JP6787828B2 - Composition for suppressing biofilm formation - Google Patents

Description

The present invention relates to a composition for suppressing biofilm formation and a method for suppressing biofilm formation.

A biofilm is a structure formed by a community of microorganisms such as bacteria and molds attached to the surface of a solid or liquid together with secretions and the like. Biofilms generated in drainage facilities and water circulation systems in homes or factories cause slimy pipes, clogging, and foul odors. Biofilms also cause equipment degradation, such as drainage pipe corrosion. The harmful effects of biofilm formation are also seen as a problem in reverse osmosis membranes used in seawater desalination plants and piping equipment in paper mills. In addition, biofilms cause microbial contamination. Biofilms generated in hot spring facilities may cause infectious diseases. In the medical field, biofilms formed on tubes such as dialysis and medical devices such as endoscopes and contact lenses may be sources of infection. Biofilm formation in the skin and oral cavity can also cause disease. In the food sector, biofilms formed on foods or cookware can cause spoilage and food poisoning.

When microorganisms form a biofilm, it becomes resistant to conventional cleaning and sterilization methods, and its elimination is not easy. In order to prevent the formation of biofilms in drainage facilities and water circulation systems, it is necessary to replace and clean the water regularly, which increases the maintenance cost of the facilities and systems.

Biofilms in water circulation systems and the like include gram-negative microorganisms such as Pseudomonas, Sphingomonas, and Sphingopyxis, such as Pseudomonas aeruginosa. Furthermore, there are reports that microorganisms of the genera Klebsiella, Flavobacterium and Roseomonas were found in biofilms in water-cooled cooling towers (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, chlorine-based chemicals have problems such as damage to pipes and equipment, and organic nitrogen-sulfur-based chemicals have problems such as skin damage. Therefore, none of the agents can be used at a concentration that can sufficiently sterilize, and biofilm formation cannot be suppressed for a long period of time.

Patent Document 1 discloses an industrial antibacterial agent containing o-phthalaldehyde and a benzaldehyde compound such as p-phthalaldehyde or m-phthalaldehyde. Patent Document 2 discloses an antibacterial composition containing a compound such as salicylaldehyde and 4-hydroxybenzaldehyde.

Japanese Unexamined Patent Publication No. 9-295906 Japanese Unexamined Patent Publication No. 2003-192581

Biofouling, 2011, 27 (4): 393-402 Biocontrol Science, 2013, 18 (4): 205-209

The present invention provides a composition for suppressing biofilm formation, which can effectively suppress biofilm formation.

The present inventors have improved the handleability of the salicylaldehyde compound and the composition containing the specific salicylaldehyde compound and the organic solvent, and effective in forming a biofilm even when used at a low concentration. It was found that it can be suppressed.

Therefore, the present invention provides a composition for suppressing biofilm formation, which contains a compound represented by the following formula (I) and an organic solvent.
The present invention also provides a method for suppressing biofilm formation, which comprises adding the composition for suppressing biofilm formation to the target water.

(During the ceremony,
R ¹ , R ² , R ³ and R ⁴ are independently hydrogen atoms, hydrocarbon groups with 1 to 6 carbon atoms, or −CH ₂ −R ⁵ , where R ¹ , R ² , R Not all ³ and R ⁴ are 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 independently hydrogen atoms or methyl groups, respectively. )

The composition for suppressing biofilm formation of the present invention is excellent in handleability and can suppress the formation of biofilm even when used at a low concentration.

The composition for suppressing biofilm formation of the present invention is used for suppressing biofilm formation in various environments such as home or factory equipment. Preferably, the biofilm formation inhibitory composition of the present invention is provided by flowing or storing water in a water flow pipe, a tank or pool for storing water, a water circulation system, and equipment attached thereto. Used to control biofilm formation in functioning equipment. Among the above facilities, the composition for suppressing biofilm formation of the present invention is preferably used in facilities in which at least a part thereof reaches a temperature at which a biofilm is likely to be formed, for example, 20 ° C. or higher, preferably 25 ° C. or higher. .. Preferable examples of equipment to which the composition for suppressing biofilm formation of the present invention is applied include factory equipment using a water-cooled cooling tower, a building cooling system, an industrial cooling pool, industrial water supply, water storage, or Examples include drainage channels, running hot water heating systems, wastewater treatment equipment, reverse osmosis membranes used in seawater desalination plants, and piping equipment in paper mills.

As used herein, the term "target water" refers to water to which the composition for suppressing biofilm formation of the present invention is applied. Preferably, the "target water" is water that flows or is stored in the equipment that functions by flowing or storing the above-mentioned water, for example, used in a factory equipment or a building cooling system using a water-cooled cooling tower. Water used, industrial cooling pool water, industrial water supply, water in storage or drainage channels, hot water used in running water heating systems, wastewater from wastewater treatment facilities, used in seawater desalination plants Examples thereof include water passing through a back-penetrating film, water in a piping facility of a paper manufacturing factory, and preferably cooling water of a water-cooled cooling tower. The composition for suppressing biofilm formation of the present invention is added to the above-mentioned target water.

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

(1. Composition for suppressing biofilm formation)
The composition for suppressing biofilm formation of the present invention (hereinafter, also referred to as the composition of the present invention) contains a compound represented by the following formula (I) (hereinafter, also referred to as a compound of formula (I)) and an organic solvent. To do.

In formula (I), R ¹ , R ² , R ³ , and R ⁴ are each independently a hydrogen atom, a hydrocarbon group having 1 to 6 carbon atoms, or −CH _{2 −} R ⁵ . However, R ¹ , R ² , R ³ , and R ⁴ are not all hydrogen atoms at the same time.

In formula (I), the hydrocarbon groups 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 chain alkenyl group having 2 to 6 carbon atoms. From the viewpoint of water solubility of the compound of formula (I), 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 are preferable examples. More preferable examples of the hydrocarbon group having 1 to 6 carbon atoms are 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 pentyl group and a hexyl group. , 1-propenyl group, 2-propenyl (allyl) group, 2-t-amyl group, cyclohexyl group, cyclopentyl group and the like. In formula (I), the hydrocarbon groups having 1 to 6 carbon atoms can be independently selected for R ^{1 to} R ⁴ , respectively.

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 a compound. R ^a and R ^b are independent hydrogen atoms or methyl groups, respectively. Preferably -NR ^a R ^b is a dimethylamino group.

In one embodiment, R ¹ is a hydrocarbon group having 1 to 6 carbon atoms, and R ² , R ³ and R ⁴ are hydrogen atoms. In another embodiment, R ¹ and R ³ are each independently a hydrocarbon group having 1 to 6 carbon atoms, and R ² and R ⁴ are hydrogen atoms. In another embodiment, R ¹ and R ⁴ are independently hydrocarbon groups having 1 to 6 carbon atoms, and R ² and R ³ are hydrogen atoms. 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. 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.

In a preferred embodiment, in formula (I),
R ¹ is 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, and is more preferably 1 to 6 carbon atoms from the viewpoint of water solubility. It is a linear or branched alkyl group of 4, or a linear or branched alkenyl group having 2 to 4 carbon atoms, and more preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, or an isobutyl group. , S-butyl group, t-butyl group, 1-propenyl group, or 2-propenyl group, more preferably methyl group, ethyl group, propyl group, isopropyl group, isobutyl group, t-butyl group, or 2-. It is a propenyl group;
R ² , R ³ and R ⁴ are hydrogen atoms.
In a more preferred embodiment, in formula (I),
R ¹ is a methyl group, an ethyl group, a propyl group, an isopropyl group, an isobutyl group, or a t-butyl group;
R ² , R ³ and R ⁴ are hydrogen atoms.

In another preferred embodiment, in formula (I),
R ¹ and R ³ are independently linear or branched alkyl groups having 1 to 6 carbon atoms or linear or branched alkenyl groups having 2 to 6 carbon atoms, respectively, from the viewpoint of water solubility. It is 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, an ethyl group, a propyl group or an isopropyl group. Group, butyl group, isobutyl group, s-butyl group, t-butyl group, 1-propenyl group, or 2-propenyl group, more preferably methyl group, ethyl group, propyl group, isopropyl group, isobutyl group, or It is a t-butyl group;
R ² and R ⁴ are hydrogen atoms.

In another preferred embodiment, in formula (I),
R ¹ and R ⁴ are independently linear or branched alkyl groups having 1 to 6 carbon atoms or linear or branched alkenyl groups having 2 to 6 carbon atoms, respectively, from the viewpoint of water solubility. It is 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, an ethyl group, a propyl group or an isopropyl group. Group, butyl group, isobutyl group, s-butyl group, t-butyl group, 1-propenyl group, or 2-propenyl group, more preferably methyl group, ethyl group, propyl group, isopropyl group, isobutyl group, or It is a t-butyl group, more preferably a methyl group or an ethyl group;
R ² and R ³ are hydrogen atoms.

In another preferred embodiment, in formula (I),
R ¹ , R ³ and R ⁴ are hydrogen atoms; and
R ² is 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, and is more preferably 1 to 6 carbon atoms from the viewpoint of water solubility. It is a linear or branched alkyl group of 4, or a linear or branched alkenyl group having 2 to 4 carbon atoms, and more preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, or an isobutyl group. , S-butyl group, t-butyl group, 1-propenyl group, or 2-propenyl group, more preferably methyl group, ethyl group, propyl group, isopropyl group, isobutyl group, or t-butyl group. It is preferably a methyl group or an ethyl group.

In another preferred embodiment, in formula (I),
R ¹ , R ² and R ⁴ are hydrogen atoms; and
R ³ is 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, and is more preferably 1 to 6 carbon atoms from the viewpoint of water solubility. It is a linear or branched alkyl group of 4, or a linear or branched alkenyl group having 2 to 4 carbon atoms, and more preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, or an isobutyl group. , S-butyl group, t-butyl group, 1-propenyl group, or 2-propenyl group, more preferably methyl group, ethyl group, propyl group, isopropyl group, isobutyl group, or t-butyl group. , More preferably a methyl group or an ethyl group.

Preferred examples of the compound of formula (I) used in the present invention include 3-methylsalitylaldehyde, 3-tert-butylsalitylaldehyde, 3,6-dimethylsalitylaldehyde, 3,5-di-tert-butylsalitylaldehyde, and the like. Examples thereof include 4-methylsalicyylaldehyde and 5-methylsalitylaldehyde, more preferably 3-methylsalicylaldehyde.

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

The type of the organic solvent used in the present invention is not particularly limited, and may be an aliphatic solvent or an aromatic solvent. From the viewpoint of dissolving and stabilizing the compound of the above formula (I), the SP value of the organic solvent is preferably 9.0 or more, more preferably 9.2 or more, still more preferably 10.0 or more. And preferably 11.0 or less, more preferably 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, and even more preferably 9.2 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: Aggregation energy constant of Hoy peculiar to atomic group or group [Unit: cal / mol]
The aggregation energy constant G of Hoy peculiar to the atomic group or group is described in JSME, 1971, vol. See the values described in 44 (4): 186-192 (written by Toyohiko Yoshida).

Preferably, the organic solvent includes an ether-based organic solvent, an amide-based organic solvent, an alcohol-based organic solvent, a ketone-based organic solvent, a sulfoxide-based organic solvent, and an ester-based organic solvent, and more preferably, an aliphatic ether. Examples thereof include a system organic solvent and an amide system organic solvent.
Preferred examples of the aliphatic ether-based organic solvent include glycol ether-based organic solvents and glyceryl ether-based organic solvents.
Preferred examples of the glycol ether-based organic solvent include mono or polyalkylene glycol monoalkyl ether. Examples of the alkylene glycol include ethylene glycol, propylene glycol, butylene glycol and the like, and "poly" preferably represents the polymerization of alkylene glycol of 2 or more and 3 or less. The alkyl group of the alkyl ether preferably has 1 or more carbon atoms, preferably 8 or less carbon atoms, more preferably 6 or less carbon atoms, still more preferably 4 or less carbon atoms, still more preferably 2 or less carbon atoms, or preferably 1 to 1 carbon atoms. 8, more preferably 1 to 6, still more preferably 1 to 4, still more preferably 1 to 2 alkyl groups. Specifically, ethylene glycol monobutyl ether, 2-isobutoxyethanol, 2- (2-n-butoxyethoxy) ethanol, 2- (2-isobutoxyethoxy) ethanol, triethylene glycol monobutyl ether, 2-ethoxyethanol, Examples thereof 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-based organic solvent include monoalkyl glyceryl ether, and the alkyl group preferably has 6 to 10 carbon atoms.
Examples of alcohol-based organic solvents include methanol, ethanol, propanol, isopropanol, n-butanol, iso-butanol, sec-butanol, 2-ethylhexanol, cyclohexanol, benzyl alcohol, ethylene glycol, diethylene glycol, propylene glycol, and dipropylene. Glycol, hexylene glycol, glycerin and the like can be mentioned.
Preferable examples of the amide-based 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-based organic solvent include acetone, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, diacetone alcohol and the like.
Dimethyl sulfoxide is preferable as the sulfoxide-based organic solvent.
Examples of the ester-based 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 preferably 14 or less, more preferably 12 or less, more preferably 8 or less, still more preferably 6 or less. .. Alternatively, the organic solvent has preferably 3 to 14, more preferably 3 to 8, still more preferably 3 to 6, still more preferably 4 to 6.

Preferred examples of the organic solvent used in the present invention are 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), Included are 2-propanol (9.71), 1-pentanol (9.57), 1-hexanol (9.36), and 1-octanol (9.08). In the above, the numerical value in parentheses is the SP value.

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

In the composition of the present invention, the total content of the compound of the above formula (I) is preferably 0.1% by mass or more, more preferably 0.% by mass, based on the total amount of the composition, from the viewpoint of the biofilm formation inhibitory action. 5% by mass or more, more preferably 1% by mass or more, still more preferably 3% by mass or more, still more preferably 5% by mass or more, still more preferably 8% by mass or more, and the solubility of the compound of formula (I). From the viewpoint, the total amount of the composition is preferably 90% by mass or less, more preferably 80% by mass or less, further preferably 70% by mass or less, still more preferably 50% by mass or less, still more preferably 30% by mass or less. More preferably, it is 20% by mass or less. Preferably, the total content of the compound of formula (I) in the composition of the present invention is preferably 0.1 to 90% by mass, more preferably 0.5 to 80% by mass, based on the total amount of the composition. It is more preferably 1 to 70% by mass, further preferably 3 to 50% by mass, still more preferably 5 to 30% by mass, still more preferably 8 to 20% by mass.

From the viewpoint of the solubility of the compound of formula (I), the total content of the organic solvent in the composition of the present invention is preferably 10% by mass or more, more preferably 30% by mass or more, based on the total amount of the composition. , More preferably 50% by mass or more, still more preferably 70% by mass or more, still more preferably 80% by mass or more, and from the viewpoint of the biofilm formation inhibitory action, preferably 99.9% of the total amount of the composition. It is 9% by mass or less, more preferably 99% by mass or less, still more preferably 97% by mass or less, still more preferably 95% by mass or less, still more preferably 92% by mass or less. Preferably, the total content of the organic solvent in the composition of the present invention is preferably 10 to 99.9% by mass, more preferably 30 to 99% by mass, still more preferably 50, based on the total amount of the composition. It is ~ 97% by mass, more preferably 70 to 95% by mass, still more preferably 80 to 92% by mass.

Preferably, the total content of the compound of formula (I) and the total content of the organic solvent in the composition of the present invention are preferably 0.1 to 90% by mass, respectively, in the total amount of the composition. 10-99.9% by mass, more preferably 1 to 70% by mass and 30 to 99% by mass, still more preferably 3 to 50% by mass and 50 to 97% by mass, still more preferably 5 to 30% by mass and 70 to 95% by mass. It is by mass, more preferably 8 to 20% by mass and 80 to 92% by mass.

Further, the mass ratio of the compound of formula (I) to the organic solvent (mass of compound of formula (I) / mass of organic solvent) in the composition of the present invention is preferably 0.001 from the viewpoint of suppressing biofilm formation. The above is more preferably 0.005 or more, further preferably 0.01 or more, still more preferably 0.05 or more, still more preferably 0.1 or more, and is preferable from the viewpoint of solubility of the compound of formula (I). Is 5 or less, more preferably 3 or less, still more preferably 1 or less, still more preferably 0.5 or less. The mass ratio of the compound of formula (I) to the organic solvent in the composition of the present invention is preferably 0.001 to 5, more preferably 0.005 to 3, still more preferably 0.01 to 1, and further. It is preferably 0.05 to 0.5, more preferably 0.1 to 0.5.

In the composition of the present invention, the total content of the compound of formula (I) and the organic solvent is preferably the total mass of the composition from the viewpoint of suppressing biofilm formation and solubility of the compound of formula (I). Is 50% by mass or more, more preferably 70% by mass or more, still more preferably 80% by mass or more, still more preferably 85% by mass or more, still more preferably 90% by mass or more, still more preferably 95% by mass or more, still more preferably 99. It is 5% by mass or more, and preferably 100% by mass or less.

The composition of the present invention may be a composition composed of the compound of the formula (I) and the organic solvent, but may also contain other components. Examples of such other components include water, antibacterial and antifungal agents, antiseptic and fungicides, antibiotics, penetration promoters, surfactants, deodorants, air fresheners, chelating agents, and compositions of the present invention. Examples include substances for cleaning or preventing deterioration of equipment and facilities, antibacterial agents or bactericidal agents. The type of the other component and its concentration are not particularly limited as long as the biofilm formation inhibitory action of the composition of the present invention is not inhibited.

The composition of the present invention may contain water as an optional component. The content of water in the composition is preferably 0% by mass or more from the viewpoint of suppressing biofilm formation, and preferably 50% by mass or less from the viewpoint of solubility of the compound of formula (I). It is preferably 30% by mass or less, more preferably 20% by mass or less, still more preferably 10% by mass or less.

(2. Biofilm formation suppression method)
The present invention also provides a method for suppressing biofilm formation by applying the composition for suppressing biofilm formation of the present invention to target water. Preferably, the method of the present invention is a method for suppressing biofilm formation in the target water. The method of the present invention comprises adding a biofilm formation inhibitory composition containing the above-mentioned compound of formula (I) and an organic solvent to the target water. In the method of the present invention, when the composition of the present invention is added to the target water, the composition of the present invention prepared in advance may be added to the target water from the viewpoint of the solubility of the compound of formula (I). preferable. For example, the compound of formula (I) and the organic solvent may be mixed in advance to prepare the composition of the present invention, and the obtained composition may be added to the target water, and the obtained composition may be further organically added. A diluted solution diluted with a solvent or water may be added to the target water. The target water to which the composition of the present invention is added is also simply referred to as a "treatment liquid" in the following specification.

Specific methods for adding the biofilm formation-suppressing composition of the present invention to the target water include (1) the target water flowing or stored in a facility that functions by flowing or storing the above-mentioned water. A method of directly adding the composition of the present invention continuously or periodically, (2) pre-adding the composition of the present invention to a part or all of the target water before being flushed or stored in the facility. (For example, a method of adding the composition of the present invention to water to be replaced with the target water in the facility, a method of adding the composition of the present invention to the target water after purification treatment such as filtration treatment, and before returning to the facility again. Method of adding water, etc.).

The total concentration of the compound of formula (I) in the treatment liquid is preferably 0.01 ppm or more (mass ppm, the same applies hereinafter in the present specification), more preferably, in the total amount of the treatment liquid from the viewpoint of suppressing biofilm formation. Is 0.1 ppm or more, more preferably 1 ppm or more, still more preferably 5 ppm or more, and from the viewpoint of suppressing the environmental load due to the increase in the concentration of the drug, the total amount of the treatment liquid is preferably 1000 ppm or less, more preferably 1000 ppm or less. It is 500 ppm or less, more preferably 300 ppm or less, still more preferably 100 ppm or less, still more preferably 50 ppm or less. Preferably, the total concentration of the compound of formula (I) in the treatment liquid is preferably 0.01 to 1000 ppm, more preferably 0.1 to 500 ppm, still more preferably 1 to 300 ppm, and further, in the total amount of the treatment liquid. It is preferably 5 to 300 ppm, more preferably 5 to 100 ppm, still more preferably 5 to 50 ppm.

More preferably, in the method of the present invention, the compound of formula (I) is used in an amount such that the concentration in the treatment liquid becomes less than the minimum inhibitory concentration (MIC) of the causative microorganism of the biofilm. ..

The total concentration of the organic solvent in the treatment liquid is preferably 1 ppm or more, more preferably 5 ppm or more, still more preferably 10 ppm or more, in the total amount of the treatment liquid from the viewpoint of dissolving the compound of the formula (I). Further preferably, it is 20 ppm or more, and from the viewpoint of suppressing biofilm formation, the total amount of the treatment liquid is preferably 5000 ppm or less, more preferably 3000 ppm or less, still more preferably 1500 ppm or less, still more preferably 1000 ppm or less, still more preferably. It is 500 ppm or less, more preferably 300 ppm or less, still more preferably 200 ppm or less, still more preferably 100 ppm or less. Preferably, the total concentration of the organic solvent in the treatment liquid is preferably 1 to 5000 ppm, more preferably 1 to 3000 ppm, still more preferably 5 to 1500 ppm, still more preferably 5 to 1000 ppm, in the total amount of the treatment liquid. It is more preferably 5 to 500 ppm, still more preferably 10 to 500 ppm, still more preferably 20 to 300 ppm, still more preferably 20 to 200 ppm, still more preferably 20 to 100 ppm.

The total concentration of the compound of the formula (I) and the total concentration of the organic solvent in the treatment liquid are preferably 0.01 to 1000 ppm and 1 to 5000 ppm, respectively, in the total amount of the treatment liquid, and more preferably 0. It is 1 to 500 ppm and 1 to 3000 ppm, more preferably 1 to 300 ppm and 5 to 1000 ppm, further preferably 5 to 300 ppm and 10 to 500 ppm, further preferably 5 to 100 ppm and 20 to 200 ppm, and further. It is preferably 5 to 50 ppm and 20 to 100 ppm.

The amount of the composition of the invention used in the method of the invention is considerably smaller than the amount of water of interest to which it is added. Therefore, the mass ratio of the compound of formula (I) and the organic solvent used in the method of the present invention to the target liquid and the preferable concentration of the compound of formula (I) and the organic solvent in the above-mentioned treatment liquid are substantially the same. Can be regarded as. That is, the total amount of the compound of formula (I) added to the target liquid is preferably 0.01 to 1000 ppm, more preferably 0.1 to 500 ppm, still more preferably 1 to 300 ppm, still more preferably, relative to the total amount of the target liquid. Is 5 to 300 ppm, more preferably 5 to 100 ppm, still more preferably 5 to 50 ppm. The total amount of the organic solvent added to the target liquid is preferably 1 to 5000 ppm, more preferably 1 to 3000 ppm, still more preferably 5 to 1500 ppm, still more preferably 5 to 1000 ppm, based on the total amount of the target liquid. It is preferably 5 to 500 ppm, more preferably 10 to 500 ppm, still more preferably 20 to 300 ppm, still more preferably 20 to 200 ppm, still more preferably 20 to 100 ppm. The total amount of the compound of formula (I) added to the target liquid and the total amount of the organic solvent are preferably 0.01 to 1000 ppm and 1 to 5000 ppm, respectively, with respect to the total amount of the target liquid, respectively. It is preferably 0.1 to 500 ppm and 1 to 3000 ppm, more preferably 1 to 300 ppm and 5 to 1000 ppm, still more preferably 5 to 300 ppm and 10 to 500 ppm, still more preferably 5 to 100 ppm and 20 to 200 ppm. It is more preferably 5 to 50 ppm and 20 to 100 ppm.

In the present invention, the preferable range of the mass ratio of the compound of formula (I) to the organic solvent in the treatment liquid (mass of compound of formula (I) / mass of organic solvent) is those in the composition of the present invention described above. It is the same as the preferable range of the mass ratio.

In the method of the present invention, the concentrations of the formula (I) and the organic solvent in the treatment liquid need not be maintained within the predetermined ranges described above at all times, and are described above when necessary or periodically. It may be adjusted to a predetermined range and maintained for a certain period of time. From the viewpoint of the biofilm formation inhibitory effect, the concentration of the compound of the formula (I) and the organic solvent in the treatment liquid is kept within the above-mentioned predetermined range, preferably 2 weeks or more, more preferably 1 month or more, still more preferably. It is desirable to maintain the temperature for 3 months or longer, more preferably for 6 months or longer. The upper limit of the period for maintaining the concentrations of the compound (I) compound and the organic solvent in the target water within the above-mentioned predetermined ranges is not particularly limited, but is preferably 10 years or less from the viewpoint of equipment maintenance. It is more preferably 5 years or less, still more preferably 2 years or less. The amount and frequency of the compound (I) compound and organic solvent added to the target water are the total volume and replacement volume of the target water, the frequency of use of equipment or equipment containing the target water, internal temperature, contamination status or maintenance schedule, It can be set as appropriate according to the above.

The temperature of the target water to be treated and the temperature of the treatment liquid in the method of the present invention can be appropriately set according to the system in which the target water and the treatment liquid are used. For example, the temperatures of the target water and the treatment liquid are set independently, preferably 5 ° C. or higher, more preferably 10 ° C. or higher, still more preferably 15 ° C. or higher, still more preferably 20 ° C. or higher, still more preferably 25 ° C. or higher. The above is preferably 60 ° C. or lower, more preferably 55 ° C. or lower, and further preferably 50 ° C. or lower.

The present invention also provides the use of a combination of the compound of formula (I) and the organic solvent for suppressing biofilm formation. Preferably, a composition for suppressing biofilm formation containing the above-mentioned compound of formula (I) and an organic solvent is used for suppressing biofilm formation. Also preferably, the use is for suppressing biofilm formation in the target water. The type, concentration, and method of use of the compound of formula (I) and the organic solvent are as described above.

The present invention also includes the following substances, manufacturing 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、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）。
〔２〕前記式（I）で表される化合物が、
好ましくは、３−メチルサリチルアルデヒド、３−ｔｅｒｔ−ブチルサリチルアルデヒド、３，６−ジメチルサリチルアルデヒド、３，５−ジ−ｔｅｒｔ−ブチルサリチルアルデヒド、４−メチルサリチルアルデヒド、及び５−メチルサリチルアルデヒドからなる群より選ばれる１種以上であり、
より好ましくは、３−メチルサリチルアルデヒドである、
〔１〕記載のバイオフィルム形成抑制用組成物。
〔３〕前記有機溶媒が、
ＳＰ値が、好ましくは９．０以上、より好ましくは９．２以上、さらに好ましくは１０．０以上であり、かつ好ましくは１１．０以下、より好ましくは１０．８以下であるか、あるいは、
ＳＰ値が、好ましくは９．０〜１１．０、より好ましくは９．２〜１１．０、さらに好ましくは９．２〜１０．８である、
〔１〕又は〔２〕記載のバイオフィルム形成抑制用組成物。
〔４〕前記有機溶媒が、
好ましくは、エーテル系有機溶媒、アミド系溶媒、アルコール系有機溶媒、ケトン系有機溶媒、スルホキシド系有機溶媒、及びエステル系溶媒からなる群より選ばれる１種以上であり、
より好ましくは、脂肪族エーテル系有機溶媒及びアミド系溶媒からなる群より選ばれる１種以上である、〔３〕記載のバイオフィルム形成抑制用組成物。
〔５〕前記有機溶媒の炭素数が、
好ましくは３以上、より好ましくは４以上であり、かつ好ましくは１４以下、より好ましくは１２以下、より好ましくは８以下、さらに好ましくは６以下であるか、あるいは、
好ましくは３〜１４、より好ましくは３〜８、さらに好ましくは３〜６、さらに好ましくは４〜６である、
〔４〕記載のバイオフィルム形成抑制用組成物。
〔６〕好ましくは、前記有機溶媒が、ジメチルホルムアミド（１０．２）、ジエチレングリコールモノメチルエーテル（１０．６４）、ヘキシレングリコール（９．９７）、１−メトキシ−２−プロパノール（１０．１３）、ジアセトンアルコール（９．９２）、ジプロピレングリコールモノメチルエーテル（９．８４）、１−ブタノール（９．８８）、３−（２−エチルヘキシル）−１、２プロパンジオール（９．８７）、２−プロパノール（９．７１）、１−ペンタノール（９．５７）、１−ヘキサノール（９．３６）、及び１−オクタノール（９．０８）（括弧内の数値はＳＰ値である）からなる群より選ばれる１種以上である、〔１〕又は〔２〕記載のバイオフィルム形成抑制用組成物。
〔７〕好ましくは、前記式（I）で表される化合物の含有量が０．１質量％以上かつ９０質量％以下である、〔１〕〜〔６〕のいずれか１項記載のバイオフィルム形成抑制用組成物。
〔８〕好ましくは、前記有機溶媒の含有量が１０質量％以上かつ９９．９質量％以下である、〔１〕〜〔７〕のいずれか１項記載のバイオフィルム形成抑制用組成物。
〔９〕好ましくは、前記式（I）で表される化合物及び前記有機溶媒の含有量が、それぞれ０．１〜９０質量％及び１０〜９９．９質量％である、〔１〕〜〔８〕のいずれか１項記載のバイオフィルム形成抑制用組成物。
〔１０〕好ましくは、前記式（I）で表される化合物（Ａ）と前記有機溶媒（Ｂ）との質量比（Ａ）／（Ｂ）が０．００１以上かつ５以下である、〔１〕〜〔９〕のいずれか１項記載のバイオフィルム形成抑制用組成物。
〔１１〕好ましくは、前記式（I）で表される化合物と前記有機溶媒の合計含有量が５０質量％以上かつ好ましくは１００質量％以下である、〔１〕〜〔１０〕のいずれか１項記載のバイオフィルム形成抑制用組成物。
〔１２〕好ましくは、対象水中での前記式（I）で表される化合物の濃度が０．０１ｐｐｍ以上かつ１０００ｐｐｍ以下になる量で使用される、〔１〕〜〔１１〕のいずれか１項記載のバイオフィルム形成抑制用組成物。
〔１３〕好ましくは、対象水中での前記有機溶媒の濃度が１ｐｐｍ以上かつ５０００ｐｐｍ以下になる量で使用される、〔１〕〜〔１２〕のいずれか１項記載のバイオフィルム形成抑制用組成物。
〔１４〕好ましくは、対象水中での前記式（I）で表される化合物の濃度及び前記有機溶媒の濃度が、それぞれ０．０１〜１０００ｐｐｍ及び１〜５０００ｐｐｍになる量で使用される、〔１〕〜〔１３〕のいずれか１項記載のバイオフィルム形成抑制用組成物。
〔１５〕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〕〜〔１４〕のいずれか１項記載のバイオフィルム形成抑制用組成物。 [1] A composition for suppressing biofilm formation, which contains a compound represented by the following formula (I) and an organic solvent:

(During the ceremony,
R ¹ , R ² , R ³ and R ⁴ are independently hydrogen atoms, hydrocarbon groups with 1 to 6 carbon atoms, or −CH ₂ −R ⁵ , except that R ¹ , R ² , R Not all ³ and R ⁴ are 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 independently hydrogen atoms or methyl groups).
[2] The compound represented by the formula (I) is
Preferably, from 3-methylsalitylaldehyde, 3-tert-butylsalitylaldehyde, 3,6-dimethylsalitylaldehyde, 3,5-di-tert-butylsalitylaldehyde, 4-methylsalitylaldehyde, and 5-methylsalitylaldehyde. One or more species selected from the group
More preferably, it is 3-methylsalicylaldehyde.
[1] The composition for suppressing biofilm formation according to the above.
[3] The organic solvent is
The SP value is preferably 9.0 or more, more preferably 9.2 or more, further preferably 10.0 or more, and preferably 11.0 or less, more preferably 10.8 or less, or
The SP value is preferably 9.0 to 11.0, more preferably 9.2 to 11.0, and even more preferably 9.2 to 10.8.
The composition for suppressing biofilm formation according to [1] or [2].
[4] The organic solvent is
It is preferably one or more selected from the group consisting of an ether-based organic solvent, an amide-based solvent, an alcohol-based organic solvent, a ketone-based organic solvent, a sulfoxide-based organic solvent, and an ester-based solvent.
More preferably, the composition for suppressing biofilm formation according to [3], which is one or more selected from the group consisting of an aliphatic ether-based organic solvent and an amide-based solvent.
[5] The carbon number of the organic solvent is
It is preferably 3 or more, more preferably 4 or more, and preferably 14 or less, more preferably 12 or less, more preferably 8 or less, still more preferably 6 or less, or
It is preferably 3 to 14, more preferably 3 to 8, still more preferably 3 to 6, still more preferably 4 to 6.
[4] The composition for suppressing biofilm formation according to the above.
[6] Preferably, the organic solvent is dimethylformamide (10.2), diethylene glycol monomethyl ether (10.64), hexylene glycol (9.97), 1-methoxy-2-propanol (10.13), and the like. Diacetone alcohol (9.92), dipropylene glycol monomethyl ether (9.84), 1-butanol (9.88), 3- (2-ethylhexyl) -1, 2 propanediol (9.87), 2- From the group consisting of propanol (9.71), 1-pentanol (9.57), 1-hexanol (9.36), and 1-octanol (9.08) (the numbers in parentheses are SP values). The composition for suppressing biofilm formation according to [1] or [2], which is one or more selected.
[7] The biofilm according to any one of [1] to [6], wherein the content of the compound represented by the formula (I) is preferably 0.1% by mass or more and 90% by mass or less. Composition for suppressing formation.
[8] The composition for suppressing biofilm formation according to any one of [1] to [7], wherein the content of the organic solvent is preferably 10% by mass or more and 99.9% by mass or less.
[9] Preferably, the contents of the compound represented by the formula (I) and the organic solvent are 0.1 to 90% by mass and 10 to 99.9% by mass, respectively, [1] to [8]. ], The composition for suppressing biofilm formation according to any one of the above items.
[10] Preferably, the mass ratio (A) / (B) of the compound (A) represented by the formula (I) to the organic solvent (B) is 0.001 or more and 5 or less [1]. ] To [9], the composition for suppressing biofilm formation according to any one of the above items.
[11] Preferably, any one of [1] to [10], wherein the total content of the compound represented by the formula (I) and the organic solvent is 50% by mass or more and preferably 100% by mass or less. The composition for suppressing biofilm formation according to the above item.
[12] Any one of [1] to [11] is preferably used in an amount such that the concentration of the compound represented by the formula (I) in the target water is 0.01 ppm or more and 1000 ppm or less. The above-mentioned composition for suppressing biofilm formation.
[13] The composition for suppressing biofilm formation according to any one of [1] to [12], which is preferably used in an amount such that the concentration of the organic solvent in the target water is 1 ppm or more and 5000 ppm or less. ..
[14] Preferably, the concentration of the compound represented by the formula (I) and the concentration of the organic solvent in the target water are used in an amount of 0.01 to 1000 ppm and 1 to 5000 ppm, respectively. [1] ] To [13]. The composition for suppressing biofilm formation according to any one of the above items.
[15] Preferably, the biofilm is a biofilm in a facility that functions by flowing or storing water, or a biofilm in water that flows or is stored in the facility, [1]-[14]. The composition for suppressing biofilm formation according to any one of the above.

[16] A composition for suppressing biofilm formation containing a compound represented by the formula (I) according to any one of [1] to [15] and an organic solvent is added to the target water. , Biofilm formation suppression method.
[17] Preferably, the composition is added so that the concentration of the compound represented by the formula (I) in the target water to which the biofilm formation suppressing composition is added is 0.01 ppm or more and 1000 ppm or less. [16]. The method according to [16], wherein is added to the target water.
[18] Preferably, the composition is added to the target water so that the concentration of the organic solvent in the target water to which the biofilm formation suppressing composition is added is 1 ppm or more and 5000 ppm or less. The method according to [16] or [17].
[19] Preferably, the concentrations of the compound represented by the formula (I) and the organic solvent in the target water to which the composition for suppressing biofilm formation is added are 0.01 to 1000 ppm and 1 to 5000 ppm, respectively. The method according to any one of [16] to [18], wherein the composition is added to the target water so as to be.
[20] The method according to [16], wherein 0.01 to 1000 ppm of the compound represented by the formula (I) is added to the total amount of the target water.
[21] The method according to [16] or [20], wherein 1 to 5000 ppm of the organic solvent is added to the total amount of the target water.
[22] [16], [20] or [21], 0.01 to 1000 ppm of the compound represented by the formula (I) and 1 to 5000 ppm of the organic solvent are added to the total amount of the target water. ] The method described.
[23] The above-mentioned item 1 of [17] to [19], which further comprises maintaining the concentration of the compound represented by the formula (I) or the organic solvent in the target water for 2 weeks or more. the method of.
[24] Preferably, the biofilm is a biofilm in equipment that functions by flowing or storing water, or a biofilm in water that flows or is stored in the equipment, [16]-[23]. The method according to any one item.
[25] The target water is preferably water that flows or is stored in a facility that functions by flowing or storing water, and more preferably cooling water of a water-cooled cooling tower. [16] to [ 24] The method according to any one of paragraphs 1.

Hereinafter, the present invention will be described in more detail based on Examples, but the present invention is not limited thereto.

(Reagent and medium)
Component A: Compound of formula (I) 3-Methyl salicylaldehyde (Tokyo Chemical Industry Co., Ltd.)
Component B: Organic solvent (SP value in parentheses)
Diethylene glycol monomethyl ether (10.64) (Wako Pure Chemical Industries, Ltd.)
Hexylene glycol (9.97) (Wako Pure Medicine)
Medium R2A medium (Wako Pure Medicine)

(Preparation of test solution)
As shown in Table 1, the compound of formula (I) and an organic solvent were mixed to prepare a test solution.

Test example 1. Biofilm suppression test 1) Preparation of test bacterial suspension For biofilm-forming bacteria isolated from the cooling water collected from the water-cooled cooling tower, the same as the following 2) to 3) using R2A medium without test solution added. The amount of biofilm formed (OD570) was measured by culturing according to the above procedure. Bacteria having an OD570 of 0.7 or more were selected and cultured in R2A medium at 30 ° C. for 24 hours with shaking. The resulting measured turbidity (OD600) of the culture solution to prepare a suspension of diluted to 10 ⁵ cfu / mL in R2A medium.

2) Culture A culture solution was prepared using the suspension of the test bacteria prepared in 1) above and the test solution shown in Table 1, and 150 μL was added to each well of the 96-well microplate to start the culture. The amount of the test solution added was adjusted so that the concentration of the compound of formula (I) in the culture solution was 20 ppm. As a control, water was added instead of the test solution.

3) Measurement of amount of biofilm The 96-well microplate was statically cultured at 30 ° C. for 48 hours, and then the culture solution was removed and washed with water. Subsequently, each well was stained with 0.1% crystal violet, 200 μL of ethanol was added, and the absorbance (OD570) was measured to determine the amount of biofilm (BF) formed.

4) Results Table 2 shows the results of the biofilm formation suppression test. When the concentration of the compound of formula (I) was 20 ppm, there was an effect of suppressing biofilm formation. In addition, the biofilm formation inhibitory effect of the compound of formula (I) improved as the A / B value increased. When the A / B values were the same, diethylene glycol monomethyl ether had a higher biofilm formation inhibitory effect than hexylene glycol.

Claims (11)

A composition for suppressing biofilm formation, which contains a compound represented by the following formula (I) and an organic solvent:

(During the ceremony,
R ¹ , R ² , R ³ and R ⁴ are independently hydrogen atoms, hydrocarbon groups with 1 to 6 carbon atoms, or −CH ₂ −R ⁵ , where R ¹ , R ² , R Not all ³ and R ⁴ are 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 independently hydrogen atoms or methyl groups). The composition for suppressing biofilm formation according to claim 1, wherein the organic solvent has an SP value of 9.0 or more and 11.0 or less. The composition for suppressing biofilm formation according to claim 1 or 2, wherein the organic solvent is at least one selected from the group consisting of an aliphatic ether-based organic solvent and an amide-based organic solvent. The composition for suppressing biofilm formation according to any one of claims 1 to 3, wherein the compound represented by the formula (I) is 3-methylsalitylaldehyde. The composition for suppressing biofilm formation according to any one of claims 1 to 4, wherein the content of the compound represented by the formula (I) is 0.1 to 90% by mass. The composition for suppressing biofilm formation according to any one of claims 1 to 5, wherein the content of the organic solvent is 10 to 99.9% by mass. Any one of claims 1 to 6, wherein the mass ratio (A) / (B) of the compound (A) represented by the formula (I) to the organic solvent (B) is 0.001 or more and 5 or less. The composition for suppressing biofilm formation according to the above item. Biofilm formation inhibition, which comprises adding a biofilm formation inhibitory composition containing the compound represented by the formula (I) according to any one of claims 1 to 7 and an organic solvent to the target water. Method. The composition is added to the target water so that the concentration of the compound represented by the formula (I) in the target water to which the biofilm formation inhibitory composition is added is 0.01 to 1000 ppm. , The method according to claim 8. The method according to claim 8 or 9, wherein the composition is added to the target water so that the concentration of the organic solvent in the target water to which the biofilm formation suppressing composition is added is 1 to 5000 ppm. .. The method according to any one of claims 8 to 10, wherein the target water is cooling water for a water-cooled cooling tower.