JP2018167182A - Biofilm formation inhibitor - Google Patents

Abstract

To provide a substance that can effectively inhibit biofilm formation.SOLUTION: A biofilm formation inhibitor has a compound represented by the following formula (I) as an active ingredient (where R, R, R, and Rindependently represent a hydrogen atom, a hydroxy group, an alkoxy group, a C1-6 hydrocarbon group, or -CH-R, where, all of R, R, R, and Rare not hydrogen atoms at the same time; Ris a hydroxy group, a halogen atom, or -NRR; Rand Rindependently represent a hydrogen atom or a methyl group).SELECTED DRAWING: None

Description

  The present invention relates to a biofilm formation inhibitor and a biofilm formation suppression method.

  A biofilm is a structure formed by a community of microorganisms such as bacteria and mold attached to a solid or liquid surface together with secretions. Biofilms generated in household or factory drainage facilities, water circulation systems, and the like cause slimming of pipes, and foul odors. Biofilms also cause equipment degradation, such as sewer pipe corrosion. In the reverse osmosis membranes used in seawater desalination plants, piping facilities in paper mills, etc., adverse effects due to biofilm formation are regarded as problems. In addition, biofilms cause microbial contamination. Biofilm generated in hot spring facilities may cause infections. In the medical field, biofilms formed on medical instruments such as dialysis tubes, endoscopes, and contact lenses may be the source of infection. Biofilm formation in the skin and oral cavity can cause disease. In the food field, biofilms formed on food or cooking utensils can cause rot and food poisoning.

  When microorganisms form a biofilm, it becomes resistant to ordinary washing and sterilization methods, and thus it is not easy to eliminate them. In order to prevent biofilm formation in a drainage facility or a water circulation system, it is necessary to periodically replace or clean the water, which increases the maintenance cost of the facility or system.

  Biofilms in water circulation systems and the like include gram-negative microorganisms such as Pseudomonas genus such as Pseudomonas aeruginosa, Sphingomonas genus, and Sphingopyxis genus. Furthermore, there are reports that microorganisms of the genera Klebsiella, Flavobacterium and Roseomonas were found from the biofilm in the water-cooled cooling tower (Non-patent Documents 1 and 2). Conventionally, bactericides such as chlorine-based chemicals and organic nitrogen-sulfur-based chemicals have been used to prevent biofilms in drainage facilities and water circulation systems. However, chlorinated drugs have a problem of damage to piping and equipment, and organic nitrogen sulfur-based drugs have problems such as skin damage. Therefore, any drug cannot be used at a concentration that can be sufficiently sterilized, and biofilm formation cannot be suppressed for a long time.

  Patent Document 1 discloses an industrial antibacterial agent containing a compound such as o-phthalaldehyde and p-phthalaldehyde or m-phthalaldehyde. Patent Document 2 discloses an antibacterial composition containing a compound such as isophthalaldehyde. Non-Patent Literature 3, Non-Patent Literature 4 and Non-Patent Literature 5 disclose 4-hydroxyphthalaldehyde and the like as compounds having antibacterial activity.

JP-A-9-295906 JP 2003-192581 A

Biofouling, 2011,, 27 (4): 393-402 Biocontrol Science, 2013, 18 (4): 205-209 Z. Naturforsch, 2007, 62c: 487-497 Z. Naturforsch, 2011, 66c: 571-580 European Journal of Medicinal Chemistry, 2015, 92: 750-753

  The present invention provides a biofilm formation inhibitor that can effectively suppress biofilm formation.

  As a result of intensive studies, the present inventors have found that biofilm formation can be effectively suppressed even when a specific phthalaldehyde compound is used at a low concentration.

Therefore, this invention provides the biofilm formation inhibitor which uses the compound represented by following formula (I) as an active ingredient.
Moreover, this invention provides the biofilm formation suppression method including adding the compound represented by following formula (I) to object water.

(Where
R ¹ , R ² , R ³ , and R ⁴ are each independently a hydrogen atom, a hydroxyl group, an alkoxy group, a hydrocarbon group having 1 to 6 carbon atoms, or —CH ₂ —R ⁵ , provided that R ¹ , R ² , R ³ , and R ⁴ are not all hydrogen atoms at the same time;
R ⁵ is a hydroxy group, a halogen atom, or —NR ^a R ^b ;
R ^a and R ^b are each independently a hydrogen atom or a methyl group. )

  The biofilm formation inhibitor of the present invention can suppress biofilm formation even when used at a low concentration.

  The biofilm formation inhibitor of the present invention is used for suppressing biofilm formation under various environments such as home or factory facilities. Preferably, the biofilm formation inhibitor of the present invention functions by flowing or storing water therein, such as pipes through which water flows, tanks and pools for storing water, water circulation systems, and devices attached thereto. Used to suppress biofilm formation in equipment. Among the above facilities, the biofilm formation inhibitor of the present invention is suitably used at a temperature at which at least a part thereof reaches a temperature at which a biofilm is easily formed, for example, 20 ° C. or higher, preferably 25 ° C. or higher. Suitable examples of equipment to which the biofilm formation inhibitor of the present invention is applied include factory equipment and building cooling systems using water-cooled cooling towers, industrial cooling pools, industrial water supply, water storage or drainage paths. And hot water heating systems, wastewater treatment facilities, reverse osmosis membranes used in seawater desalination plants, and paper mill piping facilities.

  In the present specification, “target water” refers to water to which the biofilm formation inhibitor of the present invention is applied. Preferably, the “target water” is water that flows or is stored in facilities that function by flowing or storing the above-mentioned water, for example, a factory facility using a water-cooled cooling tower or a cooling system for a building. Used in industrial water, industrial cooling pool water, industrial water supply, water in storage or drainage channels, hot water used in hot water heating systems, wastewater from wastewater treatment facilities, seawater desalination plants The water which passes a reverse osmosis membrane, the water in the piping installation of a paper mill, etc. are mentioned, Preferably the cooling water of a water cooling type cooling tower is mentioned. The biofilm formation inhibitor of the present invention is added to the target water.

  Biofilms generated in the above facilities include gram-negative microorganisms such as Pseudomonas genus such as Pseudomonas aeruginosa, Sphingomonas genus, and Sphingopyxis genus. Furthermore, gram-negative microorganisms of the genus Klebsiella, the genus Flavobacterium and the genus Roseomonas have been reported as microorganisms present in biofilms in water-cooled cooling towers (Non-patent Documents 1 and 2).

  In the present invention, a compound represented by the following formula (I) (hereinafter also referred to as a compound of the formula (I) in the present specification) is used as an active ingredient for suppressing biofilm formation.

In the formula (I), R ¹ , R ² , R ³ , and R ⁴ are each independently a hydrogen atom, a hydroxyl group, an alkoxy group, a hydrocarbon group having 1 to 6 carbon atoms, or —CH ₂ —R ⁵ . is there. However, R ¹ , R ² , R ³ , and R ⁴ are not all hydrogen atoms at the same time.

In the formula (I), the hydrocarbon group having 1 to 6 carbon atoms for R ^{1 to} R ⁴ may be saturated or unsaturated, or may be linear or branched. Alternatively, it may be a cyclic group. From the viewpoint of availability of the compound, the hydrocarbon group is preferably unsubstituted. Examples of the hydrocarbon group having 1 to 6 carbon atoms include a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkenyl group having 2 to 6 carbon atoms. From the viewpoint of water solubility of the compound of formula (I), preferred examples include a linear or branched alkyl group having 1 to 4 carbon atoms and a linear or branched alkenyl group having 2 to 4 carbon atoms. More preferable examples of the hydrocarbon group having 1 to 6 carbon atoms include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, s-butyl group, t-butyl group, pentyl group, and hexyl group. 1-propenyl group, 2-propenyl (allyl) group, 2-t-amyl group, cyclohexyl group, cyclopentyl group and the like. In the formula (I), the hydrocarbon group having 1 to 6 carbon atoms may be independently selected for R ^{1 to} R ⁴ .

Examples of the alkoxy group for R ^{1 to} R ⁴ include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, an isobutoxy group, an s-butoxy group, and a t-butoxy group. In the formula (I), the alkoxy groups may be independently selected for R ^{1 to} R ⁴ .

In formula (I), R ⁵ is a hydroxy group, a halogen atom, or —NR ^a R ^b . Examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom, and a chlorine atom is preferable from the viewpoint of availability of the compound. R ^a and R ^b are each independently a hydrogen atom or a methyl group. Preferably, —NR ^a R ^b is a dimethylamino group.

In one embodiment, R ¹ is a hydroxyl group and R ² , R ³ and R ⁴ are hydrogen atoms. In another embodiment, R ⁴ is a hydroxyl group and R ¹ , R ² and R ³ are hydrogen atoms.

In another embodiment, R ² is a hydrocarbon group having 1 to 6 carbon atoms, R ¹ and R ³ are hydrogen atoms, and R ⁴ is a hydroxyl group. The hydrocarbon group having 1 to 6 carbon atoms for R ² is preferably a linear or branched alkyl group having 1 to 6 carbon atoms or a linear or branched chain having 2 to 6 carbon atoms from the viewpoint of water solubility. A branched alkenyl group, more preferably a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear or branched alkenyl group having 2 to 4 carbon atoms, and more preferably a methyl group. , Ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, s-butyl group, or t-butyl group, and more preferably a methyl group or an ethyl group.

In another embodiment, R ¹ , R ² and R ³ are each independently a hydrocarbon group having 1 to 6 carbon atoms, and R ⁴ is a hydroxyl group. The hydrocarbon group having 1 to 6 carbon atoms for R ¹ , R ² and R ³ is preferably independently from the viewpoint of water solubility, preferably a linear or branched alkyl group having 1 to 6 carbon atoms, or A linear or branched alkenyl group having 2 to 6 carbon atoms, more preferably a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear or branched alkenyl group having 2 to 4 carbon atoms More preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, an s-butyl group, a t-butyl group, a 1-propenyl group, or a 2-propenyl group, A methyl group or an ethyl group is preferable.

In another embodiment, R ¹ , R ³ and R ⁴ are hydrogen atoms and R ² is a hydrocarbon group having 1 to 6 carbon atoms. The hydrocarbon group having 1 to 6 carbon atoms for R ² is preferably independently from the viewpoint of water solubility, preferably a linear or branched alkyl group having 1 to 6 carbon atoms, or 2 to 6 carbon atoms. A linear or branched alkenyl group, more preferably a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear or branched alkenyl group having 2 to 4 carbon atoms, and more preferably Is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, an s-butyl group, a t-butyl group, a 1-propenyl group, or a 2-propenyl group, more preferably a methyl group or ethyl It is a group.

In another embodiment, R ¹ , R ² and R ⁴ are hydrogen atoms and R ³ is a hydrocarbon group having 1 to 6 carbon atoms. The hydrocarbon group having 1 to 6 carbon atoms for R ³ is preferably independently from the viewpoint of water solubility, preferably a linear or branched alkyl group having 1 to 6 carbon atoms, or 2 to 6 carbon atoms. A linear or branched alkenyl group, more preferably a linear or branched alkyl group having 1 to 4 carbon atoms, or a linear or branched alkenyl group having 2 to 4 carbon atoms, and more preferably Is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, an s-butyl group, a t-butyl group, a 1-propenyl group, or a 2-propenyl group, more preferably a methyl group or ethyl It is a group.

  Preferable examples of the compound represented by the formula (I) used as an active ingredient in the present invention include 4-hydroxyisophthalaldehyde, 2-hydroxyisophthalaldehyde, and 2-hydroxy-5-methylisophthalaldehyde. .

  The compound used as an active ingredient in the present invention may be any one of the compounds of formula (I) exemplified above, or may be a combination of any two or more.

  The biofilm formation inhibitor of the present invention may contain only one or two or more of the above-mentioned formula (I) compounds which are active ingredients, or further other than the above-mentioned formula (I) compound. It may contain components. Therefore, the form of the composition may be sufficient as the biofilm formation inhibitor of this invention. Examples of the other components include chelating agents, organic solvents, substances to which the biofilm formation inhibitor of the present invention is applied, substances for cleaning or preventing deterioration, antibacterial agents, and bactericides. The type and concentration of the other components are not particularly limited as long as the biofilm formation inhibitory action of the compound of formula (I) is not inhibited.

  Examples of the chelating agent include carboxylic acid-based, phosphoric acid-based, and phosphonic acid-based chelating agents. Examples of the carboxylic acid chelating agent include polyvalent carboxylic acid, hydroxycarboxylic acid, aminocarboxylic acid, phosphonocarboxylic acid, and salts thereof. Examples of the polyvalent carboxylic acid include citric acid, succinic acid, malic acid, fumaric acid, tartaric acid, malonic acid, maleic acid and the like. Examples of the hydroxycarboxylic acid include aliphatic hydroxycarboxylic acids such as citric acid and malic acid. As aminocarboxylic acids, ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), iminodiacetic acid, diethylenetriaminepentaacetic acid (DPTA), N-hydroxyethyl-ethylenediaminetriacetic acid (HEDTA), methylglycine diacetic acid (MGDA) , Aspartic acid diacetic acid (ASDA), glutamic acid diacetic acid (GLDA), and the like. Examples of the phosphonocarboxylic acid include 2-phosphonobutane-1,2,4-tricarboxylic acid. Examples of the phosphoric acid chelating agent include tripolyphosphoric acid and a salt thereof. Examples of phosphonic acid chelating agents include hydroxyphosphonic acids such as 1-hydroxyethane-1,1-diphosphonic acid (HEDP), aminophosphonic acids such as aminotrimethylenephosphonic acid (ATMP), and salts thereof. . Examples of the salt include alkali metal salts such as sodium and potassium, ammonium salts, and amine salts.

  The kind of the organic solvent is not particularly limited, and may be aliphatic or aromatic. From the viewpoint of dissolving and stabilizing the compound of formula (I), the SP value of the organic solvent is preferably 9.0 or more, more preferably 9.2 or more, and still more preferably 10.0 or more. And preferably it is 11.0 or less, More preferably, it is 10.8 or less. Alternatively, the SP value of the organic solvent is preferably 9.0 to 11.0, more preferably 9.2 to 11.0, still more preferably 10.0 to 11.0, and still more preferably 10.0 to 10. .8.

In the present specification, the SP value is a measure of compatibility between substances and is a value calculated by the following method:
SP value = {(dΣG) / M} ^1/2
M: molecular weight [unit: g / mol]
d: Density [Unit: g / cm ³ ]
G: atomic group or group specific Hoy cohesive energy constant [unit: cal / mol]
The above-mentioned atomic group or group-specific Hoy cohesive energy constant G is described in Color Materials Association, 1971, vol. 44 (4): Refer to the values described in 186-192 (written by Toyohiko Yoshida).

Preferably, the organic solvent includes an ether organic solvent, an amide organic solvent, an alcohol organic solvent, a ketone organic solvent, a sulfoxide organic solvent, and an ester organic solvent, and more preferably an aliphatic ether. And organic amide organic solvents.
Preferable examples of the aliphatic ether organic solvent include glycol ether organic solvents and glyceryl ether organic solvents.
Preferable examples of glycol ether organic solvents include mono- or polyalkylene glycol monoalkyl ethers. Examples of the alkylene glycol include ethylene glycol, propylene glycol, butylene glycol and the like, and “poly” preferably represents polymerization of 2 or more and 3 or less alkylene glycol. The alkyl group of the alkyl ether is preferably an alkyl group having 1 or more carbon atoms and preferably 8 or less, more preferably 6 or less, still more preferably 4 or less, still more preferably 2 or less, or preferably 1 to 1 carbon atoms. 8, More preferably, 1-6, More preferably, 1-4, More preferably, 1-2 alkyl group is mentioned. Specifically, ethylene glycol monobutyl ether, 2-isobutoxyethanol, 2- (2-n-butoxyethoxy) ethanol, 2- (2-isobutoxyethoxy) ethanol, triethylene glycol monobutyl ether, 2-ethoxyethanol, Examples include 1-methoxy-2-p-propanol, 2- (2-ethoxyethoxy) ethanol, 2-methoxyethanol, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, and diethylene glycol monomethyl ether.
Preferable examples of the glyceryl ether organic solvent include monoalkyl glyceryl ether, and the alkyl group preferably has 6 to 10 carbon atoms.
Examples of alcohol organic solvents include methanol, ethanol, propanol, isopropanol, n-butanol, iso-butanol, sec-butanol, 2-ethylhexanol, cyclohexanol, benzyl alcohol, ethylene glycol, diethylene glycol, propylene glycol, dipropylene Examples include glycol, hexylene glycol, and glycerin.
Preferable examples of the amide organic solvent include dialkylformamide, and the alkyl group preferably has 1 to 3 carbon atoms, and specifically, dimethylformamide and diethylformamide are preferable.
Examples of the ketone organic solvent include acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, diacetone alcohol and the like.
As the sulfoxide-based organic solvent, dimethyl sulfoxide is preferable.
Examples of the ester organic solvent include ethyl formate, butyl formate, ethyl acetate, dioctyl adipate, and the like.

  The carbon number of the organic solvent used in the present invention is preferably 3 or more, more preferably 4 or more, and is preferably 14 or less, more preferably 12 or less, more preferably 8 or less, and even more preferably 6 or less. . Or carbon number of this organic solvent becomes like this. Preferably it is 3-14, More preferably, it is 3-8, More preferably, it is 3-6, More preferably, it is 4-6.

  Preferable examples of the organic solvent used in the present invention include dimethylformamide (10.2), diethylene glycol monomethyl ether (10.64), hexylene glycol (9.97), 1-methoxy-2-propanol (10.13). ), Diacetone alcohol (9.92), dipropylene glycol monomethyl ether (9.84), 1-butanol (9.88), 3- (2-ethylhexyl) -1,2 propanediol (9.87), Examples include 2-propanol (9.71), 1-pentanol (9.57), 1-hexanol (9.36), and 1-octanol (9.08). In the above, the numerical values in parentheses are SP values.

  The organic solvent used in the present invention may be any one of the organic solvents described above, or may be a combination of any two or more.

  The biofilm formation inhibitor of the present invention can use a low concentration of the compound of formula (I) as an active ingredient. In a preferred embodiment, the biofilm formation inhibitor of the present invention is used in an amount such that the total concentration of the compound of formula (I) in the target water is as follows: From the viewpoint of suppressing biofilm formation, preferably 1 ppm ( In terms of mass ppm, the same applies hereinafter in the present specification) or more, more preferably 50 ppm or more, more preferably 300 ppm or more, and preferably 2000 ppm or less, more preferably 1000 ppm or less, from the viewpoint of suppressing the environmental burden due to high drug concentration. More preferably, it is 750 ppm or less.

  When the compound of formula (I) is 4-hydroxyisophthalaldehyde, its concentration in the target water is preferably 1 ppm or more, more preferably 300 ppm or more, still more preferably 500 ppm or more, and preferably 2000 ppm or less, more preferably 1000 ppm or less, more preferably 750 ppm or less, or preferably 1 to 2000 ppm, 1 to 1000 ppm, 1 to 750 ppm, 300 to 2000 ppm, 300 to 1000 ppm, 300 to 750 ppm, 500 to 2000 ppm, 500 to 1000 ppm, or 500 -750 ppm.

  When the compound of formula (I) is 2-hydroxyisophthalaldehyde, its concentration in the target water is preferably 1 ppm or more, more preferably 50 ppm or more, further preferably 300 ppm or more, and preferably 2000 ppm or less, Or preferably, it is 1-2000 ppm, 50-2000 ppm, or 300-2000 ppm.

  When carrying out biofilm formation inhibition according to the present invention, it is preferable to add the compound of formula (I) in the target water in such an amount that the concentration in the target water is within the predetermined range described above. In the present invention, it is not necessary to always maintain the concentration of the compound of formula (I) in the target water within the above-mentioned predetermined range, and when necessary or periodically, the concentration of the compound of formula (I) in the target water. What is necessary is just to adjust a density | concentration to the predetermined range mentioned above and to maintain for a fixed time. From the viewpoint of the biofilm formation inhibitory effect, the concentration of the compound of formula (I) in the target water is preferably within the predetermined range described above, preferably 1 day or more, more preferably 2 days or more, still more preferably 3 days or more, More preferably, it is maintained for 1 week or more, more preferably 2 weeks or more, more preferably 1 month or more, further preferably 3 months or more, more preferably 6 months or more. The upper limit of the period for maintaining the concentration of the compound of formula (I) in the target water is not particularly limited, but is preferably 10 years or less, more preferably from the viewpoint of equipment maintenance. 5 years or less, more preferably 2 years or less. The amount and frequency of the compound of formula (I) to be added to the target water will be adjusted according to the total volume of the target water and the volume to be replaced, the frequency of use of the equipment or equipment containing the target water, the internal temperature, the contamination status or the maintenance schedule. Can be set as appropriate.

  In the present invention, as a specific method of adding the compound of formula (I) to the target water, (1) directly to the target water flowing or stored in the facility that functions by flowing or storing the water described above, A method of continuously or periodically adding the compound of formula (I), (2) a method of adding the compound of formula (I) in advance to a part or all of the target water before flowing or storing in the facility (For example, the method of adding the compound of formula (I) to the water to be replaced with the target water in the equipment, after purifying treatment such as filtration, and then adding the compound of formula (I) to the target water before returning to the equipment again And the like).

  The present invention also includes the following substances, production methods, uses, methods and the like as exemplary embodiments. However, the present invention is not limited to these embodiments.

（式中、
Ｒ¹、Ｒ²、Ｒ³、及びＲ⁴は、それぞれ独立に、水素原子、水酸基、アルコキシ基、炭素数１〜６の炭化水素基、又は−ＣＨ₂−Ｒ⁵であり、ただし、Ｒ¹、Ｒ²、Ｒ³、及びＲ⁴の全てが同時に水素原子であることはなく；
Ｒ⁵は、ヒドロキシ基、ハロゲン原子、又は−ＮＲ^aＲ^bであり；
Ｒ^a及びＲ^bは、それぞれ独立に水素原子又はメチル基である）
を有効成分とする、バイオフィルム形成抑制剤。
〔２〕好ましくは、前記式（I）で表される化合物が、以下：
Ｒ¹が水酸基であり、Ｒ²、Ｒ³及びＲ⁴が水素原子である化合物；
Ｒ⁴が水酸基であり、Ｒ¹、Ｒ²及びＲ³が水素原子である化合物；
Ｒ²が炭素数１〜６の炭化水素基であり、Ｒ¹及びＲ³が水素原子であり、Ｒ⁴が水酸基である化合物；
Ｒ¹、Ｒ²及びＲ³が、それぞれ独立に炭素数１〜６の炭化水素基であり、Ｒ⁴が水酸基である化合物；
Ｒ¹、Ｒ³及びＲ⁴が水素原子であり、Ｒ²が炭素数１〜６の炭化水素基である化合物；
Ｒ¹、Ｒ²及びＲ⁴が水素原子であり、Ｒ³が炭素数１〜６の炭化水素基である化合物、
からなる群より選ばれる１種以上である、〔１〕記載のバイオフィルム形成抑制剤。
〔３〕好ましくは、前記式（I）で表される化合物が、４−ヒドロキシイソフタルアルデヒド及び２−ヒドロキシイソフタルアルデヒドからなる群より選ばれる１種以上である、〔１〕記載のバイオフィルム形成抑制剤。
〔４〕対象水中での前記式（I）で表される化合物の濃度が、以下：好ましくは１ｐｐｍ以上、より好ましくは５０ｐｐｍ以上、さらに好ましくは３００ｐｐｍ以上であって、かつ好ましくは２０００ｐｐｍ以下、より好ましくは１０００ｐｐｍ以下、さらに好ましくは７５０ｐｐｍ以下、になる量で使用される、〔１〕〜〔３〕のいずれか１項記載のバイオフィルム形成抑制剤。
〔５〕前記対象水中での前記式（I）で表される化合物の濃度が、以下：好ましくは１日以上、より好ましくは２日以上、さらに好ましくは３日以上、さらに好ましくは１週間以上、さらに好ましくは２週間以上、さらに好ましくは１ヶ月以上、さらに好ましくは３ヶ月以上、さらに好ましくは半年以上であって、かつ好ましくは１０年以下、より好ましくは５年以下、さらに好ましくは２年以下、の期間維持される、〔４〕記載のバイオフィルム形成抑制剤。
〔６〕好ましくは、前記バイオフィルムが、水を流す又は貯留することによって機能する設備におけるバイオフィルム、又は該設備に流れる又は貯留される水におけるバイオフィルムである、〔１〕〜〔５〕のいずれか１項記載のバイオフィルム形成抑制剤。 [1] A compound represented by the following formula (I):

(Where
R ¹ , R ² , R ³ , and R ⁴ are each independently a hydrogen atom, a hydroxyl group, an alkoxy group, a hydrocarbon group having 1 to 6 carbon atoms, or —CH ₂ —R ⁵ , provided that R ¹ , R ² , R ³ , and R ⁴ are not all hydrogen atoms at the same time;
R ⁵ is a hydroxy group, a halogen atom, or —NR ^a R ^b ;
R ^a and R ^b are each independently a hydrogen atom or a methyl group)
A biofilm formation inhibitor comprising as an active ingredient.
[2] Preferably, the compound represented by the formula (I) is:
A compound in which R ¹ is a hydroxyl group and R ² , R ³ and R ⁴ are hydrogen atoms;
A compound wherein R ⁴ is a hydroxyl group and R ¹ , R ² and R ³ are hydrogen atoms;
A compound in which R ² is a hydrocarbon group having 1 to 6 carbon atoms, R ¹ and R ³ are hydrogen atoms, and R ⁴ is a hydroxyl group;
Compounds wherein R ¹ , R ² and R ³ are each independently a hydrocarbon group having 1 to 6 carbon atoms, and R ⁴ is a hydroxyl group;
A compound in which R ¹ , R ³ and R ⁴ are hydrogen atoms and R ² is a hydrocarbon group having 1 to 6 carbon atoms;
A compound in which R ¹ , R ² and R ⁴ are hydrogen atoms and R ³ is a hydrocarbon group having 1 to 6 carbon atoms;
The biofilm formation inhibitor according to [1], which is one or more selected from the group consisting of:
[3] Preferably, the compound represented by the formula (I) is at least one selected from the group consisting of 4-hydroxyisophthalaldehyde and 2-hydroxyisophthalaldehyde, and inhibits biofilm formation according to [1] Agent.
[4] The concentration of the compound represented by the formula (I) in the target water is as follows: preferably 1 ppm or more, more preferably 50 ppm or more, further preferably 300 ppm or more, and preferably 2000 ppm or less. The biofilm formation inhibitor according to any one of [1] to [3], which is used in an amount of preferably 1000 ppm or less, more preferably 750 ppm or less.
[5] The concentration of the compound represented by the formula (I) in the target water is as follows: preferably 1 day or more, more preferably 2 days or more, further preferably 3 days or more, more preferably 1 week or more. More preferably 2 weeks or more, more preferably 1 month or more, further preferably 3 months or more, more preferably half a year or more, and preferably 10 years or less, more preferably 5 years or less, further preferably 2 years. The biofilm formation inhibitor according to [4], which is maintained for the following period.
[6] Preferably, the biofilm is a biofilm in a facility that functions by flowing or storing water, or a biofilm in water flowing or stored in the facility, according to [1] to [5] The biofilm formation inhibitor according to any one of the above.

（式中、
Ｒ¹、Ｒ²、Ｒ³、及びＲ⁴は、それぞれ独立に、水素原子、水酸基、アルコキシ基、炭素数１〜６の炭化水素基、又は−ＣＨ₂−Ｒ⁵であり、ただし、Ｒ¹、Ｒ²、Ｒ³、及びＲ⁴の全てが同時に水素原子であることはなく；
Ｒ⁵は、ヒドロキシ基、ハロゲン原子、又は−ＮＲ^aＲ^bであり；
Ｒ^a及びＲ^bは、それぞれ独立に水素原子又はメチル基である）
を対象水中に添加することを含む、バイオフィルム形成抑制方法。
〔８〕好ましくは、前記式（I）で表される化合物が、以下：
Ｒ¹が水酸基であり、Ｒ²、Ｒ³及びＲ⁴が水素原子である化合物；
Ｒ⁴が水酸基であり、Ｒ¹、Ｒ²及びＲ³が水素原子である化合物；
Ｒ²が炭素数１〜６の炭化水素基であり、Ｒ¹及びＲ³が水素原子であり、Ｒ⁴が水酸基である化合物；
Ｒ¹、Ｒ²及びＲ³が、それぞれ独立に炭素数１〜６の炭化水素基であり、Ｒ⁴が水酸基である化合物；
Ｒ¹、Ｒ³及びＲ⁴が水素原子であり、Ｒ²が炭素数１〜６の炭化水素基である化合物；
Ｒ¹、Ｒ²及びＲ⁴が水素原子であり、Ｒ³が炭素数１〜６の炭化水素基である化合物、
からなる群より選ばれる１種以上である、〔７〕記載の方法。
〔９〕好ましくは、前記式（I）で表される化合物が、４−ヒドロキシイソフタルアルデヒド及び２−ヒドロキシイソフタルアルデヒドからなる群より選ばれる１種以上である、〔７〕記載の方法。
〔１０〕前記対象水中に添加された前記式（I）で表される化合物の濃度が、以下：好ましくは１ｐｐｍ以上、より好ましくは５０ｐｐｍ以上、さらに好ましくは３００ｐｐｍ以上であって、かつ好ましくは２０００ｐｐｍ以下、より好ましくは１０００ｐｐｍ以下、さらに好ましくは７５０ｐｐｍ以下である、〔７〕〜〔９〕のいずれか１項記載の方法。
〔１１〕前記対象水中での前記式（I）で表される化合物の濃度を、以下：好ましくは１日以上、より好ましくは２日以上、さらに好ましくは３日以上、さらに好ましくは１週間以上、さらに好ましくは２週間以上、さらに好ましくは１ヶ月以上、さらに好ましくは３ヶ月以上、さらに好ましくは半年以上であって、かつ好ましくは１０年以下、より好ましくは５年以下、さらに好ましくは２年以下、の期間維持することをさらに含む、〔１０〕記載の方法。
〔１２〕好ましくは、前記バイオフィルムが、水を流す又は貯留することによって機能する設備におけるバイオフィルム、又は該設備に流れる又は貯留される水におけるバイオフィルムである、〔７〕〜〔１１〕のいずれか１項記載の方法。
〔１３〕好ましくは、前記対象水が、水を流す又は貯留することによって機能する設備に流れる又は貯留されている水である、〔７〕〜〔１２〕のいずれか１項記載の方法。 [7] A compound represented by the following formula (I):

(Where
R ¹ , R ² , R ³ , and R ⁴ are each independently a hydrogen atom, a hydroxyl group, an alkoxy group, a hydrocarbon group having 1 to 6 carbon atoms, or —CH ₂ —R ⁵ , provided that R ¹ , R ² , R ³ , and R ⁴ are not all hydrogen atoms at the same time;
R ⁵ is a hydroxy group, a halogen atom, or —NR ^a R ^b ;
R ^a and R ^b are each independently a hydrogen atom or a methyl group)
A method for inhibiting biofilm formation, comprising adding to the target water.
[8] Preferably, the compound represented by the formula (I) is:
A compound in which R ¹ is a hydroxyl group and R ² , R ³ and R ⁴ are hydrogen atoms;
A compound wherein R ⁴ is a hydroxyl group and R ¹ , R ² and R ³ are hydrogen atoms;
A compound in which R ² is a hydrocarbon group having 1 to 6 carbon atoms, R ¹ and R ³ are hydrogen atoms, and R ⁴ is a hydroxyl group;
Compounds wherein R ¹ , R ² and R ³ are each independently a hydrocarbon group having 1 to 6 carbon atoms, and R ⁴ is a hydroxyl group;
A compound in which R ¹ , R ³ and R ⁴ are hydrogen atoms and R ² is a hydrocarbon group having 1 to 6 carbon atoms;
A compound in which R ¹ , R ² and R ⁴ are hydrogen atoms and R ³ is a hydrocarbon group having 1 to 6 carbon atoms;
The method according to [7], which is one or more selected from the group consisting of:
[9] The method according to [7], wherein the compound represented by the formula (I) is preferably one or more selected from the group consisting of 4-hydroxyisophthalaldehyde and 2-hydroxyisophthalaldehyde.
[10] The concentration of the compound represented by the formula (I) added to the target water is as follows: preferably 1 ppm or more, more preferably 50 ppm or more, further preferably 300 ppm or more, and preferably 2000 ppm. The method according to any one of [7] to [9], which is more preferably 1000 ppm or less, and still more preferably 750 ppm or less.
[11] The concentration of the compound represented by the formula (I) in the target water is as follows: preferably 1 day or more, more preferably 2 days or more, further preferably 3 days or more, more preferably 1 week or more. More preferably 2 weeks or more, more preferably 1 month or more, further preferably 3 months or more, more preferably half a year or more, and preferably 10 years or less, more preferably 5 years or less, further preferably 2 years. The method according to [10], further comprising maintaining for the following period.
[12] Preferably, the biofilm is a biofilm in a facility that functions by flowing or storing water, or a biofilm in water that flows or stored in the facility, [7] to [11] The method of any one of Claims.
[13] The method according to any one of [7] to [12], wherein the target water is preferably water that flows or is stored in a facility that functions by flowing or storing water.

  EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to this.

  The test compounds used in the following examples are shown in Table 1.

Test Example 1 Measurement of Biofilm Formation Inhibitory Activity 1) Preparation of Test Bacteria Pseudomonas aeruginosa PAO1 strain (ATCC 15692) was statically cultured at 37 ° C. for 24 hours in an LB medium (Lysogeny Broth; manufactured by Becton Dickinson). Turbidity (OD600) of the obtained culture solution was measured and diluted with Mueller Hinton Broth (manufactured by BBL) to prepare 15 mL of a suspension having a turbidity (OD600) of 1/10 ⁶ .

2) Culture After adding 6 μL of a DMSO solution of a test compound (Tokyo Kasei) to each well of a 96-well microplate (351172; manufactured by Nippon Becton Dickinson), the suspension of Pseudomonas aeruginosa prepared in 1) above is used. Cultivation was started by adding 145 μL to each well. As test compounds, test compounds a and b (4-hydroxyisophthalaldehyde, 2-hydroxyisophthalaldehyde) described in Table 1 were used. The concentration of the test compound in the culture solution was adjusted to 2.5 to 2000 ppm. .

3) Measurement The 96-well microplate was incubated at 30 ° C. for 24 hours. Each well after culturing was stained with 0.1% crystal violet, then washed twice with physiological saline, 200 μL of ethanol was added, and the absorbance (OD570) was measured to determine the amount of biofilm formed.

4) Results Tables 2 and 3 show the biofilm formation amount (OD570) of the test bacteria. Since the tests shown in Table 2 and Table 3 were measured on different days, the amount of additive-free biofilm formed was different.

Based on OD570 described in Table 2 and Table 3, the biofilm (BF) inhibition rate for the test compound-free group (DMSO only) was calculated according to the following formula:
BF suppression (%)
= {1- (Test Compound Addition Group OD570 / Test Compound No Addition Group OD570)} × 100
Table 4 shows the BF inhibition (%) for each test compound.

Test Example 2 Evaluation of Biofilm Formation Inhibitory Activity in Flow Cell Water was collected from a water-cooled cooling tower that was actually used. From the collected water, Pseudomonadales, Flavobacteriales, RB41, Actinomycetales, Burkholderiales, Sphingomonadales, Gemmatales, Rhizobiales, Xanthomonadales, Chlamydiales, Methylophilales, Pirellulales, Bacillales and the like were detected.
Two test pieces (SUS304, 1 cm × 8 cm; manufactured by Engineering Test Service) were set in a flow cell (capacity 4 cm ³ ; manufactured by SER). After adding a test compound (4-hydroxyisophthalaldehyde) to water collected from a water-cooled cooling tower and adjusting to a predetermined temperature (10 ° C.), this solution is supplied to the flow cell at 1.43 mL per minute and discharged. I let you. The residence time of the supplied solution in the flow cell was about 2.8 minutes. During the test, the temperature in the flow cell was maintained at 30 ° C. The concentration of the test compound in the water in the flow cell was adjusted to 2.5, 5, 10 or 20 ppm. As a control, the same experiment was performed without the addition of the test compound. One week later, the amount of the biofilm (BF) formed was determined by measuring the weight of the test piece taken out from the flow cell over time. The results are shown in Table 5.
BF formation = Test piece weight after test-Test piece weight before test

Claims (6)

Compound represented by the following formula (I):

(Where
R ¹ , R ² , R ³ , and R ⁴ are each independently a hydrogen atom, a hydroxyl group, an alkoxy group, a hydrocarbon group having 1 to 6 carbon atoms, or —CH ₂ —R ⁵ , provided that R ¹ , R ² , R ³ , and R ⁴ are not all hydrogen atoms at the same time;
R ⁵ is a hydroxy group, a halogen atom, or —NR ^a R ^b ;
R ^a and R ^b are each independently a hydrogen atom or a methyl group)
A biofilm formation inhibitor comprising as an active ingredient.   The biofilm formation inhibitor according to claim 1, wherein the compound represented by the formula (I) is at least one selected from the group consisting of 4-hydroxyisophthalaldehyde and 2-hydroxyisophthalaldehyde.   The biofilm formation inhibitor of Claim 1 or 2 used in the quantity from which the total density | concentration of the compound represented by the said formula (I) in object water becomes 2000 ppm or less. Compound represented by the following formula (I):

(Where
R ¹ , R ² , R ³ , and R ⁴ are each independently a hydrogen atom, a hydroxyl group, an alkoxy group, a hydrocarbon group having 1 to 6 carbon atoms, or —CH ₂ —R ⁵ , provided that R ¹ , R ² , R ³ , and R ⁴ are not all hydrogen atoms at the same time;
R ⁵ is a hydroxy group, a halogen atom, or —NR ^a R ^b ;
R ^a and R ^b are each independently a hydrogen atom or a methyl group)
A method for inhibiting biofilm formation, comprising adding to the target water.   The method for inhibiting biofilm formation according to claim 4, wherein the compound represented by the formula (I) is at least one selected from the group consisting of 4-hydroxyisophthalaldehyde and 2-hydroxyisophthalaldehyde.   The biofilm formation suppression method of Claim 4 or 5 whose total density | concentration of the compound represented by the said formula (I) added to the said object water is 2000 ppm or less.