WO2002008372A1

WO2002008372A1 - Antimicrobial compositions

Info

Publication number: WO2002008372A1
Application number: PCT/EP2001/007889
Authority: WO
Inventors: Martin Vincent Jones; Kenneth Leslie Rabone
Original assignee: Unilever Plc; Unilever Nv; Hindustan Lever Limited
Priority date: 2000-07-21
Filing date: 2001-07-09
Publication date: 2002-01-31
Also published as: AU2001287591A1

Abstract

An antimicrobial composition comprises a nonionic surfactant, optionally a terpene-like component, a cationic biocide that is compatible with the nonionic surfactant and the terpene-like component, and a source of alkalinity which ensures a pH of at least 8.5 in the composition. The combination of at least two of the nonionic, cationic and terpene-like components provides a synergystic antimicrobial action that is greater than the additive anti-microbial action of the at least two individual components.

Description

ANTIMICROBIAL COMPOSITIONS

INTRODUCTION

The invention relates to an antimicrobial composition and in particular to a specific combination of components which provide a synergistic anti-microbial action.

Hard-surface cleaning compositions generally comprise one or more surfactants, and, optionally, one or more hygiene agents. Typically, the surfactants used in such cleaning compositions are selected from anionic, nonionic, amphoteric and cationic surfactants. Nonionics are very commonly used due to their effectiveness on fatty soils and the ease with which their foaming can be controlled. Of these surfactants, nonionics are reported as showing low biocidal activity, whereas certain anionic, cationic and amphoteric surfactants show biocidal activity under specific conditions of, for example, pH and concentration. Generally, the biocidal activity of surfactants is, with a few notable exceptions, low and it is commonplace to add a separate hygiene agent to compositions.

Typical hygiene agents include strong acids, alkalis, phenolics and oxidants such as peracids and hypohalites. These, of which a typical example is hypochlorite, are generally highly reactive species which exhibit this reactivity in terms of one or more of, short shelf life, toxic, corrosive and irritant properties. In general, these reactive components are required at relatively high levels in formulations. Other less chemically reactive hygiene agents, such as 2 , 4, 4 ' -trichloro-2 ' -hydroxy diphenyl ether (available in the marketplace as IRGASA DP300 [RTM] ) , are effective at relatively low concentrations but are more expensive than simpler species and may be specific as regards their spectrum of activity. Many organic acids, including benzoic, salicylic and sorbic are known as preservatives in cosmetics and some food products, but these preservatives generally show lower biocidal activity than the above-mentioned chemically reactive hygiene agents when used at the same level .

EP 0126545 discloses abrasive, hard-surface cleaning compositions comprising terpenes or benzyl alcohol and nonionic surfactants to provide for cleaning of greasy and particulate soils. The compositions disclosed are preferably of pH 8-11.

WO 89/12673 discloses acaricidal compositions which comprise benzyl alcohol (as an acaricide) and nonionic surfactants. The pH of the formulation is preferably 7.5-12.5 neat and 3.0-10.0 on dilution. The surfactants used are specialised and mixed to give extremely low interfacial tension and comprise either a phenol ethoxylate or an amphoteric surfactant . Cationic surfactants are included in the exemplary formulations to con er antimicrobial properties .

WO 93/11211 discloses the use of low levels of phenol derivatives and oxyethylated aliphatic alcohol derivatives in alkaline hard surface cleaning compositions . The maximum level of phenol derivative is 0.03%wt.

WO 94/14942 discloses neutral cleaning compositions which contain a combination of alcohols including benzyl alcohol together with ethoxylated nonionic surfactants . The pH range specified for these compositions is 9-5. US 4311618 discloses cleaning formulations which can contain a broad range of nonionic surfactants of H B ranging from 5- 20 and optionally substituted aromatic alcohols and/or phenols as hygiene agents.

Natural phenolics are known to include a number of biocidal compounds including Thymol and Carvacrol (Daouk et al . J. Food Prot (1995) 58 (10) 1147-9) which have been shown to be effective against moulds, yeasts and bacteria (J Essent. Oil. Res. (1995) 7 (3) 299-303).

In hard surface cleaning it is often necessary to disinfect a surface. A 'disinfectant' can be understood to be a hygiene agent that shows a 100,000 fold or better reduction in the number of viable micro-organisms in a specified culture when used at a level of around 0.5 wt% . This is generally known as a ' 5 log kill' .

Some surfactants have been found to potentiate the effects of certain hygiene agents. DE 3619375 (Henkel) discloses that alkyl polyglycoside (APG) surfactants show a synergy with relatively low molecular weight alcohols and organic acids as regards hygiene and discloses compositions which comprise APG and organic acids. These compositions are used at strongly acidic pH, generally below pH 3.

Other surfactant/biocide combinations are believed to show a reduced effect as compared with the biocide per se. In 'Surface Active Agents' (Porter 1990, Elsevier) it is stated that while low concentrations of nonionics (below the critical micelle concentration) can have a synergistic effect on quaternary compounds when these have biocidal properties, nonionic surfactant in general have an inhibiting effect on biocides . One theory which has been put forward for this is that the biocide is adsorbed into micelles of the surfactant and therefore become less available for action. Similar results have been noted for phenols (cit ultra, page 107, section 4.5.4) and it is believed that relatively large concentrations of nonionic surfactant are likely to destroy the biocidal activity of phenols. Synergy has been reported only for a ratio where phenol is in excess of nonionic surfactant, antagonism is shown for all other ratios.

WO 98/01524 discloses a marked synergy as regards antimicrobial effectiveness between aromatic alcohols or phenols, other than phenol itself and ethoxylated alkanol nonionic surfactants, outside of the physiological pH range,

It is an object of the present invention to provide a microbiocidal composition that is effective at low concentrations .

STATEMENT OF INVENTION

The applicants have discovered that it is possible to formulate a mixture of nonionic, a terpene-like component and a cationic biocide in alkaline conditions which provides an effective broad spectrum antimicrobial action at low concentrations against both Gram-negative and Gram-positive microbes by exploiting synergistic interactions between at least two of the components at alkaline pH.

According to the invention there is provided a composition comprising a nonionic surfactant, a compatible cationic biocide, a terpene-like component and a source of alkalinity which ensures a pH of at least 8.5 in the composition, wherein the combination of at least two of the nonionic, cationic and terpene-like components provides a synergistic antimicrobial action which is greater than the additive anti-microbial action of the at least two individual components .

In this specification, the term " compatible cationic biocide" refers to a cationic biocide that, by virtue of its structure (for example, a cationic polymer) is not deactivated by nonionic surfactant (for example, by micellisation) .

In this specification the term " terpene-like component" refers to one or more compounds related to the monoterpenes and monoterpenoids . In particular, CIO compounds based on two isoprene units, that is:

The compounds may be acyclic, (as Citral, Citronellal, Citronellol and Geraniol) or alicyclic (as Terpineol, Limonene and Menthol) bridged alicyclic (as Pinene or

Camphor) or aromatic (as Thymol or Carvacrol) . Included are related and derived compounds such as esters and mixtures thereof. In one embodiment of the invention the terpene-like component is present in the composition in an amount of at least 0.1% by weight, suitably between 0.1 and 2% by weight. Preferably the terpene-like component consists of Citral, Thymol or a combination of Citral and Thymol . The combination of terpene-like component and nonionic surfactant is especially effective against Gram-negative microbes .

The cationic biocide should be effective against Gram positive microorganisms. Preferably the cationic biocide is a biguanide, typically polyhexamethylenebiguanide (PHMB) , and ideally PHMB known sold under the trade name VANTOCIL IB. Suitably the cationic should be present in an amount of at least 0.1% by weight and preferably not more than 2% by weight. Preferably the cationic is present at between 0.1 and 1% by weight .

Suitable nonionic surfactants include alkoxylated alcohols, preferably ethoxylated alcohols. Suitable nonionic detergent active compounds can be broadly described as compounds produced by the condensation of alkylene oxide groups, which are hydrophilic in nature, with an organic hydrophobic compound which may be aliphatic or alkyl aromatic in nature.

The length of the hydrophilic or polyoxyalkylene radical which is condensed with any particular hydrophobic group can be readily adjusted to yield a water-soluble compound having the desired degree of balance between hydrophilic and hydrophobic elements.

The preferred alkoxylated alcohols are selected from the group comprising ethoxylated alcohols of the general formula :

^-(OC^Ctt^-OH

wherein R₁ is straight or branched, C₈ to C₁₈ alkyl or hydroxyalkyl and m is, on average, 1-14. Ethoxylated alcohols suitable for use in the present invention include NEODOL 91-8 available in the marketplace from Shell. Typically the nonionic is present in an amount of at least 1% by weight, suitably between 5 and 10% by weight.

In an optional embodiment of the invention the composition includes an iodophore, typically iodine.

A preferred composition according to the invention comprises:

- at least 0.03% cationic biocide;

- at least 0.1% of a terpene-like component; and

- at least 1%, typically 5%, ethoxylated nonionic surfactant .

Typically, such a composition comprises:

- between 0.03% and 0.15% cationic surfactant;

- between 0.1% and 2% of a terpene-like component; and

- between 2% and 8% ethoxylated nonionic surfactant.

Ideally the composition will have a pH of less than or equal to 12, preferably between 9 and 11.

As one means of obtaining a pH in the above range, the composition may include a builder that is effective at maintaining the biocidal action of the cationic biocide in the presence of hardness ions. Suitably the builder will comprises an alkaline metal carbonate as a precipitant builder. Other builders are well known from laundry formulations, for example, sodium tripolyphosphate . complexing agents such as ethylene diamine tetra-acetic acid, sodium salt may also be used. Mixtures of sodium carbonate and sodium bicarbonate are also useful. Such carbonate builder systems have been found to provide a high reserve alkalinity that is useful for instances where the composition is diluted. By reserve alkalinity is meant the ability of a formulation to maintain a high pH on dilution.

The compositions according to the invention are suitable for use neat or in dilution. In this regard the composition may be diluted in a solvent, typically water, at amounts up to 50, preferably 100, more preferably 600 times their weight. It has been found that such diluted compositions not only provide an effective antimicrobial effect but also provide disinfectancy . In this specification the terms ^Λλ disinfectant" or " disinfectancy" should be taken as meaning the ability to reduce microbial numbers by five orders of magnitude from an initial inoculum N₀ of about 10^s microbes per millilitre, that is a 5 log reduction (that is, log₁₀(N₀/N) • 5, where N is the residual number of microbes) .

The invention also relates to a use of a composition according to the invention to disinfect a surface, and to the use, in a process for the preparation of a disinfecting composition for the treatment of a surface, which composition has a pH of at least 8.5, of a nonionic, typically ethoxylated, detergent, a cationic surfactant and a terpene-like component.

The invention also relates to a disinfectant composition comprising a nonionic surfactant and a cationic biocide which is compatible with the nonionic, wherein the combination of the nonionic and cationic components provides a synergistic antimicrobial action which is greater than the additive anti-microbial action of the two individual components. Typically the cationic biocide is a biguanide, especially PHMB. Preferably the composition further comprises a source of alkalinity which ensures a pH of at least 8.5 in the composition. The invention also relates to the use of a composition according to the invention as an antibacterial, especially disinfecting, agent and the use, in a process for the preparation of a disinfecting composition for the treatment of non-living surfaces, of said composition.

DETAILED DESCRIPTION OF THE INVENTION

The following bacterial strains were used in the suspension tests of the following examples:

Pseudomonas aeruginosa ATCC 15442

Staphylococcus aureus NCTC 6538

Micro-organisms were taken from slopes and cultured at 37 degrees C (bacteria) or 28 degrees C (yeast) with constant agitation for 24 hours in nutrient broth (bacteria) or Sabouraud-dextrose liquid (yeast) . Cells were recovered by centrifugation (10 min, 4100 rpm and resuspended in A strength Ringer's buffer to give a suspension of 10⁹ - 10¹⁰ cfus/ml. Test solutions were prepared according to the examples laid out below in sterile distilled water. Sufficient bacterial suspension was added to each test solution to give a final concentration of 10⁸ bacteria/ml. After a 5 min contact time, 1 ml of the test solution was added aseptically to 9ml of inactivation liquid (3% (w/v) Tween 80 ™, 0.3% (w/v) lecithin, 0.1% (w/v) Bacteriological peptone made up in pH7.2 phosphate buffer and then serially diluted into ^XA strength Ringer's buffer.

Viable organisms were determined by culturing on nutrient or Tryptone-soya peptone agar (bacteria) and Malt Extract agar for 48 hours at 37 degrees C (bacteria) or 28 degrees C (yeast) . In the examples below the minimum concentration of each test formulation required to achieve disinfectancy was determined from the extent by which the formulation could be diluted and still disinfect, wherein disinfectancy is achieved if there is a 10⁵ reduction in viable organisms by the diluted formulation.

Referring initially to Table 1, the results of which are plotted in Figure 1 (in which N = nonionic, T = thymol, C = Citral and V = PHMB) , a number of microbiocidal synergies can be seen. Thus, referring to Fig. 1, comparing nonionic (N) on its own and PHMB (V) on its own with the combination of nonionic and PHMB (N/V) it is clear that the additive biocidal action of the combination is greater than the sum of the biocidal action of the components when used individually. Similarly comparing N/T and V on their own with the combination N/T/V, it is clear that the triple combination of nonionic, thymol and PHMB provides a biocidal action which is considerably greater than the sum of the biocidal actions of the individual components. A similar synergy is exhibited with the V/N/C/T combination.

The data of Table 2 illustrates the change in the microbicidal susceptibility with water hardness particularly of Ps . aeruginosa as reflected by the increase in the minimum disinfection concentration. The data of Table 3 illustrates the change in the minimum disinfection concentration for Ps . aeruginosa as a function of formulation composition.

The data of Table 4 is shown as a 2-dimentional representation of a 3-dimentional response surface in Figure 2 clearly showing the combination of Neodol 91-8 and Vantocil IB required to obtain the maximum dilutability as exemplified by the smallest value for the minimum disinfection concentration (MDC) .

TABLE 1

TABLE 2

TABLE 3

TABLE 4

The invention is not limited to the examples hereinbefore described which may be varied in formulation and detail without departing from the spirit of the invention.

Claims

1. A composition comprising a nonionic surfactant, a terpene-like component, a cationic biocide which is compatible with the nonionic and the terpene-like component, and a source of alkalinity which ensures a pH of at least 8.5 in the composition, wherein the combination of at least two of the non-ionic, cationic and terpene-like components provides a synergistic antimicrobial action which is greater than the additive anti-microbial action of the at least two individual components .

2. A composition as claimed in claim 1 in which the terpene-like component comprises acyclic compounds such as citral, citronellal, citronellol and geraniol, alicyclic compounds such as terpineol, limonene and menthol, bridged alicyclic compounds such as pinene or camphor, aromatic compounds such as thymol or carvacrol and related or derived compounds such as esters and combinations thereof.

3. A composition as claimed in any preceding claim in which the cationic biocide is a biguanide.

4. A composition as claimed in any preceding claim in which the nonionic is an alcohol ethoxylate.

5. A composition as claimed in any preceding claim comprising: - at least 0.03% cationic biocide;

- at least 0.1% of a terpene-like component; and

- at least 1%, typically 5%, ethoxylated nonionic surfactant .

6. A composition as claimed in claim 5 comprising:

- between 0.03% and 0.15% cationic biocide;

- between 0.1% and 2% of a terpene-like component; and - between 2% and 10% ethoxylated nonionic surfactant.

7. A composition as claimed in any of claims 2 to 6 in which the terpene-like component comprises a mixture of citral and thymol.

8. A composition as claimed in any preceding claim having a pH of less than or equal to 12, preferably between 9 and 11.

9. A composition as claimed in any preceding claim in which the nonionic is Neodol 91-8.

10. A composition as claimed in any preceding claim further including a builder which is effective at prolonging the biocidal action of the cationic in a hard water

11. A composition as claimed in claim 10 in which the builder comprises an alkaline metal carbonate, an alkaline metal hydrogen carbonate, or mixtures thereof.

12. A composition as claimed in any preceding claim diluted up to 1 in 600 times, typically in water.

13. A process for disinfecting a surface comprising the step of treating the surface with a composition according to any of claim 1 to 11 or a diluted composition according to claim 12.

14. A use of a composition according to any of claims 1 to 12 to disinfect a surface.

15. A use, in a process for the preparation of a disinfecting composition for the treatment of a surface, which composition has a pH of at least 8.5, of a nonionic, typically ethoxylated, detergent, a cationic biocide and a terpene-like component.

16. A disinfectant composition comprising a nonionic surfactant and a cationic biocide which is compatible with the nonionic, wherein the combination of the nonionic and cationic components provides a synergistic antimicrobial action which is greater than the additive anti-microbial action of the two individual components.

17. A composition as claimed in claim 16 in which the cationic biocide is a biguanide, especially PHMB.

18. A composition as claimed in claims 16 or 17 further comprising a source of alkalinity which ensures a pH of at least 8.5 in the composition.

19. Use of a composition as claimed in claims 16 to 18 as an antibacterial, especially disinfecting, agent.

20. A use, in a process for the preparation of a disinfecting composition for the treatment of nonliving surfaces, of a composition as claimed in claims 16 to 18.

21. A process for disinfecting non-living surfaces which comprises the step of treating the surface with a composition according to any of claims 16 to 18.