JPH06321716A - Germicidal algicide - Google Patents

Abstract

PURPOSE:To obtain a germicidal algicide, capable of manifesting sufficient germicidal and algicidal activities even at a low concentration used with hardly any foaming properties and malodor. CONSTITUTION:This germicidal algicide contains a tetraalkylphosphonim salt expressed by the formula R<1>3R<2>P<+>X<-> (R<1> is 1-3C alkyl group; R<2> is 12-18C alkyl group; X<-> is halide ion of F<->, Cl<-> or Br<-> or anion of inorganic or organic acid) as an active ingredient.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fungicidal algicidal agent containing a tetraalkylphosphonium 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 that a phosphonium salt compound is used 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 earnest studies, the present inventors have found that certain phosphonium salt compounds are extremely powerful bactericidal and algaecidal in comparison with closely related phosphonium salt compounds and quaternary ammonium salts. It has a strong power and a wide spectrum of sterilization and algae killing, and even when it is vigorously stirred like a cooling tower,
The present invention has been completed by finding that the foaming is small and the odor is small. That is, the bactericidal / algicidal agent to be provided by the present invention is represented by the following general formula (1): R ¹ ₃ R ² P ⁺ X ⁻ (wherein R ¹ is an alkyl group having 1 to 3 carbon atoms, and R ² is carbon. An alkyl group having 12 to 18 atoms, X ⁻ represents a halogen ion of F ⁻ , Cl ⁻ or Br ⁻ , an anion of an inorganic acid or an organic acid), and a tetraalkylphosphonium salt represented by It is configured as a feature.

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 a methyl group, an ethyl group, a propyl group or the like having 1 to 10 carbon atoms.
3 is an alkyl group. R ² is an alkyl group having 12 to 18 carbon atoms such as dodecyl group, tetradecyl group, hexadecyl group, octadecyl group.

X ^- is, for example, a halogen ion of fluorine, chlorine or bromine, a carboxyl ion such as formic acid, acetic acid, oxalic acid, a sulfate ion, a phosphate ion, a methyl or dimethyl phosphate ion, an ethyl or a diethyl phosphate ion,
Examples thereof include inorganic or organic anions such as antimony fluoride ion, phosphorus fluoride ion, arsenic fluoride ion, boron fluoride ion, and perchlorate ion. Among them, halogen ion such as fluorine, chlorine or bromine is preferable.

Examples of such tetraalkylphosphonium salts include trimethyl n-dodecylphosphonium chloride, trimethyl n-octadecylphosphonium chloride, triethyl n-tetradecylphosphonium chloride, triethyl n-hexadecylphosphonium chloride, triethyl n-octadecylphosphonium chloride, Tripropyl n-tetradecylphosphonium chloride, tripropyl n-hexadecylphosphonium chloride, tripropyl n-octadecylphosphonium chloride, triethyl n-hexadecylphosphonium bromide, triethyl n-hexadecylphosphonium tetrafluoroborate, triethyl n-octadecylphosphonium perk Examples include Loreto.

In the tetraalkylphosphonium salt according to the above formula (1), for example, a combination of R ¹ having 2 or less carbon atoms and R ² having an alkyl group having 16 to 18 carbon atoms has excellent bactericidal / algicidal activity. In particular, triethyl n-hexadecylphosphonium chloride has a high bactericidal / algicidal effect.

Method for producing bactericidal / algicidal agent The tetraalkylphosphonium salt which is the bactericidal / algicidal agent of the present invention may be produced by any method, but one example is shown below as an industrial production method. Formula (2) R ¹ ₃ P (wherein R ¹ represents the same meaning.) And trialkylphosphine represented by the general formula (3) R ² X (wherein, R ² is the same meaning as And X represents a halogen atom of F, Cl or Br.), And the bactericidal and algicidal agent of the present invention can be obtained. The reaction of the compounds of the above general formulas (2) and (3) is carried out in the presence of a solvent at a solvent reflux temperature of 15 to 48.
It is better to react for a time. Further, the alkyl halide is preferably used in an equimolar to 5-fold molar amount with respect to the trialkylphosphine.

Suitable organic solvents include n-hexane, n-heptane, n-octane, benzene, toluene, xylene and the like. The bactericidal algaecide according to the present invention,
If necessary, other fungicidal algaecides may be used in combination. 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-isothiazolin-3-one, 2-bromo-2-nitropropane-1,3-diol, 1,5-pentanediol, phenol, chlorhexidine, povidone iodine, alkyl chloride polyaminoethyleneglycine, chlorine One or more kinds of organic fungicides such as agents and inorganic antibacterial agents such as silver-substituted zeolite and silver-substituted apatite may be used in combination.

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, oil and fat, emulsion,
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 broad activity spectrum effective against various bacteria, fungi, algae, viruses and the like, and has an excellent bactericidal activity especially against resistant Staphylococcus aureus (MRSA). It has a bactericidal and growth-suppressing effect on bacteria and an algaecidal effect on algae. Although the minimum bactericidal concentration (MIC) is not uniform depending on the type of tetraalkylphosphonium salt, the type of preparation or the type of various bacteria, and the environment, the concentration of tetraalkylphosphonium salt is exhibited at 0.1 ppm or more, and it is generally close. The bactericidal activity is extremely higher than that of known bactericides based on phosphonium salts and quaternary ammonium salts. Moreover, the tetraalkylphosphonium salt according to the present invention is more stable against heat than the quaternary ammonium salt compound and other organic compounds, and has a high decomposition temperature of about 350 ° C. It is also stable.

[0013]

EXAMPLES The present invention will be further described below with reference to examples. Example 1 (triethyl n-hexadecylphosphonium
Synthesis of chloride) 300 ml The flask was fully purged with nitrogen while triethylphosphine 37.19g and (0.315 mol) are dissolved with toluene 134.99G. Then 1-chlorohexadecane (95.0%) 95.08 g (0.364)
mol) is added. The reaction was carried out by stirring for 30 hours while refluxing the liquid temperature in the flask near the boiling temperature of toluene (118 to 120 ° C). The completion of the reaction was confirmed by a color reaction between unreacted triethylphosphine and carbon disulfide. After completion of the reaction, the mixture was cooled to room temperature to precipitate crystals. The precipitated crystals were dissolved in diethyl ether, further cooled to 5 ° C to reprecipitate the crystals, and separated by filtration. After repeating the same recrystallization operation several times, the obtained crystal was vacuum dried at room temperature (5 Torr, 5 hours). As a result, 24.1 g of white crystal triethyl n-hexadecylphosphonium chloride (purity: 98. 0%, yield 19.
8%). The purity was measured by the perchloric acid titration method. The compound was identified by ¹ H-NMR and FAB.
/ Mass.

Examples 2 to 8 and Comparative Examples 1 to 4 The same operation as in Example 1 was carried out using various trialkylphosphines instead of triethylphosphine and various alkyl halides instead of 1-chlorohexadecane. The tetraalkylphosphonium salt shown in Table 1 was obtained. Table 1 shows the compounds obtained in Examples 1 to 8 and Comparative Examples 1 to 4.

[0015]

[Table 1]

Test 1 (bactericidal test against bacteria and filamentous fungi) The tetraalkylphosphonium salts obtained in Examples 1 to 8 and Comparative Examples 1 to 4 were tested for bactericidal activity. 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 ) (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 μm / 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 μm / 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. Table 2 shows the results of measuring the viable cell count after 30 minutes at a drug concentration of 1 ppm.

[0019]

[Table 2]

Test 2 (Algicidal test against algae) The tetraalkylphosphonium salts obtained in Examples 1 to 8 and Comparative Examples 1 to 4 were subjected to an algicidal test. 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]

Test 3 (Bubbling property and odor test) The tetraalkylphosphonium salts and comparative drugs obtained in Examples 1 to 8 were subjected to a foaming test and the presence or absence of odor was confirmed. (1) Test method 50 ml of 0.2% aqueous solution of each drug was prepared and 100 ml
Place in a graduated cylinder with a common stopper and shake for 2 minutes, then
The foam height is measured after standing for 0 to 60 minutes. Also, the presence or absence of odor was confirmed. (2) Test results Table 4 shows the test results.

[0023]

[Table 4]

[0024]

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.

[Procedure amendment]

[Submission date] August 1, 1994

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] Full text

[Correction method] Change

[Correction content]

[Document name] Statement

[Title of Invention] Bactericidal and algicidal agent

[Claims]

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fungicidal algicidal agent containing a tetraalkylphosphonium salt as an active ingredient.

[0002]

2. Description of the Related Art At present, a great variety of bactericides are used not only for medical purposes but also in various fields such as industry, agriculture and food. Most of the fungicides used so far have been highly toxic fungicides, but recently,
From the problems of environmental pollution and economical problems, it is desired to develop a bactericide having a sufficient antibacterial activity even at a low concentration. Further, it has been conventionally known that a phosphonium salt compound is used 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 earnest studies, the present inventors have found that certain phosphonium salt compounds are extremely powerful bactericidal and algaecidal in comparison with closely related phosphonium salt compounds and quaternary ammonium salts. It has a strong power and a wide spectrum of sterilization and algae killing, and even when it is vigorously stirred like a cooling tower,
The present invention has been completed by finding that the foaming is small and the odor is small. That is, the bactericidal / algicidal agent to be provided by the present invention is represented by the following general formula (1): R ¹ ₃ R ² P ⁺ X ⁻ (wherein R ¹ is an alkyl group having 1 to 3 carbon atoms, and R ² is carbon. An alkyl group having 12 to 18 atoms, X ⁻ represents a halogen ion of F ⁻ , Cl ⁻ or Br ⁻ , an anion of an inorganic acid or an organic acid), and a tetraalkylphosphonium salt represented by It is configured as a feature.

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 a methyl group, an ethyl group, a propyl group or the like having 1 to 10 carbon atoms.
3 is an alkyl group. R ² is an alkyl group having 12 to 18 carbon atoms such as dodecyl group, tetradecyl group, hexadecyl group, octadecyl group.

X ^- is, for example, a halogen ion of fluorine, chlorine or bromine; formic acid, acetic acid, oxalic acid, benzoic acid, phthalate.
Aliphatic carboxylic acid ion such as acid or aromatic carboxylic acid
Ion; Sulfate ion; Phosphate ion; Methyl or dimethyl phosphate ester ion, Ethyl or diethyl phosphate ester ion, Butyl or dibutyl phosphate ester
Alkyl phosphate ester ions such as ru ion; antimony fluoride ion, phosphorus fluoride ion, arsenic fluoride ion, boron fluoride ion, perchlorate ion; methanesulfur
Alkylsulfonate ions such as phosphonate ion; p-ben
Substituted or unsubstituted benzenesulfonate ion such as zensulfonate ion ; 1- hydroxyorgano-1,1-
Diphosphonate ion, 1-hydroxyethane-1,1-
Examples thereof include inorganic or organic anions such as diphosphonate ion, and among them, halogen ion of fluorine, chlorine or bromine, alkylsulfonate ion, and substituted or unsubstituted benzenesulfonate ion are preferable. Especially Alkyls
Rufonate ion, substituted or unsubstituted benzene sulfone
Acid ions and alkyl phosphate ester ions
It is preferable because it is less corrosive.

Examples of such tetraalkylphosphonium salts include trimethyl n-dodecylphosphonium chloride, trimethyl n-octadecylphosphonium chloride, triethyl n-tetradecylphosphonium chloride, triethyl n-hexadecylphosphonium chloride, triethyl n-octadecylphosphonium chloride, Tri-n-propyl n-tetradecylphosphonium chloride, tri-n-propyl n-hexadecylphosphonium chloride, tri-n-propyl n-octadecylphosphonium chloride, triethyl n-hexadecylphosphonium bromide, triethyl n-hexadecylphosphonium tetrafluoroborate, Triethyl n
-Octadecylphosphonium perchlorate, trieth
Ru-n-tetradecylphosphonium diethyl phosphate
, Triethyl n-hexadecylphosphonium methanesulfonate, triethyl n-hexadecylphosphonium p-toluenesulfonate, triethyl n -hexadecyl
Luphosphonium acetate, tri-n-propyl n-hexadecylphosphonium methanesulfonate, tri-n-propyl n-hexadecylphosphonium p-toluenesulfonate, and the like.

In the tetraalkylphosphonium salt according to the above formula (1), for example, a combination of R ¹ having 2 or less carbon atoms and R ² having an alkyl group having 16 to 18 carbon atoms has excellent bactericidal / algicidal activity. In particular, triethyl n-hexadecylphosphonium chloride and triethyl n-hexadecylphosphonium p-toluenesulfonate have high bactericidal / algicidal effects.

Method for producing bactericidal / algicidal agent The tetraalkylphosphonium salt which is the bactericidal / algicidal agent of the present invention may be produced by any method, but one example is shown below as an industrial production method. Formula (2) R ¹ ₃ P (wherein R ¹ represents the same meaning.) And trialkylphosphine represented by the general formula (3) R ² X (wherein, R ² is the same meaning as And X represents a halogen atom of F, Cl or Br.), And the bactericidal and algicidal agent of the present invention can be obtained. When the anion is an inorganic acid or an organic acid, it can be obtained by reacting the tetraalkylphosphonium halide halide obtained in the above reaction with, for example, an alkyl sulfonate at room temperature. The reaction of the compounds of the above general formulas (2) and (3) is 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 with respect to the trialkylphosphine.

Suitable organic solvents include n-hexane,
Examples thereof include n-heptane, n-octane, benzene, toluene, xylene, n-propanol and n-butanol. 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-isothiazolin-3-one, 2-bromo-2-nitropropane-1,3-diol, 1,5-pentanediol, phenol, chlorhexidine, povidone iodine, alkyl chloride polyaminoethyleneglycine, organic chlorine, etc. One type or two or more types of bactericidal agents and inorganic antibacterial agents such as silver-substituted zeolite and silver-substituted apatite may be used in combination.

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, oil and fat, emulsion,
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 broad activity spectrum effective against various bacteria, fungi, algae, viruses and the like, and has an excellent bactericidal activity especially against resistant Staphylococcus aureus (MRSA). For example, it has a bactericidal and growth inhibitory effect against bacteria, and a fungicidal effect and algaecidal effect against fungi and algae. Its minimum bactericidal concentration (M B C)
Varies depending on the type of tetraalkylphosphonium salt, formulation, type of various bacteria, and environment,
The tetraalkylphosphonium salt is exhibited at a concentration of 0.1 ppm or more, and generally has extremely high bactericidal activity as compared with well-known bactericides based on phosphonium salts and quaternary ammonium salts. Moreover, the tetraalkylphosphonium salt according to the present invention is more stable to heat than the quaternary ammonium salt compound and other organic compounds, and has a decomposition temperature of 3
It is as high as around 50 ° C and is chemically stable.

[0013]

EXAMPLES The present invention will be further described below with reference to examples. Example 1 (triethyl n-hexadecylphosphonium
Synthesis of chloride) 300 ml The flask was fully purged with nitrogen while triethylphosphine 37.19g and (0.315 mol) are dissolved with toluene 134.99G. Then 1-chlorohexadecane (95.0%) 95.08 g (0.364)
mol) is added. The reaction was carried out by stirring for 30 hours while refluxing the liquid temperature in the flask near the boiling temperature of toluene (118 to 120 ° C). The completion of the reaction was confirmed by a color reaction between unreacted triethylphosphine and carbon disulfide. After completion of the reaction, the mixture was cooled to room temperature to precipitate crystals. The precipitated crystals were dissolved in diethyl ether, further cooled to 5 ° C to reprecipitate the crystals, and separated by filtration. After repeating the same recrystallization operation several times, the obtained crystal was vacuum dried at room temperature (5 Torr, 5 hours). As a result, 24.1 g of white crystal triethyl n-hexadecylphosphonium chloride (purity: 98. 0%, yield 19.
8%). The purity was measured by the perchloric acid titration method. The compound was identified by ¹ H-NMR and FAB.
/ Mass.

Examples 2 to 8 and Comparative Examples 1 to 4 The same operation as in Example 1 was carried out using various trialkylphosphines in place of triethylphosphine and various alkyl halides in place of 1-chlorohexadecane. The tetraalkylphosphonium salt shown in Table 1 was obtained.

Example 9 (Synthesis of triethyl n-hexadecylphosphonium p-toluene sulfonate) 9.58 g (0.59%) of triethyl n-hexadecylphosphonium chloride (98.91%) was added to a 200 ml flask.
(025 mol) is charged and dissolved with 100 ml of demineralized water. Next, sodium p-toluenesulfonate (98.
(0%) 4.95 g (0.025 mol) was added, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the lower layer of the reaction solution separated into two layers was separated, and the remaining solution in the reaction vessel was washed with demineralized water. Then, after sufficiently washing with n-hexane, n-hexane was recovered under reduced pressure at 80 ° C. and 5 Torr. As a result, viscous transparent liquid triethyl n-hexadecylphosphonium p-toluenesulfonate 12.78 g (purity 9
7.18%, yield 92.48%) was 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.

[0016] Embodiment examples 10-12 triethyl n- hexadecyl phosphonium chloride Various tetraalkyl phosphonium chloride instead of ride, also using various sulfonate in place of sodium p- toluenesulfonic acid, similar to that in Example 9 operating The tetraalkylphosphonium salt shown in Table 1 was obtained. Table 1 shows the compounds obtained in Examples 1 to 12 and Comparative Examples 1 to 4.

[0017]

[Table 1]

Test 1 (bactericidal test against bacteria and filamentous fungi) The tetraalkylphosphonium salts obtained in Examples 1 to 12 and Comparative Examples 1 to 4 were tested for bactericidal activity. 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 ) ( Methicillin 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

(2) Test method and its result (2-1) Test method The samples of Examples 1 to 8 and Comparative Examples 1 to 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) Bacteria culture Bacteria: 10 μl of the working solution was placed in a sterilized petri dish, and 15 ml of a culture medium for bacteria (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) Evaluation of the disinfecting power determination method and results disinfecting force performs observation of each bacteria and colonies filamentous fungus with the naked eye, was killed that media can not be determined transparent colony. The lowest concentration of the sample solution bacteria have been killed and the minimum disinfecting concentration of the compound (M B C),
The results are shown in Table 1. Table 2 shows the results of measuring the viable cell count after 30 minutes at a drug concentration of 1 ppm.

[0021]

[Table 2]

Test 2 (Algicidal test against algae) The tetraalkylphosphonium salts obtained in Examples 1 to 12 and Comparative Examples 1 to 4 were subjected to an algicidal test. 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.

[0023]

[Table 3]

Test 3 (Bubbleness and Smell Test) With respect to the tetraalkylphosphonium salts obtained in Examples 1 to 12 and the comparative drug, a foamability test and the presence or absence of smell were confirmed. (1) Test method 50 ml of 0.2% aqueous solution of each drug was prepared and 100 ml
Place in a graduated cylinder with a common stopper and shake for 2 minutes, then
The foam height is measured after standing for 0 to 60 minutes. Also, the presence or absence of odor was confirmed. (2) Test results Table 4 shows the test results.

[0025]

[Table 4]

[0026]

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.

Front page continuation (72) Inventor Seiji Shimura 9-15-1, Kameido, Koto-ku, Tokyo Nihon Kagaku Kogyo Co., Ltd. R & D Headquarters (72) Inventor Kazunori Tanaka Shionoshinhamano Shiinata, Fukuda-cho, Iwata-gun Address 328, KAI Kasei Co., Ltd. (72) Inventor, Koichi Iwabuchi, Shioda, Fukuda-cho, Iwata-gun, Shizuoka Prefecture Hamada Shinano, 328 Kai Kasei Co., Ltd. (72) Inventor, Yoshihiro Konagai, Fukuda-cho, Iwata-gun, Shizuoka Nitta Hamano No.328 KAI Kasei Co., Ltd.

Claims (4)

[Claims] 1. R ¹ ₃ R ² P ⁺ X ⁻ (wherein R ¹ is an alkyl group having 1 to 3 carbon atoms, R ² is an alkyl group having 12 to 18 carbon atoms, and X is the following general formula (1): ^- is F ^-, Cl ^- or Br ^- halogen ion, microbicidal and algicidal as an active ingredient tetraalkylphosphonium salt represented by anion shows a) inorganic or organic acids. 2. The anion in the general formula (1) is F ⁻ ,
The bactericidal / algicidal agent according to claim 1, which is a halogen ion of Cl ⁻ or Br ⁻ . 3. The bactericidal / algicidal agent according to claim 1, wherein the tetraalkylphosphonium salt is triethyl n-hexadecylphosphonium chloride. 4. The bactericidal / algicidal agent according to any one of claims 1 to 3, which contains at least 0.1 ppm of a tetraalkylphosphonium salt.