ANTIMICROBIAL ADDITIVE COMPOSITIONS FOR COATINGS

Abstract

An antimicrobial formulation that can be directly added into a composition or onto a surface of a composition (e.g., forming a surface coating on a composition or device). The antimicrobial formulation includes sodium pentaborate, di-sodium tetraborate decahydrate, titanium diborite, titanium borate, sodium pyrithione, zinc pyrithione, benzhetonium chloride, or any combination thereof.

Claims

1. A paint comprising: di-sodium tetraborate decahydrate at a concentration ranging from 1 wt % to 20 wt %, zinc pyrithione and/or sodium pyrithione at a concentration ranging from 0.005 wt % to 10 wt %, and benzethonium chloride at a concentration ranging from 0.01 wt % to 10 wt %.

2. The paint of claim 1, wherein the antimicrobial formulation further comprises sodium pentaborate at a concentration ranging from 1 wt % to 20 wt %.

3. The paint of claim 1, wherein the antimicrobial formulation further comprises titanium diboride at a concentration ranging from 0.2 wt % to 20 wt %.

4. The paint of claim 1, wherein the antimicrobial formulation further comprises titanium borate at a concentration ranging from 0.2 wt % to 20 wt %.

5. The paint of claim 1, wherein the antimicrobial formulation further comprises sodium pyrithione at a concentration ranging from 0.001 wt % to 10 wt %.

6. The paint of claim 1, further comprising at least one of sodium pentaborate, titanium diboride, titanium borate, or sodium pyrithione.

7. The paint of claim 1, further comprising at least two of sodium pentaborate, titanium diboride, titanium borate, or sodium pyrithione.

8. The paint of claim 1, further comprising at least three of sodium pentaborate, titanium diboride, titanium borate, or sodium pyrithione.

9. The paint of claim 1, further comprising each of sodium pentaborate, titanium diboride, titanium borate, or sodium pyrithione.

10. The paint of claim 1, wherein the antimicrobial formulation reduces antimicrobial activity of Escherichia cob, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Methicillin-resistant Staphylococcus aureus (MRSA), Salmonella typhi, Vancomycin-resistant Enterococcus (VRE) when contacted therewith.

11. The paint of claim 1, further comprising antifungal activity in which the formulation reduces Candida albicans activity.

12. The paint of claim 1, wherein the paint is a non-aerosol.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0036] These and other features, aspects and advantages of the present invention are better understood when the following detailed description of the invention is read with reference to the accompanying drawings, in which:

[0037] FIGS. 1A, 1B, 1C, 1D, 1E, and 1F show images of the antimicrobial effects of the formulation on Escherichia coli.

[0038] FIGS. 2A, 2B, 2C, 2D, 2E, and 2F show images of the antimicrobial effects of the formulation on Staphylococcus aureus.

[0039] FIGS. 3A, 3B, 3C, 3D, 3E, and 3F show images of the antimicrobial effects of the formulation on Pseudomonas aeruginosa.

[0040] FIGS. 4A, 4B, 4C, 4D, 4E, and 4F show images of the antimicrobial effects of the formulation on Klebsiella pneumoniae.

[0041] FIGS. 5A, 5B, 5C, 5D, 5E, and 5F show images of the antimicrobial effects of the formulation on Methicillin-Resistant Staphylococcus aureus (MRSA).

[0042] FIGS. 6A, 6B, 6C, 6D, 6E, and 6F show images of the antimicrobial effects of the formulation on Salmonella typhi.

[0043] FIGS. 7A, 7B, 7C, 7D, 7E, and 7F show images of the antimicrobial effects of the formulation on Vancomycin-resistant Enterococcus (VRE).

[0044] FIGS. 8A, 8B, 8C, 8D, 8E, and 8F show images of the antimicrobial effects of the formulation on Candida albicans.

[0045] FIGS. 9A, 9B, 9C, 9D, 9E, and 9F show images of the antimicrobial effects of the formulation on Aspergillus niger.

DETAILED DESCRIPTION

[0046] The present invention will now be described more fully hereinafter with reference to the accompanying drawings in which exemplary embodiments of the invention are shown. However, the invention may be embodied in many different forms and should not be construed as limited to the representative embodiments set forth herein. The exemplary embodiments are provided so that this disclosure will be both thorough and complete, and will fully convey the scope of the invention and enable one of ordinary skill in the art to make, use and practice the invention. Like reference numbers refer to like elements throughout the various drawings.

[0047] In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings:

[0048] It must be noted that, as used in the specification and the appended claims, the singular forms a, an and the include plural referents unless the context clearly dictates otherwise.

[0049] Optional or optionally means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

[0050] As used herein, the term about is used to provide flexibility to a numerical range endpoint by providing that a given value may be slightly above or slightly below the endpoint without affecting the desired result.

[0051] Concentrations, amounts, and other numerical data may be expressed or presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within the ranges as if each numerical value and sub-range is explicitly recited. As an illustration, a numerical range of about 1 to 5 should be interpreted to include not only the explicitly recited values of about 1 to about 5, but also include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 3, and 4 and sub-ranges such as from 1-3, from 2-4, and from 3-5, etc. as well as 1, 2, 3, 4, and 5, individually. The same principle applies to ranges reciting only one numerical value as a minimum or a maximum. Furthermore, such an interpretation should apply regardless of the breadth of the range or the characteristics being described.

[0052] The compositions and methods described herein can comprise, consist of, or consist essentially of the essential elements and limitations described herein, as well as any additional or optional ingredients, components, or limitations described herein.

[0053] It should be noted that the Figures, Working Examples, and Detailed Description include numerous abbreviations therein. These abbreviations are as follows: sodium pentaborate (SPO), di-sodium tetraborate decahydrate (DSTD), titanium diborate (TD), titanium borate (TB), sodium pyrithione (SP), zinc pyrithione (CP), benzhetonium chloride (BK).

[0054] In view of FIGS. 1A-9F, it should be further noted that the abbreviations shown on the petri dishes include the below listed formulations: [0055] A: negative control (addition free paint) [0056] B: 0.75 wt % zinc pyrithione (CP)+3 wt % sodium pentaborate (SPO)+96.25 wt % paint [0057] C: 0.5 wt % zinc pyrithione (CP)+3 wt % sodium pentaborate (SPO)+96.5 wt % paint [0058] D: 0.2 wt % zinc pyrithione (CP)+3 wt % sodium pentaborate (SPO)+96.8 wt % paint [0059] E: 3 wt % sodium pentaborate (SPO)+97 wt % paint [0060] F: 5 wt % sodium pentaborate (SPO)+95 wt % paint

[0061] Disclosed are antimicrobial formulations that include boron containing compounds, zinc containing compounds, and/or chlorine containing compounds that are configured to be included within and impart antimicrobial, anti-viral, and/or anti-fungal activity to coating compositions such as paints (e.g., water-based or oil based paints), rosins and/or to be included on a surface of various personal care products such as disposal gloves, child or adult diapers, bandages, wound dressings, gauzes bandages, concrete, plasterboards, wood, plastic(s) (e.g., PVC materials) or partial plastics, glass, metal, plaster, leather, fabric(s), or paper to directly impart antimicrobial, anti-viral, and/or anti-fungal activity. In certain other aspects, each of the boron containing compounds, zinc containing compounds, and/or chlorine containing compounds disclosed herein may be included within a surface coating to further impart antimicrobial, anti-viral, and/or anti-fungal activity to a composition and/or device.

[0062] The specific boron containing compounds disclosed herein are sodium pentaborate at a concentration ranging from 1 wt % to 20 wt % of the composition, di-sodium tetraborate decahydrate at a concentration ranging from 1 wt % to 20 wt % of the composition, titanium diborite at a concentration ranging from 1 wt % to 20 wt % of the composition, and titanium borate at a concentration ranging from 1 wt % to 20 wt % of the composition. In certain aspects, at least one of the above boron containing compounds is included within the coating compositions disclosed herein and/or applied on the surface of the personal care products such as disposal gloves, child or adult diapers, bandages, wound dressings, gauzes bandages, concrete, plasterboards, wood, plastic(s) (e.g., PVC materials) or partial plastics, glass, metal, plaster, leather, fabric(s), or paper to directly impart antimicrobial activity. In certain aspects, at least two of the above boron containing compounds mentioned immediately above are included within the coating compositions disclosed herein and/or applied on the surface of the personal care products such as disposal gloves, child or adult diapers, bandages, wound dressings, gauzes bandages, concrete, plasterboards, wood, plastic(s) (e.g., PVC materials) or partial plastics, glass, metal, plaster, leather, fabric(s), or paper to directly impart antimicrobial activity. In certain aspects, at least three of the above boron containing compounds mentioned immediately above are included within the coating compositions disclosed herein and/or applied on the surface of the personal care products such as disposal gloves, child or adult diapers, bandages, wound dressings, gauzes bandages, concrete, plasterboards, wood, plastic(s) (e.g., PVC materials) or partial plastics, glass, metal, plaster, leather, fabric(s), or paper to directly impart antimicrobial activity. In certain aspects, all four of the above boron containing compounds mentioned immediately above are included within the coating compositions disclosed herein and/or applied on the surface of the personal care products such as disposal gloves, child or adult diapers, bandages, wound dressings, gauzes bandages, concrete, plasterboards, wood, plastic(s) (e.g., PVC materials) or partial plastics, glass, metal, plaster, leather, fabric(s), or paper to directly impart antimicrobial activity. In certain aspects, sodium pentaborate is present at a concentration ranging from 3 wt % to 12 wt % of an overall composition, and more preferably from 5 wt % to 10 wt % of the overall composition. In certain aspects, sodium di-sodium tetraborate decahydrate is present at a concentration ranging from 3 wt % to 12 wt % of an overall composition, and more preferably from 5 wt % to 6 wt % of the overall composition.

[0063] In certain aspects, the zinc containing compound disclosed herein is zinc pyrithione at a concentration ranging from 0.005 wt % to 10 wt % of the composition. In certain aspects, the zinc pyrithione is at a concentration ranging from 0.1 wt % to 3.5 wt % of an overall composition, and more preferably at a concentration ranging from 0.5 wt % to 3.0 wt % of an overall composition. In certain aspects, the zinc containing compound disclosed herein may be combined with one, two, three, or all four of the boron containing compounds disclosed herein to achieve the coating compositions, rosins, personal care products, etc. disclosed herein having antimicrobial, anti-viral, and/or anti-fungal activity.

[0064] In certain aspects, the chlorine containing compounds disclosed herein is benzethonium chloride ranging from 0.01 wt % to 10 wt % of the composition. In certain aspects, the chlorine containing compound disclosed herein may be combined with the zinc containing compound (zinc pyrithione) disclosed herein and/or any of one, two, three, or all four of the boron containing compounds disclosed herein to achieve the coating compositions, rosins, personal care products, etc. disclosed herein having antimicrobial, anti-viral, and/or anti-fungal activity.

[0065] In certain aspects, it is desirable to prepare polymeric composites, which have antimicrobial and/or anti-viral activity. In this aspect and when preparing the polymeric composite, the polymeric composite will preferably include zinc pyrithione at concentration ranging from 0.005 wt % to 10 wt % of the overall composition and benzethonium chloride at a concentration ranging from 0.001 wt % to 10 wt % of the overall composition, preferably homogeneously mixed and/or dispersed therein to provide antimicrobial and/or antiviral activity to the polymeric composites.

[0066] In certain aspects, the formulation comprises sodium pyrithione at a concentration ranging from 0.001 wt % to 10 wt % of an overall composition. In certain aspects, the sodium pyrithione is at a concentration ranging from 0.1 wt % to 3.5 wt % of an overall composition, and more preferably at a concentration ranging from 0.5 wt % to 3.0 wt % of an overall composition. In certain additional aspects and when preparing the polymeric composite, the polymeric composite will preferably include sodium pyrithione at a concentration ranging from 0.001 wt % to 10 wt % of the overall composition and di-sodium tetraborate decahydrate at a concentration ranging from 1 wt % to 20 wt % of the overall composition, preferably homogeneously mixed and/or dispersed therein to provide antimicrobial and/or antiviral activity to the polymeric composites.

[0067] In certain additional aspects, also disclosed are formulations having sodium pyrithione at a concentration ranging from 0.1 wt % to 0.3 wt % of the overall composition and sodium pentaborate at a concentration ranging from 3 wt % to 11 wt % of the overall composition and more preferably sodium pyrithione at a concentration ranging from 0.1 wt % to 0.3 wt % of the overall composition and sodium pentaborate at a concentration ranging from 5 wt % to 10 wt % of the overall composition.

[0068] In certain additional aspects, also disclosed are formulations having sodium pyrithione at a concentration ranging from 0.1 wt % to 0.3 wt % of the overall composition and disodium tetraborate decahydrate at a concentration ranging from 5 wt % to 10 wt % of the overall composition and more preferably sodium pyrithione at a concentration ranging from 0.1 wt % to 0.3 wt % of the overall composition and disodium tetraborate decahydrate at a concentration ranging from 5 wt % to 6 wt % of the overall composition.

[0069] In certain additional aspects, also disclosed are formulations having zinc pyrithione at a concentration ranging from 0.1 wt % to 3.0 wt % of the overall composition and sodium pentaborate at a concentration ranging from 3 wt % to 11 wt % of the overall composition and more preferably zinc pyrithione at a concentration ranging from 0.1 wt % to 0.3 wt % of the overall composition and sodium pentaborate at a concentration ranging from 5 wt % to 10 wt % of the overall composition.

[0070] In certain additional aspects, also disclosed are formulations having zinc pyrithione at a concentration ranging from 0.1 wt % to 3.0 wt % of the overall composition and disodium tetraborate decahydrate at a concentration ranging from 3 wt % to 11 wt % of the overall composition and more preferably zinc pyrithione at a concentration ranging from 0.1 wt % to 0.3 wt % of the overall composition and disodium tetraborate decahydrate at a concentration ranging from 5 wt % to 10 wt % of the overall composition.

WORKING EXAMPLES

Experimental Studies

[0071] In this application; boron compounds, sodium pyrithione, zinc pyrithione, benzhetonium chloride and combinations are mixed with paint and similar coating materials separately or with different combinations and concentrations to obtain coatings and/or coating formulations having antimicrobial properties. In particular, sodium pentaborate, di-sodium tetraborate decahydrate, titanium diborate, titanium borate were chosen as boron containing compounds that impart antimicrobial activity to these coatings and coating formulations.

Antimicrobial Tests

Modified Disc Diffusion Method;

[0072] In view of FIGS. 1A-9F, standard NCCLS disc diffusion method [8] was modified and used to determine the activity on microorganisms of boron compounds. 108 cfu/ml bacteria, 106 cfu/ml yeast and 104 spore/ml mold cultures were prepared and applied as spreading inoculation on Nutrient Agar (NA), Sabouraud Dextrose Agar (SDA) and Potato Dextrose Agar (PDA). 20 ?l sterilized water dripped on empty discs and discs were immersed into sodium pentaborate (SPO), di-sodium tetraborate decahydrate (DSTD), zinc pyrithione (CP) separately. SPO, DSTD, CP coded discs placed on inoculated petri dishes. As negative control, 20 ?l sterilized water dripped petri dishes were used. As positive controls, Ofloxacin (10 ?g/disc) and nystatin (30 ?g/disc) contaminated discs were used for bacteria and fungus. Modified and inoculated discs were incubated for bacteria 24 hours at 37?1? C. for yeast 48 hours 36?1? C., mold 72 hours 25?1? C. Antimicrobial activity inhibition zone observed and evaluated for the test microorganisms.

[0073] All tests were repeated at least 2 times. Antimicrobial activity test results are shown in Table 1.

Antimicrobial Activity Tests of Developed Antimicrobially Activated Substance:

[0074] Applied modified disc diffusion methods' formulations were tested to measure antimicrobial activities.

Experimental Results Given in Table 2.

Antimicrobial Surface Activity Tests for Antimicrobial Ingredients:

[0075] ISO 22196:2011(E) test method was applied to test the antibacterial surface activities. Coating material including 0.75 wt % zinc pyrithione (CP)+3 wt % sodium pentaborate (SPO)+95.44 wt % paint, applied on plastic surface 50 mm?50 mm dimension and hold 24 hours to dry. Staphylococcus aureus ATCC 6538P, Escherichia coli ATCC 8739, Methicillin-resistant S. aureus (MRSA) ATCC 43300, Pseudomonas aeruginosa ATCC 15442, Klebsiella pneumoniae ATCC #4352 strains were used in antimicrobial activity tests. Initial concentrations of test microorganisms set up as 2.5-10?10.sup.5 cfu/ml. Control sample was tested at Time: 0 and Time: 24 and this was repeated three times. Developed paint surface were tested at 24th hour and the test repeated three times. Each sample were placed into petri dishes and inoculated. 40 mm?40 mm?0.05 mm sterilized plastics were capped in petri dish to attach and spread the inoculate. Samples incubated at 35? C. and 90% relative humidity.

[0076] End of incubation (24 h) D/E Neutralizing Broth was added to each sample and shaken for a specific time. Neutralizing Broth serially diluted samples inoculated in Nutrient Agar petri dishes and incubated at 35? C. and 24-48 hours.

Counting Results are Given in Table 3.

[0077] Application 1: 0.78 g (of 48% pure) zinc pyrithione, 1.5 g sodium pentaborate and 47.72 g water based paint were mixed and homogenized for 50 g antimicrobial paint mixture. Produced paint mixture was tested for antimicrobial activity.

[0078] Application 2: 0.52 g (of 48% pure) zinc pyrithione, 1.5 g sodium pentaborate and 47.98 g of water based paint were mixed and homogenized for 50 g of antimicrobial paint mixture. Produced paint mixture was tested for antimicrobial activity.

[0079] Application 3: 0.2 g (of 48% pure) zinc pyrithione, 1.5 g sodium pentaborate and 48.3 g water based paint were mixed and homogenized for 50 g of antimicrobial paint mixture. Produced paint mixture was tested for antimicrobial activity.

[0080] Application 4: 1.5 g sodium pentaborate and 48.5 g water based paint were mixed and homogenized for 50 g of antimicrobial paint mixture. Produced paint mixture was tested for antimicrobial activity.

[0081] Application 5: 2.5 g sodium pentaborate and 47.5 g water based paint were mixed and homogenized for 50 g of antimicrobial paint mixture. Produced paint mixture was tested for antimicrobial activity.

Experimental Results

Antimicrobial Test Results:

[0082] Antimicrobial activity test results are given in Table 1. All tests were repeated twice.

TABLE-US-00001 TABLE 1 Antimicrobial effect of Sodium Pentaborate (SPO), di-sodium tetraborate decahydrate (DSTD), Zinc pyrithione (CP) on selected microorganisms. Compounds Microorganisms SPO DSTD CP Bacteria Escherichia coli + + + Staphylococcus aureus + + + Pseudomonas aeruginosa + + + Klebsiella pneumoniae + + + Methicillin-resistant Staphylococcus aureus + + + (MRSA) Salmonella typhi + + + Vancomycin-resistant Enterococcus (VRE) + + + Yeast Candida albicans + + + Mold Aspergillus spp. + + + Penicillium spp. + + +

[0083] Antimicrobial activity test results of antimicrobial effective formulas are given in Table 2. All tests were repeated twice. Visuals of antimicrobial tests are given in FIGS. 1A-9F.

TABLE-US-00002 TABLE 2 Antimicrobial effect of active including paint mixtures on microorganisms. A.sup.1 B.sup.2 C.sup.3 D.sup.4 E.sup.5 F.sup.6 E. coli ? + + + ? + S. aureus ? + + + + + P. aeruginosa ? + + + + + K. pneumoniae ? + + + + + MRSA ? + + + ? + S. typhi ? + + + ? + VRE ? + + + ? ? C. albicans ? + + + + + A. niger ? + + + + + .sup.1A: Negative Control (Additive Free) .sup.2B: %0.75 CP + %3 SPO + %96.25 Paint .sup.3C: %0.5 CP + %3 SPO) + %96.5 Paint .sup.4D: %0.2 CP + %3 SPO + %96.8 Paint .sup.5E: %3 SPO + %97 Paint .sup.6F: %5 SPO + %95 Paint

[0084] Antimicrobial activities were tested on isolates of bacteria (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, MRSA, Salmonella typhi ve VRE), mold (Candida albicans) and fungi (Aspergillus niger ve Penicillium spp.). According to the results, boron compounds and Zinc pyrithione paints and surfaces painted by these ingredients have antibacterial effect on all tested microorganisms. Antimicrobial activity tests are given in Table 3.

TABLE-US-00003 TABLE 3 Surface activity tests of B formulation applied plastic surfaces and control Microorganism U.sub.0.sup.1 U.sub.24.sup.2 A.sub.24.sup.3 R.sup.4 % Reduction.sup.5 Escherichia coli 4.01 5.89 ?0.20 6.09 99.99992 Staphylococcus 4.36 4.45 ?0.20 4.65 99.9980 aureus Pseudomonas 4.14 5.60 ?0.20 5.80 99.9998 aeruginosa Klebsiella 4.24 5.24 ?0.20 5.44 99.9996 pneumoniae MRSA 4.04 5.14 ?0.20 5.34 99.9995 .sup.1U.sub.0: t = 0 Logarithmical average of living bacteria on non-activated painted surface at t = 0 moment. .sup.2U.sub.t: t = 24 h Logarithmical average of living bacteria on non-activated painted surface at t = 24 .sup.3A.sub.24: t = 24 Logarithmical average of living bacteria on antimicrobially painted surfaces at t = 24 .sup.4R: Antimicrobial activity calculation R = (U.sub.24 ? U.sub.o) ? (A.sub.24 ? U.sub.o) = U.sub.24 ? A.sub.24 .sup.5% Reduction: Percentage decrease between living bacteria on antimicrobially painted surface at initial moment and final moment concentrations.

[0085] According to ISO 22196:2011 (E) test method, products having antibacterial activity (R) higher than 2/0 called antibacterial products. According to the test results given above (as an example B formulation results given), the developed product addible to coating material formulation may be called antibacterial product.

[0086] Reduction percentage can be converted into logarithmical reduction: [0087] 90% reduction=1 log reduction; from 1.000.000 to 100.000 [0088] 99% reduction=2 log reduction; from 1.000.000 to 10.000 [0089] 99.9% reduction=3 log reduction; from 1.000.000 to 1000 [0090] 99.99% reduction=4 log reduction; from 1.000.000 to 100 [0091] 99,999% reduction=5 log reduction; from 1.000.000 to 10 [0092] 99.99999% reduction=6 log reduction; from 1.000.000 to 1

[0093] The foregoing description provides embodiments of the invention by way of example only. It is envisioned that other embodiments may perform similar functions and/or achieve similar results. Any and all such equivalent embodiments and examples are within the scope of the present invention and are intended to be covered by the appended claims.

REFERENCES

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