WO2013034416A1

WO2013034416A1 - Antimicrobial method and composition

Info

Publication number: WO2013034416A1
Application number: PCT/EP2012/065985
Authority: WO
Inventors: Robert Joseph CORNMELL; Stephen Golding; Ian Peter Stott; Katherine Mary Thompson; David William Thornthwaite
Original assignee: Unilever N.V.; Unilever Plc; Hindustan Unilever Limited
Priority date: 2011-09-09
Filing date: 2012-08-16
Publication date: 2013-03-14

Abstract

The present invention relates to a method for disinfection involving an antimicrobial composition, an antimicrobial composition suitable for use in such a method and antimicrobial compounds. It particularly relates to an antimicrobial composition for personal cleaning, oral care or hard surface cleaning applications. It was found that compositions comprising selected terpinyl derivatives and a carrier provide antimicrobial action. In a preferred aspect the compositions of the invention also comprise 1 to 80 %-wt of surfactant.

Description

ANTIMICROBIAL METHOD AND COMPOSITION

FIELD OF THE INVENTION

The present invention relates to a method for disinfecting a surface. The invention particularly relates to a method for disinfecting a surface on the human body. The invention also relates to an antimicrobial composition. BACKGROUND TO THE INVENTION

Sanitising and disinfecting soap or cleaning compositions are of great benefit to individuals, since proper use generally may reduce the number of germs and pathogens the individual is exposed to. Thus, such compositions may for instance play an important role in reducing the occurrence and spread of

infectious diseases.

Sanitising and disinfecting soap compositions comprising chlorine-based antimicrobial agent such as triclosan are known. Such compositions require a rather long contact time to provide efficacious antimicrobial action. In practice, users, in particular children, do not spend a long time on cleansing and as a result cleaning with such compositions does not provide adequate prevention from surface or topical infection or adequate protection against diseases. The user, in spite of cleaning his hands, is generally likely to end up with

relatively inadequate bacterial removal from his skin.

Therefore, he may cause contamination of further animate and/or inanimate surfaces and contribute to the spreading of pathogens and consequent diseases. Users in general and children in particular who wash contaminated hands before meals with slow- acting antimicrobial compositions for a relatively short time are at risk of contracting diseases. Similarly in the area of hard surface cleaning, e.g. cleaning of floors, table tops or utensils, the antimicrobial actives in the compositions are in contact with the substrate for less than a few minutes after which the surface is either wiped off or rinsed with water. These short time scales of cleaning action are ineffective in providing the desired benefit since most known antimicrobials commonly used in such products take many minutes to hours to provide the desired kill of microbes. Therefore, there is a need of providing a method for

disinfection and an antimicrobial composition usable in such a method, wherein the method provides more efficacious

antimicrobial action during a relatively short cleaning period, preferably about 30 seconds or less.

Kubo et al [I Kubo, M. Himehima, H. Muroi; J. Agric. Food Chem. 39, 1984 (1991)] tested the antimicrobial activity of the ten most abundant volatile components of the Elattaria cardamomum seed, including alpha-terpinyl acetate. However, the activity of these natural substances was deemed not potent enough to be considered for practical use.

US 2010/111889 Al discloses a malodour control system,

comprising an aldehyde, an ester, an ionone and a macrocyclic musk. The ester may for instance be alpha-terpinyl propionate, terpinyl acetate, or beta-terpinyl-iso-butyrate . Odour

neutralization may be provided using ingredients that interact with and, through chemical reactions or sequestration, isolate or chemically or physically alter the malodour-producing compounds. US 2006/204488 Al discloses an antimicrobial composition comprising a lower chain alcohol, a preservative, a terpenoid, a skin conditioner, a thickener and an emulsifier. It also discloses a method of disinfection a substrate comprising the step of applying to the substrate an effective amount of the composition .

Despite the general availability of antimicrobial compounds, compositions, and methods, there remains a continuous need to find alternative antimicrobial methods, and compositions and/or active compounds that are suitable for use in such compositions and/or methods. In particular, alternative methods providing fast antimicrobial action remain highly desirable in view of current consumer habits. In case such alternatives are based on alternative compositions, they may reduce the dependency on current raw materials. Moreover, in the field of

antimicrobials, the availability of alternatives may reduce the risk of development of microbial resistance or insensitivity to particular antimicrobial compounds.

In addition, there is a continued need to reduce the total amount of active ingredients required in such an antimicrobial composition. This need may for instance be driven by the desire for cost-efficiency, because such compositions are particularly relevant to developing countries. Moreover, reducing the amounts may also be beneficial for environmental reasons.

A particular problem of terpinoids such as alpha-terpineol is that their olfactory properties, though appreciated in some fragrance compositions, may be considered too intense by some users when they are applied at concentrations efficacious in rapid disinfection. Additionally, a lower concentration of odoriferous compounds or the availability of antimicrobial compounds that are less odoriferous allows greater flexibility to the manufacturer in providing alternative scents to his composition at lower doses. Hence there is a need to provide alternatives that preferably require lower concentrations and/or have a more acceptable sensory profile.

In view of the above-observed problems and drawbacks of the prior art, it is an object of the present invention to provide an alternative method for sanitising and/or disinfecting, in particular of surfaces.

It is a particular object of the present invention to provide an alternative method for disinfecting surfaces based on an alternative antimicrobial composition.

It is another object of the invention to provide such a method, requiring a lower dose of antimicrobial composition. Similarly, it is an object of the present invention to provide a method based on an antimicrobial composition in which the olfactory contribution of the antimicrobially active compounds is reduced or in which the active compound contributes to providing a consumer-acceptable or even consumer-appreciated scent.

It is another object of the invention to provide a method for disinfection with a reduced disinfection time. In particular, it is an object of the invention to provide a method for disinfection that gives improved disinfection during cleansing of surfaces of the human body, such as the skin and the oral cavity.

It is a further particular object of the invention to provide such antimicrobial compositions that contribute to reducing the required contact time in a method for disinfection of a

surface .

In view of the other objects, it is also an object of this invention to provide antimicrobial compositions that are applicable in a method for disinfection of a surface.

SUMMARY OF THE INVENTION

We have now found that one or more of the above objects are met by the present invention. Thus, we have now found that a method for disinfection involving the step of applying an

antimicrobial composition comprising a terpinyl derivative provides for similar or more efficacious anti-microbial action at similar or lower concentrations of the applied composition when compared to for instance alpha-terpineol or alpha- terpineol acetate. We have consequently also found an

antimicrobial composition comprising a terpinyl derivative, whereby the composition is applicable in foresaid method. We have thereto also found several terpinyl derivatives that provide such compositions with antimicrobial properties. Accordingly, in a first aspect the invention provides a method of disinfecting a surface comprising the steps of

i. applying to the surface an antimicrobial composition comprising

a. 0.001 to 5% by weight of a terpinyl derivative, and

b. a carrier; and

ii. rinsing the surface with a suitable solvent or wiping the surface with a suitable wipe;

wherein the terpinyl derivative is selected from

i . alph -terpinyl esters and amides of the structure:

11. beta-terpinyl esters and amides of the following

structure

gamma-terpinyl esters and amides of the following structure

0

delta-terpinyl esters and amides of the following structure

v.4-te sters and amides of the following structure

vi . p-menth-l-en-9-yl esters and amides of the following structure

vii. dihydrocarvyl esters and amides of the following

structure

viii. isopulegyl esters and amides of the following

structure

and wherein X is NH or 0, and

wherein Ri is a linear or branched C₂ to C17 alkyl group, or

a linear or branched substituted C₂ to C17 alkyl group, or a linear or branched C₂ to C17 alkenyl group, or

a linear or branched C₂ to C17 substituted alkenyl group, or R₂OR₃, wherein R₂ is a linear or branched C_x alkyl group and

R₃ is a linear or branched C_y alkyl group, such that x + y is between and including 2 and 17, or

an alkyl ethoxylate (C¾) _x (OC₂H₄) _yOH group, wherein x is between 1 and 10, and y is between 1 and 10, or

an aliphatic C5 to C7 ring, or

a substituted aliphatic C5 to C7 ring, or

an unsaturated C5 to C7 ring, or

a substituted unsaturated C₅ to C₇ ring, or

an aryl group, or

a substituted aryl group, or

an aryloxy group, or

a substituted aryloxy group;

and mixtures of these terpinyl derivatives. According to a second aspect of the invention, there is

provided an antimicrobial composition comprising:

a. 0.005 to 5% by weight of a terpinyl derivative, and

b. a carrier;

wherein the terpinyl derivative is selected from alpha-terpinyl caproate,

alpha-terpinyl enanthate,

alpha-terpinyl nonanoate,

alpha-terpinyl cyclohexanoate,

beta-terpinyl isovalerate,

alpha-terpinyl butanamide,

beta-terpinyl propanamide,

gamma-terpinyl propanamide, delta-terpinyl propanamide,

and mixtures thereof.

According to a third aspect of the invention there is provided a terpinyl derivative compound selected from alpha-terpinyl caproate, alpha-terpinyl enanthate, alpha-terpinyl nonanoate, alpha-terpinyl cyclohexanoate, beta-terpinyl isovalerate, alpha-terpinyl butanamide, beta-terpinyl propanamide, gamma- terpinyl propanamide, delta-terpinyl propanamide, and mixtures thereof.

In a fourth aspect, the invention provides use of a terp derivative for improved hygiene, wherein the terpinyl

derivative is selected from

i . alph -terpinyl esters and amides of the structure:

11. beta-terpinyl esters and amides of the following

structure

gamma-terpinyl esters and amides of the following structure

delta-terpinyl esters and amides of the following structure

v.4-te sters and amides of the following structure

vi . p-menth-l-en-9-yl esters and amides of the following structure

vii. dihydrocarvyl esters and amides of the following

structure

viii. isopulegyl esters and amides of the following

structure

and wherein X is NH or 0, and

wherein Ri is

a linear or branched C₂ to C17 alkyl group, or

an aliphatic C5 to C7 ring, or

a substituted aliphatic C5 to C7 ring, or

an unsaturated C5 to C7 ring, or

a substituted unsaturated C₅ to C₇ ring, or

an aryl group, or

a substituted aryl group, or

an aryloxy group, or

a substituted aryloxy group;

and mixtures of these terpinyl derivatives. DETAILED DESCRIPTION OF THE INVENTION

For the avoidance of doubt, any feature of one aspect of the present invention may be utilised in any other aspect of the invention. The word "comprising" is intended to mean "inclding" but not necessarily "consisting of" or "composed of." Thus, the term "comprising" is meant not to be limiting to any subsequently stated elements but rather to optionally also encompass non-specified elements of major or minor functional importance. In other words, the listed steps or options need not be exhaustive. Whenever the words "including" or "having" are used, these terms are meant to be equivalent to

"comprising" as defined above. It is noted that the examples given in the description below are intended to clarify the invention and are not intended to limit the invention to those examples per se.

Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be

understood as modified by the word "about". Unless specified otherwise, numerical ranges expressed in the format "from x to y" are understood to include x and y. When for a specific feature multiple preferred ranges are described in the format "from x to y", it is understood that all ranges combining the different endpoints are also contemplated.

Throughout this description, the term disinfection refers to a reduction of the number of viable microorganisms in a given medium or on a given surface by physical or chemical means. Typically, disinfection involves the destruction or

inactivation of said microorganisms. Both animate and inanimate media and surfaces are contemplated. The antimicrobial method involves a composition comprising a terpinyl derivative and a carrier. Various steps of the method and various components of the antimicrobial composition are described below. The method and compositions of the present invention are preferred for non-therapeutic use, and more particularly preferred for use in cleaning surfaces of human body including skin, hair or oral cavity or for hard surface cleaning applications. Thus, the method of the present

invention preferably is a non-therapeutic method, and more preferably a method for cleaning surfaces of human body

including skin, hair or oral cavity or for hard surface

cleaning applications.

Method of disinfecting a surface

According to the first aspect of the invention, there is provided a method of disinfecting a surface. Preferably, the surface is skin. Thus, for example, a surface like the hands, face, body, or the oral cavity is contacted with the

composition of the invention. Alternatively, the surface is any hard surface. Typically, such hard surfaces are surfaces that commonly require cleaning and preferably also require

sanitisation or disinfection. Such surfaces may be found in many household or industrial environments, and may include for example kitchen and bathroom surfaces, table tops, floors, walls, windows, utensils, cutlery, and crockery. Such surfaces may be made from many different materials, including for instance plastics, wood, metal, ceramics, glass, concrete, marble, and painted surfaces.

The method according to the first aspect of the present

invention includes the step of applying to the surface an antimicrobial composition comprising

a. 0.001 to 5% by weight of a terpinyl derivative, and

b. a carrier. The composition may be applied to the surface by any suitable means known to the skilled person. For instance, a suitable means may be pouring, dropping, spraying or wiping in case of liquid compositions.

Preferably, the method includes diluting or dissolving the composition with a suitable solvent, preferably water, before or whilst applying the composition to the surface. Such

dissolving is preferred in particular in case the composition is a solid composition. Alternatively, solid compositions may also be directly spread, rubbed, or sprayed, e.g. in the form of a powder.

Terpinyl derivatives of step (i)

The terpinyl derivative of the composition to be applied is described here, the carrier is described below. The

antimicrobial composition to be applied comprises 0.001 to 5% by weight of a terpinyl derivative. The composition comprises preferably 0.005 to 4.5 wt-%, more preferably 0.01 to 4 wt-%, even more preferably 0.02 to 3 wt-%, yet more preferably 0.03 to 2 wt-%, still more preferably 0.04 to 1 wt ~6 , even more preferably 0.05 to 0.75 wt-% and still more preferably 0.1 to 0.5 wt-% of a terpinyl derivative. In compositions intended to be diluted before application, the minimum preferred

concentrations of the terpinyl derivative can be higher. For example, when washing hands with water and a composition according to the invention, the lather produced, typically is a 50 wt% dilution of the original composition. Similarly, in body wash situations, soap bars or soap liquids are typically diluted until about 8 wt% soap in water, corresponding to an approximately tenfold dilution of the product. Therefore, compositions according to the invention intended for dilution upon use preferably comprise 0.05 to 4.5 wt-%, more preferably 0.1 to 4 wt-%, even more preferably 0.2 to 3 wt-%, still more preferably 0.4 to 1 wt-%, and still more preferably 0.5 to 1 wt-% of the terpinyl derivative. Thus, the concentration of the terpinyl derivative in the antimicrobial composition is

preferably such that, when the composition is diluted or dissolved with a suitable medium during use, (e.g. when washing hands with water and a composition according to the invention) the concentration in the diluted or dissolved mixture is still sufficient to be antimicrobially efficacious.

The terpinyl derivative may be a single compound or may be a mixture of the terpinyl compounds as detailed below. In certain preferred embodiments, mixtures of terpinyl derivatives are preferred, since such mixtures may show increased antimicrobial activity against a wider range of microbes. Conversely, for reasons including e.g. control over the formulation, it is preferred that in case the composition according to the

invention comprises a mixture of such terpinyl derivatives, the mixture preferably comprises at least 30%, more preferably at least 50%, even more preferably at least 70% and still more preferably at least 90% by weight of one terpinyl derivative with respect to the total weight of the terpinyl derivatives. These preferred concentration ranges of the terpinyl derivative are important since below the preferred lower concentration limits of the terpinyl derivative, the desired fast acting antimicrobial kinetics would not be met. At concentrations higher than the higher preferred concentrations of the terpinyl derivative, while the kinetics of action would not be

compromised, the present inventors have found that unlike in therapeutic/pesticidal/herbicidal applications where sensorial aspects are not critical, in the present application, which is preferably a personal cleaning, oral care or hard surface cleaning application, the product is in contact with hands, mouth or other body parts, the sensorial aspects like smell and skin feel would be compromised. Thus, the composition should preferably not be sensorially unpleasant.

Terpinyl radical

The term terpinyl radical denotes the terpinyl headgroup, i.e. a terpinyl parent alcohol moiety in the way in which it is comprised as a substituent in a particular terpinyl derivative. The terpinyl derivative of the invention is selected from esters and amides with a terpinyl headgroup selected from alpha-terpinyl , beta-terpinyl , gamma-terpinyl , delta-terpinyl , 4-terpinyl, p-menth-l-en-9-yl, dihydrocarvyl , and isopulegyl headgroups . The structures of these derivatives are

schematically depicted in Table 1 below.

Table 1

*) X = 0 or NH, Ri: see below

Where applicable, the different stereoisomers of these terpinyl radicals are contemplated. Thus, compositions comprising enantiomerically pure radicals, racemic mixtures and other mixtures of different stereoisomers are equally preferable.

The parent terpinyl alcohol groups corresponding to these radicals are all members of the menthenol class of compounds [A L Gunatilaka, Natural products in Plants: Chemical Diversity in the Wiley Encyclopedia of Chemical Biology, pp 1-17 and E

Breitmaier, Terpenes: flavors, fragrances, pharmaca,

pheromones; p. 17, Wiley-VCH, 2006], also termed

oxytetrahydrocymenes [F Heusler, The Chemistry of the Terpenes, trans. F J Pond, P Blakistons's son & Co, Philadelphia, 1902, p. 21] which may be defined as monohydroxy alcohol derivatives of p-menthene, with the generic formula C₁₀H₁₇OH. Combinations of these terpineol parent alcohols are often found together in nature, because it is generally believed that their

biosyntheses proceed via closely related synthetic pathways. Without wishing to be bound by theory, it is believed that the mode of antimicrobial action of the derivatives of these terpinyl radicals is similar.

The terpinyl radicals may also be referred to by the

alternative names as detailed below in Table 2.

Table 2 alpha- p-menth-l-en- terpinyl 8-yl

p-menth-8-en- beta-terpinyl 1-yl gamma- p-menth-4 (8) - terpinyl en-l-yl

delta- p-menth-1 (7) - terpinyl en-8-yl

p-menth-1-en-

4-terpinyl 4-yl

p-menth-l-en- p-menth-l-en- 9-yl 9-yl

p-menth-8-en- dihydrocar yl 2-yl

p-menth-8-en- isopulegyl 3-yl

In nature, the isomeric compounds alpha-terpineol , beta- terpineol and gamma-terpineol are among the most abundant terpineols and often occur together in mixtures. Similarly, there is a relatively good availability of (mutually isomeric) alpha-, beta- and gamma-terpinyl derivatives and mixtures thereof. Therefore, preferably, the terpinyl derivative is selected form alpha-terpinyl , beta-terpinyl , and gamma- terpinyl derivatives, and mixtures thereof. Among these, alpha- terpinyl derivatives are often the most abundant compounds.

Hence, the terpinyl derivative of the present invention is even more preferably selected from alpha-terpinyl derivatives and mixtures thereof. Particularly preferred are mixtures of alpha- terpinyl, beta-terpinyl, and gamma-terpinyl derivatives.

The terpinyl derivative in the antimicrobial composition according to the invention is selected from terpinyl esters and amides. That is, terpinyl derivatives according to the

structures in the above table, wherein X is NH or 0.

Preferably, the terpinyl derivative is a terpinyl ester (i.e. X = 0) . Terpinyl esters are preferred, since they commonly occur in nature or may be readily synthesized from the relevant parent terpinyl alcohol and acid. Additionally, such terpinyl esters may possess pleasant sensory properties.

Alternatively, the terpinyl derivative is a terpinyl amide (i.e. X = NH) . Terpinyl amides advantageously are less

hydrolytically sensitive than terpinyl esters.

In case terpinyl esters are selected, the terpinyl derivative is preferably selected from alpha-terpinyl esters, beta- terpinyl esters, and gamma-terpinyl esters, and mixtures thereof. More preferably, the terpinyl ester is an alpha- terpinyl ester, due to the ready commercial availability of the parent alpha-terpineol and some alpha-terpinyl esters as fine chemicals. The terpinyl ester preferably is a mixture of terpinyl esters, more preferably a mixture of alpha-terpinyl esters, beta-terpinyl esters, and gamma-terpinyl esters.

Ri substituents

The antimicrobial composition according to the first aspect of the invention comprises a terpinyl derivative selected from the general structures inTable 1 above, wherein Ri is

a linear or branched C₂ to C17 alkyl group, or

a linear or branched C₂ to C17 substituted alkenyl group, or R₂OR₃, wherein R₂ is a linear or branched C_x alkyl group and R₃ is a linear or branched C_y alkyl group, such that x + y is between and including 2 and 17, or

an alkyl ethoxylate (CH₂) _x (OC₂H₄) _yOH group, wherein x is between 1 and 10, and y is between 1 and 10, or

an aliphatic C5 to C7 ring, or

a substituted aliphatic C5 to C7 ring, or an unsaturated C5 to C7 ring, or

a substituted unsaturated C₅ to C₇ ring, or

an aryl group, or

a substituted aryl group, or

an aryloxy group, or

a substituted aryloxy group;

and mixtures of these terpinyl derivatives.

In case Ri is selected to include a substituted group or substituted ring, the substituents can be any substituent known to the skilled person, for example halogens, hydroxyl groups, ethers, carboxylic acids, carboxylate salts, esters, amines, amides, ammonium salts, nitriles, nitrates, thiols, thioethers, sulfones, sulfates, phosphones, or phosphates. Particularly preferred substituted terpinyl derivatives are bifunctional derivatives, such as -for example- 1, 4-bis- (alpha-terpinyl) - succinate or 1, 6-bis- (alpha-terpinyl) -adipamide .

An advantage of the terpinyl derivatives in which Ri is an alkyl group is their synthetic availability. Terpinyl

derivatives in which Ri is selected from alkyl groups,

aliphatic rings, aryl groups and aryloxy groups according to the invention, may advantageously provide increased

organosolubility, which may be preferred in certain

compositions according to the invention. Conversely, the alkyl ethoxylate (CH₂) _x (OC₂H₄) _yOH substituents may be preferred as Ri if increased water-solubility is preferred.

Preferably, Ri is

a linear or branched C₂ to C₁₇ alkyl group, or

a linear or branched C₂ to C₁₇ alkenyl group, or R₂OR₃, wherein R₂ is a linear or branched C_x alkyl group and

an aliphatic C5 to C7 ring, or

an unsaturated C5 to C7 ring, or

an aryl group, or

an aryloxy group;

wherein Ri is preferably unsubstituted . More preferably, Ri is a linear or branched C₂ to C17 alkyl group, or an aliphatic C5 to C7 ring, or an aryl group.

In case the carrier or the dissolution medium during later application is water-based, it may be advantageous if the terpinyl derivative is sufficiently water-soluble. The terpinyl derivative is sufficiently water-soluble if it is soluble to at least the minimum concentration required in the antimicrobial composition according to the invention. Therefore, even more preferably, Ri is a linear or branched C₂ to C₁₂ alkyl group, or an aliphatic C5 to C7 ring, or an aryl group. Still more

preferably Ri is a linear or branched C₂ to C4 alkyl group, or an aliphatic C6 ring, or an aryl group.

Regarding the terpinyl derivatives of the present invention, it is particularly preferred that a preferred terpinyl radical is combined with a preferred X group and a preferred Ri group.

Thus -for example- preferable terpinyl derivatives may be selected from alpha-terpinyl esters, beta-terpinyl esters, and gamma-terpinyl esters, and mixtures thereof, wherein Ri is a linear or branched C₂ to C17 alkyl group, or a linear or

branched C₂ to C17 alkenyl group, or R₂OR₃, wherein R₂ is a linear or branched C_x alkyl group and R₃ is a linear or branched C_y alkyl group, such that x + y is between and including 2 and 17, or an aliphatic C5 to C7 ring, or an unsaturated C5 to C7 ring, or an aryl group, or an aryloxy group.

Thus, it is even more preferred that the terpinyl derivative is selected from alpha-terpinyl propionate, alpha-terpinyl

butyrate, alpha-terpinyl iso-butyrate, alpha-terpinyl

cyclohexanoate, alpha-terpinyl valerate, alpha-terpinyl

caproate, alpha-terpinyl enanthate, alpha-terpinyl caprylate, alpha-terpinyl caprate, and alpha-terpinyl laurate, and

mixtures thereof.

It is similarly preferred that the terpinyl derivative is selected from mixtures of alpha-terpinyl esters, beta-terpinyl esters and gamma-terpinyl esters, wherein the esters are selected from propionate esters, butyrate esters, iso-butyrate esters, cyclohexanoate esters, valerate esters, caproate esters, enanthate esters, caprylate exters, caprate esters, and laurate esters and mixtures thereof. Alternatively, it may also be preferred that the terpinyl derivative is selected from alpha-terpinyl isovalerate, alpha- terpinyl 2-methyl-butyrate, alpha-terpinyl nonanoate, alpha- terpinyl benzoate, alpha-terpinyl anthranilate, alpha-terpinyl cinnamate, and palmitate.

Alternatively, it may also be preferred that the terpinyl derivative is selected from beta-terpinyl propionate, cis-beta- terpinyl propionate, trans-beta-terpinyl propionate, beta- terpinyl butyrate, cis-beta-terpinyl butyrate, trans-beta- terpinyl butyrate, beta-terpinyl isobutyrate, cis-beta-terpinyl valerate, trans-beta-terpinyl vlalerate, beta-terpinyl

isovalerate, trans-beta-terpinyl benzoate and cis-beta-terpinyl benzoate . Alternatively, it may also be preferred that the terpinyl derivative is selected from gamma-terpinyl propionate, gamma- terpinyl butyrate and gamma-terpinyl valerate. Alternatively, it may also be preferred that the terpinyl derivative is selected from delta-terpinyl propionate, 4- terpinyl propionate, p-menth-l-en-9-yl propionate,

dihydrocarvyl propionate, isopulegyl propionate, and isopulegyl isobutyrate .

It is particularly preferred that the terpinyl derivative is selected from alpha-terpinyl propionate, alpha-terpinyl

butyrate, alpha-terpinyl iso-butyrate, alpha-terpinyl and cyclohexanoate, and mixtures thereof.

It is similarly preferred that the terpinyl derivative is selected from mixtures of alpha-terpinyl esters, beta-terpinyl esters and gamma-terpinyl esters, wherein the esters are selected from propionate esters, butyrate esters, iso-butyrate esters, cyclohexanoate esters, and mixtures thereof.

Alternatively, preferred terpinyl derivatives may be selected, which are amides. Preferred amides are ( S ) -alpha-terpinyl propanamide, alpha-terpinyl-butanamide, alpha-terpinyl 2- methylpropanamide, alpha-terpinyl 2-benzamide, beta-terpinyl propanamide, gamma-terpinyl propanamide, and delta-terpinyl propanamide .

Mixtures of preferred terpinyl derivatives are also preferred.

Suitable terpinyl derivatives according to the present

invention may be sourced from biological resources. For

example, alpha-terpinyl esters where Ri is a C2 or C3 substituent, commonly occur in nature, often in combination with alpha-terpineol . Alpha-terpinyl esters are used as

fragrance and flavour components [T B Adams, J B Hallaghan, J M Putnam, T L Gierke, J Doull, I C Munnro, P Newberne, P S

Portoghese, R L Smith, B M Wagner, C S Weil, L A Woods and R A Ford, Food and Chemical Technology, Volume 34, 1996, pp. 763- 828], [K Bauer, D Garbe, H Surburg, "Common Fragrance and

Flavor Materials", Wiley VCH, Weinheim, 1997, page 69] and several are GRAS (Generally Regarded As Safe) materials. For instance, alpha-terpinyl butyrate provides balsamic notes as described in US 2004/0242452.

Alternatively, suitable terpinyl derivatives according to the present invention may be obtained via synthetic chemical methods. Such methods are generally well-known. For example, terpinyl esters may be obtained from the parent terpinyl alcohol, by esterification methods as described in literature, e.g. [C Wiles, P Watts, S J Haswell and E Pombo-Villar,

Tetrahedron 59, 10173 (2003) ]

Method of disinfecting a surface - rinsing step

The method according to the first aspect of the present

invention also includes the step of rinsing the surface with a suitable solvent or wiping the surface with a suitable wipe. This step serves to remove the composition from the surface. Here, removing the composition also encompasses partially removing the composition, because traces of the composition may remain on the surface. In many typical situations, including washing of the skin or hard-surface cleaning, it is acceptable or sometimes even desirable if part of the composition - in particular certain active ingredients - remains on the surface. Therefore, this step preferably involves removing at least 5%, more preferably at least 10%, even more preferably at least 25%, still more preferably at least 50% and yet more preferably at least 75% of the composition by weight. The solvent for rinsing the surface is preferably water but could also be for example a mixture of water and alcohol. It is then rinsed preferably with sufficient amounts of water after a pre-determined period of time to remove any visible or sensory residue of the composition. Alternately an alcohol wipe or a water/alcohol impregnated wipe may be used to wipe the surface to be visibly free of the anti-microbial composition. The step of rinsing the substrate is preferably carried out less than 5 minutes, more preferably less than 2 minutes, further more preferably less than a minute and in many cases even more preferably less than 15 seconds after the step of applying the composition on the substrate. Even though partial microbial kill may be almost instantaneous upon application of the composition according to the invention, it is preferred that the step of removing the composition from the surface is started out at least 5 seconds, preferably at least 10 seconds, more preferably at least 15 seconds after commencement of the step of applying the composition on the surface, in order to effect optimal antimicrobial action. Combinations of these times into time intervals are preferred too. Therefore, it is particularly preferred that the step of removing the

composition from the surface (i.e. step ii) is started between 2 minutes and 5 seconds, more preferably between 1 minute and 10 seconds, even more preferably between 30 and 10 seconds and still more preferably between 20 and 15 seconds after commencement of the step of applying the composition on the surface (i.e. step i) . Disinfection time

These times between applying the composition and rinsing or wiping are preferably related to the disinfection time, in order to ensure optimal cleansing and sanitising of the

surface. Therefore, the invention preferably relates to a method, wherein the disinfection time T of said method is less than 300 seconds, preferably less than 60 seconds, and more preferably less than 15 seconds; wherein T is defined as the time that elapses from the moment of adding the composition to a microbial culture until the number of microbes per unit volume of the culture is reduced by a factor of 100 000; and wherein the initial number of microbes preferably exceeds about 100 000 000 microbes per millilitre and wherein the composition is preferably a liquid composition.

The disinfecting action (which can be expressed in terms of the disinfection time T) of the method is preferably determined according to the protocol of Example 2 as described

hereinafter. This test relates to a standardised test

environment in which the microbial culture is kept in

suspension. Alternatively, one of the test methods as described in WO 2010/046238 may for instance be applied to establish the disinfecting action.

Such test methods may preferably also be used by the skilled person to determine the optimal concentrations of the thymol and the terpinyl derivative in an antimicrobial composition according to the present invention.

Alternatively, since the method is directed towards surface disinfection, the disinfection time may also be determined by test methods involving a surface. Therefore, the invention preferably relates to a method according to the present

invention, wherein the surface disinfection time T2 of said method is less than 60 seconds, preferably less than 15

seconds, wherein T2 is defined as the time starting from the moment of applying the composition to the surface to be

disinfected after which the number of microbes per unit area is reduced by a factor of 10000 (i.e. a 4 log reduction), wherein the initial number of microbes preferably exceeds 10³, more preferably 10⁵, and even more preferably 10⁷ microbes per square centimetre. Such tests may for instance be performed as

described in WO 2010/046238, or as described in European

Standards EN 13697:2001 and EN 1500:1997.

Compositions according to the second aspect of the invention According to the second aspect of the invention, there is also provided an antimicrobial composition comprising:

a. 0.001 to 5% by weight of a terpinyl derivative, and

b. a carrier;

wherein the terpinyl derivative is selected from alpha-terpinyl caproate,

alpha-terpinyl enanthate,

alpha-terpinyl nonanoate,

alpha-terpinyl cyclohexanoate,

beta-terpinyl isovalerate,

alpha-terpinyl butanamide,

beta-terpinyl propanamide,

gamma-terpinyl propanamide, and

delta-terpinyl propanamide,

and mixtures thereof. The antimicrobial composition according to the second aspect of the invention preferably is suitable for use in the method according to the first aspect of the invention. Therefore, similar to the antimicrobial composition to be applied in the method of the first aspect of the invention, the antimicrobial composition according to the second aspect of the invention comprises 0.001 to 5% by weight of a terpinyl

derivative. The composition comprises preferably 0.005 to 4.5 wt-%, more preferably 0.01 to 4 wt-%, even more preferably 0.02 to 3 wt-%, yet more preferably 0.03 to 2 wt-%, still more preferably 0.04 to 1 wt-% and still more preferably 0.05 to 0.5 wt-% of a terpinyl derivative.

The terpinyl derivative may be a single compound or may be a mixture of the selected terpinyl compounds. In case the

composition according to the invention comprises a mixture of such terpinyl derivatives, the mixture preferably comprises at least 30%, more preferably at least 50%, even more preferably at least 70% and still more preferably at least 90% by weight of one terpinyl derivative with respect to the total weight of the terpinyl derivatives. The terpinyl derivative is preferably selected from alpha- terpinyl caproate, alpha-terpinyl enanthate, alpha-terpinyl nonanoate, alpha-terpinyl cyclohexanoate, beta-terpinyl

isovalerate, and mixtures thereof. More preferably, the

derivative is selected from alpha-terpinyl caproate, alpha- terpinyl enanthate, alpha-terpinyl nonanoate, alpha-terpinyl cyclohexanoate, and mixtures thereof.

Alternatively, if the composition comprises alpha-terpinyl esters, it may preferably also comprise beta-terpinyl esters and gamma-terpinyl esters. In that case, the terpinyl

derivative may be selected from mixtures of alpha-terpinyl esters, beta-terpinyl esters and gamma terpinyl esters, wherein the esters are caproate esters, enanthate esters, nonanoate esters, or cyclohexanoate esters, whereby the composition preferably comprises at least 0.001 %, more preferably at least 0.005 %, even more preferably at least 0.01 %, yet more

preferably at least 0.02 %, still more preferably at least 0.03 %, still more preferably at least 0.04 % and stil more

preferably at least 0.05 % by weight of alpha-terpinyl esters.

The general structures of the terpinyl derivatives of the composition according to the second aspect of the invention are among the structures of the terpinyl derivatives of the

composition to be applied in the method according to the first aspect of the invention, as described above. Additional features of the antimicrobial compositions

The explanations, definitions and further features of

antimicrobial compositions described below apply both to the compositions applicable in step (i) of the method according to the first aspect of the invention and to the antimicrobial compositions according to the second aspect of the invention.

Carrier

The antimicrobial composition according to the first or the second aspect of the invention comprises a carrier. The carrier is preferably selected from the group consisting of water, oil, solvent, inorganic particulate material, starch and mixtures thereof. The carrier is preferably from 0.1 to 99% by weight of the composition. The antimicrobial composition may be in form of a solid, liquid, gel, paste or soft solid and the carrier may be selected by a person skilled in the art depending on the format of the antimicrobial composition. Examples of inorganic particulate materials include clay, talc, calcite, dolomite, silica, and aluminosilicate . Examples of oils include mineral oils, oils of biological origin (e.g.

vegetable oils), and petroleum-derived oils and waxes. The oils of biological origin are preferably triglyceride-based.

Preferably, the carrier oil is not a perfume oil. Thus, the carrier oil preferably does not substantially contribute to the odour of the composition, more preferably it does not

contribute to that odour. Examples of solvents include alcohols (in particular ethanol and isopropanol) , ethers and acetone. The starch may be natural starch obtained from food grains or may be a modified starch.

Air can for instance be used as a carrier when the acyclic terpene alcohols according to the invention and/or the thymol are atomised or otherwise dispersed as a fine mist.

Particularly preferred carriers are water or oil/solvent and even more preferred is a carrier that is a mixture of water and oil. Thus, in many of the envisaged applications like personal care/washing, oral care and hard surface cleaning, the

antimicrobial composition may be formulated with either an aqueous base or a oil/solvent base. Compositions with an aqueous base (water being the carrier) , may also for instance be products in gel format. Compositions with a purely

oil/solvent base may for instance be products in anhydrous stick form or propellant-containing products.

Thus, the antimicrobial composition may for instance,

preferably be an antimicrobial anhydrous stick personal care composition on a purely oil/solvent base wherein the

composition has a water content of less than 0.01% by weight, and wherein the composition preferably is free of water.

Alternatively, the antimicrobial composition may for instance, preferably be an antimicrobial propellant-drivable personal care composition, also comprising a propellant. Air can also be used as propellant, for instance in the form of compressed or liquefied air.

However, the most preferred product format has an emulsion base (water and/or oil being the carrier) or is capable of forming an emulsion upon dilution, e.g. soap products in liquid, solid, lotion or semisolid form for hand wash, face wash, body wash, or shaving applications; toothpaste/ dentifrices for oral care applications or products for hard surface cleaning in bars or liquids form. If the product comprises an emulsion base, it preferably also comprises one or more surfactants as described below .

Surfactants

The antimicrobial composition according to the first or the second aspect of the invention preferably comprises from 1 to 80% by weight of surfactant. Surfactants may for instance advantageously contribute to the cleaning efficacy or the formulation stability of a composition. In general, the

surfactants may be chosen from the surfactants described in well-known textbooks like "Surface Active Agents" Vol. 1, by Schwartz & Perry, Interscience 1949, Vol. 2 by Schwartz, Perry & Berch, Interscience 1958, and/or the current edition of

"McCutcheon ' s Emulsifiers and Detergents" published by

Manufacturing Confectioners Company or in

"Tenside-Taschenbuch" , H. Stache, 2nd Edn., Carl Hauser Verlag, 1981; "Handbook of Industrial Surfactants" (4th Edn.) by

Michael Ash and Irene Ash; Synapse Information Resources, 2008. Any type of surfactant, i.e. anionic, cationic, nonionic, zwitterionic or amphoteric can be used. Preferably, the

surfactant is anionic, nonionic, or a mixture of anionic and nonionic surfactants. More preferably, the surfactant is anionic .

A particularly preferred surfactant is soap. Soap is a suitable surfactant for personal washing applications of the method of disinfecting a surface and the antimicrobial composition according to the invention. The soap is preferably C8-C24 soap, more preferably a C10-C20 soap and most preferably C12-C16 soap. The soap may or may not have one or more carbon-carbon double bonds or triple bonds. The cation of the soap can for instance be an alkali metal, alkaline earth metal or ammonium.

Preferably, the cation of the soap is selected from sodium, potassium or ammonium. More preferably the cation of the soap is sodium or potassium.

The soap may be obtained by saponifying a fat and/or a fatty acid. The fats or oils may be fats or oils generally used in soap manufacture, such as tallow, tallow stearines, palm oil, palm stearines, soya bean oil, fish oil, castor oil, rice bran oil, sunflower oil, coconut oil, babassu oil, palm kernel oil, and others. In the above process the fatty acids are derived from oils/fats selected from coconut, rice bran, groundnut, tallow, palm, palm kernel, cotton seed, soyabean, castor etc. The fatty acid soaps can also be synthetically prepared (e.g. by the oxidation of petroleum or by the hydrogenation of carbon monoxide by the Fischer-Tropsch process) . Resin acids, such as those present in tall oil, may be used. Naphthenic acids are also suitable.

Tallow fatty acids can be derived from various animal sources and generally comprise about 1 to 8% myristic acid, about 21 to 32 wt-% palmitic acid, about 14 to 31 wt-% stearic acid, about 0 to 4 wt-% palmitoleic acid, about 36 to 50 wt-% oleic acid and about 0 to 5 wt-% linoleic acid. A typical distribution is 2.5 wt-% myristic acid, 29 wt-% palmitic acid, 23 wt-% stearic acid, 2 wt-% palmitoleic acid, 41.5 wt-% oleic acid, and 3 wt-% linoleic acid. Other similar mixtures, such as those from palm oil and those derived from various animal tallow and lard are also included.

Coconut oil refers to fatty acid mixtures having an approximate carbon chain length distribution of 8 wt-% Cs, 7 wt-% Cio, 48 wt-% Ci2, 17 wt-% Ci₄, 8 wt-% Ci₆, 2 wt-% Ci₈, 7 wt-% oleic and 2 wt-% linoleic acids (the first six fatty acids listed being saturated) . Other sources having similar carbon chain length distributions, such as palm kernel oil and babassu kernel oil, are included within the term coconut oil.

A typical fatty acid blend consists of 5 to 30 wt-% coconut fatty acids and 70 to 95 wt-% fatty acids ex hardened rice bran oil. Fatty acids derived from other suitable oils/fats such as groundnut, soybean, tallow, palm, palm kernel, etc. may also be used in other desired proportions. The soap, when present in solid forms of the present invention, is preferably present in an amount of 30 to 80%, more preferably from 50 to 80 ~6 , even more preferably 55 to 75% by weight of the composition. The soap, when present in liquid forms of the composition is preferably present in 0.5 to 20%, more preferably from 1 to 10% by weight of the composition.

Other preferred surfactants are fatty acid glycinates and fatty amphocarboxylates . The fatty acid glycinates are fatty acid amides of salts of glycine, including for example sodium cocoyl glycinate. The fatty amphocarboxylates are amphoteric

surfactants including for example sodium lauroamphoacetate (i.e. sodium 2- [ 1- (2-hydroxyethyl ) -2-undecyl-4 , 5- dihydroimidazol-l-ium-l-yl ] acetate) . Yet another example of suitable surfactants are derivatives of isethionates , including acylisethionates . The method of disinfecting a surface according to the first aspect of the invention and the antimicrobial composition according to the second aspect of the invention are also useful in hard surface cleaning applications. In such applications, preferred surfactants are nonionic surfactants, such as C8-C22, preferably Cs-Ci₆ fatty alcohol ethoxylates, comprising between 1 and 8 ethylene oxide groups when the product is in the liquid form. When the product for hard surface cleaning applications is in the solid form, surfactants are preferably selected from primary alkyl sulphates, secondary alkyl sulphonates, alkyl benzene sulphonates, ethoxylated alkyl sulphates, or alcohol ethoxylate nonionic surfactants. The composition may further comprise an anionic surfactant, such as alkyl ether sulphate preferably those having between 1 and 3 ethylene oxide groups, either from natural or synthetic source and/or sulphonic acid. Especially preferred are sodium lauryl ether sulphates. Alkyl polyglucoside may also be present in the composition,

preferably those having a carbon chain length between C6 and C16. Other classes of useful surfactants include cationic surfactants, such as long chain quaternary ammonium compounds and amphoteric surfactants such as betaines and alkyl dimethyl amine oxides. Suitable surfactant concentrations in liquid forms of hard surface cleaning application are generally from about from 0.5 to 10%, preferably from 1 to 5 % by weight of the composition. In solid compositions, surfactant is

preferably present in 5 to 40%, preferably from 10 to 30% by weight of the composition. The method of disinfecting a surface according to the first aspect of the invention and the antimicrobial composition according to the second aspect of the invention are also useful in oral care compositions e.g. in a dentifrice/ toothpaste or an oral rinse product. In such applications, preferred

surfactants are anionic, nonionic or amphoteric in nature, preferably anionic or amphoteric. The anionic surfactant is preferably an alkali metal alkyl sulphate, more preferably a sodium lauryl sulphate (SLS) . Mixtures of anionic surfactants may also be employed. The amphoteric surfactant is preferably a betaine, more preferably an alkylamidopropyl betaine (wherein the alkyl group is a linear Cio-Cis chain) , and most preferably is cocoamidopropyl betaine (CAPB) . Mixtures of amphoteric surfactants may also be employed. Suitable surfactant

concentrations in oral care application are generally from about 2% to about 15%, preferably from about 2.2% to about 10%, more preferably from about 2.5 to about 5% by weight of the total composition. Thus, it is highly preferred that the antimicrobial

compositions include soap, alkyl sulphate or linear alkyl benzene sulphonate as the surfactants. More preferably, the surfactant is a soap, an alkyl sulphate or a linear alkyl benzene sulphonate.

The antimicrobial composition may be in form of a solid, a liquid, a gel or a paste. A person skilled in the art can prepare compositions in various formats by choosing one or more carrier materials and/or surfactant. The antimicrobial

compositions of the present invention are useful for cleansing and care, in particular for skin cleansing and skin care. It is envisaged that the antimicrobial composition can be used as a leave-on product or a wash-off product, preferably a wash-off product. The antimicrobial composition of the present invention can also be used for cleansing and care of hard surfaces such as glass, metal, plastic and the like. Liquid and solid compositions

A particularly preferred carrier in the antimicrobial

composition according to the first or the second aspect of the invention is water. When water is the carrier, both liquid and solid compositions are possible. Different amounts of water may be preferred depending on the product format. When water is present, it is preferably present in at least 1 ~6 , more

preferably at least 2%, further more preferably at least 5% by weight of the composition. When water is the carrier, a

preferred liquid antimicrobial composition according to the first or the second aspect of the invention comprises:

a. 0.05 to 5% by weight of the terpinyl derivative b. 10 to 99.9% by weight of water, and;

c. 1 to 30% by weight of surfactant. The liquid antimicrobial composition is useful for skin

cleansing, in particular for hand wash or face wash.

When water is the carrier, a preferred solid antimicrobial composition according to the invention comprises:

a. 0.05 to 5% by weight of the terpinyl derivative, b. 5 to 30% by weight of water, and;

c. 30 to 80% by weight of surfactant.

The solid antimicrobial composition is preferably in form of a shaped solid, more preferably a bar. The solid antimicrobial composition is particularly useful for skin cleansing in particular for hand wash or a face wash. Such a bar-shaped solid antimicrobial composition may for instance be a soap bar. Soap bar compositions are well-known and may be similar to the following non-limiting example composition, comprising 75.6 wt-% of anhydrous sodium soap, 1.0 wt-% of glycerine, 0.5 wt-% of sodium carbonate, 0.2 wt-% of EHDP (ethane-l-hydroxy-1 , 1-disphosphonate) acid, 0.04 wt-% of EDTA (ethylenediaminetetraacetic acid) tetrasodium salt, 8.5 wt-% of hydrated magnesium silicate (Talc), 0.7 wt-% of sodium chloride, 0.05 wt-% of dyes, 0.75 wt-% perfume, 0.05 to 10 wt-% of preservatives and antimicrobial agents including the

terpinyl derivates according to the present invention, and water up to 100 wt-%.

Alternatively, inorganic particulate material is also a

suitable carrier. When inorganic particulate material is the carrier, the antimicrobial composition is in a solid form.

Preferably the inorganic particulate material is talc. When the inorganic particulate material is talc, the solid antimicrobial composition is particularly useful as a talcum powder for application on face or body.

According to another alternative, a solvent (different from water) is a preferred carrier. Although any solvent can be used, alcohol is a preferred solvent. Short chain alcohols -in particular ethanol, propanol and isopropanol- are particularly preferred as carrier for an antimicrobial wipe or an

antimicrobial hand sanitiser composition.

Solvents like ethanol and isopropanol generally show

antimicrobial efficacy themselves. However, they are also volatile and may readily evaporate during application of the composition. Thus, their levels on the surface that is treated might even reduce until below the minimum level required for antimicrobial action, before the minimum period needed for disinfection has passed. In contrast, the terpinyl derivatives according to the present invention are much less volatile and may therefore yield prolonged antimicrobial action after applying them to the skin.

Additional ingredients

The composition according to the first or second aspect of the invention may further comprise various additional ingredients known to a person skilled in the art. Such additional

ingredients include but are not limited to: perfumes, pigments, preservative, emollients, sunscreens, emulsifiers, gelling agents, or thickening agents, humectants (e.g. glycerine, sorbitol), sequestrants (e.g. EDTA) or polymers (e.g. cellulose derivatives for structuring such as methyl cellulose) .

Some of the terpinyl derivatives according to the invention are known for their olfactory properties, and have been applied for instance in perfume compositions. However, the present

invention is directed towards antimicrobial compositions.

Therefore, the composition is preferably not a perfume

composition. Here, a perfume composition is defined as a composition comprising a plurality of olfactory components, where these components are solely intended to provide the composition with a harmonious scent.

Compounds according to the invention

According to a third aspect of the invention there is provided a terpinyl derivative compound selected from alpha-terpinyl caproate, alpha-terpinyl enanthate, alpha-terpinyl nonanoate, alpha-terpinyl cyclohexanoate, beta-terpinyl isovalerate, alpha-terpinyl butanamide, beta-terpinyl propanamide, gamma- terpinyl propanamide, delta-terpinyl propanamide, and mixtures thereof .

Preferably, the terpinyl derivative compound according to this aspect of the invention is selected from alpha-terpinyl

caproate, alpha-terpinyl enanthate, alpha-terpinyl nonanoate, alpha-terpinyl cyclohexanoate, and mixtures tehereof .

Use according to the invention

The invention preferably provides for non-therapeutic benefits. Thus, according to the fourth aspect of the invention, there is provided use of a terpinyl derivative for improved hygiene. Such use relates for example to use of an antimicrobial

composition comprising a terpinyl derivative according to the invention for reduction in microbial count, preferably fast reduction of antimicrobial count. Thus, such use preferably is use in a method for disinfection. Fast reduction in

antimicrobial count therefore preferably relates to use for disinfection whereby the disinfection time is less than 300 seconds, preferably less than 60 seconds, and more preferably less than 15 seconds. Here, the disinfection is preferably defined similar to the disinfection times T and T2 as described above . Preferably, the use according to the invention relates to use of a terpinyl derivative in an antimicrobial composition.

Suitable antimicrobial compositions are compositions according to the first or the second aspect of the invention. Similarly, the preferences regarding the terpinyl derivative according to the first aspect of the invention also are

preferred with respect to the terpinyl derivatives according to the fourth aspect of the invention. Alternatively, the terpinyl derivatives according to the second aspect of the invention are preferred .

Thus, there is provided use of a terpinyl derivative according to the invention for improved hygiene of surfaces of the human body. Such surfaces include e.g. skin, hands and the oral cavity. According to a preferred aspect, the invention relates to use of a terpinyl derivative for improved hand hygiene.

According to another preferred aspect, the invention relates to use of a terpinyl derivative for improved oral hygiene.

EXAMPLES

The invention is illustrated by the following non-limiting examples.

Example 1: Synthesis of alpha-terpinyl esters

Thymol, alpha-terpineol and alpha-terpinyl acetate were purchased as fine chemicals from Sigma Aldrich.

Other esters were synthesised by reaction of the alpha- terpineol alcohol with the appropriate acid chloride using a literature method [C Wiles, P Watts, S J Haswell and E Pombo- Villar, Tetrahedron 59, 10173 (2003) ] . Alternatively, esters were similarly synthesised starting from a commercial mixture of terpinyl esters, comprising about 70 wt-% of alpha- terpineol, 4 wt-% of beta-terpineol and 26 wt-% of gamma- terpineol . Alpha-terpineol (5 g, 32 mmol) was dissolved in dry THF (40 ml) and to it was added a suspension of sodium hydride (60%

dispersion in oil, 1.44g, 36 mmol) in dry THF (20 ml) . The mixture was then stirred at room temperature under an atmosphere of argon for 15 minutes before addition of the acid chloride (1.4 equivalents, 45 mmol) and then stirred at room temperature under argon for 2-3 hours. After this period, the reaction was quenched by dropwise addition of water to the reaction vessel until effervescence ceased. Saturated sodium bicarbonate solution (30 ml) was then added and the aqueous phase was separated and washed with dichloromethane (3 x 50 ml) . Organics were then combined, dried using a hydrophobic frit and concentrated to dryness. TLC indicated the presence of impurities so the crude materials were purified by column chromatography, eluting with a gradient of petroleum ether and ethyl acetate (varying from 2 to 10% ethylacetate) . Relevant fractions were identified by TLC, combined and concentrated to dryness yielding the desired products whose structures were confirmed by NMR.

Example 2: Assessment of antimicrobial efficacy

The efficacies of antimicrobial agents can be usefully compared by determining the Minimum Biocidal Concentration (MBC) . The MBC is defined as the absolute lowest concentration of actives that provides complete kill (zero bacterial growth) in a particular test environment.

Experimental method

Antimicrobial efficacy is tested against a representative pathogenic bacterial organism, Gram negative Escherichia coli. Concentrations of actives are expressed in terms of the

percentage weight/volume (%w/v) throughout Example 2. Bacterial stock

An overnight culture of Escherichia coli (10536 strain) was prepared in 50 ml total volume of TSB broth, grown for ca.

18 hrs at 37°C and shaken at 150 rpm. 1 ml of this overnight E. coli culture was transferred to 50 ml of fresh TSB broth and incubated at 37°C at 150 rpm for ca. 4 hours. This culture was separated into equal volumes and centrifuged at 4000 rpm for 15 minutes, washed with sterile saline (0.85% NaCl) ,

centrifuged once more and re-suspended in saline to give a final concentration of 0.8 OD₆2₀ equivalent to about 10⁸ cells per millilitre for this particular organism. Here, OD₆2₀ indicates the absorbance of a sample in a cuvette of 1.0 cm path length at a wavelength of 620 nm. This bacterial stock was used for assaying against antimicrobial actives (in

triplicate) .

Protocol

The following assay describes the testing of 8 materials using 6 dilutions across half of a 96-well micro titre plate (MTP) . Using this approach it is possible to assay 16 actives (without replicates) with one full dilution plate, replicating this set up in two halves of the plate columns, 1-6 and 7-12. 1M solutions of the test actives were prepared in

dimethylsulphoxide (DMSO) . Stock solutions of the actives at 1.11 times the desired final concentration were prepared by diluting the DMSO solutions in water, so that for example a 0.89% w/v solution was prepared for a desired "in test"

concentration of 0.8% w/v in order to allow for the further dilution of the active when the bacterial suspension is added (dilution from 270μ1 to 300 μΐ) , as described below.

Aliquots (270 μΐ) of the materials at 1.11 times the final concentration were dispensed into the wells of the MTP along one column (Al-Hl) . This MTP was labelled as the "Screening plate" . In another MTP, labelled as the "Dilution plate", 270μ1 of D/E neutralising solution from DIFCO Composition was added to column 1. The composition of the neutralising solution was as follows: pancreatic digest of casein, 5.0g/L; Yeast Extract, 2.5 g/L; Dextrose, 10 g/L, sodium thioglycollate, 1.0 g/L, sodium thiosulphate, 6.0 g/L; sodium bisulphite, 2.5 g/L;

Polysorbate 80, 5.0 g/L; lecithin 7.0 g/L; bromocresol purple, 0.02 g/L with a pH in the range 7.610.2. 270μ1 of tryptone diluent solution was added to all the

remaining wells of the Dilution MTP (columns 2-6) .

Bacterial stock (30 μΐ) was then added to the prepared 270 μΐ of the solution of actives in the Screening Plate and mixed, using a multichannel pipette with 8 tips to aspirate and dispense the same volume of bacterial stock in parallel to 8 wells in rows A-H. After a contact time of 15 seconds, the mixtures were quenched by transferring 30μ1 volumes of the mixtures into the 270μ1 D/E neutralising solution in the prepared dilution plate, using aspiration to mix. After exactly 5 minutes in the D/E neutralising solution, 30μ1 volumes were transferred from column 1 to column 2 of the Dilution MTP and mixed, before transferring further 30μ1 volumes from column 2 into column 3. This process was repeated serially diluting the bacteria across the plate to column 6.

30μ1 volumes from each well in the Dilution MTP were

transferred onto pre-labelled segment of Tryptone Soya Agar (TSA) plates starting from the lowest bacterial concentration (highest dilution, column 6) to the highest bacterial

concentration (column 1) . The TSA plates were allowed to stand for ca. 2 hours so that the 30μ1 inocula spots could dry and the plates were then inverted and incubated overnight at 37°C before enumerating the bacterial colonies at the labelled dilutions to determine the effects of the actives on bacterial growth . Calculation of results

Mean bacterial survival numbers N_MBS (expressed in Log CFU/ml) are obtained by first determining the segment of the TSA plate where the number of bacterial colonies is countable. From the colony number in this segment, N_MBS is calculated by the

formula:

M_BS = log{ N_COL · 10^DF · 100 / 3 }

Here, N_coi is the colony count, and DF is the dilution factor taken from the MTP-well corresponding to the TSA plate segment (i.e. DF may range from 1 for the quench, to 6 for the highest dilution) . The factor 100/3 is a conversion factor from the volume of the inocula spot to one millilitre.

Every assay test was performed in triplicate. The reported mean bacterial survival results are the average of such a triplet, the error is the corresponding standard deviation.

Thus, a value of N_MBS of about 7 corresponds to a count of about 3 colonies from the fifth dilution well, i.e. with DF = 5. Such a count of about 7 is generally observed when bacteria are exposed to non-biocidal materials. In case no surviving colonies are observed in any segment of the TSA plate, this is interpreted as complete kill and a value of N_MBS=0 is reported.

Validation

All test results were validated by running every test assay in parallel with four control experiments on the same MTP. All control experiments are executed exactly according to the above protocol, but with the following active ingredients:

A 0.025 % (w/v) thymol

B 0.15 % (w/v) alpha-terpineol C 0.025 % (w/v) thymol + 0.15 % (w/v) alpha-terpineol

D no active component

The control experiments A, B and D validate a test assay by not showing bacterial kill, whereas control experiment C,

comprising a synergistic combination of thymol and alpha- terpineol according to WO 2010/046238 Al validates a test assay by showing complete bacterial kill.

A reference experiment according to the above protocol, but without active component, showed that DMSO does not affect bacterial growth at the concentrations present in the test solutions in this protocol ( <5 % (w/v) ) , as can be seen in Table 3. Table 3

Resul ts

The above method was applied to asses the antibacterial

efficacy of terpinyl esters. In each of the below examples, the terpinyl ester, as prepared from the above described mixture of terpineols, comprised about 70 wt-% of alpha-terpinyl ester, 4 wt-% of beta-terpinyl ester, and 26 wt-% of gamma-terpinyl ester, all with the same acid residue. Therefore, in the results presented below, the mixtures are identified by their main constituent, the alpha-terpinyl ester. The reported concentrations refer to the total of the terpinyl esters. Table 4 shows the antibacterial activities of the terpinyl esters. Table 4: Antibacterial activities of alpha-Terpineol and alpha- Terpinyl esters alone and in combination with thymol

Antimicrobial compositions

As described above, the MBC for an active can be defined as the lowest measured concentration of the active that provides zero bacterial bacterial survival for the particular bacteria in the particular medium. For alpha-terpineol, the comparative

compositions (1) to (4), show that the MBC is 0.4% (w/v). The same analysis has been carried out for the terpinyl esters and is summarised in Table 5 below. The reported MBC values for the terpinyl esters constitute upper boundaries to the MBC. Table 5: Minimum Biocidal concentrations of antimicrobial components

It is clear from the data in Table 5 that the propionate, butyrate and cyclohexanoate esters of alpha-terpineol are more efficacious antimicrobials than alpha-terpineol itself and can be used at lower concentrations.

Claims

1. A method of disinfecting a surface comprising the steps of i. applying to the surface an antimicrobial composition comprising

a. 0.001 to 5% by weight of a terpinyl derivative, and

b. a carrier; and

wherein the terpinyl derivative is selected from

i . alph -terpinyl esters and amides of the structure:

11. beta-terpinyl esters and amides of the following

structure

gamma-terpinyl esters and amides of the following structure

delta-terpinyl esters and amides of the following structure

v.4-te sters and amides of the following structure

vi . p-menth-l-en-9-yl esters and amides of the following structure

vii. dihydrocarvyl esters and amides of the following

structure

viii. isopulegyl esters and amides of the following

structure

and wherein X is NH or 0, and wherein Ri is

a linear or branched C2 to C17 alkyl group, or

a linear or branched substituted C2 to C17 alkyl group, or a linear or branched C2 to C17 alkenyl group, or

a linear or branched C2 to C17 substituted alkenyl group, or

R₂OR₃, wherein R₂ is a linear or branched C_x alkyl group and

an aliphatic C5 to C7 ring, or

a substituted aliphatic C5 to C7 ring, or

an unsaturated C5 to C7 ring, or

a substituted unsaturated C₅ to C₇ ring, or

an aryl group, or

a substituted aryl group, or

an aryloxy group, or

a substituted aryloxy group;

and mixtures of these terpinyl derivatives.

2. A method according to claim 1,

wherein the terpinyl derivative is a terpinyl ester

3. A method according to claim 2,

wherein the terpinyl derivative is selected from alpha- terpinyl esters, beta-terpinylesters , and gamma-terpinyl esters, and mixtures thereof.

4. A method according to claim 3

wherein the terpinyl derivative is an alpha-terpinyl ester

5. A method according to claim 3 or 4

wherein Ri is

a linear or branched C2 to C17 alkyl group, or

a linear or branched C2 to C17 alkenyl group, or

R₂OR₃, wherein R₂ is a linear or branched C_x alkyl group and

an aliphatic C5 to C7 ring, or

an unsaturated C5 to C7 ring, or

an aryl group, or

an aryloxy group.

6. A method according to claim 5

wherein Ri is

a linear or branched C2 to C4 alkyl group, or

an aliphatic C6 ring, or

an aryl group.

7. A method according to claim 6, wherein the terpinyl

derivative is selected from

alpha-terpinyl propionate,

alpha-terpinyl butyrate,

alpha-terpinyl iso-butyrate, and

alpha-terpinyl cyclohexanoate, and mixtures thereof.

8. A method according to any one of claims 1 to 7, wherein the antimicrobial composition comprises from 1 to 80% by weight of surfactant.

9. A method according to any one of claims 1 to 8, wherein the disinfection time T is less than 300 seconds, preferably less than 60 seconds, and more preferably less than 15 seconds; wherein T is defined as the time that elapses from the moment of adding the antimicrobial composition to a microbial culture until the number of microbes per unit volume of the culture is reduced by a factor of 100 000; and wherein the initial number of microbes preferably exceeds about 100 000 000 microbes per millilitre and wherein the antimicrobial composition is preferably a liquid

composition .

10. An antimicrobial composition comprising:

a. 0.001 to 5% by weight of a terpinyl derivative, and

b. a carrier;

wherein the terpinyl derivative is selected from alpha-terpinyl caproate,

alpha-terpinyl enanthate,

alpha-terpinyl nonanoate,

alpha-terpinyl cyclohexanoate,

beta-terpinyl isovalerate,

alpha-terpinyl butanamide,

beta-terpinyl propanamide,

gamma-terpinyl propanamide,

delta-terpinyl propanamide,

and mixtures thereof.

11. An antimicrobial composition according to claim 10

comprising from 1 to 80% by weight of surfactant.

12. A terpinyl derivative compound selected from

alpha-terpinyl caproate,

alpha-terpinyl enanthate,

alpha-terpinyl nonanoate, alpha-terpinyl cyclohexanoate,

beta-terpinyl isovalerate,

alpha-terpinyl butanamide,

beta-terpinyl propanamide,

gamma-terpinyl propanamide,

delta-terpinyl propanamide,

and mixtures thereof.

13. Use of a terpinyl derivative for improved hygiene, wherein the terpinyl derivative is selected from

i . alph -terpinyl esters and amides of the structure:

11. beta-terpinyl esters and amides of the following

s ructure

gamma-terpinyl esters and amides of the following structure

0

R,

delta-terpinyl esters and amides of the following structure

v.4-te sters and amides of the following structure

vi . p-menth-l-en-9-yl esters and amides of the following structure

vii. dihydrocarvyl esters and amides of the following

structure

viii. isopulegyl esters and amides of the following

structure

and wherein X is NH or 0, and wherein Ri is

a linear or branched C2 to C17 alkyl group, or

a linear or branched C2 to C17 substituted alkenyl group, or

R₂OR₃, wherein R₂ is a linear or branched C_x alkyl group and

an aliphatic C5 to C7 ring, or

a substituted aliphatic C5 to C7 ring, or

an unsaturated C5 to C7 ring, or

a substituted unsaturated C₅ to C₇ ring, or

an aryl group, or

a substituted aryl group, or

an aryloxy group, or

a substituted aryloxy group;

and mixtures of these terpinyl derivatives.

14. Use according to claim 13 for improved hand hygiene.

15. Use according to claim 13 for improved oral hygiene.