JP5513776B2 - Biofilm remover composition - Google Patents

Description

The present invention relates to a biofilm remover composition, and more particularly to a biofilm remover composition for preventing harm caused by biofilms in various fields involving microorganisms.

A biofilm is also called a biofilm or slime, and generally refers to an aqueous system in which microorganisms adhere to and grow on the surface of substances to produce macromolecular substances such as polysaccharides and proteins from within microbial cells to form structures. . When a biofilm is formed, harm caused by microorganisms occurs, causing problems in various industrial fields. For example, when a biofilm is formed in the piping of a food plant, the biofilm peels off and leads to contamination by foreign substances in the product, and causes food poisoning due to microorganism-derived toxins. Furthermore, biofilm formation on the metal surface causes metal corrosion and promotes aging of the equipment.
Furthermore, compared to microorganisms that are dispersed and suspended in an aqueous system, microbial control agents such as bactericides and bacteriostatic agents are often unable to exert sufficient effects on microbial aggregates that have formed biofilms. . For example, in the medical field, many cases of nosocomial infections have been reported in recent years due to microorganisms remaining in narrow gaps and holes in medical devices to form biofilms. In the human oral cavity, it is well known that biofilms formed on teeth, so-called dental plaque (plaque), cause caries and periodontal disease, and these problems have been studied for a long time.

Until now, in order to prevent the harm of biofilm, the idea of not allowing bacteria to grow by giving bactericidal or bacteriostatic action to microorganisms, particularly bacteria, has been generally studied. Patent Document 1 describes an antibacterial preparation containing arginine hydrochloride, arginine ethyl ester, arginine glutamic acid or other arginine or a derivative thereof and a compound exhibiting antibacterial activity, but the effect is not yet satisfactory. .
Furthermore, as disclosed in Patent Document 2, a method for reducing harm by removing a biofilm using an enzyme has been studied, but it has not been completely removed.

JP-A-8-151324 JP-A-6-262165

  Accordingly, an object of the present invention is to provide a biofilm remover composition that can effectively remove biofilms composed of microorganisms and microorganism-producing substances in various regions.

  Therefore, the present inventor has conducted earnest research to obtain a biofilm remover composition that can effectively remove biofilm, and a specific guanidine compound or a salt thereof can effectively remove biofilm. As a result, the present invention has been completed.

  That is, this invention provides the biofilm remover composition containing the compound or its salt which has 1 or 2 guanidyl group and C8-C18 hydrocarbon group in a molecule | numerator.

  According to the present invention, it is possible to effectively remove biofilms composed of microorganisms and microorganism-producing substances in various regions.

The biofilm remover composition of the present invention contains a compound having 1 or 2 guanidyl groups and a hydrocarbon group having 8 to 18 carbon atoms or a salt thereof (hereinafter referred to as “compound A”) in the molecule. . Compound A preferably has one guanidyl group in the molecule from the viewpoint of the biofilm removal effect, and the number of carbon atoms of the hydrocarbon group in the molecule is preferably 8 to 14, and 10 to 12 Is more preferable.
As preferred compound A having one guanidyl group, the following general formula (1)

(In the formula, R represents an optionally substituted hydrocarbon group having 8 to 18 carbon atoms.)
Or a salt thereof.

  In the general formula (1), examples of the hydrocarbon group represented by R include an alkyl group and an alkenyl group, and an alkyl group is preferable. These may be linear or branched. The number is from 8 to 18, preferably from 8 to 14, and more preferably from 10 to 12 carbons. The alkyl group and alkenyl group may be single or mixed. Moreover, the mixed alkyl composition derived from natural origin, for example, palm oil or palm kernel oil, may be sufficient. In addition, the hydrocarbon group represented by R may include a substituent such as ether, carbonyl, amino, amide, carboxyl, phenyl, naphthyl, a linking group, and a functional group. Specific examples of the hydrocarbon group represented by R include 2-ethylhexyl group, n-octyl group, decyl group, dodecyl group, myristyl group, 3- (2-ethylhexyloxy) propyl group, phenethyl group, naphthalenemethyl group and the like. Preferably, it is a decyl group, a dodecyl group, a 3- (2-ethylhexyloxy) propyl group, or a phenethyl group.

  Compound (1) is generally obtained by reacting cyanamide with an alkylamine salt, but the production method is not particularly limited. These compounds may contain unreacted products and by-products as long as the biofilm removability is not inhibited.

  Examples of the compound A having two guanidyl groups and a hydrocarbon group having 8 to 18 carbon atoms in the molecule include compounds represented by the following general formula (2) or salts thereof.

(In formula, X shows the C8-C18 hydrocarbon group which may have a substituent.)

  In the general formula (2), examples of the hydrocarbon group represented by X include an alkylene group and an alkenylene group, and an alkylene group is preferable. These may be linear or branched. It is a thing of number 8-18, and a thing of carbon numbers 8-14 is preferable. The alkylene group and alkenylene group may be single or mixed. Moreover, the mixed alkyl composition derived from natural origin, for example, palm oil or palm kernel oil, may be sufficient. In addition, the hydrocarbon group represented by X may contain a substituent such as ether, carbonyl, amino, amide, and carboxyl, a linking group, and a functional group. Specifically, an octylene group, a decylene group, a dodecylene group, and the like are preferable, and an octylene group is more preferable.

  The compound (2) is generally obtained by reacting an alkylenediamine salt with cyanamide, but the production method is not particularly limited. These compounds may contain unreacted products and by-products as long as the biofilm removability is not inhibited.

  Examples of the salt in Compound A include salts of inorganic acids such as hydrochloride, sulfate and phosphate, and salts of organic acids such as acetate, lactate, carbonate, succinate, citrate and acidic amino acid salt. Preferable examples include hydrochloride, acetate, lactate, carbonate, succinate, and citrate.

  The concentration of Compound A in the biofilm remover composition of the present invention can be appropriately determined depending on the use and dosage form. However, in the case of acting on the biofilm, it is usually used in the form of an aqueous solution. Is preferably 0.001 to 10% by weight from the viewpoint of cost and handleability, more preferably 0.002 to 7% by weight, still more preferably 0.005 to 5% by weight, and still more preferably 0. .01 to 2% by weight.

  The biofilm remover composition of the present invention can be used in combination with a surfactant for the purpose of enhancing the solubility of Compound A, improving the biofilm removal performance, and further enhancing the cleaning effect. As the surfactant, one or more selected from anionic surfactants, nonionic surfactants, amphoteric surfactants and cationic surfactants can be used. Nonionic surfactants and amphoteric surfactants can be used. Agents are preferred.

  Examples of the anionic surfactant include lignin sulfonate, alkylbenzene sulfonate (preferably alkylbenzene sulfonate having an alkyl group having 10 to 16 carbon atoms), and alkyl sulfonate (preferably having 8 to 18 carbon atoms). Alkyl sulfonate having an alkyl group), polyoxyethylene (hereinafter referred to as POE) alkyl sulfonate (preferably having an alkyl group having 10 to 16 carbon atoms, and an average of 1 to 4 moles of oxyethylene groups were added. POE alkyl sulfonate), POE alkyl phenyl ether sulfonate (preferably POE alkyl phenyl ether sulfonate having an alkyl group having 6 to 12 carbon atoms and an average of 1 to 4 moles of oxyethylene group added), POE Alkyl phenyl ether phosphate ester salt (preferably carbon number POE alkylphenyl ether phosphate ester salt having an alkyl group of -12 and an average of 1 to 4 moles of oxyethylene groups added, POE arylphenyl ether sulfonate (preferably an average of 1 to 5 moles of oxyethylene groups added POE aryl phenyl ether sulfonate), alkyl sulfate salts (preferably alkyl sulfate salts having an alkyl group having 8 to 18 carbon atoms), POE alkyl ether sulfate salts (preferably alkyl groups having 8 to 18 carbon atoms) POE alkyl ether sulfate ester salt having an average of 1 to 4 moles of oxyethylene groups added), POE arylphenyl ether phosphate ester salt (preferably POE arylphenyl ether phosphorus having an average of 1 to 5 moles of oxyethylene groups added) Acid ester salt), naphth Len sulfonate, naphthalene sulfonate formalin condensate, POE tribenzyl phenyl ether sulfonate (preferably POE tribenzyl phenyl ether sulfonate with 1 to 5 moles of oxyethylene group added), alkyl phosphate (preferably Is an alkyl phosphate having an alkyl group having 8 to 18 carbon atoms), a POE alkyl phosphate (preferably a POE alkyl having an alkyl group having 8 to 18 carbon atoms and having an average of 1 to 5 moles of oxyethylene groups added thereto. Phosphate), POE tribenzylphenyl ether phosphate ester salt (preferably POE tribenzylphenyl ether phosphate ester salt having an average of 1 to 5 moles of oxyethylene group added), dialkylsulfosuccinate (preferably 8 to 8 carbon atoms) Dialkylsulfoco having 18 alkyl groups Succinate), fatty acid salts (soap), POE alkyl ether acetates (preferably POE alkyl ether acetates having an alkyl group having 8 to 18 carbon atoms and having an average of 1 to 15 moles of oxyethylene groups added), etc. Among them, it is more preferable to use alkyl sulfate ester salt, POE alkyl ether sulfate ester salt or POE alkyl ether acetate salt.

Nonionic surfactants include POE alkyl ethers (preferably POE alkyl ethers having an alkyl group having 8 to 18 carbon atoms and an average of 3 to 30 moles of oxyethylene groups), POE alkyl phenyl ethers (preferably POE alkylphenyl ether having an alkyl group having 8 to 18 carbon atoms and having an average of 3 to 30 moles of oxyethylene group added thereto, POE arylphenyl ether (preferably POE arylphenyl having an average of 3 to 30 moles of oxyethylene group added thereto) Ether), POE styrenated phenyl ether (preferably POE styrenated phenyl ether to which 3 to 30 moles of oxyethylene groups are added), POE tribenzyl phenyl ether (preferably POE tribenzyl phenyl to which 3 to 30 moles of oxyethylene groups are added) Monohydric alcohol derivative type nonionic surfactants such as (Nil ether); (poly) glycerin fatty acid ester (preferably (poly) glycerin fatty acid ester having a fatty acid residue having 8 to 18 carbon atoms), sucrose fatty acid ester (preferably Is a sucrose fatty acid ester having a fatty acid residue having 8 to 18 carbon atoms), a sorbitan fatty acid ester (preferably a sorbitan sugar fatty acid ester having a fatty acid residue having 8 to 18 carbon atoms), a POE sorbitan fatty acid ester (preferably oxyethylene). POE sorbitan fatty acid ester having an average of 3 to 30 moles added), alkyl polyglycoside (preferably alkyl polyglycoside having an alkyl group having 8 to 18 carbon atoms), fatty acid alkanolamide (preferably fatty acid alkanol having 8 to 18 carbon atoms) Multivalent such as amide) Alcohol derivatives type nonionic surfactants, and the like.
Moreover, 3-30 mol is preferable and, as for the average addition mole number of ethylene oxide in the said POE type nonionic surfactant, 3-20 mol is more preferable.
Among these, POE alkyl ether, (poly) glycerin fatty acid ester, alkyl polyglycoside, sorbitan fatty acid ester or POE sorbitan fatty acid ester are preferably used, POE alkyl ether and alkyl polyglycoside are more preferable, and POE alkyl ether is further used. preferable.
The POE alkyl ether is more preferably one in which ethylene oxide is added to an alcohol having an alkyl group having 10 to 18 carbon atoms (preferably having 10 to 14 carbon atoms). Such alcohols are preferably primary or secondary, and the alkyl group may be linear or branched. The degree of addition of alkylene oxide is preferably 3 to 30 mol, more preferably 3 to 20 mol, and further preferably 5 to 20 mol as the average number of added moles.

  Examples of amphoteric surfactants include alkylcarboxybetaines, alkylsulfobetaines, alkylhydroxysulfobetaines, fatty acid amide betaines, and alkyldimethylamine oxides. Among them, alkyldimethylamine oxide is preferably used. 8-18 are preferable and, as for carbon number of these alkyl groups, 10-14 are more preferable.

  Examples of the cationic surfactant include alkyltrimethylammonium salts and dialkyldimethylammonium salts. Among them, alkyltrimethylammonium salts are preferable. As for carbon number of these alkyl groups, 8-18 are preferable. Moreover, as said salt, a halide is preferable and a chloride and a bromide are more preferable.

  These surfactants can be used in combination with Compound A at any ratio depending on the purpose, but the content ratio of Compound A to the surfactant is 10/1 to 1/50, more preferably 5/1 to 1. / 20, more preferably 1/5 to 1/15.

  As a dosage form of the biofilm remover composition of the present invention, a solution dissolved in a solvent such as water, ethanol, isopropanol, or a solid, gel, emulsified / dispersed, powder, aerosol, depending on the application and purpose These can be selected appropriately from these, and in addition to the product form that matches the working concentration, leave it in a high-concentration product form and dilute it in the scene of use, or incorporate a surfactant in the scene of use It can also be used.

  The biofilm remover composition of the present invention is a thickener, a viscosity modifier, a pH adjuster, a solvent, a fragrance, a colorant, an antioxidant, an antiseptic, a fluorescent agent, as long as the object of the present invention is not impaired. An excipient, a soil release agent, a bleaching agent, a bleaching activator, a powdering agent, a granulating agent, a coating agent and the like can be blended.

  The biofilm remover composition of the present invention can be used in a wide range of fields where there is a risk of biofilm harm. For example, the present invention can be applied to detergents for food production or beverage production plants with a high risk of bacterial contamination, kitchens, kitchens, bathrooms, toilets, drains for kitchens, kitchens, etc., drain pipes. It can also be applied to cooling water systems such as industrial cooling towers, desalination equipment, pulp and paper manufacturing systems, and circulating water systems such as bathtubs, pools, and artificial ponds. The present invention can also be applied to medical devices in which biofilms are easily formed, for example, cleaning agents such as endoscopes, catheters, and artificial dialysis machines. Furthermore, it can also be used for denture care agents, contact lens cleaners, and the like.

The biofilm removal method of the present invention can be carried out by bringing the biofilm remover composition into contact with the surface on which the biofilm is formed. Examples of the contact method include dipping, coating, or spraying. Further, physical force such as sponge, towel, brush, water flow, etc. may be applied. In addition, the time for which the biofilm remover composition is allowed to act varies depending on the amount of attached biofilm, the concentration at which the biofilm remover composition acts, the working temperature, and the presence or absence of physical force, but usually several seconds. In consideration of workability, it is preferably 10 seconds or longer, more preferably 10 seconds to 1 hour, still more preferably 10 seconds to 30 minutes, and even more preferably 20 seconds to 20 hours. Minutes. After the action, it is desirable to quickly rinse away the removed biofilm with running water or the like.
Moreover, although the temperature which makes a biofilm remover composition act can be used at 0-98 degreeC, 0-60 degreeC is preferable from viewpoints of work environment, workability, etc., and 10-40 degreeC is more preferable.
The biofilm remover composition of the present invention may be used in a water dilution system. When a certain amount of the water dilution of the composition is accumulated and the object is immersed, or when the object is widespread, The mist may be sprayed using a spray device, or the foamed material may be sprayed using a foaming machine. Further, the composition may be applied by pouring a water-diluted solution or brushing.
Alternatively, the object may be wiped off by impregnating the towel with a water-diluted solution. The aqueous dilution of the composition preferably has a weight concentration of component (A) of 0.005 to 5% by weight, more preferably 0.01 to 3% by weight when used. It is preferable to be 02 to 2% by weight.

Production Example 1: Production method of compound (1)
Synthesis of 1-octylguanidine lactate 90.1 g (1.0 mol) of lactic acid and 40.0 g of isopropanol were charged into a 1 L four-necked flask equipped with a reflux condenser, a dropping funnel, a thermometer and a stirring blade. Into this, 155.1 g (1.2 mol) of octylamine was added dropwise over 20 minutes with stirring in a nitrogen atmosphere. The reaction solution was heated to 90 to 93 ° C., and 84.1 g (1.0 mol) of a 50% cyanamide aqueous solution was added dropwise over 4 hours. Thereafter, aging was performed at 92 ° C. for 4 hours. After cooling, the solvent was removed, acetone was added, the mixture was stirred for 2 hours, and allowed to stand until crystals were precipitated. The acetone was removed by filtration, and the acetone was completely distilled off under reduced pressure. To the obtained crystals, an isopropanol / hexane mixed solution was added and dissolved by heating at 60 ° C., and then crystals were precipitated at room temperature and further under ice cooling. The solvent was removed by filtration, and the solvent was completely distilled off at 60 ° C./reduced pressure to obtain 118 g of 1-octylguanidine / lactate white powder.
Similarly, those in which R is C10 (linear) [compound (1-2)] and C12 (linear) [compound (1-3)] were synthesized.

Production Example 2: Production Method of Compound (1-4) Synthesis of Decylguanidine Succinate Using 11.8 g (0.1 mol) of succinic acid, 37.75 g (0.24 mol) of decylamine, and 16.8 g (0.2 mol) of 50% cyanamide aqueous solution This was synthesized in the same manner as in Production Example 1.

Production Example 3: Production Method of Compound (1-5) Synthesis of Dodecylguanidine Carbonate Using 6.2 g (0.1 mol) of carbonic acid, 44.47 g (0.24 mol) of dodecylamine, and 16.8 g (0.2 mol) of 50% cyanamide aqueous solution, Synthesis was performed in the same manner as in Production Example 1.

  Similarly, the compounds (1-6), (1-7) and (2-1) were synthesized as shown below.

Production Example 4: Production Method of Compound (1-6) Synthesis of 3- (2-ethylhexyloxy) propylguanidine succinate 17.7 g (0.15 mol) of succinic acid, 67.44 g (0.36 mol) of 2-ethylhexyloxypropylamine, Synthesis was performed in the same manner as in Production Example 1 using 25.22 g (0.3 mol) of a 50% cyanamide aqueous solution.

Production Example 5: Production Method of Compound (1-7) Synthesis of Phenethylguanidine Succinate Using 17.7 g (0.15 mol) of succinic acid, 43.62 g (0.36 mol) of phenethylamine, and 25.22 g (0.3 mol) of 50% cyanamide aqueous solution This was synthesized in the same manner as in Production Example 1.

Production Example 6 Production Method of Compound (2-1) Synthesis of 1,8-octylenediguanidine lactate 18.02 g (0.2 mol) of lactic acid, 17.3 g (0.12 mol) of 1,8-octylenediamine, 50% aqueous cyanamide solution 16.8 g (0.2 mol) was synthesized in the same manner as in Production Example 1.

Production Example 7: Production Method of Comparative Compound (1) Synthesis of Hexylguanidine Lactate Into a 1 L four-necked flask equipped with a reflux condenser, a dropping funnel, a thermometer and a stirring blade, 22.52 g (0.25 mol) of lactic acid, isopropanol 10.0g was charged. Into this, 30.35 g (0.3 mol) of hexylamine was added dropwise over 20 minutes with stirring in a nitrogen atmosphere. The reaction solution was heated to 90 to 93 ° C., and 21.02 g (0.25 mol) of a 50% cyanamide aqueous solution was added dropwise over 4 hours. Thereafter, aging was performed at 92 ° C. for 4 hours. After cooling, the solvent was removed, acetone was added, the mixture was stirred for 2 hours, and allowed to stand until crystals were precipitated. The acetone was removed by filtration, and the acetone was completely distilled off under reduced pressure. Acetone was added to the obtained crystals and dissolved by heating at 50 ° C., and then crystals were precipitated at room temperature and further under ice cooling. The solvent was removed by filtration, and the solvent was completely distilled off at 50 ° C./vacuum to obtain 28 g of hexylguanidine lactate white powder.

<Biofilm removal ability test>
Pseudomonas aeruginosa NBRC13275, Serratia marcescens NBRC12648, Staphylococcus epidermidis NBRC12773, soybean-Casein Digest Agar (SCD agar medium: Nippon Pharmaceutical Co., Ltd.) ], A very small amount of bacterial mass from a colony formed by pre-culturing at 37 ° C. for 24 hours, and using a sterilized bamboo skewer, 1.5 mL each of Mueller Hinton medium was added to each well. Inoculated into plates. After culturing at 37 ° C. for 24 hours, the culture solution was discarded, and each well was rinsed 5 times with 2 mL of purified water to form and attach a biofilm to the microplate wall. Immediately, 2 mL of the prepared biofilm remover composition shown in Table 1 was added and allowed to act at room temperature (20 ° C.) for 10 minutes, and then the biofilm remover composition in each well was discarded. Each well was rinsed twice with 2 mL of purified water, and then 2 mL of 0.1% crystal violet was added to stain the biofilm remaining on the microplate wall. After rinsing the excess staining solution with water, 2 mL of 80% ethanol was added, and the crystal violet stained biofilm was uniformly dissolved, and then the absorbance was measured at 570 nm to obtain a measured value. Similarly, after the well not treated with the biofilm remover composition was treated with 0.1% crystal violet, the absorbance was measured to obtain an initial value. In addition, 1.5 mL each of Mueller Hinton medium was injected into 24 wells, but the same was not inoculated with the bacterial mass, and the absorbance was measured to obtain a blank value. Each test was performed five times and the average value was used. The removal rate was calculated by the following formula. Concentrations in the table are shown as effective concentration (% by weight) with respect to the total amount, and pH was adjusted with potassium hydroxide or hydrochloric acid as necessary.

Removal rate (%) = 100 × [{(initial value−blank value) − (measured value−blank value)} / (initial value−blank value)]

The obtained results are shown in Table 1.

  From the above results, it can be seen that the biofilm can be effectively removed by using the biofilm remover composition of the present invention.

Claims (3)

The following general formula (1)

(Wherein R represents an optionally substituted hydrocarbon group having 8 to 14 carbon atoms),
Or the following general formula (2)

(In the formula, X represents an optionally substituted hydrocarbon group having 8 to 14 carbon atoms.)
A compound having 1 or 2 guanidyl groups and a hydrocarbon group having 8 to 14 carbon atoms in the molecule, or a salt thereof, 0.005 to 5% by weight, and polyoxyethylene alkyl ether Or a biofilm remover composition containing a surfactant that is alkyldimethylamine oxide and having a mass ratio of compound A to surfactant of 1/5 to 1/15.   The biofilm removal method of making the biofilm removal agent composition of Claim 1 contact a biofilm. The method for removing a biofilm according to claim 2 , wherein the time for allowing the biofilm remover composition to act on the biofilm is 20 seconds to 20 minutes.