JP5713770B2 - Industrial antiseptic and antifouling composition - Google Patents

Description

  The present invention relates to an industrial antiseptic and antifouling composition containing a quinolone compound excluding oxolinic acid or a salt thereof.

  Quinolone compounds have long been used as antibacterial agents. As quinolone antibacterial agents, there are known old quinolone antibacterial agents such as nalidixic acid and pipemidic acid and new quinolone antibacterial agents such as norfloxacin. Old quinolone antibacterials mainly exhibit antibacterial activity against Gram-negative bacilli, and new quinolone antibacterials are intended to expand the antibacterial spectrum and improve the antibacterial activity.

  Among the quinolone compounds, oxolinic acid is known as one applied to industrial antibacterial applications (Patent Documents 1 to 3). However, other quinolone compounds widely used as antibacterial agents are not known for application to industrial antiseptic and antifouling. Moreover, in order to improve the antibacterial activity of oxolinic acid, an antibacterial composition combined with zinc oxide has been disclosed (Patent Document 4), and the present applicant has also used an industrial antibacterial composition combined with other predetermined antibacterial compounds. An application has been filed (Japanese Patent Application No. 2009-18810). On the other hand, as for other quinolone compounds, an antibacterial agent used in combination with a hydrolyzate of lactoferrin or an antibacterial peptide derived from the hydrolyzate is disclosed (Patent Document 5). However, there has been no report that the antibacterial spectrum of quinolone antibacterial agents has been expanded and the antibacterial activity has been improved, particularly in antiseptic and antifouling compositions applicable to industrial applications.

JP-A-9-176966 JP-A-9-208408 Japanese Patent Laid-Open No. 9-249827 JP 2002-284601 A JP 11-92375 A

  Therefore, in the present invention, quinolone compounds other than oxolinic acid can also be applied to industrial antiseptic and antifouling, and in an industrial antiseptic and antifouling composition containing the compound, the antibacterial spectrum The purpose was to expand and improve antibacterial activity.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that quinolone compounds other than oxolinic acid have antibacterial properties against bacteria that do not exhibit pathogenicity, such as Bacillus subtilis, and are resident in the environment. Found to have activity. Furthermore, by using together with a specific antibacterial compound, it has been found that the antibacterial spectrum is broadened and a synergistic improvement in antibacterial activity is obtained, and the present invention has been completed.

That is, the present invention relates to the following [1] to [10].
[1] An industrial antiseptic / antifouling composition comprising a quinolone compound represented by the formula (1), the compound excluding oxolinic acid, or a salt thereof.

Wherein, A ₁ ring may be optionally substituted, one or two an aromatic ring which may be 6-membered heterocyclic ring carbon atom is replaced by a nitrogen atom, R ₁ and R ₂ are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group. R ₁ may form a ring together with the substituent of A ₁ ring. ]

[2] Further, an isothiazoline compound represented by formula (2), a benzisothiazoline compound represented by formula (3), a benzimidazole compound represented by formula (4), and a haloacetylene compound represented by formula (5) Industrial antiseptic / antifouling according to the above [1], comprising one or more selected from the group consisting of a compound, a tetrahydrothiophene dioxide compound represented by the formula (6), and salts thereof Composition.

[Wherein R ₃ represents a hydrogen atom or an optionally substituted hydrocarbon group, and R ₄ and R ₅ are the same or different and each represents a hydrogen atom, a halogen atom or an optionally substituted hydrocarbon group. Show. ]

[Wherein, A ₂ ring represents an optionally substituted benzene ring, and Y represents a hydrogen atom or an optionally substituted hydrocarbon group. ]

[Wherein, A ₃ ring represents an optionally substituted benzene ring, Z represents —NHCOOR ₆ (wherein R ₆ represents a hydrogen atom or an alkyl group) or a substituted group. A good 5-membered or 6-membered nitrogen-containing heterocyclic group is shown. ]

[Wherein, X ₁ represents a halogen atom, R ₇ and R ₈ are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group, and m represents an integer of 0 or 1. ]

[Wherein Y ₁ , Y ₂ , Y ₃ and Y ₄ are the same or different and each represents a hydrogen atom, a halogen atom or an optionally substituted hydrocarbon group. ]

[3] The above-mentioned [1], wherein the quinolone-based compound, excluding oxolinic acid, is one or more selected from the group consisting of compounds represented by formula (7) and formula (8) Or the industrial antiseptic / antifouling composition according to [2].

[Wherein, R ₁ and R ₂ are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group, R ₉ represents a hydrogen atom, a halogen atom or an amino group, and R ₁₀ represents a hydrogen atom or a halogen atom. , R ₁₁ represents an optionally substituted hydrocarbon group or an optionally substituted cyclic amino group. ]

[Wherein, R ₁ and R ₂ are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group, R ₉ represents a hydrogen atom, a halogen atom or an amino group, and R ₁₀ represents a hydrogen atom or a halogen atom. , R ₁₁ is an optionally substituted hydrocarbon group or an optionally substituted cyclic amino group, R ₁₂ is a hydrogen atom, a halogen atom, an optionally substituted alkoxy group or an optionally substituted hydrocarbon Indicates a group. R ₁ may form a ring together with R ₁₂ . ]

[4] A quinolone compound excluding oxolinic acid is enoxacin, tosufloxacin, norfloxacin, sarafloxacin, difloxacin, fleroxacin, lomefloxacin, enrofloxacin, ciprofloxacin, gatifloxacin, sparfloxacin, [1] above, which is one or more selected from the group consisting of danofloxacin, moxifloxacin, garenoxacin, sitafloxacin, orbifloxacin, nadifloxacin, ofloxacin, levofloxacin, pazufloxacin and marbofloxacin Or the industrial antiseptic / antifouling composition according to [2].
[5] The isothiazoline-based compound is 2-methyl-4-isothiazolin-3-one, 2-n-octyl-4-isothiazolin-3-one, 4-chloro-2-n-octyl-4-isothiazoline-3- ON, 5-chloro-2-methyl-4-isothiazolin-3-one, 5-chloro-2-n-octyl-4-isothiazolin-3-one and 4,5-dichloro-2-n-octyl-4- The industrial antiseptic / antifouling composition according to the above [2], which is one or more selected from the group consisting of isothiazolin-3-one.
[6] The isothiazoline-based compound is selected from 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-n-octyl-4-isothiazolin-3-one The industrial antiseptic / antifouling composition according to the above [2], which is one or more selected from the group consisting of:
[7] The benzoisothiazoline compound is one or two selected from the group consisting of 1,2-benzisothiazolin-3-one and Nn-butyl-1,2-benzisothiazolin-3-one The industrial antiseptic and antifouling composition according to [2] above.
[8] The above, wherein the benzimidazole compound is one or more selected from the group consisting of methyl 2-benzimidazole carbamate, ethyl 2-benzimidazole carbamate and 2- (4-thiazolyl) benzimidazole. 2] Industrial antiseptic and antifouling composition.
[9] The industrial antiseptic / antifouling composition according to the above [2], wherein the haloacetylene compound is 3-iodo-2-propynyl N-butylcarbamate.
[10] The industrial antiseptic / antifouling composition according to the above [2], wherein the tetrahydrothiophene dioxide compound is 3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide.

  According to the present invention, an industrial antiseptic and antifouling composition comprising an quinolone compound other than oxolinic acid or a salt thereof and having antibacterial activity against various bacteria present in the environment can be obtained. . In addition, by using a specific antibacterial compound in combination, the antibacterial spectrum is expanded and the antibacterial activity is synergistically improved, so that it can be used in various modes and can be used for a wide range of industrial applications. An antiseptic / antifouling composition can be obtained.

  In the present invention, as the quinolone compound other than the oxolinic acid, a quinolone compound represented by the following formula (1) and excluding the oxolinic acid is used.

Wherein, A ₁ ring may be optionally substituted, one or two an aromatic ring which may be 6-membered heterocyclic ring carbon atom is replaced by a nitrogen atom, R ₁ and R ₂ are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group. R ₁ may form a ring together with the substituent of A ₁ ring. ]

In the above formula (1), a 6-membered aromatic ring which may be substituted or a heterocyclic ring in which one or two carbon atoms are substituted with a nitrogen atom, represented by A ₁ ring Among them, examples of the 6-membered aromatic ring that is the heterocyclic ring include pyridine, pyrimidine, pyridazine, and pyrazine, and examples of the 6-membered aromatic ring that is not the heterocyclic ring include benzene. Among these, benzene, pyridine and pyrimidine are preferable, and benzene or pyridine is particularly preferable.

Represented by A ₁ ring as the substituent of "may be substituted with one or two aromatic rings which may be 6-membered heterocyclic ring carbon atoms are substituted by nitrogen atoms", a hydroxyl group A halogen atom, an optionally substituted alkoxy group, an optionally substituted hydrocarbon group, an optionally substituted amino group, and the like.

  Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom, and a fluorine atom or a chlorine atom is preferable.

  Examples of the alkoxy group of the “optionally substituted alkoxy group” include an alkoxy group having 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy and the like. An alkoxy group having 1 to 4 carbon atoms is preferred. Examples of the substituent of the “optionally substituted alkoxy group” include a halogen atom such as fluorine, chlorine and bromine; an alkoxy group having 1 to 4 carbon atoms; an aryl group having 1 to 14 carbon atoms such as phenyl and naphthyl; Can be mentioned.

  The hydrocarbon group of the “optionally substituted hydrocarbon group” is preferably a hydrocarbon group having 1 to 20 carbon atoms, more preferably a hydrocarbon group having 1 to 14 carbon atoms, such as an alkyl group or an alkenyl group. Alkynyl group, cycloalkyl group, aryl group and aralkyl group.

  Examples of the alkyl group include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, 1-methylbutyl, 1-ethylpropyl, 1,1- Dimethylpropyl, n-hexyl, isohexyl, 1-ethyl-1-methylpropyl, 2-ethylbutyl, n-heptyl, isoheptyl, 2,2-dimethylpentyl, n-octyl, isooctyl, 1-methylheptyl, 1-ethylhexyl, C1-C10 alkyl groups such as 1-propylpentyl, 1,1-dimethylhexyl, 1-ethyl-1-methylpentyl, 1,1-diethylbutyl, 2-ethylhexyl, nonyl, decyl, preferably carbon number 1-8 alkyl groups are mentioned.

  Examples of the alkenyl group include ethenyl (vinyl), 1-propenyl, 2-propenyl (allyl), isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 1-pentenyl, Examples thereof include alkenyl groups having 2 to 6 carbon atoms such as 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, and 5-hexenyl.

  Examples of the alkynyl group include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, Examples thereof include alkynyl groups having 2 to 6 carbon atoms such as 2-hexynyl, 3-hexynyl, 4-hexynyl and 5-hexynyl.

  Examples of the cycloalkyl group include cycloalkyl groups having 3 to 8 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.

  Examples of the aryl group include aryl groups having 6 to 14 carbon atoms such as phenyl, naphthyl, anthracenyl, phenanthrenyl and the like.

  Examples of the aralkyl group include aralkyl groups having 7 to 14 carbon atoms such as benzyl, phenylethyl, naphthylmethyl and the like.

  Substituents of the above-mentioned “optionally substituted hydrocarbon group” include hydroxyl groups; halogen atoms of chlorine, fluorine, bromine and iodine; cyano groups; amino groups; carboxyl groups; acetyl, propanoyl, butanoyl, hexanoyl, etc. An acyl group having 1 to 6 carbon atoms; an alkoxy group having 1 to 4 carbon atoms such as methoxy, ethoxy, propoxy and butoxy; an aryloxy group having 6 to 20 carbon atoms, preferably 6 to 10 carbon atoms such as phenoxy and naphthyloxy An aralkyloxy group having 7 to 14 carbon atoms such as benzyloxy and phenylethyloxy; an alkylthio group having 1 to 4 carbon atoms such as methylthio, ethylthio, propylthio and butylthio; an arylthio group having 6 to 20 carbon atoms such as phenylthio and the like; Can be mentioned. The hydrocarbon group may have two or more of the substituents, and the substituents may be the same or different.

  The amino group of the “optionally substituted amino group” includes pyrrolidinyl, piperidyl, piperazinyl, azabicyclo [2.2.1] heptanyl, azabicyclo [2.2.2] octanyl, diazabicyclo [2.2.1]. Cyclic amino groups such as heptanyl, diazabicyclo [2.2.2] octanyl, octahydropyrrolopyridinyl, isoindolinyl, azaspiro [2.4] heptanyl are also included. Examples of the substituent of the “optionally substituted amino group” include a hydroxyl group, an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, and an amino group.

The A ₁ ring is preferably substituted with 2 to 4 substituents. Examples of the substituent include a halogen atom; a cycloalkyl group having 3 to 6 carbon atoms substituted with an amino group; pyrrolidinyl, piperidyl, piperazinyl, diazabicyclo [2.2.1] heptanyl, octahydropyrrolopyridinyl, A cyclic amino group such as isoindolinyl, azaspiro [2.4] heptanyl; the cyclic amino group substituted by a hydroxyl group, an amino group or an alkyl group having 1 to 6 carbon atoms; an alkoxy group having 1 to 4 carbon atoms; substituted by a halogen atom The above alkoxy group is preferred.

In the above formula (1), the “optionally substituted hydrocarbon group” represented by R ₁ or R ₂ is the same group as the “optionally substituted hydrocarbon group” of the aforementioned A ₁ ring. Is mentioned. The group represented by R ₁ may form a ring together with the substituent at the 8-position of the A ₁ ring. Examples of such rings include hydropyridine rings, hydrooxazine rings, hydrooxadiazine rings and the like.

  In the present invention, compounds represented by the formulas (7) and (8) are preferably used as quinolone compounds other than oxolinic acid.

[Wherein, R ₁ and R ₂ are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group, R ₉ represents a hydrogen atom, a halogen atom or an amino group, and R ₁₀ represents a hydrogen atom or a halogen atom. , R ₁₁ represents an optionally substituted hydrocarbon group or an optionally substituted cyclic amino group. ]

[Wherein, R ₁ and R ₂ are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group, R ₉ represents a hydrogen atom, a halogen atom or an amino group, and R ₁₀ represents a hydrogen atom or a halogen atom. , R ₁₁ is an optionally substituted hydrocarbon group or an optionally substituted cyclic amino group, R ₁₂ is a hydrogen atom, a halogen atom, an optionally substituted alkoxy group or an optionally substituted hydrocarbon Indicates a group. R ₁ may form a ring together with R ₁₂ . ]

  The compound represented by the above formula (7) is a compound having a naphthyridine skeleton.

In the above formulas (7) and (8), the group represented by R ₁ or R ₂ is as defined above. Examples of the halogen atom represented by R ₉ or R ₁₀ include a fluorine atom, a chlorine atom, and a bromine atom. The same applies to the “optionally substituted hydrocarbon group” and “optionally substituted cyclic amino group” represented by R ₁₁ . The above formula (7) and formula (8), the group represented by R _1, an alkyl group having 1 to 4 carbon atoms ethyl, and the like; carbon atoms are halogenated, such as 2-fluoroethyl 1-4 A cycloalkyl group having 3 to 6 carbon atoms such as cyclopropyl, cyclopentyl and cyclohexyl; a halogenated cycloalkyl group having 3 to 6 carbon atoms such as fluorocyclopropyl; halogenation such as fluorophenyl and difluorophenyl Preferred aryl groups. The group represented by R ₂ is preferably a hydrogen atom, the group represented by R ₉ is preferably a hydrogen atom, a fluorine atom or an amino group, and the group represented by R ₁₀ is preferably a hydrogen atom or a fluorine atom. Examples of the group represented by R ₁₁ include an aminocyclopropyl group; a pyrrolidinyl, piperidyl, piperazinyl, diazabicyclo [2.2.1] substituted by a hydroxyl group, an amino group, or an alkyl group having 1 to 4 carbon atoms such as methyl or ethyl. Heptyl, octahydropyrrolopyridinyl, isoindolinyl, azaspiro [2.4] heptanyl are preferred.

Further, in the above formula (8), the “optionally substituted alkoxy group” and the “optionally substituted hydrocarbon group” represented by R ₁₂ are the same as described above. In the above formula (8), the group represented by R ₁₂ includes a hydrogen atom; a halogen atom such as a fluorine atom or a chlorine atom; an alkyl group having 1 to 4 carbon atoms such as methyl; Alkoxy group: The alkoxy group substituted with a halogen atom such as difluoromethoxy is preferred. In the above formula (8), the group represented by R ₁ may form a ring together with the group represented by R ₁₂ , and examples of the ring include a hydropyridine ring, a hydroxazine ring, and a hydrooxadiazine ring. Etc. Therefore, in the above formula (8), a benzoquinolidine skeleton, a pyridobenzoxazine skeleton or a pyridobenzooxadiazine skeleton in which a group represented by R ₁ and a group represented by R ₁₂ form a ring Those possessed are also exemplified as preferred compounds.

  In the present invention, as the quinolone compound other than oxolinic acid, one or more kinds selected from the group consisting of the compounds represented by the above formulas (7) and (8) can be selected and used.

  Examples of quinolone compounds other than oxolinic acid that are more preferably used in the present invention include enoxacin having a naphthyridine skeleton, tosufloxacin, norfloxacin having a quinoline skeleton, sarafloxacin, difloxacin, fleloxacin, lomefloxacin, enrofloxacin, ciprofloxacin, gatifloxin Xacin, sparfloxacin, danofloxacin, moxifloxacin, garenoxacin, sitafloxacin, orbifloxacin, nadifloxacin with benzoquinolidine skeleton, ofloxacin with pyridobenzoxazine skeleton, levofloxacin, pazufloxacin, pyridobenzo Examples include marbofloxacin having an oxadiazine skeleton, and one or more of these may be selected and used. Can.

  In the present invention, quinolone compounds other than oxolinic acid can be used in the form of pharmaceutically acceptable salts. Such salts include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid; formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid , Salts with organic acids such as succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid; salts with alkali metals such as sodium and potassium; and alkaline earth metals such as magnesium and calcium Salt; ammonium salt; trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, 1,6-hexamethylenediamine, tert-butylamine, cyclohexylamine, benzylamine, dicyclohexylamine, N, N-di Organic polymers such as benzylethylenediamine Such as the salt of the emissions, and the like.

  As the quinolone compound other than oxolinic acid or a salt thereof used in the present invention, a commercially available product may be used, or a product prepared according to a known technique may be used, but it is convenient to use a commercially available product.

  In the industrial antiseptic / antifouling composition of the present invention, in addition to the quinolone compound or salt thereof other than the oxolinic acid, an isothiazoline compound, benzisothiazoline compound, haloacetylene compound, benzimidazole compound, tetrahydrothiophene You may use together 1 type, or 2 or more types of antibacterial compounds selected from the group which consists of a dioxide type compound and these salts. By using the antibacterial compound in combination, the antibacterial spectrum is expanded and the antibacterial activity is synergistically improved.

  The isothiazoline-based compound is represented by the following formula (2).

[Wherein R ₃ represents a hydrogen atom or an optionally substituted hydrocarbon group, and R ₄ and R ₅ are the same or different and each represents a hydrogen atom, a halogen atom or an optionally substituted hydrocarbon group. Show. ]

In the formula (2), the “optionally substituted hydrocarbon group” represented by R ₃ is the same as the above-mentioned “optionally substituted hydrocarbon group” for the substituent of the A ₁ ring. Is mentioned. In addition, the said substituent may be same or different and 1-5 pieces, Preferably 1-3 pieces may be substituted.

As the “optionally substituted hydrocarbon group” represented by R ₃ , an unsubstituted hydrocarbon group is preferable, and among them, an alkyl group or a cycloalkyl group is preferable. As the alkyl group, an alkyl group having 1 to 8 carbon atoms is preferable, and an alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and the like, and n -8 carbon atoms such as octyl, isooctyl, 1-methylheptyl, 1-ethylhexyl, 1-propylpentyl, 1,1-dimethylhexyl, 1-ethyl-1-methylpentyl, 1,1-diethylbutyl, 2-ethylhexyl Are more preferable, and methyl, ethyl, n-butyl, and n-octyl are more preferable. As the cycloalkyl group, a cycloalkyl group having 3 to 8 carbon atoms is preferable, and cyclohexyl is more preferable.

In the present invention, in the above formula (2), the group represented by R ₃ is preferably an alkyl group having 1 to 8 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms, and an alkyl group having 1 to 8 carbon atoms. More preferably, alkyl groups having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, and n-octyl, isooctyl, 1-methylheptyl, 1-ethylhexyl. More preferable are alkyl groups having 8 carbon atoms such as 1-propylpentyl, 1,1-dimethylhexyl, 1-ethyl-1-methylpentyl, 1,1-diethylbutyl, 2-ethylhexyl, methyl, ethyl, n- Butyl and n-octyl are particularly preferred.

In formula (2), examples of the halogen atom represented by R ₄ or R ₅ include fluorine, chlorine, bromine and iodine atoms, and among these, a chlorine atom is preferred.

In addition, the “optionally substituted hydrocarbon group” represented by R ₄ or R ₅ is the same as the “optionally substituted hydrocarbon group” described above for the substituent of the A ₁ ring. A substituted hydrocarbon group is preferable, and an alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and the like is particularly preferable.

In the present invention, in the above formula (2), the groups represented by R ₄ and R ₅ are the same or different and each is preferably a hydrogen atom or a halogen atom, more preferably a hydrogen atom or a chlorine atom.

  Specific examples of the isothiazoline-based compound that can be used in the present invention include 2-methyl-4-isothiazolin-3-one, 2-ethyl-4-isothiazolin-3-one, and 2-n-octyl-4-isothiazoline-3- ON, 5-chloro-2-methyl-4-isothiazolin-3-one, 5-chloro-2-ethyl-4-isothiazolin-3-one, 5-chloro-2-n-octyl-4-isothiazoline-3- ON, 4-chloro-2-n-octyl-4-isothiazolin-3-one, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one, 4,5-dichloro-2-cyclohexyl- 4-isothiazolin-3-one etc. are mentioned. Of these, 2-methyl-4-isothiazolin-3-one, 2-n-octyl-4-isothiazolin-3-one, 4-chloro-2-n-octyl-4-isothiazolin-3-one, 5- Chloro-2-methyl-4-isothiazolin-3-one, 5-chloro-2-n-octyl-4-isothiazolin-3-one and 4,5-dichloro-2-n-octyl-4-isothiazoline-3- On is preferred, with 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one and 2-n-octyl-4-isothiazolin-3-one being particularly preferred.

  In the present invention, as the isothiazoline-based compound, one or more can be selected from the group consisting of the above compounds.

  The benzoisothiazoline compound is represented by the following formula (3).

[Wherein, A ₂ ring represents an optionally substituted benzene ring, and Y represents a hydrogen atom or an optionally substituted hydrocarbon group. ]

In formula (3), examples of the substituent of the “optionally substituted benzene ring” represented by A ₂ ring include a hydroxyl group; a halogen atom of chlorine, fluorine, bromine and iodine; a cyano group; an amino group; a carboxyl group; C1-C10 acyl groups such as butanoyl, octanoyl, decanoyl; C1-C4 alkoxy groups such as methoxy, ethoxy, propoxy, butoxy; C6-C20 such as phenoxy, naphthyloxy, preferably carbon numbers An aryloxy group having 6 to 10 carbon atoms; an aralkyloxy group having 7 to 14 carbon atoms such as benzyloxy and phenylethyloxy; an alkylthio group having 1 to 4 carbon atoms such as methylthio, ethylthio, propylthio and butylthio; 6 carbon atoms such as phenylthio To 20 arylthio groups, etc., including halogen atoms and methyl, ethyl, An alkyl group having 1 to 4 carbon atoms such as pill and butyl is preferable. These substituents may be the same or different, and 1 to 4, preferably 1 or 2 may be substituted on the benzene ring. The “optionally substituted benzene ring” represented by A ₂ ring is preferably an unsubstituted benzene ring.

In the formula (3), the “optionally substituted hydrocarbon group” represented by Y is the “optionally substituted hydrocarbon group” shown as one of the substituents of the A ₁ ring described above. Although the same thing is mentioned, an unsubstituted hydrocarbon group is preferable, a C1-C8 alkyl group is more preferable, and a C1-C4 alkyl group (especially n-butyl) is especially preferable.

  In the present invention, in the formula (3), the group represented by Y is preferably a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and a hydrogen atom or an alkyl group having 1 to 4 carbon atoms (particularly n-butyl). Particularly preferred.

  Preferable specific examples of the benzoisothiazoline compound include 1,2-benzisothiazoline-3-one, Nn-butyl-1,2-benzisothiazoline-3-one, and the like.

  In the present invention, as the benzoisothiazoline-based compound, one or more kinds selected from the group consisting of the above compounds can be selected and used.

  The benzimidazole compound is represented by the following formula (4).

[Wherein, A ₃ ring represents an optionally substituted benzene ring, Z represents —NHCOOR ₆ (wherein R ₆ represents a hydrogen atom or an alkyl group) or a substituted group. A good 5-membered or 6-membered nitrogen-containing heterocyclic group is shown. ]

In the formula (4), as may be included in the "which may be substituted benzene ring" substituent represented by A ₃ rings, there may be mentioned those similar to the substituent of A ₂ rings above , Halogen atoms, and alkyl groups having 1 to 4 carbon atoms such as methyl, ethyl, propyl, and butyl. These substituents may be the same or different, 1 to 4 to the benzene ring represented by A ₃ rings, preferably may include one or two. As the benzene ring which may be substituted represented by A ₃ ring, a benzene ring is preferably unsubstituted.

In the group represented by —NHCOOR ₆ represented by Z in the above formula (4), the alkyl group represented by R ₆ includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert -Alkyl groups having 1 to 8 carbon atoms such as butyl, n-pentyl, n-hexyl, n-heptyl and n-octyl, and among them, 1 to C carbon atoms such as methyl, ethyl, n-propyl and the like. The alkyl group of 3 is particularly preferred.

  In the formula (4), the optionally substituted 5- or 6-membered nitrogen-containing heterocyclic group represented by Z contains 1 to 4 nitrogen atoms as ring constituent atoms, or 1 to 1 5-membered or 6-membered monocyclic heterocyclic group containing, as a ring-constituting atom, one heteroatom selected from oxygen atom and sulfur atom in addition to two nitrogen atoms, and this 5-membered or 6-membered And a condensed heterocyclic group in which a benzene ring or a 5-membered ring is condensed to the nitrogen-containing heterocyclic ring. The 5- or 6-membered nitrogen-containing monocyclic heterocyclic group includes pyridyl groups such as 2-pyridyl, 3-pyridyl and 4-pyridyl; thiazolyl groups such as 2-thiazolyl, 4-thiazolyl and 5-thiazolyl; 3 -Isothiazolyl groups such as isothiazolyl, 4-isothiazolyl and 5-isothiazolyl; imidazolyl groups such as 1-imidazolyl, 2-imidazolyl, 4-imidazolyl and 5-imidazolyl; pyrrolyl groups such as 1-pyrrolyl, 2-pyrrolyl and 3-pyrrolyl A pyrrolinyl group such as 2-pyrrolinyl and 3-pyrrolinyl; a furanyl group; a pyrrolidinyl group such as 1-pyrrolidinyl, 2-pyrrolidinyl and 3-pyrrolidinyl; an imidazolidinyl group such as 2-imidazolidinyl, 4-imidazolidinyl and 5-imidazolidinyl; Pyrazolidinyl groups such as pyrazolidinyl; 5-pyrazoli A pyrazolyl group such as 2-oxazolyl, 4-oxazolyl and 5-oxazolyl; an isoxazolyl group such as 3-isoxazolyl, 4-isoxazolyl and 5-isoxazolyl; a tetrazolyl group such as 1H-tetrazolyl and 2H-tetrazolyl; 2 -Pyrimidinyl groups such as pyrimidinyl, 4-pyrimidinyl and 5-pyrimidinyl; pyridazinyl groups such as 3-pyridazinyl and 4-pyridazinyl; pyrazinyl groups such as 2-pyrazinyl and 3-pyrazinyl; 1,2-thiazin-3-yl, 1 , 2-thiazin-4-yl, 1,3-thiazin-2-yl, 1,3-thiazin-4-yl, 1,4-thiazin-2-yl, 1,4-thiazin-3-yl, etc. Thiazinyl group; piperazinyl group such as 1-piperazinyl, 2-piperazinyl, 3-piperazinyl 1,2,3-thiadiazin-4-yl, 1,2,3-thiadiazin-5-yl, 1,2,3-thiadiazin-6-yl, 1,2,4-thiadiazin-3-yl, 1, Thiadiazinyl groups such as 3,4-thiadiazin-2-yl; 1,3,4-oxadiazol-2-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadi Oxadiazolyl groups such as azol-5-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl; 1,2,3-thiadiazol-4-yl, A thiadiazolyl group such as 1,2,3-thiadiazol-5-yl; a triazolyl group such as 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl; 2-thiomorpholinyl, 3- Thiomorpholinyl, 4-thiomorpholine Thiomorpholinyl groups such as linyl, 5-thiomorpholinyl, 6-thiomorpholinyl; morpholinyl groups such as 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 5-morpholinyl, 6-morpholinyl; oxoimidazoles such as 2-oxoimidazolinyl Dinyl group; 1,2,4-triazine-3,5-dione-1-yl, 1,2,4-triazine-3,5-dione-2-yl, 1,2,4-triazine-3, Examples include dioxotriazinyl groups such as 5-dione-4-yl; piperidyl groups such as 1-piperidyl, 2-piperidyl, 3-piperidyl, 4-piperidyl and the like. Examples of the condensed heterocyclic group include quinolyl groups such as 2-quinolyl, 3-quinolyl and 4-quinolyl; isoquinolyl groups such as 3-isoquinolyl and 4-isoquinolyl; indolyl groups such as 2-indolyl and 3-indolyl; Isoindolyl groups such as isoindol-3-yl; quinolidinyl groups such as 8-quinolidinyl; purinyl groups such as 1H-purin-6-yl and 3H-purin-6-yl; cinnolinyl groups such as 3-cinnolinyl and 5-cinnolinyl An indazolyl group such as 3-indazolyl; a pteridinyl group such as 2-pteridinyl; a phthalazinyl group such as 4-phthalazinyl; a quinazolinyl group such as 2-quinazolinyl and 4-quinazolinyl; a quinoxalinyl group such as 2-quinoxalinyl and 3-quinoxalinyl; -An indolizinyl group such as indolizinyl; Benzooxazinyl groups such as zooxazin-2-yl; phenothiazinyl groups such as 2-phenothiazinyl and 3-phenothiazinyl; phenazinyl groups such as 2-phenazinyl and 3-phenazinyl; 2-phenoxazinyl, 3-phenoxazinyl, 4- Examples include phenoxazinyl groups such as phenoxazinyl. Of the above heterocyclic groups, a 5-membered nitrogen-containing heterocyclic group is preferable, and a thiazolyl group is particularly preferable.

  Examples of the substituent of the heterocyclic ring include alkyl groups having 1 to 4 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl; methoxy, ethoxy, n-propoxy Alkoxy groups having 1 to 4 carbon atoms such as isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy; halogen atoms such as fluorine, chlorine, bromine; hydroxyl groups; amino groups; nitro groups; mercapto groups Can be mentioned.

  The optionally substituted 5- or 6-membered nitrogen-containing heterocyclic group represented by Z is preferably an unsubstituted 5- or 6-membered nitrogen-containing heterocyclic group, and an unsubstituted 5-membered nitrogen-containing heterocyclic group Are more preferable, and a thiazolyl group is particularly preferable.

In the present invention, in the formula (4), the group represented by Z is a group represented by -NHCOOR ₆ (wherein R ₆ is an alkyl group having 1 to 8 carbon atoms) or an unsubstituted 5-membered group. Alternatively, a 6-membered nitrogen-containing heterocyclic group is preferable, and a group represented by -NHCOOR ₆ (wherein R ₆ is an alkyl group having 1 to 3 carbon atoms) or an unsubstituted 5-membered nitrogen-containing heterocyclic group is A group represented by —NHCOOR ₆ (wherein R ₆ is an alkyl group having 1 to 3 carbon atoms) or a thiazolyl group is particularly preferable.

  Preferable specific examples of the benzimidazole compound include methyl 2-benzimidazole carbamate, ethyl 2-benzimidazole carbamate, 2- (4-thiazolyl) benzimidazole and the like.

  In this invention, as a benzimidazole type compound, it can select and use 1 type (s) or 2 or more types from the group which consists of said compound.

  The haloacetylene compound is represented by the following formula (5).

[Wherein, X ₁ represents a halogen atom, R ₇ and R ₈ are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group, and m represents an integer of 0 or 1. ]

In the formula (5), examples of the halogen atom represented by X ₁ include fluorine, chlorine, bromine and iodine atoms, and an iodine atom is particularly preferable.

In the formula (5), the “optionally substituted hydrocarbon group” represented by R ₇ or R ₈ is the above-mentioned “optionally substituted hydrocarbon group” as one of the substituents of the A ₁ ring. And the like. Among them, an unsubstituted hydrocarbon group is preferable, an alkyl group having 1 to 10 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms is more preferable, an alkyl group having 1 to 10 carbon atoms is further preferable, and an alkyl group having 1 to 4 carbon atoms is more preferable. Alkyl groups are even more preferred, and n-butyl is particularly preferred.

One of R ₇ and R _{8 is} a hydrocarbon group which may be substituted, the other is preferably a hydrogen atom, and one of R ₇ and R ₈ is an alkyl group having 1 to 10 carbon atoms. More preferably, the other is a hydrogen atom, one of R ₇ and R ₈ is an alkyl group having 1 to 4 carbon atoms (particularly n-butyl), and the other is particularly preferably a hydrogen atom.

  In formula (5), m represents an integer of 0 or 1, and when m is 0, the haloacetylene compound is an acid amide derivative, and when m is 1, the haloacetylene compound is a carbamate derivative. Of these, carbamate derivatives of haloacetylene compounds in which m is 1 are preferred.

  Specific examples of haloacetylene compounds include 3-chloropropiolic acid amide, N-methyl-3-chloropropiolic acid amide, N-ethyl as acid amide derivatives of haloacetylene compounds when m is 0. -3-chloropropiolic amide, N-propyl-3-chloropropiolic amide, N-butyl-3-chloropropiolic amide, N-hexyl-3-chloropropiolic amide, N-octyl-3 (N-substituted-) 3-chloropropiolic amides such as chloropropiolic amide, N-cyclohexyl-3-chloropropiolic amide; 3-bromopropiolic amide, N-methyl-3-bromopropi All acid amide, N-ethyl-3-bromopropiolic acid amide, N-propyl-3-bromopropiolic acid N-butyl-3-bromopropiolic acid amide, N-hexyl-3-bromopropiolic acid amide, N-octyl-3-bromopropiolic acid amide, N-cyclohexyl-3-bromopropiolic acid amide, etc. (N-substituted-) 3-bromopropiolic amides; 3-iodopropiolic amides, N-methyl-3-iodopropiolic amides, N-ethyl-3-iodopropiolic amides, N-propyl -3-iodopropiolic amide, N-butyl-3-iodopropiolic amide, N-hexyl-3-iodopropiolic amide, N-octyl-3-iodopropiolic amide, N-cyclohexyl-3 -(N-substituted-) 3-iodopropiolic amides such as iodopropiolic amide. Of these, (N-substituted-) 3-iodopropiolic acid amide is preferable, and N-butyl-3-iodopropiolic acid amide is more preferable.

  Further, as a carbamate derivative of a haloacetylene compound when m is 1, 3-iodo-2-propynyl N-methylcarbamate, 3-iodo-2-propynyl N-ethylcarbamate, 3-iodo-2-propynyl N -Propyl carbamate, 3-iodo-2-propynyl N-butyl carbamate, 3-iodo-2-propynyl N-hexyl carbamate, 3-iodo-2-propynyl N-octyl carbamate, 3-iodo-2-propynyl N-cyclohexyl Examples thereof include 3-iodo-2-propynyl N-alkyl carbamate such as carbamate, among which 3-iodo-2-propynyl N-butyl carbamate is preferable.

  In this invention, as a haloacetylene type compound, 1 type (s) or 2 or more types can be selected and used from the group which consists of said compound.

  The tetrahydrothiophene dioxide compound is represented by the following formula (6).

[Wherein Y ₁ , Y ₂ , Y ₃ and Y ₄ are the same or different and each represents a hydrogen atom, a halogen atom or an optionally substituted hydrocarbon group. ]

In the formula (6), examples of the halogen atom represented by Y ₁ , Y ₂ , Y ₃ or Y ₄ include fluorine, chlorine, bromine and iodine atoms, with a chlorine atom being particularly preferred. In addition, the “optionally substituted hydrocarbon group” represented by Y ₁ , Y ₂ , Y ₃ or Y ₄ is the above “optionally substituted hydrocarbon” as one of the substituents of the A ₁ ring. The same thing as "hydrocarbon group" is mentioned, Especially, C1-C4 alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, are preferable.

As Y ₁ , Y ₂ , Y ₃ and Y ₄ , all of Y ₁ , Y ₂ , Y ₃ and Y ₄ are halogen atoms, or Y ₁ , Y ₂ and Y ₃ are halogen atoms and Y ₄ is It is preferably a hydrogen atom, or Y ₁ and Y ₄ are halogen atoms and Y ₂ and Y ₃ are preferably hydrogen atoms, and all of Y ₁ , Y ₂ , Y ₃ and Y ₄ are halogen atoms. More preferably, all of Y ₁ , Y ₂ , Y ₃ and Y ₄ are particularly preferably chlorine.

  Specific examples of the tetrahydrothiophene dioxide compound include 3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide, 3,3,4,4-tetrabromotetrahydrothiophene-1,1-dioxide, 3,4-dichlorotetrahydrothiophene-1,1-dioxide, 3,3,4-trichlorotetrahydrothiophene-1,1-dioxide, 3,3,4-tribromotetrahydrothiophene-1,1-dioxide Of these, 3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide is particularly preferred.

  In the present invention, the tetrahydrothiophene dioxide-based compound can be used by selecting one or more from the group consisting of the above compounds.

  The above-mentioned isothiazoline compounds, benzisothiazoline compounds, benzimidazole compounds, haloacetylene compounds and tetrahydrothiophene dioxide compounds may be used as salts with acids in the case of basic compounds. In some cases, it may be used as a salt with a base.

  Salts with acids include salts with inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid; formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, Examples include salts with organic acids such as citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.

  As a salt with a base, a salt with an alkali metal such as sodium or potassium; a salt with an alkaline earth metal such as magnesium or calcium; an ammonium salt; a trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine or triethanolamine And salts with organic amines such as ethylenediamine, 1,6-hexamethylenediamine, tert-butylamine, cyclohexylamine, benzylamine, dicyclohexylamine, N, N-dibenzylethylenediamine, and the like.

  Isothiazoline compounds, benzisothiazoline compounds, benzimidazole compounds, haloacetylene compounds, tetrahydrothiophene dioxide compounds, and salts thereof may be commercially available products, or those prepared according to known techniques may be used. However, it is convenient to use a commercially available product.

  In the industrial antiseptic / antifouling composition of the present invention, the content of the quinolone compound excluding oxolinic acid or a salt thereof is sufficient to obtain sufficient antibacterial activity against general bacteria present in the environment. 0.1 wt% to 40 wt% is preferable, and 1 wt% to 40 wt% is more preferable.

  When the above antibacterial compound is used in combination, a quinolone compound excluding oxolinic acid or a salt thereof is used to impart a broader antibacterial spectrum and sufficient antibacterial activity to the industrial antiseptic and antifouling composition of the present invention. And the antibacterial compound such as the isothiazoline-based compound (the total amount of each compound when two or more compounds are used) is preferably 9: 1 to 1: 9 (weight ratio). : 2 to 2: 8 (weight ratio) is more preferable. Further, although depending on the dosage form, application object, use environment, etc., the content of the quinolone compound or its salt excluding oxolinic acid is preferably 0.1% by weight to 40% by weight, and 1% by weight to 40% by weight. % Is more preferable. The content of the antibacterial compound such as the isothiazoline-based compound (the total amount of each compound when two or more are used) is preferably 0.1% by weight to 40% by weight, and more preferably 1% by weight to 40% by weight. preferable.

  The industrial antiseptic / antifouling composition of the present invention is dissolved in a solvent, or suspended or dispersed using a surfactant or a dissolution aid, etc., as a liquid agent, a suspending agent or a dispersing agent, or a surfactant. It can be emulsified with an agent and provided as an emulsion. In addition, surfactants and solid carriers can be added to provide wettable powders, flowable powders, powders, and the like.

  Examples of the solvent that can be used in the present invention include water; lower alcohols such as methanol, ethanol, n-propanol, isopropanol, and n-butanol; ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, 1, 3-butanediol, 1,4-butanediol, 1,5-pentanediol, ethylene glycol monomethyl ether (methyl carbitol), ethylene glycol monoethyl ether (ethyl carbitol), ethylene glycol monobutyl ether (butyl carbitol), Polyhydric alcohols such as diethylene glycol monomethyl ether and diethylene glycol monoethyl ether; acetone, methyl ethyl ketone, methyl alcohol Ketones such as butyl ketone and propylene carbonate; ethers such as dioxane, tetrahydrofuran and ethyl ether; ethyl acetate, butyl acetate, isobutyl acetate, 3-methyl-3-methoxybutyl acetate, γ-butyrolactone, dimethyl adipate, dimethyl glutarate Esters such as dimethyl succinate; aromatic solvents such as benzene, toluene, xylene, methylnaphthalene, dimethylnaphthalene, isopropylnaphthalene, diisopropylnaphthalene, ethylbiphenyl, diethylbiphenyl, solvent naphtha; carbon tetrachloride, chloroform, methylene chloride Halogenated hydrocarbon solvents such as: polar organic solvents such as dimethylformamide, dimethylacetamide, dimethyl sulfoxide, acetonitrile, N-methylpyrrolidone, etc. Is mentioned. These solvents may be used alone or in combination of two or more. Of these solvents, water, lower alcohols and polyhydric alcohols are preferably used.

  Examples of the surfactant that can be used in the present invention include nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester, polyoxyethienonyl phenyl ether, polyoxyethylene polyoxypropylene glycol; Examples include anionic surfactants such as ester salts, alkyl (aryl) sulfonates, dialkyl sulfosuccinates, polyoxyethylene alkylaryl ether phosphate esters, lignin sulfonates, and naphthalene sulfonate formalin condensates. . These may be used alone or in combination of two or more.

  Examples of the dissolution aid that can be used in the present invention include carboxylic acids such as capric acid and adipic acid; esters such as diisopropyl adipate, diisopropyl sebacate, isopropyl myristate, and isopropyl palmitate; higher grades such as octyldodecanol and oleyl alcohol. Examples of alcohols include amines such as monoethanolamine and diethanolamine, and these may be used alone or in combination of two or more.

  Examples of solid carriers that can be used in the present invention include minerals such as kaolin clay, attapulgite clay, bentonite, montmorillonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, and natural substances such as corn cob flour and walnut shell flour. Organic substances; synthetic organic substances such as urea; salts such as calcium carbonate and ammonium sulfate; fine powders or granules of synthetic inorganic substances such as synthetic hydrous silicon oxide.

  The industrial antiseptic / antifouling composition of the present invention is preferably prepared at 5 to 40 ° C. Mixing with a solvent or the like is preferably carried out by treatment for about 0.5 to 5 hours. Surfactant, solubilizer and solid carrier are blended in an amount of about 0.1% to 10%, 0.1% to 10% and 30% to 95% by weight, respectively, based on the total amount of the composition can do.

  In the antiseptic and antifouling composition for industrial use according to the present invention, in addition to other antibacterial and antifungal agents, algaeproofing agents, etc., as long as they do not affect the antibacterial activity, stability, safety, etc. of the composition, Additives generally used in the formulation, such as a pH adjuster, an antioxidant, a light stabilizer, and an antifoaming agent, can be added.

  The industrial antiseptic / antifouling composition of the present invention has good antibacterial activity against bacteria. Examples of the bacteria include Gram-negative rods such as Escherichia coli, Pseudomonas aeruginosa, Serratia and Legionella; Gram-positive rods such as Bacillus cereus and Clostridium; Gram-negative cocci such as Branhamella; Gram-positive cocci such as Staphylococcus aureus In addition to pathogenic bacteria such as Bacillus subtilis, bacteria that do not exhibit pathogenicity but are resident in the environment can be mentioned.

In the industrial antiseptic / antifouling composition of the present invention, when the above antibacterial compound is used in combination, the antibacterial spectrum is broader than when the quinolone compound excluding oxolinic acid or its salt is used alone, and only bacteria In addition, it has a wide and good antibacterial activity against molds and yeasts. As the fungi, Mucor (Mucor) genus (Mucor), Rhizopus Zygomycetes such as (Rhizopus) genus (Rhizopus); Aspergillus (Aspergillus) genus (Aspergillus), Penicillium (Penicillium) genus (Penicillium), Cladosporium ( Cladosporium) species (Aspergillus niger), Aureobasidium (Aureobasidium) sp., Alternaria (Alternaria) belonging to the genus (Susukabi), Acremonium (Acremonium) spp., Fusarium (Fusarium) genus Gliocladium (Gliocladium) genus Trichoderma ( Trichoderma) Deuteromycetes genera like; Chaetomium (Chaetomium) genus Yurochiumu (Eurotium) genus Neurospora (Neurospora) genus Ascomycetes such as (N. crassa), etc., as the yeasts, Schizosaccharomyces (Schizosaccharomyces) genus , Genus Protomyces , Taphrina, etc. Ascomycetous fungi; True Ascomycetes such as Endomyces ; Hemicystous fungi such as Saccharomyces ; Incomplete forms of Ascomycetous yeast such as Candida ; Filobasidiella ) atypical Basidiomycetes genus like; Rhodotorula (Rhodotorula) genus Trichosporon (Trichosporon) genus Suporoboromisesu (Sporobolomyces) incomplete type Basidiomycetes yeast genera and the like; Rhodosporidium di um (Rhodosporidium) genus scan poly audio Bors Examples include basidiomycetous yeasts such as ( Sporidiobolus ) genus and Xanthophyllomyces genus.

The antiseptic / antifouling composition of the present invention comprises cyanobacteria ( Cyanophyceae ), green algae ( Chlorophyceae ), green worms ( Euglenophyceae ), axle algae ( Charophyceae ), golden algae ( Chrysophyceae ), yellow green algae ( Xanthophyceae ), Since microbacteria such as diatoms ( Bacillariophyceae ) can exhibit a wide and good inhibitory action, an anti-algae effect is also expected.

  Therefore, the industrial antiseptic and antifouling composition of the present invention can be applied to various industrial waters such as paper pulp mills, cooling water circulation processes, coated papers, paper coating liquids, paints, adhesives, synthetic rubber latex, printing It can be effectively used for controlling harmful microorganisms in various industrial products such as inks, plastic products, cement admixtures, and sealing agents. More specifically, antibacterial and antifungal agents such as slime control agents for paper pulp mills and cooling water circulation processes, antibacterial and antifungal agents for paper products and resin products, paints, synthetic rubber latex, resins, inks, silicone sealants, etc. It is useful as such.

  The amount of the industrial antiseptic / antifouling composition of the present invention can be appropriately selected according to the application target, the type of microorganisms to be controlled (bacteria, molds, yeasts, algae, etc.) and the control period. For example, when used as a slime control agent, the amount of the antibacterial component is 0.1 mg to 500 mg, preferably 0.5 mg to 100 mg per 1 kg of the product. The amount of the antibacterial component per kg is 1 mg to 5,000 mg, preferably 10 mg to 1,000 mg. And 10 mg to 50,000 mg, preferably 100 mg to 10,000 mg.

  Hereinafter, the present invention will be described in detail with reference to examples.

[Example 1]
Methylcarbitol containing norfloxacin (1-ethyl-4-oxo-6-fluoro-7-piperazino-1,4-dihydroquinoline-3-carboxylic acid; manufactured by Wako Pure Chemical Industries, Ltd.) at 10% by weight And the mixture was stirred and mixed at room temperature for 30 minutes to obtain an industrial antiseptic and antifouling composition as a white suspension.

About Example 1, Example 2-22 mentioned later, and Comparative Examples 1-7, antibacterial activity was evaluated by the method shown below. In other words, as test bacteria, Bacillus subtilis IFO3513, Staphylococcus aureus IFO12732, Escherichia coli IFO3972, Pseudomonas aeruginosa IFO3080, Serratia marcescens IFO3735 in the fungi Aspergillus niger (Aspergillus niger IFO6341), blue mold (Penicillium citrinum IFO6352), Cladosporium class dos polio Lee Death (Cladosporium cladosporioides IFO6348), Out Leo Basi di Umm pullulans (Aureobasidium pullulans IFO6353), Alternaria species (Alternaria sp. ), Mucor Supinessensu (Mucor spinescens IFO6071), glyceryl okra di um Birensu (Gliocladium virens IFO6355), the yeasts Rhodotorula rubra (Rhodotorula rubra IFO0907), using a Saccharomyces cerevisiae (Saccharomyces cerevisiae IFO0209), in the case of bacteria, the real Glucose broth agar medium (pH 6.0) to which each of the industrial antiseptic and antifouling compositions of Examples and Comparative Examples was added was inoculated with a bacterial suspension for inoculation using a microplanter (manufactured by Sakuma Seisakusho). Cultured at 33 ° C. for 18 hours. In the case of molds and yeasts, a mold spore suspension or inoculation was carried out on a glucose broth agar medium (pH 6.0) to which the industrial antiseptic and antifouling compositions of Examples and Comparative Examples were added, respectively. The yeast suspension was inoculated, cultured at 33 ° C. for 18 hours, and further cultured at 28 ° C. for 2 days. After the cultivation, the growth of each bacterium was observed to determine the minimum inhibitory concentration (MIC) (μg / mL). The results for the industrial antiseptic / antifouling composition according to Example 1 are shown in Table 1.

  As is clear from Table 1, the industrial antiseptic and antifouling composition of Example 1 exhibits a MIC of 62.5 μg / mL or less against Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa, and has a good antibacterial activity. It was shown that. In particular, it showed excellent antibacterial activity against Bacillus subtilis, which is a non-pathogenic bacterium resident in the environment.

[Examples 2 to 22]
The composition of the industrial antiseptic / antifouling composition of Examples 2 to 22 of the present invention is shown in Table 2, and the composition of the industrial antiseptic / antifouling composition of Comparative Examples 1 to 7 is shown in Table 3. In the preparation of the compositions of the following examples and comparative examples, norfloxacin was manufactured by Wako Pure Chemical Industries, Ltd. as described above.

  Examples of the isothiazoline-based compound include “ZONEN-MT” (containing 50% by weight of 2-methyl-4-isothiazolin-3-one, manufactured by Chemicrea Co., Ltd.), “Caisson LX1400” (2-methyl-4-isothiazoline-3-one And 14% by weight of a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one, manufactured by Rohm and Haas), “Caisson 893T” (2-n-octyl-4-isothiazolin-3-one 99. 5% by weight contained, manufactured by Rohm and Haas).

  As the benzoisothiazoline compound, “BIT” (containing 1,2-benzisothiazolin-3-one 80% by weight, manufactured by Dow Chemical Company) was used.

  As the benzimidazole compound, “Coatside” (containing 10% by weight of methyl 2-benzimidazole carbamate hydrochloride, manufactured by Nippon Enviro Chemicals Co., Ltd.) was used.

  As the haloacetylene compound, “IPBC” (containing 99.4% by weight of 3-iodo-2-propynyl N-butylcarbamate, manufactured by Focus) was used.

  As the tetrahydrothiophene dioxide compound, a 20% by weight diethylene glycol monomethyl ether solution (manufactured by Nippon Enviro Chemicals Co., Ltd.) of slab curve (3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide) was used.

  The antiseptic and antifouling compositions for industrial use of Examples and Comparative Examples were prepared by adding each antibacterial compound to methyl carbitol according to the compositions shown in Tables 2 and 3 and stirring and mixing at room temperature for 30 minutes. Obtained as a white suspension or solution.

  Evaluation of antibacterial activity when norfloxacin and the above-mentioned predetermined antibacterial compound are used in combination (Examples 2 to 22) is norfloxacin, isothiazoline compound, benzisothiazoline compound, benzimidazole compound, haloacetylene compound and tetrahydrothiophene di The theoretical value of MIC was calculated from the MIC values when the oxide compounds were used alone (Example 1 and Comparative Examples 1 to 7) for the antiseptic / antifouling compositions of the above Examples by the following formulas. The MIC values measured in the above were compared with those. When the measured value of MIC is smaller than the theoretical value, that is, when “measured value / theoretical value” is smaller than 1, the antibacterial activity is enhanced from the algebraic sum when each of the above components is used alone. Therefore, it was evaluated that a synergistic effect was observed.

Theoretical value of MIC = C _A × x / 100 + C _B × y / 100
C _A ; MIC value when norfloxacin is used alone (Example 1) C _B ; isothiazoline compound, benzisothiazoline compound, benzimidazole compound, haloacetylene compound and tetrahydrothiophene dioxide compound alone MIC value when used (Comparative Examples 1 to 7) x: ratio of norfloxacin in antibacterial component (% by weight)
y: Ratio of the isothiazoline compound, benzisothiazoline compound, benzimidazole compound, haloacetylene compound or tetrahydrothiophene dioxide compound in the antibacterial component (% by weight)

  The evaluation results of antibacterial activity are shown in Tables 4 to 10. "100/0", "75/25", "50/50", "25/75" and "0/100" in each table are norfloxacin, isothiazoline compound, benzoisothiazoline compound, benzimidazole compound The compounding weight ratio with a compound, a haloacetylene compound or a tetrahydrothiophene dioxide compound is shown. In addition, in each table below, when norfloxacin and each of the above antibacterial compounds are used at the weight ratio, only test bacteria having an MIC value of less than 1000 μg / mL in at least one weight ratio are obtained. Indicated.

  Table 4 above shows industrial preservatives containing norfloxacin and isothiazoline-based compounds in a weight ratio of 100: 0, 75:25, 50:50, 25:75 as 2-methyl-4-isothiazolin-3-one. The evaluation result about an antifouling composition (Examples 1-4) is shown. The industrial antiseptic and antifouling compositions of Examples 2 to 4 showed effective antibacterial activity against bacteria as with the composition of Example 1. And for Bacillus subtilis, when the measured value / theoretical value of MIC is less than 1 for all compositions, norfloxacin and 2-methyl-4-isothiazolin-3-one are used alone (Example 1 and Compared to Comparative Example 1), a synergistic improvement in antibacterial activity was observed. In addition, the composition of Example 3 for S. aureus, the composition of Example 2 for Escherichia coli, and the composition of Example 4 for Serratia bacteria show a synergistic improvement in antibacterial activity. It was. For Pseudomonas aeruginosa, no synergistic improvement in antibacterial activity was observed in any of the compositions.

  Table 5 above shows a mixture of norfloxacin and 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one as isothiazoline-based compounds at 100: 0, 75:25. Evaluation results for industrial antiseptic / antifouling compositions (Examples 1 and 5 to 7) contained in weight ratios of 50:50 and 25:75 are shown. About the composition of Examples 5-7, antibacterial activity was recognized with respect to Serratia bacteria, molds, and yeasts in which the composition of Example 1 did not show so good antibacterial activity. In addition, except for the cases of Escherichia coli and Pseudomonas aeruginosa for the composition of Example 5, Bacillus subtilis and Pseudomonas aeruginosa for the composition of Example 6, and Pseudomonas aeruginosa for the composition of Example 7, the actual measured value / theory of MIC When the value is less than 1, norfloxacin and a mixture of 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one are used alone (Example 1 and Comparative Example) Compared to 2), a synergistic improvement in antibacterial activity was observed for each bacterium, mold and yeast tested.

  Table 6 above shows industrial use containing norfloxacin and 2-n-octyl-4-isothiazolin-3-one as isothiazoline-based compounds in weight ratios of 100: 0, 75:25, 50:50, 25:75. The evaluation result about antiseptic | preservation antifouling composition (Example 1, 8-10) is shown. The compositions of Examples 8 to 10 did not show effective antibacterial activity against Serratia bacteria, but showed effective antibacterial activity against molds and yeasts for which the composition of Example 1 was ineffective. It was. In addition, except for the cases of Bacillus subtilis for the compositions of Examples 9 and 10 and Staphylococcus aureus for all the compositions of Examples 8 to 10, the measured / theoretical value of MIC was smaller than 1, norfloxacin and 2-n− Compared with the case where octyl-4-isothiazolin-3-one was used alone (Example 1 and Comparative Example 3), a synergistic improvement in antibacterial activity was observed.

  Table 7 above shows industrial preservatives containing norfloxacin and 1,2-benzisothiazolin-3-one in a weight ratio of 100: 0, 75:25, 50:50, 25:75 as benzoisothiazoline compounds. The evaluation result about antifouling composition (Example 1, 11-13) is shown. The compositions of Examples 11 to 13 also showed antibacterial activity against fungi and yeasts except mucor spinens and glyocradium vilens. However, there was no synergistic improvement in antibacterial activity against E. coli and Pseudomonas aeruginosa. However, for other test strains, S. aureus, Aspergillus niger, Blue mold, Alternaria sp., Rhodotorula rubra, Saccharomyces cerevisiae for the composition of Example 11, and Rhodotor la rubra for the composition of Example 12, Example 13. Except for the case of S. aureus and Aspergillus niger, the measured / theoretical value of MIC was smaller than 1, and norfloxacin and 1,2-benzisothiazolin-3-one were each used alone (Example 1). As compared with Comparative Example 4), a synergistic improvement in antibacterial activity was observed.

  Table 8 shows industrial antiseptic / antifouling containing norfloxacin and methyl 2-benzimidazole carbamate hydrochloride as a benzimidazole compound in a weight ratio of 100: 0, 75:25, 50:50, 25:75. The evaluation result about a composition (Example 1, 14-16) is shown. The compositions of Examples 14 to 16 exhibited antibacterial activity against Staphylococcus aureus, bacteria other than Serratia, molds other than Alternaria, mucor spines, and rhodotoralbra. In addition, when the measured / theoretical value of MIC is less than 1 for the test bacteria that showed antibacterial activity, norfloxacin and methyl 2-benzimidazole carbamate hydrochloride were used alone (Example 1 and Comparative Example). Compared with 5), a synergistic improvement in antibacterial activity was observed.

  Table 9 shows industrial preservative containing norfloxacin and 3-iodo-2-propynyl N-butylcarbamate as a haloacetylene compound in a weight ratio of 100: 0, 75:25, 50:50, 25:75. -The evaluation result about antifouling composition (Example 1, 17-19) is shown. The compositions of Examples 17 to 19 exhibited antibacterial activity against bacteria, molds and yeasts other than Staphylococcus aureus and Serratia bacteria. In addition, when the measured / theoretical value of MIC is smaller than 1 for the test bacteria that showed antibacterial activity, norfloxacin and 3-iodo-2-propynyl N-butylcarbamate were used alone (Example 1). Compared with Comparative Example 6), a synergistic improvement in antibacterial activity was observed.

  Table 10 shows that norfloxacin and tetrahydrothiophene dioxide-based compounds are slab curve (3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide) 100: 0, 75:25, 50:50, The evaluation result about the industrial antiseptic / antifouling composition (Examples 20, 20 to 22) contained at a weight ratio of 25:75 is shown. The compositions of Examples 20-22 showed antimicrobial activity against all fungi tested. In addition, except for the cases of Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa for the composition of Example 20, and Escherichia coli and Pseudomonas aeruginosa for the compositions of Examples 21 and 22, the measured / theoretical value of MIC is smaller than 1. A synergistic improvement in antibacterial activity was observed as compared with cases where norfloxacin and slab curve were each used alone (Example 1 and Comparative Example 7).

[Example 23]
Ofloxacin standard (rac-9-fluoro-2,3-dihydro-3α ^* -methyl-10- (4-methyl-1-piperazinyl) -7-oxo-7H-pyrido [1,2,3-de]- 1,4-benzoxazine-6-carboxylic acid (manufactured by Wako Pure Chemical Industries, Ltd.) was added to methyl carbitol so as to be 10% by weight and prepared by stirring and mixing at room temperature for 30 minutes. An antiseptic and antifouling composition for industrial use which is a suspending agent was obtained.

[Examples 24-44]
In Table 2 above, norfloxacin was replaced with ofloxacin and prepared in the same manner to obtain industrial antiseptic and antifouling compositions of Examples 24-44. As for ofloxacin, the same standard product manufactured by Wako Pure Chemical Industries, Ltd. was used.

  The antiseptic activity of the industrial antiseptic and antifouling compositions of Examples 23 to 44 was evaluated in the same manner as described above. In addition, the antiseptic activity of the industrial antiseptic and antifouling compositions of Comparative Examples 1 to 7 was also evaluated. As for the industrial antiseptic / antifouling compositions of Examples 24-44, it was also evaluated whether or not synergistic improvement in antibacterial activity was observed by using ofloxacin and other antibacterial compounds in the same manner as described above. did.

  The MIC measurement results for Example 23 are shown in Table 11.

  As can be seen from Table 11, the industrial antiseptic and antifouling composition of Example 23 containing ofloxacin was less than 62.5 μg / mL against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. In contrast, it showed an MIC of 125 μg / mL, indicating good antibacterial activity against bacteria. In particular, it showed excellent antibacterial activity against Bacillus subtilis, which is a non-pathogenic bacterium resident in the environment.

  The evaluation result of antibacterial activity was shown to Tables 12-18 about Examples 24-44 which used ofloxacin and another antibacterial compound together. "100/0", "75/25", "50/50", "25/75" and "0/100" in each table are ofloxacin, isothiazoline compound, benzoisothiazoline compound, benzimidazole compound The compounding weight ratio with a compound, a haloacetylene compound or a tetrahydrothiophene dioxide compound is shown. In the following tables, for ofloxacin and each of the antibacterial compounds described above, only test bacteria having an MIC value of less than 1000 μg / mL in at least one weight ratio when used at the weight ratio described above. Indicated.

  Table 12 above shows industrial preservatives containing ofloxacin and isothiazoline-based 2-methyl-4-isothiazolin-3-one in weight ratios of 100: 0, 75:25, 50:50, 25:75. The evaluation result about an antifouling composition (Examples 23-26) is shown. The industrial antiseptic and antifouling compositions of Examples 24 to 26 showed good antibacterial activity against bacteria in the same manner as the composition of Example 23. Except for the case against Serratia bacteria, the MIC actual value / theoretical value is less than 1 for all the compositions, and ofloxacin and 2-methyl-4-isothiazolin-3-one were used alone (Example 23). As compared with Comparative Example 1), a synergistic improvement in antibacterial activity was observed.

  Table 13 above shows a mixture of ofloxacin and isothiazoline-based compounds 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one at 100: 0, 75:25. , 50:50, 25:75 The evaluation result about the antiseptic | preservation antifouling | stain-proof composition (Example 23, 27-29) contained in the weight ratio is shown. About the composition of Examples 27-29, favorable antimicrobial activity was recognized with respect to the molds and yeasts in which the composition of Example 23 did not show effective antimicrobial activity. Except for the cases of S. aureus and E. coli for the compositions of Examples 27-29 and Pseudomonas aeruginosa for the compositions of Examples 27 and 28, the measured / theoretical value of MIC was less than 1, and ofloxacin and 2- Each bacterium tested compared to when methyl-4-isothiazolin-3-one / 5-chloro-2-methyl-4-isothiazolin-3-one mixture was used alone (Example 23 and Comparative Example 2), A synergistic improvement in antibacterial activity was observed for mold and yeast.

  Table 14 above shows industrial use containing ofloxacin and 2-n-octyl-4-isothiazolin-3-one, which is an isothiazoline-based compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. The evaluation result about antiseptic | preservation antifouling composition (Example 23, 30-32) is shown. Effective antibacterial activity was observed against the tested bacteria, molds and yeasts, except that the compositions of Examples 31 and 32 did not show effective antibacterial activity against Serratia bacteria. In addition, when effective antibacterial activity was observed, the measured / theoretical value of MIC was smaller than 1, and ofloxacin and 2-n-octyl-4-isothiazolin-3-one were used alone (implementation) Compared with Example 23 and Comparative Example 3), a synergistic improvement in antibacterial activity was observed.

  Table 15 shows industrial preservatives containing ofloxacin and 1,2-benzisothiazolin-3-one, which is a benzoisothiazoline-based compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. The evaluation result about antifouling composition (Example 23, 33-35) is shown. Antibacterials in which the composition of Example 33 is effective against Aspergillus niger, Blue mold, Aureobasidium pullulans, Alternaria spp., Mucor spinescens and Rhodotorula rubra, and the compositions of Examples 33-35 against Gliocladium bilens Effective antibacterial activity was observed except that it did not show activity. In addition, among the cases where effective antibacterial activity was observed, the measured / theoretical values of MICs were other than those for S. aureus and Pseudomonas aeruginosa for the compositions of Examples 33 to 35 and for Mucor spinesens for Example 35. A synergistic improvement in antibacterial activity was observed as compared to the case where ofloxacin and 1,2-benzisothiazolin-3-one were each used alone (Example 23 and Comparative Example 4).

  Table 16 above shows industrial antiseptic / antifouling containing ofloxacin and methyl 2-benzimidazole carbamate hydrochloride, which is a benzimidazole compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. The evaluation result about a composition (Example 23, 36-38) is shown. For the compositions of Examples 36-38, no effective antibacterial activity was found for Alternaria, Mucor spinescens and Saccharomyces cerevisiae, the composition of Example 38 against Serratia sp. Antibacterial activity was observed against moss and yeast. In addition, when the measured / theoretical value of MIC was less than 1 for the test bacteria that showed antibacterial activity, ofloxacin and methyl 2-benzimidazole carbamate hydrochloride were each used alone (Example 23 and Comparative Example) Compared with 5), a synergistic improvement in antibacterial activity was observed.

  Table 17 above shows industrial preservatives containing ofloxacin and 3-iodo-2-propynyl N-butyl carbamate, which is a haloacetylene compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. -The evaluation result about an antifouling composition (Example 23, 39-41) is shown. Except that the composition of Example 41 did not show effective antibacterial activity against Serratia bacteria, it showed antibacterial activity against the tested bacteria, molds and yeasts. In addition, when the measured / theoretical value of MIC is less than 1 for the test bacteria that showed antibacterial activity, ofloxacin and 3-iodo-2-propynyl N-butylcarbamate were each used alone (Example 23). Compared with Comparative Example 6), a synergistic improvement in antibacterial activity was observed.

  Table 18 shows that ofloxacin and sura curve (3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide), which is a tetrahydrothiophene dioxide-based compound, are 100: 0, 75:25, 50:50. The evaluation result about the industrial antiseptic / antifouling composition (Example 23, 42 to 44) contained in a weight ratio of 25:75 is shown. The compositions of Examples 42-44 showed antibacterial activity against all fungi tested. In addition, except for the cases against Escherichia coli, Pseudomonas aeruginosa and Serratia bacteria, the measured value / theoretical value of MIC is smaller than 1, compared to the case where ofloxacin and sura curve were used alone (Example 23 and Comparative Example 7), A synergistic improvement in antibacterial activity was observed.

[Example 45]
Difloxacin standard product (1- (4-fluorophenyl) -4-oxo-6-fluoro-7- (4-methylpiperazino) -1,4-dihydroquinoline-3-carboxylic acid; manufactured by Wako Pure Chemical Industries, Ltd.) It was added to methyl carbitol so as to be 10% by weight and prepared by stirring and mixing at room temperature for 30 minutes to obtain an industrial antiseptic / antifouling composition as a white suspension.

[Examples 46 to 66]
In Table 2 above, norfloxacin was replaced with difloxacin and prepared in the same manner to obtain industrial antiseptic and antifouling compositions of Examples 46-66. As difloxacin, the same standard product manufactured by Wako Pure Chemical Industries, Ltd. was used.

  The antiseptic activity of the industrial antiseptic and antifouling compositions of Examples 45 to 66 was evaluated in the same manner as described above. In addition, the antiseptic activity of the industrial antiseptic and antifouling compositions of Comparative Examples 1 to 7 was also evaluated. About the industrial antiseptic and antifouling compositions of Examples 46 to 66, as described above, it was also evaluated whether or not a synergistic improvement in antibacterial activity was observed by using difloxacin in combination with other antibacterial compounds. did.

  The MIC measurement results for Example 45 are shown in Table 19.

  As can be seen from Table 19, the industrial antiseptic / antifouling composition of Example 45 containing difloxacin is less than 62.5 μg / mL against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. In contrast, it showed an MIC of 250 μg / mL, indicating that it has good antibacterial activity against bacteria. In particular, it showed excellent antibacterial activity against Bacillus subtilis, which is a non-pathogenic bacterium resident in the environment.

  The evaluation result of antibacterial activity was shown to Tables 20-26 about Examples 46-66 which use a difloxacin and another antibacterial compound together. “100/0”, “75/25”, “50/50”, “25/75” and “0/100” in each table are difloxacin, an isothiazoline compound, a benzoisothiazoline compound, and a benzimidazole compound. The compounding weight ratio with a compound, a haloacetylene compound or a tetrahydrothiophene dioxide compound is shown. In addition, in the following tables, for difloxacin and each of the above antibacterial compounds, when used in the above weight ratio, only test bacteria having an MIC value of less than 1000 μg / mL in at least one weight ratio are obtained. Indicated.

  Table 20 above shows industrial preservatives containing difloxacin and 2-methyl-4-isothiazolin-3-one, which is an isothiazoline-based compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. The evaluation result about an antifouling composition (Examples 45-48) is shown. The industrial antiseptic and antifouling compositions of Examples 46 to 48 showed good antibacterial activity against bacteria as with the composition of Example 45. Except for the case against Serratia bacteria, the measured / theoretical value of MIC is smaller than 1, and difloxacin and 2-methyl-4-isothiazolin-3-one are used alone (Example 45 and Comparative Example 1). A synergistic improvement in antibacterial activity was observed.

  Table 21 above shows a mixture of difloxacin and the isothiazoline-based compounds 2-methyl-4-isothiazolin-3-one and 5-chloro-2-methyl-4-isothiazolin-3-one at 100: 0, 75:25. Evaluation results for industrial antiseptic / antifouling compositions (Examples 45, 49 to 51) contained in weight ratios of 50:50 and 25:75 are shown. About the composition of Examples 49-51, favorable antimicrobial activity was recognized with respect to the molds and yeasts in which the composition of Example 45 did not show effective antimicrobial activity. Except for the compositions of Examples 50 and 51 against Staphylococcus aureus and the composition of Example 51 against Escherichia coli, the measured / theoretical value of MIC is less than 1, difloxacin and 2-methyl-4-isothiazoline- Compared to the case where the 3-one-5-chloro-2-methyl-4-isothiazolin-3-one mixture was used alone (Example 45 and Comparative Example 2), each tested bacteria, mold and yeast A synergistic improvement in antibacterial activity was observed.

  Table 22 above shows industrial use containing difloxacin and 2-n-octyl-4-isothiazolin-3-one, which is an isothiazoline-based compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. The evaluation result about antiseptic | preservation antifouling composition (Example 45, 52-54) is shown. The composition of Example 53 did not show effective antibacterial activity against Serratia and the composition of Example 54 against Escherichia coli and Serratia, but otherwise, against the tested bacteria, molds and yeasts, Effective antibacterial activity was observed. In addition, when effective antibacterial activity was observed, the actual measurement value / theoretical value of MIC was smaller than 1, and difloxacin and 2-n-octyl-4-isothiazolin-3-one were each used alone (implementation) Compared to Example 45 and Comparative Example 3), a synergistic improvement in antibacterial activity was observed.

  Table 23 shows industrial preservatives containing difloxacin and 1,2-benzisothiazolin-3-one, which is a benzoisothiazoline compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. The evaluation result about an antifouling composition (Example 45, 55-57) is shown. The composition of Example 55 does not show effective antibacterial activity against Aspergillus, Alternaria, Mucor spinescens, Gliocladium virens and Rhodotor la rubra, and Example 56 against Glyocladium bilens Besides, effective antibacterial activity was observed. Further, among the cases where effective antibacterial activity was observed, the measured value / theoretical value of MIC except for the case of Escherichia coli and Serratia bacteria for the composition of Example 55 and Pseudomonas aeruginosa for the compositions of Examples 55 to 57. Was less than 1, and a synergistic improvement in antibacterial activity was observed compared to difloxacin and 1,2-benzisothiazolin-3-one used alone (Example 45 and Comparative Example 4), respectively.

  Table 24 above shows industrial antiseptic / antifouling containing difloxacin and methyl 2-benzimidazole carbamate hydrochloride, which is a benzimidazole compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. The evaluation result about a composition (Example 45, 58-60) is shown. For the compositions of Examples 58-60, no effective antibacterial activity against Serratia spp. Was observed for the genus Alternaria, Mucor spinescens and Saccharomyces cerevisiae, and the composition of Example 60. However, antibacterial activity was observed against other bacteria, molds and yeasts tested, the measured / theoretical value of MIC was less than 1, and difloxacin and methyl 2-benzimidazole carbamate hydrochloride were used alone In comparison with the case (Example 45 and Comparative Example 5), a synergistic improvement in antibacterial activity was observed.

  Table 25 shows industrial preservatives containing difloxacin and 3-iodo-2-propynyl N-butyl carbamate, which is a haloacetylene compound, in a weight ratio of 100: 0, 75:25, 50:50, 25:75. -The evaluation result about antifouling composition (Example 45, 61-63) is shown. Except that the composition of Example 63 did not show effective antibacterial activity against E. coli, Pseudomonas aeruginosa and Serratia bacteria, it showed antibacterial activity against the tested bacteria, molds and yeasts. For the test bacteria that showed antibacterial activity, the measured / theoretical value of MIC was less than 1 for the composition of Example 61, except for Serratia bacteria, and difloxacin and 3-iodo-2-propynyl N -A synergistic improvement in antibacterial activity was observed as compared to the cases where butyl carbamate was used alone (Example 45 and Comparative Example 6).

  Table 26 above shows difloxacin and Sura curve (3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide), which is a tetrahydrothiophene dioxide-based compound, at 100: 0, 75:25, 50:50. The evaluation result about the industrial antiseptic / antifouling composition (Example 45, 64 to 66) contained at a weight ratio of 25:75 is shown. The compositions of Examples 64-66 showed antimicrobial activity against all fungi tested. Except for the case of Escherichia coli and Pseudomonas aeruginosa for the composition of Example 65 and Serratia for the compositions of Examples 64 and 66, the measured / theoretical value of MIC was less than 1, and difloxacin and slab curve were each independently As compared with the case (Example 45 and Comparative Example 7), a synergistic improvement in antibacterial activity was observed.

  As described above, in the antiseptic / antifouling compositions of the examples of the present invention, the quinolone compounds norfloxacin, ofloxacin and difloxacin are also present against non-pathogenic bacteria that are resident in the environment such as Bacillus subtilis. It was found to have antibacterial activity. Further, by using a predetermined antibacterial compound in combination, the antibacterial activity increased synergistically, and a wide range of synergistic improvements in the antibacterial activity was observed for bacteria, fungi and fungi of yeast.

  According to the present invention, there is provided an industrial antiseptic and antifouling composition that can be used for a wide range of industrial applications such as industrial water and the control of harmful microorganisms in various industrial products, and in which each of these applications has synergistically improved antibacterial activity. Can be provided.

  This application is based on Japanese Patent Application No. 2010-99228 for which it applied in Japan, The content is altogether included in this specification.

Claims (5)

One or more selected from the group consisting of a quinolone compound represented by formula (8) and a salt thereof, a benzimidazole compound represented by formula (4), and a haloacetylene compound represented by formula (5) compounds, tetrahydrothiophene dioxide-based compound represented by the formula (6), and one or containing two or more, industrial for preservative-antifouling composition is selected from the group consisting of salts.

[Wherein, R ₁ represents an alkyl group having 1 to 4 carbon atoms or a fluorophenyl group, R ₂ , R ₉ and R ₁₂ represent hydrogen atoms, R ₁₀ represents a halogen atom, and R ₁₁ represents 1 carbon atom. The piperazinyl group which may be substituted by the alkyl group of -4 is shown. R ₁ may form an oxazine ring together with R ₁₂ . ]

Wherein, _{A 3} ring represents a benzene ring, Z is -NHCOOR ₆ (wherein, _{R 6} represents. An alkyl group having 1 to 3 carbon atoms) a group represented by. ]

[Wherein, X ₁ represents a halogen atom, R ₇ represents an alkyl group having 1 to 4 carbon atoms , R ₈ represents a hydrogen atom, and m is 1 . ]

_Wherein, Y _1, Y 2, _{Y 3} and _{Y 4} are the same or different and each indicates a hydrogen atom or a halogen _atom, all of Y _1, Y 2, _{Y 3} and _{Y 4} is a halogen atom Or Y ₁ , Y ₂ and Y ₃ are halogen atoms and Y ₄ is a hydrogen atom, or Y ₁ and Y ₄ are halogen atoms and Y ₂ and Y ₃ are hydrogen atoms . ] Quinolone compound represented by the formula (8) is, Bruno Rufurokisashin, di Furokisashin, is one or more selected from ofloxacin and Rebofurokisashi emissions by Li Cheng group, preservative-industrial according to claim 1 Antifouling composition. Benzimidazole-based compound represented by the formula (4) is methyl 2-benzimidazole carbamate Mae preparative, industrial preservatives, antifouling composition of claim 1. The industrial antiseptic / antifouling composition according to claim 1 , wherein the haloacetylene compound represented by the formula (5) is 3-iodo-2-propynyl N-butylcarbamate. The industrial antiseptic / antifouling composition according to claim 1 , wherein the tetrahydrothiophene dioxide compound represented by the formula (6) is 3,3,4,4-tetrachlorotetrahydrothiophene-1,1-dioxide. .