JPH06321711A - Germicide and method for sterilization - Google Patents

Abstract

PURPOSE:To obtain a germicide, containing a phthalocyanine iron and an organic peroxide in combination and capable of carrying out effective sterilization at an extremely low concentration and a low temperature. CONSTITUTION:The germicide contains phthalocyanine iron expressed by the formula (one or more of R1 to R8 are carboxyl and the rest are H) and an organic peroxide in combination. The phthalocyanine iron coordinates bivalent iron in the center of the structure and has one or more carboxyl groups. Among them, the phthalocyanine iron having 8 carboxyl groups is especially preferred. Methyl ethyl ketone peroxide, t-butyl hydroperoxide, di-t-butyl peroxide, etc., are cited as the organic peroxide. A solution of the organic peroxide at >=0.05% concentration and a solution of the phthalocyanine iron at >=10muM concentration are mixed by respectively applying thereof to a substance, a place or a tool for carrying out the sterilization by a method for spraying, coating, etc., to manifest germicidal effects.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a germicide and a germicidal method.

[0002]

As is well known, sterilization using a bactericide is
It means chemically killing a microorganism existing in or attached to a control substance to eliminate its infectious ability. Currently, as bactericides, phenol derivatives such as cresol soap solution, alcohols such as ethanol, halogen compounds such as chlorhexidine, surfactants such as inverse soap solution, aldehydes such as formaldehyde, and hydrogen peroxide. Oxidizing agents are used. However, there is no known bactericide which exhibits a bactericidal effect by mixing an organic peroxide and iron phthalocyanine.

Conventionally, a sterilization method is known in which a bactericidal effect is exhibited by mixing hemin, which is one of iron complexes, and an organic peroxide. (Magnetic Resonance and Medicine, Vol.3, pp.
96-101, (1992): Arch. Biochem. Biophys., Vol. 294, p.
p.55-63, (1992))

[0004]

One of the conditions for an excellent bactericide is its strong bactericidal effect at low concentrations. However, the effective concentration of the bactericide currently used in hospitals and the like is considerably high. That is, for example, cresol soap solution is 3%, ethanol is 70%, and reverse soap solution is 1-10.
%, Chlorhexidine is 0.2 to 1%, formaldehyde is 1 to 5%, glutaraldehyde is 0.5 to 2%,
Hydrogen peroxide is used at a concentration of 1 to 3.5%. In addition, there are many pathogenic microorganisms that can survive even at low temperatures, which poses a problem in cold storage such as infusion. From this, 4 ℃ which is generally used for refrigeration
It is desired to have an effective bactericide even at or below that level. Glutaraldehyde, which is favorably used in hospitals and the like, has a markedly lower bactericidal activity at low temperatures than room temperature. For example, in order to obtain an effect equivalent to room temperature at 0 ° C., the concentration or sterilization time needs to be 20 times or more. An object of the present invention is to provide a bactericide and a sterilization method effective at low concentration and low temperature.

[0005]

The present invention is based on the general formula (1)

[0006]

[Chemical 2]

A bactericide and a substance consisting of iron phthalocyanine represented by the formula (wherein at least one of R _{1 to} R ₈ is a carboxyl group and the other is a hydrogen atom) and an organic peroxide are represented by the general formula (1 ) A sterilization method characterized by applying iron phthalocyanine represented by the formula (1) and an organic peroxide.

The phthalocyanine iron that can be used in the present invention is a phthalocyanine iron having a divalent iron coordinated in the center of the structure and having one or more carboxyl groups. 8 in this
Iron phthalocyanine having a number of carboxyl groups is particularly desirable. The phthalocyanine iron complex is preferably used as a solution in a neutral to alkaline region. As the diluting solution for adjusting the concentration of the phthalocyanine iron solution, water such as tap water and sterilized water as well as solutions containing various salts such as various buffer solutions and physiological saline can be used.

Examples of the organic peroxides include peroxy ethers such as methyl ethyl ketone peroxide, cyclohexanone peroxide, 3,3,5-trimethylcyclohexinosan peroxide, methyl cyclohexanone peroxide, ketone peroxides such as acetylacetone peroxide, t-butyl hydroperoxide, and the like. Cumene hydroperoxide, di-isopropylbenzene hydroperoxide, p-menthane hydroperoxide,
Hydroperoxides such as 2,5-dimethylhexane-2,5-dihydroperoxide and 1,1,3,3-tetramethylbutylhydroperoxide, 1,1-bis (t-
Butylperoxy) 3,3,5-trimethylcyclohexane, 1,1-bis (t-butylperoxy) cyclohexane, 2,2-bis (t-butylperoxy) octane, 2,2-bis (t-butylperoxy) butane , Di-t-butyl peroxide, di-t-butyl cumyl peroxide, α, α′-bis (t-butylperoxyisopropyl) benzene, 2,5-dimethyl-2,5-di-
Dialkyl peroxide such as (t-butylperoxy) hexyne-3, diacetyl peroxide, diisobutyryl peroxide, dioctyl peroxide, didecanoyl peroxide, dilauroyl peroxide, di-
Diacyl peroxide such as (3,3,5-trimethylhexanoyl) peroxide, succinic acid peroxide, dibenzoyl peroxide, di- (2,4-dichlorobenzoyl) peroxide, di- (m-toluoyl) peroxide, di-isopropylperoxy Dicarbonate, di-2-ethylhexyl peroxydicarbonate, di-n-propylperoxydicarbonate, di-
Myristyl peroxydicarbonate, di-2-ethoxyethyl peroxydicarbonate, di-methoxyisopropyl peroxydicarbonate, di (3-methyl-
Peroxydicarbonate such as 3-methoxybutyl) peroxydicarbonate, n-butyl-4,4-bis (t-butylperoxy) valerate, t-butylperoxyacetate, t-butylperoxyisobutyrate, t-butylperoxypyrrole. Valate, t-butyl peroxy neodecanoate, cumyl peroxy neodecanoate, t-butyl peroxy-2-ethylhexanoate, t-butyl peroxy-3,3,5-trimethylhexanoate, t-butyl Peroxylaurate, t
-Butylperoxybenzoate, di-t-butylperoxyisophthalate, 2,5-dimethyl-2,5-di (benzoylperoxy) hexane, t-butylperoxymaleate, peroxyester such as t-butylperoxyisopropylcarbonate, or Acetylcyclohexyl sulfonyl peroxide and the like.

The bactericide and sterilization method of the present invention are preferably used in the following procedure. As a bactericide, the concentration is 0.
Sterilization by mixing 05% or more of organic peroxide and a phthalocyanine iron solution having a concentration of 10 μM or more by adhering the respective solutions to a substance, a place or an instrument to be sterilized by a method such as spraying or coating. Bring out the effect.
As a sterilization method, an article contaminated with pathogenic bacteria such as medical equipment, cooking equipment, utensils such as tableware, clothes, or indoor parts is immersed in a phthalocyanine iron solution having a concentration of 10 μM or more, and then the final organic peroxide is added. The purpose is achieved by adding a solution or suspension of an organic peroxide so that the concentration is 0.05% or more. On the contrary, 0.05% in advance
The same effect can be obtained by adding the phthalocyanine iron solution so that the final concentration of the phthalocyanine iron is 10 μM or more after the immersion in the above organic peroxide. Furthermore, spray each solution onto these substances, places or instruments,
Similar effects can be obtained by mixing by adhering by a method such as coating.

If the phthalocyanine iron concentration is less than 10 μM or the organic peroxide concentration is less than 0.05%, the bactericidal effect cannot be sufficiently obtained. Further, even if the iron phthalocyanine concentration exceeds 100 μM, the bactericidal effect is not improved, and concentrations lower than that are sufficiently effective.

[0012]

According to the sterilizing method and the sterilizing agent of the present invention, effective sterilization can be performed at an extremely low concentration and at a low temperature as compared with the conventional sterilizing method and the sterilizing agent.

[0013]

Example A test bacterial solution was prepared as follows. Ie Staphylococcus aureus (Staphylococcus aureus; Stap
hylococcus aureus) on normal agar medium overnight,
The suspension was suspended in phosphate buffered saline (hereinafter abbreviated as PBS), and the bacterial solution was adjusted with PBS so that the number of bacteria was 10 8 per 1 ml.

Sterilization was performed as follows. To a sterilized test tube, 700 μl of PBS, 100 μl of test bacterial solution, and 100 μl of an aqueous solution of iron phthalocyanine were added. 100 μl of a PBS suspension of organic peroxide was quickly added to this solution, stirred for 10 seconds, and then allowed to stand at room temperature for 30 minutes. To test the bactericidal effect, 100 μl of the above mixture was applied to a Brain Heart Infusion agar plate medium, and then 15 to 2 at 37 ° C.
After culturing for 4 hours, the number of viable bacteria was determined from the number of formed colonies.

Example 1 As an aqueous solution of iron phthalocyanine, 95.6 μg / ml
Phthalocyanine iron 8-carboxylic acid (100 μM iron equivalent)
Was used as a PBS suspension of organic peroxide, and a t-butyl hydroperoxide PBS suspension was used for the experiment according to the method described above. The concentration of t-butyl hydroperoxide was 0 to 0.5% (final concentration). The results are shown in Table 1. In the presence of 0.05% or more of t-butyl hydroperoxide, the viable cell count was reduced to less than 1 part per million.

Further, the same experiment was conducted except that distilled water was added instead of the aqueous solution of iron phthalocyanine. The results are shown in Table 1. No decrease in viable cell count was observed without the addition of iron phthalocyanine.

[0017]

[Table 1]

Example 2 Phthalocyanine iron 8 was prepared as an aqueous solution of iron phthalocyanine.
Carboxylic acid was added to a concentration of 0.2 to 100 μM, and t-butyl hydroperoxide as an organic peroxide was added to a final concentration of 0.1%, and an experiment was conducted according to the above method. The results are shown in Table 2. 0.
When 1% t-butyl hydroperoxide was added, it was confirmed that the viable cell count decreased depending on the concentration of phthalocyanine iron 8-carboxylic acid. That is, in the presence of phthalocyanine iron 8-carboxylic acid corresponding to an iron concentration of 20 μM or more, the viable cell count was reduced to 1 / million or less.

As an aqueous solution of iron phthalocyanine,
Phthalocyanine iron 8-carboxylic acid (final concentration 0.2-10
(0 μM) was added, and distilled water was added instead of the aqueous solution of t-butyl hydroperoxide, and the same experiment was performed.
The results are shown in Table 2. No decrease in viable cell count was observed in the absence of t-butyl hydroperoxide.

[0020]

[Table 2]

Example 3 Phthalocyanine iron 8 as an aqueous solution of iron phthalocyanine
Carboxylic acid was added to a concentration of 0.2 to 100 μM, and t-butyl hydroperoxide as an organic peroxide was added to a final concentration of 1%, and an experiment was conducted according to the above method. The results are shown in Table 3. 1% t
When -butyl hydroperoxide was added, a decrease in the viable cell count was confirmed depending on the concentration of phthalocyanine iron 8-carboxylic acid. That is, in the presence of 2 μM or more of phthalocyanine iron 8-carboxylic acid, the viable cell count was reduced to one millionth or less.

As an iron complex, an aqueous solution of hemin was added so that the concentration was 0.2 to 100 μM, and t-butyl hydroperoxide was added as an organic peroxide so that the final concentration was 1%. The experiment was performed according to the method of. The results are shown in Table 3. When 1% t-butyl hydroperoxide was added, the concentration of hemin was 5 μM.
In the above cases, the viable cell count was reduced to one millionth or less.

[0023]

[Table 3]

Example 4 An experiment was carried out according to the above-mentioned method, using phthalocyanine iron-8-carboxylic acid in an amount corresponding to a concentration of 10 μM as iron phthalocyanine and methyl ethyl ketone peroxide in a final concentration of 0 to 1% as an organic peroxide. The results are shown in Table 4. A decrease in the viable cell count was confirmed depending on the concentration of methyl ethyl ketone peroxide, and in the presence of 0.05% or more of methyl ethyl ketone peroxide, the viable cell count was reduced to 1 / million or less.

Further, an experiment was carried out in accordance with Example 4 except that distilled water was added instead of the aqueous solution of iron phthalocyanine. The results are shown in Table 4. Without addition of iron phthalocyanine, no reduction in viable count was observed at less than 0.2% methyl ethyl ketone peroxide.

[0026]

[Table 4]

Example 5 Phthalocyanine iron 8 as an aqueous solution of iron phthalocyanine
Carboxylic acid was added to a concentration of 0.2 to 100 μM, and methyl ethyl ketone peroxide as an organic peroxide was added to a final concentration of 0.1%, and an experiment was conducted according to the above method. The results are shown in Table 5.
When 0.1% of methyl ethyl ketone peroxide was added, it was confirmed that the viable cell count decreased depending on the concentration of phthalocyanine iron 8-carboxylic acid. That is, in the presence of phthalocyanine iron 8-carboxylic acid corresponding to an iron concentration of 5 μM or more, the viable cell count was reduced to one millionth or less.

As an aqueous solution of iron phthalocyanine,
Phthalocyanine iron 8-carboxylic acid (final concentration 0.2-10
0 μM) was added, and distilled water was added instead of the aqueous solution of methyl ethyl ketone peroxide, and the experiment was conducted according to Example 1. The results are shown in Table 5. No decrease in viable cell count was observed in the absence of methyl ethyl ketone peroxide.

[0029]

[Table 5]

Example 6 Phthalocyanine iron 8 was prepared as an aqueous solution of iron phthalocyanine.
Carboxylic acid was added to a concentration of 100 μM, and t-butyl hydroperoxide as an organic peroxide was added to a final concentration of 0.02 to 1%, and an experiment was conducted according to the above method at 0 ° C. It was The results are shown in Table 6. When 100 μM of phthalocyanine iron 8-carboxylic acid was added, it was confirmed that the viable cell count decreased depending on the concentration of t-butyl hydroperoxide. Ie 0.0
In the presence of 5% or more t-butyl hydroperoxide, a remarkable decrease in the viable cell count was confirmed, and in the presence of 0.2% or more t-butyl hydroperoxide, the viable cell count was one part per million.
Reduced to

Further, glutaraldehyde (final concentration 0.02 to 1%) was added as a commercially available bactericide, and the same experiment was conducted. The results are shown in Table 6. Number of viable bacteria is one millionth
A concentration of 0.5% or more was required to reduce the amount below.

[0032]

[Table 6]

Claims (2)

[Claims] 1. A compound represented by the general formula (1): (In the formula, at least one of R _{1 to} R ₈ is a carboxyl group, and the others are hydrogen atoms) A bactericide comprising iron phthalocyanine and an organic peroxide. 2. A sterilization method comprising applying a phthalocyanine iron represented by the general formula (1) and an organic peroxide to the substance.