Antimicrobial composition

Abstract: An antimicrobial composition comprises an inorganic metal antimicrobial agent, preferably a zirconium phosphate, a thiazole antimicrobial agent, preferably an isothiazolin-3-one compound, a haloalkylthio antimicrobial agent, preferably a haloalkylthiosulfimide compound, an imidazole antimicrobial agent, preferably a cyclic compound of benzimidazole, and an urea antimicrobial agent, preferably a halophenyl derivative of dimethyl urea, as the essential compounds. The composition exhibits an excellent antimicrobial activity against various kinds of eumycetes, bacteria, actinomycetes, yeast and algae, is excellent in the quickness and persistency of the effect, and is extremely stable in itself.

Description: Field of Invention The present invention relates to an antimicrobial composition or mixture, more specifically to a composition exhibiting excellent antimicrobial and antiseptic activities against various kinds of eumycetes, bacteria, actinomycetes, yeast and algae. Background Art Antiblastic and antifungal agents have recently been used for the purpose of attaining clean, comfortable and healthy surroundings or for the purpose of inhibiting resources and articles from being deteriorated by microorganisms, and therefore have held an extremely important position in various articles and fields, for example, textiles, timbers, building materials, leathers, adhesives, metal working lubricants, rubbers, plastics, films, paper-pulp industry, cooling water, high-technology industry, electrical machinery and apparatus, optical instruments, air conditioners, stockbreeding, fishery, agriculture, forestry, drugs, agricultural chemicals, water, cosmetics, toiletries, sanitary goods, preservation of food, hospitals, homes for the aged, public institutions, household goods, sporting goods, school supplies, and toys. Further, such antiblastic and antifungal agents have recently been required not only to be applicable to various fields as described above but also to be efficacious against various kinds of microorganisms. For example, it is expected to develop an antiblastic and antifungal agent capable of inhibiting the growth of all of the 57 kinds of microorganism found in general architecture which were recognized by International Bio-Deterioration Symposium (Philadelphia, U.S.A.) in 1985 (at the sixth meeting held at Emanuel College, U.K.). Further, it is also expected to develop antiblastic, antifungal and antialgal agents capable of inhibiting the growth of not only eumycetes and bacteria but also algae. In general, various inorganic metal compounds, organometallic compounds, organic compounds and natural products which have been used as antiblastic and antifungal agents each exhibit an inhibitory activity against several to ten or so kinds of microorganism. However, there has not been found any combination of two or more of these compounds which inhibits additional kinds of microorganism beyond their respective inhibitory powers. Further, there were even cases wherein a combination of two or more of the above compounds only inhibited fewer kinds of microorganism than the sum of the kinds of microorganism which the compounds could inhibit separately. Under these circumstances, in JP-A 8-92012, an antimicrobial composition was developed, which comprises a nitrile antimicrobial agent, a pyridine antimicrobial agent, a haloalkylthio antimicrobial agent, an organoiodine antimicrobial agent and a thiazole antimicrobial agent as the active ingredients and exhibits excellent antibacterial, antifungal and antialgal activities by virtue of the additivity and synergism of these agents. However, even this antimicrobial composition was not sufficiently satisfactory in its effect as an antimicrobial agent, such as the kinds of fungi which can be inhibited, quickness of expression of antimicrobial power and persistency thereof, and other characteristics for antimicrobial agents, and in the stability of the composition in itself, and so on. The Derwent abstract of JP-A-7-207525 refers to a synthetic fibre which contains 0.01 to 2.0 % by weight of a benzothiazole compound. The fibre is stated to have antimicrobial properties. GB-A-1389940 relates to compositions, particularly paints,containing certain isothiazole compounds, from which compositions coatings having improved mildew resistance may be obtained. EP-A-0732052 discloses an antimicrobial polymer composition which further comprises thiabendazole. EP-A-0680695 discloses microbicidal compositions comprising 4,5-dichloro-2-n-octyl-3-isothiazole and 2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine or N,N-dimethyl-N'-phenyl-(N'-fluorodichloromethylthio)sulfamide. US-A-5185357 discloses an antifungal composition made up of at least one benzimidazole compound according to a particular structural formula and at least one isothiazoline-3-one compound according to another structural formula. Chemical Abstracts vol 116, no 1 (1992) abstract 2297q refers to polymer-incorporated synergistic fungicidal and algicidal compositions containing 2-(4-thiazolyl)benzimidazole and 2-octyl-4-isothiazolin-3-one. EP-A-0390394 refers to compositions comprising an isothiazolinone or an isothiazolothione and a substituted urea or a halogen-containing aromatic alkyl sulfoxide or sulfone. The compositions are stated to be useful as industrial biocides. GB-A-1542829 discloses microbicidal compositions containing a benzimidazolyl-alkylcarbamate of a particular structural formula and a halogenomethyl-thiophthalimide of a particular structural formula, N,N'-dimethyl-N'-phenyl-(N'-fluorodichloromethyl-thio)-sulfamide or tetramethylthiuram disulfide and 1-methylol-2-thiono-1,2-dihydrobenzthiazole. US-A-4008351 refers to the use of mixtures of two of 2-(4'-thiazolyl)-benzimidazole, N-(fluorodichloromethylthio)-phthalimide and N-dimethyl-N'-phenyl-N'-(fluorodichloromethylthio)-sulfamide to produce films or sheets having antibacterial and antifungal activities. Disclosure of the Invention The inventors of the present invention have intensively studied to solve the above problems and have found that an antimicrobial composition which can exhibit an excellent antimicrobial activity against various kinds of eumycetes, molds, bacteria, actinomycetes, yeast and algae, be excellent in quickness and persistency of the effect, and have high stability in itself can be obtained by blending together in particular amounts an inorganic metal antimicrobial agent selected from titania antimicrobial agents, glass antimicrobial agents and silver salt complexes, an isothiazolin-3-one antimicrobial agent, a haloalkylthio antimicrobial agent, an imidazole antimicrobial agent and a urea antimicrobial agent. The present invention provides an antifungal article or material comprising the composition defined above and a carrier. The present invention provides a process for preventing the growth and activity of microorganisms by applying the composition as defined above to a locus where microorganisms would otherwise grow. The present invention provides an antimicrobial composition comprising 1 to 96 % by weight of the said inorganic metal antimicrobial agent, 1 to 96 % by weight of the said thiazole antimicrobial agent, 1 to 96 % by weight of a haloalkylthio antimicrobial agent, 1 to 96 % by weight of an imidazole antimicrobial agent, and 1 to 96 % by weight of a urea antimicrobial agent. In a preferred form, the present invention provides an antimicrobial composition comprising 38 to 58 % by weight of the inorganic metal antimicrobial agent, 1 to 16 % by weight of the thiazole antimicrobial agent, 2 to 22 % by weight of the haloalkylthio antimicrobial agent, 3 to 23 % by weight of the imidazole antimicrobial agent, and 11 to 31 % by weight of the urea antimicrobial agent. The antimicrobial composition of the present invention can exhibit an excellent activity against a much larger number of kinds of microorganism such as eumycetes, bacteria, actinomycetes, and yeast than conventional antimicrobial compositions. Further, the composition can exhibit an excellent activity against algae for the first time. The antimicrobial composition of the present invention can be excellent in persistency of the effect. It can continue to be effective for long periods, even after new bacteria have introduced themselves. The antimicrobial composition of the present invention exhibits an excellent activity even if the concentration thereof is lower than that of conventional antimicrobial compositions. The antimicrobial composition comprises plural kinds of antimicrobial agents so that a resistant bacteria may not be produced. Modes for Carrying Out the Invention The antimicrobial composition of the present invention will now be described in detail. The inorganic metal antimicrobial agent to be used for the antimicrobial composition of the present invention is a titania antimicrobial agent, a glass antimicrobial agent or a silver salt complex. Among these agents, a zirconium phosphate-silver salt complex is being preferably used. The isothiazolin-3-one compounds used include 1,2-benzisothiazolin-3-one, 2-(n-octyl)-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-one, and 4,5-dichloro-2-cyclohexyl-4-isothiazolin-3-one. Among them, 1,2-benzisothiazolin-3-one is particularly preferable. The haloalkylthio antimicrobial agent to be used in the composition of the present invention includes haloalkylthiophthalimide compounds, haloalkylthiotetrahydrophthalimide compounds, haloalkylthiosulfamide compounds, and haloalkylthiosulfimide compounds. The haloalkylthiophthalimide compounds include N-fluorodichloromethylthiophthalimide and N-trichloromethylthiophthalimide; the haloalkylthiotetrahydrophthalimide compounds include N-1,1,2,2-tetrachloroethylthiotetrahydrophthalimide and N-trichloromethylthiotetrahydrophthalimide; the haloalkylthiosulfamide compounds include N-trichloromethylthio-N-(phenyl)methylsulfamide, N-trichloromethylthio-N-(4-chlorophenyl)methylsulfamide, N-(1-fluoro-1,1,2,2-tetrachloroethylthio)-N-(phenyl)methylsulfamide, N-(1,1-difluoro-1,2,2-trichloroethylthio)-N-(phenyl)-methylsulfamide, N,N-dimethyl-N'-phenyl-N'-(fluorodichloromethylthio)sulfamide, N,N-dichlorofluoromethylthio-N'-phenylsulfamide, and N,N-dimethyl-N'-(p-tolyl)-N'-(fluorodichloromethylthio)sulfamide. Among these compounds, N,N-dimethyl-N'-phenyl-N'-(fluorodichloromethylthio)sulfamide is particularly preferable. The imidazole antimicrobial agent to be used in the composition of the present invention includes benzimidazolecarbamic acid compounds, sulfur-containing benzimidazole compounds, and cyclic compounds of benzimidazole, among which cyclic compounds of benzimidazole are preferable. The benzimidazolecarbamic acid compounds include methyl 2-benzimidazolecarbamate, methyl 1-butylcarbamoyl-2-benzimidazolecarbamate, methyl 6-benzoyl-2-benzimidazolecarbamate, and methyl 6-(2-thiophenecarbonyl)-2-benzimidazolecarbamate. The sulfur-containing benzimidazole compounds include 2-thiocyanomethylthiobenzimidazole and 1-dimethylaminosulfonyl-2-cyano-4-bromo-6-trifluoromethylbenzimidazole. The cyclic compounds of benzimidazole or benzimidazole compounds being substituted with another cyclic compound include 2-(4-thiazolyl)benzimidazole, 2-(2-chlorophenyl)-benzimidazole, 2-(1-(3,5-dimethylpyrazolyl))benzimidazole, and 2-(2-furyl)benzimidazole. Among these compounds, 2-(4-thiazolyl)-benzimidazole is particularly preferable. The urea antimicrobial agent to be used in the composition of the present invention includes halophenyl derivatives of dimethylurea, among which 3-(3,4-dichlorophenyl)-1,1-dimethylurea is preferable. All of the above compounds are well-known ones and can readily be prepared by conventional processes. Further, many of them are commercially available, and such commercially available ones can also be used in the present invention. The antimicrobial composition of the present invention can be prepared by mixing the above components together in suitable amounts, and the preferable amount of the composition to be added is 0.06 to 0.2% by weight based on the object of an article. The form of the antimicrobial composition of the present invention is not particularly limited, but the composition may take various forms including water-based, powdery and solvent-based ones. That is, the above components are converted into a desirable form by the use of optional components generally used for the form, and applied to various articles and in various fields, for example, textiles, timber, building materials, leathers, adhesives, metal working lubricants, rubbers, plastics, films, paper-pulp industry, cooling water, high-technology industry, electrical machinery and apparatus, optical instruments, air conditioners, stockbreeding, fishery, agriculture, forestry, drugs, agricultural chemicals, water, cosmetics, toiletries, sanitary goods, preservation of food, hospitals, homes for the aged, public institutions, household goods, sporting goods, school supplies, and toys. The antimicrobial composition of the present invention is efficacious against various kinds of eumycetes, bacteria, actinomycetes, yeast and algae, specifically against not only 57 kinds of microorganism found in general architecture which were recognized by International Bio-Deterioration Symposium (Philadelphia, U.S.A.), but also other microorganisms. Further, the composition has advantageous effects, thought to be by virtue of the combination of inorganic and organic antimicrobial agents in that the antimicrobial spectrum can be extremely broad, that the composition can be extremely quick in its effect, and that the effect can persist for a long time. The antimicrobial composition of the present invention can be extremely stable in itself, and therefore can have the following characteristics: 1 ○ the composition is free from lowering of activity or environmental pollution caused by the dissolution or volatilization of antimicrobial agents, because it comprises both an inorganic antimicrobial agent insoluble in aqueous media or organic solvents and organic antimicrobial agents insoluble in aqueous media; 2 ○ when the composition is incorporated into a plastic, film, sheet, cloth or synthetic paper, there occurs little change in the properties in heating for molding or processing, so that the resulting product suffers little from yellowing or lowering in the transparency; and 3 ○ when the composition is incorporated into a synthetic fiber, the resulting fiber is not affected by washing with an anionic detergent or the like. Further, the antimicrobial composition of the present invention can be free from reductive discoloration which is one of the disadvantages of inorganic antimicrobial compositions, and is effective over a wide pH range. Further, the composition can be composed of chemicals registered as existing chemical substances stipulated by the Ministry of International Trade and Industry and is therefore not problematic in safety. Brief Explanation of the Drawing Fig. 1 is a graph showing the mortality of Escherichia coli as observed in Example 2 wherein an antimicrobial composition of the present invention was used. Examples The present invention will now be described in detail by referring to the following Examples, though the present invention is not limited to them. Example 1 An antimicrobial composition was prepared by mixing together zirconium phosphate-silver as the inorganic metal antimicrobial agent, 1,2-benzisothiazolin-3-one as the thiazole antimicrobial agent, N,N-dimethyl-N'-phenyl-N'-(fluorodichloromethylthio)sulfamide as the haloalkylthio antimicrobial agent, 2-(4-thiazolyl)benzimidazole as the imidazole antimicrobial agent and 3-(3,4-dichlorophenyl)-1,1-dimethylurea as the urea antimicrobial agent in suitable amounts. An experiment was conducted to determine the minimum concentrations (ppm) of the antimicrobial composition at which the growth of the kinds of microorganism which will be listed (including 57 kinds of microorganism found in common buildings or living circumstances which were recognized by International Bio-Deterioration Symposium) was inhibited. More precisely, potato-agar media, Sabouraud's agar media and sucrose-agar media containing the above antimicrobial composition in various concentrations were prepared and test microorganisms of each kind prepared by single cell culture were planted on the media. The resulting media were kept in an incubator at 30°C and a relative humidity of 95% for 7 days. The lowest concentration of the antimicrobial composition at which the test microorganisms did not grow was taken as the minimal inhibitory concentration (MIC value). MIC is a concentration per the medium. The MIC values of the kinds of microorganism thus determined are as follows. microorganisms having the MIC values of less than 1 ppm Tribonema sp. Algae Anacystis nidulans Algae Penicillium frequentance Mold Penicillium citrinum Mold Fusarium semitectum Mold Alternaria alternata Mold Eurotium tonophilum Mold Penicilium variable Mold Penicilium Purpurogenum Mold Aspergillus awamori Mold Blastomyces dermatidis Yeast Dactylium dendroides Mold Medurella mycetomii Mold Microsporum canis Mold Blastomyces italicum Yeast Rhizoctonia Violacea Bacteria Cerespora beticola Mold Cerespora musao Mold Claviceps purpurea Mold Colletotrichum trifolii Mold Penicillium glaucum Mold Pullularia pullulans Mold Trichophyton mentagrophytes Mold Botrytis cinerea Mold Endothia paracitica Bacteria Sclerotina sclerotiorum Bacteria Venturia inaequalis Bacteria Penicillium roqueforti Mold Monilia laxa Mold Monilia fructigana Mold Lenzites trabea Mold Ceratocystis sp. Mold Diplodia viticola Bacteria Neurospora sitophilia Mold Oidium sp. Mold microorganisms having the MIC values of at least 1 ppm and less than 10 ppm Aspergillus niger Mold Aspergillus oryzae Mold Aspergillus flavus Mold Aspergillus versicolor Mold Aspergillus fumigatus Mold Aspergillus nidulans Mold Aspergillus glaucus Mold Aspergillus terreus Mold Aspergillus phoenicus Mold Aspergillus tamari Mold Aspergillus wentii Mold Aspergillus restrictus Mold Aspergillus ochraceous Mold Chaetomium clivaceum Mold Chaetomium globosum Mold Cladosporium cladosporioides Mold Cladosporium sphaerospermum Mold Cladosporium herbarum Mold Bacillus cereus Bacteria Vibreo perahaemolyticus Bacteria Ascophyta pisi Bacteria Rhizoctonia solani Bacteria Alternaria pisi Mold Alternaria candidus Mold Trichophyton gypseum Mold Trichophyton rubrum Mold Penicillium luteum Mold Penicillium expansum Mold Phomosis citri Mold Diplodia natalensis Mold Fusarium oxysporum Mold Penicillium chrysogenum Mold Venticillium albo-atrum Mold Ustilago zeae Mold Penicillium citreo-viride Mold Oscillatoria aurea Algae Stichococcus bacillavis Mold Pestalotia neglecta Mold Fusarium roseum Mold Alternaria brassicicola Mold Geotrichum candidum Mold Geotrichum lactus Mold Gliocladium vireus Mold Phacidipycnus funfuracea Mold Phymatotricum omnivorum Mold Sclerotina fructincola Mold Aureobasidium pullulans Mold Fusarium solani Mold Penicillium notatum Mold Penicillium rubrum Mold Trichothecium roseum Mold Lenzites trabae Mold Monilia nigra Mold Microsporum audouini Mold Penicillium cyclopium Mold Colletotrichum lindemuthianum Mold Ceratocystis ulmi Mold Phoma terrestrius Mold Candida albicans Yeast Microsporum gypseum Mold Penicillium oxalicum Mold Penicillium spinulosum Mold Penicillium funiculosum Mold Penicillium digitatum Mold Fusarium roseum Mold Schizothrix sp. Algae Hormidium sp. Algae Ulothlichaceae sp. Algae microorganisms having the MIC values of at least 10 ppm and less than 20 ppm Candida acutus Yeast Phaffia rhodozyma Bacteria Sporobolomyces roseus Yeast Pichia anomala Bacteria Pichia membranaefaciens Bacteria Zygosaccharomyces rouxii Yeast Zygosaccharomyces bailii Yeast Rhodotorula gulinis Mold Rhodotorula lactosa Mold Streptococcus lactis Bacteria Aerobacter aerogenes Mold Clostridium acetobutylicum Mold Clostridium sporogenes Mold Campylabacter jejuni Bacteria Cryptococcus lutealus Mold Schizosaccharomyces pombe Yeast Saccharomycodes ludwigii Bacteria Saccharomycodes pasteurianus Mold Pichia membranaefaciens Mold Debaryamyces hansenii Bacteria Hansemula anomala Bacteria Kloeckera apiculata Bacteria Candida utilis Yeast Aspergillus luchensis Mold Penicillium islandicum Mold Trichophyton ajelloi Mold Cryptococcus neoformans Mold Helminthosporium sp. Mold Rhizopus nigricans Mold Rhizopus oryzae Mold Hormoderdrum pedrosoi Mold Mucor racemosus Mold Sporotrichum schenckii Mold Stachybotrys sp. Mold Chlorella vulgaires Algae Epicoccum purpurascens Mold Pestalotia adusta Mold Penicillium nigricans Mold Penicillium lilacinum Mold Phoma glomerata Mold Paecilomyces lilacinus Yeast Cladosporium resinae Mold Gluconobacter suboxydans Bacteria Serratia marcesens Bacteria Micrococcus glatamicus Bacteria Streptococcus faecalis Bacteria Streptococcus thermophilus Bacteria Podiococcus soyae Bacteria Podiococcus acidilactici Bacteria Lactobacillus acidophilus Bacteria Lactobacillus plantarum Bacteria Autotrophic bacteria Bacteria Streptomyces griseus Actinomycetes Streptomyces aureofaciens Actinomycetes Streptomyces kasugaensis Actinomycetes Acuremonium charticola Mold Chlorococcum sp. Algae Oscilatoria sp. Algae microorganisms having the MIC values of at least 20 ppm and less than 30 ppm Anabana sp. Algae Cladophora glomerata Algae Ankistrodemus angustus Algae Chlamydomonas reinhardii Algae Trentephohlia odarata Algae Alternaria tenuis Mold Cryptococcus albidas Mold Paecilomyces variotti Yeast Fusarium proliferatum Mold Anacystis sp. Algae Chlorella emersonii Algae microorganisms having the MIC values of at least 30 ppm and less than 50 ppm Rhizopus storonifer Mold Escherichia coli Bacteria Staphylococcus aureus Bacteria Pseudomonas aeruginosa Bacteria Salmonella typhimurium Bacteria Legionella pneamophila Bacteria Leptospira interrogans Bacteria Rickettsia rickettsii Bacteria Mycobacterium tubercolosis Bacteria Proteus mirabilis Bacteria Proteus vulgaris Bacteria Staphylococcus epidermidis Bacteria Micrococcus candidus Bacteria Bacillus mycoides Bacteria Pseudomonas fluresceus Bacteria Bacillus subtillis Bacteria Bacillus megaterium Bacteria Streptoverticillum reticulum Bacteria Nigrospora oryazae Mold Trichoderma koningii Mold Trichoderma T-1 Mold Trichoderma viride Mold Fusarium moniliforme Mold Myrothecium verrucaria Mold Streptococcus faecalis Bacteria Salmonella enteritidis Bacteria Pseudomonas flourescens Bacteria Salmonella enterrica Bacteria Salmonella arizonae Bacteria Salmonella paratyphi Bacteria Salmonella choleraesuis Bacteria Campylobacter fetus Bacteria Streptococcus agalactiae Bacteria Serratia marcesceus Bacteria Serratia liguefaciens Bacteria Klebsiella oxytoca Bacteria Clostridium perfringens Bacteria Clostridium diffcile Bacteria Bacillus anthracis Bacteria Vibrio fluvialis Bacteria Vibrio mimicus Bacteria Vibrio ulnificus Bacteria Vibrio omma Bacteria Mucor mucedo Mold Mucor pusillus Mold Rhyzopus delemar Mold Absidia glauca Mold Pleurococcus sp. Algae Scytonema hofmannii Algae microorganisms having the MIC values of at least 50 ppm and less than 70 ppm Wallemia sebi Mold Saccharomyces cerevisiae Yeast Klebsiella pneumoniae Bacteria Bacillus punctatum Bacteria Bacterium vulgaro Bacteria Bacterium pyocyaneum Bacteria Thio bacilus sp. Bacteria Fusarium nivale Mold Fusarium avenaceum Mold Fusarium acuminatum Mold Pythium vanterpoolii Bacteria Phyrarium cinereum Bacteria Aster yellows Bacteria Sugeran mosaic Bacteria Corticium fuciforme Bacteria Lepiota criststa Bacteria Lepiota castanae Bacteria Mesotaenium Algae Zygogonium Algae Trentephohlia aurea Algae Example 2 The mortality of the antimicrobial composition used in Example 1 was determined by the use of Escherichia coli. Specifically, 4.6 x 10 6 of Escherichia coli was prepared and transplanted to a test piece made of polypropylene containing 0.1% by weight of the antimicrobial composition described above, placed on a medium for the culture of Escherichia coli. The resulting system was cultured in a circulator (temp: 37°C, humidity: 95%) to determine the mortality. The results are shown in Fig. 1. It can be understood from the results shown in Fig. 1 that the antimicrobial composition of the present invention can destroy most (at least 99 %) of Escherichia coli only in one hour and the effect can persist for 40 days or more without any change. Example 3 The antiblastic test of the antimicrobial composition of the present invention used in Example 1 was determined by the use of Staphylococcus aureus as the test microorganism. Specifically, 1.1 x 10 6 of Staphylococcus aureus was prepared and transplanted to a test sample placed on a medium for the culture of Pseudomonas aeruginosa, and the resulting system was cultured in a circulator (temp: 37°C, humidity: 95%). The viable count was determined after 1, 24 and 48 hours and 30 days. The test samples used were test piece (Invention) produced by injection-molding a polypropylene containing 0.1% by weight of the antimicrobial composition used in Example 1 and test pieces produced by injection-molding a polypropylene, being free from the antimicrobial composition. The results are given in Table 1. Viable count after one hour Viable count after 24 hours Viable count after 48 hours Viable count after 30 days Compn.-free piece 3.7×10 7 4.1×10 8 5.0×10 8 5.5×10 8 Invention 4.3×10 3 3.6×10 3 2.8×10 3 1.1×10 2 Example 4 The antimicrobial composition of the present invention used in Example 1 was examined for antifungal activity. Specifically, a test solution containing 10 6 of 15 kinds of eumycetes was prepared and sprayed on a test sample placed on a Sabouraud's agar media (wet method). The resulting system was cultured in a circulator (temp: 28°C±5°C, humidity: 90%±10%) to determine the fungal growth. The test samples used were test pieces (Invention) produced by injection-molding a polypropylene containing 0.1% by weight of the antimicrobial composition used in Example 1 and test pieces produced by injection-molding a polypropylene, being free from the antimicrobial composition. The results of existence of the fungal growth observed after 10, 20 and 40 days are given in Table 2, wherein the symbol "+" means a case wherein fungi grew, and the symbol "-" a case wherein fungi did not grow. after 10 days after 20 days after 40 days Compn.-free piece + + + Invention - - - Example 5 1)Preparation of an antimicrobial composition An antimicrobial composition was prepared by mixing the five kinds of antimicrobial agent described in the following Table 3. kind of antimicrobial agent name of compound content (wt.%) inorganic metal zirconium phosphate-silver 48 thiazole 1,2-benzisothiazolin-3-one 6 haloalkylthio N,N-dimethyl-N'-phenyl-N'-(fluorodichloromethylthio)-sulfamide 12 imidazole 2-(4-thiazolyl)benzimidazole 13 urea 3-(3,4-dichlorophenyl)-1,1-dimethylurea 21 2)Preparation of a test solution The above antimicrobial composition was suspended in a sterilized saline solution in an amount of 1%. It was used as the test solution. Another sterilized saline solution, being free from the antimicrobial composition, was used as a control. 3)Preparation of a solution of fungi Staphylococcus aureus IID 1677 resistant to methicillin (MRSA) was used as the test fungi. MRSA was shaken and cultured at 35°C for 20 hours on an NB medium prepared by adding 0.2% of meat extract to a broth medium, produced by Eiken Kagaku. The cultured medium was diluted 200 times by a sterilized phosphate-buffered saline solution. It was used as the solution of fungi. 4)Antimicrobial activity experiment 1 ml of the solution of fungi was added to 100 ml of the test solution and the control, and mixed. The resulting system was stored at 25 °C for 24 hours. The number of living strains was determined by drawing two lines in parallel of the bacteria with a platinum needle at 35°C for 2days using SCDLPA agar media produced by Nihon Seiyaku. The results are shown in Table 4. It was confirmed that, with 1 ml of the test solution diluted ten times, the number of living strains could be determined by a preliminary test. fungus the living number (/ml) starting time after 24 hours MRSA test solution 1.2 x 10 5 <10 control 1.2 x 10 5 3.0 x 10 3 "<10" means no detection. Example 6 1)Preparation of an antimicrobial composition The antimicrobial composition prepared in Example 5 was used. 2)Preparation of a test solution The test solution was prepared in the same manner as in Example 5, except that a sterilized purified water was used instead of a sterilized saline solution. 3)Preparation of a solution of fungi Escherichia coli ATCC 43895 (colibacilli, serotype O157:H7, species to produce Vero toxin I, II) was used as the test fungi. The solution of fungi was prepared in the same manner as in Example 5, except that a sterilized phosphate buffer was used instead of a sterilized phosphate-buffered saline solution. 4)Antimicrobial activity experiment The antimicrobial activity experiment was carried out in the same manner as in Example 5. The results are shown in Table 5. It was confirmed that, with 1 ml of the test solution diluted ten times, the number of living strains could be determined by a preliminary test. fungus the living number (/ml) starting time after 24 hours colibacilli O157:H7 test solution 3.0 x 10 5 <10 control 3.0 x 10 5 3.4 x 10 5 "<10" means no detection.

Claims: An antimicrobial composition comprising 1 to 96 % by weight of an inorganic metal antimicrobial agent selected from titania antimicrobial agents, glass antimicrobial agents and silver salt complexes, 1 to 96 % by weight of an isothiazolin-3-one antimicrobial agent, 1 to 96 % by weight of an haloalkylthio antimicrobial agent, 1 to 96 % by weight of an imidazole antimicrobial agent, and 1 to 96 % by weight of a urea antimicrobial agent. A composition as claimed in claim 1, wherein the haloalkylthio antimicrobial agent is selected from haloalkylthiophthalimide compounds, haloalkylthiotetrahydrophthalimide compounds, haloalkylthiosulfamide compounds, and haloalkylthiosulfimide compounds. A composition as claimed in claim 2, wherein the haloalkylthio antimicrobial agent is a haloalkylthiosulfamide compound. A composition as claimed in any of claims 1 to 3, wherein the imidazole antimicrobial agent is selected from benzimidazolecarbamic acid compounds, sulfur-containing benzimidazole compounds, and cyclic compounds of benzimidazole. A composition as claimed in claim 4, wherein the imidazole antimicrobial agent is a cyclic compound of benzimidazole. A composition as claimed in any of claims 1 to 5, wherein the urea antimicrobial agent is a halophenyl derivative of dimethylurea. A composition as claimed in any of claims 1 to 6, comprising 38 to 58 % by weight of the inorganic metal antimicrobial agent, 1 to 16 % by weight of the isothiazolin-3-one antimicrobial agent, 2 to 22 % by weight of the haloalkylthio antimicrobial agent, 3 to 23 % by weight of the imidazole antimicrobial agent, and 11 to 31 % by weight of the urea antimicrobial agent. A composition as claimed in any of claims 1 to 7, wherein the inorganic metal antimicrobial agent is a zirconium phosphate-silver complex. A composition as claimed in claim 1, wherein the inorganic metal antimicrobial agent is a zirconium phosphate-silver complex, the isothiazolin-3-one antimicrobial agent is 1,2-benzisothiazolin-3-one, the haloalkylthio antimicrobial agent is N, N-dimethyl-N'-phenyl-N'-(fluorodichloromethylthio)-sulfamide, the imidazole antimicrobial agent is 2-(4-thiazolyl) benzimidazole and the urea antimicrobial agent is 3-(3,4-dichlorophenyl)- 1,1-dimethylurea. An antifungal article comprising a composition as claimed in any of claims 1 to 9 and a carrier. A process for preventing the growth and activity of microorganisms by applying the composition as claimed in any of claims 1 to 9 to a locus where microorganisms would otherwise grow. A process as claimed in claim 11, wherein the microorganism is selected from Rhizopus oryzae, Rhizopus storonifer, Mucor mucedo, Mucor pusillus and Rhizopus delemer.

Inventors: SUGANUMA AKIO, SUGANUMA, AKIO
Applicants: FUJIWARA HITOSHI, SUGANUMA AKIO, FUJIWARA, HITOSHI, SUGANUMA, AKIO
Application year: 1997
Main classification: A01N59
IPC codes: A01N59, A01N37, A01N47