JP7059890B2 - disinfectant - Google Patents

Description

The present invention relates to a disinfectant having excellent bactericidal activity and virus inactivating effect.

In recent years, infectious diseases caused by bacteria and viruses have become a problem, and various disinfectants are commercially available from the viewpoint of infection prevention.
The disinfectants are a monovalent lower alcohol-based disinfectant represented by ethanol and isopropanol, a surfactant-containing disinfectant represented by benzalkonium chloride, and a biguanide-based disinfectant represented by chlorhexidine gluconate. It is roughly divided into types. Of these, the biguanide-based disinfectant is known to be characterized by having less odor and less irritation to the skin.

For example, Patent Document 1 discloses that a disinfectant in which chlorhexidine gluconate is dissolved in a solvent such as isoprene glycol is excellent in sustainability of bactericidal activity against Escherichia coli.
Patent Document 2 discloses that a disinfectant in which chlorhexidine gluconate, glycerin, and a silicone polymer are dissolved in water reduces Gram-positive and Gram-negative bacteria.

JP-A-2002-161001. Special Table 2012-500195 Gazette

However, the disinfectant described in Patent Document 1 has not been confirmed to be effective against bacterial species other than Escherichia coli. There are many pathogenic bacteria other than E. coli, such as Staphylococcus aureus, which has been reported as a major cause of infections, including bloodstream infections, surgical site infections, and pneumonia. Therefore, there is a demand for a disinfectant having a wide bactericidal spectrum and having high bactericidal activity.
The disinfectant described in Patent Document 2 is effective against gram-positive and gram-negative bacteria, but has no inactivating effect against viruses. Here, the virus inactivating effect means that the activity such as infectivity and toxicity of the virus is lost.
Infections caused by viruses can also cause serious health hazards, such as the influenza virus, which is the causative virus of respiratory infections that are prevalent worldwide. Therefore, it is desirable that the disinfectant not only has a wide bactericidal spectrum but also has an inactivating effect on viruses.

In addition, a monohydric lower alcohol may be added to impart an inactivating effect to the virus to the disinfectant. In that case, users with an alcohol-sensitive constitution tend to avoid using it because they are concerned about the effect on the skin. Therefore, a disinfectant that does not contain a monohydric lower alcohol and has an inactivating effect on viruses is desirable.

Therefore, it is an object of the present invention to provide a disinfectant having excellent bactericidal activity and virus inactivating effect without using a monohydric lower alcohol.

As a result of diligent studies in view of the above problems, the present inventors have found that (a) chlorhexidine or a salt thereof, (b) paraoxybenzoic acid ester, (c) carboxylic acid having 2 to 6 carbon atoms, and (d) 3 carbon atoms. We have found that the above-mentioned problems can be solved by a disinfectant having a value of about 8 and containing a specific amount of a divalent or trivalent polyhydric alcohol, a pH in a certain range, and a monohydric lower alcohol-free disinfectant. The invention was completed.

That is, the gist of the present invention is the following [1] to [2].
[1] (a) chlorhexidine or a salt thereof in an amount of 0.01 to 1% by mass, (b) a paraoxybenzoic acid ester in an amount of 0.001 to 0.5% by mass, and (c) a carboxylic acid having 2 to 6 carbon atoms in 0. .1 to 10% by mass, (d) 3 to 8 carbon atoms, 0.1 to 30% by mass of divalent or trivalent polyvalent alcohol, pH 2 to 5, monovalent A disinfectant that does not contain lower alcohol.
[2] The disinfectant according to the above [1], which further contains (e) phenoxyethanol in an amount of 0.1 to 10% by mass.

According to the present invention, it is possible to provide a disinfectant having high bactericidal activity and excellent virus inactivating effect.

Hereinafter, the present invention will be described in more detail.
In addition, in this specification, when a preferable numerical range (for example, content) is described step by step, each lower limit value and upper limit value can be combined independently. For example, in the description of "preferably 10 to 100, more preferably 20 to 90", "preferably lower limit value: 10" and "more preferable upper limit value: 90" may be combined to form "10 to 90". can.

The disinfectant of the present invention contains (a) chlorhexidine or a salt thereof in an amount of 0.01 to 1% by mass, (b) a paraoxybenzoic acid ester in an amount of 0.001 to 0.5% by mass, and (c) having 2 to 6 carbon atoms. It contains 0.1 to 10% by mass of carboxylic acid, (d) 0.1 to 30% by mass of divalent or trivalent polyhydric alcohol having 3 to 8 carbon atoms, and has a pH of 2 to 5, and 1 It is a disinfectant that does not contain low-value alcohol.
Hereinafter, the disinfectant of the present invention will be described in detail.

The disinfectant of the present invention does not contain a monohydric lower alcohol. Since it does not contain monovalent lower alcohol, it is less irritating to the skin and is an easy-to-use disinfectant for users with alcohol hypersensitivity. Here, the monohydric lower alcohol means a monohydric alcohol having 1 to 5 carbon atoms. The fact that the monohydric lower alcohol is not contained means that the monohydric lower alcohol is not intentionally blended. For example, a monohydric lower alcohol that can be contained as an unavoidable impurity in the disinfectant is acceptable. Will be done.

<(A) Chlorhexidine or its salt>
The disinfectant of the present invention contains (a) chlorhexidine or a salt thereof (hereinafter, may be simply referred to as component (a)).
The component (a) is chlorhexidine or a salt thereof, for example, chlorhexidine gluconate, chlorhexidine palmitate, chlorhexidine phosphanate, chlorhexidine acetate, chlorhexidine hydrochloride, chlorhexidine chloride, chlorhexidine iodide, chlorhexidine perchlorate, chlorhexidine nitrate. , Chlorhexidine sulfate, Chlorhexidine sulfite, Chlorhexidine thiosulfate, Chlorhexidine hydrogen phosphate, Chlorhexidine fluorophosphate, Chlorhexidine formate, Chlorhexidine propionate, Chlorhexidine iodobutyrate, N-chlorhexidine valerian, Chlorhexidine caproate, Chlorhexidine caproate Chlorhexidine malate, chlorhexidine tartrate, chlorhexidine monoglycolate, chlorhexidine diglycolate, chlorhexidine lactate, α-hydroxyisobutyric chlorhexidine, chlorhexidine glucoheptate, chlorhexidine isothiate, chlorhexidine benzoate, chlorhexidine benzoate, chlorhexidine silicate, chlorhexidine silicate. Examples thereof include chlorhexidine and chlorhexidine 2-hydroxynaphthoate. Among these, chlorhexidine gluconate, chlorhexidine acetate, and chlorhexidine hydrochloride are preferable, and chlorhexidine gluconate is more preferable.

The content of the component (a) in the disinfectant is 0.01 to 1% by mass. If the content is less than 0.01% by weight, the disinfectant may not exhibit a broad sterilization spectrum. When the content is higher than 1% by mass, it is not expected that the bactericidal activity is greatly improved by increasing the amount of the component (a), which is not preferable from the viewpoint of cost effectiveness. The content of the component (a) is preferably 0.05 to 0.5% by mass, more preferably 0.1 to 0.3% by mass.

<(B) Paraoxybenzoic acid ester>
The disinfectant of the present invention contains (b) a paraoxybenzoic acid ester (hereinafter, may be simply referred to as a component (b)).
The component (b) is preferably an alkyl ester of paraoxybenzoic acid, and more preferably an alkyl ester having 1 to 4 carbon atoms of paraoxybenzoic acid.
Specifically, the component (b) preferably contains at least one compound selected from the group consisting of methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate. More preferably, it is at least one compound selected from the group consisting of methyl paraoxybenzoate and propyl paraoxybenzoate. Among these, it is particularly preferable to use methyl paraoxybenzoate and propyl paraoxybenzoate in combination.

The total content of the component (b) in the disinfectant is 0.001 to 0.5% by mass. When the content is lower than 0.001% by mass, the bactericidal activity and the virus inactivating effect are lowered. If the content is higher than 0.5% by mass, the usability may be deteriorated. The content of the component (b) is preferably 0.1 to 0.5% by mass.
When methyl paraoxybenzoate and propyl paraoxybenzoate are used in combination as the component (b), it is preferable to use methyl paraoxybenzoate in the same amount or more as propyl paraoxybenzoate. The mass ratio of methyl paraoxybenzoate to propyl paraoxybenzoate (methyl paraoxybenzoate / propyl paraoxybenzoate) is preferably 1 to 50, more preferably 5 to 25.

<(C) Carboxylic acid having 2 to 6 carbon atoms>
The disinfectant of the present invention contains (c) a carboxylic acid having 2 to 6 carbon atoms (hereinafter, may be simply referred to as a component (c)).
The component (c) is not particularly limited as long as it is a carboxylic acid having 2 to 6 carbon atoms, but is lactic acid, malic acid, citric acid, tartaric acid, gluconic acid, adipic acid, fumaric acid, succinic acid, maleic acid and sorbic acid. , Acetic acid, and propionic acid are preferably contained at least one selected from the group consisting of, acetic acid, and propionic acid. The carboxylic acid may be D-form, L-form or DL-form.
The component (c) preferably contains a carboxylic acid having a valence of 3 or more (hereinafter, also referred to as carboxylic acid A), and the carboxylic acid A and the carboxylic acid having a valence of 2 or less (hereinafter, also referred to as carboxylic acid B). ) Is more preferable. When used in combination, the mass ratio of carboxylic acid A to carboxylic acid B (carboxylic acid A / carboxylic acid B) is preferably 1/20 to 20/1, more preferably 1/10 to 10/1. Citric acid is preferable as the carboxylic acid A, and lactic acid or malic acid is preferable as the carboxylic acid B.

The total content of the component (c) in the disinfectant is 0.1 to 10% by mass. When the content is lower than 0.1% by mass, the bactericidal activity and virus inactivating effect of the carboxylic acid cannot be expected to be improved. When the content of the carboxylic acid is higher than 10% by mass, the pH of the disinfectant does not depend only on the component (c), but it becomes difficult to control the pH to the target. The total content of the component (c) in the disinfectant is preferably 0.2 to 8% by mass, more preferably 0.5 to 5% by mass.

<(D) Divalent or trivalent polyhydric alcohol having 3 to 8 carbon atoms>
The disinfectant of the present invention (d) has 3 to 8 carbon atoms and contains a divalent or trivalent polyhydric alcohol (hereinafter, may be simply referred to as component (d)).
The component (d) is not particularly limited as long as it has 3 to 8 carbon atoms and is a divalent or trivalent polyhydric alcohol. The component (d) is at least one compound selected from 1,2-octanediol, 1,2-hexanediol, 1,2-pentanediol, 1,3-butylene glycol, propylene glycol, and glycerin. It is preferably contained, and more preferably it contains at least one compound selected from 1,3-butylene glycol, propylene glycol and glycerin. Among these, it is particularly preferable that the component (d) contains 1,3-butylene glycol.

The total content of the component (d) in the disinfectant is 0.1 to 30% by mass. When the content is less than 0.1% by mass, the bactericidal activity of the disinfectant is low, and it becomes difficult to apply the disinfectant to the fingers and stretch it for use, which makes it difficult to use the disinfectant. If the content is higher than 30% by mass, stickiness or the like may appear at the time of use, and the feeling of use may be deteriorated. The content of the component (d) is preferably 0.5 to 20% by mass, more preferably 4 to 15% by mass.

<(E) Phenoxyethanol>
The disinfectant of the present invention may contain (e) phenoxyethanol (hereinafter, may be simply referred to as component (e)). The content of the component (e) in the disinfectant is preferably 0.1 to 10% by mass. Within this range, the bactericidal activity can be particularly enhanced. The content of the component (e) is more preferably 0.1 to 1% by mass.

The disinfectant of the present invention may have a composition containing water as a solvent. As the water, it is preferable to use purified water.

The disinfectant has a pH of 2-5 at 25 ° C. When the pH is higher than 5, the bactericidal activity and the virus inactivating effect are reduced. When the pH is less than 2, the bactericidal activity and the virus inactivating effect do not decrease, but the irritation to the skin may become stronger. The pH is measured in accordance with the 17th revised Japanese Pharmacopoeia General Test Method 2.54.

The disinfectant of the present invention is a moisturizer as an optional component other than the components (a) to (d), the component (e) to be blended as necessary, and water as long as the effect of the present invention is not impaired. , A pH adjuster or the like, a solubilizer, a stabilizer or the like may be contained.

Examples of the moisturizing agent include N-cocoyl-L-arginine ethyl ester DL-pyrrolidone carboxylic acid and its salt, hyaluronic acid and its salt, sodium lactate, urea and the like, and 2-methacryloyl represented by the formula (1). Examples thereof include a copolymer having a weight average molecular weight of 50,000 to 1,000,000 (hereinafter referred to as copolymer A) obtained by copolymerizing 70 to 90 mol% of oxyethylphosphorylcholine and 30 to 10 mol% of butyl methacrylate. Can include one or more of these. Of these, the use of the copolymer A is particularly preferable.

The pH adjuster of the present invention is a water-soluble basic compound capable of adjusting the pH by combining with the component (c), and examples thereof include basic inorganic salts, amines, and basic amino acids. be able to. Examples of the pH adjuster include hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide; sodium citrate, sodium lactate, calcium lactate, sodium tartrate, sodium succinate, sodium acetate, potassium acetate and the like. Salts of carboxylic acids; hydroxides of ammonium such as ammonium hydroxide; alkanolamines such as monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, triisopropanolamine; 2-amino-2- Alkylamines such as methyl-1-propanol and 2-amino-2-methyl-1,3-propanediol; basic amino acids such as lysine and arginine; POE alkylamines and the like can be mentioned and one of these. The above can be included. Of these, the use of sodium citrate is particularly preferable.

Examples of the solubilizer include polyoxyethylene hydrogenated castor oil, polyethylene glycol monolaurate, polyethylene glycol monostearate, polyoxyethylene sorbitan monooleate, polyoxyethylene lauryl ether, polyoxyethylene cetyl ether and the like. One or more of these can be included. Of these, the use of polyethylene glycol monostearate is preferable.

Examples of the stabilizer include polyethylene glycol, polyvinylpyrrolidone, disodium glycyrrhizinate, hydroxypropyl cellulose, glycine and the like, and one or more of these can be included.

The method for preparing the disinfectant is not particularly limited, but after preparing a premixed solution (1) in which the component (b) is stirred and dissolved in the component (d), the premixed solution (1) and the component are added to purified water. It can be prepared by adding (a) and component (c) and mixing.

The product form (appearance) of the disinfectant having the composition described above is not particularly limited, and examples thereof include liquid, gel-like, foam-like, and paste-like forms. Of these, foam is preferable because it does not easily spill from the fingers when the disinfectant is used and is easy to spread over the entire fingers.

The method of using the disinfectant is not particularly limited, but for example, a method of filling an appropriate bottle and picking up an appropriate amount as it is, a method of discharging with a pump former or the like and using a suitable amount by hand, a non-woven fabric, etc. A method of impregnating and using it on the skin can be applied.

The disinfectant having the composition and product form described above can be used against the causative bacteria and viruses that cause diseases such as infectious diseases to humans in a normal living environment by using the disinfectant having the above-exemplified usage method. It is effective. There are no particular restrictions on the types of these causative bacteria and causative viruses. Specifically, examples of the bacterium include Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida, and examples of the virus include influenza virus and herpes virus.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited thereto.

The components used in the examples and comparative examples are as follows.
[Each component of disinfectant]
<Component (a)>
Chlorhexidine gluconate <component (b)>
Methyl paraoxybenzoate Propyl paraoxybenzoate <Component (c)>
Carboxylic acid A (carboxylic acid with a valence of 3 or more) ... Carboxylic acid Carboxylic acid B (Carboxylic acid with a valence of 2 or less) ... DL-lactic acid, DL-apple acid <component (d)>
1,3-butylene glycol <component (e)>
Phenoxyethanol

<Water>
Purified water <moisturizer>
Copolymer A: Copolymer having a weight average molecular weight of 600,000 obtained by copolymerizing 80 mol% of 2-methacryloyloxyethyl phosphorylcholine and 20 mol% of butyl methacrylate <pH adjuster>
Sodium citrate <solubilizer>
Polyethylene glycol monostearate

(Example 1)
Methyl paraoxybenzoate (component (b)) and propyl paraoxybenzoate (component (b)) are added to 1,3-butylene glycol (component (d)), and the mixture is stirred at 25 ° C. until these are dissolved. A premixed solution (1) was prepared. Then, in the purified water, a premix solution (1), chlorhexidine gluconate (component (a)), citric acid (component (c), carboxylic acid A), phenoxyethanol (component (e)), a moisturizer, a pH adjuster. , And a solubilizer were added and mixed until uniform to obtain a disinfectant. The blending amount of each component was adjusted so that the amount in the disinfectant was as shown in Table 1. The pH adjuster was blended in an appropriate amount in the range of 0.05 to 1.0% by mass so as to have a desired pH.
The obtained disinfectants were evaluated as follows. The results are shown in Table 1.

1. 1. Evaluation of bactericidal activity The evaluation of bactericidal activity was carried out as follows.
<Test bacterial species>
Escherichia coli NBRC3972
Pseudomonas aeruginosa NBRC13275
Staphylococcus aureus NBRC13276
Candida albicans NBRC1594
<Preparation of test bacterial solution>
For each of the bacterial species listed above, a test bacterial solution was prepared to a constant concentration (1 × ^10-8 CFU / mL) using a sterilized physiological saline solution. The CFU is a Colony Forming Unit, which is the number of units capable of forming a colony.

<MIC (Minimum Inhibition Concentration) Test>
Using the disinfectant obtained as described above as a sample, 100 μL of the sample was serially diluted 2-fold with SCD medium to prepare a dilution series having a final sample concentration of 0.05%. After adding 50 μL of each test bacterial solution to the prepared dilution series, the cells were cultured at 37 ° C. for 24 hours. After completion of the culture, the turbidity of the medium was visually judged, and the minimum concentration (μg / mL) in which the growth of bacteria was not observed was used as the MIC. When the MIC was 7.8 or less, it was judged to have bactericidal activity against the target bacterial species. The results are shown in Table 1.

2. 2. Evaluation of influenza virus inactivating effect With respect to the disinfectant obtained as described above, influenza A virus H1N1 (A / PR / 8/34; A mixed solution 1 was prepared by adding 0.1 mL of a suspension of TC updated ATCC VR-1469) and 0.1 mL of a pollutant (0.03 g / L bovine serum albumin), and left at 20 ° C. for 15 seconds. The test virus suspension, pollutants and disinfectants used at this time were adjusted to the test temperature (20 ± 1 ° C.) in advance.
Subsequently, 0.5 mL of the mixed solution 1 was added to 4.5 mL of the drug inactivating agent (SCDLP medium containing 10% fetal bovine serum) and mixed to prepare the mixed solution 2. 0.1 mL of the mixed solution 2 was added to 0.9 mL of EMEM (Eagle's minimal essential medium), and the mixture was mixed to prepare the mixed solution 3. The virus infectivity titer of this mixed solution 3 was measured by the plaque measurement method, and the virus inactivation rate was calculated. Regarding the virus inactivation rate, when the inactivation rate is greater than 99.99%, it is "◎", when it is 99.99% or less, when it is greater than 99.9%, it is "○", and when it is 99.9% or less, it is "◎". × ”. The results are shown in Table 1.

3. 3. Evaluation of herpesvirus inactivating effect The inactivating effect of the disinfectant obtained as described above on herpes simplex virus was evaluated by the following method.
0.1 mL of a suspension of herpes simplex virus type 1 (Herpes simplex virus 1; Strine: KOS ATCC VR-1494) infected and cultured with Vero cells (cells derived from African green monkey kidney) in 0.8 mL of disinfectant. , Further, 0.1 mL of a pollutant (0.03 g / L bovine serum albumin) was added to prepare a mixed solution 1, and the mixture was left at 20 ° C. for 60 seconds. The test virus suspension, pollutants and disinfectants used at this time were adjusted to the test temperature (20 ± 1 ° C.) in advance.
Subsequently, 0.5 mL of the mixed solution 1 was added to 4.5 mL of the drug inactivating agent (SCDLP medium containing 10% fetal bovine serum) and mixed to prepare the mixed solution 2. 0.1 mL of the mixed solution 2 was added to 0.9 mL of EMEM (Eagle's minimal essential medium), and the mixture was mixed to prepare the mixed solution 3. The virus infectivity titer of this mixed solution 3 was measured by the plaque measurement method, and the virus inactivation rate was calculated. Regarding the virus inactivation rate, when the inactivation rate is greater than 99.99%, it is "◎", when it is 99.99% or less, when it is greater than 99.9%, it is "○", and when it is 99.9% or less, it is "◎". × ”. The results are shown in Table 1.

(Examples 2 to 12, Comparative Examples 1 to 4)
Disinfectants were prepared and evaluated in the same manner as in Example 1 except that the composition of the disinfectant was changed as shown in Table 1. The results are shown in Table 1.

Although the disinfectant of the present invention used in each example does not contain a monohydric lower alcohol, it has a high inactivating effect on viruses and a bactericidal effect on various bacterial species, and is widespread. It was found that it has a good bactericidal spectrum and is excellent in bactericidal activity.
On the other hand, the disinfectants shown in Comparative Examples 1 to 4, which do not contain any of the components (a) to (d), are inferior in at least one of the inactivating effect and the bactericidal activity against the virus. rice field.

Claims (2)

(A) 0.01 to 1% by mass of chlorhexidine or a salt thereof,
(B) Paraoxybenzoic acid ester 0.001 to 0.5% by mass,
(C) 0.1 to 10% by mass of carboxylic acid having 2 to 6 carbon atoms,
(D) It has 3 to 8 carbon atoms and contains 0.1 to 30% by mass of a divalent or trivalent polyhydric alcohol.
A disinfectant having a pH of 2 to 5 and containing no monohydric lower alcohol. Further, (e) containing 0.1 to 10% by mass of phenoxyethanol,
The disinfectant according to claim 1.