Biofilm formation inhibitor, method for inhibiting formation of biofilm, resin composition, molded article, and coating agent

Abstract

Provided are: a biofilm formation inhibitor that can inhibit the formation of a biofilm even when used at a low concentration at which antibacterial activity is not exhibited; a method for inhibiting the formation of a biofilm; a resin composition; a molded article; and a coating agent. The biofilm formation inhibitor comprises a diterpene compound (A) having an octanol / water partition coefficient (logP) of 6 or more.

Description

Biofilm formation inhibitor, biofilm formation inhibition method, resin composition, molded body, and coating agent

[0001] The present invention relates to a biofilm formation inhibitor, a method for inhibiting biofilm formation, a resin composition, a molded article, and a coating agent.

[0002] Biofilms are communities of organisms encapsulated in a viscous substance formed by bacteria. They pose a problem in various industrial fields, including the medical field, which deals with oral diseases and infectious diseases, and the water treatment field, which deals with water supply and wastewater treatment. Biofilms protect bacteria from antibacterial agents and disinfectants, making disinfection and sterilization difficult. Furthermore, the viscosity of biofilms allows bacteria to adhere firmly, making their removal difficult. Therefore, once biofilms are formed, they can lead to a deterioration in environmental hygiene and, in medical settings, to the worsening of diseases such as infectious diseases. Therefore, inhibiting biofilm formation can significantly contribute to improving environmental hygiene and the quality of medical care.

[0003] In the medical field, since Gram-positive cocci such as enterococci may form biofilms on the surfaces of medical instruments, etc., an oral composition containing a carrier such as water or glycerin and a terpenoid dispersed in the carrier has been proposed to inhibit the formation of biofilms by enterococci (see, for example, Patent Document 1). Also in the medical field, since Gram-positive cocci such as Staphylococcus aureus may form biofilms on the surfaces of medical instruments, a biofilm formation inhibitor containing abietic acid or dehydroabietic acid has been proposed to inhibit the formation of biofilms by Staphylococcus aureus (see, for example, Patent Document 2).

[0004] JP 2004-521880 A, WO 2010 / 119638

[0005] However, the compositions described in Patent Documents 1 and 2 do not have a sufficient effect of inhibiting biofilm formation.

[0006] The present invention has been made in consideration of these conventional problems, and aims to provide a biofilm formation inhibitor, a method for inhibiting biofilm formation, a resin composition, a molded body, and a coating agent that can inhibit biofilm formation.

[0007] A biofilm formation inhibitor according to one embodiment of the present invention that solves the above-mentioned problems is a biofilm formation inhibitor that contains a diterpene (A) having an octanol / water partition coefficient (log P) of 6 or more.

[0008] Furthermore, one aspect of the present invention is a method for inhibiting biofilm formation, which comprises contacting the biofilm formation inhibitor with at least one of a target object or a target location.

[0009] Furthermore, a resin composition according to one embodiment of the present invention is a resin composition containing the diterpenes (A) and a resin.

[0010] A molded article according to one embodiment of the present invention is a molded article obtained by molding the above-described resin composition.

[0011] A coating agent according to one embodiment of the present invention is a coating agent containing the diterpenes (A).

[0012] <Biofilm Formation Inhibitor> A biofilm formation inhibitor according to one embodiment of the present invention contains a diterpene (A) having an octanol / water partition coefficient (log P) of 6 or more.

[0013] The octanol / water partition coefficient (log P) is preferably 6 or more. In this embodiment, by including diterpenes (A) having an octanol / water partition coefficient (log P) of 6 or more, biofilm formation can be suppressed. Although the details are unknown, the following speculation is conceivable. In this embodiment, since the octanol / water partition coefficient (log P) of the diterpenes (A) is 6 or more, it is speculated that the biofilm formation inhibitor has high affinity with bacterial cells and biofilms. Therefore, it is speculated that the biofilm formation inhibitor is likely to inhibit biofilm formation because the diterpenes (A) easily act on bacterial cells and biofilms. Furthermore, the biofilm formation inhibitor of this embodiment has the characteristic of being able to suppress biofilm formation even at a low concentration that does not exhibit antibacterial properties (for example, a concentration one-eighth of the MIC (minimum inhibitory concentration)).

[0014] Such an effect is obtained by containing a diterpene (A) having an octanol / water partition coefficient (log P) of 6 or more, and cannot be obtained by abietic acid (AA, log P: 5.75) or dehydroabietic acid (DAA, log P: 5.66), which have an octanol / water partition coefficient (log P) of less than 6.

[0015] The octanol / water partition coefficient (log P) is "the ratio of the substance concentration in octanol to the substance concentration in water when a substance is dissolved in a mixture of octanol and water," and is an index value of the hydrophobicity (or hydrophilicity) of a substance. The larger the value, the higher the hydrophobicity (lipophilicity) tends to be. The octanol / water partition coefficient (log P) can be calculated using software from the structure of the substance (see, for example, JP 2018-188420 A, JP 2019-043985 A, JP 2021-522873 A, and WO 2020 / 045514). It can also be calculated from the structure of diterpenes (A) using the software "MOE (Molecular Operating Environment) 2022.02 (MOLSIS)." In this embodiment, the value calculated from the structure of diterpene (A) using the software "MOE (Molecular Operating Environment) 2022.02 (MOLSIS)" is used.

[0016] The diterpenes (A) are not particularly limited as long as they have an octanol / water partition coefficient (log P) of 6 or more. For example, the diterpenes (A) include diterpenes such as labdanes, pyramanes, and abietanes, as well as various derivatives of these diterpenes. The diterpenes (A) may be used singly or in combination of two or more. Among these, the diterpenes (A) are preferably diterpenes having a structure represented by the following general formula (1). This makes it easier for the biofilm formation inhibitor to inhibit biofilm formation, and it can also inhibit biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0017] (In formula (1), * indicates a bonding site with other substituents. Also, the dashed line portion indicates that a carbon-carbon bond may exist there. When a carbon-carbon bond exists at a dashed line portion, a carbon-carbon bond exists at any one of all dashed line portions.)

[0018] Diterpenes having the structure represented by general formula (1) are compounds that can be extracted from plants of the Pinaceae family, such as pine and cedar, or plants of the Lamiaceae family. The diterpenes having the structure represented by general formula (1) are not particularly limited. Examples of diterpenes having the structure represented by general formula (1) include diterpenes having the structure represented by the following general formula (2) and diterpenes having the structure represented by the following general formula (3).

[0019] (In formula (2), * indicates a bonding site to other substituents.)

[0020] (In formula (3), * indicates a bonding site with other substituents. Also, the dashed line portions indicate that there is a carbon-carbon bond at one of the positions, and a carbon-carbon bond exists at any one of the positions among all the dashed line portions.)

[0021] Diterpenes having a structure represented by general formula (2) are diterpenes having a skeleton derived from tetrahydroabietic acid. Diterpenes having a skeleton derived from tetrahydroabietic acid are not particularly limited. Examples of diterpenes having a skeleton derived from tetrahydroabietic acid include tetrahydroabietic acid (log P: 6.65) and various derivatives of tetrahydroabietic acid (esters, salts, amides (primary amides, secondary amides, tertiary amides, etc.), alcohols, amines (primary amines, secondary amines, tertiary amines, etc.)). Diterpenes having a structure represented by general formula (3) are not particularly limited. Examples of diterpenes having a structure represented by general formula (3) include diterpenes having a skeleton derived from dihydroabietic acid. Diterpenes having a skeleton derived from dihydroabietic acid are not particularly limited, but examples include dihydroabietic acid (log P: 6.12) and various derivatives of dihydroabietic acid (esters, salts, amides (primary amides, secondary amides, tertiary amides, etc.), alcohols, amines (primary amines, secondary amines, tertiary amines, etc.)).

[0022] The alcohols forming the esters in the various derivatives of tetrahydroabietic acid and the various derivatives of dihydroabietic acid are not particularly limited. Examples of such alcohols include dihydric alcohols such as ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, neopentyl glycol, dimer diol, bisphenol A, and bisphenol F, trihydric alcohols such as glycerin, trimethylolethane, and trimethylolpropane, tetrahydric alcohols such as pentaerythritol and diglycerin, and hexahydric alcohols such as dipentaerythritol. The above alcohols may be used alone or in combination of two or more.

[0023] The salts of the various derivatives of tetrahydroabietic acid and the various derivatives of dihydroabietic acid are not particularly limited. Examples of such salts include alkali metal salts, alkaline earth metal salts, amine salts, and ammonium salts. The alkali metal contained in the alkali metal salt is not particularly limited. Examples of alkali metals include sodium, potassium, etc., and these alkali metals may be used alone or in combination of two or more. The alkaline earth metal contained in the alkaline earth metal salt is not particularly limited. Examples of alkaline earth metals include beryllium, magnesium, calcium, strontium, barium, etc., and these alkaline earth metals may be used alone or in combination of two or more.

[0024] The diterpenes (A) of this embodiment may be diterpenes having a structure represented by the above-mentioned general formula (1), or may be diterpenes having a structure other than the structure represented by the general formula (1).

[0025] Diterpenes having a structure other than that represented by general formula (1) are not particularly limited. Examples of diterpenes having a structure other than that represented by general formula (1) include various derivatives of dehydroabietic acid (esters, salts, amides (primary amides, secondary amides, tertiary amides, etc.), alcohols, amines (primary amines, secondary amines, tertiary amines, etc.)), various derivatives of abietic acid (esters, salts, amides (primary amides, secondary amides, tertiary amides, etc.), alcohols, amines (primary amines, secondary amines, tertiary amines, etc.)), and the like. The alcohols forming the esters in the various derivatives of dehydroabietic acid and the various derivatives of abietic acid are not particularly limited, and examples thereof include those described above. Furthermore, the salts in the various derivatives of dehydroabietic acid and the various derivatives of abietic acid are also not particularly limited, and examples thereof include those described above.

[0026] The log P values ​​of representative examples of diterpenes having a structure represented by general formula (1) and diterpenes having a structure other than that represented by general formula (1) are shown in Table 1 below. For reference, Table 1 also shows some diterpenes having a log P value of less than 6.

[0027]

[0028] Details of the abbreviations in Table 1 are as follows: DAA skeleton: skeleton derived from dehydroabietic acid, AA skeleton: skeleton derived from abietic acid, THAA skeleton: skeleton derived from tetrahydroabietic acid, DHAA skeleton: skeleton derived from dihydroabietic acid, Me: methyl, Na: sodium, K: potassium, Gly: glycerin, Gly diester: diester in which two diterpene carboxylic acid molecules are esterified to one glycerin molecule, Gly triester: triester in which three diterpene carboxylic acid molecules are esterified to one glycerin molecule, TEG monoester: monoester in which one diterpene carboxylic acid molecule is esterified to one triethylene glycol molecule, TEG diester: diester in which two diterpene carboxylic acid molecules are esterified to one triethylene glycol molecule.

[0029] The structures of the pimaric acid-derived skeleton, DAA skeleton, AA skeleton, THAA skeleton, and DHAA skeleton in Table 1 are shown in the following general formulas (4) to (8).

[0030] (In formula (4), * indicates a bonding site to other substituents.)

[0031] (In formula (5), * indicates a bonding site to other substituents.)

[0032] (In formula (6), * indicates a bonding site to other substituents.)

[0033] (In formula (7), * indicates a bonding site to other substituents.)

[0034] (In formula (8), * indicates a bonding site with other substituents. In addition, each broken line indicates that there is a carbon-carbon bond at one of the broken line portions, and a carbon-carbon bond exists at any one of the broken line portions.)

[0035] Among these, the diterpenes (A) preferably comprise at least one selected from the group consisting of diterpenes having a structure represented by the general formula (2), diterpenes having a structure represented by the general formula (3), and various derivatives of dehydroabietic acid, and more preferably at least one selected from the group consisting of tetrahydroabietic acid (the THAA skeleton represented by the general formula (7) is bonded to COOH), various derivatives of tetrahydroabietic acid, dihydroabietic acid (the DHAA skeleton represented by the general formula (8) is bonded to COOH), various derivatives of dihydroabietic acid, and various derivatives of dehydroabietic acid, and more preferably at least one of tetrahydroabietic acid or dihydroabietic acid. This makes the biofilm formation inhibitor more likely to suppress biofilm formation, and even at a low concentration that does not exhibit antibacterial properties, it can suppress biofilm formation.

[0036] The diterpenes (A) may be rosins containing the above-mentioned diterpenes. Such rosins are not particularly limited, but examples include hydrogenated rosin, disproportionated rosin, rosin esters, alkali metal salts of rosin, alkaline earth metal salts of rosin, rosin amines, rosin alcohols, and rosin amides. One type of rosin may be used alone, or two or more types may be used in combination.

[0037] (Hydrogenated Rosin) Hydrogenated rosin can be obtained by various known means. Specifically, for example, hydrogenation can be performed under known hydrogenation conditions by hydrogenating natural rosin (gum rosin, tall oil rosin, wood rosin) or purified rosin (hereinafter, natural rosin and purified rosin are collectively referred to as unmodified rosin) derived from Pinus massoniana, Slash pine (Pinus elliottii), Merkusii, Caribbean pine (Pinus caribaea), Pinus kesiya, Loblolly pine (Pinus taeda), and Great King pine (Pinus palustris). Hydrogenation conditions include, for example, heating unmodified rosin to about 100 to 300°C under a hydrogen pressure of about 2 to 20 MPa in the presence of a hydrogenation catalyst. Preferably, the hydrogen pressure is about 5 to 20 MPa and the reaction temperature is about 150 to 300°C. Various known hydrogenation catalysts can be used, such as supported catalysts and metal powders. Supported catalysts include palladium-carbon, rhodium-carbon, ruthenium-carbon, and platinum-carbon. Metal powders include nickel and platinum. Palladium-, rhodium-, ruthenium-, and platinum-based catalysts are preferred because they increase the hydrogenation rate of unmodified rosin and shorten the hydrogenation time. The amount of hydrogenation catalyst used is typically about 0.01 to 5 parts by mass, and preferably about 0.01 to 2 parts by mass, per 100 parts by mass of unmodified rosin.

[0038] If necessary, hydrogenation may be carried out in a state where the unmodified rosin is dissolved in a solvent. The solvent used is not particularly limited, as long as it is inert to the reaction and easily dissolves the raw materials and the product. Examples of solvents include cyclohexane, n-hexane, n-heptane, decalin, tetrahydrofuran, and dioxane, and these can be used alone or in combination of two or more. The amount of solvent used is not particularly limited, but it is usually sufficient to use the solvent so that the solids content is 10% by mass or more, preferably in the range of about 10 to 70% by mass, based on the unmodified rosin.

[0039] The hydrogenated rosin may be further subjected to various treatments, such as purification, hydrogenation, and disproportionation, which will be described later, either alone or in combination. The purification treatment is not particularly limited. Examples include distillation, extraction, recrystallization, and adsorption.

[0040] Furthermore, for the purpose of improving the color tone, the hydrogenated rosin may be further subjected to a dehydrogenation treatment. The dehydrogenation treatment is not particularly limited, and ordinary conditions can be adopted. For example, the dehydrogenation treatment is carried out by subjecting the hydrogenated rosin to an initial hydrogen pressure of 10 kg / cm in the presence of a dehydrogenation catalyst in a sealed container. 2 less than 5 kg / cm 2 The dehydrogenation is carried out at a temperature of about 100 to 300°C, with a lower limit of 200°C and an upper limit of 280°C. There are no particular limitations on the dehydrogenation catalyst, and various known catalysts can be used. Preferred examples include palladium-, rhodium-, and platinum-based catalysts, which are typically used supported on a carrier such as silica or carbon. The amount of the catalyst used is typically about 0.01 to 5% by weight, with a lower limit of 0.05% by weight and an upper limit of 3% by weight, based on the weight of the hydrogenated rosin.

[0041] (Disproportionated Rosin) Disproportionated rosin can be obtained using various known means. Specifically, for example, it can be obtained by a method (disproportionation) in which unmodified rosin is heated in the presence of a disproportionation catalyst. As the disproportionation catalyst, various known catalysts can be used, including supported catalysts such as palladium-carbon, rhodium-carbon, and platinum-carbon; metal powders such as nickel and platinum; and iodides such as iodine and iron iodide. The amount of the catalyst used is usually about 0.01 to 5 parts by mass, and preferably about 0.01 to 1 part by mass, per 100 parts by mass of unmodified rosin. The reaction temperature is about 100 to 300°C, and preferably about 150 to 290°C.

[0042] Furthermore, the disproportionated rosin obtained may be further subjected to the above-mentioned various treatments of purification, disproportionation and hydrogenation either alone or in combination of two or more thereof.

[0043] Furthermore, for the purpose of improving color tone, disproportionated rosin may be subjected to the above-mentioned dehydrogenation treatment, similar to hydrogenated rosin.

[0044] (Rosin Esters) The rosin esters are not particularly limited. Examples of rosin esters include a reaction product of unmodified rosin and alcohol (unmodified rosin ester), a reaction product of hydrogenated rosin and alcohol (hydrogenated rosin ester), and a reaction product of disproportionated rosin and alcohol (disproportionated rosin ester). The alcohol in the rosin esters is not particularly limited, and examples include those described above.

[0045] Furthermore, for the purpose of improving color tone, purified rosin may be subjected to the above-mentioned dehydrogenation treatment in the same manner as hydrogenated rosin.

[0046] Rosin esters can be obtained by various known means. Specific examples include reacting unmodified rosin, hydrogenated rosin, or disproportionated rosin with an alcohol at a temperature of about 150 to 300°C for about 1 to 24 hours. The amounts of unmodified rosin, hydrogenated rosin, disproportionated rosin, and alcohol charged are not particularly limited, but are typically determined so that the OH group of the alcohol / COOH group of the rosin (equivalent ratio) is about 0.8 to 8, preferably about 1.1 to 1.3.

[0047] In the method for producing rosin esters, the rosin esters obtained may be further subjected to various treatments such as the above-mentioned purification, hydrogenation, disproportionation, etc. Furthermore, the various treatments may be performed alone or in combination of two or more.

[0048] The hydrogenated rosin ester and the disproportionated rosin ester may be produced by subjecting a reaction product of unmodified rosin with an alcohol to a modification reaction by hydrogenation or disproportionation, respectively.

[0049] (Alkali Metal Salt of Rosin) An alkali metal salt of rosin (hereinafter also simply referred to as an alkali metal salt) is a salt obtained by neutralizing rosin with a metal compound containing an alkali metal (hereinafter also simply referred to as an alkali metal compound).

[0050] The rosin in the alkali metal salt is not particularly limited as long as it is a rosin-based resin having a carboxyl group. Examples of the rosin in the alkali metal salt include unmodified rosin, hydrogenated rosin, and disproportionated rosin.

[0051] The alkali metal contained in the alkali metal salt is not particularly limited. For example, the alkali metal contained in the alkali metal salt is sodium, potassium, etc. The alkali metal may be used alone or in combination of two or more.

[0052] The alkali metal compound is not particularly limited as long as it forms a salt with rosin. Examples of the alkali metal compound include hydroxides, oxides, chlorides, nitrates, acetates, sulfates, carbonates, etc. of alkali metals. One type of alkali metal compound may be used alone, or two or more types may be used in combination.

[0053] The alkali metal compound is preferably sodium hydroxide or potassium hydroxide. The form of the alkali metal compound is not particularly limited, but is preferably an aqueous solution.

[0054] The alkali metal salt can be obtained by reacting (neutralizing) rosin with an alkali metal compound.

[0055] Examples of methods for reacting rosin with an alkali metal compound include a method in which rosin is directly reacted with an alkali metal compound in the presence or absence of a solvent (direct method), and a method in which a salt exchange is carried out by reacting a metal salt of rosin other than an alkali metal with an alkali metal compound in the presence of a solvent (metasetic method). The reaction temperature is not particularly limited, but is usually in the range from room temperature to the boiling point of the solvent. The reaction time varies depending on the reaction temperature, but is usually about 10 minutes to 24 hours. After completion of the reaction, the solvent may be distilled off.

[0056] The solvent is not particularly limited. Examples of the solvent include water; alcohol-based solvents such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, ethylene glycol, and propylene glycol; ether alcohol-based solvents such as diethylene glycol, triethylene glycol, and 2-methoxyethanol; aromatic hydrocarbon-based solvents such as toluene and xylene; ester-based solvents such as ethyl acetate and butyl acetate; and ketone-based solvents such as methyl ethyl ketone and methyl isobutyl ketone. Water is preferred as the solvent.

[0057] The reaction of rosin with an alkali metal compound is carried out so that the amount of alkali metal introduced relative to the COOH groups of the rosin is usually 5 to 100 equivalent %, preferably 10 to 100 equivalent %.

[0058] (Alkaline Earth Metal Salt of Rosin) An alkaline earth metal salt of rosin (hereinafter also simply referred to as alkaline earth metal salt) is a neutralized salt of rosin with a metal compound containing an alkaline earth metal (hereinafter also simply referred to as alkaline earth metal compound).

[0059] The rosin in the alkaline earth metal salt is not particularly limited as long as it is a rosin-based resin having a carboxyl group. Examples of the rosin in the alkaline earth metal salt include unmodified rosin, hydrogenated rosin, and disproportionated rosin.

[0060] The alkaline earth metal contained in the alkaline earth metal salt is not particularly limited. Examples of alkaline earth metals include beryllium, magnesium, calcium, strontium, barium, etc. The alkaline earth metals may be used alone or in combination of two or more.

[0061] The alkaline earth metal is preferably at least one selected from the group consisting of magnesium and calcium.

[0062] The alkaline earth metal compound is not particularly limited as long as it can form a salt with rosin. Examples of alkaline earth metal compounds include hydroxides, oxides, chlorides, nitrates, acetates, sulfates, carbonates, etc. of alkaline earth metals. One type of alkaline earth metal compound may be used alone, or two or more types may be used in combination.

[0063] The alkaline earth metal compound is preferably magnesium hydroxide, magnesium oxide, calcium hydroxide, or calcium oxide.

[0064] The alkaline earth metal salt can be obtained by reacting (neutralizing) rosin with an alkaline earth metal compound.

[0065] Examples of methods for reacting rosin with an alkaline earth metal compound include a method (direct method) in which rosin is directly reacted with an alkaline earth metal compound in the presence or absence of an organic solvent; and a method (metathesis method) in which a salt exchange is carried out by reacting a rosin salt of a metal other than an alkaline earth metal with an alkaline earth metal compound in the presence of water and / or an organic solvent. The reaction temperature is not particularly limited, but is typically about 150 to 270°C in the direct method, and typically ranges from room temperature to the boiling point of the solvent in the methaesis method. The reaction time varies depending on the reaction temperature, but is typically about 10 minutes to 24 hours. After completion of the reaction, the solvent may be removed by distillation.

[0066] The organic solvent is not particularly limited, and examples thereof include aromatic hydrocarbon solvents such as toluene and xylene, ester solvents such as ethyl acetate and butyl acetate, and ketone solvents such as methyl ethyl ketone and methyl isobutyl ketone.

[0067] The reaction of rosin with an alkaline earth metal compound is carried out so that the amount of alkaline earth metal introduced relative to the COOH groups of the rosin is usually 5 to 100 equivalent %, preferably 10 to 100 equivalent %.

[0068] (Rosin Amines) The rosin amines are not particularly limited. For example, rosin amines are amines obtained by reacting rosin with ammonia and then hydrogenating the reacted rosin (U.S. Pat. No. 2,534,297). Alternatively, rosin amides, as described below, are produced from rosin and amines, and the amide group in the rosin amides is reduced (hydride reduction, hydrogenation). The rosin in the rosin amines is not particularly limited as long as it is a rosin-based resin having a carboxyl group. For example, the rosin in the rosin amines may be unmodified rosin, hydrogenated rosin, disproportionated rosin, or the like. An amine obtained from unmodified rosin is also referred to as unmodified rosin amine, an amine obtained from hydrogenated rosin as hydrogenated rosin amine, and an amine obtained from disproportionated rosin as disproportionated rosin amine.

[0069] (Rosin Alcohols) The rosin alcohols are not particularly limited. For example, rosin alcohols are alcohols obtained by a method of hydrogenating and reducing carboxyl groups in rosin (Japanese Patent Laid-Open No. 2014-133866). The rosin in the rosin alcohols is not particularly limited as long as it is a rosin-based resin having a carboxyl group. For example, the rosin in the rosin alcohols includes unmodified rosin, hydrogenated rosin, disproportionated rosin, etc. Note that alcohol obtained from unmodified rosin is also referred to as unmodified rosin alcohol, alcohol obtained from hydrogenated rosin alcohol, and alcohol obtained from disproportionated rosin alcohol.

[0070] (Rosin Amides) The rosin amides are not particularly limited. For example, rosin amides are amides obtained by reacting (amidating) rosin with ammonia or amines. The rosin in the rosin amides is not particularly limited as long as it is a rosin-based resin having a carboxyl group. For example, the rosin in the rosin amides is unmodified rosin, hydrogenated rosin, disproportionated rosin, etc. Note that an amide obtained from unmodified rosin is also referred to as unmodified rosin amide, an amide obtained from hydrogenated rosin is also referred to as hydrogenated rosin amide, and an amide obtained from disproportionated rosin is also referred to as disproportionated rosin amide.

[0071] The amines in the rosin amides are not particularly limited as long as they have at least one amino group in the molecule. Examples of the amines in the rosin amides include aliphatic monoamines, aliphatic polyamines, alicyclic monoamines, alicyclic polyamines, aromatic monoamines, and aromatic polyamines. The amino groups in the amines are also not particularly limited. Examples of the amino groups in the amines include primary amino groups, secondary amino groups, and tertiary amino groups.

[0072] The method for reacting rosin with amines is not particularly limited, and various known methods can be used. Specific examples include a method in which rosin is converted into an acid chloride by a thionyl chloride method, and the acid chloride is reacted with amines (amidation) in the presence or absence of an organic solvent.

[0073] The organic solvent is not particularly limited as long as it is inert to the reaction components, and examples of the organic solvent include benzene, toluene, xylene, dimethyl ether, diisobutyl ether, tetrahydrofuran, acetone, methyl ethyl ketone, and methyl isobutyl ketone.

[0074] In the reaction (amidation), a basic substance or a tertiary amine may be used as a catalyst, if necessary. The basic substance is not particularly limited, and examples thereof include sodium hydroxide, potassium hydroxide, sodium bicarbonate, and sodium carbonate. The tertiary amine is not particularly limited, and examples thereof include trimethylamine, triethylamine, tributylamine, and pyridine. Furthermore, the above-mentioned tertiary amines can also be used as reaction solvents when the above-mentioned aromatic monoamine is soluble therein.

[0075] Furthermore, the diterpenes (A) may be rosins containing diterpenes having a structure represented by general formula (1). Such rosins are not particularly limited, but examples thereof include rosins containing diterpenes having a structure represented by general formula (1) such as rosins containing at least one of diterpenes having a structure represented by general formula (2) and diterpenes having a structure represented by general formula (3).

[0076] The rosins containing at least one of the diterpenes having the structure represented by the general formula (2) and the diterpenes having the structure represented by the general formula (3) are not particularly limited, but examples thereof include the above-mentioned hydrogenated rosins containing at least one of tetrahydroabietic acid and dihydroabietic acid, various derivatives of such hydrogenated rosins (hydrogenated rosin esters, various salts of hydrogenated rosins (alkali metal salts of hydrogenated rosins, alkaline earth metal salts of hydrogenated rosins, amine salts of hydrogenated rosins, hydrogenated rosins), and the like. and the like. Examples of the disproportionated rosins include the above-mentioned disproportionated rosins containing at least one of tetrahydroabietic acid and dihydroabietic acid, various derivatives of such disproportionated rosins (disproportionated rosin esters, various salts of disproportionated rosin (alkali metal salts of disproportionated rosin, alkaline earth metal salts of disproportionated rosin, amine salts of disproportionated rosin, ammonium salts of disproportionated rosin), disproportionated rosin amides, disproportionated rosin alcohols, and disproportionated rosin amines).

[0077] The diterpenes (A) may be rosins containing diterpenes having a structure other than that represented by general formula (1). Examples of rosins containing diterpenes having a structure other than that represented by general formula (1) include various derivatives of the disproportionated rosin containing dehydroabietic acid (disproportionated rosin esters, various salts of disproportionated rosin (alkali metal salts of disproportionated rosin, alkaline earth metal salts of disproportionated rosin, amine salts of disproportionated rosin, ammonium salts of disproportionated rosin), disproportionated rosin amides, disproportionated rosin alcohols, disproportionated rosin amines), various derivatives of the unmodified rosin containing abietic acid (alkali metal salts of unmodified rosin, alkaline earth metal salts of unmodified rosin, amine salts of unmodified rosin, ammonium salts of unmodified rosin), unmodified rosin amides, unmodified rosin alcohols, unmodified rosin amines), etc.

[0078] Among these, the diterpenes (A) are preferably at least one selected from the group consisting of diterpenes having a structure represented by general formula (2) and rosins containing at least one of diterpenes having a structure represented by general formula (3), and various derivatives of disproportionated rosin containing dehydroabietic acid; more preferably at least one selected from the group consisting of hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid, various derivatives of the hydrogenated rosin, disproportionated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid, various derivatives of the disproportionated rosin, and various derivatives of disproportionated rosin containing dehydroabietic acid; and even more preferably at least one selected from the group consisting of hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid and esters of the hydrogenated rosin (hydrogenated rosin esters). This makes it even easier for the biofilm formation inhibitor to inhibit biofilm formation, and it can inhibit biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0079] When the diterpenes (A) of this embodiment are the rosins, the content of the diterpenes having the structure represented by general formula (1) in the rosins is not particularly limited. For example, the content of the diterpenes having the structure represented by general formula (1) is preferably 5% by mass or more, more preferably 10% by mass or more, even more preferably 15% by mass or more, even more preferably 20% by mass or more, even more preferably 30% by mass or more, even more preferably 40% by mass or more, even more preferably 50% by mass or more, even more preferably 60% by mass or more, even more preferably 70% by mass or more, even more preferably 80% by mass or more, and particularly preferably 90% by mass or more, relative to 100% by mass of the rosins. Furthermore, the content of the diterpenes having the structure represented by general formula (1) is preferably 100% by mass or less, relative to 100% by mass of the rosins. By containing diterpenes having a structure represented by general formula (1) within the above range, the biofilm formation inhibitor is more likely to suppress biofilm formation, and can suppress biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0080] When the diterpenes (A) of this embodiment are the rosins, the content of the diterpenes having the structure represented by general formula (2) in the rosins is not particularly limited. For example, the content of the diterpenes having the structure represented by general formula (2) is preferably 5% by mass or more, more preferably 10% by mass or more, even more preferably 15% by mass or more, even more preferably 20% by mass or more, even more preferably 30% by mass or more, even more preferably 40% by mass or more, even more preferably 50% by mass or more, even more preferably 60% by mass or more, even more preferably 70% by mass or more, even more preferably 80% by mass or more, and particularly preferably 90% by mass or more, relative to 100% by mass of the rosins. Furthermore, the content of the diterpenes having the structure represented by general formula (2) is preferably 100% by mass or less, relative to 100% by mass of the rosins. By containing diterpenes having a structure represented by general formula (2) within the above range, the biofilm formation inhibitor is more likely to suppress biofilm formation, and can suppress biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0081] When the diterpenes (A) of this embodiment are the rosins, the content of the diterpenes having the structure represented by general formula (3) in the rosins is not particularly limited. For example, the content of the diterpenes having the structure represented by general formula (3) is preferably 5% by mass or more, more preferably 10% by mass or more, more preferably 15% by mass or more, even more preferably 20% by mass or more, even more preferably 30% by mass or more, even more preferably 40% by mass or more, even more preferably 50% by mass or more, even more preferably 60% by mass or more, and particularly preferably 70% by mass or more, relative to 100% by mass of the rosins. The content of the diterpenes having the structure represented by general formula (3) is preferably 100% by mass or less, relative to 100% by mass of the rosins. By having the content of the diterpenes having the structure represented by general formula (3) within the above range, the biofilm formation inhibitor is more likely to suppress biofilm formation, and can suppress biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0082] When the diterpenes (A) of this embodiment are the rosins, the content of tetrahydroabietic acid in the hydrogenated rosin is not particularly limited. For example, the content of tetrahydroabietic acid is preferably 10% by mass or more, more preferably 15% by mass or more, even more preferably 20% by mass or more, even more preferably 30% by mass or more, even more preferably 40% by mass or more, even more preferably 50% by mass or more, even more preferably 60% by mass or more, even more preferably 70% by mass or more, even more preferably 80% by mass or more, and particularly preferably 90% by mass or more, relative to 100% by mass of the hydrogenated rosin. Furthermore, the content of tetrahydroabietic acid is preferably 100% by mass or less, relative to 100% by mass of the hydrogenated rosin. By having the content of tetrahydroabietic acid within the above range, the biofilm formation inhibitor is more likely to suppress biofilm formation, and can suppress biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0083] When the diterpenes (A) of this embodiment are the rosins, the content of dihydroabietic acid in the hydrogenated rosin is not particularly limited. For example, the content of dihydroabietic acid is preferably 1% by mass or more, more preferably 5% by mass or more, even more preferably 10% by mass or more, even more preferably 15% by mass or more, even more preferably 20% by mass or more, even more preferably 30% by mass or more, even more preferably 40% by mass or more, even more preferably 50% by mass or more, even more preferably 60% by mass or more, and particularly preferably 70% by mass or more, relative to 100% by mass of the hydrogenated rosin. By having the dihydroabietic acid content within the above range, the biofilm formation inhibitor is more likely to suppress biofilm formation, and can suppress biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0084] When the diterpenes (A) of this embodiment are the rosins, the content of tetrahydroabietic acid in the disproportionated rosin is not particularly limited. For example, the content of tetrahydroabietic acid is preferably 10% by mass or more, more preferably 15% by mass or more, even more preferably 20% by mass or more, even more preferably 30% by mass or more, and particularly preferably 40% by mass or more, relative to 100% by mass of the disproportionated rosin. Furthermore, the content of tetrahydroabietic acid is preferably less than 50% by mass, relative to 100% by mass of the disproportionated rosin. By having the content of tetrahydroabietic acid within the above range, the biofilm formation inhibitor is more likely to inhibit biofilm formation, and can inhibit biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0085] When the diterpenes (A) of this embodiment are the rosins, the content of dihydroabietic acid in the disproportionated rosin is not particularly limited. For example, the content of dihydroabietic acid is preferably 5% by mass or more, more preferably 10% by mass or more, even more preferably 15% by mass or more, even more preferably 20% by mass or more, even more preferably 30% by mass or more, and particularly preferably 40% by mass or more, relative to 100% by mass of the disproportionated rosin. Furthermore, the content of dihydroabietic acid is preferably less than 50% by mass, relative to 100% by mass of the disproportionated rosin. By having the dihydroabietic acid content within the above range, the biofilm formation inhibitor is more likely to inhibit biofilm formation, and can inhibit biofilm formation even at a low concentration that does not exhibit antibacterial properties.

[0086] The diterpenes (A) of the present embodiment may be derived from natural products extracted from the above-mentioned plants or may be synthetic compounds. The diterpenes (A) of the present embodiment include all stereoisomers (diastereomers, epimers, enantiomers, etc.) and racemates thereof.

[0087] The physical properties of the diterpenes (A) of this embodiment are not particularly limited except for the octanol / water partition coefficient (log P). The solubility of the diterpenes (A) in water at 20°C is not particularly limited, but is preferably 1% by mass or less, more preferably 0.1% by mass or less. By having a water solubility within the above range, when the biofilm formation inhibitor is applied (e.g., coated) to an object or location where a biofilm may form, the biofilm formation inhibitor can suppress the breakdown of the coating film due to moisture in the environment or human sweat, or the exudation of the diterpenes (A) from the coating film. Therefore, the biofilm formation inhibitor has excellent coating film durability. Diterpenes having a solubility in water of more than 1% by mass at 20°C are not particularly limited, but examples include alkali metal salts of tetrahydroabietic acid, alkali metal salts of dihydroabietic acid, alkali metal salts of dehydroabietic acid, alkali metal salts of abietic acid, and alkali metal salts of rosin.

[0088] The biofilm formation inhibitor of this embodiment may contain additives as needed. The additives are not particularly limited. Examples of additives include solvents, abrasives, gelling agents, humectants, anti-corrosive agents, seasonings, sweeteners, analgesics, anti-calculus agents, whitening agents, surfactants, binders, preservatives, opacifying agents, colorants, pH buffers, disinfectants, and the like. These may be used alone or in combination of two or more. The content ratio of the additives is appropriately set depending on the purpose and application.

[0089] The type of bacteria from which biofilms that can be targeted by the biofilm formation inhibitor of this embodiment originate is not particularly limited. Examples of the type of bacteria include gram-positive bacteria and gram-negative bacteria.

[0090] The gram-positive bacteria are not particularly limited. Examples of gram-positive bacteria include Staphylococcus (e.g., Staphylococcus aureus, Staphylococcus epidermidis), Enterococcus, Streptococcus (e.g., diplococcus, tetrastreptococcus, octastreptococcus, etc., Streptococcus pneumoniae, hemolytic streptococcus, and Streptococcus mutans), Bacillus (e.g., Bacillus anthracis, Bacillus subtilis), and Clostridium (e.g., tetanus). Examples of bacteria that may be present include bacteria of the genus Micrococcus (e.g., Micrococcus luteus), Corynebacterium (e.g., Corynebacterium xerosis, Corynebacterium diphtheriae), Propionibacterium (e.g., Propionibacterium acnes), Mycobacterium (e.g., Mycobacterium tuberculosis), and Actinomyces (e.g., A. israelii).

[0091] The Gram-negative bacteria are not particularly limited. Examples of Gram-negative bacteria include Escherichia (e.g., Escherichia coli), Salmonella, Pseudomonas (e.g., Pseudomonas aeruginosa), Helicobacter, Neisseria (e.g., Neisseria gonorrhoeae and Neisseria meningitidis), Burkholderia (e.g., Burkholderia cepacia), Klebsiella (e.g., Klebsiella pneumoniae), Vibrio (Vibrio parahaemolyticus), Rickettsia, and Spirochaetes.

[0092] Among these, the biofilm formation inhibitor of the present embodiment preferably inhibits the formation of a biofilm derived from Gram-positive bacteria, which makes the biofilm formation inhibitor particularly suitable for use in applications where a biofilm derived from Gram-positive bacteria is formed.

[0093] In particular, the Gram-positive bacteria is preferably at least one species selected from the group consisting of the genera Staphylococcus, Enterococcus, and Streptococcus, which makes it easier for the biofilm formation inhibitor to inhibit the formation of biofilms derived from the genera Staphylococcus, Enterococcus, and Streptococcus.

[0094] Furthermore, the Gram-positive bacteria is preferably at least one selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans, which makes it easier for the biofilm formation inhibitor to inhibit the formation of biofilms derived from Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans.

[0095] The content of diterpenes (A) in the biofilm formation inhibitor of this embodiment may be any concentration as long as it is capable of inhibiting biofilm formation, but it has the characteristic that excellent biofilm formation inhibitory effect can be obtained even at a concentration equal to or lower than the MIC for the above biofilm. MIC refers to the minimum inhibitory concentration, and represents the minimum drug concentration capable of inhibiting bacterial growth when a drug susceptibility test is performed using the agar plate dilution method or the broth microdilution method.

[0096] The content of diterpenes (A) in the biofilm formation inhibitor of this embodiment is such that an excellent biofilm formation inhibitory effect is obtained even at a concentration below the MIC, an excellent biofilm formation inhibitory effect is obtained even at a concentration of one-half the MIC or less, an excellent biofilm formation inhibitory effect is obtained even at a concentration of one-quarter the MIC or less, and an excellent biofilm formation inhibitory effect is obtained even at a concentration of one-eighth the MIC or less. In other words, the biofilm formation inhibitor of this embodiment can inhibit biofilm formation without exhibiting antibacterial properties. Therefore, the biofilm formation inhibitor can suppress the occurrence of drug-resistant bacteria. Furthermore, the content of diterpenes (A) in the biofilm formation inhibitor of this embodiment is preferably at a concentration of one-hundredth or more of the MIC, and more preferably at a concentration of one-sixty-fourth or more of the MIC, in order to obtain an excellent biofilm formation inhibitory effect.

[0097] <Method for inhibiting biofilm formation> A method for inhibiting biofilm formation according to one embodiment of the present invention is a method in which the biofilm formation inhibitor described above is brought into contact with at least one of a target object or a target location.

[0098] The target object or target location is not particularly limited as long as it is an object or location where microorganisms are likely to grow and a biofilm can form. Examples of the target object or target location include plumbing areas such as kitchens, bathrooms, washrooms, and toilets, plumbing-related facilities, equipment, and components, wastewater and water treatment facilities in homes and other businesses, equipment and components related to the wastewater and water treatment facilities, and the oral cavity (e.g., teeth, dentures, gums, tongue, oral mucosa, etc.). The target object or target location may also be a hospital, medical facilities, medical equipment, etc. The medical equipment is not particularly limited. Examples of medical equipment include respiratory device endoscopes, gastroscopes, hematology flow channels, dialysis equipment, respiratory path maintenance devices, ISEs, HPLCs, and catheters used in these applications. Medical equipment may also include artificial hearts, stents, artificial joints, dental implant materials, etc.

[0099] The biofilm formation inhibition method of this embodiment inhibits biofilm formation by contacting at least one of these target objects or target locations with a biofilm formation inhibitor. As described above, the biofilm formation inhibitor can inhibit biofilm formation even at a low concentration that does not exhibit antibacterial properties. Therefore, the biofilm formation inhibition method of this embodiment can easily and effectively inhibit biofilm formation in the target object or target location and can suppress the occurrence of drug-resistant bacteria, even when using a biofilm formation inhibitor at a low concentration that does not exhibit antibacterial properties.

[0100] When carrying out the method for inhibiting biofilm formation, the manner in which the biofilm formation inhibitor is brought into contact with the target object or target location is not particularly limited. For example, the manner in which the biofilm formation inhibitor is brought into contact with the target object or target location includes spraying, application, atomization, coating, penetration, washing, kneading into resin, etc. These are selected appropriately depending on the form of the biofilm formation inhibitor.

[0101] <Resin Composition and Molded Article> A resin composition according to one embodiment of the present invention contains the diterpenes (A) and a resin.

[0102] The resin is not particularly limited, and examples of the resin include vinyl chloride resins, styrene resins, polyamides, polyamideimides, polyimides, polyesters, polycarbonates, polyacetals, ABS resins, phenoxy resins, polymethyl methacrylate resins, polyphenylene ethers, polyphenylene sulfide, polyetherimides, liquid crystal polymers, polyetherketones, polyethersulfones, polysulfones, fluororesins, and polyolefin resins (e.g., polyethylene and polypropylene).

[0103] The content of diterpenes (A) is not particularly limited. For example, the content of diterpenes (A) in the resin composition is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably 5% by mass or more. Furthermore, the content of diterpenes (A) in the resin composition is preferably 50% by mass or less, more preferably 30% by mass or less. By having the content of diterpenes (A) within the above range, the resin composition can suppress biofilm formation even when it contains a low concentration of diterpenes (A) that does not exhibit antibacterial properties.

[0104] A molded article according to one embodiment of the present invention is a molded article obtained by molding the resin composition described above. The shape of the molded article is not particularly limited. For example, the shape of the molded article can be appropriately selected depending on the application and purpose. For example, the shape of the molded article may be a plate, plate, rod, sheet, film, cylinder, ring, circle, ellipse, polygon, irregular shape, hollow, frame, box, panel, or the like.

[0105] Furthermore, the molded body of this embodiment may be any of the various molded bodies that constitute the target object and target location described above in relation to the method for inhibiting biofilm formation.

[0106] The molding method for the molded article is not particularly limited, and examples of molding methods for the molded article include injection molding, injection compression molding, extrusion molding, profile extrusion, press molding, sheet molding, film molding, transfer molding, inflation molding, blow molding, gas-assisted blow molding, blow molding, extrusion blow molding, IMC (in-mold coating molding), rotational molding, multilayer molding, two-color molding, insert molding, sandwich molding, foam molding, and pressure molding.

[0107] The use of the obtained molded article is not particularly limited, and examples of uses of the molded article include packaging materials, agricultural materials, civil engineering materials, fibers, building materials, automobile parts, home appliance parts, sanitary and medical materials, and other industrial materials.

[0108] The molded article of this embodiment can suppress the formation of a biofilm even when it contains a diterpene (A) at a low concentration that does not exhibit antibacterial properties.

[0109] <Coating Agent> A coating agent according to one embodiment of the present invention contains the diterpene (A) described above. The coating agent is not particularly limited. Examples of the coating agent include various thermosetting coating agents and photocurable coating agents.

[0110] The content of diterpenes (A) is not particularly limited. For example, the content of diterpenes (A) in the coating agent is preferably 0.01% by mass or more, more preferably 0.1% by mass or more. Furthermore, the content of diterpenes (A) in the coating agent is preferably 50% by mass or less, more preferably 30% by mass or less. By having the content of diterpenes (A) within the above range, the coating agent can suppress biofilm formation by applying it to an object or a target location, even if it contains a low concentration of diterpenes (A) that does not exhibit antibacterial properties.

[0111] The components constituting the coating agent other than the diterpenes (A) are not particularly limited. For example, the other components of the coating agent may be any of the components that are blended into conventionally known thermosetting or photocurable coating agents, such as binder resins (acrylic resins, urethane resins, polyester resins, epoxy resins, alkyd resins, phenolic resins, melamine resins, silicone resins, etc.), polymerization initiators (radical polymerization initiators, cationic polymerization initiators, anionic polymerization initiators, radical photopolymerization initiators, cationic photopolymerization initiators, anionic photopolymerization initiators, etc.), solvents (ketone solvents, aromatic solvents, alcohol solvents, glycol solvents, glycol ether solvents, ester solvents, petroleum-based solvents, haloalkane solvents, amide solvents, etc.), silicone oils, adhesion promoters such as silane coupling agents, fillers, leveling agents, rheology modifiers, diluents, surfactants, dispersants, antifoaming agents, dehydrating agents, antioxidants, antioxidants, antistatic agents, infrared absorbers, ultraviolet absorbers, light stabilizers, fluorescent agents, dyes, pigments, fragrances, abrasives, rust inhibitors, thixotropy-imparting agents, etc.

[0112] The object and the target location to which the coating agent is applied are not particularly limited. For example, the object and the target location may be the object and the target location described above in relation to the method for inhibiting biofilm formation.

[0113] By applying the coating agent of this embodiment to an object or a target location, the surface of the object or target location can be endowed with an excellent biofilm formation inhibitory effect.

[0114] <Oral Composition> An oral composition according to one embodiment of the present invention contains the diterpenes (A) described above.

[0115] The form of the oral composition is not particularly limited. Examples of the oral composition include toothpaste, gel, powder, solution (mouthwash, dental rinse), suspension, emulsion, troche (lozenge), vehicle, tablet, gum, etc. The method for preparing the oral composition is not particularly limited, and known methods may be used depending on the form of the oral composition.

[0116] The method of using the oral composition is not particularly limited, and a known method can be adopted depending on the form of the oral composition. For example, when the oral composition is a toothpaste, the oral cavity (e.g., teeth, dentures, gums, tongue, oral mucosa, etc.) is treated with the oral composition at any frequency.

[0117] The components other than the diterpenes (A) constituting the oral composition are not particularly limited. For example, the other components of the oral composition may be any components that are incorporated into conventionally known oral compositions, such as water, surfactants, abrasives, humectants, monohydric alcohols, binders, flavorings, sweeteners, pH adjusters, preservatives, colorants, disinfectants, natural polymers (e.g., gelatin, collagen, konjac mannan, pullulan, chitosan, starch, etc.), synthetic polymers (e.g., polyethylene glycol, carboxyvinyl polymer, etc.), polysaccharides (e.g., dextran, polyacryl dextran, etc.), lecithin (soybean lecithin, egg yolk lecithin, etc.), polylactic acid, polyglycolic acid, albumin, cyclodextrin, etc.

[0118] The method of using the oral composition is not particularly limited, and a known method can be adopted depending on the form of the oral composition. For example, when the oral composition is a toothpaste, the oral cavity (e.g., teeth, dentures, gums, tongue, oral mucosa, etc.) is treated with the oral composition at any frequency.

[0119] An embodiment of the present invention has been described above. The present invention is not particularly limited to the above embodiment. Note that the above embodiment mainly describes an invention having the following configuration.

[0120] (1) A biofilm formation inhibitor comprising a diterpene (A) having an octanol / water partition coefficient (log P) of 6 or more.

[0121] According to this configuration, the biofilm formation inhibitor can inhibit the formation of a biofilm.

[0122] (2) The biofilm formation inhibitor according to (1), wherein the diterpenes (A) have a structure represented by the following general formula (1): (In formula (1), * indicates a bonding site with other substituents. Also, the dashed line portion indicates that a carbon-carbon bond may exist there. When a carbon-carbon bond exists at a dashed line portion, a carbon-carbon bond exists at any one of all dashed line portions.)

[0123] With this configuration, the biofilm formation inhibitor is more likely to inhibit the formation of biofilms.

[0124] (3) A biofilm formation inhibitor according to (1) or (2), wherein the diterpenes (A) include at least one of tetrahydroabietic acid and dihydroabietic acid.

[0125] With this configuration, the biofilm formation inhibitor is more likely to suppress the formation of biofilms.

[0126] (4) A biofilm formation inhibitor according to (1) or (2), wherein the diterpenes (A) are hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid.

[0127] With this configuration, the biofilm formation inhibitor is more likely to suppress the formation of biofilms.

[0128] (5) A biofilm formation inhibitor according to (1) or (2), wherein the diterpenes (A) are rosin esters, and the rosin esters are reaction products of hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid with an alcohol.

[0129] With this configuration, the biofilm formation inhibitor is more likely to suppress the formation of biofilms.

[0130] (6) A biofilm formation inhibitor according to any one of (1) to (5), wherein the solubility of the diterpenes (A) in water at 20°C is 1% by mass or less.

[0131] According to this configuration, when the biofilm formation inhibitor is applied (e.g., coated) to an object or a location where a biofilm may form, the biofilm formation inhibitor can inhibit the breakdown of the coating film due to moisture in the environment or human sweat, or the exudation of the diterpenes (A) from the coating film, thereby providing excellent coating film durability.

[0132] (7) A biofilm formation inhibitor according to any one of (1) to (6), which inhibits the formation of a biofilm derived from Gram-positive bacteria.

[0133] With this configuration, the biofilm formation inhibitor is particularly suitable for use in applications where biofilms derived from Gram-positive bacteria are formed, and is therefore likely to inhibit biofilm formation.

[0134] (8) The biofilm formation inhibitor according to (7), wherein the Gram-positive bacteria is at least one species selected from the group consisting of Staphylococcus, Enterococcus, and Streptococcus.

[0135] With this configuration, the biofilm formation inhibitor is particularly likely to inhibit the formation of biofilms derived from the genera Staphylococcus, Enterococcus, and Streptococcus.

[0136] (9) A biofilm formation inhibitor according to (7) or (8), wherein the Gram-positive bacteria is at least one selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans.

[0137] With this configuration, the biofilm formation inhibitor is particularly likely to inhibit the formation of biofilms derived from Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans.

[0138] (10) A method for inhibiting biofilm formation, comprising contacting at least one of a target object or a target location with a biofilm formation inhibitor described in any one of (1) to (9).

[0139] With this configuration, the biofilm formation inhibiting method can easily inhibit the formation of biofilms on a target object (such as a medical catheter) or a target location (particularly a bathroom or sink).

[0140] (11) A resin composition comprising the diterpene (A) according to any one of (1) to (9) and a resin.

[0141] According to this configuration, the resin composition can suppress the formation of a biofilm.

[0142] (12) A molded article obtained by molding the resin composition according to (11).

[0143] With this configuration, the molded article can suppress the formation of a biofilm in the molded article.

[0144] (13) A coating agent comprising the diterpenes (A) according to any one of (1) to (9).

[0145] According to this configuration, the coating agent can suppress the formation of a biofilm by being applied to a target object or a target location.

[0146] The present disclosure also provides the following:

[0147] (Item A1) A biofilm formation inhibitor comprising a diterpene (A) having an octanol / water partition coefficient (log P) of at least 6. (Item A2) The biofilm formation inhibitor according to the above item, wherein the diterpene (A) has a structure represented by the following general formula (1): (In formula (1), * indicates a bonding site with another substituent. Also, the dashed line portion indicates that a carbon-carbon bond may be present there. When a carbon-carbon bond is present in a dashed line portion, a carbon-carbon bond is present at any one of all dashed line portions.) (Item A3) A biofilm formation inhibitor according to any of the above items, wherein the diterpenes (A) have a structure represented by the following general formula (2): (In formula (2), * indicates a bonding site with another substituent.) (Item A4) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) have a structure represented by the following general formula (3): (In formula (3), * indicates a bonding site with another substituent. Furthermore, each dashed line indicates that there is a carbon-carbon bond at one of the positions, and a carbon-carbon bond is present at any one of all the dashed line positions.) (Item A5) The biofilm formation inhibitor according to any of the above items, wherein the diterpenes (A) comprise at least one selected from the group consisting of diterpenes having a structure represented by general formula (2) above, diterpenes having a structure represented by general formula (3) above, and derivatives of dehydroabietic acid. (Item A6) The biofilm formation inhibitor according to any of the above items, wherein the diterpenes (A) comprise at least one selected from the group consisting of tetrahydroabietic acid, derivatives of tetrahydroabietic acid, dihydroabietic acid, derivatives of dihydroabietic acid, and derivatives of dehydroabietic acid. (Item A7) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) include at least one of tetrahydroabietic acid and dihydroabietic acid. (Item A8) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing diterpenes having the structure represented by general formula (1). (Item A9) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing diterpenes having the structure represented by general formula (2). (Item A10) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing diterpenes having the structure represented by general formula (3). (Item A11) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing at least one selected from the group consisting of diterpenes having a structure represented by the general formula (2) above, diterpenes having a structure represented by the general formula (3) above, and derivatives of dehydroabietic acid.(Item A12) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing at least one selected from the group consisting of tetrahydroabietic acid, derivatives of tetrahydroabietic acid, dihydroabietic acid, derivatives of dihydroabietic acid, and derivatives of dehydroabietic acid. (Item A13) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing at least one of tetrahydroabietic acid and dihydroabietic acid. (Item A14) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing at least one selected from the group consisting of disproportionated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid, derivatives of the disproportionated rosin, hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid, and derivatives of the hydrogenated rosin. (Item A15) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are disproportionated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid. (Item A16) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are derivatives of disproportionated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid. (Item A17) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid. (Item A18) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are derivatives of hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid.(Item A19) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosin esters, which are reaction products of hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid with an alcohol. (Item A20) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing diterpenes having the structure represented by general formula (1), and the content of the diterpenes having the structure represented by general formula (1) is 20% by mass or more and 100% by mass or less, relative to 100% by mass of the rosins. (Item A21) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are rosins containing diterpenes having the structure represented by general formula (2), and the content of the diterpenes having the structure represented by general formula (2) is 10% by mass or more and 100% by mass or less, relative to 100% by mass of the rosins. (Item A22) The biofilm formation inhibitor according to any of the above items, wherein the diterpenes (A) are rosins containing diterpenes having the structure represented by general formula (3), and the content of the diterpenes having the structure represented by general formula (3) is 5% by mass or more and 100% by mass or less, relative to 100% by mass of the rosins. (Item A23) The biofilm formation inhibitor according to any of the above items, wherein the diterpenes (A) are hydrogenated rosin containing tetrahydroabietic acid, and the content of tetrahydroabietic acid is 10% by mass or more and 100% by mass or less, relative to 100% by mass of the hydrogenated rosin. (Item A24) The biofilm formation inhibitor according to any of the above items, wherein the diterpenes (A) are hydrogenated rosin containing dihydroabietic acid, and the content of dihydroabietic acid is 1% by mass or more and 100% by mass or less, relative to 100% by mass of the hydrogenated rosin. (Item A25) The biofilm formation inhibitor according to any one of the preceding items, wherein the diterpenes (A) are esters of hydrogenated rosin containing tetrahydroabietic acid, and the content of tetrahydroabietic acid is 10% by mass or more and 100% by mass or less relative to 100% by mass of the hydrogenated rosin.(Item A26) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are esters of hydrogenated rosin containing dihydroabietic acid, and the dihydroabietic acid content is 1% by mass or more and 100% by mass or less, relative to 100% by mass of the hydrogenated rosin. (Item A27) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are disproportionated rosin containing tetrahydroabietic acid, and the tetrahydroabietic acid content is 10% by mass or more and 100% by mass or less, relative to 100% by mass of the disproportionated rosin. (Item A28) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) are disproportionated rosin containing dihydroabietic acid, and the dihydroabietic acid content is 5% by mass or more and 100% by mass or less, relative to 100% by mass of the disproportionated rosin. (Item A29) The biofilm formation inhibitor according to any one of the above items, wherein the solubility of the diterpenes (A) in water at 20°C is 1% by mass or less. (Item A30) The biofilm formation inhibitor according to any one of the above items, wherein the solubility of the diterpenes (A) in water at 20°C is 0.1% by mass or less. (Item A31) The biofilm formation inhibitor according to any one of the above items, wherein the diterpenes (A) do not include an alkali metal salt of tetrahydroabietic acid, an alkali metal salt of dihydroabietic acid, an alkali metal salt of dehydroabietic acid, an alkali metal salt of abietic acid, or an alkali metal salt of rosins. (Item A32) The biofilm formation inhibitor according to any one of the above items, which inhibits the formation of a biofilm derived from Gram-positive bacteria. (Item A33) The biofilm formation inhibitor according to Item A32, wherein the Gram-positive bacteria is at least one species selected from the group consisting of Staphylococcus, Enterococcus, and Streptococcus. (Item A34) The biofilm formation inhibitor according to Item A32 or A33, wherein the Gram-positive bacteria is at least one species selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus mutans.(Item A35) A method for inhibiting biofilm formation, comprising contacting at least one of a target object or a target location with the biofilm formation inhibitor described in any of the above items. (Item A36) A resin composition comprising the diterpene (A) described in any of the above items and a resin. (Item A37) A resin composition comprising the diterpene (A) described in any of the above items and a polyolefin resin. (Item A38) A molded article obtained by molding the resin composition described in Item A37. (Item A39) A coating agent comprising the diterpene (A) described in any of the above items.

[0148] The present invention will be explained in more detail below with reference to examples. The present invention is not limited to these examples. Unless otherwise specified, "%" means "% by mass" and "parts" means "parts by mass." The materials used in the following examples and comparative examples are as follows. The units of values ​​in the columns relating to each component and the total in the tables are "% by mass."

[0149] The samples used in this example are listed below. The octanol / water partition coefficient log P and solubility in water at 20°C were calculated using the following method. (Octanol / water partition coefficient log P) Calculation was performed from the sample structure using the software "MOE (Molecular Operating Environment) 2022.02 (MOLSIS)." (Solubility in water at 20°C) The sample was pulverized into powder, and the pulverized sample was added to deionized water in a mass ratio of 1:10 and mixed at 20°C for 2 hours. Filtration was performed using a filter (Advantec membrane filter H050A047A), and the filtrate was collected. The collected filtrate was dried at 105°C for 5 hours, and the solubility was calculated from the dried mass using the following formula. (Sample concentration A) % = (Sample after grinding) g / (Sample after grinding + deionized water) g × 100 (Non-volatile content of aqueous solution B) % = (Mass after drying) g / (Amount of filtrate collected) g × 100 Solubility in water % = (Non-volatile content of aqueous solution B) % / (Sample concentration A) %

[0150] The amounts of tetrahydroabietic acid and dihydroabietic acid in hydrogenated rosin 1, hydrogenated rosin 2, hydrogenated rosin K salt, and disproportionated rosin used in this example were determined by the following method. 0.1 g of a sample was dissolved in 2.0 g of n-hexanol, and 0.1 g of this solution was homogeneously mixed with 0.4 g of an on-column methylating agent (phenyltrimethylammonium hydroxide (PTAH) in methanol (0.2 mol / L, manufactured by GL Sciences Inc.)), and 1 μL of the mixture was injected into a commercially available gas chromatograph mass spectrometer (GC / MS) for measurement. The total peak area of ​​the component with mass number 320 was taken as the peak area representing the methyl ester of tetrahydroabietic acid, and the total peak area of ​​the component with mass number 318 was taken as the peak area representing the methyl ester of dihydroabietic acid. The ratios of each peak area to the total peak area representing methylated resin acids (the total peak area of ​​components with mass numbers 314 to 320) were calculated to determine the contents of tetrahydroabietic acid and dihydroabietic acid. The analytical apparatus and column are shown below. Gas chromatograph mass spectrometer: "Agilent 6890", "Agilent 5973N" manufactured by Agilent Technologies, Inc. Column: "Advance-DS" manufactured by Shinwa Chemical Industry Co., Ltd.

[0151] The amounts of tetrahydroabietic acid and dihydroabietic acid in the hydrogenated rosin ester used in this example were determined by the following method: The hydrogenated rosin ester and potassium hydroxide were added to n-hexanol, and the mixture was refluxed (hydrolyzed) for 2 hours, and then neutralized with hydrochloric acid to obtain a resin acid. 0.1 g of the resin acid was dissolved in 2.0 g of n-hexanol, and 0.1 g of this solution was homogeneously mixed with 0.4 g of an on-column methylating agent (phenyltrimethylammonium hydroxide (PTAH) in methanol (0.2 mol / L, manufactured by GL Sciences Inc.)), and 1 μL of the mixture was injected into a commercially available gas chromatograph mass spectrometer (GC / MS) for measurement. The total peak area of ​​the component with mass number 320 was taken as the peak area representing the methyl ester of tetrahydroabietic acid, and the total peak area of ​​the component with mass number 318 was taken as the peak area representing the methyl ester of dihydroabietic acid. The ratio of each peak area to the total peak area representing the methylated resin acid (the total peak area of ​​components with mass numbers 314 to 320) was calculated to determine the contents of tetrahydroabietic acid and dihydroabietic acid. The analytical apparatus and column are shown below. Gas chromatograph mass spectrometer: "Agilent 6890", "Agilent 5973N" manufactured by Agilent Technologies, Inc. Column: "Advance-DS" manufactured by Shinwa Chemical Industry Co., Ltd.

[0152] Furthermore, the contents of triethylene glycol (hereinafter also referred to as TEG) monoester and TEG diester in the hydrogenated rosin ester used in this example were calculated from gel permeation chromatography (GPC) measurements of the hydrogenated rosin ester, and the area ratio of the peak derived from the TEG monoester to the total peak area, and the area ratio of the peak derived from the TEG diester to the total peak area. The measurement conditions are described below. (Measurement conditions) Apparatus: High-speed GPC apparatus HLC-8320GPC manufactured by Tosoh Corporation Column: TSKgel guard column HXL-L / G2000HXL / G1000HXL manufactured by Tosoh Corporation Eluent: Tetrahydrofuran Flow rate: 1.0 mL / min Temperature: 40°C RI detector: Bryce type double path, double flow system, red LED (wavelength: 630 to 670 nm) manufactured by Tosoh Corporation Measurement sample: The sample was diluted with the above eluent so that the concentration of rosins was 0.1% and measured.

[0153] (Sample Production) Production Example 1: 600 parts of Chinese hydrogenated rosin (manufactured by Guangxi Wuzhou Richeng Lin Chemical Co., Ltd.) were placed in a 1-liter flask and distilled under a reduced pressure of 400 Pa to obtain a component distilled at 195 to 250°C. 100 parts of the component distilled at 195 to 250°C, 1.5 parts of 5% palladium alumina, and 100 parts of cyclohexane were placed in a 1-liter autoclave. The system was thoroughly purged with hydrogen gas, and the initial hydrogen pressure was set to 6 MPa. The temperature was raised to 200°C, and then the hydrogen pressure was increased to 10 MPa. The reaction was carried out for 4 hours while appropriately replenishing the pressure loss. The catalyst was filtered off, and cyclohexane was distilled off under reduced pressure to obtain hydrogenated rosin. The resulting hydrogenated rosin was recrystallized twice in acetone and dried under reduced pressure to obtain tetrahydroabietic acid. The resulting tetrahydroabietic acid had an octanol / water partition coefficient log P of 6.65 and a solubility in water at 20°C of 0.01%.

[0154] Production Example 2: An autoclave was charged with 100 parts of crude Chinese gum rosin, 100 parts of mineral turpene, and 5 parts of Raney nickel catalyst as a hydrogenation catalyst. After hydrogen substitution, the pressure was increased to 10 MPa and the reaction was carried out at 110°C for 5 hours. The catalyst was filtered under a nitrogen atmosphere to obtain a mineral turpene solution of semi-hydrogenated rosin. 0.2 parts of paratoluenesulfonic acid was added to 100 parts of this solution, and the reaction was isomerized at a reaction temperature of 150°C for 2 hours. Subsequently, mineral turpene and paratoluenesulfonic acid were distilled off under reduced pressure to obtain crude crystals. The crude crystals were recrystallized four times in acetone to obtain dihydroabietic acid. The obtained dihydroabietic acid had an octanol / water partition coefficient log P of 6.12 and a solubility in water at 20°C of 0.00%.

[0155] Production Example 3 Hydrogenated rosin (55% tetrahydroabietic acid, 25% dihydroabietic acid) was charged into a vacuum distillation vessel, heated to 250°C and maintained at that temperature for 1 hour, and then distilled under a nitrogen blanket at a reduced pressure of 1 kPa to obtain hydrogenated rosin 1. The obtained hydrogenated rosin 1 was a hydrogenated rosin containing 60% tetrahydroabietic acid and 27% dihydroabietic acid, and had a solubility in water at 20°C of 0.05%.

[0156] Production Example 4: A 3-liter autoclave was charged with 100 parts of Chinese gum rosin and 0.2 parts of 5% palladium carbon (water content: 50%) as a hydrogenation catalyst. After removing oxygen from the system, the system was pressurized with hydrogen at 100 kg / cm. 2 After pressurizing the mixture, the temperature was raised to 260°C with stirring, and a hydrogenation reaction was carried out at the same temperature for 3 hours to obtain a crude hydrogenated rosin. Next, the crude hydrogenated rosin was distilled under a nitrogen blanket at a reduced pressure of 3 mmHg, and the main fraction distilled at 195 to 250°C was obtained as hydrogenated rosin 2. The obtained hydrogenated rosin 2 was a hydrogenated rosin containing 28% tetrahydroabietic acid and 52% dihydroabietic acid, and had a solubility in water at 20°C of 0.03%.

[0157] Production Example 5 To 100 parts of the dehydroabietic acid obtained in Comparative Production Example 1 described below, 650 parts of an ethanolic potassium hydroxide solution (trade name "0.5 mol / L potassium hydroxide solution (ethanolic) (N / 2)", manufactured by Kanto Chemical Co., Inc.) was added dropwise. Acetone was added to the mixture, and the mixture was filtered to obtain a potassium salt of dehydroabietic acid as a residue. The obtained potassium salt of dehydroabietic acid had an octanol / water partition coefficient log P of 6.29 and a solubility in water at 20°C of 99.1%.

[0158] Production Example 6: 600 parts of Chinese hydrogenated rosin (manufactured by Guangxi Wuzhou Richeng Lin Chemical Co., Ltd.) were placed in a 1-liter flask and distilled under a reduced pressure of 400 Pa to obtain a component distilled at 195 to 250°C. 100 parts of the component distilled at 195 to 250°C, 1.5 parts of 5% palladium alumina, and 200 parts of cyclohexane were placed in a 1-liter autoclave. The system was thoroughly purged with hydrogen gas, and the initial hydrogen pressure was set to 6 MPa. The temperature was raised to 200°C, and then the hydrogen pressure was increased to 10 MPa. The reaction was continued for 4 hours while appropriately replenishing the pressure loss. The catalyst was filtered off, and cyclohexane was removed by distillation under reduced pressure to obtain hydrogenated rosin. To 100 parts of the hydrogenated rosin, 650 parts of an ethanolic potassium hydroxide solution (trade name "0.5 mol / L Potassium Hydroxide Solution (Ethanol) (N / 2)" manufactured by Kanto Chemical Co., Inc.) was added dropwise. Acetone was added to the mixture, and the mixture was filtered to obtain a hydrogenated rosin potassium salt as a filtrate. The resulting hydrogenated rosin potassium salt was a hydrogenated rosin potassium salt containing 95% tetrahydroabietic acid and 1% dihydroabietic acid, and the octanol / water partition coefficients log P of the tetrahydroabietic acid potassium salt and the dihydroabietic acid potassium salt were 7.27 and 6.75, respectively, and the solubility of the hydrogenated rosin potassium salt in water at 20°C was 97.9%.

[0159] Production Example 7: 100 parts of crude Chinese gum rosin was mixed with 0.03 parts of 5% palladium carbon (water content 50%) as a disproportionation catalyst, and the mixture was stirred under a nitrogen blanket at 280°C for 4 hours to carry out a disproportionation reaction, yielding crude disproportionated rosin. The crude disproportionated rosin was then distilled under a nitrogen blanket at a reduced pressure of 3 mmHg, and the main fraction, which had an acid value of 176.5, a softening point of 82°C, and a color of Gardner 4, was taken as purified disproportionated rosin. Next, 100 parts of the purified disproportionated rosin and 0.3 parts of 5% palladium carbon (water content 50%) were charged into a 1-liter shaking autoclave, and after removing oxygen from the system, the system was pressurized with hydrogen at 0.5 kg / cm. 2 The mixture was pressurized to 500 K and heated to 275°C, and a dehydrogenation reaction was carried out at the same temperature for 3 hours to obtain a disproportionated rosin. The obtained disproportionated rosin contained 12% tetrahydroabietic acid and 8% dihydroabietic acid, and had a solubility in water at 20°C of 0.02%.

[0160] Production Example 8: 100 parts of Chinese hydrogenated rosin (manufactured by Guangxi Wuzhou Richeng Forest Chemical Co., Ltd.) and 50 parts of triethylene glycol were charged into a 1-liter flask, heated to 200°C under an argon stream to melt, and then reacted at 250°C for 5 hours and then at 270°C for 5 hours to obtain a hydrogenated rosin ester. The obtained hydrogenated rosin ester was a rosin ester containing 40% TEG diester of hydrogenated rosin containing tetrahydroabietic acid and dihydroabietic acid and 45% TEG monoester of the hydrogenated rosin, and had a solubility in water at 20°C of 0.66%. The octanol / water partition coefficients log P of the TEG diester of tetrahydroabietic acid, the TEG diester of dihydroabietic acid, the TEG monoester of tetrahydroabietic acid, and the TEG monoester of dihydroabietic acid in the hydrogenated rosin ester were 13.05, 14.11, 6.78, and 6.25, respectively. Furthermore, the hydrogenated rosin in the hydrogenated rosin ester was a hydrogenated rosin containing 12.7% tetrahydroabietic acid and 81.5% dihydroabietic acid.

[0161] Comparative Production Example 1: Disproportionated rosin (acid value 167, softening point 77°C, manufactured by Arakawa Chemical Industries, Ltd.) was melted in an argon stream and then heated under reduced pressure of 133 Pa to obtain a fraction (purified disproportionated rosin) at 195-200°C. 100 parts of the purified disproportionated rosin was dissolved in 240 parts of ethanol with heating, 20 parts of monoethanolamine was added, and the mixture was allowed to react under reflux for 1 hour, after which 250 parts of water was added. The resulting dehydroabietic acid monoethanolamine salt was extracted twice with 200 mL of isooctane to remove unsaponifiable matter and dihydroabietic acid salt. After standing overnight, the crystals were filtered and further recrystallized three times with 125 parts of ethanol to sufficiently increase the purity of the dehydroabietic acid. The amine salt was then decomposed with hydrochloric acid and filtered. The crystals were dissolved in ether, thoroughly washed with water, and then completely solidified. The solution was recrystallized again in ethanol to obtain dehydroabietic acid. The resulting dehydroabietic acid had an octanol / water partition coefficient log P of 5.66 and a solubility in water at 20°C of 0.00%.

[0162] Comparative Preparation Example 2 Commercially available abietic acid (Kanto Chemical Co., Inc.) was recrystallized four times in acetone and dried under reduced pressure to obtain abietic acid. The obtained abietic acid had an octanol / water partition coefficient log P of 5.75 and a solubility in water at 20°C of 0.65%.

[0163] (Calculation of MIC for each sample) For each of the above samples, the MICs of Streptococcus mutans (strain 8148) and Staphylococcus aureus (strain N315) were measured by broth microdilution. Mueller-Hinton medium supplemented with streptohemosupplement was used for Streptococcus mutans, and Mueller-Hinton medium supplemented with cations was used for Staphylococcus aureus. Using each medium, a two-fold dilution series of the drug was prepared in a 96-well plate, and approximately 10,000 viable bacteria were added to each well. Static culture was performed at 37°C for 24 hours, and the lowest concentration at which bacterial growth was not visually confirmed was determined as the MIC.

[0164] Examples 1 to 11 and Comparative Examples 1 to 4 For each of the above samples, the biofilm formation rate against Streptococcus mutans or Staphylococcus aureus was evaluated by the following method. The results are shown in Tables 2 and 3.

[0165] (Method for calculating biofilm formation inhibition rate) Streptococcus mutans (strain 8148) was diluted 100-fold with brain heart infusion medium (supplemented with 1% glucose). Staphylococcus aureus (strain N315) was also diluted 100-fold with brain heart infusion medium (supplemented with 1% glucose). Then, 100 μL of each dilution was dispensed into a 96-well plate. A sample solution prepared by diluting each of the above samples to an appropriate concentration with DMSO as a solvent was added. The concentration in each medium was adjusted to 1 / 8 of the MIC. A control medium was used without the sample. These were statically cultured at 37°C for 24 hours. This allowed biofilms to form on the 96-well plate. Planktonic bacteria were then washed and removed with distilled water, and the formed biofilms were stained with crystal violet. After washing each well with distilled water, the crystal violet was eluted with 200 μL of 30% acetic acid, and the absorbance at 570 nm was measured to determine the biofilm formation rate (relative to the control).

[0166]

[0167]

[0168] Details of the abbreviations in Tables 2 and 3 are as follows: THAA: tetrahydroabietic acid, DHAA: dihydroabietic acid, DAA: dehydroabietic acid, AA: abietic acid, K: potassium

[0169] As shown in Table 2, when the samples of Examples 1 to 6 of the present invention (containing diterpenes with a log P of 6 or more) were used, the biofilm formation rate against Streptococcus mutans was less than 50%, even though the concentration was one-eighth of the MIC. On the other hand, when the samples of Comparative Examples 1 and 2 (with a log P of less than 6) were used, the biofilm formation rate against Streptococcus mutans exceeded 50%.

[0170] Furthermore, as shown in Table 3, when the samples of Examples 7 to 11 of the present invention (containing diterpenes with a log P of 6 or more) were used, the biofilm formation rate against Staphylococcus aureus was less than 30%, despite the concentration being one-eighth of the MIC. On the other hand, when the samples of Comparative Examples 3 and 4 (with a log P of less than 6) were used, the biofilm formation rate against Staphylococcus aureus exceeded 30%.

[0171] (Production of Resin Composition) Example 12 95 parts of polypropylene (trade name "Novatec MA3" manufactured by Japan Polypropylene Corporation) and 5 parts of hydrogenated rosin 1 of Production Example 3 were placed in a roller mixer-type kneading apparatus (manufactured by Toyo Seiki Seisaku-sho, Ltd., apparatus name "Labo Plastomill Model 10C100") and kneaded for 10 minutes at a roller rotation speed of 40 rpm and a temperature of 190°C to obtain a kneaded product (resin composition).

[0172] Example 13 95 parts of polypropylene (trade name "Novatec MA3" manufactured by Japan Polypropylene Corporation) and 5 parts of hydrogenated rosin 2 of Production Example 4 were placed in a roller mixer-type kneading apparatus (manufactured by Toyo Seiki Seisaku-sho, Ltd., apparatus name "Labo Plastomill Model 10C100") and kneaded for 10 minutes at a roller rotation speed of 40 rpm and a temperature of 190°C to obtain a kneaded product (resin composition).

[0173] Comparative Example 5 100 parts of polypropylene (trade name "Novatec MA3", manufactured by Japan Polypropylene Corporation) was charged into a roller mixer type kneading apparatus (manufactured by Toyo Seiki Seisaku-Sho, Ltd., apparatus name "Labo Plastomill Model 10C100") and kneaded for 10 minutes at a roller rotation speed of 40 rpm and a temperature of 190°C to obtain a kneaded product (resin composition).

[0174] The biofilm formation rate of each of the above resin compositions against Staphylococcus aureus was evaluated by the following method. The results are shown in Table 4.

[0175] (Method for calculating biofilm formation inhibition rate) The resin compositions of Examples 12-13 and Comparative Example 5 were injection molded using a hand truder (manufactured by Toyo Seiki Seisakusho, Ltd.) at a resin melting temperature of 200°C and a mold temperature of 40°C to prepare test specimens (length 1 cm x width 1 cm x thickness 1 mm). Next, Staphylococcus aureus (N315 strain) cultured overnight was diluted 100-fold with brain heart infusion medium (supplemented with 1% glucose), and 0.75 mL of each dilution was dispensed into a 24-well plate, to which each of the above test specimens was added and overlaid with a washer. The test specimen obtained from the resin composition of Comparative Example 5 served as a control. These were cultured stationary at 37°C for 24 hours. This allowed a biofilm to form on the surface of the test specimen. Thereafter, floating bacteria were washed and removed with distilled water, and the formed biofilm was stained with crystal violet. After washing and removing excess crystal violet with distilled water, the crystal violet was eluted with 1 mL of 30% acetic acid. The absorbance of crystal violet at 570 nm was measured to determine the biofilm formation rate (relative to the control).

[0176]

[0177] As shown in Table 4, in the case of resin compositions containing hydrogenated rosins 1 and 2 of the present invention (containing diterpenes with a log P of 6 or more), the biofilm formation rate against Staphylococcus aureus was significantly lower than that of resin compositions not containing diterpenes.

Claims

1. A biofilm formation inhibitor comprising a diterpene (A) having an octanol / water partition coefficient (log P) of 6 or more.

2. The biofilm formation inhibitor according to claim 1, wherein the diterpene (A) has a structure represented by the following general formula (1). (In formula (1), * indicates a bonding site with other substituents. Also, the dashed line portion indicates that a carbon-carbon bond may be present there. When a carbon-carbon bond is present at a dashed line portion, a carbon-carbon bond is present at any one of all dashed line portions.) 3. A biofilm formation inhibitor as described in claim 1 or 2, wherein the diterpenes (A) include at least one of tetrahydroabietic acid and dihydroabietic acid.

4. A biofilm formation inhibitor as described in claim 1 or 2, wherein the diterpenes (A) are hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid.

5. A biofilm formation inhibitor as described in claim 1 or 2, wherein the diterpenes (A) are rosin esters, and the rosin esters are reaction products of hydrogenated rosin containing at least one of tetrahydroabietic acid and dihydroabietic acid with an alcohol.

6. A biofilm formation inhibitor as described in claim 1 or 2, wherein the solubility of the diterpenes (A) in water at 20°C is 1 mass% or less.

7. A biofilm formation inhibitor according to claim 1 or 2, which inhibits the formation of a biofilm derived from Gram-positive bacteria.

8. The biofilm formation inhibitor according to claim 7, wherein the Gram-positive bacteria is at least one species selected from the group consisting of the genera Staphylococcus, Enterococcus, and Streptococcus.

9. The biofilm formation inhibitor according to claim 7, wherein the gram-positive bacteria is at least one selected from the group consisting of Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus mutans.

10. A method for inhibiting biofilm formation, comprising contacting at least one of a target object or a target location with the biofilm formation inhibitor described in claim 1 or 2.

11. A resin composition comprising the diterpene (A) according to claim 1 or 2 and a resin.

12. A molded article produced by molding the resin composition according to claim 11.

13. A coating agent comprising the diterpene (A) according to claim 1 or 2.