JP2009051756A - Bactericidal composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a bactericidal composition exhibiting excellent bactericidal effects even on spores of bacteria, and capable of removing protein stain and scale stain. <P>SOLUTION: The bactericidal composition comprises (A) an organic carboxylic acid, (B) an inorganic acid and (C) a quaternary ammonium salt. Preferably, the ratio (A)/(B) of the organic carboxylic acid (A) to the inorganic acid (B) by mass is 0.1-200, and the ratio (C)/(B) of the quaternary ammonium salt (C) to the inorganic acid (B) by mass is 0.1-50. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a bactericide composition for sterilizing and washing food processing machines, kitchen equipment, medical equipment and peripheral equipment, and a sterilization method using the same.

  Currently, there are various known chemicals used for sterilization and disinfection purposes. Especially, sodium hypochlorite, oxygen-based disinfectant hydrogen peroxide, and hydrogen peroxide in water. Percarbonates, perborates and the like that generate water are mainly used. However, these fungicides have various problems. For example, sodium hypochlorite has a problem in handling that it cannot remove scale dirt such as calcium carbonate, is corrosive to metals, and generates chlorine gas when mixed with an acidic substance. Hydrogen peroxide needs to act for a long time at a high concentration in order to obtain a high degree of bactericidal effect. Quaternary ammonium salts have low bactericidal activity at low pH and are ineffective against bacterial spores and molds. In addition, since it is inactivated by protein, prior cleaning is required. For example, in order to sterilize and wash the dialysate flow path of an artificial hemodialysis apparatus, a drug that can kill microorganisms including bacterial spores and remove scale dirt and protein dirt is required. At present, sterilization cleaning of the dialysate flow path is performed by a complicated method in which two or more kinds of drugs such as sodium hypochlorite and acetic acid are combined.

  Patent Document 1 discloses a method for sterilizing bacterial spores characterized by heating a solution of a dimer-type bis quaternary ammonium salt to which an edible acid is added and bringing the solution into contact with an object to be sterilized. .

Patent Document 2 discloses an aqueous composition containing a hydrophobic peracid and a cationic surfactant, which is said to be effective against Bacillus spores.
JP-A-10-295785 JP 2006-22048 A

  However, since Patent Document 1 aims at sterilization in a short time, a high concentration of edible acid is required (10% by weight in the examples), and the solution is used at a high temperature, for example, about 70 to 80 ° C. There is a need. In addition, the combination with benzalkonium chloride cannot achieve the purpose, and the quaternary ammonium salt that can be used is limited to the dimer type. The peracid used in Patent Document 2 has poor storage stability when a cationic surfactant coexists, and it is necessary to mix two concentrated stock solutions at the time of use.

An object of the present invention is to provide a bactericidal composition that exhibits an excellent bactericidal effect on bacterial spores, for example, can kill bacterial spores at a concentration of 10 ⁶ cfu / mL, and at the same time remove protein stains and scale stains. It is to provide. Moreover, it is providing the sterilization method using such a disinfectant composition.

  The present invention includes (A) an organic carboxylic acid (hereinafter referred to as component (A)), (B) an inorganic acid (hereinafter referred to as component (B)) and (C) a quaternary ammonium salt (hereinafter referred to as component (C). ] It is related with the disinfectant composition containing this. The present invention also relates to a sterilization method in which the disinfectant composition of the present invention is brought into contact with an object at a temperature of 10 ° C. or more and 60 ° C. or less.

ADVANTAGE OF THE INVENTION According to this invention, the bactericidal effect with respect to a bacterial spore is high, for example, the bactericidal composition which can kill the bacterial spore of the density | concentration of 10 < ⁶ > cfu / mL or more is obtained. Moreover, the disinfectant composition of the present invention has an excellent cleaning effect against protein stains and scale stains.

  According to the sterilization method using the bactericide composition of the present invention, it is possible to sterilize microorganisms in various food processing machines, kitchen equipment, medical equipment and peripheral equipment. Examples of bacteria include Escherichia coli, Salmonella, Staphylococcus aureus, Pseudomonas aeruginosa, and fungi such as Aspergillus niger and Candida. Furthermore, it is important to kill bacterial spores such as Bacillus subtilis and fungi spores such as Aspergillus niger and Candida that exhibit strong resistance to bactericides and have heat resistance. Bacterial spores are dormant cells produced in an environment unsuitable for growth, and have multiple layered outer shells on the outside of the cells, which are highly resistant to drugs and heat. However, the bactericidal composition of the present invention provides a high bactericidal effect against these bacterial spores. At that time, an excellent removal effect can be obtained against protein stains and scale stains.

<(A) component>
Examples of the organic carboxylic acid include aliphatic monovalent carboxylic acids having 1 to 4 carbon atoms such as formic acid, acetic acid, propionic acid, and butyric acid, glycol acids, citric acid, malic acid, tartaric acid, lactic acid, gluconic acid, etc. Examples thereof include aliphatic dicarboxylic carboxylic acids having 2 to 4 carbon atoms such as 6 aliphatic hydroxycarboxylic acids, oxalic acids, malonic acids, and maleic acids. Among these, at least one selected from the group consisting of glycolic acid, citric acid, malic acid, lactic acid, and tartaric acid is preferable from the viewpoint of bactericidal properties and protein stain removability. In the present invention, the component (A) is a component that contributes to sterilization and removal of protein stains.

<(B) component>
Examples of the inorganic acid include one or more selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid. Component (B) is effective for sterilization and scale removal.

<(C) component>
The quaternary ammonium salt is preferably at least one selected from a benzethonium salt, an alkylpyridinium salt, or a compound represented by the following general formula (1).
_{R 1 R 2 R 3 R 4} N + X - wherein (1)
[In the formula (1), at least one of R ₁ , R ₂ , R ₃ and R ₄ is alkyl having a total carbon number of 8 to 28 which may be substituted with an alkoxyl group, an alkanoylamino group or an alkanoyloxy group. A group or an alkenyl group, the remainder being a phenyl group, a benzyl group, an alkyl group having 1 to 5 carbon atoms, and — (R ₅ O) _m H (wherein R ₅ represents an alkylene group having 2 to 3 carbon atoms, m represents a group selected from 2 to 40). X ⁻ represents a halogen atom or an organic anionic group. ]

  Among these, at least one selected from the group consisting of benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, and alkyl chloride (C10 to C22) trimethylammonium is preferable from the viewpoint of bactericidal properties. Furthermore, benzalkonium chloride is more preferable.

  Component (C) is effective for bactericidal action. In particular, by further coexisting the component (C) with the component (A) and the component (B), a synergistic effect is obtained in the bactericidal action, and the total of the components (A), (B) and (C) The amount used can be reduced.

<Fungicide composition>
Organic carboxylic acids exist in water as dissociable acids and non-dissociable acids, but in the present invention, non-dissociable acids play an important role in expressing the effects of the invention. In the present invention, it is considered that by using an inorganic acid in combination, the organic carboxylic acid is present as a non-dissociable acid in water, so that the bactericidal effect is remarkably improved.

  The coexistence of an organic carboxylic acid and an inorganic acid can be judged by a neutralization titration curve with NaOH or the like. That is, since the neutral inflection point of the inorganic acid portion that is a strong acid and the neutral inflection point of the organic carboxylic acid portion that is a weak acid are observed in two stages, the existence of both can be understood. In addition, the types and concentrations of the anions of the organic carboxylic acid and the inorganic acid can be known by high performance liquid chromatography and ion chromatography, respectively.

  In the disinfectant composition of the present invention, the mass ratio of the component (A) to the component (B) is preferably (A) / (B) = 0.1 to 200, more preferably 1 to 50, and particularly preferably 5 to 20. . Moreover, it is preferable that mass ratio of (B) component and (C) component is (C) / (B) = 0.1-50, 0.5-20, especially 1-10.

  At the time of use, the fungicide composition of the present invention contains the component (A) in an amount of 0.1 to 2.0% by mass, further 0.4 to 1.6% by mass, particularly 0.8 to 1.4% by mass. It is preferable to do. Moreover, it is preferable to contain (B) component 0.01-1.0 mass%, 0.05-0.5 mass%, especially 0.08-0.25 mass%. Moreover, it is preferable to contain (C) component 0.02-0.5 mass%, 0.05-0.35 mass%, especially 0.1-0.25 mass%. In these ranges, a better sterilizing effect can be obtained, the load of wastewater treatment can be reduced, and the economic efficiency is also improved. Further, when the component (A) and the component (B) are within these ranges, the influence on the apparatus member is small. The composition containing the components (A) to (C) at this concentration can be directly subjected to sterilization and washing. After satisfying such a concentration, the disinfectant composition preferably has a pH at a washing temperature of 0.1 to 3. Furthermore, the pH of the present invention at the time of use is preferably not higher than the pKa value of the organic carboxylic acid. If an organic polyvalent carboxylic acid or a plurality of types of organic carboxylic acids are used, the smallest pKa of those organic carboxylic acids is used. It is preferable that it is not more than a value, more preferably not more than a value obtained by further subtracting 0.5 from the smallest pKa value.

  The disinfectant composition of the present invention may be provided as a high-concentration disinfectant stock solution, and the stock solution is diluted with water at the time of use to disinfect the disinfectant composition, preferably at the concentration at the time of use (A) to (A C) A fungicidal composition containing the component can be prepared. The high-concentration fungicide composition that can be used as a bactericide stock solution has a component (A) of 10 to 60% by mass, a component (B) of 0.1 to 10% by mass, and a component (C) of 0.1 to 30%. Preferably, the component (A) is contained in an amount of 30 to 50% by mass, the component (B) is contained in an amount of 2 to 8% by mass, and the component (C) is preferably contained in an amount of 2 to 20% by mass. The component (A) is preferably 35 to 45% by mass, the component (B) is 3 to 6% by mass, and the component (C) is preferably 5 to 15% by mass. In these ranges, it is easy to handle and excellent in stability. Such a high-concentration disinfectant composition is a composition for use after dilution, and is usually diluted 10 to 150 times.

  The disinfectant composition of the present invention can be used for sterilizing and washing food processing machines, kitchen equipment, medical equipment and peripheral equipment. Medical devices include artificial hemodialyzers (including peripheral devices), endoscopes and biopsy forceps, as well as scissors, tweezers, forceps, needle holders, vagina Examples include mirrors, retractors, serpentine tubes, tubes, catheters, carts, and the like. In particular, the bactericidal composition of the present invention is suitable for an artificial hemodialysis apparatus.

  In the case of an artificial hemodialysis apparatus, in addition to sterilization, it is required to remove calcium carbonate derived from the dialysate composition and to wash away protein stains removed from blood by dialysis. Endoscopes are also required for sterilization and removal of protein stains, and are applicable to the disinfectant composition of the present invention.

  The disinfectant composition of the present invention can contain the above components (A) to (C) and other components as long as the effects of the present invention are not hindered, and can be a liquid composition containing water. Examples of other components include rust preventives, antifoaming agents, pigments, and fragrances.

  When the bactericide composition of the present invention is used in a medical device such as an artificial hemodialysis machine, it is preferable not to contain any surfactant other than the component (C) in consideration of the interaction with various filter materials.

  The disinfectant composition of the present invention is subjected to a disinfection method in which the composition is brought to a temperature of 10 ° C. or more and 60 ° C. or less and brought into contact with an object. At that time, the fungicide composition of the present invention is preferably used as it is or as a composition obtained by diluting a high-concentration fungicide stock solution with water as described above with the components (A) to (C). It is used as a composition containing in the concentration range at the time of use. Therefore, according to the present invention, (A) component 0.1-2.0 mass%, (B) component 0.01-1.0 mass%, (C) component 0.02-0.5 mass%, and water There is provided a sterilization method in which a sterilizing composition containing saponification is brought into contact with an object at a temperature of 10 ° C. or more and 60 ° C. or less. The contact of the disinfectant composition of the present invention with an object is carried out by bringing an appropriate diluent into contact. However, it is important to sufficiently bring the diluent into contact with the object. In the case of washing or the like, a method of adjusting the flow rate at the time of passing through, for example, 0.1 to 50 liters / minute, or a method of adjusting the residence time after passing through, for example, 10 minutes to 50 hours can be used. In the dipping method, air bubbling or ultrasonic waves can be used in combination. Moreover, it can be used as a cleaning agent for a medical device washer such as a washer disinfector.

<Examples 1-6 and Comparative Examples 1-5>
(1) Bactericidal effect of bacterial spores After Bacillus subtilis ATCC6051 is pre-cultured on an SCD agar medium (manufactured by Nippon Pharmaceutical Co., Ltd.) at 30 ° C. for 4 weeks, an appropriate amount of colonies formed on the agar medium are scraped off. The suspension was suspended in 1 mL of sterilized water and microscopically confirmed to form bacterial spores (hereinafter referred to as spores). This suspension was subjected to centrifugal washing twice, and then adjusted to a bacterial concentration of 10 ⁸ to 10 ⁹ cfu / mL with an appropriate amount of sterilized water.

  0.1 mL of this spore suspension was inoculated into 1.9 mL of the bactericidal composition shown in Table 1 and allowed to act under the bactericidal conditions shown in Table 1. After acting for a predetermined time at a predetermined temperature, 0.1 mL of this mixed solution was mixed with 1.9 mL of phosphate buffer (pH 6.4) and inactivated. 0.4 ml of this inactivation solution is smeared on two standard agar media with a diameter of 9 cm (0.2 ml per plate) and cultured at 35 ° C. for 24 hours, and the total number of colonies formed on the two media By counting the number of remaining viable bacteria. When no colony was observed, the detection limit was set to less than 50. The results are shown in Table 1. The balance of the fungicide composition in Table 1 is water.

(2) Fungicidal effect of mold spores Black Aspergillus niger IFO6341 was pre-cultured on potato dextrose agar medium (manufactured by Nippon Pharmaceutical Co., Ltd.) at 25 ° C. for 4 weeks. The microbial cells generated on the medium were scraped and suspended uniformly in about 5 mL of sterile water using a glass homogenizer. This suspension was centrifugally washed twice, and then adjusted to a bacterial concentration of 10 ⁷ to 10 ⁸ cfu / mL with an appropriate amount of sterilized water.

  0.1 mL of this spore suspension was inoculated into 1.9 mL of the bactericidal composition shown in Table 1, and allowed to act under the bactericidal conditions shown in Table 1. After acting for a predetermined time at a predetermined temperature, 0.1 mL of this mixed solution was mixed with 1.9 mL of phosphate buffer (pH 6.4) and inactivated. 0.4 ml of this inactivation solution is smeared on two standard agar media with a diameter of 9 cm (0.2 ml per plate) and cultured at 25 ° C. for 72 hours to obtain the total number of colonies formed on the two media. By counting the number of remaining viable bacteria. When no colony was observed, the detection limit was set to less than 50. The results are shown in Table 1.

(3) Removal of protein stains and calcium carbonate Replace a part of the line with a silicon tube contaminated under the following conditions, assemble the line in a loop so that the liquid can be circulated through the pump, and the disinfectant listed in Table 1 The composition was circulated under predetermined conditions. The circulation conditions were a circulation time of 40 minutes, a circulation temperature of 25 ° C., and a circulation flow rate of 500 mL / min. After circulation, the contaminated silicon tube was removed and the internal contamination degree was evaluated. The results are shown in Table 1.

* Contamination condition of silicon tube A standard dialysis solution (Fuso Pharmaceutical Co., Ltd., kinderly solution AF-1) was filled in about 40 cm of a silicon tube having an inner diameter of 6 mm, and left to stand for 3 days. After confirming the precipitation of white crystals of calcium carbonate, the dialysate was discarded. Further, about 2 mL of horse blood was added to the inner surface of the same silicone tube, and the horse blood was left to stand at 60 ° C. for 2 hours to thermally deteriorate and fix.

* Evaluation method for protein stains After completion of washing, the silicon tube was removed, about 5 cm including the blood stain portion was cut vertically, and the protein adhesion state was visually evaluated by the following four steps by the amide black staining method.
Visual evaluation criteria: Degree of staining of the evaluation target surface “None” = not stained “Slightly” = light blue “Medium” = blue "Many" = dark blue

* Evaluation method of calcium carbonate adhesion amount The remaining silicon tube used for the evaluation of protein stains is filled with 0.1N hydrochloric acid solution to elute the adhering calcium carbonate, and the Ca concentration of the eluate is determined. Measurement was made to determine the amount of adhered calcium carbonate. The amount of CaCO ₃ eluted with respect to the internal volume of about 30 cm of the silicon tube is shown in units of mg / L.

The component (C) in the table is as follows.
Sanisole C: benzalkonium chloride (manufactured by Kao Corporation) [wherein R _{1 in} formula (1) is a benzyl group, R ₂ and R ₃ are methyl groups, and R ₄ is a mixed alkyl group having 12 to 16 carbon atoms. Compound〕
Cotamine 60W: Cetyltrimethylammonium chloride (manufactured by Kao Corporation) [compound in which R ₁ , R ₂ and R _{3 in} formula (1) are methyl groups and R ₄ is an alkyl group having 16 carbon atoms]

<Examples 7 to 9>
40.0 g of DL-malic acid is dissolved in 36.0 g of ion-exchanged water. Thereto, 97% concentrated sulfuric acid and Sanisole C (effective content 50.2% by mass) were added and dissolved in 4.12 g and 15.9 g, respectively. Ion exchange water was added to make the whole 100.0 g to obtain a high concentration bactericide stock solution. This stock solution of bactericide was stable without precipitation or the like even when stored at −5 ° C. and 60 ° C. for 2 months. A test similar to Example 1 was conducted using a bactericide composition obtained by diluting this high-concentration bactericide solution 30 times, 40 times and 50 times. The results are shown in Table 2.

  From the results of Tables 1 and 2, it was shown that the fungicide composition of the present invention is a fungicide composition that has excellent bactericidal properties and can effectively remove calcium carbonate and protein stains at the same time.

Claims (11)

A disinfectant composition containing (A) an organic carboxylic acid, (B) an inorganic acid, and (C) a quaternary ammonium salt. The mass ratio of (A) organic carboxylic acid and (B) inorganic acid is (A) / (B) = 0.1-200, and the mass ratio of (B) inorganic acid and (C) quaternary ammonium salt is ( The disinfectant composition according to claim 1, wherein C) / (B) = 0.1-50. (A) 0.1-2.0 mass% of organic carboxylic acid, (B) 0.01-1.0 mass% of inorganic acid and (C) quaternary ammonium salt 0.02-0.5 mass% The disinfectant composition according to claim 1 or 2, which is contained. (A) 10-60 mass% of organic carboxylic acid, (B) 0.1-10 mass% of inorganic acid, and (C) quaternary ammonium salt 0.1-30 mass% are contained. The disinfectant composition as described. (A) The organic carboxylic acid is selected from the group consisting of an aliphatic monovalent carboxylic acid having 1 to 4 carbon atoms, an aliphatic hydroxycarboxylic acid having 2 to 6 carbon atoms, and an aliphatic divalent carboxylic acid having 2 to 4 carbon atoms. The disinfectant composition according to any one of claims 1 to 4, wherein the composition is one or more selected from the above. (A) The organic carboxylic acid is at least one selected from the group consisting of formic acid, acetic acid, propionic acid, glycolic acid, citric acid, malic acid, lactic acid, and tartaric acid. Fungicide composition. (B) The disinfectant composition according to any one of claims 1 to 6, wherein the inorganic acid is at least one selected from the group consisting of hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid. The disinfectant composition according to any one of claims 1 to 7, wherein (C) the quaternary ammonium salt is selected from a benzethonium salt, an alkylpyridinium salt, or a compound represented by the following general formula (1).
_{R 1 R 2 R 3 R 4} N + X - wherein (1)
[In the formula (1), at least one of R ₁ , R ₂ , R ₃ and R ₄ is alkyl having a total carbon number of 8 to 28 which may be substituted with an alkoxyl group, an alkanoylamino group or an alkanoyloxy group. A group or an alkenyl group, the remainder being a phenyl group, a benzyl group, an alkyl group having 1 to 5 carbon atoms, and — (R ₅ O) _m H (wherein R ₅ represents an alkylene group having 2 to 3 carbon atoms, m represents a group selected from 2 to 40). X ⁻ represents a halogen atom or an organic anionic group. ] (C) The quaternary ammonium salt is at least one selected from the group consisting of benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, and alkyl chloride (10 to 22 carbon atoms) trimethylammonium. The disinfectant composition according to any one of the above. The disinfectant composition according to any one of claims 1 to 9, which is used for disinfecting and washing an artificial hemodialysis apparatus. The sterilization method which makes the temperature of 10 degreeC or more and 60 degrees C or less contact the target object with the disinfectant composition of any one of Claims 1-10.