Boosted IPBC for bacterial control in wet conditions

Abstract

A biocidal composition comprising an antimicrobially effective combination of IPBC, zinc oxide, and a bacterial membrane disrupting agent, and a working composition effective for preserving wet and dry films of a working composition comprising water, one or more organic compounds, and IPBC, zinc oxide, and a bacterial membrane disrupting agent. Also provided are a method of enhancing the antimicrobial activity of IPBC in a wet working composition comprising water and one or more organic compounds, comprising treating the working composition with IPBC in the presence of zinc oxide and a bacterial membrane disrupting agent, and a method of treating an aqueous working formulation comprising one or more organic compounds to prevent, inhibit, or reduce wet state bacterial contamination of the formulation, comprising treating the working formulation with a biocidal composition comprising an antimicrobially effective combination of IPBC, zinc oxide, and a bacterial membrane disrupting agent.

Description

[Technical field]

[0001] Related Applications

[0001] This application is based on and claims priority to U.S. Provisional Patent Application No. 63 / 191,612, filed May 21, 2021, and U.S. Provisional Patent Application No. 63 / 332,344, filed April 19, 2022, which are incorporated herein by reference. [Background technology]

[0002] Iodopropynyl butylcarbamate (IPBC) is an industrially important biocide with broad spectrum activity against fungal organisms, but with a large gap in efficacy against bacterial organisms. It is widely understood in the industry that IPBC can only inhibit the growth of selective bacteria. In particular, Pseudomonas species are particularly known to be resistant to treatment with IPBC. As a result, coating manufacturers, for example, have had to use multiple biocide products to adequately protect coating compositions from microbial attack in both the wet and dry film states. Currently, coating manufacturers must purchase and compound at least two biocidal components separately: a wet preservative and a dry film preservative.

[0003]

[0003] Thus, there remains a need for a biocidal composition that, as a single product (i.e., a single product which, when incorporated into a coating or working composition, simultaneously prevents or retards microbiological growth both when the composition is in a wet state and when converted into a dry film), provides adequate protection of coating compositions and other working compositions against a wide range of microbiological hazards, particularly against both bacterial and fungal attack in the wet state (e.g., in a can) and fungal and / or algal attack in the dry film state. Furthermore, due to worldwide regulatory pressure to reduce or eliminate the use of sensitizing and CMR preservatives, there is a need for these biocidal compositions to be free of isothiazolinones, pyrithiones, and formaldehyde. Summary of the Invention

[0004]

[0004] The present disclosure provides a single biocidal product containing the biocide iodopropynyl butylcarbamate (IPBC) that can provide aqueous working compositions containing one or more organic compounds, particularly coating compositions such as paints and stains, and joint compounds with a sufficient level of protection against a wide variety of organisms (bacteria, fungi) in both the wet state and in the dry film. By using the biocidal composition of the present invention described herein, the need to formulate coating compositions using multiple sources of different biocides can be avoided. That is, sufficient wet and dry film resistance to biological attack on the coating composition, particularly bacterial attack in the wet state, can be achieved without adding other biocide-containing ingredients to the coating composition.

[0005]

[0005] According to the present disclosure, zinc oxide enhances the bactericidal activity of IPBC in aqueous compositions, and the combination of IPBC and zinc oxide acts synergistically. The combination of IPBC and zinc oxide achieves strong and unexpected bactericidal activity against IPBC-resistant bacteria (such as Pseudomonas). The further combination of IPBC and zinc oxide with 1,2-hexanediol is unexpectedly highly effective in controlling wet bacterial growth, reusing the fungicide IPBC to kill wet bacteria without losing dry film activity. The biocidal compositions of the present disclosure represent an important advancement and fill an important market need for isothiazolinone-, pyrithione-, and formaldehyde-free in-can and dry film preservation.

[0006] The biocidal compositions according to the present disclosure therefore offer the following practical advantages over the conventional use of separate wet and dry film preservative packages in the coatings industry: i) Reduced costs for the end user (coating formulator); ii) fewer different inventory items to be purchased, stored and maintained by the end user; iii) simplification of operations by metering only one biocide-containing product into the coating composition instead of several; iv) Less environmental impact due to less energy use resulting from the manufacture, packaging, and transport of a single biocide-containing product rather than multiple biocide-containing products; and v) Free of isothiazolinones, pyrithiones and formaldehyde, providing favorable regulatory impact on end-use products.

[0007]

[0007] Various exemplary aspects of the present disclosure can be summarized as follows.

[0008] Aspect 1: A biocidal composition comprising an antimicrobially effective combination of IPBC and zinc oxide.

[0009] Embodiment 2: The biocidal composition of embodiment 1, wherein the IPBC and zinc oxide are present in a weight ratio of from 25:1 to 1:25.

[0008]

[0010] Embodiment 3: The biocidal composition of embodiment 1 or 2, wherein the zinc oxide comprises zinc oxide nanoparticles.

[0011] Embodiment 4: A biocidal composition according to embodiments 1 to 3, further comprising one or more bacterial membrane disrupting agents.

[0009]

[0012] Embodiment 5: A biocidal composition according to embodiments 1 to 4, wherein the one or more bacterial membrane disrupting agents comprise one or more vicinal diols.

[0013] Embodiment 6: The biocidal composition of embodiments 1-5, wherein the one or more vicinal diols comprises 1,2-hexanediol.

[0010]

[0014] Embodiment 7: A biocidal composition according to embodiments 4 to 6, wherein the one or more bacterial membrane disrupting agents comprise one or more glycol ethers.

[0015] Embodiment 8: A biocidal composition according to embodiments 1-7, wherein the one or more bacterial membrane disrupting agents consist of hexyl carbitol, TPnB glycol ether, butoxytriglycol, or triacetin.

[0011]

[0016] Embodiment 9: The biocidal composition of embodiments 1-8, further comprising one or more additional biocidal substances.

[0017] Embodiment 10: A biocidal composition according to embodiments 1 to 9, wherein the one or more additional biocidal substances comprise one or more antifungal substances and / or one or more algicidal substances.

[0012]

[0018] Embodiment 11: A biocidal composition according to embodiments 1-10, comprising 1 wt% to 25 wt% IPBC, 1 wt% to 25 wt% zinc oxide, and 40 wt% to 80 wt% of one or more vicinal diols.

[0013]

[0019] Embodiment 12: A biocidal composition according to embodiments 1-11, comprising 10 wt.% IPBC, 5 wt.% zinc oxide, and 60 wt.% of one or more vicinal diols.

[0020] Embodiment 13: The biocidal composition of embodiment 7, comprising 1 wt.% to 25 wt.% IPBC, 1 wt.% to 25 wt.% zinc oxide, and 40 wt.% to 80 wt.% of one or more glycol ethers.

[0014]

[0021] Embodiment 14: A biocidal composition according to embodiments 1-13, comprising about 10% by weight of IPBC, about 5% by weight of zinc oxide, and about 60% by weight of one or more glycol ethers.

[0022] Aspect 15: A working composition comprising water, one or more organic compounds, and a biocidal composition effective for antimicrobial preservation of the working composition in a wet state, the biocidal composition comprising IPBC and zinc oxide.

[0015]

[0023] Embodiment 16: The working composition according to embodiment 15, wherein the IPBC and zinc oxide are present in a weight ratio of 25:1 to 1:25.

[0024] Embodiment 17: The working composition of embodiment 15 or 16, wherein the zinc oxide comprises zinc oxide nanoparticles.

[0016]

[0025] Embodiment 18: The working composition according to embodiments 15 to 17, wherein the biocidal composition further comprises one or more bacterial membrane disrupting agents.

[0026] Embodiment 19: The working composition of embodiment 18, wherein the one or more bacterial membrane disrupting agents comprise one or more vicinal diols.

[0017]

[0027] Embodiment 20: The working composition of embodiment 18 or 19, wherein the one or more vicinal diols comprise 1,2-hexanediol.

[0028] Embodiment 21: The working composition of embodiment 18, wherein the one or more bacterial membrane disrupting agents comprise one or more glycol ethers.

[0018]

[0029] Embodiment 22: The working composition according to embodiment 21, wherein the one or more bacterial membrane disrupting substances comprise hexyl carbitol, TPnB glycol ether, butoxytriglycol or triacetin.

[0019]

[0030] Embodiment 23: The working composition of embodiments 15-22, further comprising one or more additional biocidal substances.

[0031] Embodiment 24: The working composition according to embodiment 23, wherein the one or more additional biocidal substances comprise one or more antifungal substances and / or one or more algicidal substances.

[0020]

[0032] Embodiment 25: The working composition of any one of embodiments 15 to 19, wherein the biocidal composition comprises 1 wt.% to 25 wt.% IPBC, 1 wt.% to 25 wt.% zinc oxide, and 40 wt.% to 80 wt.% of one or more vicinal diols.

[0021]

[0033] Embodiment 26: The working composition according to embodiment 26, wherein the biocidal composition comprises 10% by weight of IPBC, 5% by weight of zinc oxide, and 60% by weight of one or more vicinal diols.

[0022]

[0034] Embodiment 27: The working composition of any one of embodiments 15-21, comprising 1 wt.% to 25 wt.% IPBC, 1 wt.% to 25 wt.% zinc oxide, and 40 wt.% to 80 wt.% of one or more glycol ethers.

[0023]

[0035] Example 28: The working composition of example 27, comprising about 10% by weight of IPBC, about 5% by weight of zinc oxide, and about 60% by weight of one or more glycol ethers.

[0036] Example 29: The working composition of any one of Examples 15-28, wherein the one or more organic compounds include one or more polymeric binders or fillers.

[0024]

[0037] Aspect 30: The working composition of any one of aspects 15-29, which constitutes a cosmetic, toiletry, personal care, household, laundry, cleaning, disinfecting, paint, coating, mineral slurry, pigment, pulp slurry, paper slurry, paper, metal working fluid, construction, plant nutrient, polymer grid, wallboard joint compound, wallboard, spackling, sealant, stucco, mastic, asphalt emulsion, wood preservative, lazule, stain, gypsum, adhesive, textile, leather treatment, hide treatment, nonwoven, building material, stucco, concrete, or caulking product.

[0025]

[0038] Example 31: The working composition of any one of Examples 15-29, wherein the one or more polymeric binders or fillers include one or more acrylate, butadiene, PVA, EVA, styrene, or vinyl acetate polymers.

[0026]

[0039] Aspect 32: A method of enhancing antimicrobial activity of IPBC in a wet working composition comprising water and one or more organic compounds, the method comprising treating the working composition with IPBC in the presence of zinc oxide.

[0027]

[0040] Aspect 33: The method of aspect 32, wherein the IPBC and zinc oxide are present in a weight ratio of 25:1 to 1:25.

[0041] Example 34: The method of example 32 or 33, wherein the zinc oxide comprises zinc oxide nanoparticles.

[0028]

[0042] Embodiment 35: The method according to embodiments 32 to 34, wherein the working composition is further treated with one or more bacterial membrane disrupting agents.

[0043] Embodiment 36: The method of embodiment 32 to 35, wherein the one or more bacterial membrane disrupting agents comprise one or more vicinal diols.

[0029]

[0044] Embodiment 37: The method of embodiment 36, wherein the one or more vicinal diols comprise 1,2-hexanediol.

[0045] Embodiment 38: The method of embodiment 32 to 35, wherein the one or more bacterial membrane disrupting agents comprise one or more glycol ethers.

[0030]

[0046] Embodiment 39: The method of embodiment 38, wherein the one or more bacterial membrane disrupting agents comprise hexyl carbitol, TPnB glycol ether, butoxytriglycol or triacetin.

[0031]

[0047] Embodiment 40: The method according to embodiments 32-39, wherein the working composition is further treated with one or more additional biocidal substances.

[0048] Embodiment 41: The method of embodiment 32 to 40, wherein the one or more additional biocidal substances comprise one or more antifungal substances and / or one or more algicidal substances.

[0032]

[0049] Aspect 42: The method of any one of aspects 32 to 41, comprising treating the working composition with an antimicrobially effective amount of a wet biocidal composition comprising 1 wt.% to 25 wt.% IPBC, 1 wt.% to 25 wt.% zinc oxide, and 40 wt.% to 80 wt.% of one or more vicinal diols.

[0033]

[0050] Embodiment 43: The method of embodiment 32-42, wherein the biocidal composition comprises 10% by weight of IPBC, 5% by weight of zinc oxide, and 60% by weight of one or more vicinal diols.

[0034]

[0051] Embodiment 44: The method of embodiment 32-43, comprising 1 wt% to 25 wt% IPBC, 1 wt% to 25 wt% zinc oxide, and 40 wt% to 80 wt% of one or more glycol ethers.

[0035]

[0052] Example 45: The method of any one of Examples 32 to 44, comprising about 10% by weight of IPBC, about 5% by weight of zinc oxide, and about 60% by weight of one or more glycol ethers.

[0053] Aspect 46: A method of treating an aqueous working formulation comprising one or more organic compounds to prevent, inhibit or reduce wet state bacterial contamination of the formulation, the method comprising treating the working formulation with a biocidal composition comprising an antibacterially effective combination of IPBC and zinc oxide.

[0036]

[0054] Aspect 47: The method of aspect 46, wherein the IPBC and zinc oxide are present in a weight ratio of 25:1 to 1:25.

[0055] Example 48: The method of example 46 or 47, wherein the zinc oxide comprises zinc oxide nanoparticles.

[0037]

[0056] Aspect 49: The method according to aspects 46 to 48, further comprising the step of treating the working formulation with one or more bacterial membrane disrupting agents.

[0038]

[0057] Embodiment 50: The method according to embodiments 46 to 49, wherein the one or more bacterial membrane disrupting agents comprise one or more vicinal diols.

[0058] Embodiment 51: The method of embodiment 50, wherein the one or more vicinal diols comprise 1,2-hexanediol.

[0039]

[0059] Embodiment 52: The method of embodiment 46 to 49, wherein the one or more bacterial membrane disrupting agents comprise one or more glycol ethers.

[0060] Embodiment 53: The method of embodiment 46 to 52, wherein the one or more bacterial membrane disrupting agents comprise hexyl carbitol, TPnB glycol ether, butoxytriglycol or triacetin.

[0040]

[0061] Embodiment 54: The method according to embodiment 46 to 53, further comprising treating the working formulation with one or more additional biocidal substances.

[0062] Embodiment 55: The method of embodiment 46 to 54, wherein the one or more additional biocidal substances comprise one or more antifungal substances and / or one or more algicidal substances.

[0041]

[0063] Aspect 56: The method of any one of aspects 46 to 50, comprising treating the working formulation with a biocidal composition comprising 1 wt.% to 25 wt.% IPBC, 1 wt.% to 25 wt.% zinc oxide, and 40 wt.% to 80 wt.% of one or more vicinal diols.

[0042]

[0064] Embodiment 57: The method of embodiment 46 to 56, wherein the biocidal composition comprises 10% by weight of IPBC, 5% by weight of zinc oxide, and 60% by weight of one or more vicinal diols.

[0043]

[0065] Embodiment 58: The method of embodiment 46-52, comprising 1 wt% to 25 wt% IPBC, 1 wt% to 25 wt% zinc oxide, and 40 wt% to 80 wt% of one or more glycol ethers.

[0044]

[0066] Embodiment 59: The method of embodiment 46 to 58, comprising about 10% by weight of IPBC, about 5% by weight of zinc oxide, and about 60% by weight of one or more glycol ethers.

[0067] Embodiment 60: The method of embodiments 46-59, wherein the one or more organic compounds comprise one or more polymeric binders or fillers.

[0045]

[0068] Aspect 61: The method of any one of aspects 46 to 60, wherein the working composition comprises a cosmetic, toiletry, personal care, household, laundry, cleaning, disinfecting, paint, coating, mineral slurry, pigment, pulp slurry, paper slurry, paper, metalworking fluid, construction, plant nutrient, polymer grid, wallboard joint compound, wallboard, spackling, sealant, stucco, mastic, asphalt emulsion, wood preservative, lazule, stain, plaster, adhesive, textile, leather treatment, hide treatment, nonwoven, building material, stucco, concrete, or caulking product.

[0046]

[0069]

[0046] Embodiment 62: The method of embodiment 60, wherein the one or more polymeric binders or fillers comprise one or more acrylate, butadiene, PVA, EVA, styrene, or vinyl acetate polymers.

[0047]

[0070] Other features and aspects of the disclosure are described in more detail below.

[0071] A full and enabling disclosure of the present disclosure is more particularly set forth in the remainder of the specification, including reference to the accompanying drawings, in which: [Brief description of the drawings]

[0048] [Figure 1]

[0072] Figure 1 shows the growth curves of Pseudomonas aeruginosa (ATCC#10145) in the presence of 0.125-0.5 mM PAβN with and without IPBC; [Diagram 2]

[0073] Figure 2 shows the growth curves of P. aeruginosa (ATCC#10145) with and without nanoparticulate ZnO, as well as the checkerboard assay with varying levels of IPBC and nanoparticulate ZnO; [Diagram 3]

[0074] Figure 3 shows the killing curves of IPBC and ZnO for Pseudomonas aeruginosa (ATCC#10145); [Figure 4]

[0075] Figure 4 shows the effect of 1,2-hexanediol on membrane permeability of Pseudomonas aeruginosa (ATCC#10145); [Diagram 5]

[0076] FIG. 5 shows the kill curves of Pseudomonas aeruginosa (ATCC#10145) for combinations of IPBC, ZnO and 1,2-hexanediol at sub-inhibitory concentrations of 1,2-hexanediol; [Figure 6]

[0077] FIG. 6 is a plot of the synergy index (SI) of a preferred composition of the invention ("Omniphase Z") versus the minimum inhibitory concentration (MIC) of IPBC against various microorganisms; [Figure 7]

[0078] Figure 7 shows comparative challenge test results on joint compounds and paints against various microorganisms; [Figure 8]

[0079] Figure 8 shows comparative dry film bacterial resistance test results for paints; [Figure 9]

[0080] Figure 9 shows the effect of 1,2-hexanediol, 1,2-octanediol, texanol, and various glycol ethers on the membrane permeability of P. aeruginosa (ATCC#10145); [Figure 10]

[0081] Figure 10 shows the ROC curves showing the relationship between the degree of membrane permeation caused by various solvents and the ability to preserve paints containing IPBC / ZnO; [Figure 11]

[0082] FIG. 11 shows the kill curves of Pseudomonas aeruginosa (ATCC#10145) Omniphase Z formulated with hexyl carbitol ("1750-8"); and [Figure 12]

[0083] FIG. 12 is a plot of the synergy index (SI) of Omniphase Z prepared with hexyl carbitol ("1750-8") versus the minimum inhibitory concentration (MIC) of IPBC against various microorganisms.

[0049]

[0084] Repeat use of reference characters in the present specification and drawings is intended to represent same or analogous features or elements of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0050]

[0085] It will be understood by those skilled in the art that this discussion is a description of exemplary embodiments only, and is not intended to limit the broader aspects of the present disclosure.

[0086] The spectrum of activity of IPBC against various bacterial species in the working composition is expanded by the presence of zinc oxide. Further combination with 1,2-hexanediol significantly boosted the activity of ZnO / IPBC in paints, stains, and joint compounds, significantly outperforming 1,2-hexanediol, IPBC, and the combination of IPBC and 1,2-hexanediol in wet bacterial challenge tests. Formulations containing 10% IPBC, 5% ZnO, and 60% 1,2-hexanediol were prepared and tested in a variety of matrices and showed broad wet bacterial and fungal control properties in stains, paints, and joint compounds, and dry film fungal and bacterial control properties in paints. The biocidal composition of the present disclosure is an important advancement and fills an important market need for isothiazolinone-, pyrithione-, and formaldehyde-free in-can and dry film preservation.

[0051] IPBC

[0087] The biocidal compositions of the present disclosure contain 3-iodoprop-2-yn-1-yl butyl carbamate (CAS number 55406-53-6, sometimes referred to herein as "IPBC"). IPBC is also sometimes referred to as 3-iodo-2-propynyl N-butyl carbamate, 3-iodo-2-propynyl butyl carbamate, iodopropynyl butyl carbamate, or iodocarb. IPBC is present in the biocidal composition in an amount of 1% to 25%, 5% to 20%, 5% to 15%, or about 10% by weight based on the weight of the composition.

[0052] Zinc oxide

[0088] The biocidal composition of the present disclosure also includes zinc oxide (sometimes referred to herein as "ZnO"). Preferably, the zinc oxide includes a zinc oxide particle size of less than 50 microns. The zinc oxide may also be present as nanoparticles. The zinc oxide is present in the biocidal composition in an amount of 1% to 25%, 2% to 20%, 3% to 15%, 4% to 10%, or about 5% by weight based on the weight of the composition. The weight ratio of IPBC to ZnO should be controlled to be within the range of 25:1 to 1:25, inclusive. In various embodiments of the present disclosure, the weight ratio of IPBC to ZnO in the biocidal composition of the present disclosure is 20:1 to 1:20, 15:1 to 1:15, 10:1 to 1:10, 5:1 to 1:5, or 4:1 to 1:4. In another embodiment, the weight ratio of IPBC to ZnO is 2:1.

[0053] Membrane disrupting substances

[0089] The biocidal composition of the present disclosure may optionally include one or more substances capable of disrupting microbial membranes, particularly bacterial membranes. The boosting of IPBC / ZnO activity may be associated with membrane permeabilization. For example, the degree of permeabilization caused by a bacterial membrane disrupting substance correlates with the ability of the membrane disrupting substance to boost the IPBC / ZnO antimicrobial performance in the coating composition.

[0054]

[0090] In various embodiments of the present disclosure, the membrane disrupting agent comprises one or more vicinal diols. Vicinal diols useful in various embodiments of the present disclosure include 1,2-hexanediol, such as propanediol, methylpropanediol, butylene glycol, 1,2-pentanediol, caprylyl glycol, 1,2-decanediol, caprylyl glyceryl ether, ethylhexylglycerin, glyceryl monolaurate, glyceryl monocaprate, glyceryl monocaprylate, and combinations thereof. In further embodiments of the present disclosure, the one or more vicinal diols comprise 1,2-hexanediol (CAS number 6920-22-5, also known as DL-1,2-hexanediol, 1,2-dihydroxyhexane, dl-hexane-1,2-diol, or 5,6-dihydroxyhexane). Furthermore, in various embodiments disclosed herein, the membrane disrupting agent comprises one or more glycol ethers. Glycol ethers useful in various embodiments disclosed herein include hexyl carbitol, hexyl CELLOSOLVE™, butyl CELLOSOLVE™, and ethoxy triglycol, DOWANOL™ Eph6 glycol ether (polyethylene glycol phenyl ether), UCAR™ Filmer IBT (2,2,4-trimethyl-1,3-pentanediol monoisobutyrate), DOWANOL™ LoV 485 glycol ether (bis-dipropylene glycol n-butyl ether adipate), DOWANOL™ TPnB glycol ether (tripropylene glycol n-propyl ether), DOWANOL™ PnP glycol ether (propylene glycol n-propyl ether), butoxy triglycol, Arcosolv PnB (1-butoxy-2-propanol), Texanol, or combinations thereof.

[0055]

[0091] The one or more vicinal diols are present in the biocidal composition of the present disclosure in an amount of 40% to 80% by weight of the composition. In various embodiments of the present disclosure, the one or more vicinal diols are present in the biocidal composition of the present disclosure in an amount of about 60% by weight of the composition. In another embodiment, the weight ratio of IPBC to zinc oxide to vicinal diol is 10:5:60 (2:1:12). A preferred biocidal composition of the present disclosure comprises 1% to 25% by weight of IPBC, 1% to 25% by weight of zinc oxide, and 40% to 80% by weight of 1,2-hexanediol, based on the weight of the biocidal composition. A particularly preferred biocidal composition of the present disclosure comprises 10% by weight of IPBC, 5% by weight of zinc oxide, and 60% by weight of 1,2-hexanediol, based on the weight of the biocidal composition.

[0056]

[0092] The one or more glycol ethers are present in the biocidal composition of the present disclosure in an amount of 40% to 80% by weight of the composition. In various embodiments of the present disclosure, the one or more glycol ethers are present in the biocidal composition of the present disclosure in an amount of about 60% by weight of the composition. In another embodiment, the weight ratio of IPBC to zinc oxide to glycol ether is 10:5:60 (2:1:12). A preferred biocidal composition of the present disclosure comprises 1% to 25% by weight of IPBC, 1% to 25% by weight of zinc oxide, and 40 to 80% by weight of hexyl carbitol, based on the weight of the biocidal composition. A particularly preferred biocidal composition of the present disclosure comprises 10% by weight of IPBC, 5% by weight of zinc oxide, and 60% by weight of hexyl carbitol, based on the weight of the biocidal composition.

[0057] Biocides

[0093] In addition to IPBC, one or more other biocides may be present in the biocidal composition of the present disclosure. In one embodiment, the biocidal composition of the present disclosure does not include an additional biocide. In another embodiment, the additional biocide or biocides include one or more antifungal and / or algicidal biocides. The one or more additional biocides may include methyl benzimidazol-2-yl carbamate ("BCM") and / or 3-(3,4-dichlorophenyl)-1,1-dimethylurea ("Diuron"). Other biocides that may be present in the biocidal composition of the present disclosure include, but are not limited to, any of the biocidal compounds known in the art. Supplemental wet state activators that may be used include, but are not limited to, 5-chloro-2-methyl-2H-isothiazol-3-one / 2-methyl-2H-isothiazol-3-one ("CMIT / MIT") and 2-bromo-2-nitropropane-1,3-diol ("Bronopol"). Adjunct algicides that can be used include, but are not limited to, 2-tert-butylamino-4-ethylamino-6-methylthio-1,3,5-triazine ("Terbutryn") and 3-(4-isopropylphenyl)-1,1-dimethylurea ("Isoproturon").

[0058]

[0094] The biocide present in the biocidal composition will advantageously be in the form of relatively fine particles, for example particles having a particle size of from 5 to 75 microns. The desired particle size can be achieved by conventional techniques such as grinding, crushing, sieving, and the like.

[0059] Surfactants

[0095] The biocidal compositions of the present disclosure may utilize one or more surfactants, which function as emulsifiers and help keep the water-insoluble components of the formulation in the form of a stable dispersion of small particles suspended in the aqueous phase (an emulsion).

[0060]

[0096] Suitable types of nonionic surfactants include, but are not limited to, polyoxyalkylene glycol alkyl ethers (e.g., polyoxyethylene glycol alkyl ethers, polyoxypropylene alkyl ethers, polyoxyethylene / propylene alkyl ethers), glucoside alkyl ethers, polyoxyalkylene glycol alkyl phenol ethers (e.g., polyoxyethylene glycol alkyl phenol ethers, polyoxypropylene glycol alkyl phenol ethers, polyoxyethylene / propylene glycol alkyl phenol ethers), glycerin alkyl esters, polyoxyalkylene glycol sorbitan alkyl esters (e.g., polyoxyethylene glycol sorbitan alkyl esters), sorbitan alkyl esters, cocamide MEA, cocamide DEA, block copolymers of polyethylene glycol and polypropylene glycol (poloxamers), polyalkoxylated tallow amines, alkoxylated fatty acids, and the like, and combinations thereof.

[0061]

[0097] Specific nonionic surfactants include alkoxylated aliphatic monoalcohols and alkoxylated aromatic monoalcohols. Such surfactants are typically prepared by reacting one or more alkylene oxides (e.g., ethylene oxide, propylene oxide, mixtures of ethylene oxide and propylene oxide) with one or more monoalcohols (e.g., aliphatic alcohols, which may be linear or branched, primary or secondary, or aromatic alcohols, such as phenols, including alkyl- and aralkyl-substituted phenols). The number of moles of alkylene oxide reacted per mole of monoalcohol can vary as desired, but typically averages about 2 to about 50. When two or more alkylene oxides are used, the alkylene oxides can be reacted as a mixture (to provide polyoxyalkylene segments with random copolymer structures) or sequentially (to provide polyoxyalkylene segments with block copolymer structures).

[0062]

[0098] Another type of nonionic surfactant for use in the present disclosure is the ethoxylated C 10 ~C 18 Aliphatic alcohols, particularly linear primary C alkoxylated alcohols which are reacted with about 6 to about 15 moles of ethylene oxide per mole of aliphatic alcohol to provide alkoxylated alcohols containing an average of about 6 to about 15 oxyethylene repeat units per molecule. 12 ~C 16 An alkoxylated fatty monoalcohol is an alkoxylated fatty monoalcohol that is an aliphatic alcohol (or a mixture of such alcohols). For example, the alkoxylated fatty monoalcohol is an ethoxylated C 2 alk ... 12 ~C 16 It may be a linear aliphatic alcohol, in particular an ethoxylated tridecanol containing an average of about 10 ethylene oxide units is suitable for use in the present disclosure.

[0063]

[0099] Another type of nonionic surfactant for use in the present disclosure is an alkoxylated C2-C8 fatty alcohol that contains both ethylene oxide and propylene oxide units. The C2-C8 fatty alcohol can be, for example, n-butanol. The ethylene oxide and propylene units may be arranged in blocks (for example, the surfactant can include a polyoxyethylene block and a polyoxypropylene block). Also suitable for use as a nonionic surfactant are alkoxylated phenols, particularly ethoxylated phenols in which the phenol may be substituted with one or more alkyl groups (especially long chain alkyl groups such as nonyl groups as in tristyrylphenol or dodecyl groups or aralkyl groups).

[0064]

[0100] Suitable anionic surfactants include, but are not limited to, surfactants containing an anionic functional group at the head, such as a sulfate ester group, a sulfonate ester group, a phosphate ester group, and a carboxylate ester group. The cationic counterion to the anionic functional group can be, for example, an alkali metal (e.g., Na, K) or an amine (ammonium) cation, such as a quaternary ammonium. Classes of anionic surfactants useful in the present disclosure include alkyl sulfates, alkyl ether sulfates, sulfated alkanolamides, glyceride sulfates, alkylaryl sulfonates (including linear alkylbenzene sulfonates, branched alkylbenzene sulfonates, and alkylnaphthalene sulfonates), alpha-olefin sulfonates, lignosulfonates, sulfocarboxylic acid compounds (e.g., sodium lauryl sulfoacetate, sulfosuccinates (including dialkyl sulfosuccinates), sulfosuccinamate, organophosphorus surfactants, sacrosides, hydroxyalkanesulfonates, alkanesulfonates, alkylphenoxypolyoxyethylenepropylsulfonates, salts of polyoxyethylene alkylsulfophenyl ethers, sodium N-methyl-N-oleyl taurate, disodium monoamide N-alkylsulfosuccinates, and stannous acid surfactants. These include, but are not limited to, oil sulfonates, sulfated castor oil, sulfated tallow oil, salts of sulfate esters of fatty alkyl esters, salts of alkyl sulfate esters, salts of alkyl sulfate esters, sulfate esters of polyoxyethylene alkyl ethers, salts of sulfate esters of fatty monoglycerides, sodium salts of monosulfated monoglycerides of hydrogenated coconut oil fatty acids, salts of sulfate esters of polyoxyethylene alkyl phenyl ethers, salts of alkyl phosphate esters, salts of phosphoric acid esters of polyoxyethylene alkyl ethers, salts of phosphoric acid esters of polyoxyethylene alkyl phenyl ethers, partially saponified compounds of styrene-maleic anhydride copolymers, partially saponified compounds of olefin-maleic anhydride copolymers, naphthalenesulfonate-formaldehyde condensates, higher alkyl sulfoacetates, and higher fatty acid esters of 1,2-dihydroxypropanesulfonic acid, and combinations thereof.Among these anionic surfactants, sulfonate surfactants, especially C8-C such as alkylarylsulfonates, especially dodecylbenzenesulfonate. 18 salts of alkylbenzene sulfonic acids, and combinations thereof.

[0065]

[0101] The total amount of surfactant is used in an amount effective to provide a physically stable dispersion in combination with any thickening and / or suspending agents that may be present in the composition. The amount of surfactant required to achieve a physically stable dispersion depends on many factors, including, for example, the type and amount of biocide and thickening / suspending agent present, and the type of surfactant utilized. Typically, however, a sufficient amount of surfactant is used such that the weight ratio of biocide:surfactant is within the range of about 5:1 to about 50:1 or about 6:1 to about 20:1.

[0066]

[0102] Additionally, certain surfactants and surfactant combinations also have well-known membrane disruptive activity, which is common to some cationic surfactants, but also applies to certain non-ionic and ionic surfactants.

[0067] Thickening / Suspending Agents

[0103] The biocidal composition of the present disclosure may include one or more substances that can function as thickening or suspending agents to physically stabilize the biocidal composition. In particular, the type and amount of thickening and / or suspending agent is selected such that the resulting biocidal composition has a viscosity of at least 300 cps at 25°C. In other embodiments, the viscosity of the biocidal composition at 25°C is at least 400 cps or at least 500 cps. In general, it will be desirable for the viscosity of the biocidal composition not to increase to a point where pumping or handling the biocidal composition becomes difficult. Viscosity is measured using a Brookfield viscometer (spindle #5, 100 rpm).

[0068]

[0104] Suitable thickening / suspending agents include, but are not limited to, clays (including natural clays and organically modified clays), silicates (e.g., silicates such as modified silica and fumed silica), polysaccharides (e.g., gums such as xanthan gum, cellulosic polymers), polyacrylates, and the like, and combinations thereof.

[0069] Optional Additional Ingredients

[0105] In addition to those listed above, one or more other components may additionally be present in the biocidal compositions of the present disclosure. However, in certain embodiments, the biocidal composition consists essentially of or consists of the aforementioned components, except that in such embodiments, one or more antifoam agents may optionally be present.

[0070]

[0106] Optional additional components include, but are not limited to, dispersants, defoamers (antifoaming agents, e.g., silicone-based defoamers, mineral oil-based defoamers, hydrophobic silica-based defoamers), sequestering / chelating agents, pH adjusters, fillers, colorants, antifreeze agents, corrosion inhibitors (anticorrosion additives), UV stabilizers, antioxidants, solvents, co-solvents, scale inhibitors, and the like.

[0071] Manufacturing method

[0107] Biocidal compositions according to the present disclosure may be prepared by adapting any of the techniques known in the art for creating dispersions of water-insoluble substances in water using surfactants (emulsifiers), thickeners, suspending agents, and combinations of these components. For example, water is charged to a suitable sized mixing vessel, followed by the surfactants desired to be included in the biocidal composition. While stirring the surfactant / water mixture, the biocide and a portion of the thickener / suspending agent are added. Mixing at high speed and / or high shear may be continued until a homogenous emulsion having the desired particle size (typically 5-75 microns) is obtained. During this process, the mixture may be heated to a temperature somewhat above room temperature. The remaining thickener / suspending agent may then be added and the mixture stirred until homogenous again. The mixture may be cooled to room temperature before the final addition of the thickener / suspending agent. The biocidal composition may then be transferred by pump or other means to one or more suitable storage vessels, such as tanks, drums or totes.

[0072] Working Composition

[0108] The biocidal compositions of the present disclosure are useful for imparting resistance to microbial growth, including bacterial, fungal and algal growth, in a wide range of working compositions, particularly in water-based products. Biocidal compositions are typically prepared to contain relatively high concentrations of the active ingredient (i.e., biocide), and are therefore generally used as concentrates that are combined with one or more other ingredients in relatively small amounts to formulate a final product suitable for use for the intended purpose.

[0073]

[0109] In one embodiment, the working composition of the present disclosure comprises a biocidal composition comprising water, one or more organic compounds, and a combination of IPBC and zinc oxide effective for antibacterial preservation of the working composition in a wet state. The IPBC and zinc oxide may be present in the working composition in a weight ratio of 25:1 to 1:25.

[0074]

[0110] In various aspects, the working composition is a paint or coating composition, and other ingredients may include one or more pigments, a polymeric resin binder or filler (e.g., latex resin), and a carrier vehicle such as water. Specific polymeric resins include acrylate, butadiene, PVA, EVA, styrene, or vinyl acetate polymers. In one embodiment of the present disclosure, the biocidal composition is administered to a coating composition, particularly a water-based coating composition such as a latex paint, in an amount of 0.2 to 3% by weight of the coating composition.

[0075]

[0111] In another embodiment, the working composition of the present disclosure may be a joint sealing compound. Joint sealing compounds (also known as wallboard joint compounds, drywall joint compounds, or wallboard mud) are used to attach tape to wallboard (also known as drywall, plasterboard, or sheetrock) to cover the tape and hide surface defects of the wallboard. Typical wallboard joint compounds contain large or greater proportions of gypsum or limestone and water, and relatively small proportions of stone, clay, and polymers.

[0076]

[0112] The biocidal compositions of the present disclosure may be employed, for example, in any of the following types of products: cosmetics, toiletries, personal care, household, laundry, cleaning, disinfecting, paints, coatings, mineral slurries, pigments, pulp slurries, paper slurries, paper, metal working fluids, construction, plant nutrients, polymer grates, wallboard joint compounds, wallboard, spackling, sealants, stucco, mastics, asphalt emulsions, wood preservatives, lazules, stains, plaster, adhesives, textiles, leather treatments, hide treatments, nonwovens, building materials, stucco, concrete, or caulking products, and other applications where inhibition or prevention of the growth of undesirable microorganisms in both wet and dry film states is desired.

[0077] How to use

[0113] Another embodiment of the present disclosure includes a method of enhancing antimicrobial activity of IPBC in a wet working composition comprising water and one or more organic compounds, comprising treating the working composition with IPBC in the presence of zinc oxide. The IPBC and zinc oxide may be present in a weight ratio of 25:1 to 1:25, 20:1 to 1:20, 15:1 to 1:15, 10:1 to 1:10, 5:1 to 1:5, or 4:1 to 1:4. In other embodiments, the weight ratio of IPBC to ZnO is 2:1. The zinc oxide may comprise zinc oxide nanoparticles. In a further embodiment of the method, the working composition is further treated with one or more bacterial membrane disrupting agents. The one or more bacterial membrane disrupting agents may comprise 1,2-hexanediol, hexyl carbitol, TPnB glycol ether, butoxy triglycol, or triacetin.

[0078]

[0114] In a further embodiment of the method, the working composition is further treated with one or more additional biocidal substances, which may include one or more antifungal substances and / or one or more algicidal substances.

[0079]

[0115] In a further embodiment, the method of use comprises treating the working composition with an antimicrobially effective amount of a wetted biocidal composition comprising 1% to 25% IPBC, 1% to 25% zinc oxide, and 40% to 80% 1,2-hexanediol, based on the weight of the biocidal composition. The biocidal composition used in the method may further comprise 10% IPBC, 5% zinc oxide, and 60% 1,2-hexanediol, based on the weight of the biocidal composition.

[0080]

[0116] In a further embodiment, the method of use comprises treating the working composition with an antimicrobially effective amount of a wetted biocidal composition comprising 1% to 25% IPBC, 1% to 25% zinc oxide, and 40% to 80% hexyl carbitol, based on the weight of the biocidal composition. The biocidal composition used in the method may further comprise 10% IPBC, 5% zinc oxide, and 60% hexyl carbitol, based on the weight of the biocidal composition.

[0081]

[0117] Another aspect of the present disclosure includes a method of treating an aqueous working formulation containing one or more organic compounds to prevent, inhibit or reduce wet state bacterial contamination of the formulation, comprising treating the working formulation with a biocidal composition comprising an antibacterially-effective combination of IPBC and zinc oxide as described herein above.

[0082]

[0118] Although the embodiments are described herein in a manner that enables a clear and concise specification to be written, it is intended and will be understood that the embodiments can be variously combined or separated without departing from the present disclosure, for example, it will be understood that all preferred features described herein are applicable to all aspects of the present disclosure described herein.

[0083]

[0119] In some embodiments, the disclosure herein can be construed to exclude any element or process step that does not materially affect the basic and novel characteristics of the composition or process. In addition, in some embodiments, the disclosure can be construed to exclude any element or process step not specified herein.

[0084]

[0120] As used herein, the terms "about," "approximately," or "generally," when used to modify a value, indicate that the value may be increased or decreased by 10% and remain within the disclosed aspects, such as 7.5%, such as 5%, such as 4%, such as 3%, such as 2%, such as 1%, or any range or value therebetween. Additionally, when used to describe the amount of a substance in a material, the term "substantially free" is not limited to complete or total absence, but may correspond to the absence of any appreciable or detectable amount of the described substance in the material. Thus, for example, a material may be "substantially free" of a substance if the amount of the substance in the material is less than the precision of an industry-accepted device or test for measuring the amount of the substance in the material. In certain exemplary embodiments, a material may be "substantially free" of a substance if the amount of the substance in the material is less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, less than 0.5%, or less than 0.1% by weight of the material. It will be understood that in certain exemplary embodiments, the compositions described herein may be substantially free of materials not specifically mentioned.

[0085]

[0121] As used in this application and claims, the singular forms "a", "an" and "the" include the plural forms unless the context clearly dictates otherwise. Additionally, the term "includes" means "comprises". The methods and compositions of the present disclosure, including their components, may include, consist of, or consist essentially of the essential elements and limitations of the embodiments described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise useful in nutritional compositions.

[0086]

[0122] Unless otherwise indicated, all numerical values ​​expressing properties such as amounts of ingredients, molecular weights, percentages, etc., used in the specification or claims are understood to be modified by the term "about". Thus, unless otherwise indicated, either implicitly or explicitly, the numerical parameters recited are approximations that may depend on the desired properties sought and / or the detection limits in standard testing conditions / methods. When directly and explicitly distinguishing the embodiments from the prior art discussed, the numerical values ​​of the embodiments are not approximations unless the word "about" is recited.

[0087]

[0123] As used herein, "optional" or "optionally" means that the subsequently described material, event, or circumstance may or may not be present or occur, and includes examples in which the material, event, or circumstance is present or occurs and examples in which it does not occur. As used herein, "w / w%" and "% by weight" mean percentage by total weight or percentage by weight relative to other components in a composition.

[0088]

[0124] The phrase "effective amount" refers to an amount of a compound that enhances, improves, stimulates, or promotes a response to a particular condition or disorder, or a particular symptom of a condition or disorder.

[0125] Although the present disclosure has been illustrated and described herein with reference to specific embodiments, the present disclosure is not intended to be limited to the details shown. Rather, various changes in details may be made within the scope and equivalents of the claims and without departing from the present disclosure. EXAMPLES

[0089] Experimental Method Growth curve

[0126] To generate a growth curve, an overnight culture of P. aeruginosa (ATCC#10145) was lifted from plate count agar, resuspended in dHO, and cultured at OD in sterile Mueller Hinton Broth (MHB). 600= 0.01. The cultures were dispensed into the wells of an open 96-well plate along with the indicated biocides. The OD 600 was measured initially and then every 30 min with constant double orbital shaking for 16 h at 37° C. Because samples spiked with test compound were opaque, curves were generated by background subtraction from wells containing sterile MHB and then subtracting from the initial (t=0) measurements.

[0090] Minimum inhibitory concentration test

[0127] MICs were determined by microbroth dilution using the following specific test parameters: Format 96 well plate Strength: Approx. 1.0 * 10 5 CFU / mL Standardization OD 600 Incubation temperature: 35℃ Incubation time: 2 days Test endpoint: No growth (by turbidity) Test medium MHB

[0128] The required biodilution by OD600 was calculated such that an OD600 of 1.0 corresponds to 8x108 CFU / mL. Biocide dilutions were performed 2-fold for each assay.

[0091] Calculation of Synergy Index

[0129] The synergy index (SI) score was calculated according to the mass action equation: SI = [MIC[A] in mixture / MIC[A] alone] + [MIC[B] in mixture / MIC[B] alone].

[0092]

[0130] Combinations of components were judged to be synergistic (SI ≤ 0.5), additive (SI > 0.5 to 1), irrelevant (SI > 1 to < 2), or antagonistic (SI ≥ 2) as defined by the EUCAST guidelines. See the European Committee on Antimicrobial Susceptibility Testing (EUCAST) of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID). EUCAST Definitive Document E.Def 1.2, May 2000: Terminology relating to methods for the determination of susceptibility of bacteria to antimicrobial agents, Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis. 6, 503-508(2000);Helander IM, Mattila-Sandholm T., Fluorometric assessment of gram-negative bacterial permeabilization, J. Appl. Microbiol. 88:213-219(2000).

[0093] Checkerboard assay

[0131] The checkerboard assay consisted of Polyphase PW40 (40% IPBC) and 20% nanoparticulate ZnO dispersion (Sigma #721077) with Pseudomonas aeruginosa (ATCC#10145) at approximately 1.0 * 10 5 CFU / mL were added separately to 100 microliters of Mueller Hinton Broth. The plates were then incubated overnight at 37°C with constant double orbital shaking. The following day, the dispersions were left on the bench for 2 hours and the plates were photographed. Growth in this assay was defined as the turbidity of the supernatant.

[0094] Bactericidal curve

[0132] Overnight cultures of Pseudomonas aeruginosa (ATCC#10145) grown in Tryptic Soy Broth were cultured at OD in Mueller Hinton Broth containing the indicated levels of test compound. 600 =0.7. Samples containing IPBC were spiked with Polyphase PW40 (40% IPBC). Samples containing ZnO were spiked with 50% ZnO dispersion ("1678-54"). Time points were collected by spiking 1 mL of sample into 9 mL of Dey-Engley Neutralizing Broth and performing serial dilutions in 1x Butterfield's Phosphate Buffer. Counts were obtained from pour plates in Tryptic Soy Agar after overnight incubation at 35°C.

[0095] NPN uptake assay

[0133] NPN uptake assays were performed approximately as previously described (see Helander IM, Mattila-Sandholm T., Fluorometric assessment of gram-negative bacterial permeabilization, J. Appl. Microbiol. 88:213-219(2000), doi: 10.1046 / j.1365-2672.2000.00971.x). Cultures of P. aeruginosa (ATCC#10145) were grown overnight in Tryptic Soy Broth (TSB) and cultured at OD in sterile TSB. 600 = 0.1 and grown to early exponential phase. Cells were then centrifuged (10,000 g, 5 min), washed twice with assay buffer (5 mM HEPES-KOH, 5 mM glucose, pH 7.2) and assayed at OD 0. 600The cells were resuspended in assay buffer until the chromatin concentration reached 10 μM NPN = 1. 100 microliters of washed cells in assay buffer were then mixed with 100 microliters of assay buffer containing 20 μM NPN in a 96-well optical bottom black plate (Thermo). 2 microliters of test substance were then added, mixed briefly, and placed in the plate reader where fluorescence (excitation 350 nm, emission 420 nm) was monitored at 1 minute intervals for 10 minutes. Controls containing no cells or only water were included in the assay. NPN uptake was calculated at each time point using the following formula and averaged across all time points and triplicates: NPN uptake = (F サンプル -F 細胞なし )-(F 細胞 -F 細胞なし ) Bacterial and fungal challenge tests (standard)

[0134] Bacterial and fungal challenge tests were performed according to Troy's standard challenge test procedure SOP MI-07. The bacteria were Alcaligenes faecalis (ATCC#25094), Enterobacter aerogenes (ATCC#13048), Escherichia coli (ATCC#11229), and Pseudomonas aeruginosa (ATCC#10145). All bacteria were mixed overnight cultures on plate count agar (PCA) and counted at OD 600 After mixing at equal CFU, the OD 600 =0.7(about 10 8 The final bacterial consortium was created by diluting the total number of bacteria in the inoculum to 10 (CFU / mL). When indicated, additional bacterial organisms were added to the inoculum to provide equal CFU of each organism in the inoculum. The fungi used for the wet fungal challenge were Aspergillus niger (ATCC#6275) and Penicillium funiculosum (ATCC#12667). Fungal consortia were prepared on Malt Agar slants, counted using a hemocytometer prior to use, and diluted to 10 6The mixtures were prepared immediately prior to inoculation. For inoculation, 0.5 mL was added to 50 g of test sample, resulting in approximately 10 spores per challenge. 6 CFU / g of bacteria or 10 4 Spores / g of fungus were administered. After each challenge, at the indicated intervals, small amounts of test samples were plated onto PCA (for bacteria) or Malt agar (for fungi) for viability determinations. Bacterial plates were incubated at 32°C for 3–5 days, and Malt agar plates were incubated at 28°C for 1 week before reading. Viability plates were scored on a semiquantitative scale, which estimates approximate CFU / g by visual assessment of colony density along the streak line. Readings were recorded as the average of two duplicate semiquantitative readings ranging from "0" to "4". Samples were mixed before viability determinations and after each inoculation.

[0096] [Table 1]

[0097] Bacterial challenge test (industrial strength)

[0135] Where industrial strength inoculum was indicated, the bacterial challenge test organisms were Alcaligenes faecalis (ATCC#25094), Enterobacter aerogenes (ATCC#13048), Escherichia coli (ATCC#11229), Pseudomonas aeruginosa (ATCC#10145), Staphylococcus aureus (ATCC#6538), Microbacterium paraoxydans (Troy Isolate), Burkholderia cenocepacia (Troy Isolate), Citrobacter werkmanii (Troy Isolate), and Acinetobacter spp. (Troy Isolate). All bacteria were mixed from separate overnight cultures grown in Tryptic Soy Broth (TSB) and incubated at OD 600 After mixing at equal CFU, the OD 600 =7(about 10 9The final bacterial consortium was created by diluting the mixture to 0.1 mL (CFU / mL) per inoculation. Each mixture was prepared immediately before each inoculation. Inoculation was performed by adding 0.1 mL to 50 g of the indicated test sample, with approximately 10 7 CFU / g. After each challenge, at the indicated intervals, small aliquots of test samples were plated onto PCAs for viability determinations. Plates were then incubated at 32°C for 3–5 days and then assessed on a semiquantitative scale. This scale estimates approximate CFU / g by visual assessment of colony density along the streak line. Measurements are recorded as the average of two duplicate semiquantitative readings ranging from "0" to "4". Samples were mixed before viability determinations and after each inoculation.

[0098] [Table 2]

[0099] Challenge test scoring

[0136] The challenge test was scored by a weighted sum of squares for each of the 12 data points collected for each test sample. Weighting was done proportionally to the streak day, with day 1 weighted at 10%, day 2 weighted at 20%, and day 3 weighted at 70%. The sum of all 12 values ​​was then taken and divided by the score of the unprotected sample to get a total proliferation score. The "weighted performance" score reported is 1 minus the proliferation score.

[0100] Dry film mold resistance test

[0137] Dry film mold resistance testing was generally performed according to ASTM D5590 for a mixture of the organisms Aureobasidium pullulans (ATCC#9348) and Aspergillus niger (ATCC#6275) and Penicillium funiculosum (ATCC#11797). Suspensions of these organisms were prepared from Malt Agar slants and counted at 1·10 in a hemocytometer. 6The coating was adjusted to spores / mL. Test films were created by applying a thin layer of paint to Whatman #2 filter paper and allowing it to dry for 3-5 days. The prepared films were cut to 1 inch by 1 inch, 0.2 mL of the suspension was inoculated onto Malt Agar, and incubated at 28°C for 1 month. The coverage of fungal growth on the coating surface was then rated from "0" to "4" by degree of coverage according to ASTM D5590. Zones of inhibition were reported separately as z(x), where x is the average size of the zone in millimeters.

[0101] Dry film bacterial resistance test

[0138] Polyphase PW40 or Omniphase Z at IPBC levels of 300, 500, 700, and 900 ppm were added to films of test paint "Interior Paint #4", mixed, and cast into 127 μm (5 mil) films on black Leneta. After drying, the films were evaluated for bacterial resistance according to JIS Z2801 for 24-hour contact against Escherichia coli (ATCC#8739) and Staphylococcus aureus (ATCC#6538). Log reductions were calculated relative to the unprotected paint.

[0102] Test Biocide Compositions Ref-「1721-18-2」[「A」]

[0103] [Table 3]

[0104] Ref-「1721-18-4」[「B」]

[0105] [Table 4]

[0106] Ref - "1721-18-5" ["C"]

[0107] [Table 5]

[0108] Ref-"1721-52" / "1721-66" / "Omniphase Z"

[0109] [Table 6]

[0110] Reference-「1678-54」[50% ZnO]

[0111] [Table 7]

[0112] Reference-「1721-80」[40% ZnO]

[0113] [Table 8]

[0114] Ref-“1721-81” [20% ZnO, 20% IPBC]

[0115] [Table 9]

[0116] Ref-「1729-79」[1,2-Hexanediol Omniphase Z]

[0117] [Table 10]

[0118] Ref-“1729-79” [DMDA Omniphase Z]

[0119] [Table 11]

[0120] Ref- "1750-8" [Hexyl Carbitol Omniphase Z]

[0121] [Table 12]

[0122] Composition of commercial products

[0123] [Table 13]

[0124] Unsaved Matrix

[0139] Unpreserved test matrices of paints and stains were obtained from the following Troy projects:

[0125] [Table 14]

[0126]

[0140] The joint compound was prepared in-house according to the following recipe:

[0127] [Table 15]

[0128] Example 1:

[0141] Using IPBC-resistant Pseudomonas, growth of P. aeruginosa (ATCC#10145) was measured in the presence of 0.125-0.5 mM PAβN (Sigma #P4157) with or without IPBC (0.1% w / w Polyphase PW40, 400 ppm IPBC) over a 16-hour period at 37°C. Studies showed that PAβN alone had minimal effect on Pseudomonas growth, but 0.25 mM or higher PAβN in conjunction with 400 ppm IPBC completely inhibited Pseudomonas growth over a 16-hour period (Figure 1A).

[0129]

[0142] Because PAβN also causes membrane destabilization at high concentrations, we eliminated the role of efflux by adding MgCl2 to stabilize the membrane. See Lamers, RP et al., The efflux inhibitor phenylalanine-arginine beta-napthylamide (PAbetaN) permeabilizes the outer membrane of gram-negative bacteria, PLoS ONE 8:e60666(2013). Growth curves collected in the presence of 1 mM MgCl2 showed a weak IPBC enhancement effect, with Pseudomonas able to grow but delayed before exponential growth in a PAβN concentration-dependent manner (Figure 1B). Control results showed no inhibition of Pseudomonas in the presence of IPBC, MgCl2, or the combination (Figure 1C). Together, these results suggest that the low membrane permeability and active efflux of IPBC are important factors in Pseudomonas resistance to IPBC.

[0130] Example 2:

[0143] To determine whether nanoparticulate ZnO could enhance IPBC, the growth curves of P. aeruginosa (ATCC#10145) were repeated as in Figure 1. The source of IPBC was again Polyphase PW40, and the nanoparticulate ZnO was delivered using a 20% nanoparticulate ZnO suspension from Sigma-Aldrich (St. Louis, MO). Testing showed complete growth inhibition over 16 hours with the combination of IPBC and ZnO nanoparticles, whereas growth was observed in the presence of 400 ppm IPBC or 1000 ppm nanoparticulate ZnO alone (Figure 2A). To further explore this effect, checkerboard assays were performed with 100–500 ppm ZnO nanoparticles in combination with 100–500 ppm IPBC. After 24 hours of incubation with constant agitation to keep the dispersion suspended, wells containing only IPBC or ZnO nanoparticles were turbid, whereas all wells containing the combination of IPBC and nanoparticulate ZnO were clear (Figure 2B).

[0131] Example 3:

[0144] The activity of IPBC and standard ZnO against a variety of bacterial organisms was examined using minimum inhibitory concentration (MIC) testing. However, because nanoparticulate ZnO is more expensive than standard and involves additional regulatory scrutiny by the EPA, the ability of standard grade ZnO to enhance the activity of IPBC against a variety of bacterial species was evaluated. MIC testing demonstrated that IPBC and ZnO were synergistic (SI < 0.5) against most bacteria, but showed additive effects against bacteria already highly susceptible to IPBC (Table 1).

[0132] Example 4:

[0145] The usefulness of IPBC / ZnO combinations for paint preservation was tested. Mixtures containing 40% IPBC, 40% ZnO, or 20% IPBC and 20% ZnO were added to paints at 0.5-2.5% w / w (2,000-10,000 ppm ai) and tested for bacterial resistance using industrial inoculum. Challenge tests showed poor preservative properties overall for the three mixtures, but ZnO and ZnO / IPBC showed improved activity over IPBC (Table A1), achieving complete kill of the inoculum 7 days after challenge at 2.5% w / w (10,000 ppm).

[0133]

[0146] To measure the bactericidal effect of IPBC / ZnO, P. aeruginosa (ATCC#10145) was again used, as it was considered to be the most resistant to IPBC (Table 1). Kill curves were run for Pseudomonas with 2000 ppm IPBC, 2000 ppm ZnO, and 1000 ppm each, showing that this combination reduced the survival rate of Pseudomonas by 2 log after 2 hours of contact. 10 (99%) and a 5 log reduction in Pseudomonas viability after 24 hours of contact. 10 (>99.99%). However, measurements after 48 h showed that Pseudomonas growth had returned, indicating that either the preservative had been depleted by its own action or that the surviving Pseudomonas had undergone metabolic changes to overcome growth inhibition (Figure 3).

[0134] [Table 16]

[0135] Example 5:

[0147] The boosting effect of 1,2-hexanediol to enhance overall efficacy in an industrial system was evaluated. The ability of PAβN to enhance IPBC activity was due, at least in part, to increased membrane permeability (Figure 1). The ability of 1,2-hexanediol to increase the membrane permeability of Pseudomonas aeruginosa (ATCC#10145) was examined. To quantify this effect, the fluorescent probe 1-N-phenylnaptylamine (NPN) was used as an indicator of membrane permeability. NPN is only weakly fluorescent in solution and does not normally enter cells efficiently, but it becomes highly fluorescent when bound to intracellular phospholipids. The NPN assay showed that 1% 1,2-hexanediol significantly increased the permeability of the Pseudomonas membrane (Figure 4).

[0136] Example 6:

[0148] To measure the activity enhancement of mixtures containing 1,2-hexanediol along with IPBC / ZnO, a formulation containing 10% IPBC, 5% ZnO, and 60% 1,2-hexanediol ("Omniphase Z") was formulated and tested for MIC values ​​against the same organisms as in Table 1. The MIC value of 1,2-hexanediol was also measured to calculate the synergy index value. The MIC test showed that "Omniphase Z" showed synergistic effects against most of the test organisms, but additive or antagonistic effects against the organisms most sensitive to IPBC: Burkholderia, Bacillus, and Microbacterium. Consistently, there was a clear positive relationship between the susceptibility of the test organisms to IPBC and the synergy index of the "Omniphase Z" formulation (Figure 6). Moreover, in contrast to the kill curve results obtained by IPBC / ZnO (Figure 3), the addition of 1,2-hexanediol was able to completely kill Pseudomonas (Figure 5).

[0137] Example 7:

[0149] To distinguish the relative in-matrix fungicidal activity of 1,2-hexanediol from various combinations lacking one or more boosters, test formulations of 15% IPBC alone or in combination with 1,2-hexanediol or ZnO were prepared, tested, and compared with the performance of pure 1,2-hexanediol. Challenge studies were performed using a standard inoculum (10 6 CFU / g / challenge and industrial mixture for paints (10 7 CFU / g / challenge) were used for four inocula, and the test mixtures were added at concentrations ranging from 0.4 to 1.6% w / w (4000 to 16,000 ppm). Challenge results showed that the mixture of 1,2-hexanediol, IPBC and ZnO outperformed all other mixtures in joint compounds and coatings (Figure 7, Table 3). The data strongly suggest that IPBC contributes significantly to the wet germicidal activity when combined with 1,2-hexanediol and ZnO, and that the combination of all three provides useful industrial preservative properties.

[0138] [Table 17]

[0139] [Table 18]

[0140] Example 8:

[0150] The activity of formulated "Omniphase Z" ("1721-66" or "1721-52") in additional matrices and further functionality for wet and dry film microbial control was characterized. Challenge tests in paints with four inoculations showed that "Omniphase Z" provided wet bacterial and fungal control at 0.75 w / w, as well as dry film fungal control (Tables A4, A5, A6). In colorants, "Omniphase Z" protected against wet bacterial and fungal growth at 0.8% w / w with four inoculations (Tables A7, A8). Furthermore, "Omniphase Z" significantly outperformed conventional IPBC against dry film bacterial growth when tested according to JIS Z2801 (Figure 8).

[0141] Example 9:

[0151] Four additional solvents with similar chemical properties to 1,2-hexanediol were tested for their ability to improve the antimicrobial activity of IPBC / ZnO in paints against Pseudomonas. Paint challenge testing of these solvents showed that the three glycol ether solvents and triacetin showed some improvement in the bacterial resistance of paints containing IPBC / ZnO (Table A9). Hexylcarbitol performed very similarly to 1,2-hexanediol in boosting the antimicrobial activity of IPBC / ZnO in paints.

[0142] Example 10:

[0152] The boost in activity of IPBC / ZnO in paints was previously theorized to be related to membrane permeabilization (Example 5). Various glycol ethers were tested for their relative ability to permeabilize Pseudomonas membranes using the NPN assay. The results showed that while there was a wide variation in the membrane permeabilization activity of 1% w / v solutions of glycol ethers, hexyl carbitol, hexyl Cellosolve, and the ester alcohol Texanol had the highest membrane disruption potential against Pseudomonas (Figure 9).

[0143] Example 11:

[0153] The relative activity of vicinal diols, glycol ethers and alcohol ester texanols to impart the antimicrobial activity of IPBC / ZnO was measured in paints at 0.5% w / w. To isolate the potential protective effect of the materials themselves, activity was measured in paints with and without IPBC / ZnO. Bacterial challenge tests with four inoculations showed that all materials, except 1,2-octanediol, were unable to prevent bacterial growth in the paints by themselves, but several imparted strong antimicrobial protection to the paints when combined with IPBC / ZnO, which is ineffective by itself (Table A10). The results indicate that neither IPBC / ZnO nor the various glycols alone are sufficient to preserve the paints, but in combination they show very effective preservative activity (Table A10).

[0144] Example 12:

[0154] To determine whether the degree of membrane permeation by each material predicted its ability to enhance the antimicrobial activity of IPBC / ZnO in paints, logistic regression was performed to determine whether NPN incorporation (Figure 9) predicted pass / fail criteria from the bacterial challenge test (Table A10). Pass ("1") was defined as a rating of "0" 7 days after the fourth bacterial challenge, and fail ("0") was defined as any other value. The logistic regression data strongly indicates that NPN incorporation is highly predictive of a passing outcome in the challenge test when IPBC / ZnO is also included in the paint (AUC-0.5=0.33) and significantly less predictive when IPBC / ZnO is not present (AUC-0.5=0.17). The ROC curve is shown in Figure 10. These results collected for these materials clearly indicate that membrane permeation is a key feature that enhances the antimicrobial activity of IPBC / ZnO in paints.

[0145] Example 13:

[0155] Of the effective 1,2-hexanediol substitutes tested, hexylcarbitol was selected for the formulation. 10% IPBC, 5% ZnO, 50% hexylcarbitol, 10% Texanol, and additional fillers, stabilizers, and thickeners were used to create the solvent-dispersed formulation “1750-8.” Characterization of formulation “1750-8” began with MIC testing to confirm the synergistic effect of IPBC / ZnO and hexylcarbitol. MIC testing of IPBC / ZnO, hexylcarbitol, and “1750-8” against a variety of IPBC-susceptible and IPBC-resistant bacterial species demonstrated strong synergy between the components (Table 4, Figure 12).

[0146] [Table 19]

[0147] Example 14:

[0156] The ability of formulation 1750-8 to kill the IPBC-resistant organism Pseudomonas in solution was evaluated. Studies showed that 0.6% w / w or greater of 1750-8 caused >6 log kill and inhibition could be maintained for up to 48 hours (Figure 6).

[0148] Example 15:

[0157] Bacterial challenge tests with four inoculations showed that 0.6% w / w showed good inhibition of bacterial growth in the test paint, with higher levels showing better activity (Table 16). Attached table

[0149] [Table 20]

[0150] [Table 21]

[0151] [Table 22]

[0152]

Table 23

[0153]

Table 24

[0154]

Table 25

[0155]

Table 26

[0156]

Table 27

[0157]

Table 28

[0158]

Table 29-1

[0159]

Table 29-2

[0160]

Table 30

[0161]

[0158] These and other modifications and variations to the present disclosure may be implemented by those skilled in the art without departing from the spirit and scope of the present disclosure, as specifically defined by the appended claims. In addition, it should be understood that aspects of the various embodiments may be interchanged in whole or in part. Furthermore, those skilled in the art will appreciate that the foregoing description is illustrative only and is not intended to limit the disclosure as further described in the appended claims.

Claims

1. A biocidal composition comprising an antimicrobially effective combination of IPBC and zinc oxide.

2. 2. The biocidal composition of claim 1, wherein the IPBC and zinc oxide are present in a weight ratio of from 25:1 to 1:

25.

3. 3. A biocidal composition according to claim 1 or 2, wherein the zinc oxide comprises zinc oxide nanoparticles.

4. A biocidal composition as described in claim 1, further comprising one or more bacterial membrane disrupting substances.

5. A biocidal composition as described in claim 4, wherein the one or more bacterial membrane disrupting substances comprise one or more vicinal diols.

6. The biocidal composition of claim 4, wherein the one or more bacterial membrane disrupting substances comprise 1,2-hexanediol.

7. A biocidal composition as described in claim 4, wherein the one or more bacterial membrane disrupting substances comprise one or more glycol ethers.

8. A biocidal composition as described in claim 4, wherein the one or more bacterial membrane disrupting substances comprise hexyl carbitol, TPnB glycol ether, butoxytriglycol, or triacetin.

9. A biocidal composition as described in claim 1, further comprising one or more additional biocidal substances.

10. A biocidal composition as described in claim 9, wherein the one or more additional biocidal substances comprise one or more antifungal substances and / or one or more algaecidal substances.

11. 6. A biocidal composition according to claim 5 comprising from 1% to 25% by weight of IPBC, from 1% to 25% by weight of zinc oxide and from 40% to 80% by weight of one or more vicinal diols.

12. A biocidal composition as described in claim 11, comprising 10% by weight IPBC, 5% by weight zinc oxide, and 60% by weight of one or more vicinal diols.

13. 8. A biocidal composition according to claim 7 comprising from 1% to 25% by weight of IPBC, from 1% to 25% by weight of zinc oxide and from 40% to 80% by weight of one or more glycol ethers.

14. The biocidal composition of claim 13, comprising about 10% by weight IPBC, about 5% by weight zinc oxide, and about 60% by weight of one or more glycol ethers.

15. A working composition comprising water, one or more organic compounds, IPBC and an acid. and a biocidal composition effective for antimicrobial preservation of said working composition in a wet state, said biocidal composition comprising zinc oxide.

16. 16. The working composition of claim 15, wherein the IPBC and zinc oxide are present in a weight ratio of from 25:1 to 1:

25.

17. 17. A working composition according to claim 15 or 16, wherein the zinc oxide comprises zinc oxide nanoparticles.

18. The working composition of claim 15, wherein the biocidal composition further comprises one or more bacterial membrane disrupting agents.

19. 20. The working composition of claim 18, wherein the one or more bacterial membrane disrupting agents comprise one or more vicinal diols.

20. 20. The working composition of claim 18 or 19, wherein the one or more vicinal diols comprises 1,2-hexanediol.

21. 20. The working composition of claim 18, wherein the one or more bacterial membrane disrupting agents comprise one or more glycol ethers.

22. 22. The working composition of claim 21, wherein the one or more bacterial membrane disrupting agents comprise hexyl carbitol, TPnB glycol ether, butoxytriglycol or triacetin.

23. A working composition as described in claim 15, further comprising one or more additional biocidal substances.

24. 24. The working composition of claim 23, wherein the one or more additional biocidal substances comprise one or more antifungal substances and / or one or more algicidal substances.

25. The working composition of claim 15, wherein the biocidal composition comprises 1% to 25% by weight of IPBC, 1% to 25% by weight of zinc oxide, and 40% to 80% by weight of one or more vicinal diols.

26. 26. The working composition of claim 25, wherein the biocidal composition comprises 10% by weight IPBC, 5% by weight zinc oxide, and 60% by weight of one or more vicinal diols.

27. The working composition of claim 15, comprising 1% to 25% by weight of IPBC, 1% to 25% by weight of zinc oxide, and 40% to 80% by weight of one or more glycol ethers.

28. 28. The working composition of claim 27, comprising about 10% by weight IPBC, about 5% by weight zinc oxide, and about 60% by weight of one or more glycol ethers.

29. The working composition of claim 15, wherein the one or more organic compounds include one or more polymeric binders or fillers. composition.

30. A working composition according to claim 15 comprising a cosmetic, toiletry, personal care, household, laundry, cleaning, disinfecting, paint, coating, mineral slurry, pigment, pulp slurry, paper slurry, paper, metal working fluid, construction, plant nutrient, polymer grid, wallboard joint compound, wallboard, spackling, sealant, stucco, mastic, asphalt emulsion, wood preservative, lazule, stain, plaster, adhesive, textile, leather treatment, hide treatment, nonwoven, building material, stucco, concrete, or caulking product.

31. The working composition of claim 29, wherein the one or more polymeric binders or fillers comprise one or more acrylate, butadiene, PVA, EVA, styrene, or vinyl acetate polymers.

32. 1. A method for enhancing the antimicrobial activity of IPBC in a wet working composition comprising water and one or more organic compounds, the method comprising treating the working composition with IPBC in the presence of zinc oxide.

33. 33. The method of claim 32, wherein the IPBC and zinc oxide are present in a weight ratio of from 25:1 to 1:

25.

34. 34. The method of claim 32 or 33, wherein the zinc oxide comprises zinc oxide nanoparticles.

35. The method of claim 32, wherein the working composition is further treated with one or more bacterial membrane disrupting substances.

36. The method of claim 35, wherein the one or more bacterial membrane disrupting substances comprise one or more vicinal diols.

37. 37. The method of claim 36, wherein the one or more vicinal diols comprise 1,2-hexanediol.

38. The method of claim 35, wherein the one or more bacterial membrane disrupting substances comprise one or more glycol ethers.

39. 39. The method of claim 38, wherein the one or more bacterial membrane disrupting agents comprise hexyl carbitol, TPnB glycol ether, butoxytriglycol, or triacetin.

40. The method of claim 32, wherein the working composition is further treated with one or more additional biocidal substances.

41. The method of claim 40, wherein the one or more additional biocidal substances comprise one or more antifungal substances and / or one or more algaecidal substances.

42. The method of claim 32, wherein the working composition comprises a wet, antimicrobially effective amount of a biocidal agent comprising 1% to 25% by weight of IPBC, 1% to 25% by weight of zinc oxide, and 40% to 80% by weight of one or more vicinal diols. The method comprises treating the surface of the substrate with a composition comprising:

43. The method of claim 42, wherein the biocidal composition comprises 10% by weight IPBC, 5% by weight zinc oxide, and 60% by weight of one or more vicinal diols.

44. The method of claim 32, comprising 1% to 25% by weight of IPBC, 1% to 25% by weight of zinc oxide, and 40% to 80% by weight of one or more glycol ethers.

45. The method of claim 44, comprising about 10% by weight IPBC, about 5% by weight zinc oxide, and about 60% by weight of one or more glycol ethers.

46. 1. A method of treating an aqueous working formulation containing one or more organic compounds to prevent, inhibit or reduce wet state bacterial contamination of said formulation, comprising treating said working formulation with a biocidal composition comprising an antibacterially effective combination of IPBC and zinc oxide.

47. 47. The method of claim 46, wherein the IPBC and zinc oxide are present in a weight ratio of from 25:1 to 1:

25.

48. 48. The method of claim 46 or 47, wherein the zinc oxide comprises zinc oxide nanoparticles.

49. The method of claim 46, further comprising treating the working formulation with one or more bacterial membrane disrupting substances.

50. The method of claim 49, wherein the one or more bacterial membrane disrupting substances comprise one or more vicinal diols.

51. 51. The method of claim 50, wherein the one or more vicinal diols comprises 1,2-hexanediol.

52. The method of claim 49, wherein the one or more bacterial membrane disrupting substances comprise one or more glycol ethers.

53. The method of claim 49, wherein the one or more bacterial membrane disrupting substances comprise hexyl carbitol, TPnB glycol ether, butoxytriglycol or triacetin.

54. The method of claim 46, further comprising treating the working formulation with one or more additional biocidal substances.

55. The method of claim 54, wherein the one or more additional biocidal substances comprise one or more antifungal substances and / or one or more algaecidal substances.

56. The method of claim 46, wherein the working formulation comprises 1% to 25% by weight of IPBC, 1% to 25% by weight of zinc oxide, and 40% to 80% by weight of glycerol. 0% by weight of one or more vicinal diols.

57. The method of claim 56, wherein the biocidal composition comprises 10% by weight IPBC, 5% by weight zinc oxide, and 60% by weight of one or more vicinal diols.

58. The method of claim 46, comprising 1% to 25% by weight of IPBC, 1% to 25% by weight of zinc oxide, and 40% to 80% by weight of one or more glycol ethers.

59. The method of claim 58, comprising about 10% by weight IPBC, about 5% by weight zinc oxide, and about 60% by weight of one or more glycol ethers.

60. The method of claim 46, wherein the one or more organic compounds include one or more polymeric binders or fillers.

61. The method of claim 46, wherein the working composition comprises a cosmetic, toiletry, personal care, household, laundry, cleaning, disinfecting, paint, coating, mineral slurry, pigment, pulp slurry, paper slurry, paper, metal working fluid, construction, plant nutrient, polymer grid, wallboard joint compound, wallboard, spackling, sealant, stucco, mastic, asphalt emulsion, wood preservative, lazule, stain, plaster, adhesive, textile, leather treatment, hide treatment, nonwoven, building material, stucco, concrete, or caulking product.

62. 61. The method of claim 60, wherein the one or more polymeric binders or fillers comprise one or more acrylate, butadiene, PVA, EVA, styrene, or vinyl acetate polymers.

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