JPH03141202A - Method and composition for destroying micro- organisms or preventing growth thereof - Google Patents

Abstract

PURPOSE: To effectively disrupt or restrain the growth of harmful microorganisms in an environment contaminated or liable to be contaminated with the harmful microorganism, by bringing a lethal or effectively restraining amount of a specific antimicrobial glycol ether into contact with the above harmful microorganism. CONSTITUTION: Growth of harmful microorganism in an environment contaminated or liable to be contaminated with the harmful microorganisms is disrupted or restrained by bringing a lethal or effectively restraining amount of an antimicrobial glycol ether of the formula (R is an alkyl, aryl, arylalkyl or aryloxyalkyl) (e.g. 2-n-butoxy-1-butanol, 2-n-hexyloxy-1-butanol) into contact with the above harmful microorganisms. For example, the compound of the formula is used for controlling the deterioration of cosmetics due to harmful microorganism (esp. as a disinfectant or antiseptic). The compound of the formula has a broad active spectrum, also raises its activity synergistically with other bactericides.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to methods and disinfectant and preservative compositions for destroying or inhibiting the growth of harmful microorganisms.

Disinfectants based on heptano and/or social aldehydes which also contain alkyl alkanols with the general formula % are DE-PS 2
Known from No. 5 16 670: It is used in formulations, especially as aqueous disinfectants, due to its sometimes penetrating properties, its characteristic odor of alkylalkanols, and its low solubility in water. Its use is limited by the limited amount it can produce, and its compatibility with other drugs and poor stability in the solutions used.

Aqueous disinfectants based on alcohol have also been known for a long time, but have the most diverse disadvantages. They are antimicrobially active compounds of relatively inert nature and have little interaction with the components of the formulated composition. As with other classes of active compounds, they differ in their actions depending on their chemical structure. Certain properties further limit their potential practical applications: odor, volatility, flammability, and low water-solubility.

Low grade? Alcohols (ethanol, impropanol, and tortoise-propanol) have sufficient bactericidal or microbicidal activity for disinfection purposes only at concentrations of about 40% or higher, depending on their chemical structure, and therefore in practice at high concentrations. Can only be used in compositions of

Their preservative and microbicidal action is significantly reduced at active compound concentrations below 15%.

Other alcohols with known antimicrobial activity, such as benzyl alcohol, 2-phenoxyethanol and phenethyl alcohol, are significantly more effective. The limit of activity of these compounds lies at an active compound concentration of about 1%. Because of the characteristic odor and limited water-solubility, this leads to formulation problems for the concentrate and a reduction in the odor value of the use solution.

Other highly active alcohols, such as 2-ethylhexanol or 2,4-dichlorobenzyl alcohol, are actually used because of their penetrating and characteristic odor, or because of their unique properties in human toxicology and ecological environmental toxicology. Either they cannot be used because they are unacceptable from a point of view, or they can only be used in very limited amounts in combination with other classes of active compounds.

Therefore, it has a weak or mild odor, has adequate water solubility, and is good for disinfection and preservation, which is also evaluated to be acceptable from the viewpoint of human toxicology and ecological toxicology. It is desirable to have an alcohol with strong antimicrobial properties.

Both the formulated disinfectant concentrate and the diluted solution for use have a mild odor that is virtually imperceptible, and are also environmentally compatible and provide the user with a racially practical solution. solution,
It has a mild odor as well as good water-solubility, while
It would be desirable to provide disinfectants and preservatives that allow the use of higher concentrations of active compounds, such as those required in problem areas, for example areas contaminated with contaminants.

According to the present invention, there is provided a method for destroying or inhibiting the growth of harmful microorganisms in an environment contaminated with harmful microorganisms or easily contaminated with harmful microorganisms. contacting said environment with a lethal or inhibitory effective amount of an antimicrobial glycol ether.

However, in the above formula, R is: 1) a linear, branched, or cyclic alkyl group having 4 to 12 carbon atoms, and the alkyl chain may be interrupted by up to two oxygen atoms; b) an aryl group having 6 to 12 carbon atoms, the aryl nucleus of which may be substituted with one or more lower alkyl, lower alkoxy or halogen groups; or C) an aryl group having 6 to 12 carbon atoms; 7 to 13 arylalkyl or aryloxyalkyl, the alkyl chain may also be interrupted by up to two oxygen atoms, and the aryl group is substituted by 6 lower alkyl, lower alkoxy, chloro or bromo groups; It's okay.

Both the lower alkyl and lower alkoxy groups mentioned above have 1 to 4 carbon atoms.

Surprisingly, it has been discovered that the disinfectants and preservatives according to the invention not only have an outstandingly broad spectrum of action, but also synergize with other known bactericidal compounds to increase their action.

In addition to the microbial activity, the detersive power of the alcohol used according to the invention is a further advantage. Based on their lipophilicity and solubility, these alcohols have the ability to penetrate into and dissolve organic contaminants. The superior microbial activity of glycol ethers is probably also due to their good penetration into organic structures (for example into the cell walls of microorganisms). These compounds, in combination with the aldehydic, cationic, and phenolic compounds according to the invention, thus exert a preparatory effect on cellular components to the extent that they result in a synergistic increase in the action under the permeation-enhancing influence of the glycol ethers. It can give destructive power.

The solubilizing properties of the glycol ethers used according to the invention also make it easier to incorporate less water soluble formulation ingredients into disinfectants or preservatives.

Phenol glycol heptanoethers prepared from alkylene oxides and phenolic compounds in aqueous solution at a temperature of 20-130 °C and a pressure of 0-5 bar in the presence of water-soluble alkali metal salts or alkaline earth metal salts are FR- P.S.
No. 1,386,347, which is used in antiparasitic agents, and aqueous disinfectants are not disclosed there.

Some of the glycol ethers used in disinfectants according to the invention are further described in Preparation of Fungicidal Triazole Compounds, Chemical Abstracts Vol. 106, 98097.
As an intermediate product for organic synthesis for
32228, Vol. 65, 45704), and furthermore, bile excretion promoters and anticonvulsants (Chemical Abstracts Vol. 82, 139302m, 139303n,
139306r, 111568d). However, there is no indication that they are suitable as disinfectants and preservatives.

The glycol ethers and alcohols present in the disinfectant according to the invention have a wide range of actions, such as action against Durham-positive and Durham-negative bacteria, fungi, yeasts, molds, mycobacteria and viruses. Yes, and is particularly selected for its activity against Durham-negative bacteria, fungi, mycobacteria, and viruses. They have both pathogen-inhibiting and bactericidal properties. Activity appears in the suspension and on the area. Due to their volatility, activity through the gas phase is also possible.

The solubility of the compounds used plays a further important role. Thus, good water-solubility, together with good antimicrobial activity, facilitates the formulation of concentrates and is advantageous for the stability of working solutions and concentrates. The required amount of solubilizing additives, solvents and emulsifiers can be significantly reduced, resulting in cost savings and better compatibility with the environment.

Compounds of formula (I) can be used in combination with compounds of general formula R-0-CH2.CHOH-CzHs (II).

The solubility of the compound of general formula (I) in water is
I), for example 2-phenoxy-1-
The solubility of butanol (C,.H+40z) in water is 0.
The solubility of 1-phenoxy-2-butanol (C1oH140□) in water is greater than 5% and less than 0.6%, and the solubility in water is greater than 0.3% and less than 0.4%. In contrast, for example, 2-ethylhexanol (CaH+
aO) has a very good bactericidal action even at high dilutions, but has a pungent odor and a solubility in water of only more than 0.02% and less than 0.05%.

The good microbial activity of the preparation according to the invention is due to the
Ethanol or phenoxypropanol, approximately 86% 1
This contrasts well with known biocide alcohols, such as commercially available mixtures of -phenoxy-2-propatol and about 14% 2-7 enoxy-1-propatol.

Particularly preferred are dL compounds which contain, in addition to the compound of general formula (D), a compound of general formula (II), particularly at least 20% of the former, but compounds containing 5% or more of the former are also satisfactory.

The alcohols according to the invention can also be used both as individual substances and as mixtures.

Disinfectants and preservatives based on the present glycol ethers of the invention are suitable for use on the one hand with aldehyde compounds, phenolic compounds and cationic compounds that act synergistically with them, such as formaldehyde, geltalodialdehyde, succinic dialdehyde, glyoxal, glyoxylic acid. or parachlorometacresol, 0-phenylphenol, O-benzylparachlorophenol, 2,6-dimethyl-4-bromophenol, thymol, eugenol, parahydrobenzoic acid and their salts, methyl-, ethyl-, pro- and ru-, Butyl- and benzyl-bara hydroxybenzoic acid esters and their salts or benzalkonium chloride, didecyldimethylammonium chloride, didecylmethyl-2-hydroxyethylammonium chloride, dodecylguanidinium acetate, polyhexamethylene biguanide salt, coconut propylene A very small amount of diaminenidinium diacetate and octenidine salt, etc.
Or it can be contained in a normal amount. On the other hand, they may also contain other known active compounds, such as alcohols such as phenoxyethanol or phenoxydibrobanol, active oxygen compounds such as H20□, acids such as food acids, benzoic acid or sorbic acid. It can also include preservative carboxylic acids such as. Furthermore, they can contain customary additives such as surfactants, wetting agents, emulsifiers, fragrances, colorants. P of the formulation! (2) can be adjusted to acidity, neutrality, or alkalinity using a conventional method.

The invention will be explained in more detail below using Examples.

Example 1 To prepare 2-phenoxy-1-butanol, 25
132°2c (
0.75 mol) of 2-phenoxybutyric acid in 23.5 ((0.62 mol) L) in 250 ml of tetrahydrofuran.
It was added dropwise to iA IH4 at 30°C or lower. The mixture was stirred overnight at room temperature. After adding ice water, dilute sulfuric acid was added to the reaction product and the product was extracted twice with 500 ml each of methylene chloride. The combined organic phase of the two extracts was washed with sodium bicarbonate solution and water, dried over sodium sulfate and concentrated. Product yield is 115.7g
(92.7%) and was a light red oily substance with a slight odor. When you distill this thing, you get a line point. gives a colorless oil with a slight odor and a solubility in water of >0.5% to 0.6% at 122°C. The NMR spectrum shows the presence of the above mentioned compounds.

Example 2 1-phenoxy-2-butanol and 2-phenoxy-1
- To prepare a phenoxybutanol mixture of butanol, 47 g (0.5 mol) of phenol, 40.2 g
(0,55 mol) of 1,2-butene oxide and 0.5
g (45% strength) of N5OH were heated for 6 hours at bath temperatures up to 140°C. After cooling, 200 ml of ether was added and unreacted phenol was extracted using a dilute aqueous solution of sulfur hydroxide.

The ether phase was washed with water, dried over sodium sulfate and concentrated. A pale yellow oil with a slight odor is obtained. Product yield was virtually quantitative (96%). Distillation of this substance (boiling point 81.132°C) yields a colorless oil with a slight odor, which is approximately 20°C
solidify. Chemical shifts and integrals in NMR analysis indicate the presence of the above compounds. Solubility in water is 〉0.3
It is 0.4%. Analysis results by gas chromatography showed that the mixture contained 91.6% 1-7 enoxy-2-butanol and 8.4% 1-7 enoxy-2-butanol.
% of 2-phenoxy-1-butanol (“phenyl(I)
and ■)'').

Example 3 72, lζ (I mol) of 1,2-butene oxide, 1o
Benzyloxybutanol was prepared as a mixture by heating s, 1 g (x mol) of benzyl alcohol and 11 of concentrated sulfuric acid under reflux for 8 hours under an acid catalyst. A batch of the mixture was extracted into 200 ml of diethyl ether, the mixture was neutralized with sodium bicarbonate, dried over sodium sulfate and concentrated. When distilled, the boiling point, 2=
A yellow oil with a slight odor was obtained at 128-134°C.

The glycol ether mixtures listed in Table I below were prepared in a manner similar to Example 2.

minimum inhibitory concentration
cancentrh-1ion) and inhibition circle test (in
The numerical values of hibiting xreola test) are listed in the following table ■ and table ■.

Example 4 The preservative activity of the glycol ethers according to the invention was studied in the following formulations: Shampoo consisting of: 15 parts by weight of lauryl ether-sulfate N1 salt ["Texapon N70" from Henkel] (registered trademark name)], 3.5
A shampoo consisting of 711 parts of sodium chloride, 81.5 parts of fully demineralized water was adjusted to pH 6 with citric acid.

b) Body lotion phase 1 consisting of the following elements: 3.3 parts by weight of polyoxyethylene fatty acid ester [1
1.2.7 parts by weight of glycerol sorbitan fatty acid ester (Allace L 481, manufactured by I, C, I America, Inc.)
), 7.0 parts by weight of caprylic/capric triglyceride [Dynamite-Nopel Miglyol 8
12(R) 1.17°0 parts by weight of liquid paraffin and Phase 2: 3.8 parts by weight of 1.2-propylene glycol, 0.7
A water-in-oil emulsion was prepared by combining 1 part by weight of MgSO4.7H20, 69 parts by weight, and 9 parts by weight of completely demineralized water.

C) Daytime cream phase l consisting of the following elements: 6.0 parts by weight of polyoxine ethylene fatty acid ester N;
C,! Allatone 983S (registered trademark) from America Inc.], 11.0 parts by weight of cetyl alcohol [Ufutute 16 (registered trademark name) from Henkel Inc.], 5.0 parts by weight of stearic acid [Nibnol C18/98 from Henkel Inc. (registered trademark name)], 44.0 weight liquid paraffin oil, 3.
0 parts by weight of octyldodecanol [Henkel Oitanol G® 1 and Phase 2, 3.8 parts by weight of glycerol, 76.6 parts by weight of water] were treated to form an oil-in-water emulsion. Ta.

0.1, 0.2 each of 2-phenoquine-1-butanol.
0.4, 0.8 or 1.6 parts by weight were kneaded into the above-mentioned cosmetics, and the preservative (preservative) activity was tested in a storage load test.

Outstandingly good concentration-dependent activities were obtained over several inoculation cycles.

Example 5 Among the glycol ethers of the present invention, R group is 7 enyl,
M (I+m), 2-methquinphenyl, 4-methoxyphenyl, 4-tert-buderphenyl, benzyl, 2-7
If enogyethyl, 2-ethylhexyl or di-lahydrofurfuryl 6 groups were used in place of phenoxy-1-butanol as in Example 4, comparable activities were achieved.

Example 6 As an example of a synergistic formulation, a P II B ester-based cationic, aldehydic, phenolic disinfectant and preservative was prepared as follows: 8) Cationic disinfectant : In a mixture of 50 parts by weight of a 50% strength aqueous solution of benzalkonium chloride, 12 parts by weight of fatty alcohol ethoxylate and 38 parts by weight of completely demineralized water, 10 f parts by weight of water are mixed with 2-phenoxylate. -1-Butanol was substituted. Compared to formulations without glycol ether, a pleasant-smelling disinfectant was obtained with improved activity, especially against Durham-negative bacteria and mycobacteria.

A similar improvement in activity was observed when glycol ethers in which the R group was a benzyl group or a phenyl (I+n) group were similarly used.

b) 30% strength formaldehyde solution of 30 parts by weight of aldehydic disinfectant, 15
Geltarodialdehyde solution with a concentration of 50% in parts by weight, 12
Parts by weight of alkanesulfonic acid ester, 10Iiffi
10 parts of water in a mixture of 33 parts by weight of completely demineralized water and 33 parts by weight of completely demineralized water.
The mixture was replaced with a certain amount of 2-phenoxy-1-butanol. A disinfectant was obtained which dissolved organic soils better in the solution for use and showed an increase in activity compared to a formulation without glycol ether.

Glycol ethers in which the substituents R are 2-methoxyphenyl and tetrahydrofurfuryl gave stable formulations with improved microbiological activity.

Comparable results were obtained when formaldehyde in the above disinfectant was replaced by 10 parts by weight of succinic aldehyde. In this case as well, an increase in activity was observed due to the inclusion of glycol ether.

C) Phenolic Disinfectant A disinfectant was prepared from the following ingredients: a mixture of O-phenylphenol and chlorometacresol (4:1), 15 parts by weight of alkanesulfonic acid ester, 10 parts by weight. 10 parts by weight of water in a mixture of Improper Tool, 4 parts by weight of 45% strength sodium hydroxide solution and 61 parts by weight of completely demineralized water were replaced by 2-phenoxy-1-butanol. Compared to a formulation without glycol ether, an alkaline disinfectant with higher activity, especially against Durham-negative bacteria and viruses, and better cleaning power was obtained.

2-phenoxy-1-butanol, R is phenyl (I
A similar synergistic increase in the effect was observed when replacing 4-2-n) with the corresponding glycol ether of 4-sec-butylphenyl.

d) Preservative based on rose hydroxybenzoic acid (PI113) ester A mixture of the following composition was prepared by IJyI: 4 parts by weight of P
II B methyl ester, 5 pawls of PII B ethyl ester, 5 fflffi parts of P H13 propyl ester, 2 parts by weight of P HB butyl ester, remaining weight Q
parts of 2-7 enoxy l-butanol (100 parts total)
.

A clear colorless solution with a slight odor was obtained, which has excellent preservative properties in cosmetic formulations as a 0.1-0.8% solution, especially in the case of oil-in-water emulsions. and for example, P in propylene glycol
It had synergistically much stronger activity than the solution of I-1B ester.

The following table ■ shows, on the one hand, the comparative values in the bacterial count reduction test (Δ) and, on the other hand, the minimum inhibitory concentration (MIC) values compared with commercially available detergents or with separately selected comparative products.

2-phenoquine-1-butanol, designated 303/137, is the component used according to the invention and has consistently shown better results.

Claims (1)

[Claims] 1. A lethal dose or inhibition of the antimicrobial glycol ether of the general formula ▲ mathematical formula, chemical formula, table, etc. ▼ (I) in an environment contaminated or easily contaminated by harmful microorganisms. A method for destroying or inhibiting the growth of harmful microorganisms in an environment contaminated with or susceptible to being contaminated by harmful microorganisms, comprising contacting an effective amount of harmful microorganisms. However, in the above formula, R is a) straight chain, branched, or cyclic C_4 to C_1
__2 alkyl group, the alkyl chain of which may be interrupted by up to two oxygen atoms; b) an aryl group having 6 to 12 carbon atoms, provided that the aryl nucleus is one or or c) an arylalkyl or aryloxyalkyl group having from 7 to 13 carbon atoms, provided that the alkyl chain is substituted by up to two oxygen atoms. The aryl group may be substituted by a lower alkyl, lower alkoxy, chloro or bromo group. 2. The compound of formula I is the following compound: 2-n-butoxy-1-butanol, 2-n-hexyloxy-1-butanol, 2-(2-ethylhexyloxy)-1-butanol, 2-decyloxy-1 -butanol, 2-dodecyloxy-1-butanol, 2-(
2-(2-butoxyethoxy)-ethoxy)-1-butanol, 2-cyclohexyloxy-1-butanol,
2-(2-methylphenoxy)-1-butanol, 2-
(3-methylphenoxy)-1-butanol, 2-(4
-methylphenoxy)-1-butanol, 2-(2-methoxyphenoxy)-1-butanol, 2-(4-methoxyphenoxy)-1-butanol, 2-(4-butylphenoxy)-1-butanol, 2- (4-tert-butylphenoxy)-1-butanol, 2-benzyloxy-
1-Butanol, 2-(2-phenylethoxy)-1-
Butanol, 2-(2-phenoxyethoxy)-1-butanol, 2-(3-phenylpropyloxy)-1-
Butanol, 2-(3-phenoxypropyloxy)-
1-butanol, 2-(2-phenoxypropyloxy)-1-butanol and 2-(2-phenoxy-1-methyl-ethoxy)-1-butanol; Method. 3. A claim in which the compound of formula (I) is used in combination with a compound of the general formula: R-O-CH_2-CHOH-C_2H_5 (II), where R is defined in claim 1. The method according to item 1 or 2. 4. The method according to claim 1, wherein 4,2-phenoxy-1-butanol or 2-phenoxy-1-butanol and 1-phenoxy-2-butanol are used. 5. The method according to any one of claims 1 to 4, which is used for treating compositions used by humans for body care, such as cosmetics, in order to protect them from deterioration caused by microbial action. Method. 6. The method of claim 5, wherein the concentration of the compound of formula I in the composition is at least 0.1% by weight. 7. The method according to claim 6, wherein the concentration is 0.1 to 2.0% by weight. 8. The method according to claim 6, wherein the concentration is 0.5 to 1.5% by weight. 9. The method according to any one of claims 1 to 4, which is used for treating the surface of an inanimate object. 10. The method according to any one of claims 1 to 4, which is used for treating the skin of a mammal, for example a human. 11. A disinfectant or preservative comprising a compound of formula (I) and optionally a compound of formula (II), formulated into a personal care product according to any one of claims 1 to 8. 12. Disinfectant or preservative additives containing 2 to 40% by weight of glycol ether of formula I. 13. a) mono- and dialdehydes having 1 to 5 carbon atoms, b) cationic compounds which are quaternary ammonium compounds, biguanidine or octenidine, and/or c) phenolic compounds, especially p-hydroxybenzoic acid esters; Disinfectant or preservative according to claim 11 or 12, comprising a synergistic combination with.