Patent Grant
10975260
This disclosure generally relates to compounds having biocidal properties and/or a potential for increased biocidal properties. This disclosure also relates to surfaces that include such a compound and one or more cationic centers, wherein the compound and the cationic centers are attached to the surface by surface modifications, coating formulations or otherwise. In particular, this disclosure relates to modified surfaces that include at least one compound that comprises an N-halamine precursor group. The modified surfaces also include a cationic center, where there is a ratio of cationic centers to N-halamine precursor groups upon the modified surface.
Microorganisms, such as bacteria, archaea, yeast or fungi, can cause disease, spoilage of inventory, process inefficiencies, disruptions of healthy natural environments and infrastructure degradation. More specifically, healthcare-associated infections (HAIs) are a serious and growing challenge to health care systems around the world. HAIs cause over 100,000 deaths annually and have become the 3rd leading cause of death in Canada. It is estimated that in any given year, HAIs directly cost the United States healthcare system between about $30B and about $45B. Added to this challenge is the increasing prevalence of microorganisms that are resistant to currently available antimicrobial intervention products and processes, including preventative approaches (disinfectants used to control environmental contamination) and reactive approaches (remedies including the use of antibiotics). Therefore, it is necessary to deploy biocidal technologies in various environments as a strategy for controlling unwanted levels or types of micro-organisms.
A common approach for disinfecting of both hard and soft surfaces is the use of liquid disinfectants. Selection of a suitable disinfectant for any given application is dependent upon the environment where the disinfectant will be applied. Selection criteria include the types of micro-organisms targeted, contact time for the disinfectant, level of toxicity tolerable in each application, cleanliness (or lack thereof) of the surface to be cleaned, sensitivity of the surface materials to oxidization (i.e., leading to corrosion of the substrate), the presence or absence of biofilms, the amount of organic load present on substrate surfaces, and local regulations that may restrict the use of certain active ingredients within a disinfectant. Some environments are far more challenging to adequately disinfect than others.
It is known to modify soft surfaces, such as textiles, to provide biocidal properties. For example, the antimicrobial properties of silver have been known since at least the 1960s. Specifically, silver nanoparticles possess broad-spectrum antimicrobial activities and exhibit few toxicological side effects. Currently there are commercially available textiles that incorporate silver, for example, there is a LULULEMON® (LULULEMON is a registered trademark of Lululemon Athletica Canada Inc.), SILVERSCENT® (SILVERSCENT registered trademark of Lululemon Athletica Inc.) product that incorporates the X-STATIC® (X-STATIC registered trademark of Noble Fiber Technologies, LLC) silver product. Additionally, UNDER ARMOUR® (UNDER ARMOUR registered trademark of Under Armour, Inc.) markets a Scent Control technology that comprises a blend of at least silver and zinc. The biocidal activity of these silver-incorporated textiles is limited by the amount of silver that is present and available to react with micro-organisms. The amount of silver available in a fabric is finite and may decrease as the textiles are laundered.
It is also known to modify textiles that incorporate polyethylene terephthalate (PET). These modifications may be achieved by forming a surface network of polyacrylamide (PAM) and PET, and then converting immobilized amides within the surface network to N-chloramine. Composite fabrics with such surface networks have been termed PAM-PETs. PAM-PETs have been challenged with different strains of multi-drug resistant bacteria including health-care acquired Staphylococcus aureus, an MRSA (isolate #70065); community-acquired S. aureus, also an MRSA (isolate #70527); multi-drug-resistant (MDR) ESBL E. coli (isolate #70094); MDR Pseudomonas aeruginosa (isolate #73104); and S. aureus ATCC 25923. The PAM-PET composite fabric demonstrated close to a 6-log reduction of all the tested bacteria. Furthermore, the N-chloramine on the PAM-PET was evaluated. After 29 regeneration cycles, the PAM-PET (chlorine 306 ppm) was still able to provide 6-log reduction of HA-MRSA (isolate #70527) within 20 minutes of contact.
International patent application number PCT/CA2013/000491 teaches using forming a semi-interpenetrating network upon a PET surface. The network provides at least one alkynyl group for covalently bonding cyclic amide, azido-5,5-dimethyl-hydantoin (ADMH). This modified PET sample could bring 7-log reductions of both MDR ESBL #70094 and CA-MRSA #70527. PCT/CA/2013/00491 also teaches linking the ADMH molecule with a short-chain QAC to create N-(2-azidoethyl)-3-(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)-N,N-dimethylpropan-1-aminium chloride (ADPA) and covalently bonding this molecule onto the PET using the Cu (I)-catalyzed azide-alkyne cyclo addition (CuAAC, commonly termed as “click chemistry”).
However, forming the surface semi-interpenetrating network as taught by PCT/CA/-2013/00491, as used in the first step of modification as a priming process, cannot be easily scaled up to industrially relevant levels. For example, the process requires multiple processing steps as well as the introduction of environmentally unfriendly additives, such as a methanol bath at elevated temperature. Additionally, the process requires UV irradiation to promote crosslinking in a methanol-saturated environment, which may cause safety concerns.
Embodiments of the present disclosure relate to a modified surface that includes at least one cationic center and at least one compound. The surface can be modified by various methods. The result of these methods is that the at least one cationic center and the at least one compound are connected to the modified surface. The at least one cationic center and the at least one compound are connected to the modified surface so that both of the at least one cationic center and the at least one compound are available upon the modified surface to react with other chemicals or microorganisms that may come into contact with or near to the modified surface. The availability of the at least one cationic center and the at least one compound cause the modified surface to have a functionality that it would not otherwise have.
In some embodiments of the present disclosure the number of molecules of the cationic center relative to the number of molecules of the at least one compound may influence the functionality of the modified surface. In other words, the ratio of the number of cationic center molecules to the number of molecules of the at least one compound may influence the functionality of the modified surface.
In some embodiments of the present disclosure the at least one cationic center may comprise a positively charged atom with one or more functional groups that are bound thereto. In some embodiments of the present disclosure the quaternary cationic center may be a quaternary ammonium, a quaternary phosphonium, or a quaternary sulfonium. In other embodiments of the present disclosure the cationic center may be another type of positively charged atom.
In some embodiments of the present disclosure the at least one compound may comprise an N-halamine group or a precursor thereof. When connected to the modified surface, the N-halamine group or the precursor thereof provides biocidal activity or the potential for increased biocidal activity.
In some embodiments of the present disclosure, the at least one cationic center is connected to the modified surface separately from the at least one compound, where the at least one compound comprises at least one N-halamine group or a precursor thereof. In these embodiments of the present disclosure, the at least one cationic center is connected to the modified surface by connecting a cationic compound to the modified surface. The cationic compound is a different compound from the at least one compound.
In some embodiments of the present disclosure, the at least one cationic center is connected to the modified surface together with the at least one compound. In these embodiments of the present disclosure, a single compound is connected to the modified surface, the single compound comprises both an N-halamine precursor group and a cationic center. This single compound is referred to herein as a combined compound.
In some embodiments of the present disclosure, the at least one cationic center is connected to the modified surface both separately from and together with the at least one compound. In these embodiments of the present disclosure, a cationic compound and a combined compound are connected to the modified surface. The cationic compound and the combined compound are different compounds.
Some embodiments of the present disclosure relate to cationic compounds that provide a cationic center but do not include an N-halamine group or an N-halamine precursor group. Some embodiments of the present disclosure relate to cationic compounds with the following general formula [I]:
wherein R1, R2 and R3 are each selected from a group consisting of: azide; an alkyne; CH3; CH2CH3; phenyl; C3H6NH2; CH3H5═CH2; C3H4≡CH; CH2CH2R13;
an alcohol; a primary amine; a secondary amine; a tertiary amine; an ether; an epoxide; a carbonyl group; a derivative of a carbonyl group including an acyl, an aldehyde, a ketone, a carboxylic acid, an anhydride, an ester, and an amide; an alkyl halide including a vinyl chloride, a vinyl fluoride; a vinyl group; a derivative of a vinyl group, including a vinyl acetate, a methyl methacrylate, a vinyl-pyridine; a vinyl-benzylidene; an isocyanate group; a carboxyl group and an associated carboxylate ion; a thiol; a phenol group; an imidazole and a combination thereof;
wherein A1+ and A2+ are each a cationic center that is independently selected from a group consisting of N+, P+, S+ or nil;
wherein R4, R5, R6 and R7 are independently selected from a group consisting of an alkyl chain of the formula CbH(2b) where b is an integer between 0 and 20 and a phenyl;
wherein if A1+ is 5, then at least one of R4 or R5 is nil;
wherein if A2+ is 5, then at least one of R6 or R7 is nil;
wherein X1−, X2−, X3−, X4− are each counter ion that is independently selected from a group consisting of nil, Cl−, Br−, I− and F−;
wherein n and n2 is an integer selected from 0 to 20;
wherein p is an integer selected from 0 to 20;
wherein q is an integer between 1 and infinity;
wherein only one of W1 and W2 is nil, or both are each independently selected from a group consisting of P+, N+, S+, N, C, benzene, a cycloaliphatic or another moiety that is capable of bonding with 3 or more further moieties, such further moieties including carbon chains or otherwise, when W1 is other than P+, N+, S+ then X1− is nil and when W2 is other than P+, N+, S+ then X2− is nil;
wherein R8, R9 and R10 are each selected from a group consisting of: azide; an alkyne; CH3; CH2CH3; phenyl; C3H6NH2; CH3H5═CH2; C3H4≡CH; CH2CH2R13;
an alcohol; a primary amine; a secondary amine; a tertiary amine; an ether; an epoxide; a carbonyl group; a derivative of a carbonyl group including an acyl, an aldehyde, a ketone, a carboxylic acid, an anhydride, an ester, and an amide; an alkyl halide including a vinyl chloride, a vinyl fluoride; a vinyl group; a derivative of a vinyl group, including a vinyl acetate, a methyl methacrylate, a vinyl-pyridine, a vinyl-benzylidene; an isocyanate group; a carboxyl group and an associated carboxylate ion; a thiol; a phenol group; an imidazole and a combination thereof;
wherein when W1 is S+, at least one of R1, R2 and R3 is nil and the other two moieties together with S+ may form one of
wherein when W2 is S+, at least one of R8, R9 and R10 is nil and the other two moieties together with S+ may form one of
wherein R11 is selected from a group consisting of H, CH3 and CN;
wherein R12 is selected from a group consisting of H, OH, NH2, OCH3, OCH2CH3; and
wherein R13 may be selected from a group consisting of OH, SH, OCN, CN, NC, SNN and NCS.
Some embodiments of the present disclosure relate to cationic compounds with the following general formulas [II] through [VIs]:
Some embodiments of the present disclosure relate to compounds that comprise at least one N-halamine precursor group. Some embodiments of the present disclosure relate to N-halamine-bearing compounds with the following general formula [VII]:
wherein L1, L2, L3 and L4 are independently selected from a group comprising: an alkyl chain of the formula CbH(2b) where b is an integer between 0 and 20; triazyl, an organic linker-group or nil;
wherein the organic linker-group comprises phenyl, propane, butane, pentane, hexane, cyclic propane, cyclic butane, cyclic pentane or cyclic hexane;
wherein at least one of R1, R2 and R3 is an N-halamine precursor that may be selected from a group consisting of imidazolidine-2,4-dione (hydantoin); 5,5-dimethylhydantoin; 4,4-dimethyl-2-oxazalidione; tetramethyl-2-imidazolidione; 2,2,5,5-tetramethylimidazo-lidin-4-one; a uracil derivative; and piperidine or
R1, R2 and R3 are independently selected from a group consisting of nil; H; an alkyl chain of the formula CbH(2b+1) where b is an integer between 0 and 20; a cyclic organic group including ring structures with at least four carbons and an alcohol; a primary amine; a secondary amine; a tertiary amine; an ether; an epoxide; a carbonyl group; a derivative of a carbonyl group including, an acyl, an aldehyde, a ketone, a carboxylic acid, an anhydride, an ester, and an amide; an alkyl halide, including a vinyl chloride, a vinyl fluoride a vinyl group; a derivative of a vinyl group, including a vinyl acetate, a methyl methacrylate, a vinyl-pyridine, a vinyl-benzylidene; an isocyanate group; a carboxyl group and an associated carboxylate ion; a thiol; a phenol group; and an imidazole;
wherein A1+ and A2+ are each a cationic center that is independently selected from a group consisting of N+, P+, S+ or nil;
wherein R4, R5, R6 and R7 are independently selected from a group consisting of an alkyl chain of the formula CbH(2b) where b is an integer between 0 and 20 and a phenyl
wherein if A+ is S, then at least one of R4 or R5 is nil;
wherein if A2+ is S, then at least one of R6 or R7 is nil;
wherein X1−, X2−, X3−, X4− are each a counter ion that is independently selected from a group consisting of nil, Cl−, Br−, I− and F−;
wherein m is an integer that is either one or two;
wherein n is an integer selected from 0 to 20;
wherein p is an integer selected from 0 to 20;
wherein W1 and W2 are each independently selected from a group consisting of nil, but both not being nil, P+, N+, S+, N, C, benzene, a cycloaliphatic or another moiety that is capable of bonding with 3 or more further moieties, such further moieties including H, carbon chains or otherwise, when W1 is other than P+, N+, S+ then X1− is nil and when W2 is other than P+, N+, S+ then X2− is nil;
wherein R8, R9 and R10 are each selected from a group consisting of: an azide; an alkyne; CH3; CH2CH3; phenyl; C3H6NH2; CH3H5═CH2; C3H4≡CH; CH2CH2R13;
an alcohol; a primary amine; a secondary amine; a tertiary amine; an ether; an epoxide; a carbonyl group; a derivative of a carbonyl group including an acyl, an aldehyde, a ketone, a carboxylic acid, an anhydride, an ester, and an amide; an alkyl halide including a vinyl chloride, a vinyl fluoride; a vinyl group; a derivative of a vinyl group, including a vinyl acetate, a methyl methacrylate, a vinyl-pyridine, a vinyl-benzylidene; an isocyanate group; a carboxyl group and an associated carboxylate ion; a thiol; a phenol group; an imidazole and a combination thereof;
wherein when W1 is S+, at least one of R1, R2 and R3 is nil and the other two moieties together with S+ may form one of
wherein when W2 is S+, at least one of R8, R9 and R10 is nil and the other two moieties together with S+ may form one of
wherein R11 is selected from a group consisting of CH3 and CN;
wherein R12 is selected from a group consisting of H, OH, NH2, OCH3, OCH2CH3; and
wherein R13 may be selected from a group consisting of OH, SH, OCN, CN, NC, SNN and NCS.
Some further embodiments of the present disclosure relate to N-halamine-bearing compounds with one of the following general formulas [VIII] to [XVI]:
In some embodiments of the present disclosure, a substrate is provided. In some embodiments of the present disclosure the substrate comprises at least one surface that is modified so that at least one cationic center is connected to the modified surface as a cationic compound, which is separate and distinct from a compound that comprises an N-halamine precursor group. In some embodiments of the present disclosure the substrate comprises at least one surface that is modified so that a combined compound is connected to the modified surface, the combined compound that comprises at least one cationic center and at least one N-halamine precursor group. In other embodiments of the present disclosure the substrate comprises at least one surface that is modified so that at least one cationic center is connected to the modified surface as a cationic compound, which is separate and distinct from a combined compound that comprises at least one cationic center and at least one N-halamine precursor group.
Some embodiments of the present disclosure relate to a method for connecting multiple cationic centers and multiple N-halamine precursor groups to a surface in a ratio of a number of connected cationic centers to a number of N-halamine precursor groups is within a range of about 1:1 to about 10:1.
Some embodiments of the present disclosure relate to a coating formulation for coating a substrate, the coating formulation comprising multiple cationic centers and multiple N-halamine precursor groups. A ratio of a number of the multiple cationic centers to a number of N—H binding sites within the multiple N-halamine precursor groups is within a range of about 1:1 and about 10:1.
Some embodiments of the present disclosure relate to a surface comprising multiple cationic centers and multiple N-halamine precursor groups that are both connected to the surface. A ratio of a number of the multiple cationic centers to a number of N—H binding sites within the multiple N-halamine precursor groups is within a range of about 1:1 and about 10:1.
Without being bound by any particular theory, a range of ratios of the number of cationic centers to the number of N-halamine precursor molecules that are present on a modified surface was identified. This range of ratios may provide the modified surface with desirable chlorine-uptake properties. In some embodiments of the present disclosure the desirable chlorine-uptake properties may also provide the modified surface with biocidal activity or the potential for increased biocidal activity. Independent of the chlorine uptake properties, the range of ratios between a number of cationic centers to the number of N-halamine precursor molecules that are present on a modified surface may increase chlorine-mediated biocidal-activity kinetics in comparison to other modified surfaces that do not have cationic centers connected thereto and other modified surfaces that have a ratio of cationic centers to the number of N-halamine precursor molecules outside the range described herein.
These and other features of this disclosure will become more apparent in the following detailed description in which reference is made to the appended drawings, wherein:
Embodiments of the present disclosure relate to a modified surface that includes at least one cationic center and at least one compound. The surface can be modified by various methods. The result of these methods is that the at least one cationic center and the at least one compound are connected to the modified surface. The at least one cationic center and the at least one compound are connected to the modified surface so that both of the at least one cationic center and the at least one compound are available upon the modified surface to react with other chemicals or microorganisms that may come into contact with or near to the modified surface. The availability of the at least one cationic center and the at least one compound cause the modified surface to have a functionality that it would not otherwise have.
In some embodiments of the present disclosure the number of molecules of the cationic center relative to the number of molecules of the at least one compound may influence the functionality of the modified surface. In other words, the ratio of the number of cationic center molecules to the number of compound molecules may influence the functionality of the modified surface.
In some embodiments of the present disclosure the at least one cationic center may comprise a positively charged atom with one or more functional groups that are bound thereto. In some embodiments of the present disclosure the cationic center may be a quaternary ammonium, a quaternary phosphonium, or a tertiary sulfonium. In other embodiments of the present disclosure the cationic center may be another type of positively charged atom.
In some embodiments of the present disclosure the at least one compound may comprise an N-halamine group or a precursor thereof. When connected to the modified surface, the N-halamine group or the precursor thereof provides biocidal activity or the potential for increased biocidal activity.
In some embodiments of the present disclosure, the at least one cationic center is connected to the modified surface separately from the at least one compound that comprises an N-halamine precursor group that is also connected to the modified surface. These embodiments may be achieved by connecting a cationic compound to the modified surface and connecting at least one separate compound that comprises an N-halamine precursor group.
In some embodiments of the present disclosure, the at least one cationic center is connected to the modified surface together with the at least one compound. In these embodiments of the present disclosure, a single compound is connected to the modified surface, the single compound comprises both an N-halamine precursor group and a cationic center. This single compound is be referred to herein as a combined compound.
In some embodiments of the present disclosure, the at least one cationic center is connected to the modified surface both separately from and together with the at least one compound. In these embodiments of the present disclosure, a cationic compound and a combined compound are connected to the modified surface.
Some embodiments of the present disclosure relate to cationic compounds that provide a cationic center but do not include an N-halamine precursor group. Some embodiments of the present disclosure relate to cationic compounds with the following general formula [I]:
wherein R1, R2 and R3 are each selected from a group consisting of azide; an alkyne; CH3; CH2CH3; phenyl; C3H6NH2; CH3H5═CH2; C3H4≡CH; CH2CH2R13;
an alcohol; a primary amine; a secondary amine; a tertiary amine; an ether; an epoxide; a carbonyl group; a derivative of a carbonyl group including an acyl, an aldehyde, a ketone, a carboxylic acid, an anhydride, an ester, and an amide; an alkyl halide including a vinyl chloride, a vinyl fluoride; a vinyl group; a derivative of a vinyl group, including a vinyl acetate, a methyl methacrylate, a vinyl-pyridine, a vinyl-benzylidene; an isocyanate group; a carboxyl group and an associated carboxylate ion; a thiol; a phenol group; an imidazole and a combination thereof;
wherein A1+ and A2+ are each a cationic center that is independently selected from a group consisting of N+, P+, S+ or nil;
wherein R4, R5, R6 and R7 are independently selected from a group consisting of an alkyl chain of the formula CbH(2b) where b is an integer between 0 and 20 and a phenyl;
wherein if A1+ is S, then at least one of R4 or R5 is nil;
wherein if A2+ is S, then at least one of R6 or R7 is nil;
wherein X1−, X2−, X3−, X4− are each a counter ion that is independently selected from a group consisting of nil, Cl−, Br−, I− and F−;
wherein n and n2 is an integer selected from 0 to 20;
wherein p is an integer selected from 0 to 20;
wherein q is an integer between 1 and infinity;
wherein only one of W1 and W2 is nil, or both are each independently selected from a group consisting of P+, N+, S+, N, C, benzene, a cycloaliphatic or another moiety that is capable of bonding with 3 or more further moieties, such further moieties including H, carbon chains or otherwise, when W1 is other than P+, N+, S+ then X1− is nil and when W2 is other than P+, N+, S+ then X2− is nil;
wherein R8, R9 and R10 are each selected from a group consisting of: azide; an alkyne; CH3; CH2CH3; phenyl; C3H6NH2; CH3H5═CH2; C3H4≡CH; CH2CH2R13;
an alcohol; a primary amine; a secondary amine; a tertiary amine; an ether; an epoxide; a carbonyl group; a derivative of a carbonyl group including an acyl, an aldehyde, a ketone, a carboxylic acid, an anhydride, an ester, and an amide; an alkyl halide including a vinyl chloride, a vinyl fluoride; a vinyl group; a derivative of a vinyl group, including a vinyl acetate, a methyl methacrylate, a vinyl-pyridine, a vinyl-benzylidene; an isocyanate group; a carboxyl group and an associated carboxylate ion; a thiol; a phenol group; an imidazole and a combination thereof;
wherein when W1 is S+, at least one of R1, R2 and R3 is nil and the other two moieties together with S+ may form one of
wherein when W2 is S+, at least one of R8, R9 and R10 is nil and the oxer two moieties together with S+ may form one of
wherein R11 is selected from a group consisting of H, CH3 and CN;
wherein R12 is selected from a group consisting of H, OH, NH2, OCH3, OCH2CH3; and
wherein R13 may be selected from a group consisting of OH, SH, OCN, CN, NC, SNN and NCS.
Some embodiments of the present disclosure relate to cationic compounds with the following general formulas [II], [III], [IV], [V], [VI] and [VIa] through [VIs]:
Some embodiments of the present disclosure relate to compounds that comprise at least one N-halamine precursor group. Some embodiments of the present disclosure relate to N-halamine-bearing compounds with the following general formula [VII]:
wherein L1, L2, L3 and L4 are independently selected from a group comprising: an alkyl chain of the formula CbH(2b) where b is an integer between 0 and 20; triazyl, an organic linker-group or nil;
wherein the organic linker-group comprises phenyl, propane, butane, pentane, hexane, cyclic propane, cyclic butane, cyclic pentane or cyclic hexane;
wherein at least one of R1, R2 and R3 is an N-halamine precursor that may be selected from a group consisting of imidazolidine-2,4-dione (hydantoin); 5,5-dimethylhydantoin; 4,4-dimethyl-2-oxazalidione; tetramethyl-2-imidazolidione; 2,2,5,5-tetramethylimidazo-lidin-4-one; a uracil derivative; and piperidine or
R1, R2 and R3 are independently selected from a group consisting of nil; H; an alkyl chain of the formula CbH(2b+1) where b is an integer between 0 and 20; a cyclic organic group including ring structures with at least four carbons and an alcohol; a primary amine; a secondary amine; a tertiary amine; an ether; an epoxide; a carbonyl group; a derivative of a carbonyl group including, an acyl, an aldehyde, a ketone, a carboxylic acid, an anhydride, an ester, and an amide; an alkyl halide, including a vinyl chloride, a vinyl fluoride; a vinyl group; a derivative of a vinyl group, including a vinyl acetate, a methyl methacrylate, a vinyl-pyridine, a vinyl-benzylidene; an isocyanate group; a carboxyl group and an associated carboxylate ion; a thiol; a phenol group; and an imidazole;
wherein A1+ and A2+ are each a cationic center that is independently selected from a group consisting of N+, P+, S+ or nil;
wherein R4, R5, R6 and R7 are independently selected from a group consisting of an alkyl chain of the formula CbH(2b) where b is an integer between 0 and 20 and a phenyl
wherein if A+ is S, then at least one of R4 or R5 is nil;
wherein if A2+ is S, then at least one of R6 or R7 is nil;
wherein X1−, X2−, X3−, X4− are each a counter ion that is independently selected from a group consisting of nil, Cl−, Br−, I− and F−;
an alcohol; a primary amine; a secondary amine; a tertiary amine; an ether; an epoxide; a carbonyl group; a derivative of a carbonyl group including an acyl, an aldehyde, a ketone, a carboxylic acid, an anhydride; an ester, and an amide; an alkyl halide including a vinyl chloride, a vinyl fluoride; a vinyl group; a derivative of a vinyl group, including a vinyl acetate, a methyl methacrylate, a vinyl-pyridine, a vinyl-benzylidene; an isocyanate group; a carboxyl group and an associated carboxylate ion; a thiol; a phenol group; an imidazole and a combination thereof;
wherein when W1 is S+, at least one of R1, R2 and R3 is nil and the other two moieties together with S+ may form one of
wherein when W2 is S+, at least one of R8, R9 and R10 is nil and the other two moieties together with S+ may form one of
wherein R11 is selected from a group consisting of H, CH3 and CN;
wherein R12 is selected from a group consisting of H, OH, NH2, OCH3, OCH2CH3; and
wherein R13 may be selected from a group consisting of OH, SH, OCN, CN, NC, SNN and NCS.
Some further embodiments of the present disclosure relate to N-halamine-bearing compounds with one of the following general formulas [VIII] to [XVI]:
In accordance with other embodiments of the present disclosure, a substrate is provided. The substrate may be a soft substrate or a relatively hard substrate. In some embodiments of the present disclosure the soft substrate may be a textile. In some embodiments of the present disclosure the relatively hard substrate may be one of a metal, a metal alloy, a hard polymer, a flexible polymer, a rigid polymer, a thermoplastic polymer, a thermoset polymer, glass, ceramic, wood or combinations thereof.
In some embodiments of the present disclosure the substrate comprises at least one surface that is modified so that at least one cationic center is connected to the modified surface as a cationic compound, which is separate and distinct from a compound that comprises an N-halamine precursor group. In some embodiments of the present disclosure the substrate comprises at least one surface that is modified so that a combined compound is connected to the modified surface, the combined compound that comprises at least one cationic center and at least one N-halamine precursor group. In other embodiments of the present disclosure the substrate comprises at least one surface that is modified so that at least one cationic center is connected to the modified surface as a cationic compound, which is separate and distinct from a combined compound that comprises at least one cationic center and at least one N-halamine precursor group.
The surface may be modified by any known or not yet known method of modifying a surface so that the at least one cationic center and the at least one compound are connected to the modified surface. There are various known methods for modifying a substrate's surface. These methods can generally be categorized as laboratory methods or industrial methods. The method utilized in modifying the substrate' surfaces dictates how applicable the method is for industrial-scaled use. Various industries over time have subscribed to standardized processing methods that provide the production parameters of throughput, yield and consistency of quality control. These industrial methods require specific infrastructure. However, many laboratory methods are impractical for industrial-scaled use because the specific nature of the infrastructure required for the laboratory methods are often cost prohibitive and require a high degree of technical training to operate and maintain. Laboratory methods may also have other shortfalls that are related to production parameters that are expected from industrial-scaled uses.
Some known laboratory methods that may be used to modify a substrate surface include, but are not limited to:
The industrial methods for modifying a surface may be further categorized into applications for soft substrates, such as textiles, and applications for hard substrates. Known industrial methods that are used to modify a soft-substrate surface include, but are not limited to:
The type of functionality that it is desired to incorporate on the modified surface may influence the soft-substrate industrial method chosen. Each process has a place in processing of textiles depending on the business case. The cost, yield and batch size may also play a factor in the soft-substrate industrial method chosen. Processes with reduced energy input and small batch economics are potential drivers in the coating method chosen.
Known industrial methods that are used to modify a hard-substrate surface include, but are not limited to:
At least the laboratory methods and industrial methods described herein above may be used to modify the surface of a substrate so that both of the at least one cationic center and the at least one compound are connected to and available upon the modified surface to react with other chemicals or microorganisms that may come into contact with or near to the modified surface.
In some embodiments of the present disclosure, the at least one cationic center is connected to the modified surface separately from at least one compound that comprises an N-halamine precursor group that is also connected to the modified surface. These embodiments may be achieved by connecting a cationic compound to the modified surface and connecting at least one separate compound that comprises an N-halamine precursor group. The cationic compound and the at least one separate compound are different compounds both of which are connected to the modified surface.
Some embodiments of the present disclosure relate to coating formulations that comprise a combined compound and at least one further component. These coating formulations may represent examples of the embodiments of the present disclosure that relate to modified surfaces that have the at least one cationic center connected to the modified surface together with the at least one compound that comprises an N-halamine precursor group.
Some embodiments of the present disclosure relate to coating formulations that comprise a combined compound, at least one further component and a cationic compound. These coating formulations may represent an example of the embodiments of the present disclosure that relate to modified surfaces that have at least one cationic center connected to the modified surface with an N-halamine bearing compound and at least one further cationic center that is separately connected to the modified surfaces.
In embodiments of the present disclosure that relate to coating formulations, the combined compound may further comprise a coating incorporation group (CIG). In other embodiments of the present disclosure that relate to coating formulations one or both of the combined compound and the cationic compound comprise a CIG. The CIG includes one or more functional groups, or moieties, that react with the at least one further component of the coating formulation. In some examples, the coating composition may further comprise a component that acts as a crosslinking agent. In some embodiments of the present disclosure, when a CIG of a compound is present it may incorporate the one or both of the combined compound or the cationic compound into a polymer within the coating composition. For example when the CIG is:
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.
As used herein, the term “about” refers to an approximately +/−10% variation from a given value. It is to be understood that such a variation is always included in any given value provided herein, whether or not it is specifically referred to.
As used herein, the term “activity” refers to biocidal activity.
As used herein, the terms “biocide”, refers to a chemical compound, a chemical composition or a chemical formulation that can kill or render harmless one or more microbes.
As used herein, the term “cationic center”, refers to compounds in which four organic groups are linked to a single positively-charged atom (cation) of the structure XR4+ where X is one of nitrogen, phosphorus or sulfur and R is an organic group.
As used herein, the term “cationic compound” refers to a chemical compound that comprises at least one cationic center but does not include an N-halamine group.
As used herein, the terms “halo” or “halogen” by themselves or as part of another substituent, have the same meaning as commonly understood by one of ordinary skill in the art, and preferably refer to chlorine, bromine or iodine atom.
As used herein, the terms “microbe” and “microbes” refer to one or more single celled, or multi-cellular, microorganisms exemplified by at least one of bacterium, archaea, yeast or fungi.
As used herein, the term “N-halamine” refers to a functional group containing one or more nitrogen-halogen covalent bonds that is normally formed by the halogenation of imide, amide or amine groups of a compound. The presence of the halogen renders the functional group biocidal. N-halamines, as referred to in the present disclosure, include both cyclic and acyclic N-halamine functional groups.
As used herein, the term “N-halamine bearing-group” refers to a chemical compound that comprises an N-halamine precursor group or an N-halamine functional group.
As used herein, the terms “N-halamine precursor” and ““N-halamine precursor group” may be used synonymously and can be any N—H, preferably with the absence of an alpha hydrogen, as part of either a cyclic or acyclic organic structure. These functional groups may contain one or more nitrogen-hydrogen bonds that can be converted into a one or more nitrogen-halogen bonds normally formed by the halogenation of imide, amide or amine groups of the functional group. The presence of the halogen may convert an N-halamine precursor into an N-halamine, which may render the functional group biocidal.
As used herein, the term “nil” means absent and/or a direct bond.
As used herein, the term “organic linker group” includes at least the following functional groups phenyl, propane, butane, pentane, hexane, cyclic propane, cyclic butane, cyclic pentane or cyclic hexane.
As used herein “QAS” is a reference to a quaternary ammonium compound with the following structure:
As used herein, the terms “quaternary ammonium cation”, “quaternary ammonium compound”, “quaternary ammonium salt”, “QAC”, and “quat” may be used interchangeably throughout the present disclosure to refer to ammonium compounds in which four organic groups are linked to a nitrogen atom that produces a positively charged ion (cation) of the structure NR4+.
Methodology
Soft-Surface Iodiometric Titration
The modified surfaces were tested for chlorination uptake. For example, the samples of modified surfaces that were tested for mass changes were cut to 1″×1″ squares. To chlorinate the samples, 50 mL of ultrapure water was added to a 250 mL Erlenmeyer flask. A bleach solution of 72678 ppm of chlorine was then added to the flask to achieve the desired range of chlorination solution concentrations (for example 68.79 μL to achieve 100 ppm, and 1031 μL to achieve 1500 ppm). After briefly stirring the bleach into the solution, the uncoated samples were added and secured in a shaker, and then shaken for 1 hour. After an hour, the solution was drained from the flask and washed 4 times with distilled water to remove excess chlorine. The Coated Samples were then set out for an hour in open air to dry.
The concentration of active chlorine on the fabric samples was analyzed by a traditional iodometric titration method. Each 1×1 inch sample was immersed in a solution of 30 mL distilled water and 25 mL of 0.001N sodium thiosulfate standard solution. After stirring in a 100 mL beaker with a magnetic stir rod for 60 min, 2 mL of 5% acetic acid buffer solution was added. Then, with continued stirring, the solution was titrated with 0.001N iodine standard solution by monitoring millivolt changes with a redox electrode (platinum Ag/AgCl). The active chlorine concentration of the samples was then calculated from the following equation [Eq. A]:
where V1 and V2 are the volumes (mL) of the iodine solution consumed in titrations of blank sodium thiosulfate solution and that with PET sample in, respectively. N is the normality of iodine solution; and W is the weight of the samples in grams. This process was done for each final product to determine the active chlorine concentrations resulting from chlorination for both AS1 and NC2 samples.
Hard-surface Iodiometric Titration
The active-chlorine surface loading of the hard surfaces that were coated with Coating Formulations 24 to 53 were tested. Briefly, after exposing the coated substrate to chlorine the substrate was washed 4-5 times in distilled water, pat down with a towel and then allowed to air dry. The following modification of the iodiometric-titration method described above was performed:
For each sample, a solution of 25 mL 0.001N sodium thiosulfate and 30 mL of ultrapure water was prepared in a 100 mL beaker. A magnetic stirring bar and one sample was added to each of the filled beakers. Each sample was stirred for a full hour before testing. The burette was rinsed with iodine solution three times before use. The burette was then filled with iodine solution and set up in a holder over the stirring base. While the samples were in the stirring process the titration control was performed. A volumetric pipet was used to add the same volume of sodium thiosulfate solution as to what was used for the quenching of samples in a 100 mL beaker with 30 mL ultrapure water. A small stirring bar was added to the beaker as was 2 mL a 5% acetic acid buffer and then stirring was commenced.
The electrode was set up erectly in the beaker and the start button on the conductivity/pH bench top meter was pressed to electric potential mode (mV). Iodine solution was added while observing the mV change shown on the pH meter. Electric potential (mV) first decreased then increased with the addition of the iodine solution. The endpoint of this titration is the point at which the electric potential shows a sudden jump. As for this titration the electric potential change is significant, so the mV change was used as the signal of endpoint. Record the ending reading in the burette. ΔV in this process is just the V1 in equation (2).
After stirring for an hour 2 mL of the acetic acid buffer was added to the beaker of each sample, again the volume reading on the burette was noted.
From this point, each sample was titrated where ΔV in this process is the V2 in the equation B [Eq. B] which can be used to calculate the active chlorine concentration on the hard surface as follows:
where V1 and V2 are the volumes (mL) of the iodine solution consumed in titrations of the sodium thiosulfate control and the chlorinated sample respectively. N is the normality of iodine solution (eq. mol/L) and A is the surface area of the sample in cm2.
Biocidal Activity Assessment
The biocidal properties of various of the Coated Samples were examined against clinical isolates of CA-Methicillin-resistant Staphylococcus aureus (MRSA) (#40065, community-associated,) and E. coli (ATCC 25922) using a “sandwich test” modified from AATCC 100 standard testing method. Logarithmic-phase bacterial cultures were prepared by initially suspending several colonies in tap/hard water at a density equivalent to 0.5 McFarland standard of 108 colony-forming units (CFU)/mL, and then diluted 100 times to 106 CFU/mL. 20 μL of the diluted CA-MRSA and E. coli (ATCC 25922) solutions were added into 60 mL of Tryptone Soya Broth and MacConkey Broth, respectively. After 16-18 hour incubation at 37° C., the logarithmic-phase bacterial cultures were ready for use. The test fabrics were cut into square swatches (1×1 inch), one of which was put in a sterilized container. 100 μL of the logarithmic-phase bacterial suspensions (5×105-1×106 CFU/mL) was added to the swatch center and then sandwiched with another piece of swatch. The whole “sandwich” set was held in place by sterile weights. The contact times for chlorinated samples were 1, 5, 10, 30 and 60 min, while for silver coated samples were 1, 2, 4 and 6 hours. Then, the samples were quenched with 5.0 mL of sterile 0.05M sodium thiosulfate solution to remove all oxidative chlorine, followed by 2 min of vortexing and 1 min of sonication. Serial dilutions of the solutions of vortexed and sonicated bacteria were made in tap/hard water, and they were plated on Tryptone Soya Agar. The plates were incubated at 37° C. for 24 h, and viable bacterial colonies were recorded for bactericidal efficacy analysis. The percentage reduction of bacteria (%)=(A−B)/A×100; and the logarithm reduction=log (A/B) if B>0; =log (A) if B=0, where A is the number of bacteria from blank control, and B is the number of bacteria recovered from the inoculated test specimen swatches.
Commercially available N-chloramine treated fabric (CLOROX®) was also selected for assessing the biocidal activity. Due to its high absorbency and fluffy texture, it is difficult to fully extract bacterial cells from the Clorox sample in merely 5 mL of neutralizer (sodium thiosulfate) solution. Instead, the original AATCC 100 test method was used, where 1 mL of bacterial suspension (5×105-1×106 CFU/mL) were completely absorbed by 2 pieces of square swatches 1×1 inch of N-chloramine treated fabrics (Clorox). At a selected time point, bacterial cells were extracted in 100 mL of sterile 0.05M sodium thiosulfate solution, following 2 min of vortexing and 1 min of sonication. Serial dilutions were made and plated on Tryptone Soya Agar, and viable colonies were recorded after 24-hour incubation at 37° C.
MRSA is one of the most frequently isolated organisms that contributes to healthcare associated infections (HAIs). Thus, it was selected to evaluate the biocidal activity of the coated substrates 12A along with the other commercially available modified textile products described above.
Surface Charge Assessment
The method employed the use of ultraviolet visible spectroscopy. Samples were cut into 1 cm×1 cm and were placed in 1 Wt. % solution of fluorescein (sodium salt) aqueous solution for 20 minutes. The samples were then rinsed with deionized water and placed in a 0.1 Wt. % aqueous solution of cetyltrimethylammonium chloride. The samples that were placed in the solution were then shaken for 40 minutes in a wrist action shaker. After the samples were shook 10% V/V of a phosphate buffer pH 8.0 was added. The absorbance of the resulting solution was then measured. The molar extinction coefficient that was used was 11 nM-1 cm-1. Calculations that were used are based on formula sited in the following articles which are incorporated by reference into the disclosure: N. Zander et al. (2008) Charge Density Quantification of Antimicrobial Efficacy, Army Research Laboratory, the entire disclosure of which is incorporated herein by reference; and H. Murata et al. (2007) Permanent, non-leaching antibacterial surfaces-2: How high density cationic surfaces kill bacterial cells Biomaterials 28(2), the entire disclosure of which is incorporated herein by reference.
Interpenetrating Network (IPN)
The IPN method was used to modify a textile surface so that an N-halamine bearing compound and a cationic compound are separately present on the modified surface. In these examples the textile surface was poly(ethylene terephthalate) (PET). It is understood by those skilled in the art that these examples are non-limiting and that various other laboratory methods or industrial methods can be used to separately connect an N-halamine bearing compound and a cationic compound to a modified surface. Furthermore, it is understood by those skilled in the art that this example does not limit the embodiments of the present disclosure to only textiles, or PET.
Table 1 provides the biocidal activity of a modified surface that includes samples with cyclic N-halamines and QAS.
E.Coli
Table 2 provides the input ratio of five samples that were connected on to a modified surface.
Table 3 summarizes the chlorine loading of a modified surface that includes samples with an input ratio of 30/70 QAS/AzH, 50/50 QAS/AzH, 70/30 QAS/AzH and 100/0 QAS/AzH and that was exposed to 1500 ppm of chlorine for 60 minutes.
The 100/0 QAS/AzH sample included acyclic n-halamine, which may explain the observed surface bound chlorine in samples that did not include the AzH.
Table 4 summarizes chlorine loading of a modified surface that includes samples with an input ratio of 70/0 QAS/AzH, 0/30 QAS/AzH and 70/30 QAS/AzH and that was exposed to 1500 ppm of chlorine for 60 minutes.
Table 5 summarizes biocide activity of a modified surface that includes samples with an input
ratio of 30/70 QAS/AzH and 0/70 QAS/AzH following a challenge with CA-MRSA.
Table 6 summarizes biocide activity of a modified surface that includes samples with an input ratio of 30/70 QAS/AzH and 0/70 QAS/AzH following a challenge with MDR-E. coli.
Table 7 summarizes biocide activity of a modified surface that includes samples with an input ratio of 30/70 QAS/AzH, 0/70 QAS/AzH and 70/30 QAS/AzH following a challenge with CA-MRSA.
Table 8 summarizes biocide activity of a modified surface that includes samples with an input ratio of 30/70 QAS/AzH, 50/50 QAS/AzH and 70/30 QAS/AzH following a challenge with MDR-E. coli.
Table 9 summarizes the concentration of QAS that are immobilized on a modified surface and the corresponding charge density when the modified surface includes samples with varying amounts of QAS.
Table 10 summarizes the ratio of QAS to N-chloramine on a modified surface that includes samples with varying amounts of QAS.
All of the data presented in the previous tables were obtained from modified surfaces that were prepared according to the method shown in
Table 12 summarizes the amount of chlorine upon a modified surface that includes the samples that have an input ratio of 50/50 QAS/AzH and 0/50 QAS/AzH following a 60 minute exposure to 100 ppm of chlorine.
Table 13 summarizes the concentration of QAS upon a modified surface that includes the samples that have an input ratio of 30/70 QAS/AzH; 50/50 QAS/AzH and 70/30 QAS/AzH.
Table 14 summarizes the calculated ratios of QAS to N-chloramines upon a modified surface with the samples that have an input ratio of 30/70 QAS/AzH; 50/50 QAS/AzH and 70/30 QAS/AzH.
Table 15 summarizes the biocide activity of a modified surface that includes the samples that have an input ratio of 30/70 QAS/AzH; 50/50 QAS/AzH and 70/30 QAS/AzH.
The data presented in the previous Tables 12 to 15 were obtained from modified surfaces that were prepared according to the method shown in
Soft Substrates—Direct Roll Coating
Further coating formulations were designed for soft substrates. The following further coating formulations may be suitable for coating a textile substrate, such as polycotton. Table 16 below provides a summary of chemical components used in the coating formulations for soft substrates.
Table 16.1 provides the mass and % of total mass for the chemical components used to produce the Coating Formulation 1.
Table 17 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 2.
Table 18 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 3.
Table 19 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 4.
Table 20 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 5.
Table 21 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 6.
Table 23 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 8.
Table 24 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 9.
Table 24.1 provides the chlorine titration results of virgin textile substrate exposed to 100 ppm for 60 mins.
Table 25 provides the chlorine titration results. Coated samples are chlorinated at 100 ppm and shaken for five minutes.
Table 26 provides the chlorine titration results. Coated samples are chlorinated at 100 ppm and shaken for one hour.
Table 28 represents surfaces exposed to gram positive MRSA 40065 bacteria over various contact times. The unchlorinated samples were kept in 37° C. in an incubator for 24 hours. The test method used was modified AATC 100 in 5% TBS.
Table 29 provides the chlorine titration results. Coated samples are chlorinated at 100 ppm and shaken for one hour.
Table 30 represents surfaces exposed to gram positive MRSA 40065 bacteria over various contact times. The unchlorinated samples were kept in 37° C. in an incubator for 24 hours. The test method used was modified AATC 100 in 5% TBS.
Table 31 provides the chlorine titration results. Coated samples are chlorinated at 100 ppm and shaken for one hour.
Table 32 provides the surface charge density for the formulation 8.
Table 33 represents surfaces exposed to gram positive MRSA 40065 bacteria over various contact times. The unchlorinated samples were kept in 37° C. in an incubator for 24 hours. The test method used was modified MRSA in 5% TBS.
Table 34 represents formulation 7 of the logarithmic Biocidal activity of gram positive CA-MRSA 40065 bacteria at various contact times. The unchlorinated samples were kept in 37° C. in an incubator for 24 hours. The test method used was modified MRSA in 5% TBS.
Table 35 represents formulation 8 surfaces exposed to gram positive MRSA 40065 bacteria over various contact times. The unchlorinated samples were kept in 37° C. in an incubator for 24 hours. The test method used was modified MRSA in 5% TBS.
Table 36 represents formulation 9 surfaces exposed to gram positive MRSA 40065 bacteria over various contact times. The unchlorinated samples were kept in 37° C. in an incubator for 24 hours. The test method used was modified MRSA in 5% TBS.
Hard Surfaces—Direct Roll Coating
Hard-surface coating formulations were designed that each comprise at least one N-halamine bearing compound and a cationic center. These further coating compounds may be suitable for coating hard substrates, such as hard polymers, metals and metal alloys.
Table 37 summarizes the chemical components used to make the hard-surface coating formulations.
Table 37.1 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 10.
Table 38 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 11. The ratio of the positive charge to the hydantoin in this formulation is 1.12:1.
Table 39 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 12. The ratio of the positive charge to the hydantoin in this formulation is 1.574:1.
Table 40 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 13. The ratio of the positive charge to the hydantoin in this formulation is 1.1249:1.
Table 41 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 14. The ratio of the positive charge to the hydantoin in this formulation is 1.4994:1.
Table 42 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 15. The ratio of the positive charge to the hydantoin in this formulation is 2.9988:1.
Table 43 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 16. The ratio of the positive charge to the hydantoin in this formulation is 1.2507:1.
Table 44 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 17. The ratio of the positive charge to the hydantoin in this formulation is 2:1.
Table 45 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 18. The ratio of the positive charge to the hydantoin in this formulation is 2:1.
Table 46 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 19.
Table 47 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 20. The ratio of the positive charge to the hydantoin in this formulation is 2.99:1.
Table 48 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 21. The ratio of the positive charge to the hydantoin in this formulation is 3.99:1.
Table 49 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 22. The ratio of the positive charge to the hydantoin in this formulation is 9.99:1.
Table 50 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 23.
Table 50.1 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 24.
Table 50.2 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 25.
Table 50.3 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 26.
Table 50.4 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 26.
Table 50.5 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 26.
Table 50.6 provides the mass and % of total mass for the chemical components used to produce a Coating Formulation 26.
Table 51 shows the active surface chlorine-loading on modified surfaces that include the Coating Formulations 12 and 16.
Table 52 represents surfaces exposed to gram positive MRSA 40065 bacteria over various contact times.
Table 53 The quantification of the positive charge on the surface using a benzoic acid dye analytical technique in 100 mL of water and DMSO.
Table 53.1 The quantification of the positive charge on the surface using a benzoic acid dye analytical technique in 200 mL of water and DMSO.
Table 55 provides the chlorine titration results. Coated samples are chlorinated at 200 ppm and shaken for various time increments at a ratio of 2:1 cationic center to NH.
Table 56 provides the chlorine titration results. Coated samples are chlorinated at 100 ppm and shaken for various time increments at a ratio of 2:1 cationic center to NH.
Table 57 provides the chlorine titration results. Coated samples are chlorinated at 200 ppm and shaken for 10 min. The ratio of the positive charge to piperidinol in Coating Formulation 22 is 10.0:1 and Coating Formulation 28 is 4:1.
Table 58 The quantification of the positive charge on the surface using a benzoic acid dye analytical technique, ratio of the positive charge to piperidinol in Coating Formulations 23, 17 and 18 is 2:1.
Table 59 The quantification of the positive charge on the surface using a benzoic acid dye analytical technique, the ratio of the positive charge to piperidinol in these coating formulations are shown in round parenthesis.
Table 60 represents surfaces exposed to E. coli bacteria over various contact times.
E. coli Inoculum 5.42-log
Table 61 represents surfaces exposed to E. coli bacteria over various contact times.
E. coli Incolum
Table 62 represents surfaces exposed to E. coli bacteria over various contact times.
E. coli Incolum
Table 63 provides the chlorine titration results. Coated samples are chlorinated at 100 ppm and shaken for one hour.
Table 64 provides the chlorine titration results. Coated samples are chlorinated at 100 ppm and shaken for one hour.
Table 65 shows the calculated ration of positive N atoms to molecules with N—H binding sites on N-halamine precursor bearing groups in the Coating Formulations provided.
Table 66 shows the calculated ration of positive N atoms to molecules with N—H binding sites on N-halamine precursor bearing groups in the Coating Formulations provided.
Accordingly, based on the foregoing, an article comprising a compound as described herein is contemplated. Monomers or precursors and polymers of the monomers, precursors and compounds are also contemplated, and articles prepared from monomers, precursors and polymers thereof are also contemplated.
Methods of inactivating a microorganism or of inhibiting microbial growth are also contemplated. A method comprising contacting the microorganism or a surface on which a microorganism resides with a compound, monomer of a compound, or an article coated with a compound or coating formulation as described herein is contemplated. The microorganism can be a bacteria, a virus or a fungus.
Other embodiments of the present disclosure relate to a method whereby a compound or an article comprising a compound described herein is exposed to a source of chlorine, bromine or iodine. In another embodiment, a method is contemplated, wherein the method comprises providing a compound or an article comprising a compound described herein and exposing the compound or article comprising the compound to a source of chlorine, bromine or iodine. The method finds use in rendering a surface aseptic or essentially aseptic. The method also finds use in recharging biocidal activity of a compound or article coated with a compound or coating formulation as described herein. Further embodiments of the present disclosure relate to methods of modulating the ratio of positive charge to the number of N—H binding sites that are connected upon a modified surface.
| Number | Date | Country | Kind |
|---|---|---|---|
| PCT/CA2016/051201 | Oct 2016 | WO | international |
This application claims the benefit of U.S. Provisional Application No. 62/255,076, filed Nov. 13, 2015, and of U.S. Provisional Application No. 62/287,729, filed Jan. 27, 2016, and of U.S. Provisional Application No. 62/362,460, filed Jul. 14, 2016, and of U.S. Provisional Application No. 62/393,757, filed Sep. 13, 2016, and of Patent Cooperation Treaty Patent Application No. PCT/CA2016/051201 filed on Oct. 14, 2016, the entire disclosures of which are incorporated herein by reference.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/CA2016/051311 | 11/10/2016 | WO | 00 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2017/079841 | 5/18/2017 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 20190151224 | Khatun | May 2019 | A1 |
| Number | Date | Country |
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| 2618732 | Oct 2007 | CA |
| 2741660 | May 2010 | CA |
| 2869634 | Nov 2013 | CA |
| 2869634 | Nov 2013 | CA |
| 2006135406 | Dec 2006 | WO |
| 2008156636 | Dec 2008 | WO |
| Entry |
|---|
| Cerkez et al., Langmuir 2011. 27, 4091-4097. |
| International Search Report issued in corresponding Application No. PCT/CA2016/051311, dated Dec. 22, 2016 (4 pages). |
| Written Opinion issued in corresponding Application No. PCT/CA2016/051311, dated Dec. 22, 2016 (6 pages). |
| Luis J. Bastarrachea et al.; “Antimicrobial Coatings with Dual Cationic and N-Halamine Character: Characterization and Biocidal Efficacy”; Journal of Agricultural and Food Chemistry; vol. 63; pp. 4243-4251; 2015 (9 pages). |
| Number | Date | Country | |
|---|---|---|---|
| 20180327627 A1 | Nov 2018 | US |
| Number | Date | Country | |
|---|---|---|---|
| 62393757 | Sep 2016 | US | |
| 62362460 | Jul 2016 | US | |
| 62287729 | Jan 2016 | US | |
| 62255076 | Nov 2015 | US |
