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    • 专利摘要:
    Provided is a method of inhibiting microbial growth, comprising introducing at least one dihaloformaloxime carbamate into, or on, a habitat where the microorganisms attack in an antimicrobial effective amount.
    公开号:KR19980018695A
    申请号:KR1019970038877
    申请日:1997-08-14
    公开日:1998-06-05
    发明作者:아담 치-튱 휴슈；배리 클리포드 랜쥐；제민 챨스 휴
    申请人:톰앤드；롬 앤드 하스 캄파니；
    IPC主号:
    专利说明:

    Dihaloformaldoxime carbamate antimicrobial agent
    The present invention relates to a method for inhibiting the growth of microorganisms. More particularly, the present invention relates to the use of certain dihaloformaldoxim carbamates as antimicrobial agents.
    Antimicrobials are used commercially to prevent the growth of microorganisms in cooling towers, metalworking fluid systems, paints and other habitats.
    Antimicrobial agents currently available include mixtures of 5-chloro-2-methyl-3-isothiazolone and 2-methyl-3-isothiazolone. While these isothiazolones are very effective in preventing microbial growth, there are problems of slow sterilization and instability under certain conditions. Nitrate is an effective stabilizer for 3-isothiazolones, but can cause problems, such as latex coagulation and salt accumulation in closed systems where the level of salt usually required is enclosed.
    There is therefore a continuing need for stable antimicrobial agents that are stable, have no high salt content, have low levels of use, can be sterilized at high rates, degenerate rapidly when used, and are harmless to the environment when used.
    US Pat. No. 3,553,264 (Addor) discloses certain dihaloformaldoxime carbamates, methods for their preparation, and use as post-germination herbicides. The patent also teaches the use of the dihaloformaldoxime carbamate as an intermediate in the preparation of pesticides. However, the patent does not suggest the use of such compounds as antimicrobial agents.
    The present invention
    A method of inhibiting growth of a microorganism is provided, the method comprising introducing at least one antimicrobial agent into an habitat that is attacked by the microorganism in an antimicrobial effective amount,
    Wherein the antibiotic has the formula
    Provided that X, Y are independently selected from Br, Cl or I;
    R is (C 1 -C 8 ) alkyl, aryl or substituted aryl);
    The antimicrobial agent is applied at low levels of use, has a fast sterilization rate, deteriorates quickly when used, and does not harm the environment when used.
    Hereinafter, the present invention will be described in detail.
    As used herein, the term antimicrobial agent refers to both compounds that can inhibit microbial growth (preservatives) and compounds that can reduce microbial concentrations (microbicides) within a given system. The term antimicrobial activity refers to the activity of an antimicrobial agent that eliminates, inhibits or prevents the growth of microorganisms. The terms microbial organisms, microbes and microorganisms are used interchangeably, but are not limited thereto. Microorganisms such as fungi, bacteria and algae. The following abbreviations are used throughout this specification: L = liter; mL = milliliters; g = gram; mol = mol; mmol = millimoles; wt% = wt%; mp = melting point. The antimicrobial agent is effective for microorganisms including but not limited to fungi, bacteria and algae.
    Compounds useful as antimicrobial agents in the present invention are those of Formula 1 above. Preferred compounds of the present invention are those wherein X and Y in the formula (1) is bromine. Particularly preferred compounds of the present invention include the compounds listed in the table below.
    Compound number Compound name
    1 N-methyl-dibromoformaldoxime carbamate
    2 N- (2-chloroethyl) -dibromoformaldoxime carbamate
    3 N- (4-chlorophenyl) -dibromoformaldoxime carbamate
    4 N- (2,4-dichlorophenyl) -dibromoformaldoxime carbamate
    5 N-ethyl-dibromoformaldoxime carbamate
    6 N- (n-butyl) -dibromoformaldoxime carbamate
    7 N- (n-octyl) -dibromoformaldoxime carbamate
    8 N- (n-hexyl) -dibromoformaldoxime carbamate
    9 N- (4-methylphenyl) -dibromoformaldoxime carbamate
    Alkyl as used herein refers to straight or branched chain (C 1 -C 12 ) alkyl, and substituted aryl means an aryl group in which one or more hydrogens are replaced with another substituent. Examples of suitable substituents include (C 1 -C 3 ) alkyl, (C 1 -C 3 ) alkoxy, hydroxy, nitro, halo, cyano, (C 1 -C 3 ) alkylthio and mercapto. Examples of substituted phenyl groups include 4-methylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methoxyphenyl and 4-methoxyphenyl.
    In the present invention, dibromoformaldoxim carbamate is generally used in the presence of a catalyst such as dibutyltin dilaurate in methylene chloride with dibromoformaldoxime in the presence of an alkyl or aryl isocyanate at 0-25 ° C. Synthesized by treatment at The reaction time is 2-48 hours depending on the reactivity of the isocyanate. For example, the synthesis of N-butyl dibromoformaldoxim carbamate can be represented by the following reaction structure.
    The preparation of the starting materials, dibromoformaldoxime and dichloroformaldoxime, is known from the literature. For example, the synthesis of dibromoformaldoxim can be found in Tetrahedron Letters , 25 : 487 (1984).
    Antimicrobial agents of the present invention can be used to inhibit the growth of microorganisms by introducing at least one or more of the above agents into, or into, a habitat where the microorganisms attack in an antimicrobial effective amount. Preferred habitats include, but are not limited to, cooling towers; Air washer; Boiler; Mineral slurry; Wastewater treatment; Decorative fountains; Reverse osmosis filtration; Ultrafiltration; Ballast water; Evaporative condenser; heat transmitter; Pulp and paper processing oils; Plastic; Emulsions and dispersants; Paint; Latex; Coatings such as varnishes; Building materials such as mastic, coke and sealant; Construction adhesives, such as ceramic adhesives, carpet backing adhesives, and laminating adhesives; Industrial or household adhesives; Photographic chemicals; Printing fluids; Household products such as bathroom disinfectants or hygiene; Cosmetics and toiletries; shampoo; soap; Detergent; Cold sterilant, hard surface disinfectant; Floor polishes; Laundry rinse water; Metal working oil; Conveyor lubricants; Hydraulic fluid; Leather and leather products; fiber; Textile products; Wood and wood products such as plywood, chipboard, flakeboard, laminated beam, oriented strandboard, hardboard and particleboard; Petroleum processing oils; fuel; Oilfield fluids such as injection water, fracture fluids and drilling muds; Agricultural auxiliary preservatives; Surfactant preservatives; Medical device; Diagnostic reagent preservatives; Food preservatives such as plastic or paper food wraps; Pools; and spas. Preferred habitats include cooling water towers; Air washer; Boiler; Mineral slurry; Wastewater treatment; Decorative fountains; Reverse osmosis filtration; Ultrafiltration; Ballast water; Evaporative condenser; heat transmitter; Pulp and paper processing oils; plastic; Emulsions and dispersants; Paint; Latex; And coating agents.
    The amount of antimicrobial agent of the present invention preferred for inhibiting the growth of microorganisms depends on the habitat to be protected, but is generally 0.05-10,000 ppm based on the volume of the habitat to be protected. Preference is given to using at 0.1-5000 ppm. For example, cooling water towers or habitats such as pulp and paper processing oil require 0.1-250 ppm of the compounds of the present invention to inhibit the growth of microorganisms. In the cooling water tower or pulp and paper processing oil, the preferred amount of use is 0.1-50 ppm. Other habitats, such as building materials, dielectric fluids or emulsions, require 0.5-5000 ppm of the compounds of the present invention to inhibit microbial growth, while habitats such as fungicides or hygiene may require up to 10,000 ppm.
    It is known in the art that the performance of an antimicrobial agent can be enhanced by combining with one or more other antimicrobial agents. Thus other known antimicrobial agents can be advantageously combined with the antimicrobial agents of the present invention. Compounds of the invention include methylenebis (thiocyanate); 2-n-octyl-4-isothiazolin-3-one; 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one; 5-chloro-2-methyl-4-isothiazolin-3-one; 2-methyl-4-isothiazolin-3-one; 1,2-benzisothiazolin-3-one; And isothiazolones such as 2-methyl-4,5-trimethylene-4-isothiazolin-3-one; 3-iodopropargyl-N-butylcarbamate; Methyl benzimidazol-2-ylcarbamate; Imidazolidinyl urea; Diazolidinyl urea; N '-[3,4-dichlorophenyl] -N, N-dimethylurea; 3,4,4'-trichlorocarvanide; Dimethyl dithiocarbamate; And carbamate, such as disodium ethylene bisdithiocarbamate; Zinc 2-pyridineethol-1-oxide; Sodium 2-pyridineethol-1-oxide; 10,10'-oxybisphenoxyarcin; N-trichloromethyl thioptalimide; 5-oxo-3,4-dichloro-1,2-dithiol; 3-bromo-1-chloro-5,5-dimethylhydantoin; 4,4-dimethyl-1,3-dimethylolhydantoin; 2- (thiocyanomethylthio) benzothiazole; 2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine; Iodopolyvinylpyrrolidone; 3,5-dimethyl-1H-pyrazole-1-methanol; 1- (2-hydroxyethyl) -2-octadecylimidazoline; 4- (2-nitrobutyl) morpholine; Triazine; N, N'-methylenebis (5-methyl-1,3-oxazolidine); 2,2'-oxybis (4,4,6-trimethyl-1,3,2-dioxaborinane); 2,2 '-(1-methyltrimethylenedioxy) bis (4-ethyl-1,3,2-dioxaborinane); Hexahydro-1,3,5-tris (2-hydroxyethyl) -s-triazine; 4,4-dimethyloxazolidine; 3,4,4-trimethyloxazolidine; 4,4- (2-ethyl-nitrotrimethylene) dimorpholine; 2-methylthio-4-t-butylamino-6-cyclopropylamino-s-triazine; 2,3,5,6-tetrachloro-4- (methylsulfonyl) pyridine; α- [2- (4-chlorophenyl) ethyl] -α- (1,1-dimethylethyl) -1H-1,2,4-triazolyl- (1) -ethanol; 1-[(2- (2 ', 4'-dichlorophenyl) -4-propyl-1,3-dioxolan-2-yl-methyl] -1H-1,2,4-triazole; didecyldimethylammonium Chloride; copper-8-hydroxyquinoline; 1- [2- (2,4-dichlorophenyl) -1,3-dioxalan-2-yl-methyl] -1 H-1,2,4-triazole; 2 -(4-thiazolyl) -benzimidazole; 3,5-dimethyl-1,3,5-thiadiazine-2-thione; 2-chloro-4,6-bis (ethylamino) -1,3, 5-triazine; 2-chloro-4-ethylamino-6-tert-butylamino-1,3,5-triazine; 1- (3-chloroallyl) -3,5,7-triaza-1- Azoniaadamantane chloride; copper naphthenate; 5-hydroxymethoxymethyl-1-aza-3,7-dioxabicyclo [3.3.0] octane; 5-hydroxymethyl-1-aza-3, 7-dioxabicyclo [3.3.0] octane; 7-ethyl-1,5-dioxa-3-azabicyclooctane; cetylpyridinium chloride; 3-bromo-1-chloro-5-dimethyl-5- Ethyl hydantoindecyl-di- (aminoethyl) glycine and 5-hydroxypoly- [methyleneoxyethyl] methyl-1-aza-3,7-dioxa Heterocyclic compounds such as cyclo [3.3.0] octane; hydrogen peroxide; t-butyl hydrogen peroxide; cumene hydroperoxide; sodium or calcium hypochlorite; sodium or calcium hypobromite; dichloroisocyanuric acid; trichloroisocyanuric acid ; Peroxyacetic acid; ozone; chlorine; bromine; chlorine dioxide; potassium peroxymonosulfone; percarbonate; sodium perborate; bromine; and oxides such as bromine chloride; (E, E) -2,4-hexadienoic acid Benzoic acid sodium or calcium propionate ethylenediaminetetraacetic acid disodium salt; and sodium hydroxymethylylglycinate; benzyl ester of 4-hydroxybenzoic acid; (C 1 -C 4 ) of 4-hydroxybenzoic acid; Alkyl esters; (C 1 -C 4 ) alkyl esters of 4-hydroxybenzoic acid sodium salt; dimethylamides of tall oil fatty acids; and 2,2-dibromo-3-nitrilopropionamide Carboxylic acids and derivatives thereof such as 1- (alkylamino) -3-amino-propane; 2-bromo-2-nitro-1,3-propanediol; phenoxyethanol; benzyl alcohol; 2-hydroxymethylaminoethanol; n-2-hydroxypropylaminomethanol; 2-hydroxypropyl methanethiosulfonate; p-nitrophenol; And alcohols and amines such as 4-chloro-3,5-dimethylphenol; n-alkyl dimethyl benzylammonium chloride; Cetyltrimethylammonium chloride; Didecyldimethylammonium chloride; Poly (hexamethylene biguanide) hydrochloride; Poly [oxyethylene (dimethylimminio) ethylene (dimethylimminio) ethylene dichloride; Alkyl dimethyl dichlorobenzylammonium chloride; Dodecylguanidine hydrochloride; 2- (decylthio) ethanamine hydrochloride; Quaternary ammonium compounds; Tetrakis (hydroxymethyl) phosphonium chloride; Ammonium and phosphonium salts such as tetrakis (hydroxymethyl) phosphonium sulfate; Pentane-1,5-dial; 1,2-benzenedicarboxaldehyde; Formaldehyde; 2-bromo-4'-hydroxyacetophenone; Tris (hydroxymethyl) nitromethane; And aldehydes, ketones and formaldehyde releasers such as 5-bromo-5-nitro-1,3-dioxane; 2,4,5,6-tetrachloroisophthalonitrile; 2,4,4'-trichloro-2'-hydroxydiphenyl ether; 2,2'-dihydroxy-5,5'-dichloro-diphenylmethane; And halogenated aromatic compounds such as 1,6-di- (4'-chlorophenyldiguanide) -hexane; 1,2-dibromo-2,4-dicyanobutane; Diiodomethyl-p-tolylsulfone; Dibromonitroethane; Halogenated aliphatic compounds such as hexachlorodimethylsulfone; β-bromo-β-nitrostyrene; 1,4-bis (bromoacetoxy) -2-butene; Terpenes; And alkenes such as limonene; Bismuth; Copper; silver; Copper amine complexes; Monocopper nitrate; Borate salts; Zinc oxide; Sodium bromide; Ammonium bromide; Disodium octaborate tetrahydrate; Tributyltin oxide; And inorganic compounds such as chromated copper arsenate; Cellulase; α-amylase; Protease; Polysaccharidases; Enzymes such as levan hydrolases; And surfactants such as alkyl aryl esters, polyethoxylated alcohols, polyoxyethylated ethers, phosphate esters, sulfonates, sulfonated fatty acid materials, sulfosuccinates and dodecylbenzene sulfonic acids; .
    Preferred known antimicrobial agents which are combined with the antimicrobial agents of the present invention include methylenebis (thiocyanate); 5-chloro-2-methyl-4-isothiazolin-3-one; 2-methyl-4-isothiazolin-3-one; 2-n-octyl-4-isothiazolin-3-one; 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one; 1,2-benzisothiazolin-3-one; Zinc 2-pyridinethiol-1-oxide; Sodium 2-pyridinethiol-1-oxide; N '-[3,4-dichlorophenyl] -N, N-dimethylurea; 3-iodopropargyl-N-butylcarbamate; 10,10'-oxybisphenoxyarcin; 2- (thiocyanomethylthio) benzothiazole; 3-bromo-1-chloro-5,5-dimethylhydantoin; 2,2-dibromo-3-nitrilopropionamide; pentane-1,5-dial; And 2-bromo-2-nitro-1,3-propanediol.
    Compounds of the present invention also include ultraviolet light; Ion radiation; Copper electrodes; Non-chemical methods of microbial control such as silver electrodes; And enzymes such as cellulase, α-amylase, protease, polysaccharides and levan hydrolases.
    If one of the antimicrobial agents of the present invention is combined with a second antimicrobial agent, the weight ratio of the first antimicrobial agent to the second antimicrobial agent is 99: 1 to 1:99, preferably 75:25 to 25:75. The total amount of mixed antimicrobial agent necessary to inhibit or prevent the growth of microorganisms is generally 0.05-10,000 ppm based on the volume of the habitat to be protected.
    The antimicrobial agents of the present invention may be added directly to the habitat to be protected or as a combination. The antimicrobial agents of the invention can be formulated in a variety of liquid or solid formulations. The specific form (ie, solid or liquid) and composition of the combination used will depend on the habitat to be protected and the nature of the formulation to be obtained. Solid formulations would be preferred if, for example, splash hazards were taken into account or controlled release is desired. Liquid formulations will be desirable if the formulation is to be metered into the habitat over time. Solid formulations are particularly useful in habitats such as cooling towers, latexes and plastics. Liquid formulations include paints, cosmetics; Household washer; And especially for habitats such as water treatment applications.
    In general, the antimicrobial agents of the present invention may be formulated in liquid form by dissolving the antimicrobial agent in the carrier. Suitable carriers include water, organic solvents or mixtures thereof. Any organic solvent is suitable as long as it is compatible with the end use and does not destabilize the antimicrobial agent. Suitable organic solvents include, but are not limited to, aliphatic and aromatic hydrocarbons such as mixtures of xylenes and alkylbenzenes; Halogenated aliphatic and aromatic hydrocarbons such as ethylene dichloride and monochlorobenzene; Alcohols such as monohydro, dihydro and polyhydro alcohols; Aldehydes; Ketones such as acetone, methyl ethyl ketone and methyl iso-butyl ketone; ether; Glycol ethers; Glycol ether acetates; Saturated and unsaturated fatty acids having at least 4 carbon atoms; Esters such as ethyl acetate, butyl acetate, glycol esters and phthalate esters, and phenols; Preferred organic solvents are glycol ethers; Glycol ether acetates; Aliphatic and aromatic hydrocarbons and alcohols.
    Aqueous formulations of the antimicrobial agents of the invention include dispersions such as polymer dispersions; Emulsions; Emulsion concentrates; Microemulsions; And microemulsion concentrates. The dispersions, emulsions and microemulsions can have an oil continuous phase or a water continuous phase. Aqueous formulations typically contain 0.001-50% by weight of the antimicrobial agent of the present invention, up to 99% by weight of organic solvents, 0.5-55% by weight of surfactants, up to 15% by weight of aids, and up to 95% by weight of water. Suitable surfactants include anionics such as alkyllauryl sulfonate salts and fatty alcohol alcohol ethoxylate sulfates; Cationic; Nonionics such as ethylene oxide-propylene oxide copolymers; And amphoteric. Typical auxiliaries suitable for use in aqueous formulations include, but are not limited to, thickening agents, cryoprotectants and antifoaming agents.
    Suitable solid formulations of the antimicrobial agents of the present invention include, but are not limited to, polymer encapsulants such as prepared by interfacial condensation, coacervation, in-situ polymerization and physical methods; Inclusion complexes such as clathrates; Liposomes; Matrix mixtures such as granular, dispersible granular and wettable powders; And ion exchange resins. Polymer capsules can be made in a core cell or monolithic structure. Suitable polymer capsules include but are not limited to polyurea, polyamide, polyester, urea-formaldehyde, melamine-formaldehyde, polyacrylic acid and esters thereof, phenol-formaldehyde and acetoacetate.
    Inclusion complexes can be prepared by incorporating the antimicrobial agents of the invention in a host molecule. Suitable parent molecules include, but are not limited to, α-cyclodextrin; β-cyclodextrin; γ-cyclodextrin; Cyclodextrin derivatives such as methyl-β-cyclodextrin; Crown ethers; Urea; Hydroquinone; Dichlorophenone; Hydroxybenzophenone; And 1,1,2,2-tetrakis (4-hydroxyphenyl) ethane. The inclusion complexes can be used as solid compositions and can be absorbed on solid carriers or dispersed in non-reactive solvents. Inclusion complexes are useful for water treatment, metalworking and paint habitats.
    Liposomes can be prepared by dissolving lipids such as the antimicrobial agent of the present invention and phospholipid in a suitable solvent such as chloroform. The solvent is removed, the buffer is added and the composition is stirred to produce the desired particle size. The liposome may be a multilamellar, a single thin layer, and has a large or small particle size. Liposomes are useful in solvent based paints and cosmetic habitats.
    The matrix mixture can be prepared by absorbing the antimicrobial agent of the invention with the addition of appropriate additives on a solid carrier to produce granular, wettable powder and dispersible granular. The matrix mixture can be used on its own or further produced into pellets, tablets or briquettes by any conventional means.
    Granular 1-60% by weight of the antimicrobial agent of the present invention; 30-98% by weight of absorbent carriers such as diatomaceous earth, water soluble solids, magnetic particles, or molten minerals such as silica, titania and zinc oxide; And 1-10% by weight of adjuvants; typically. Wettable powders comprise 1-60% by weight of the antimicrobial agent of the present invention; 1-5% by weight wetting agent; 1-20% by weight of dispersant; 10-95% by weight of absorbent carriers such as molten inorganic or clay; And up to 10% by weight of adjuvants typically. Dispersible granules comprise 1-60% by weight of the antimicrobial agent of the present invention; 30-95% by weight of absorbent carriers such as molten minerals or clays; 5-40% by weight of dispersant; Up to 10% by weight of surfactant; And up to 15% by weight of adjuvants typically. The dispersible granules can further be extruded or dried to produce granules.
    The following examples further illustrate the invention and do not limit the scope of the invention.
    Example 1
    Preparation of N- (n-butyl) -dibromoformaldoxim carbamate
    6.9 g (0.058 mol) of n-butyl isocyanate is added to the dibromoformaldoxime solution (11.8 g, 0.058 mol) dissolved in methylene chloride (20 ml) in an ice bath under magnetic stirring, followed by dibutyltin dilau The catalyst amount (8 drops) of the rate was added. The reaction mixture was further stirred for 16 hours at room temperature. The mixture was then washed with sodium bicarbonate dilution (2 x 50 ml), water (5 x 25 ml) and brine (50 ml). The organic layer was dried over MgSO 4 and filtered. The filtrate was concentrated in vacuo to yield 4.9 g of a yellow oil. By column chromatography eluted with hexane: ethyl acetate (9; 1) using silica gel, 12.1 g (69% yield) of pure yellow oils were obtained.
    Elemental analysis for C 6 H 10 Br 2 N 2 O 2 is as follows. Calculated value: C = 23.86%; H = 3.34%; N = 9.28%; Br = 52.92%. Observed: C = 24.07%; H = 3.47%; N = 9.31%; Br = 52.85%.
    Example 2
    Preparation of N- (4-methylphenyl) -dibromoformaldoxime carbamate
    Dibromoformaldoxim solution (2 g, 9.86 mol) dissolved in methylene chloride (20 ml) in an ice bath was added with 4-methylphenyl isocyanate (1.6 g, 12 mmol) with magnetic stirring under nitrogen and dibutyltin dilaurate A catalytic amount (5 drops) was added. The reaction mixture was further stirred for 16 hours at room temperature. The reaction mixture was washed with water (3 x 50 ml) and brine. The organic layer was dried over MgSO 4 and filtered. The filtrate was concentrated in vacuo and eluted with hexanes: ethyl acetate (8: 1) on a silica gel column to give the crude product, an off-white solid, 1.7 g (51% yield), mp = 120-124 ° C.
    Elemental analysis for C 9 H 8 Br 2 N 2 O 2 is as follows. Calculated value: C = 32.10%; H = 2.40%; N = 8.34%; Br = 47.57%. Observed: C = 33.76%; H = 2.35%; N = 8.55%; Br = 50.12%.
    Example 3
    efficacy
    The effect of anionic surfactants on the spectrum of antimicrobial activity and antimicrobial activity of the antimicrobial agents useful in the present invention was measured in the minimum inhibitory concentration (MIC) test. MIC is determined by doubling the compound in Minimal Salts Media (M9G), Trypticase Soy Broth (TSB) or Triticase Soy Broth and Anionic Surfactant (TSBA). It was. The compound was tested against Aspergillus niger , Rhodotorula rubra , Escherichia coli and Pseudomonas aeruginosa .
    The MIC test results are shown below.
    compoundE.ColiM9GE.ColiTSBP.aeruginosaTSBA.nigerTSBR.RubraTSBE.ColiTSBA 3<46363＞ 50＞ 5063 6<425063＞ 50＞ 5063 7<463＞ 5005012.5125 8<463125＞ 502532 9<43216<0.83.232
    The results show that compounds 3,6,7,8 and 9 have a surprising effect on the control of microorganisms in, on or on the habitat.
    Example 4
    Sterilization rate
    Sterilization rates for the various compounds of the present invention were determined according to the following procedure.
    5 g of 40% α olefin sulfonate (AOS) was weighed into a 100 ml flask, 35 ml of deionized water was added and the solution was swirled to prepare a 5% AOS solution. The solution was then filter sterilized.
    TSB medium was prepared by weighing 30 g of trypticase broth (TSB) in a 2 L flask, adding 1 L of deionized water and turning the flask until TSB was completely dissolved. The medium was then pressurized at 121 ° C. for 20 minutes.
    To a 250 ml flask was added 1 ml of sterile 5% AOS and 100 ml of sterile TSB, followed by turning the solution to prepare a TSB + 0.05% AOS solution.
    A nutrient stock solution was prepared by weighing 5.28 g ammonium nitrate, 2.08 g anhydrous potassium phosphate, 4.62 g dextrose, 21.50 g sodium carbonate and 40.20 g potassium sulfate. The total volume was adjusted to a maximum of 1 L with water and the flask was pivoted until all solids dissolved. The solution was then filter sterilized and stored at room temperature.
    In a 2-liter flask, 59.36 g of calcium chloride (dihydrate), 45.02 g of magnesium chloride (hexahydrate), 0.18 g of ferric oxide (hexahydrate), 0.06 g of copper chloride (dihydrate), and 0.24 g of sodium ethylenediaminetetraacetic acid were weighed and weighed. A mother stock was prepared. The total volume was adjusted up to 1 L with water. The solution was filter sterilized and stored at room temperature.
    In a 2 L flask, 238.5 g deionized water, 125.0 g 45% aqueous calcium hydroxide solution, 23.0 g 50% aqueous sodium tolyltriazole solution, 63.5 g 42-44% acrylic polymer aqueous solution and about 50% 2-phosphono-1, A concentrated 2 / 4-butanetricarboxylic acid aqueous solution was weighed to prepare a concentrated corrosion / scale inhibitor mother liquor. The flask was pivoted until all solids dissolved and the solution was filter sterilized and stored at room temperature.
    The concentrated corrosion / scale inhibitor mother liquor was used to prepare by adding 9.20 ml of concentrated corrosion / scale inhibitor mother liquor to a 2 L flask, adjusting the volume up to 1 L with water and turning. The resulting corrosion / scale inhibitor mother liquor was filter sterilized and stored at room temperature.
    Synthetic cooling tower water (SCW) was prepared by adding 900 ml of deionized water and 10.88 ml of nutrient mother liquor (pH 10-13) to a 2 L flask. The pH was lowered to pH 6 and then 10.88 ml of hard mother liquor was added. Then 10.88 ml of the corrosion / scale inhibitor mother liquor was added. The pH was then adjusted to 8 and the final volume was adjusted to 1 L with deionized water. The final solution was filter sterilized and stored at room temperature.
    Inoculum was prepared by inoculating 2TSB agar slope into the culture loop from frozen mother liquor culture. The slopes were then incubated at 30 ° C. for 2 days. Each slope was washed with 15 ml of sterile phosphate buffer (pH 7.2) to separate the cells. Cell concentration was adjusted to 0.2 OD (equivalent to about 1-2 × 10 8 bacteria / ml) at 600 nm. The working mother liquor was stored at 4 ° C. for less than 4-6 weeks. Fresh mother liquor was prepared if extra working mother liquor was needed after 6 weeks. The following organics were used to prepare mother liquor cultures.
    ATCC
    Pseudomonas aeruginosa 15442
    Klebsiella pneumonia 13883
    Enterobacter aerogenes 13048
    The sterilization rate test was performed as follows: 150 μl sterile SCW was dispensed into 96 well microtiter plates and an additional 150 μl was added to the top row of wells. Up to 1% mother liquor was added to the test compound to obtain a preferred starting concentration of 250 or 150 ppm. Two-fold dilutions were performed using a 12-channel pipette. Was inoculated at the same time as the first inoculum 1.5㎕ mixing ratio: all the 96-well Dynatech ⓡ pin using an MIC 2000 inoculated acts mother liquid culture medium 1: 1. A final concentration of 10 6 cells / ml was obtained. Inoculated plates were stored at ambient temperature. Cells surviving in each well at 4 and 24 hours were transferred into 150 μl of TSB + 0.05% AOS using a 96-pin inoculator to recover 1.5 μl. The recovery plate was incubated at 30 ° C. for 48 hours. Growth (+) or non-growth (-) was observed in the recovery plate, indicating concentration and time to obtain a minimum 2 log reduction of inoculated cells. The test results are shown in the table below.
    Effective concentration (ppm) compound4 hours24 hours 38<4 61616 8<4<4 91258
    The test results show that compounds 3, 6, 8 and 9 have a fast sterilization rate in synthetic cooling tower water, and the compounds are effective even at low levels of use.
    At least one dihaloformaloxime carbamate according to the present invention is introduced into or on a habitat where the microorganism attacks in an antimicrobial effective amount to inhibit the growth of the microorganism at a rapid sterilization rate.
    权利要求:
    Claims (10)
    [1" claim-type="Currently amended] A method of inhibiting growth of microorganisms, the method comprising introducing at least one antimicrobial agent having the following formula into, on, or in a habitat where the microorganisms attack in an antimicrobial effective amount:
    Formula 1

    Provided that X, Y is independently selected from Br, Cl or I;
    R is (C 1 -C 8 ) alkyl, aryl or substituted aryl.
    [2" claim-type="Currently amended] The method of claim 1, wherein X = Y = Br.
    [3" claim-type="Currently amended] The method of claim 2, wherein the antimicrobial agent is N-methyl-dibromoformaldoxime carbamate; N- (2-chloroethyl) -dibromoformaldoxime carbamate; N- (4-chlorophenyl) -dibromoformaldoxime carbamate; N- (2,4-dichlorophenyl) -dibromoformaldoxime carbamate; N-ethyl-dibromoformaldoxime carbamate; N- (n-butyl) -dibromoformaldoxime carbamate; N- (n-octyl) -dibromoformaldoxime carbamate; N- (n-hexyl) -dibromoformaldoxime carbamate; And N- (4-methylphenyl) -dibromoformaldoxime carbamate; characterized in that it is selected from the group consisting of
    [4" claim-type="Currently amended] According to claim 1, The habitat is a cooling tower; Air washer; Boiler; Mineral slurry; Wastewater treatment; Decorative fountains; Reverse osmosis filtration; Ultrafiltration; Ballast water; Evaporative condenser; heat transmitter; Pulp and paper processing oils; Plastic; Emulsions and dispersants; Paint; Latex; Coating agent; Lazure; Building materials; Construction adhesives; Industrial or household adhesives; Photographic chemicals; Printing fluids; Household products; Cosmetics and toiletries; shampoo; soap; Detergent; Industrial disinfectants or sanitizers; Floor polish; Laundry rinse water; Metal working oil; Conveyor lubricants; Hydraulic fluid; Leather and leather products; fiber; Textile products; Wood and wood products; Petroleum processed oils; fuel; Oilfield fluids; Surfactant preservatives; Medical device; Diagnostic reagent preservatives; Food preservatives; Characterized in that it is selected from the group consisting of pools; and hot springs;
    [5" claim-type="Currently amended] The method of claim 1, wherein the antimicrobial effective amount is 0.05-10,000 ppm based on the volume of the habitat.
    [6" claim-type="Currently amended] 6. The method of claim 5, wherein the antimicrobial effective amount is 0.1-5000 ppm based on the volume of the habitat.
    [7" claim-type="Currently amended] The method of claim 1,
    (a) the habitat is a cooling tower; Air washer; Boiler; Mineral slurry; Wastewater treatment; Decorative fountains; Reverse osmosis filtration; Ultrafiltration; Ballast water; Evaporator concentrator; heat transmitter; Pulp and paper processing oils; plastic; Emulsions and dispersants; Paint; Latex; And coating agent; It is selected from the group consisting of;
    (b) the antimicrobial effective amount is 0.1-5000 ppm;
    (c) the antimicrobial agent is N-methyl-dibromoformaldoxime carbamate; N- (2-chloroethyl) -dibromoformaldoxime carbamate; N- (4-chlorophenyl) -dibromoformaldoxime carbamate; N- (2,4-dichlorophenyl) -dibromoformaldoxime carbamate; N-ethyl-dibromoformaldoxime carbamate; N- (n-butyl) -dibromoformaldoxime carbamate; N- (n-octyl) -dibromoformaldoxime carbamate; N- (n-hexyl) -dibromoformaldoxime carbamate; And N- (4-methylphenyl) -dibromoformaldoxime carbamate; selected from the group consisting of
    [8" claim-type="Currently amended] The compound of claim 1 further comprising methylenebis (thiocyanate); Isothiazolone; Carbamate; Heterocyclic compounds; oxide; Carboxylic acid and its derivatives; Alcohols and amines; Ammonium and phosphonium salts; Aldehydes, ketones and formaldehyde realeaser; Halogenated aromatic compounds; Halogenated aliphatic compounds; Alkenes; Inorganic compounds; enzyme; And a second antimicrobial agent selected from the group consisting of surfactants.
    [9" claim-type="Currently amended] The method of claim 8, wherein the second antimicrobial agent is 5-chloro-2-methyl-4-isothiazolin-3-one; 2-methyl-4-isothiazolin-3-one; 2-n-octyl-4-isothiazolin-3-one; 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one; 1,2-benzisothiazolin-3-one; Zinc 2-pyridinethiol-1-oxide; Sodium 2-pyridinethiol-1-oxide; N '-[3,4-dichlorophenyl] -N, N-dimethylurea; 3-iodopropargyl-N-butylcarbamate; 10,10'-oxybisphenoxyarcin; 2- (thiocyanomethylthio) benzothiazole; 3-bromo-1-chloro-5,5-dimethylhydantoin; 2,2-dibromo-3-nitrilopropionamide; Pentane-1,5-dial; And 2-bromo-2-nitro-1,3-propanediol.
    [10" claim-type="Currently amended] (a) an antimicrobial agent of the formula below;
    Formula 1

    Provided that X and Y are independently selected from bromine, chlorine or iodo;
    R = an antimicrobial agent that is (C 1 -C 8 ) alkyl, aryl or substituted aryl)
    (b) methylenebis (thiocyanate); Isothiazolone; Carbamate; Heterocyclic compounds; oxide; Carboxylic acid and its derivatives; Alcohols and amines; Ammonium and phosphonium salts; Aldehyde, ketone and formaldehyde release agents; Halogenated aromatic compounds; Halogenated aliphatic compounds; Alkenes; Inorganic compounds; enzyme; And a second antimicrobial agent selected from the group consisting of a surfactant; an antimicrobial composition comprising
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    同族专利:
    公开号 | 公开日
    BR9704364A|1999-05-11|
    SG53039A1|1998-09-28|
    SK109397A3|1998-06-03|
    MX9706052A|1998-07-31|
    PL321621A1|1998-02-16|
    CN1191073A|1998-08-26|
    ZA9707083B|1998-04-14|
    JPH10279409A|1998-10-20|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    1996-08-14|Priority to US2437996P
    1996-08-14|Priority to US60/024379
    1997-08-14|Application filed by 톰앤드, 롬 앤드 하스 캄파니
    1998-06-05|Publication of KR19980018695A
    优先权:
    申请号 | 申请日 | 专利标题
    US2437996P| true| 1996-08-14|1996-08-14|
    US60/024379|1996-08-14|
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