GB1577396A - Alcoholic disinfectants - Google Patents

Abstract

The novel sporicidal disinfectants contain one or more odourless or low-odour aromatic percarboxylic acids in an alcoholic solution. The alcohols used have 1 to 4 carbon atoms. The abovementioned percarboxylic acids are defined in Patent Claim 1.

Description

(54) ALCOHOLIC DISINFECTANTS (71) We, SCHULKE - & MAYR G.M.B.H., a Company organised under the laws of the Federal Republic of Germany, of Robert-Koch-Strasse 2, 2000 Norderstedt, Germany, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to alcoholic disinfectants, and in particular to such disinfectants having sporicidal activity.

It is known that aqueous alcoholic solutions may be used as quick acting disinfectants: they dry quickly without leaving a residue, can be handled easily, are relatively non-toxic and cause very little corrosion. They may be used inter alia for disinfecting hands, surfaces and instruments.

However such alcoholic disinfectants have certain serious disadvantages: although they work quickly and effectively on the vegetative forms of bacteria and fungi, they do not kill bacteria and fungi spores, and thus allow the spores to survive and be spread from the disinfectants. It is therefore essential to employ only sporefree alcohol and water.

A further disadvantage of alcoholic disinfectants is that the alochol serving as active substance is volatile, and is evaporated quickly from a surface to be disinfected, without leaving a disinfectant residue. Such a surface could easily become recontaminated by airborne germs, and it would be desirable to add a further germ killing ingredient to the disinfectant, which could form a thin film with growth checking action against micro-organisms after the alcohol evaporates.

A number of methods are known for making aqueous alcoholic solutions sporefree and sterile. The most important of these are of a physical type, such as sterilefiltration, exposure to ultraviolet or short wave radiation and sterilisation in high pressure autoclaves. These methods can be expensive, troublesome, time consuming and are not always applicable; also in some cases they are not sufficiently effective, when for example the possibility of recontamination exists.

Of chemical methods for sterilisation, the use of ethylene oxide or p propionolactone has been proposed, although this is not generally recommended because of the toxicity of these compounds and the difficulty in handling them.

Moreover, both compounds may react with alcohol to form substances inactive as disinfectants.

Aliphatic dialdehydes such as glutaraldehyde possess a sporicidal activity, which is increased in an alkaline medium.

However, they have the disadvantage of an intensive unpleasant smell, limited stability and insufficient activity on application at low concentrations, which are necessary if the alcoholic disinfectant containing the aldehyde is to dry on the disinfected surface leaving little or no residue.

Thus there is still a need for a sporicidal ingredient for alcoholic disinfectants that is highly active against the spores and the vegetative forms of bacteria and fungi, and that does not impair the properties of the disinfectants. The concentration of the sporicidal ingredient should be capable of being selected so that a small amount of residue remains after evaporation of the aqueous alcoholic solution from the disinfected surface, this residue effectively controlling the growth of micro-organisms after disinfection. Only a highly active sporicidal ingredient can be used in this way. Also, it is sometimes desirable for the sporicidal ingredient to be unstable, so that it can decompose in the alcoholic disinfectant perhaps by reaction with the alcohol. The sporicidal ingredient should then be active enough for disinfection to occur before the decomposition.

We have now unexpectedly found that alcoholic disinfectants with a remarkable sporicidal activity may be obtained by adding thereto certain organic percarboxylic acids, or substances that form such acids therein.

In one aspect, therefore, this invention provides a disinfectant solution with sporicidal activity comprising an aromatic monopercarboxylic acid of the general formula:

(wherein R, which may be at any available position of the benzene nucleus, represents a hydrogen or halogen atom, a straight or branched chain alkyl radical having from 1 to 4 carbon atoms, or a hydroxy, trifluoromethyl, carboxy, phenyl, -SO3H, --OR', --COOR' or -SO2R1 radical, R1 being a straight or branched chain alkyl radical having from 1 to 4 carbon atoms), persorbic acid, perglutaric acid, persuccinic acid, permaleic acid, perlactic acid, percitric acid, acetylpercitric acid, permethoxyacetic acid, perethoxyacetic acid or perdiglycolic acid dissolved in an aqueous alcoholic medium.

The disinfectant of the invention may comprise two or more of the above percarboxylic acids in any proportions.

The percarboxylic acids used in the disinfectants of the invention have little or no odour, so that neither the smell of the alcoholic disinfectant nor the smell of disinfected materials will be undesirably influenced.

Because of the presence of the percarboxylic acids, the disinfectants of the invention are substantially spore-free and thus automatically sterile, which is a requirement in many applications of the disinfectants. They have an effective growth inhibiting activity against micro-organisms.

The aqueous alcoholic medium in which the percarboxylic acids are dissolved may contain at least 10%, preferably from 20 to 80, and especially 45 /n by weight of alcohol.

Primary, secondary or tertiary alcohols may be used, preferably containing from 1 to 3 hydroxy groups and from 1 to 4 carbon atoms. Examples of such alcohols are methanol, ethanol, n - propanol, i - propanol, n - butanol, sec - butanol, tert butanol, ethyleneglycol, 1,2 propyleneglycol, 1,3 - propyleneglycol or glycerin. Ethanol, i - propanol and n propanol are preferred. The disinfectants of the invention may comprise two or more alcohols mixed in any proportion.

Preferred aromatic percarboxylic acids of general formula I for use in the invention are perbenzoic acid, m - chloroperbenzoic acid, p - (tert - butyl) - perbenzoic acid, p methoxyperbenzoic acid, 2 - hydroxyperbenzoic acid, 4- hydroxyperbenzoic acid, 3 - trifluoromethylperbenzoic acid and monoperphthalic acid.

Further substances may be added to the disinfectant in order to improve its technical properties and/or its antimicrobial activity.

Examples of such additives are wetting agents, surface active agents, fat producing agents, corrosion inhibitors, odorants, antimicrobial agents, dyestuffs or pH adjustors.

It is known that organic percarboxylic acids are strong oxidising agents and can react with alcohols. Thus the percarboxylic acid may be reduced to its corresponding carboxylic acid, with concomitant oxidation of the alcohol to its corresponding carbonyl compound or carboxylic acid. It has been found however that under the conditions in which the disinfectants of the invention are used-usually within a temperature range of from 0 to 400C-the percarboxylic acids react only very slowly.

The percarboxylic acids may therefore retain their sporicidal activity over a long period, which may be extended by adding a stabiliser for the percarboxylic acids, such as hydrogen peroxide, to the disinfectant.

Since however the percarboxylic acids are not infinitely stable in aqueous alcoholic solutions, even when a stabiliser is present, it is preferred not to prepare the disinfectant until shortly before its use. The disinfectant may retain that part of its activity that is due to the percarboxylic acid for a period of up to 4 weeks.

The percarboxylic acids may also themselves decompose in time to the corresponding carboxylic acids and oxygen, and this may cause oxidation reactions in the solution. An important feature of the invention is that the carboxylic acids formed by decomposition of the percarboxylic acids also possess growth inhibiting activity against micro-organisms, and therefore the disinfectants of the invention display sustained activity against micro-organisms, especially when present on the disinfected or sterilised material in a finely divided form.

Percarboxylic acids may in certain circumstances have an undesirable corrosive effect, in which case it would be advantageous if the percarboxylic acid were to decompose soon after performing its function of killing the vegetative and spore forms of micro-organisms. If it is wished to facilitate this decomposition, a destabiliser for the percarboxylic acid should be added to the disinfectant of the invention. Suitable destabilisers are aldehydes, amines and heavy metal salts.

It is a safety feature of this invention that the concentration of percarboxylic acid in the disinfectant may be quickly and easily determined by iodometric methods.

In another aspect, this invention provides a process for preparing a disinfectant solution of the invention, in which process one or more of the organic percarboxylic acids defined hereinbefore or one or more substances that produce such a percarboxylic acid upon dissolution, is dissolved in an aqueous alcoholic medium.

Where a substance that produces a percarboxylic acid upon dissolution is employed, this is preferably a solid mixture of an H202 source together with a diacyl peroxide or a carboxylic acid anhydride, ester or amide. The diacyl peroxide may alternatively be used without an H202 source as the percarboxylic acid source.

The diacylperoxide may be a pure or mixed diacylperoxide such as benzoylperoxide, p- tert - butylbenzoylperoxide or 4 - methoxy-benzoylperoxide.

These compounds decompose by hydrolysis into a percarboxylic acid and a carboxylic acid.

The function of the H202 source is to produce H202 in solution, which will then react with the carboxylic acid anhydride, ester or amide to form the corresponding percarboxylic acid.

The preferred H202 sources are alkali metal perborates, alkali metal percarbonates, alkali metal perphosphates, alkali metal peroxides, percarbamide, peroxodisulphates and peroxomonosulphates.

The carboxylic acid anhydride employed in conjunction with the H2 2 source may be a pure or mixed anhydride and is preferably benzoic acid anhydride, 4 methoxybenzoic acid anhydride, phthalic acid anhydride, sorbic acid anhydride, glutaric acid anhydride, succinic acid anhydride, maleic acid anhydride, acetyl citric acid anhydride or diglycolic acid anhydride.

The carboxylic acid esters may be formed with an alcohol or phenol, preferably with an alcohol or phenol that itself possesses a growth-inhibiting activity against microorganisms; such an ester is 2 - benzoyloxy benzoic acid, which when dissolved in the alcohol or aqueous alcoholic solution with an H202 source forms perbenzoic acid and 2 - hydroxy - benzoic acid, both of which possess activity against micro-organisms.

Other preferred carboxylic acid esters are 3 - benzoyloxy - benzoic acid, 4 - benzoyloxy - benzoic acid and 2 - hexa - - dienoyloxy - benzoic acid and their alkali metal salts, lactide (the cyclic ester of lactic acid) and 2 - benzoyloxy - propionic acid.

The carboxylic acid amides are preferably formed with weakly basic nitrogen compounds, an especially preferred amide being tetrabenzoylglucoluril.

The percarboxylic acids or the substances from which the percarboxylic acids are produced upon dissolution, may be added to the solution in solid or liquid form.

Examples of suitable solid forms are powders, granules or tablets.

This invention also provides a method of disinfecting a locus, in which method of disinfectant solution of the invention is applied to the locus.

The following Examples will now be given, though only by way of illustration, to show some preferred aspects of the invention. The percentages quoted in the Examples were calculated on a weight basis.

Example 1 An aqueous alcoholic solution of 4 methoxyperbenzoic acid was prepared containing: 1.0 g 4 - methoxyperbenzoic acid (87.5) i - propanol (45 /a) up to 1000 g.

The resulting clear colourless solution was maintained at room temperature, and investigated iodometrically for its content of 4 - methoxy perbenzoic acid.

Content of 4 - methoxy - perbenzoic acid: Time Content 30 mins 0.0870/, 90 mins 0.087 /,, 3 days 0.074 /" Il days 0.054 13 days 0.034 /" 32 days 0.01 /" Example 2 Four separate aqueous alcoholic solutions were prepared as shown below, the quantities being parts by weight.

1 2 3 4 4 - methoxv - perbenzoic acid (87.5 /,) 0.1 0.2 0.3 0.4 non-ionic wetting agent 0. i U. 1 0.1 0.1 i - propanol (45%) 99.8 99.7 99.6 99.5 After 2 and 22 days each solution was investigated iodometrically for its content of 4 - methoxy - perbenzoic acid: Content of 4 - methoxy - perbenzoic acid; Solution 2 days 22 days 1 0.049/n 0.022% 2 0.102 /n 0.042 3 0.151% 0.062 /n 4 0.195% 0.084% Example 3 100 g of 80 /n aqueous ethanol were mixed with 1 ml of a suspension of spores (B.

subtilis, initial germ-count 6x l04/ml). 0.1 g 4- methoxyperbenzoic acid (54%) were then added.

The dependency of germ-count on time was determined according to the guidelines for the examination of chemical disinfectants published by DGHM (Deutsche Gesellshaft fur Hygiene und Mikrobiologie). The solutions were maintained at room temperature.

Time in hours Germ-count per ml 2 5x103 3 8x102 4 3x102 5 7x10' 24 48 In a comparative test without the addition of 4 - methoxyperbenzoic acid, the same germ-count was found after 48 hours as at the beginning of the test.

Example 4 The following constituents were mixed; the "parts" being by weight.

10 parts ethanol 15 parts n - propanol 20 parts i - propanol 0.2 parts corrosion inhibitor (e.g. benzo triazol) 0.2 parts wetting agent (e.g. a fatty alcohol polyglycolether) The solution was made up to 100 parts with water softened by ion-exchange.

The addition of 0.2 parts peranisic acid to this growth-checking solution produced a surface disinfectant with a wide spectrum of activity.

Example 5 The following constituents were mixed: 30 parts ethanol 50 parts i - propanol 0.3 parts sodium nitrate The solution was made up to 100 parts with water softened by ion-exchange.

The resultant solution was mixed with 0.2 parts peranisic acid and 0.1 parts 40 /n glyoxal (as destabiliser) and put quickly into spray cans. Difluorodichloromethane, carbon dioxide or nitrogen may serve as a propellant gas for the cans, the proportion by weight of solution to propellant gas being 3:1. The cans may be used as an auto-sterile alcohol spray.

WHAT WE CLAIM IS:- 1. A disinfectant solution with sporicidal activity comprising an aromatic monopercarboxylic acid of the general formula:

(wherein R represents a hydrogen or halogen atom, a straight or branched chain alkyl radical having from 1 to 4 carbon atoms, or a hydroxy, trifluoromethyl, carboxy, phenyl, --SO,H, -OR1, --COOR' or SO2R' radical, R' being a straight or branched chain alkyl radical having from 1 to 4 carbon atoms), persorbic acid, perglutaric acid, persuccinic acid, permaleic acid, perlactic acid, percitric acid, acetylpercitric acid, permethoxyacetic acid, perethoxyacetic acid or perdiglycolic acid dissolved in an aqueous alcoholic medium.

2. A disinfectant solution as claimed in claim 1, in which the aqueous alcoholic medium contains from 20 to 80 /n by weight of alcohol.

3. A disinfectant solution as claimed in claim 1 or claim 2, in which the alcohol present in the disinfectant solution contains from 1 to 3 hydroxy groups and from 1 to 4 carbon atoms.

4. A disinfectant solution as claimed in any of claims 1 to 3, in which where the disinfectant solution contains an aromatic monopercarboxylic acid of general formula 1, this is perbenzoic acid, m chloroperbenzoic acid, p - (tert - butyl) perbenzoic acid p - methoxyperbenzoic acid, 2 - hydroxyperbenzoic acid, 4 hydroxyperbenzoic acid, 3 trifluoromethylperbenzoic acid or monoperphthalic acid.

5. A disinfectant solution as claimed in any of the preceding claims, which contains hydrogen peroxide as a stabiliser for the percarboxylic acid.

6. A disinfectant solution as claimed in any of claims 1 to 4, which contains a destabliser for the percarboxylic acid.

7. A disinfectant solution as claimed in

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (17)

1. **WARNING** start of CLMS field may overlap end of DESC **.

   After 2 and 22 days each solution was investigated iodometrically for its content of

   4 - methoxy - perbenzoic acid: Content of 4 - methoxy - perbenzoic acid; Solution 2 days 22 days 1 0.049/n 0.022% 2 0.102 /n 0.042 3 0.151% 0.062 /n 4 0.195% 0.084% Example 3 100 g of 80 /n aqueous ethanol were mixed with 1 ml of a suspension of spores (B.

   subtilis, initial germ-count 6x l04/ml). 0.1 g

   4- methoxyperbenzoic acid (54%) were then added.

   The dependency of germ-count on time was determined according to the guidelines for the examination of chemical disinfectants published by DGHM (Deutsche Gesellshaft fur Hygiene und Mikrobiologie). The solutions were maintained at room temperature.

   Time in hours Germ-count per ml 2 5x103 3 8x102 4 3x102 5 7x10' 24 48 In a comparative test without the addition of 4 - methoxyperbenzoic acid, the same germ-count was found after 48 hours as at the beginning of the test.

   Example 4 The following constituents were mixed; the "parts" being by weight.

   10 parts ethanol 15 parts n - propanol 20 parts i - propanol 0.2 parts corrosion inhibitor (e.g. benzo triazol) 0.2 parts wetting agent (e.g. a fatty alcohol polyglycolether) The solution was made up to 100 parts with water softened by ion-exchange.

   The addition of 0.2 parts peranisic acid to this growth-checking solution produced a surface disinfectant with a wide spectrum of activity.

   Example 5 The following constituents were mixed: 30 parts ethanol 50 parts i - propanol 0.3 parts sodium nitrate The solution was made up to 100 parts with water softened by ion-exchange.

   The resultant solution was mixed with 0.2 parts peranisic acid and 0.1 parts 40 /n glyoxal (as destabiliser) and put quickly into spray cans. Difluorodichloromethane, carbon dioxide or nitrogen may serve as a propellant gas for the cans, the proportion by weight of solution to propellant gas being 3:1. The cans may be used as an auto-sterile alcohol spray.

   WHAT WE CLAIM IS:- 1. A disinfectant solution with sporicidal activity comprising an aromatic monopercarboxylic acid of the general formula:

   (wherein R represents a hydrogen or halogen atom, a straight or branched chain alkyl radical having from 1 to 4 carbon atoms, or a hydroxy, trifluoromethyl, carboxy, phenyl, --SO,H, -OR1, --COOR' or SO2R' radical, R' being a straight or branched chain alkyl radical having from 1 to 4 carbon atoms), persorbic acid, perglutaric acid, persuccinic acid, permaleic acid, perlactic acid, percitric acid, acetylpercitric acid, permethoxyacetic acid, perethoxyacetic acid or perdiglycolic acid dissolved in an aqueous alcoholic medium.
2. 2. A disinfectant solution as claimed in claim 1, in which the aqueous alcoholic medium contains from 20 to 80 /n by weight of alcohol.
3. 3. A disinfectant solution as claimed in claim 1 or claim 2, in which the alcohol present in the disinfectant solution contains from 1 to 3 hydroxy groups and from 1 to 4 carbon atoms.
4. 4. A disinfectant solution as claimed in any of claims 1 to 3, in which where the disinfectant solution contains an aromatic monopercarboxylic acid of general formula 1, this is perbenzoic acid, m chloroperbenzoic acid, p - (tert - butyl) perbenzoic acid p - methoxyperbenzoic acid, 2 - hydroxyperbenzoic acid, 4 hydroxyperbenzoic acid, 3 trifluoromethylperbenzoic acid or monoperphthalic acid.
5. 5. A disinfectant solution as claimed in any of the preceding claims, which contains hydrogen peroxide as a stabiliser for the percarboxylic acid.
6. 6. A disinfectant solution as claimed in any of claims 1 to 4, which contains a destabliser for the percarboxylic acid.
7. 7. A disinfectant solution as claimed in

   claim 6, in which the destabliser is an aldehyde, amine or a heavy metal salt.
8. 8. A process for preparing a disinfectant solution as claimed in claim 1, in which process one or more of the organic percarboxylic acids defined in claim 1, or one or more substances that produce such a percarboxylic acid upon dissolution, are dissolved in an aqueous alcoholic medium.
9. 9. A process as claimed in claim 8, in which where a substance that produces a percarboxylic acid upon dissolution is employed this is a diacylperoxide or a solid mixture of an H202 source together with a diacylperoxide or a carboxylic acid anhydride, ester or amide.
10. 10. A process as claimed in claim 9, in which the diacylperoxide when employed, is benzoylperoxide, p- tert - butylbenzoylperoxide or 4 - methoxybenzoylperoxide.
11. 11. A process as claimed in claim 9, in which the H202 source, when employed, is an alkali metal perborate, an alkali metal percarbonate, an alkali metal perphosphate, an alkali metal peroxide, percarbamide, a peroxidisulphate or a peroxomonosulphate.
12. 12. A process as claimed in claim 9 or claim 11, in which the carboxylic acid anhydride, when employed, is benzoic acid anhydride, 4 - methoxybenzoic acid anhydride, phthalic acid anhydride, sorbic acid anhydride, glutaric acid anhydride, succinic acid anhydride, maleic acid anhydride, acetyl citric acid anhydride or diglycolic acid anhydride.
13. 13. A process as claimed in claim 9 or claim 11, in which the carboxylic acid ester, when employed, is 4 - benzoyloxy - benzoic acid or 2- hexa - 2',4' - dienoyloxy benzoic acid and their alkali metal salts, or 2 - benzoyloxy - benzoic acid, 3 benzoyloxy - benzoic acid, lactide or 2 benzoyloxy - propionic acid.
14. 14. A process as claimed in claim 9 or claim 11, in which the carboxylic acid amide, when employed, is tetrabenzoyl glucoluril.
15. 15. A disinfectant solution wherever prepared 6y a process claimed in any of claims 8 to 14.
16. 16. A disinfectant solution as claimed in claim 1, substantially as described herein with reference to any one of the Examples.
17. 17. A method of disinfecting a locus, in which method a disinfectant solution as claimed in claim I is applied to the locus.