WO2013094927A2 - Cationic antimicrobial compound and antimicrobial composition comprising same - Google Patents

Abstract

The present invention relates to a cationic antimicrobial compound and an antimicrobial composition comprising the same. More particularly, the present invention relates to an antimicrobial compound which is prepared by a method that quaternizes ammonium alkyldimethylamine by epichlorohydrin and which may exhibit superior antimicrobial activity to eumycota including viruses. The present invention also relates to an antimicrobial composition comprising the cationic antimicrobial compound.

Description

Cationic Antimicrobial Compounds and Antimicrobial Compositions Containing the Same

The present invention relates to a cationic antimicrobial compound and an antimicrobial composition containing the same, more specifically, an antimicrobial agent prepared by quaternary ammonium alkyldimethylamine with epichlorohydrin and exhibiting excellent antimicrobial activity against fungi including bacteria. A compound and an antimicrobial composition containing the same.

Antibacterial and bactericides are divided into oxidizing and non-oxidizing fungicides.

Halogenous compounds such as chlorine and bromine are mainly used as oxidizing fungicides, and they are widely used because of their strong oxidizing power and economical efficiency. However, they have a great effect on wood erosion and metal corrosion, and are easily released into the atmosphere, thereby reducing their efficacy. Since non-specific reactions occur in the biofilm formation state, they react with the polysaccharides secreted before reacting with the microorganisms that cause them, so that there is a disadvantage in that the effective bactericidal effect is lowered.

On the other hand, non-oxidizing fungicides include 3-isothiazolinone, quaternary ammonium compounds, formaldehyde releasing compounds, glutaraldehyde, etc., and these are mainly used alone, but US Patent No. 3,282,775, US Patent No. 4,107,312, EP 0217339 Hoh et al. Also illustrate sterilizing compositions in which glutaraldehyde and quaternary ammonium chlorides are combined to impart fast action and increase sterilizing power.

The hydrogen present in the quaternary ammonium compound is an ammonium (NH ₄ ⁺⁾ refers to both substituted with an organic molecule (such as an alkyl group). Quaternary ammonium compounds show good antibacterial performance over a wide temperature and pH range. Quaternary ammonium compounds form the main component of cationic surfactants, which are known to have weaker cleaning power but stronger antimicrobial performance than anionic surfactants. Representative examples of quaternary ammonium compounds, which are cationic surfactants, are benzalkonium chloride and benzethonium chloride, which are mainly used as disinfectants for hands and instruments because they are harmless to the human body and have no metal corrosion. In addition, various quaternary ammonium compounds such as polyoxyethylene trimethyl ammonium chloride and polyoxyalkyl trialkyl ammonium chloride are used for antibacterial and deodorant processing of textile products.

Quaternary ammonium compounds are known to inactivate microorganisms by adsorbing quaternary ammonium compounds on the surface of microbial cells and then spreading antimicrobial substances through cell walls and disrupting cellular membranes, releasing K ⁺ ions and cellular components such as DNA and RNA. . This mechanism is presumed to be based on the fact that the microbial cell surface is negatively charged and is cation for quaternary ammonium compounds.

Recently, research has been conducted on the difference of antimicrobial activity when developing a new quaternary ammonium compound which is easy to apply as a coating agent or more harmless to the human body, or when changing the substituent length of the compound or changing to another substituent. .

Conventional quaternary ammonium salts have an excellent instantaneous sterilization power, but have a disadvantage in that antibacterial and sterilization properties are poor.

Therefore, the problem of the present invention is to solve the problems of the conventional quaternary ammonium salt antimicrobial agent as described above and to provide an excellent antimicrobial agent with an excellent effect on not only bacteria but also fungi, and a simple manufacturing method.

In order to achieve the above object, the present inventors quaternized the alkyldimethylamine with epichlorohydrin to prepare a new type of cationic antimicrobial agent which is very economical and has excellent antibacterial performance.

The cationic antimicrobial compound of the present invention has a very simple and economical manufacturing method and excellent antimicrobial activity, and exhibits excellent antimicrobial activity against fungi.

The antimicrobial compound of the present invention is represented by the following formula (1).

Formula 1

In Formula 1, R is a C ₆ -C ₁₈ linear or branched alkyl group, alkenyl group, or a group consisting of a mixture of one or more thereof, A is CHCH ₂ (O), CHOHCH ₂ OH, CH ₂ CH: CHOH, CH ₂ CHCH ₂ (O), CH ₂ CHOHCH ₂ OH or a group consisting of one or more thereof. The carbon number of R exhibits excellent antimicrobial functionality in the range of 6 to 18, and beyond this range, the antimicrobial function is lowered.

The inventors of the present invention prepared by quaternizing the antimicrobial compound of Formula 1 by reacting alkyldimethylamine with epichlorohydrin, but the antimicrobial compound of the present invention is not necessarily produced by this method.

The reaction uses water and at least one of an organic solvent, ie ethanol, isopropyl alcohol, ethyl acetate, acetone, benzene or toluene as a solvent.

Epichlorohydrin added to the reaction uses 0.9 to 1.1 equivalents of alkyldimethylamine. The reaction works well within the equivalent range.

The reaction temperature is 0 to 90 ° C, preferably 60 to 70 ° C, and the reaction time is 1 to 15 hours. If the temperature and time are above or below the above range, the reaction may not occur properly or the reaction may proceed excessively and produce unwanted byproducts. In this case, the produced compound has a solid content of 10 to 80%, and this solid content is a cationic antimicrobial agent as a final product.

The cationic antimicrobial compound thus obtained may be included in various products such as hair products such as detergents, fabric softeners, shampoos, cosmetics, textile products or agrochemical compositions according to methods known to those skilled in the art. It is available.

In addition, the present invention includes the antimicrobial composition comprising the compound represented by the formula (1) as a right range.

The antimicrobial composition of the present invention may contain 0.001 to 99% by weight of one or more compounds represented by Chemical Formula 1 alone or an appropriately selected additive according to the purpose of use. The present invention is not particularly limited to the selective use and content of these additives, and can be appropriately adjusted according to the method of use and the dosage form at the expert level in the art. That is, the additive of the present invention may be a material included in a conventional antimicrobial agent, for example, an excipient or a diluent, and examples thereof include saline solution, buffer solution, dextrose, isoparaffin, water, glycerol, and ethanol. It is by no means limited.

The formulation of the antimicrobial agent can be appropriately adjusted according to the method of use and use, such as liquids, suspensions, granules, fragrances, powders, syrups, aerosols, extracts, ointments, induction extracts, emulsions, whole preparations, eye drops, injections, It may be a pill, a capsule, a cream, or a pill.

The antimicrobial composition of the present invention is used to inhibit the production and growth of human pathogenic bacteria, phytopathogenic bacteria, fungi, and the like, and may be used as a fabric softener, detergent, detergent, pharmaceutical, food additive, fragrance, cosmetic and pesticide composition. When used as a cleaning agent, it can be prepared by a spray, cleaning agent, shampoo, hair rinse, hair conditioner, soap, etc., wherein the antimicrobial composition may include 0.01 to 50% by weight, but is not limited thereto. When used as a medicament can be used as a disinfectant, therapeutic agent, prophylactic agent, etc. At this time, the dosage of the antimicrobial composition may be 1 to 1000 mg per day, but is not limited thereto. When used as a quasi-drug, it can be prepared as a hair regrowth, hair dye, hair removal agent, deodorant, anti-odor agent, toothpaste, and the like, wherein the antimicrobial composition may include 0.01 to 50% by weight, but is not limited thereto. When used as a food additive, the antimicrobial composition is preferably adjusted appropriately according to the type of food and the method of use, for example, it can be used in 0.0001 to 10% by weight relative to the food weight. When used as a fragrance, it may further include a volatile substance, the antimicrobial composition may be used in 0.0001 to 90% by weight. When used as a fabric softener, the antimicrobial composition may be used in 0.0001 to 30% by weight. When used as a cosmetic, the antimicrobial composition may be included in 0.0001 to 30% by weight. When used as a pesticide composition that inhibits the growth and growth of phytopathogenic bacteria or fungi, the antimicrobial composition may be included in 0.001 to 30% by weight.

Various antimicrobial compositions containing the antimicrobial compound of the present invention as an active ingredient can be easily prepared according to conventional methods and compositions by those skilled in the art to which the present invention pertains. It is not stated separately in the explanation.

Hereinafter, the configuration of the present invention will be described in more detail with reference to the following examples. However, it is apparent to those skilled in the art that the embodiments are provided only to more specifically describe the present invention, and the scope of the present invention is not limited to the description of the embodiments.

Example 1

To a flask equipped with a mechanical stirrer, a thermometer, and a condenser, 568 g of distilled water and 213 g of dimethyllaurylamine were added and mixed at room temperature, and 93 g of epichlorohydrin was slowly added thereto. After the addition, the flask was kept at 80 ° C. for about 3 hours and the reaction was terminated. Reaction confirmation was made into amine number, and reaction was terminated in 3 or less. At this time, the pH of the reaction was measured by dilution to 5% was 8.5.

Example 2

In the same apparatus as in Example 1, 568 g of ethanol and 213 g of dimethyllaurylamine were added and mixed, and 93 g of epichlorohydrin was slowly added thereto. After the addition, the reaction was terminated after maintaining at 60 ° C. for about 5 hours. Reaction confirmation was made into amine number, and reaction was terminated in 3 or less. At this time, the pH of the reaction was measured by dilution to 5% was 8.3.

Comparative Example 1

Among the commercial cationic surfactant-type antimicrobial agents, didecyl dimethylammonium chloride, which is most widely used for various purposes, was selected as Comparative Sample 1.

Comparative Example 2

Among the cationic surfactant-type antibacterial agents, benzalconium chloride, which is widely used in medical and industrial applications, was selected as Comparative Sample 2.

Comparative Example 3

Polyhexamethylbiguanide, widely used among commercial polymer type antimicrobials, was selected as Comparative Sample 3.

[Test Methods]

CTFA (Cosmetic, Toiletry, and Fragrance Association) 's microbiology guidelines and DS Orth's linear regression method was modified. Test bacteria are prepared by inoculating in a liquid medium at the appropriate time and incubating them, diluting the cultured test bacteria in a test medium, and placing them in an appropriate container in each prepared antiseptic test product for bacteria 1 × 10 ⁶ cell / ml , Fungi were inoculated to 1 × 10 ⁶ cells / ml. The inoculated product is sampled over time from immediately after the inoculation to 2 weeks after the inoculation, followed by viable cell count test and cultured for 48 hours in a 37 ° C culture device for bacteria and 72 hours in a 25 ° C culture device for fungi. Afterwards, the viable cell count was measured.

[Strains and Media Used]

Strain used in the room buoyancy test antibacterial activity of gram-positive Staphylococcus fluorescein in mouse (Staphylococcus aureus; KCTC 1621), Staphylococcus epidermidis (Staphylococcus epidermidis; KCTC 1917) and the E. coli gram-negative bacteria (Escherichia coli KCTC 1039) and Pseudomonas aeruginosa (KCTC 2004) were used, and bacterial media were TSA (tryptic soy agar) and TSB (tryptic soy broth) from Merck (Germany).

Antifungal activity has hyomoryu of Candida albicans (Candida albicans; KCTC 7270) medium for fungi was used Merck (Germany)'s PDA (potato dextrose agar), PDB (potato dextrose broth).

All the above strains were purchased from BRC.

The results according to the antimicrobial activity test is shown in Table 1 below. The figures in Table 1 are the minimum inhibitory concentrations (MIC concentrations) and are in ppm.

Table 1

Test strain	Example 1	Example 2	Comparative Example 1	Comparative Example 2	Comparative Example 3
Staphylococcus aureus	95	90	140	180	190
Staphylococcus epider.	90	90	120	180	150
Escherichia coli	90	85	135	175	190
Pseudomonas aeruginosa	80	90	150	200	220
Candida albicans	120	120	350	420	250

The two cationic antimicrobial agents prepared in Examples 1 and 2 were confirmed to be antimicrobial activity using a minimum inhibitory concentration (MIC) measurement method for various strains of Comparative Examples 1 to 3 which are commercial antimicrobials in all bacterial and fungal strains. It can be seen that it shows excellent antimicrobial activity compared to the samples, in particular compared to the conventional quaternary ammonium cationic antimicrobial agents Comparative Examples 1 and 2 it can be seen that the antimicrobial activity against fungi such as Candida albicans is very excellent. there was.

The cationic antimicrobial compound of the present invention has a very simple and economical manufacturing method and excellent antimicrobial activity, and exhibits excellent antimicrobial activity against fungi. Therefore, the cationic antimicrobial compound of the present invention can be applied to various fields such as fabric softeners, detergents, detergents, pharmaceuticals, food additives, fragrances, cosmetics, quasi-drugs or pesticide compositions.

Claims (8)

1. Cationic antimicrobial compound represented by the following formula (1).

   <Formula 1>

   

   In Formula 1, R is selected from the group consisting of C ₆ -C ₁₈ linear or branched alkyl group, alkenyl group and one or more mixtures thereof, A is CHCH ₂ (O), CHOHCH ₂ OH, CH ₂ CH: CHOH, CH ₂ CHCH ₂ (O), CH ₂ CHOHCH ₂ OH or one selected from the group consisting of mixed.
2. The method of claim 1,

   The antimicrobial compound is prepared by reacting alkyldimethylamine with epichlorohydrin in a solvent, and the solvent is at least one selected from the group consisting of water, ethanol, isopropyl alcohol, ethyl acetate, acetone, benzene, and toluene. A cationic antimicrobial compound.
3. The method of claim 2,

   The amount of epichlorohydrin is cationic antimicrobial compound, characterized in that the reaction using 0.9 to 1.1 equivalents of alkyldimethylamine.
4. The method of claim 2,

   Cationic antimicrobial compound, characterized in that the reaction temperature is 0 ~ 90 ℃ and the reaction time is 1 ~ 15 hours.
5. The method of claim 2,

   Cationic antimicrobial compound, characterized in that the solid content of the product obtained through the reaction is 10 ~ 80%.
6. An antimicrobial composition comprising at least one cationic antimicrobial compound of claim 1.
7. The method of claim 6,

   The composition is an antimicrobial composition, characterized in that the fabric softener, detergents, detergents, pharmaceuticals, food additives, fragrances, cosmetics, quasi-drugs or pesticide composition.
8. The method of claim 7, wherein

   The detergent is an antimicrobial composition, characterized in that the shampoo, soap, body cleanser.