JPH11246314A - Antibacterial agent composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition having low irritation and an excellent antibacterial property by compounding the basic amino acid adduct (salt) of a specific epoxy compound and an antibacterial agent. SOLUTION: This antibacterial agent composition contains (A) the adduct (salt) of (i) an epoxy compound of formula I [R<1> is a 8-22C linear or branched alkyl or an alkenyl; (j) is 0 or 1] to (ii) a basic amino acid and (B) an antibacterial agent. The component ii is preferably arginine, lysine, etc. The component A is preferably a compound of formula II X is H or a group of formula III; (k) is 0-5; Y is a group of formula IV [(m) is 1-5; Z is NH2 , groups of formulas V or the liked, when (k) is 0, and Y is further amino, when (k) is 1-5}. The component B is preferably benzalkonium chloride, triclosan, etc. The component A is preferably compounded in an amount of 0.01-10 wt.%. The component B is also preferably compounded in an amount of 0.01-5 wt.%, when the component B is the benzalkonium chloride or the triclosan.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a disinfectant composition, and more particularly, to a disinfectant containing (A) an adduct of a specific epoxy compound and a basic amino acid or a salt thereof and (B) a disinfectant as active ingredients. Agent composition.

[0002]

2. Description of the Related Art Conventionally, benzalkonium chloride, triclosan, and the like have been used as general-purpose germicides in the medical and hygiene fields, but these have had a problem that they are highly irritating to skin and ocular mucosa. If the compounding amount is reduced to suppress irritation, the bactericidal effect may not be sufficient, or if a sufficient bactericidal effect is to be obtained, the irritating effect is increased and the amount is limited.

[0003]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a bactericidal composition having low irritation and excellent bactericidal action.

[0004]

Means for Solving the Problems The present inventor has conducted intensive studies in view of the above situation, and as a result, when an adduct of a specific epoxy compound and a basic amino acid such as arginine or lysine is compounded in a fungicide, The present inventors have found that the stimulant of the fungicide is reduced and the bactericidal power is enhanced, and based on this finding, the present invention has been accomplished.

That is, the present invention relates to (A) the general formula (1)

Embedded image (Wherein, R ¹ is a linear or branched alkyl or alkenyl group having 8 to 22 carbon atoms, and j represents an integer of 0 or 1) and an adduct of a basic amino acid Or a fungicide composition comprising a salt thereof and a fungicide (B) as active ingredients.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail.

In the fungicide composition of the present invention, the adduct of the epoxy compound (A) and the basic amino acid is highly safe and has a bactericidal activity, but the bactericidal activity is slightly insufficient by itself. By using this in combination with the bactericide of the component (B), there is an advantage that the bactericidal power is enhanced and skin irritation caused by the bactericide of the component (B) is reduced.

[0008] The adduct of the epoxy compound and the basic amino acid as the component (A) may be prepared by adding one to four molecules, preferably one molecule, of the epoxy compound to one molecule of the basic amino acid under a alkaline condition. It can be easily produced by reacting in a hydrophilic organic solvent such as a polyhydric alcohol or a mixed solvent of these hydrophilic organic solvents and water. In addition, when j is 0 in the above general formula (1), it indicates an epoxy alkane, and when j is 1, it indicates a glycidyl ether. For the reaction between the epoxy alkane and an amino acid, see, for example, 4
No. 8-22417.

In the adduct of the epoxy compound of the general formula (1) and a basic amino acid, from the viewpoint of solubility, j
Is more preferably an adduct of a glycidyl ether with a basic amino acid than an adduct of an epoxyalkane with a j of 0 with a basic amino acid.

The glycidyl ether wherein j is 1 in the general formula (1) can be obtained, for example, by reacting a saturated or unsaturated higher or higher alcohol having 8 to 22 carbon atoms with epichlorohydrin.
Specific examples thereof include decyl glycidyl ether, dodecyl glycidyl ether, tetradecyl glycidyl ether, stearyl glycidyl ether, and the like, each of which may be a single composition or a mixture of two or more in any proportion. There may be. The representative examples of industrially available glycidyl ethers are given below by trade names.

"Epiol L-4" manufactured by NOF Corporation
1 "(decyl glycidyl ether)," Epiol S
K ”(stearyl diglycyl ether), AC
"Heroxy 8" (mixture of dodecyl glycidyl ether and tetradecyl glycidyl ether) manufactured by I Japan Limited, "Denacol EX-192" (mixture of dodecyl glycidyl ether and tetradecyl glycidyl ether) manufactured by Nagase Kasei Kogyo Co., Ltd. And "SY-25L" (mixture of decyl glycidyl ether and dodecyl glycidyl ether) manufactured by Sakamoto Pharmaceutical Co., Ltd.

The epoxy alkane in which j is 0 in the general formula (1) includes, for example, those of the “AOEX” series manufactured by Daicel Chemical Industries, Ltd.

As the basic amino acid, any of natural and synthetic amino acids can be used. For example, arginine, lysine, ornithine, histidine, hydroxylysine, α,
Among them, γ-diaminobutyric acid and the like are preferable, and arginine and lysine are preferable, and arginine is particularly preferable. Further, any of D-form, L-form and DL-form can be used.

Among the basic amino acids, for example, in the case of lysine and ornithine, the binding site with the epoxy compound is considered to be preferentially located at the highly reactive ω-amino group, but reacted with the α-amino group. It may be something. Further, a compound in which two molecules of the epoxy compound have reacted with either the ω-amino group or the α-amino group may be used. Further, one molecule is added to each of the ω-amino group and the α-amino group.
It may be a compound that has reacted (total of two molecules) or a compound in which three or four epoxy compounds are added to one basic amino acid molecule.

In the reaction between the epoxy compound and the basic amino acid, it is preferable to use the basic amino acid as an alkali metal salt or to react it under alkaline conditions in order to increase the reactivity and prevent side reactions. However, arginine may be reacted without using these conditions.

As a reaction solvent, a hydrophilic organic solvent such as a lower alcohol or a polyhydric alcohol is used. Examples of lower alcohols include methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, and n-butyl alcohol. Examples of polyhydric alcohols include glycerin, 1,3-butylene glycol, propylene glycol, and dipropylene. Glycol and isoprene glycol. These hydrophilic organic solvents may be used alone or in a mixture of two or more kinds at any ratio. Of course, different types of lower alcohol / polyhydric alcohol mixtures may be used. In order to increase the solubility of the basic amino acid, it is more preferable to use a mixed solvent of these hydrophilic organic solvents and water. The mixing ratio between the hydrophilic organic solvent and water differs depending on the types of the basic amino acid and the epoxy compound, and is not uniformly determined. However, usually, the hydrophilic organic solvent: water = 10: 0 to 1: 9, preferably The range is from 1: 1 to 9: 1. If the ratio of the hydrophilic organic solvent is low, the solubility of the epoxy compound is low,
The reaction rate is significantly reduced.

The reaction temperature varies depending on the type and composition of the reaction solvent.
0-100 ° C, preferably in the range of 80-95 ° C,
In the case of ethyl alcohol, the temperature is usually 60 to 78 ° C, preferably 70 to 78 ° C, and the reaction is preferably performed under reflux. The method of adding the epoxy compound may be added all at once before heating, or may be added in divided or continuous manner (continuous dropping) after the start of heating. It is preferable to continuously drop the solution later.

The addition product obtained by the reaction between the epoxy compound and the basic amino acid is not usually a single compound, but one molecule of the basic amino acid and one molecule of the epoxy compound.
It is a mixture of a substance with added molecules and a substance with two or more molecules added. These mixtures may be isolated and purified into single compounds by, for example, chromatography, and then one or more of them may be used as the component (A) in the fungicide composition of the present invention, or may be used as a mixture. May be. Further, it may be a reaction mixture in which unreacted basic amino acids remain.

In a product in which a plurality of epoxy compounds are added to one molecule of a basic amino acid, that is, two or more molecules are added,
The chain length of the plurality of added epoxy compounds may be the same,
Alternatively, they may be different. When the reaction is carried out using a mixture of epoxy compounds having different chain lengths, the resulting composition is usually a mixture of those having the same chain length and those having different chain lengths. These may be isolated and purified for each single compound as described above, or may be used as a mixture without isolation and purification.

When the reaction is carried out using a mixture of glycidyl ether and epoxy alkane as the epoxy compound, the resulting composition usually contains a type in which both glycidyl ether and epoxy alkane are added within the same basic amino acid molecule. Stuff is included. These compounds may, of course, be isolated and purified for each single compound as described above, or may be used as a mixture without isolation and purification.

The reaction mixture obtained by reacting the epoxy compound with the basic amino acid may be used without any purification treatment as it is, or may be purified to such an extent that the reaction solvent is distilled off if necessary. Can be used as the component (A) in the fungicide composition of the present invention. For example, ethyl alcohol, 1,3-butylene glycol, which is often used in a disinfectant composition as a reaction solvent,
When propylene glycol or the like is used, these may be contained in the reaction mixture as long as the effects of the present invention are not impaired.

As described in detail above, various addition products can be produced in accordance with the number of molecules of the epoxy compound added to one molecule of the basic amino acid. If shown, the following general formula (2)
Can be indicated by

[0023]

Embedded image (Wherein, R ¹ and j are as defined above, X is a hydrogen atom or a substituent represented by the following general formula (3), k is an integer of 0 to 5, provided that when k is 0, Represents a substituent represented by the following general formula (4), and k represents 1 to 5
When the integer is Y represents an amino group)

[0024]

Embedded image (Wherein, R ¹ and j are each as defined above)

[0025]

Embedded image (In the formula, m represents an integer of 1 to 5, and Z represents any of the following substituents (I) to (IV).)

[0026]

Embedded image

Examples of the salt of an adduct of the epoxy compound represented by the general formula (1) and a basic amino acid include hydrochloride, hydrobromide, sulfate, phosphate, nitrate, carbonate and the like. Inorganic, acetate, citrate, lactate, glycolate, malate, p-toluenesulfonate,
Tartrate, salts of glutamic acid and its derivatives, salts of aspartic acid and its derivatives, and organic acid salts such as pyrrolidone carboxylate can be used. These can use any optical isomer. Particularly preferred salts include hydrochloride, hydrobromide, pyrrolidonecarboxylate, citrate, lactate, glycolate, glutamate, and aspartate.

The fungicide which is the component (B) in the fungicide composition of the present invention includes benzalkonium chloride, benzethonium chloride, triclosan and alkyldiaminoethylglycine hydrochloride, preferably benzalkonium chloride and triclosan. And particularly preferred is triclosan. These fungicides may be used alone or in combination of two or more.

The amount of the component (A) in the fungicide composition of the present invention is preferably 0.01 to 10% by weight, more preferably 0.1 to 5% by weight, and particularly preferably 0.2 to 1% by weight. %. If the amount is less than 0.01% by weight, the effect of the present invention may not be sufficiently exhibited. If the amount exceeds 10% by weight, a slimy feeling to the skin may occur.

With respect to the amount of component (B) in the fungicide composition of the present invention, for example, in the case of triclosan and benzalkonium chloride, it is usually 0.01 to 5% by weight, preferably 0.05 to 0.5% by weight. %, Particularly preferably 0.1
Used in the range of .about.0.5% by weight.

The mixing ratio of the components (A) and (B) varies depending on the type of fungicide. For example, in the case of triclosan and benzalkonium chloride, (A) :( B) =
The ratio is 1:10 to 10: 1, preferably 1: 5 to 10: 1, and more preferably 1: 2 to 5: 1.

The germicidal composition of the present invention can be used for hand wiping, wet tissue, hand soap, mouthwash, toothpaste,
It can be used as various disinfectants such as body shampoos, pediatric hygiene products, geriatric hygiene products, sanitary products, and medical disinfectants.

In the fungicide composition of the present invention, various commonly used additives can be added as long as the effects of the present invention are not impaired. Examples of additives include surfactants such as anionic surfactants, cationic surfactants, amphoteric surfactants and nonionic surfactants, waxes, vegetable oils, animal fats and oils, natural fats and oils derivatives, mineral fats and oils. , Lower and higher fatty acid esters, synthetic oils such as N-acylglutamic acid esters, silicone compounds, polymer substances, alcohols, polyhydric alcohols, animal and plant extracts, amino acids, nucleic acids, vitamins, enzymes, anti-inflammatory agents, preservatives , Antioxidants, ultraviolet absorbers, chelating agents, antiperspirants, oxidation dyes, pH adjusters, pearlizing agents, wetting agents, etc., cosmetic raw material standards, cosmetic varieties, quasi-drug raw materials standards, Japanese Pharmacy And ingredients described in various official documents such as the Japanese Pharmacopoeia Standards for Pharmaceutical Ingredients and the Official Standards for Food Additives.

[0034]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Production Example 1 45.9 g (0.26 mol) of L-arginine, 29.2 g of water and 42.2 g of ethanol were added to a three-necked round bottom flask, and the mixture was heated, refluxed, stirred and dispersed at 75 ° C. "Heroxy 8" (trade name, manufactured by AC Japan Limited; a mixture of dodecyl glycidyl ether and tetradecyl glycidyl ether 3: 1)
73.6 g (0.29 mol) was added dropwise over 3 hours,
The mixture was further stirred for 3 hours. After confirming the disappearance of glycidyl ether by TLC and gas chromatography, the mixture was cooled to 40 ° C. or lower, and 18.6 g of 35% hydrochloric acid was added.
(0.18 mol), 35% hydrochloric acid was further added, and p
H was adjusted to 5.2. Subsequently, freeze-drying was performed to obtain about 125 g of a solid.

Test Example 1: Primary irritation test on skin The primary irritation to skin was measured by the following test method.
Table 1 shows the results. Four New Zealand White male rabbits were patch-adhesed with a patch test patch soaked with 0.3 ml of a 1% test compound aqueous solution for 24 hours, and 24 hours after removal of the patch, the irritation was evaluated according to the Draize's evaluation criteria. Judged.

[0037]

[Table 1]

Test Example 2: Test of bactericidal activity A test solution having the composition shown in Table 2 (expressed as pure weight%, total amount 100) was prepared, and Escherichia coli (Escher) was prepared by the following method.
ichia coli ATCC 8739). The results were as shown in Table 2.

(1) Preparation of test bacterial solution: The test bacteria are cultured in a normal broth medium at 35 ° C. for 20 hours. (2) Preparation of agar medium for stamp: 400 ml of desoxycholate agar medium was poured into a stainless steel vat (200 × 260 × 45 mm) and solidified on a flat plate. (3) Pretreatment of the palm: The palm was thoroughly washed with soap and tap water, drained, sprayed with 70% ethanol, and dried with a dryer for 30 seconds. (4) Smearing of the test strain: 0.2 ml of the test solution (approximately 2500 bacteria) was dropped on the palm of the pretreated palm, mixed well with both hands, and spread over the entire surface for about 10 seconds. (5) Treatment of the test solution: 10 ml of the test solution was dropped on the palm coated with the bacterial solution, mixed well for 15 seconds with both hands, rinsed with tap water for 15 seconds, drained, and dried with warm air of a dryer for 30 seconds. Dried and strongly stamped left hand on Desoxycholate agar medium. (6) Treatment only with water washing: The palm coated with the test bacterial solution was rinsed with tap water for 15 seconds, and dried and stamped in the same manner as described above. (7) Culture and judgment: stamped agar medium at 35 ° C.
After culturing for 24 hours, the number of grown red colonies was counted, and judgment was made according to the following criteria.

[0040]

[Table 2]

[0041]

The germicidal composition of the present invention has low skin irritation and excellent germicidal activity, so it can be used for hand wipes, wet tissues, hand soaps, mouthwashes, toothpastes, body shampoos, and pediatric hygiene products. It can be suitably used as various disinfectants such as hygiene products for the aged, sanitary products, and medical disinfectants.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A01N 33:12)

Claims (3)

[Claims] (A) General formula (1) (Wherein, R ¹ is a linear or branched alkyl or alkenyl group having 8 to 22 carbon atoms, and j represents an integer of 0 or 1) and an adduct of a basic amino acid Or a fungicidal composition comprising a salt thereof and (B) a fungicide as active ingredients. 2. The fungicidal composition according to claim 1, wherein the basic amino acid in the component (A) is arginine and the fungicide in the component (B) is benzalkonium chloride or triclosan. 3. The adduct of an epoxy compound and a basic amino acid is a compound represented by the following general formula (2).
The bactericide composition according to any one of the preceding claims. Embedded image (Wherein, R ¹ and j are as defined above, X is a hydrogen atom or a substituent represented by the following general formula (3), k is an integer of 0 to 5, provided that when k is 0, Represents a substituent represented by the following general formula (4), and k represents 1 to 5
When the integer is Y represents an amino group) (Wherein, R ¹ and j are the same as defined above) (In the formula, m represents an integer of 1 to 5, and Z represents any of the following substituents (I) to (IV).)