JPH06345790A - Microbicidal and algaecidal agent - Google Patents

Abstract

PURPOSE:To provide a microbicidal and algaecidal agent exhibiting a sufficient microbicidal and algaecidal force even in a low use concentration and little in foamability and smell. CONSTITUTION:A microbicidal and algaecidal agent containing as an active ingredient a tris(hydroxyalkyl)alkylphosphonium salt of formula: (HOR<1>)3R<2>P<+>X<-> (R<1> is 1-4C alkylene; R<2> is 12-18C linear or branched alkyl; X is an anion of an inorganic acid or organic acid).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a fungicidal algicidal agent containing a tris (hydroxyalkyl) alkylphosphonium salt as an active ingredient.

[0002]

2. Description of the Related Art At present, not only for medical use but also for industrial use,
A great variety of fungicides are used in various fields such as agriculture and food. Most of the fungicides used so far have been highly toxic fungicides, but recently, due to environmental pollution problems and economic problems, sufficient antibacterial activity is exhibited even at low use concentrations. Development of the bactericide shown is desired. Further, it has been conventionally known to use a phosphonium salt compound as an active ingredient of an antibacterial preparation, and has a broad activity spectrum against bacteria, fungi and algae. These are used as sterilizing agents for general industrial materials, industrial water, process water for producing pulp and paper, water for use, and are disclosed in, for example, U.S. Pat. No. 3,281,365, JP-A-57-204286, and JP-A-57-204286. 62-1149
03, JP-A-63-60903, JP-A-2
No. 24090, for example. Among them, tetrakis hydroxymethylphosphonium sulfate (hereinafter, TH
PS is a water treatment germicide (trademark: Torside P).
S) is commercially available. In addition, nitrogen-containing compounds structurally similar to phosphonium salt compounds, especially quaternary ammonium salts and amine salts are also well known as germicides,
For example, alkyldimethylbenzylammonium chloride (benzalkonium chloride) and di-n-decyldimethylammonium chloride are mainly used.

[0003]

However, the above-mentioned phosphonium salt compound is still insufficient in the bactericidal and algaecidal effect by short-time contact. Particularly in a system in which a high concentration of organic substances is present, the bactericidal / algicidal effect is remarkably reduced, and the use thereof is extremely limited. Further, although the quaternary ammonium salt compound has a bactericidal effect to some extent, it has a property of easily foaming at a certain use concentration, and therefore its use is also limited.
Moreover, since the quaternary ammonium salt compound has a property of being easily adsorbed on the surface of a negatively charged substance,
It has the drawback of lowering the drug concentration due to adsorption and thus the bactericidal effect. The present inventors have solved the above-mentioned problems, have a broad spectrum of sterilization and algicidal action, and have sufficient bactericidal and algicidal effect by short-time contact, and can be applied to a wide range of fields including medical fields. It is intended to provide a bactericidal and algicidal agent.

[0004]

As a result of intensive studies, the present inventors have found that certain hydroxyalkylphosphonium salt compounds have extremely strong bactericidal activity as compared with closely related phosphonium salt compounds and quaternary ammonium salts. The present invention has been completed by finding that it has algae-killing power and a broad bactericidal and algae-killing spectrum, and has little bubbling and little odor even when vigorously stirred as in a cooling tower. That is, the bactericidal / algicidal agent to be provided by the present invention is represented by the following general formula (1) (HOR ¹ ) ₃ R ² P ⁺ X ⁻ (wherein R ¹ is an alkylene group having 1 to 4 carbon atoms, R ² Is a linear or branched alkyl group having 12 to 18 carbon atoms,
X ⁻ represents a tris (hydroxyalkyl) alkylphosphonium salt represented by an anion of an inorganic acid or an organic acid) as an active ingredient.

The present invention will be further described below. In the formula (1), which is an active ingredient of the bactericidal / algicidal agent of the present invention, in the formula, R ¹
Is an alkylene group having 1 to 4 carbon atoms such as a methylene group, an ethylene group, a propylene group and a butylene group. Also, R
² is an alkyl group having 12 to 18 carbon atoms such as dodecyl group, tetradecyl group, hexadecyl group, octadecyl group and the like.

X ⁻ is an inorganic or organic anion, for example, a halogen ion such as fluorine, chlorine, bromine or iodine, a carboxyl ion such as formic acid, acetic acid and oxalic acid, a sulfate ion, a phosphate ion, methyl or dimethyl phosphate. Ions, ethyl or diethyl phosphate ion, antimony fluoride ion, phosphorus fluoride ion, arsenic fluoride ion, boron fluoride ion, perchlorate ion and the like can be mentioned, with halogen ion being preferred.

Examples of such tris (hydroxyalkyl) alkylphosphonium salts include tris (hydroxymethyl) n-dodecylphosphonium chloride, tris (hydroxymethyl) n-hexadecylphosphonium chloride and tris (2-hydroxyethyl) n-dodecyl. Phosphonium chloride, tris (2-hydroxyethyl) n-hexadecylphosphonium chloride,
Tris (2-hydroxyethyl) n-octadecylphosphonium chloride, tris (3-hydroxypropyl) n-tetradecylphosphonium chloride, tris (3-hydroxypropyl) n-hexadecylphosphonium chloride, tris (3-hydroxypropyl) n
-Octadecylphosphonium chloride, tris (4-
Examples thereof include hydroxybutyl) n-hexadecylphosphonium bromide, tris (2-hydroxyethyl) n-hexadecylphosphonium bromide, and tris (3-hydroxypropyl) n-hexadecylphosphonium bromide.

[0008] (1) In the tris (hydroxyalkyl) alkyl phosphonium salt according to formula, for example, bactericidal and algicidal force combination is excellent wherein R ¹ is an alkyl group having 16 to 18 carbon atoms having 3, R ² carbon , Especially Tris (3
-Hydroxypropyl) n-hexadecylphosphonium chloride has the highest bactericidal / algicidal effect.

Method for producing bactericidal / algicidal agent of the present invention The tris (hydroxyalkyl) alkylphosphonium salt which is the bactericidal / algicidal agent of the present invention may be produced by any method. An example is shown. A tris (hydroxyalkyl) phosphine represented by the general formula (2) (HOR ¹ ) ₃ P (wherein R ¹ has the same meaning as described above), and a general formula (3) R ² X (wherein R ² is (Synonymous with the above, X represents halogen)
The bactericidal and algicidal agent of the present invention can be obtained by reacting with an alkyl halide represented by The reactions of the above general formulas (2) and (3) are preferably carried out in the presence of a solvent at the reflux temperature of the solvent for 15 to 48 hours. Further, the alkyl halide is preferably used in an equimolar to 5-fold molar amount relative to tris (hydroxyalkyl) phosphine.

Suitable organic solvents include n-hexane,
Examples thereof include n-heptane, n-octane, benzene, toluene and xylene. The bactericidal / algicidal agent according to the present invention may be used in combination with other bactericidal / algicidal agents, if necessary. For example, quaternary ammonium salts such as dimethyldi-n-decyl ammonium chloride, benzyl dimethyl n-dodecyl ammonium chloride, benzyl dimethyl n-tetradecyl ammonium chloride, 5-chloro-2-methyl-4-isothiazoline-3.
-One, 2-bromo-2-nitropropane-1,3-diol, 1,5-pentanediol, phenol, chlorhexidine, povidone iodine, alkylpolyaminoethyleneglycine chloride, organic fungicides such as chlorine agents and silver-substituted zeolite, silver Inorganic antibacterial agents such as substituted apatite 1
One kind or a combination of two or more kinds may be used.

In addition, the formulation may contain auxiliary agents such as a surfactant, a binder, a colorant, a dispersant, and a wetting agent, if necessary. In particular, a surfactant can be added in order to enhance the cleaning effect, but the surfactant is preferably a nonionic surfactant, such as polyethylene glycol such as polyoxyethylene alkylphenyl ether, sorbitan acid fatty acid ester, etc. Examples thereof include amides such as polyhydric alcohols and fatty acid alkylolamides. The bactericidal / algicidal agent according to the present invention has various industrial fields depending on the form of its formulation, for example, a slime preventive or control agent in papermaking, water, fats and oils, emulsions,
It can impart antiseptic and bactericidal functions to paper, rubber, plastics, fibers, films, paints and the like.

[0012]

The bactericidal / algicidal agent of the present invention exhibits a wide spectrum of activity effective against various bacteria, fungi, algae, viruses and the like, and particularly has an excellent bactericidal activity against resistant Staphylococcus aureus (MRSA). For example, it exhibits a bactericidal and growth-inhibiting effect against bacteria, and an algicidal and algae-proofing effect against algae. The minimum bactericidal concentration (MIC) is not uniform depending on the type of tris (hydroxyalkyl) alkylphosphonium salt, the type of preparation or the type of bacteria, and the environment, but the concentration of benzylphosphonium salt is exhibited at 0.1 ppm or more, and is generally The bactericidal activity is extremely high as compared with well-known bactericides based on phosphonium salts and quaternary ammonium salts. Moreover, the tris (hydroxyalkyl) alkylphosphonium salt according to the present invention is more stable to heat than the quaternary ammonium salt compound and other organic compounds, and has a high decomposition temperature near 350 ° C., for example. Yes,
It is also chemically stable.

[0013]

EXAMPLES The present invention will be further described below with reference to examples. Example 1 Tris (3-hydroxypropyl) n-f
Hexadecyl phosphonium synthesis Niu Mukuroraido) while fully purged with nitrogen 300ml flask tris (3-hydroxypropyl) phosphine 28.9 g (0.
115 mol), then 1-chlorohexadecane (9
5.0%) 34.9 g are added. Liquid temperature in the flask is about 1
The reaction was carried out by stirring at 50 ° C. for 10 hours. The completion of the reaction was confirmed by a color reaction between unreacted (3-hydroxypropyl) phosphine and carbon disulfide.
After completion of the reaction, the mixture was cooled to room temperature to precipitate crystals. The precipitated crystals were filtered, dissolved in a mixed solvent of (acetone + methanol), further cooled to 5 ° C., and crystals were reprecipitated. After repeating the same recrystallization operation several times, the obtained crystals were vacuum dried (5 Torr, 5 hours) at room temperature.
30.6 g (purity 96.8%, yield 54.9%) of white crystals of tris (3-hydroxypropyl) n-hexadecylphosphonium chloride were obtained. The purity was measured by the perchloric acid titration method. To confirm the compound,
^It was performed by ¹ H-NMR and FAB / MASS.

Examples 2 to 8 and Comparative Examples 1 to 4 Various tris (hydroxy) phosphines were used instead of tris (3-hydroxypropyl) phosphine in Example 1, and various alkyl halides were used instead of 1-chlorohexadecane. Using the same procedure as in Example 1, the tris (hydroxyalkyl) alkylphosphonium salts of Examples 2 to 8 were obtained. Table 1 shows the compounds of Examples 1 to 8 and Comparative Examples 1 to 4.

[0015]

[Table 1]

Test 1 (sterilization test against bacteria and filamentous fungi
(Test) A sterilizing power test was performed on the tris (hydroxyalkyl) alkylphosphonium salts obtained in Examples 1 to 8 and Comparative Examples 1 to 4. The types of strains used in the test, their test methods, and the results are shown below. (1) Strains to be tested 7 types of bacteria and 2 types of filamentous fungi, which are particularly harmful in terms of industry and hygiene, were selected, and 9 types of strains shown below were tested. Bacterial Bs: Bacillus subtilis IFO 3007 (Bacillus subtilis) Ec: Escherichia coli NIHJ (E. coli) Pa: Pseudomonus aeruginosa IAM 1054 (Pseudomonas ^{aeruginosa) Sa 1: Staphylococcus aureus ATCC 6538p} ( Staphylococcus aureus) Sa ^2: Staphylococcus aureus (MRSA ) (Resistant Staphylococcus aureus) Ss: Shigella sonnei (Shigella) St: Salmonella typhimurium (S. typhimurium) Filamentous fungus An: Aspergillus niger ATCC 6275 (black mold) Ps: Penicillium steckii IAM 7048 (blue mold)

(2) Test method and its results (2-1) Test method The samples of Examples 1-8 and Comparative Examples 1-4 were accurately weighed,
A 200 μg / ml aqueous solution was prepared. Using this preparation, 200, 100, 50, 25, 10, 5,
Each sample was diluted to a concentration of 2.5 and 1 μg / ml to prepare a sample solution.
Next, 1 platinum loop of the test strain stored in a test tube was inoculated into 10 ml of a normal broth medium (three g of meat extract, 10 g of peptone and 5 g of sodium chloride dissolved in 1,000 ml of water), and shake-cultured at 30 ° C. for 48 hours. After doing, 20
The liquid stored at ℃ was used as the culture liquid of the test bacteria. 9 ml of the obtained sample solution was placed in a sterilized 10 ml L-shaped test tube, and 1 ml of the culture solution of the above-mentioned test bacteria was ingested into the tube at 30 ° C for 30 minutes.
Let it work for a minute. After the action, add 1 ml of this solution to 100 parts of sterile water.
After being poured into a ml and uniformly diluted, 1 ml of this diluted solution was sampled to obtain a working solution. The strains in these working solutions were further cultured by the methods described below, and the bactericidal activity of each sample was determined.

(2-2) Bacterial culture: Bacterial: 10 μl of the working solution was placed in a sterile petri dish, and 15 ml of a bacterial medium (Nissui Pharmaceutical Tryptosoya agar medium) was poured and solidified and cultured at 30 ° C. for 2 days. Filamentous fungus: 15 ml of filamentous fungus (potato dextrose agar medium from Nissui Pharmaceutical Co., Ltd.) was poured into a sterile petri dish to solidify, 10 μl of the working solution was added, and the mixture was cultured at 30 ° C. for 4 days. (2-3) Bacterial Strength Judgment Method and Results For the evaluation of bacterial strength, colonies of each bacterium and filamentous fungus were observed with the naked eye, and those in which the medium was transparent and colonies could not be judged were killed. The lowest concentration of the sample solution in which the bacterium was killed was defined as the minimum bacterial concentration (MIC) of the compound,
The results are shown in Table 1. Also, 3 at a drug concentration of 1 ppm
The results of measuring the viable cell count after 0 minutes are shown in Table 2.

[0019]

[Table 2]

Test 2 (Test of algicidal activity against algae) The tris (hydroxyalkyl) alkylphosphonium salts obtained in Examples 1 to 8 and Comparative Examples 1 to 4 were tested for algicidal activity. The types of algae used in the test, their test methods, and the results are shown below. (1) Test algae Green alga Chlorella vulagaris Cyanobacteria Oscillatoria chlorina (2) Test method and results The above green algae and cyanobacteria are inoculated in a Detmer medium and cultured in a climate machine at 25 ° C to obtain a test solution. Next, a 1/3 dilution of Detmer medium [Ca (NO ₃ ) _{2
1.0g, KCl 0.25g, MgSO 4 ·} 7H 2 O 0.25
g, KH ₂ PO ₄ 0.25 g, FeCl ₃ 0.002 g / H ₂
O 3L], a chemical solution and a test solution are added so as to have a predetermined concentration, and the mixture is cultured in an artificial climate machine at 25 ° C. The culture is continuously stirred with a stirrer. The decolorized state of algae is observed after 48 hours, and the lowest concentration is defined as the minimum algicidal concentration. Table 3 shows the minimum algicidal concentration of each drug.

[0021]

[Table 3]

[0022]

The bactericidal / algicidal agent according to the present invention exhibits sufficient bactericidal / algicidal activity even at a low use concentration, and at least 0.1 p
The effect is shown at a concentration of pm. Moreover, it is a bactericidal algaecide that has less foaminess as compared with conventional phosphonium salt compounds and quaternary ammonium salt compounds, has little foaming, and has little odor even when it is vigorously stirred such as in a cooling tower. . The bactericidal and algicidal agent of the present invention has recently been attracting attention as a nosocomial infectious agent.
Since it has bactericidal power against A), it is possible to provide an effective means for this countermeasure. In addition, it can be widely applied to fields such as industrial water, process water for manufacturing pulp and paper, agriculture, and food, as well as medical use.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Seiji Shimura 9-15-1, Kameido, Koto-ku, Tokyo Nippon Kagaku Kogyo Co., Ltd. Research & Development Division (72) Inventor Kazunori Tanaka Shiooka Prefecture Iwata-gun Shiota Nitta Hamano No. 328 Kai Kasei Co., Ltd. (72) Inventor Koichi Iwabuchi Shiooka Prefecture Iwata-gun Fukuda-cho Shio Nitta Hamano No. 328 Kai Kasei Co., Ltd. (72) Inventor Yoshihiro Konagai Iwata-gun Shizuoka Fukuda Town Shio Shinhama No. 328 KAI Kasei Co., Ltd.

Claims (4)

[Claims] 1. The following general formula (1) (HOR ¹ ) ₃ R ² P ⁺ X ⁻ (wherein R ¹ is an alkylene group having 1 to 4 carbon atoms, and R ² is a straight chain having 12 to 18 carbon atoms. Or a branched alkyl group,
X ⁻ represents an anion of an inorganic acid or an organic acid), and is a bactericidal / algicidal agent containing a tris (hydroxyalkyl) alkylphosphonium salt represented by the formula. 2. The bactericidal / algicidal agent according to claim 1, wherein the anion in the general formula (1) is a halogen ion. 3. A tris (hydroxyalkyl) alkylphosphonium salt is tris (3-hydroxypropyl) n.
-Octadecylphosphonium chloride.
The disinfectant algaecide described. 4. The bactericidal / algicidal agent according to claim 1, which contains at least 0.1 ppm of a tris (hydroxyalkyl) alkylphosphonium salt.