JPH03161403A - Antibacterial and antifungal agent composition - Google Patents

Abstract

PURPOSE:To provide the subject composition employed for coatings, leather, wood, fiber products, etc., by containing chlorhexidine and a compound selected from trihalogenated phenols, diphenyl sulfides and phenylphenols as active ingredients. CONSTITUTION:The subject composition contains a compound of formula I or a salt thereof and a compound selected from compounds of formulas II, III and IV [M<1>-M<3> are H or alkali (ne earth) metal atom; X<1>-X<3> are halogen; and X<4>-X<6> are H or halogen] in a wt. ratio of 1/10-10/1. All the compounds are useful as antibacterial agents or antifungal agents but the simultaneous employment thereof gives a synergistic activity. The above-mentioned active ingredients are combined with a slid or liquid carrier or diluent and prepared into a preparation shape such as a water-dispersible agent, powder, tablet, emulsion, paste or spraying agent. The composition is employed as an antifungal agent for citrus fruits.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel antibacterial and antifungal composition, and more particularly, it is useful for household or various industrial products, such as wood products, paints, leather products, pastes, cosmetics, paper products, or The present invention relates to an antibacterial and antifungal agent combination that can be used to control bacteria and fungi that are parasitic or attached to raw materials or during the manufacturing process thereof.

Various antibacterial agents and antifungal agents are used to protect household goods or various industrial products from damage caused by bacteria and mold. In addition, for the purpose of increasing the antibacterial power and antifungal properties and/or expanding the range of applications, two or more types of antibacterial and/or antifungal agents have been conventionally combined to improve the antibacterial and antifungal properties. Attempts have been made to expand the antibacterial and antifungal vectors, but in many cases the effect is only the arithmetic average of the effects of each drug.

The present invention provides (^) chlorhexidine or a salt thereof, and (B) l) the following formula x' Trihalogenated phenols, which are the same or different and each represents a halogen atom; 2) In the following formula, M2 represents a hydrogen atom, an alkali metal atom, or an alkaline earth metal atom, and X4 represents a hydrogen atom or a halogen atom. and 3) diphenyl sulfides represented by the following formula, where Ms represents a hydrogen atom, an alkali metal atom or an alkaline earth metal atom, and xm provides a bactericidal and fungicidal composition containing as an active ingredient at least one compound selected from the listed phenylphenols representing a hydrogen atom or a halogen atom. be.

In the antibacterial and antifungal composition provided by the present invention,
The compounds used as (^) Bokubun and (B) Bokubun are both known as antibacterial or antifungal agents, but
It has been found that by using both in combination, a synergistic antibacterial and antifungal effect can be obtained which is completely unexpected from the use of each of these ingredients alone.

Hereinafter, the antibacterial and antifungal composition of the present invention will be explained in more detail.

Karikurotan: Chlorhexidine used in the composition of the present invention is a compound represented by the following formula, and its salts include, for example, gluconate, hydrochloride, acetate, and the like.

Chlorhexidine or its salts exhibits excellent antibacterial activity against bacteria, fungi, molds, etc., and is useful as a disinfectant for the skin and medical equipment, or as a preservative for drug preparations such as creams, ointments, and It is included in small amounts in eye drops, etc.

l) The trihalogenated phenol represented by the formula (I) can be used as an industrial fungicide for water-based paints, slime control in paper manufacturing, agricultural soil treatment agents, and wood preservatives. It is an antibacterial and antifungal compound that is used as a bactericidal and antifungal preservative, such as:
For example 2,4,6-trichlor7enol, 2.4.6
-}ribromophenol, 2,4-dichloro-6-bromophenol, 2-chloro-4,6-dibromophenol, and the like.

2) Specific examples of the diphenylsul7ides represented by the formula (I
id), 7-enthychlor (5.5'dichloro-2.2'
-dihydroxydi7enylsulfyl'), 2.2'
-dihydroxy7enyl sulfide, 4,4'-dihydroxydiphenyl sulfide, and the like.

The above-mentioned bithionol is known as a compound that has antibacterial effects against bacteria and fungi, such as preventing the growth of Staphylococcus aureus, exterminating dystomia and rodents in the lungs, liver, and intestines, preventing the growth of algae, and coating the bottom of ships. It is widely used as a preservative for rubber products and water-soluble polishing fluids.

Moreover, the above-mentioned fentychlor is a compound developed as an anti-infective and anti-fungal agent for external use.

3) Specific examples of the 7-enylphenols represented by the formula (II) include 2-phenylphenol, 4-phenylphenol,
-phenylphenol, 4-chloro-2-phenylphenol, 2-chloro-4-7dynylphenol and the like.

These 7-enylphenols have a wide antibacterial spectrum against bacteria, yeast, filamentous fungi, etc.
Cleaning agents, preservatives for mold and mildew of wood, cutting oil, leather, adhesives, paper, fibers, wax, etc., mold-proofing agents for citrus fruits,
It is used as such.

Blend: The compound of the present invention contains chlorhexidine or its salt as the component (^) and the formula (I) as the component (B).
), (II) and (I[I) It can be prepared by combining one or more of the compounds represented by I.

(^) The blending ratio of Bokubun and (B) component may be changed depending on the use of the composition of the present invention, but in general, (8) Bokbun/
(B) Component weight ratio: 200/l-1/200
, preferably l/40 to 40/1, more preferably 1
It can be within the range of /10 to 10/1.

When the composition of the present invention is used, it can be combined with a solid or liquid carrier or diluent to formulate it into a solid, semi-solid or liquid formulation, depending on the purpose of use. The carrier or diluent that can be used in this case can be selected from carriers or diluents commonly used for antibacterial agents or antifungal agents, depending on the desired dosage form, etc.

Specifically, such carriers or diluents include, for example,
Emulsion carriers such as acrylic acid emulsions and vinyl acetate emulsions; carriers such as plastic compounds such as polystyrene and polyvinyl chloride; aqueous diluents such as distilled water, phosphate buffered saline, and physiological saline; isopropyl alcohol, Examples include organic solvent diluents such as xylene, dimethylformamide, and dimethylsulfur oxide.

Further, the composition of the present invention may contain a spreading agent, a stabilizer, a dispersant, a wetting agent, a penetrating agent, a suspension improver, etc., if necessary. Furthermore, other medicinal ingredients such as bactericides, insecticides, and deterioration inhibitors may be added.

The Kumikaimono of the present invention can be prepared in the form of a permanent preservative, powder, tablet, emulsion, paste, spray, etc. When used, it may be used depending on the subject, purpose, etc. It can be applied as is or diluted to an appropriate concentration.

Thus, the antibacterial and antifungal composition of the present invention can be used, for example, in paints, leather, wood (bamboo) products, pastes, textile products, paper products,
Advantageously used to prevent the generation or growth of harmful microorganisms that parasitic or adhere to these products by mixing or impregnating them into various household or industrial products such as wall materials and plastic products, or by treating the surfaces of these products. can do.

Hereinafter, the present invention will be explained in more detail with reference to test examples and examples, but the scope of the present invention is not limited in any way by these examples.

Test Example 1: Two-way minimum inhibitory concentration test using agar dilution method (^): Chlorhexadine gluconate (hereinafter referred to as "
Aqueous solution of ``Hibiten''), effective concentration = 5, 10, 20, 30, component (B) 50, 100, 200, 500, and 1000 ppm: 2, 4.64 Ethanol solution of chlorphenol, active ingredient concentration : 20, 50, 100 200, 400, 800, 1000 1500 and 2 0 0 0 ppm ■Ethanol solution of Vicinol, active ingredient concentration: 20, 50, 100 200, 400, 800, 1000 1500 and 2 0 0 0 ppm ■ Ethanol solution of fentychlor, effective concentration: 100, 200, 400, 600, 800, 1000 2 0 0 0, 3 0 0 0 and 5 0 0 0
ppm 2-phenylphenol ethanol solution active ingredient concentration: too, 200, 400, 600, 800, 1000 2 0 0 0.3 0 0 0 and 5000 ppm
Effective concentration of 4-phenylphenol in ethanol solution: 100, 200, 400, 600, 800, 1000, 2000, 3000 and 5000 ppm 4-chloro-
2-7 Concentration of active ingredient in ethanol solution of di-2-2-phenylphenol: 10, 20, 50, 100, 200, 400, 600, 800 and lo00 ppm ■2-1 Effective concentration of ethanol solution of lo-lo 4-phenylphenol: 10, 20, 50, 100, 200, 400, 600, 800 and l O 0 0 ppm Dispense the above drugs (^) and (B) into a bed dish with a diameter of 9 cm to O - 1 mQ, and add the following to it. Kumiaki: Peptone 11 Glucose 409 Agar 20,? Water Dissolve 10 md of iQ Sabouraud agar medium by heating and add, stir well and mix.
Let it solidify and form a flat plate.

A spore solution containing 105 spores/mQ is prepared according to the method of JIS Z-2911, and 0.01 mQ each of this is inoculated onto the above-mentioned flat agar plate using a microbreaker. 2
After culturing at 8°C for one week, observe whether or not there is growth of bacteria.
Determine the binary minimum inhibitory concentration.

Ii minutes (B). ! The results of the measurement of the binary minimum inhibitory concentration in the case where 4-7enyl 7enol is used are
It is shown in the table and Figure 1. (A) to (H) of the first rgJ are
In both cases, the dual minimum inhibitory concentration (TDMIC) curves are far below the diagonal line shown by the dashed line, which indicates that the combination of 4-phenylphenol and chlorhexicine has a synergistic effect. It is shown in

In addition, as shown in Figure 2, the strength of the synergistic effect (Sl value) is Tr'lM T centered on the origin in square coordinates.
It is a strong value for C-curved L-ko versus Oro-Hai-sen's zakai↑夷h.

In other words, the smaller the Sl value, the more precepts (
The synergy between A) and (B) is strong, indicating that small drug concentrations have a large effect.

Table 2 below summarizes the calculation results of the Sl values.

T: 2.4.6-Trichlorophenol B: Bithionol F: Fenthichlor○; 2-phenylphenol P: 4-7enyl 7enol C10: 4-chloro-2-phenylphenol CIP:
2-k. Rollo 4-phenylphenol Test Example 2 A drug solution containing the same components (^) and (B) as used in Test Example 1 at a predetermined concentration was placed in a Petri dish with a diameter of 9 cm. l
Dispense to rnQ, add the following group V: Yeast extract 2.52 Peptone 5.02 Glucose 1.02 Agar 15.02 Water tQ standard agar medium 10 ml dissolved by heating, stir well and mix.
Let it solidify and form a flat plate.

A spore liquid containing 1010 spores/rnQ was prepared in the same manner as in Test Example 1, and it was spread onto the above agar plate using a micrograter. Inoculate 2 Qlml each. 3
After culturing at 7°C for 48 hours, the presence or absence of bacterial growth is observed and the binary minimum inhibitory concentration is determined.

Table 3 and FIG. 3 show the results when 4-phenylphenol was used as component (B). Table 4 shows the results of measuring the strength of the synergistic effect (value 51).

Example Examples of formulations of the composition of the present invention are shown below.

Formulation No. l Formulation No. 22
, 4.6- Trichlorophenol 202 Caustic soda 4. lJ 2-chloro-4-phenylphenol caustic soda 202 3.92 Chlorhexidine gluconate 5 2 Chlorhexidine gluconate surfactant 10 2 Surfactant 52 10 1 Formulation No. 3 Formulation No. 4 2-7 enylphenol 202 Caustic soda 4.72 Bithionol 202 Isoglobil alcohol 5.52 Chlorhexidine gluconic acid surfactant Chlorhexidine noreconic acid 52 10 1 Surfactant 59.52 5 Total 100 N formulation NO. 5 2.4.6- }Lichlorophenol 202 Bithionol lO2 Caustic soda
6,3l chlorioxidine gluconic acid 5 surfactant 10 2 isopropyl alcohol 48.7 total
ioo i

[Brief explanation of the drawing]

FIGS. 1 and 3 are graphs showing the relationship between the drug composition and the secondary minimum inhibitory concentration measured in Test Examples 1 and 2. Moreover, FIG. 2 is a graph showing the strength of the synergistic effect (Sl value). (+-A) Figure "T! (+-C) (+-D) (1-E) 1 Figure 2 (+-F) (+-H) (3-D) ) (3-8 ) (3-C)

Claims (1)

[Claims] (A) Chlorhexidine or its salt; (B) 1) The following formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) In the formula, M^1 is a hydrogen atom, an alkali metal atom, or an alkali represents an earth metal atom, and X^1, X^2 and X^3 are the same or different and each represents a halogen atom; 2) Trihalogenated phenols represented by the following formula ▲ Numerical formula, chemical formula, table, etc. ▼(II) In the formula, M^2 represents a hydrogen atom, an alkali metal atom, or an alkaline earth metal atom, X^4 represents a hydrogen atom or a halogen atom, and X^5 represents a hydrogen atom or a halogen atom. Diphenylsulfides represented by, and 3) The following formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (III) In the formula, M^3 represents a hydrogen atom, an alkali metal atom, or an alkaline earth metal atom, and 6 represents a hydrogen atom or a halogen atom, and at least one compound selected from the phenylphenols represented by the following as an active ingredient: An antibacterial and antifungal agent composition.