 wt %, or 2 to 4 wt %, or 2.5 to 3.5 wt %.

[0212] The one or more antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compounds is selected from the group comprising or consisting of thymol, carvacrol, 1,2-hexanediol and 1,2-octanediol. The one or more antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compounds is thymol and/or 1,2-hexanediol.

[0213] The amount of the antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compound may be 0.01-0.8 v/v % of 1,2-hexanediol and 0.01-0.8 w/v % of thymol, or 0.1-0.5 v/v % of 1,2-hexanediol and 0.1-0.5 w/v % of thymol, or 0.1-0.3 v/v % of 1,2-hexanediol and 0.1-0.3 w/v % of thymol, or 0.25-3.2 v/v % 1,2-hexanediol and 0.15-0.25 w/v % thymol.

[0214] The amount of the antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compound may be 0.30 v/v % 1,2-hexanediol and 0.24 w/v % thymol.

[0215] The solvent may be a mixture of ethanol and isopropanol. The solvent may be a mixture of water and ethanol. The amount of ethanol in a mixture of water and ethanol solvent based on the weight of the final composition may be 5 to 50 wt %, or 5 to 25 wt %, or 5 to 20 wt %, 5 to 15 wt %, or 10 to 20 wt %, or 10 to 15 wt %.

[0216] The plasticizer may be selected from the group comprising or consisting of glyceryl trioctanoate, dibutyl sebacate, triethyl citrate, triacetin, Myvacet® (acetylated monoglycerides) and diethyl phthalate. The plasticizer may be glyceryl trioctanoate.

[0217] The amount of glyceryl trioctanoate present may be from 0.01 wt % to 20 wt %, or 0.01 wt % to 10 wt %, or 0.05 wt % to 5 wt %, or 0.1 wt % to 1 wt %, or 0.01 wt % to 1 wt %, or about 0.1 wt %. Percentages based on the weight of the final composition

[0218] The surfactant or detergents or a mixture of surfactants or detergents may be polysorbate 80 and/or sodium lauryl sulfate.

[0219] The water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition may comprise or consists of [0220] a) 1 to 5 wt % a film forming materials selected from Kollicoat MAE 30 DP™, [0221] b) 0.30 to 0.75 one or more antimicrobial, antibacterial, antiviral, antiparasitic and antifungal compounds selected from the group comprising or consisting of thymol and 1,2-hexanediol, [0222] c) up to 100 wt % one or more solubilizing agents selected from water and ethanol, whereby the weight ratio ethanol to water is 5-20 to 95 to 80.

[0223] In some aspects, the water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition further comprises one or more odour masking agent, optionally selected from the group comprising or consisting of menthol, citronellal, citrus, lemon, fragrances, such as Fragrance Lemon Verbena (Making Cosmetics Lot # 071118MCLV) (preferable concentrations 0.05%, 0.1%, 0.2%, 0.5%, and 1%, or 0.1% or 0.2%), Fragrance Blood Orange (Making Cosmetics Lot #171101015), Fragrance Pink Grapefruit Passion Fruit (Making Cosmetics Lot #180728016), Fragrance Mangosteen (Making Cosmetics Lot #180620050), Fragrance Coral Reef (Making Cosmetics Lot #170815034), Fragrance Citrus Punch (Making Cosmetics Lot #180206062), lemon fragance, and orange fragance and lavender fragrance.

[0224] In some aspects, the water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition further comprises one or more anti itching agent, optionally selected from the group comprising or consisting of pramoxine hydrochloride, diphenhydramine, cetirizine, loratadine, desloratadine and fexofenadine.

[0225] In some aspects, water insoluble film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition further comprises or consists of one or more anti-inflammatory agent, optionally selected from the group comprising ibuprofen, naproxen, diclofenac, celecoxib, mefenamic acid, etoricoxib, indomethacin, aspirin, diflunisal and neosporin.

[0226] The composition of the invention may be used for coating animated and non-animated surfaces. The surfaces may be any organic surface, such as fruits, vegetables, nuts, meat, beef, fish, bone, or any edible product. The surfaces may be foods, fruits and vegetables. The surfaces may be an apple or an orange.

[0227] The composition of the invention may be used as a pesticide, insecticide or ant-microbal agent to prevent microbial deposition, growth, spread and survival.

[0228] The composition of the invention may be used in therapy, such as for use in prevention or treatment of a disorder in a mammal, such as a human. The disorder may be a skin disorder.

[0229] In some aspects, treating or preventing occurs by an application method selected from the group consisting of spraying, pressurized aerosol, fogging, rolling, brushing, mopping, wiping, dipping, injecting or any mixture thereof.

[0230] In some aspects, the film forming antimicrobial, antibacterial, antiviral, antiparasitic and antifungal composition, the composition as defined herein can optionally be composed of a combination of zero, one or more of the antivirals, antibacterial, antiparasitic, antifungal drug, mineral, vitamin, fatty acid, protein, odour masking agent, anti-itching agent, anti-inflammatory agent, and insecticidal compound.

[0231] In certain aspects, the invention relates to an environmentally friendly antimicrobial and antiviral surface disinfectant and long-lasting coating formulation. In some aspects the composition comprises film forming material, antimicrobial, antiviral, biocidal and quaternary ammonium-based compounds and polymers, and combination thereof, solubilizing agents and optionally plasticizer. In some aspects the formulation may be used to treat or prevent microbial, fungal, parasitic deposition and viral formation, spreading and survival. In some aspects, the formulation may be used to immediately kill microbes and viruses and immediately form a long-lasting, transparent coating with the ability to further protect the surface for a long period of time. In some aspects, the formulation may be used to treat any surfaces selected from the group comprising plastics, metal, steel, wood, ceramics, tissue, glass, granite, stone, marble, hard and soft surfaces, skin or mucosal surface. In some aspects the formulation may be used to treat surfaces of fruits, vegetables, nuts, meat, fish, bone or any edible products, or any mixture thereof, any type of trees, plants, flowers, crops, harvest plats, retails and hospitals, public spaces, hotels, boats, airports, packages, boxes, bin, toilets, bathrooms, domestic and professional settings, and combination thereof. In some aspects, the formulation may be administered or applied, for instance by spraying, pressurized aerosol, fogging, rolling, brushing, mopping, wiping and dipping.

[0232] In certain aspects, the invention relates to a composition comprising film forming material selected from cellulose or its derivatives, antimicrobial, antiviral and biocidal components, and combination thereof, and solubilizing agents.

[0233] In certain aspect, the invention relates to a composition comprising film forming material selected from cellulose or its derivatives, physically entrapped or covalently functionalized with antimicrobial, antiviral, biocidal and quaternary ammonium-based compounds and polymers, and combination thereof, and solubilizing agents.

[0234] In some aspects the composition comprises film forming material ethyl cellulose, the antimicrobial and antiviral comprises a combination of benzethonium chloride, benzalkonium chloride and thymol, and the solubilizing agent ethanol.

[0235] In certain aspects, the formulation comprises a combination of aqueous media and an organic liquid, or solvent mixture of any low molecular weight alcohols, water, alkylene glycol ether based, oils, buffers organic solvent, and combination thereof.

[0236] Ethyl cellulose is a biocompatible and Food and Drug Administration (FDA)-approved polymer. When combined with appropriate solvent forms a stable film immediately after applied.

[0237] In some aspects the composition comprises Environmental Protection Agency (EPA)-accepted ingredients.

[0238] In certain aspects, the invention relates to antibiotic free agents. In one aspect, the use of antibiotics is disclaimed.

[0239] In certain aspects, the formulation immediately upon application form a stable, transparent and long-lasting coating.

[0240] In certain aspects, the composition, upon application, forms a stable and transparent coating, thereby substantially killing, preventing and protecting from microbial, fungal, parasitic and viral formation, spreading and survival.

[0241] In certain aspects, the disclosure further provides medical and veterinary uses for the formulation. While human applications will become apparent from the disclosure, a preferred use relates to a method of forming an environmentally friendly antimicrobial and antiviral surface disinfectant and long-lasting coating formulation protecting various surfaces.

[0242] In certain aspects, the surface may be made from selected from the group comprising to organic and inorganic materials, plastics, metal, steel, wood, ceramics, tissue, glass, granite, stone, marble, hard and soft surfaces, skin or mucosal surface.

[0243] In certain aspects, the surface may selected from the group comprising fruits, vegetables, retails and hospitals, public spaces, hotels, boats, airports, packages, boxes, bins, toilets, edible products, bathrooms, domestic and professional settings.

[0244] In particular aspects, the formulation may be administered or applied by spraying.

EXAMPLES

[0245] In order that aspects of the invention described herein may be more fully understood, the following examples are set forth. The examples described in this application are offered to illustrate the compounds, pharmaceutical compositions, and methods provided herein and are not to be construed in any way as limiting their scope.

Materials and Methods

[0246] Chemicals and solvents were purchased from commercial suppliers or were fabricated and purified by standard techniques. The following commercial reagents were used as purchased without any further purification: ethanol SDA 3C (USA LAB ALLEY, EAS1014-55GAL, USA), ethyl cellulose (Viscosity 300 cP, 200654, Sigma Aldrich), benzethonium chloride (≥98% (HPLC), Sigma Aldrich, B8879), benzalkonium chloride (41339, Alfa Aesar) and thymol (Crstl, NF, 6WYW8, GRAINGER).

Example 1—Preparation of the Coating Solution

[0247] The various compositions ethyl cellulose (300 cP, 1.0 g), benzethonium chloride (0.2 g), benzalkonium chloride (0.1 g) and thymol (0.1 g) was dissolved in 100 ml of ethanol SDA 3C (95.2% ethanol, 4.8% isopropanol v/v) by stirring at room temperature until a homogenous solution was formed.

Example 2—Film Preparation of the Formulation on Various Surfaces

[0248] The film coating on various surfaces such as polystyrene plastics, metal, wood, and ceramics was performed using a commercial airbrush (Master airbrush multi-purpose gravity feed dual-action airbrush kit with 6-foot hose and a powerful ⅕ HP single piston quiet air compressor). The coating formulation solution (1 ml) was pipetted into the gravity fluid cup of the airbrush and subsequently the entire solution was sprayed on the selected surface from a about 15 cm distance.

[0249] Example 3—Evaluation of the Antimicrobial Properties of the Disinfectant Formulation

[0250] The bacteria strains Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains were used in all the experiments. Prior to each experiment, bacterial stock cultures were prepared by inoculating a single bacterial colony in 3.7% Brain Heart Infusion (BHI) broth at 37° C. until stationary phase. Bacterial stock cultures were then diluted to 5×10.sup.8 colony forming units (CFU)/ml. To test the antibacterial properties of disinfectant solution, about 10.sup.7 CFU of the selected bacteria was added to a plate lid surface (127.7 mm×85.4 mm) by taking a dip swap from the bacteria suspension and then further introducing the bacteria to the surface (about 10.sup.5 CFU/cm.sup.2), subsequently 1 ml of the formulation was sprayed on this surface. The antibacterial activity was measured immediately and after 10 min by collecting the bacteria by taking a swab from the surface and then further suspend the bacteria in PBS and further bacteria culturing to quantify the level of bacteria presence after incubating the agar plates for 16 h. Bacterial density on each sample (CFU/cm.sup.2) was determined by the number of colonies counted. The control sample contained only bacteria solution on the surface without any treatment of the disinfectant solution. The coating showed a bacteria density of 3.43±0.06 and the control 4.05±0.21 (CFU/cm.sup.2), which corresponds to 0.63±0.22 log reduction or 76% killing after immediate measurements. After 10 min of incubation and then further measurements of the coating showed a bacteria density of 1.81±0.10 and the control 4.03±0.15 (CFU/cm.sup.2), which corresponds to 2.21±0.18 log reduction or 99.4% killing.

Example 4—Evaluation of the Antimicrobial Properties of the Coated Formulation

[0251] The antimicrobial formulation (1 ml) was sprayed onto a plate lid surface (polystyrene plastic), which immediately formed a stable and transparent film. To test the antibacterial properties of coated surface, a solution of 5×10.sup.8 CFU/ml of the E. coli was added to a plate lid surface (127.7 mm×85.4 mm) by taking a dip swap from the bacteria suspension (about 10.sup.7 CFU) and then further introducing the bacteria to the surface (about10.sup.5 CFU/cm.sup.2).

[0252] The antibacterial activity was measured on the selected time points by collecting the bacteria by taking a swab from the surface and then further suspend the bacteria in PBS and further bacteria culturing to quantify the level of bacteria presence by incubating the agar plates for 16 h. Bacterial density on each sample (CFU/cm.sup.2) was determined by the number of colonies counted. The control sample contained only bacteria solution on the surface without any treatment of the disinfectant solution. See FIGS. 1, 2, 3A and B.

Example 5—Stability Evaluation of our Coating Formulation and Commercial Products

[0253] The stability of the coating formulation solution and its corresponding coated surface film was investigated through various experiments. See FIGS. 4-9.

[0254] Experiment 1: The stability of our coating formulation and some commercial products (Complete Home™, Detrapel®, Microban®, and MonoFoil®) was investigated by spraying the respective products onto a polystyrene plastic surface, followed by manipulating the coated surface by 50 times finger swipes and 20 seconds rinsing with water. The coated film showed no damage, whilst the commercial products were completely destroyed, except for the coating from the Detrapel®. See FIG. 4.

[0255] Experiment 2: The friction stability of our coating formulation was investigated by spraying the devised product onto a polystyrene plastic surface (1 ml solution of the coating formulation was sprayed by a commercial airbrush from a about 15 cm distance, as described in Example 2), followed by manipulating the coated surface by tape peeling, fingernail scratch 240 times, 1,200 times cloth wipes and 1,200 times finger wipes. See FIG. 5.

[0256] Experiment 3: The temperature stability of the coating formulation was investigated by coating a polystyrene plastic surface and then storing the coated materials at 60° C. and —20 C. for 24 h. See FIGS. 6A and 6B.

[0257] Experiment 4: The temperature storage stability of the coating solution was performed by mixing the ingredients and then the solution was further stored at 60° C. and −20° C. for −24 h. See FIGS. 7A and 7B.

Experiment 5: The long-term storage stability of the coating solution was investigated by storing the solution at r.t. for 33 days. See FIG. 8.

Experiment 6: The stability of the coating solution against centrifugation was investigated by centrifuging the solution at 20,000 rcf for 1 h. See FIG. 9A.

[0258] Experiment 7: The UV-light stability of the coating formulation after coating a polystyrene plastic surface was investigated by 254 nm UV-irradiation of the coated surface in a biosafety cabinet for 1 h. See FIG. 9B.

[0259] Experiment 8: The stability of the coating formulation after coating a polystyrene plastic surface was further investigated by spitting (about 2 ml) and wiping the coated surface. See FIG. 9C.

[0260] Experiment 9: The stability of the coating formulation after coating a polystyrene plastic surface was investigated by spraying the commercial Lysol®. All Purpose Cleaner disinfectant spray (about 0.5 ml) onto the surface, followed by wiping the surface. See FIG. 9D.

Materials and Methods

[0261] Chemicals and solvents were purchased from commercial suppliers or were fabricated and purified by standard techniques. The following commercial reagents were used as purchased without any further purification: Ethanol (96%, Reag. Ph Eur, Sigma Aldrich), Kollicoat® MAE DP (46.0-50.6% methacrylic acid basis, Sigma Aldrich), thymol (Crstl, NF, 6WYW8, GRAINGER) and 1,2-hexanediol (98%, Sigma Aldrich).

Example 6—Preparation of the Coating Solution

[0262] 1. Dissolve 2.3627 g of thymol and 2.8087 g of 1,2-hexanediol in 122.73 g of 96 v/v % ethanol (the 4 v/v % is water) by stirring for 2 min. [0263] 2. Under stirring, add 807.67 g of water, continue to stir for 5 min to mix well. [0264] 3. Under stirring, add 32.815 g of Kollicoat® MAE 30 DP, continue to stir for 15 min to mix well.

Additional Notes:

[0265] All steps are conducted at room temperature.

Example 7—Evaluation of the Antimicrobial Properties of the Disinfectant Formulation

[0266] The bacteria strains Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains were used in all the experiments. Before each experiment, bacterial stock cultures were prepared by inoculating a single bacterial colony in 3.7% Brain Heart Infusion (BHI) broth at 37° C. until stationary phase. The bacteria suspension was centrifuged at 1000 rcf for 10 min at 20° C. to precipitate the bacteria. The supernatant (BHI broth) was decanted and replaced with the same volume of Milli-Q water. It was then vortexed to redisperse the bacteria in water. To test the antibacterial properties of the disinfectant solution, 1104 of the bacteria water dispersion was added to a plate lid surface (127.7 mm×85.4 mm) and spread out by swabbing with a Q-Tips cotton swab, subsequently, 0.218 ml (corresponding to 50 m.sup.2/L) of the formulation was pipetted on this surface and spread out with another Q-Tips cotton swab. After 30 seconds, this swab was agitated in 500 μL of Dey-Engley neutralizing broth to detach the bacteria. After serial dilution and incubation on agar plates at 37° C. for 12-16 h, the bacterial density on each sample (CFU/cm.sup.2) was determined by the number of colonies counted. The control sample used Milli-Q water in place of the disinfectant solution.

Example 8—Evaluation of the Antimicrobial Properties of the Coated Formulation

[0267] The antimicrobial formulation (0.218 ml, corresponding to 50 m.sup.2/L) was sprayed onto a plate lid surface (polystyrene plastic, 127.7 mm x 85.4 mm) and allowed to dry for 3 min, which formed a stable and transparent film. To test the antibacterial properties of the coated surface, 1104 of a bacteria water dispersion (prepared in the same way as in Example 3) was added to a plate lid surface and spread out by swabbing with a Q-Tips cotton swab. After 10 minutes, another Q-Tips cotton swab fully soaked with water was used to swab and collect the bacteria on the surface. This swab was agitated in 500 μL of Dey-Engley neutralizing broth to detach the bacteria. After serial dilution and incubation on agar plates at 37° C. for 12-16 h, the bacterial density on each sample (CFU/cm.sup.2) was determined by the number of colonies counted. The control sample skipped the spraying and film formation steps.

Example 9—Screening of the Coating Formulations with Various Antimicrobial Ingredients

[0268] After collecting the bacteria by swabbing, the swabs were dipped into PBS, and the serial dilutions were also using PBS as the diluent. All experiments were conucted right after the spraying of coating formulations and the subsequent formation of the coating. The various antimicrobial ingrenteksns and their combination screened are presented in Table 1.

TABLE-US-00001 TABLE 1 Screening of formulations for the highest antibacterial efficacy. Thymol Second anti- Second agent E. coli killed concentration.sup.[a] microbial agent concentration.sup.[a] after 5 min 0.20.sup.[b] Citric acid 0.20 69% 0.20.sup.[b] 1,2-Hexanediol 0.20 98% 0.20.sup.[b] Lactic acid 0.20 46% 0.20.sup.[b] Octanoic acid 0.20 83% 0.20.sup.[c] 1,2-Hexanediol 0.15 87% 0.25.sup.[c] 1,2-Hexanediol 0.15 65% 0.25.sup.[c] 1,2-Hexanediol 0.20 85% 0.20.sup.[c] 1,2-Hexanediol 0.25 99.975%    0.25.sup.[c] 1,2-Hexanediol 0.25 99.915%    .sup.[a]Except for the active ingredients, all other ingredients and their concentrations were the same as the coating formulation presented in Example 1. Here, the concentrations are relative to the methacrylic acid-ethyl acrylate copolymer (1:1). It is w/w for solids and v/w for liquids. .sup.[b]The bacteria were introduced to the coating as a suspension in PBS. .sup.[c]The bacteria were introduced to the coating as a suspension in pure water.

TABLE-US-00002 TABLE 2 The time it takes for the Graco TC Pro Sprayer to coat 1 m.sup.2 of surface at 50 m.sup.2/L at different pressure levels Tip #208 Orifice size: 0.008″; Fan width: 4″ Pressure level Speed (g/s) Time it takes to coat 1 m.sup.2 (s) 1 2.23 8.97 2 2.34 8.54 3 2.76 7.24 4 3.01 6.65 5 3.24 6.16 6 3.30 6.05

Motivation for the Selection of the Active Ingredients

[0269] All the antimicrobial active agents selected are active ingredients in the EPA's List N (Disinfectants for Use Against SARS-CoV-2 (COVID-19)).

[0270] Moreover, the 1,2-hexanediol not only acts as an active antimicrobial agent but also acts as a plasticizer and therefore promote the self-assembly of the polymers towards a more robust film coating. The use of thymol have also additional advantages beside being antimicrobial, it has been reported by Palaniappan et al. that thymol is highly effective in reducing the minimum inhibitory concentration of several antibiotics..sup.1 Liu et al. reported that thymol elicited a synergistic effect with streptomycin against L. monocytogenes..sup.2 Zhou et al. found that thymol has a synergistic effect with chelators and organic acids against Salmonella Typhimurium..sup.3 The antimicrobial efficacy of soy sauce can be enhanced by thymol acting in synergism as reported by Moon et al..sup.4 In expectation for synergy, thymol was added in our final formulation.

Example 10—Antibacterial and Antifungal Tests

[0271] E. coil was grown in a BHI medium to a concentration of 10.sup.9 CFU/mL at 37° C. and 250 rpm shaking. For Candida albicans, it was grown in a Sabouraud dextrose broth to a concentration of 10.sup.8 CFU/mL at 30° C. and 250 rpm shaking (shaking was necessary to avoid dumping of the fungi). The liquid medium with bacteria or fungi was centrifuged at 1000 rcf (for bacteria) or 250 rcf (for fungi) for 20 min to precipitate the bacteria or fungi. The supernatant was carefully decanted, and the same volume of sterile pure water was added. It was then vortexed to resuspend the bacteria or fungi in water. This suspension should be used immediately. 110 μL of the suspension was pipetted to the surface and spread out by swabbing for 1 min. Here, a dry swab was used for bacteria; while for fungi, the swab was dipped into the fungi suspension to get it wet right before using it to spread. The Petri dishes were with the lids on throughout the 9 min (9 min+1 min of spreading time=10 min) waiting time for bacteria; while for fungi, the Petri dishes were with the lids on for 3 h 19 min, and remove the lids to let it dry for the remaining 40 min (4 h in total). After the waiting, all the Petri dishes (bacteria or fungi) would be dry or almost dry. 100 μL of water was pipetted onto each Petri dish, which was then swabbed using a dry and clean swab for 1 min to collect the bacteria or fungi. The swab was then dipped into 600 μL of Dey-Engley neutralizing broth and agitated up-and-down for 50 times to detach the bacteria or fungi from the swab. The broth was serially diluted to 10, 100, 1000, 10.sup.4, and 10.sup.5 times with also the Dey-Engley neutralizing broth. Including the undiluted one, 20 μL of each of the six was spotted on an agar plate. The plates were incubated at 37° C. until visible colonies could be seen and counted. It took 14 h for E. coil and 26 h for Candida albicans.

TABLE-US-00003 TABLE 3 E. coli killing efficacy of various formulas right after coating and drying with a bacteria exposure time of 10 min. The spraying coverage was 50 m.sup.2/L (157 μL per Petri dish). The antibacterial tests were conducted right after the coatings were dried and formed. The bacteria were exposed to the coating for 10 min. E. coli killing Other Alcoholics Phenolics Polymer efficacy observations Hex (0.30%) Thymol (0.24%) Kollicoat MAE 30 99.43%   DP (1%) Hex (0.45%) Thymol (0.36%) Kollicoat MAE 30 99.79%   DP (1%) Hex (0.60%) Thymol (0.48%) Kollicoat MAE 30 87.14%   DP (1%) Hex (0.75%) Thymol (0.60%) Kollicoat MAE 30 94.55%   DP (1%) Hex (0.90%) Thymol (0.72%) Kollicoat MAE 30 91.82%   DP (1%) Hex (1.50%) Thymol (1.20%) Kollicoat MAE 30 Not effective DP (1%) Oct (0.30%) Thymol (0.24%) Kollicoat MAE 30 99.57%   DP (1%) Dec (0.30%) Thymol (0.24%) Kollicoat MAE 30 Not effective DP (1%) Hex (0.30%) Thymol (0.24%) Kollicoat SR 30 D Not effective (1%) Hex (0.30%), Ter Thymol (0.24%) Kollicoat MAE 30 76% (0.30%) DP (1%) Oct (0.30%), Ter Thymol (0.24%) Kollicoat MAE 30 90% Weird odor; (0.30%) DP (1%) droplets join each other and form bigger droplets Hex (0.15%), Oct Thymol (0.24%) Kollicoat MAE 30 80% (0.15%), Ter DP (1%) (0.30%) Ter (0.30%) Thymol (0.24%) Kollicoat MAE 30 77% DP (1%) Hex (0.30%), Ter — Kollicoat MAE 30 89% (0.30%) DP (1%) Oct (0.30%), Ter — Kollicoat MAE 30 77% Weird odor; (0.30%) DP (1%) droplets join each other and form bigger droplets Ter (0.30%) Thymol (0.24%) Kollicoat MAE 30 80% DP (1.13%) Ter (0.30%) — Kollicoat MAE 30 83% DP (1%) Ter (0.60%) — Kollicoat MAE 30 82% DP (1%) — — Kollicoat MAE 30 78% DP (1%) Abbreviation: Hex = 1,2-Hexanediol; Oct = 1,2-Octanediol; Ter = (−)-α-terpineol

TABLE-US-00004 TABLE 4 E. coli killing efficacy of the coating at different aging times and bacteria exposure times and surface areas. The killing efficacy data were from three repetitions. The spraying coverage was 50 m.sup.2/L (157 μL for 78.54 cm.sup.2, 218 μL for 109.10 cm.sup.2). The well-plate lid model was Cytiva Whatman ™ Clear Polystyrene Universal Lid (Manufacturer: Cytiva 77041001). The Petri dish model was purchased from VWR (polystyrene, catalog No. 25384-302). Surface Bacteria E. coli area Aging time exposure time killing (cm.sup.2) Material (day) (min) efficacy 78.54 Polystyrene 0 10 99.43%  (Petri dish) 78.54 Polystyrene 30 10 .sup. 79% (Petri dish) 78.54 Polystyrene 30 90 .sup. 91% (Petri dish) 109.10 Polystyrene 0 10 99.88%  (well-plate lid) 109.10 Polystyrene 7 10 98.5% (well-plate lid) 109.10 Polystyrene 15 10 97.5% (well-plate lid) 109.10 Polystyrene 31 10 .sup. 60% (well-plate lid) 33.50 Ceramics (tile) 0 10 95.8%

TABLE-US-00005 TABLE 5 Candida albicans killing efficacy of the coating. Candida albicans Form Fungi exposure time killing efficacy Solid coating.sup.[1] 20 min    .sup. 60% Solid coating.sup.[1]  4 h    .sup.  97.9% Solid coating.sup.[1] 24 h     .sup. 79%.sup.[2] Liquid 30 seconds >=99.9999% .sup.[1]The spraying coverage was 50 m.sup.2/L. The antifungal tests were done right after the coatings were dried and formed..sup.[2]

[0272] The number was lower than that of 4 h exposure time. It can make sense as the killing efficacy was relative to the control and a lot of the fungi also died on the control surfaces after 24 h given there was no nutrition.

Example 11—Coating Removal

[0273] The transparent surface turned opaquer with more layers of coating applied (See FIG. 26). Removal procedure: After applying several layers of the coating formulation, it is recommended to remove them every 3-6 months before a new layer of coating is applied. The coating can be removed after an adequate amount of baking soda (sodium bicarbonate) aqueous solution is applied. To prepare the solution, 1.5 g of baking soda is dissolved in 100 mL of water. After preparation, the solution can be sprayed or wiped on the coated surface. The recommended spraying time is half the time used to spray coating formulation. For example, for 4 layers, spray the baking soda solution in the same way as the coating formulation (6 seconds per square meter) twice (or 12 seconds per square meter once). After applying the baking soda solution, wait for 30 seconds, wipe or rinse the surface with water to completely remove the coating. FIG. 26 shows a photo demonstrating the effect from the number of layers coated. The transparent surface turned opaquer with more layers of coating applied. The numbers at the top left corners of the photos are the number of layers coated. The spraying coverage was 50 m.sup.2/L for each layer.

Example 12—Viscosity Measurements of the Coating Solution

[0274] The viscosity measurement was conducted on a TA Instruments DHR-2 Rheometer. The geometry was ROTOR CONICAL/DIN H/A-AL SMART-SWAP (Part number: 546011.901; Serial number: 114773), which was made of aluminum and had a bob diameter of 28.00 mm and a bob length of 42.01 mm. The cup had a diameter of 30.36 mm and was using a Peltier environmental system. The operating gap was 5917.1 μm. The volume of the liquid added was 25 mL. Flow sweep was selected as the method. Using the sample setup and at the same shear rate of 10 s.sup.−1, the viscosity of water was measured to be 0.8789 mPa s, consistent with the literature value.

TABLE-US-00006 TABLE 6 Viscocity at a shear rate of 10 s.sup.−1. Temperature (° C.) Viscosity (mPa s) 25 1.407 6.5 2.562

[0275] FIG. 27 show a graph demonstrating the viscosity the coating solution at 25° C. and 6.5° C. as a function of shear rate.

Example 13—Scanning Electron Microscopy (SEM) Analysis

[0276] The coating solution was sprayed on small pieces ({tilde over ( )}5 mm) of glass, polystyrene plastics, both attached to SEM stubs by conductive tapes, and also sprayed on the stubs (made of aluminum) itself. The coverage was 50 m.sup.2/L. The samples were sputtered with 5 nm of Au. The SEM images were taken using the Hitachi S-4800 SEM. The detailed imaging conditions are summarized in the table 7:

TABLE-US-00007 TABLE 7 Parameters used for the SEM analysis Parameter Value Probe current Normal Focus mode HR Working distance 8.0 mm Focus depth 1.5 Accelerating voltage 3.0 kV

[0277] FIG. 28 shows a photo demonstrating the SEM images of the coated formulations on glass, plastic (polystyrene) and metal (aluminum) with 600×, 1200× and 2000× magnification.

Example 14—The Release Kinetics of Thymol from the Coating

[0278] 157 μL of the coating formulation was sprayed on each Petri dish. After the coatings were formed and dried, they were kept in a closed re-closable bag and aged for 0-30 days. At each time point, three Petri dishes (three repetitions) were taken out. 10 mL of ethanol was added to each Petri dish and put on a rocker to gently shake overnight to dissolve the coating. As some of the ethanol evaporated, the mass of the ethanol solution was weighed. The concentration of thymol in the solution was determined by the GC/MS peak area. The detailed conditions are summarized in the table 8:

TABLE-US-00008 TABLE 8 Parameters used for the GC-MS analysis. The retention time of thymol was 9.0-9.1 min. Parameter Value GC Agilent 7890B MS Agilent 5977B Column Agilent 19091S-433: 93.92873 HP-5MS 5% Phenyl Methyl Silox 0° C.-325° C. 30 m × 250 μm × 0.25 μm Temperature 0 min-2 min: hold at 50° C. program 2 min-16.667 min: 50° C. .fwdarw. 270° C., rate 15 ° C./min 16.667 min-18.667 min: hold at 270° C. 18.667 min-19.417 min: 270° C. .fwdarw. 315° C., rate 60° C./min 19.417 min-20.417 min: hold at 315° C. See FIG. 29. Carrier gas He Flow rate 1.2 mL/min Pressure 9.7853 psi Average velocity 39.923 cm/s Holdup time 1.2524 min GC Agilent 7890B MS Agilent 5977B Column Agilent 19091S-433: 93.92873 HP-5MS 5% Phenyl Methyl Silox 0° C.-325° C. 30 m × 250 μm × 0.25 μm

TABLE-US-00009 TABLE 9 The release kinetic data of thymol from the coating. Aging time % thymol left in the coating (day) relative to day 0 0 100.00 ± 22.34 7 21.45 ± 0.33 15 17.89 ± 4.01 21 19.80 ± 1.04 30 11.55 ± 2.12

Example 15—The Evaluation of Spraying Ability at Different Pressure Levels

[0279] 157 μL of the coating formulation was sprayed on each Petri dish. After the coatings were formed and dried, they were kept in a closed reclosable bag and aged for 0-30 days. At each time point, three Petri dishes.

[0280] The table in FIG. 30 demonstrate the time it takes for the Graco TC Pro SPRAYER to coat 1 m.sup.2 of surface at 50 m.sup.2/L at different pressure levels.

[0281] FIG. 31 shows a photo demonstrating the optical microscope photos of the coatings. Top two photos: Sprayed by Master Airbrush (Multi-purpose Gravity Feed Dual-action Airbrush Kit with 6 Foot Hose and a Powerful ⅕ hp Single Piston Quiet Air Compressor) with an amount of 50 m.sup.2/L. Bottom two photos: Sprayed by Graco TC Pro Cordless Airless Paint Sprayer with a TC Pro 208 0.008 in. Tip at the pressure level 4 from a distance of about 1.5 m.

[0282] FIG. 32 shows a photo demonstrating the transmission electron microscopy (TEM) image of coating solution formulation showing that it contains nanoparticles.

[0283] FIG. 33 shows a graph demonstrating the particle size distribution by number of the coating solution made in the lab (lower line) and the one made by the Mexican manufacturer (large scale production, higher line) determined by dynamic light scattering (DLS). The former has a Z-average diameter of 148.9±0.9 nm and a PDI of 0.050±0.014. The latter has a Z-average diameter of 134.7±1.0 nm and a PDI of 0.016±0.011. The two were very close, indicating that the manufacturer was producing a product consistent with what we made in the lab.

Example 16—Pilot Scale Manufacturing Procedure of the Coating Solution

[0284] Step 1. Dissolve thymol and 1,2--hexanediol in 96% ethanol by stirring for 2 mins at 1000 rmp in an industrial mixer,

[0285] Step 2. Add water and stir for 5 min at 1000 rpm in an industrial mixer.

[0286] Step 3. Add Kollicoat and stir to mix well in an industrial mixer at 300 rmp for 30 min.

[0287] Step 4. Let the mixture rest for 2 hours.

[0288] AH steps are performed at room temperature and in 10,000 L scale.

TABLE-US-00010 TABLE 10 Antimicrobial efficacy of the coating performed by third party certified lab in Mexico. Number of CFU on Veri Shield Microbe Number coated exposure of CFU on Petri Killing Microbe State time control dishes efficacy Method Escherichia Solid 10 min 8,900,000 7,000 99.921%   Our coli coating.sup.[1] standard 11229 method Staphylococcus Solid 10 min 9,200,000 5,000,000 45.652%   Our aureus coating standard 6538 method Saccharomyces Solid  4 h 15,000 0 100% Our cerevisiae coating standard 9763 method Aspergillus Solid  4 h 5,000 400  92% Our brasiliensis coating standard 16404 method Escherichia Liquid 30 s 100% NMX-BB- coli 040-SCFI- 11229 1999 Staphylococcus Liquid 30 s 100% NMX-BB- aureus 040-SCFI- 6538 1999 Saccharomyces Liquid 30 s 100% NMX-BB- cerevisiae 040-SCFI- 9763 1999 Aspergillus Liquid 30 s 99.996%   NMX-BB- brasiliensis 040-SCFI- 16404 1999 Equine Solid 15 min >99.9999%  .sup.   E 1053- Arteritis coating 97.sup.[2] virus ATCC (10.9 VR-796 m.sup.2/L, 78.54 cm.sup.2, Petri dish) .sup.[1]All solid coatings in this table had a spraying coverage of 10.9 m.sup.2/L. The surface area was 78.54 cm.sup.2 (10 cm diameter Petri dish). The Petri dish substrate was made of polystyrene. .sup.[2]Standard Test Method for Efficacy of Virucidal Agents Intended for Inanimate Environmental Surfaces

Example 17—Finger Rubs on the Coating on Ceramics and Wood

[0289] The bottom parts of the substrates were coated, and the upper parts were coated. Contrast of the coated parts and the uncoated parts and a straight line at the border between the two could be seen under light. The researcher used his finger to rub the center part up and down across the border. Up and down were counted as two rubs. The numbers of rubs are shown at the top left corner of the photos. The black circle highlights the damage done to the coating at the end.

[0290] FIG. 34 shows the first photo shows the coated ceramic surface prior finger rub. The other photos show the impact of finger rubs on the coating, with the numbers of rubs are shown at the top left corner of the photos. The black circle highlights the damage done to the coating at the end.

[0291] FIG. 35 shows the first photo shows the coated wood surface prior finger rub. The other photos show the impact of finger rubs on the coating, with the numbers of rubs are shown at the top left corner of the photos. The red circle highlights the damage done to the coating at the end.

Example 18—Coating of Apples for Preservation Purposes

[0292] 1 mL of the coating solution was sprayed on an apple. The other apple was uncoated as a control. Both were stored under ambient conditions for 92 days.

[0293] FIG. 36 shows the first photo shows the uncoated and coated apple at day 1. The second photo after day 92.

[0294] FIG. 37 shows the first photo shows the uncoated apple sliced in the middle at day 92. The second photo the coated apple sliced in the middle at day 92.

REFERENCES

[0295] 1. Palaniappan, K.; Holley, R. A., International Journal of Food Microbiology 2010, 140 (2-3), 164-168.

[0296] 2. Liu, Q.; Niu, H.; Zhang, W.; Mu, H.; Sun, C.; Duan, J., Letters in Applied Microbiology 2015, 60 (5), 421-30.

[0297] 3. Zhou, F.; Ji, B.; Zhang, H.; Jiang, H.; Yang, Z.; Li, J.; Li, J.; Ren, Y.; Yan, W., Journal of Food Production 2007, 70 (7), 1704-1709. 4. Moon, H.; Rhee, M. S., International Journal of Food Microbiology 2016, 217, 35-41.