WO2008035101A2

WO2008035101A2 - Disinfectant emulsions containing an antimicrobial compound in each phase

Info

Publication number: WO2008035101A2
Application number: PCT/GB2007/003606
Authority: WO
Inventors: Lars Kilaas; Inga Aasen; Anne Dyrli; Heidi Johnsen; Jo Klaveness; Petter Mehren; Julian Cockbain
Original assignee: MAINSANI AS
Current assignee: MAINSANI AS
Priority date: 2006-09-21
Filing date: 2007-09-21
Publication date: 2008-03-27
Anticipated expiration: 2009-03-21
Also published as: WO2008035101A3; GB0618657D0

Abstract

The invention provides a disinfectant emulsion composition having a continuous phase having dissolved therein a first antimicrobial agent and a discontinuous phase having dissolved therein a second antimicrobial agent.

Description

Disinfectant Compositions

This invention relates to disinfectant emulsion compositions, in particular to compositions for use in hand disinfection by medical personnel (e.g. physicians, surgeons, nurses) and by food production workers and by others where hand disinfection is needed or wanted.

Hand disinfectants are used extensively in hospitals and other health care institutions as well as in food production centres. In the case of health care workers, such disinfectants are used in particular before surgical procedures and typically comprise an aqueous alcoholic solution often containing a disinfectant such as chlorhexidine or benzalkonium chloride. One review of disinfectants and their activities and modes of action is McDonnell et al, Clinical Microbiology Reviews ^2:147-179 (1999).

In order that the operating theatre personnel should not pick up contamination as a result of the hand washing procedure, the disinfectant is frequently delivered by apparatus which does not require contact by the user. Such devices are disclosed in US-A-5477984, US-A- 5074322, US-A-4670010, and JP-A-2005-052352. Such devices generally spray a disinfectant solution from a reservoir over the user ' s hands .

Besides disinfectant solutions, there have been proposals for disinfectant oil-in-water emulsions, e.g. as described in WO 2005/030172, WO 2005/027872, WO 95/31966, WO 99/33459 and WO 96/33725.

There is however a continuing need for economic and effective hand disinfectants with good user compliance, i.e. which the user is willing to apply correctly. We have now found that particularly effective hand disinfectants may be produced in the form of emulsions in which the continuous and discontinuous phases each contain a dissolved antimicrobial, i.e. disinfectant, agent .

Thus viewed from one aspect the invention provides a disinfectant emulsion composition, in particular a composition for disinfecting human or animal external body surfaces and especially hands, having a continuous phase having dissolved therein a first antimicrobial agent and a discontinuous phase having dissolved therein a second antimicrobial agent.

The disinfectant emulsion compositions of the invention may be water-in-oil or oil-in-water emulsions or indeed may use two immiscible solvents neither of which is aqueous. Nonetheless the use of oil-in-water emulsions is preferred. Moreover the first and second antimicrobial agents are preferably immiscible with the solvent bases for the phase in which they are not dissolved. It is especially preferred that the composition comprise a cationic surfactant and that the oil phase contains an oil-soluble, water-immiscible antimicrobial agent and the aqueous phase comprises a disinfectant polymeric polycationic species, and optionally an alcohol. The aqueous phase however may be substantially alcohol-free, e.g. with an alcohol content of less than 5% wt., especially less than 1% wt.

The emulsion compositions of the invention will typically be supplied in stable form packaged in cartridges for insertion into dispensers, eg wall mounted dispensers. In view of this, it is especially desirable that they remain in emulsion form from packaging to dispensing rather than being provided in a non-emulsion form for conversion into an emulsion, eg by shaking, immediately before administration. Thus the emulsion should be stable to the extent that it is not broken on standing for a period of less than 1 day, especially less than 10 days.

The compositions of the invention are preferably packaged in sealed cartridges which may be attached to a disinfectant dispenser, preferably an automated dispenser having a pump for disinfectant dosing, e.g. onto the hands of the user. Such cartridges form a further aspect of the invention. Viewed from this aspect the invention provides a sealed cartridge having a fluid reservoir with an outlet port adapted to engage with a disinfectant dispenser, said reservoir containing a disinfectant composition, preferably an emulsion and especially preferably a composition according to the invention. The cartridge volume, i.e. the maximum liquid content, preferably lies in the range of 10 ml to 10 litre, more preferably 50 ml to 5 litres, especially preferred from 100 ml to 4 litres.

Viewed from a further aspect the invention provides a method of disinfecting the hands of a human subject, e.g. a health care worker, food producer or other user, which method comprises spraying an emulsion according to the invention over the hands of said subject, rubbing said emulsion onto said hands, optionally rinsing said emulsion from said hands, and optionally drying said hands. In this method, the quantity of emulsion applied will generally be in the range 0.1 to 10 mL, especially 0.2 to 5 mL. The emulsion is preferably maintained on the hands for at least 30 seconds, more preferably at least 1 minute. The disinfectant might be washed off but is preferably not washed off so as to obtain a long term disinfectant effect.

In the compositions of the invention, the oil phase preferably makes up no more than 50% of the volume, more preferably no more than 30%, especially no more than 25%. The oil phase preferably makes up at least 2% of the volume, more preferably at least 5%, especially at least 10%. The balance of the volume is the aqueous phase and any solid phase. If a solid phase is present it preferably makes up no more than 5% of the volume, especially no more than 2%.

The oil phase preferably is in microdroplet , nanodroplet or nanoparticulate form, e.g. having a mode particle diameter of 10 run to lOμm, especially 20 run to 2μm, particularly 20 to 500 ran, especially 50 to 200 ran. Mode particle diameter may readily be determined using a particle size analyser, e.g. a Coulter LS-230 apparatus.

The emulsions of the invention will typically be prepared by emulsification of an aqueous component and an oil component, e.g. using standard emulsification techniques and apparatus. Preparation of oil-in-water emulsions in which the oil droplets are nanoparticulate is described for example in WO 2005/02782 and WO 96/23409.

The aqueous and oil components preferably contain the ingredients of each phase of the emulsion in solution form before emulsification takes place.

The aqueous component for the preparation of the emulsion may comprise as a base an alcohol :water mixture in a volume ratio of 10:90 to 90:10, preferably 20:80 to 80:20, particularly 30:70 to 70:30, especially 35:65 to 50:50, eg 38:62 to 48:52. The use of alcohol contents towards the higher end of these ranges, eg 50:50 to 90:10, especially 60:40 to 80:20, particularly 65:35 to 75:25, is feasible but may result in poorer stability. The alcohol used is preferably a Ci_₆ alkanol, e.g. methanol, ethanol, n-propanol, iso-propanol, n-butanol, etc. Ethanol and isopropanol are especially preferred. The oil component for the preparation of the emulsion preferably comprises as a base a mono, di or triglyceride, particularly preferably of marine (e.g. fish oil) or plant origin, especially a plant oil, or a mixture of two or more such materials .

Particularly preferred plant oils include soybean oil, sunflower oil, safflower oil, rapeseed oil, olive oil, corn oil, peanut oil and almond oil, especially peanut oil and almond oil.

Other physiologically tolerable water-immiscible liquids may however be used if desired as the oil base, e.g. mineral oils. The use of aliphatic hydrocarbons as the oil base, or as the majority of the oil base, is generally not preferred.

As mentioned above, the aqueous phase in the emulsions of the invention preferably contains a dissolved polycationic species, i.e. a compound having a plurality of cationic groups, particularly one having a minimum of 10 cationic groups.

The polycationic species may contain the cationic groups as part of the polymer backbone; alternatively they may be pendant from the polymer backbone. Suitable polycations include oligo- and polypeptides having pendant amino functions as well as other synthetic polyamines. Particularly preferably, the polycation comprises a carbon backbone with fused thereto nitrogen- containing heteroatomic rings, e.g. azacyclopentane or azacyclohexane rings. Especially preferably the polycation comprises quaternary ammonium cationic groups . One category of such polycations includes polymers or copolymers of diallyldialkyl ammonium compounds, e.g. polydiallyldimethyl ammonium chloride (poly-DADMAC) . PoIy-DADMACs are available commercially from Sigma-Aldrich. Typically, the molecular weight of such polycations will be in the range 1000-2000000 Da, especially 50 to 1000 kDa. The polycation will preferably be used at a concentration of 0.0001 to 5 wt% relative to the weight of the basic aqueous component (i.e. relative to the total weight of water and alcohol), more preferably 0.001 to 2.0 wt%, especially 0.01 to 0.8 wt%.

The oil-soluble water-immiscible antimicrobial reagent used in the emulsions of the invention may be any physiologically tolerable material having these properties . Preferably however it is a phenolic compound, especially preferably a phenolic found in plants. Examples of such compounds include thymol, eugenol, and carvacrol. Thymol is especially preferred. Antimicrobial alcohols such as linalool may desirably be used. The use of chlorhexidine and hexachlorophene is also preferred. The oil-soluble antimicrobial is preferably used at a concentration of up to 40 wt% relative to the total weight of the oil phase, especially 1 to 25 wt%, particularly 2 to 20 wt% .

Some of the antimicrobials, or their salts, are both water and organic solvent/oil soluble and can be introduced into either or both of the oil and aqueous components from which the emulsion is prepared, e.g. chlorhexidine .

The emulsion also preferably contains a cationic surfactant which serves, i.a., to facilitate emulsification and to stabilise the resulting emulsion. Particularly preferably at least one such surfactant is dissolved in the aqueous component and at least one such surfactant is dissolved in the oil component before emulsification. Such surfactants may be the same, but preferably are different. Especially preferably at least one such surfactant is a quaternary ammonium compound, and it is particularly preferred that the oil and aqueous components each contain a different quaternary ammonium cationic surfactant. It is especially preferred that a phospholipid, or a phospholipid derivatized to enhance surfactant or emulsifier properties, is used. Such phospholipids may typically be of plant, marine or animal origin. Where a derivatized phospholipid is used, it will generally be desirable also to introduce a further water-soluble compound, eg a quaternary ammonium salt.

It is especially preferred that at least one of the cationic surfactants, particularly the one used in the oil component, is a quaternary fatty amine alcoholate, e.g. an ethoxylate. Examples of such compounds include Stepantex VK90 from Stepan Ltd and Silsense Q-Plus from Noveon Inc, Cleveland, Ohio, US.

It is also particularly preferred that at least one of the cationic surfactants, particularly the one used in the aqueous component, is a fatty quaternary amine, e.g. a fatty trimethyl ammonium compound or a fatty pyridinium compound, for example cetyl trimethyl ammonium chloride (CTAC) or cetyl pyridinium chloride (CPC), especially CTAC. Further examples of such compounds include cetyl trimethylammonium bromide (CTAB), Lanquat BC50, dialkyldimethylammonium carbonates ^•and behentrimonium chloride. Benzalkonium chloride, a mixture of benzyl dimethyl alkyl ammonium salts, is especially preferred.

The cationic surfactants are preferably used at a concentration in the aqueous component of 0.01 to 20%wt, especially at least 0.05%wt, preferably at least 0.1%wt and preferably no more than 15%wt, especially no more than 10%wt (eg 0.5 to 20 %wt., especially 2 to 15 %wt., particularly 5 to 10 %wt.), and 0.01 to 30 %wt. in the oil component, especially up to 20%wt, eg 1 to 20 %wt., particularly 5 to 15 %wt . In the resulting emulsion, they will to a significant extend distribute at the oil- water phase boundary and their total concentration in the overall emulsion is preferably 0.005 to 2 %wt., particularly 0.2 to 1.5 %wt . , especially 0.5 to 1 %wt .

In the resulting emulsion, such surfactants of course distribute heavily at the oil/water interface and the can be added to one or both of the oil and water components from which the emulsion is prepared. Thus the preferred contents may be derived from the values specified in the previous paragraph and the selected weight ratio of the oil and water phases . Most of the surfactants are soluble in water and some are soluble in organic solvents (eg benzene, ether, chloroform, etc) and so can be introduced into the oil component in dissolved form. Thus benzalkonium chloride and cetyl pyridinium chloride are typical candidates for introduction into either or both of the oil and aqueous components from which the emulsions are then prepared.

Besides the components mentioned above, the emulsion compositions of the invention may contain further ingredients. Examples of such further ingredients include, in particular, further antimicrobial agents, skin softening agents, abrasives, colorants, odors, pH modifiers, viscosity modifiers, emulsion stabilizers, antimicrobial potency enhancers, etc.

It is particularly preferred that the emulsion compositions include a skin softener, e.g. a polyol or polyether, for example glycol, propylene glycol or polyethylene glycol. Typically this may be included at concentrations of 0.01 to 10 %wt. relative to the total composition weight, especially 0.1 to 5 %wt., particularly 0.3 to 3 %wt .

To enhance the skin scrubbing effect of rubbing the hands with the emulsion of the invention, it is preferred that it contain a water-insoluble particulate ■as an abrasive, e.g. silica. The particle size for the abrasive will typically be 50 to 500 μm. The abrasive will conveniently be present as less than 5% vol of the total emulsion volume, especially less than 2% vol.

To enhance emulsion stability, it is especially preferred to include within the aqueous phase a cellulose ether, e.g. hydroxypropylmethylcellulose, for example at a concentration of 0.1 to 10% wt. relative to the weight of the aqueous base, particularly 0.2 to 5% wt.

In an especially preferred embodiment, a phospholipid, or phospholipid derivative, emulsion stabiliser is used, eg at a concentration of up to 20%wt, preferably 1 to 15%wt, particularly 3 to 10%wt, relative to the total weight of the (rest of) the oil component.

As antimicrobial potency enhancers for use in the emulsions of the invention, mention may be made of chelating agents such as EDTA and DTPA and salts thereof.

Examples of antimicrobial agents which may be used according to the invention include: hexachlorophene benzalkonium chloride, cetyl pyridinium chloride, didecyldimethylammonium chloride, dibromopropamidine and chlorhexidine. Typically these will be present at 0.01 to 5 %wt., especially 0.05 to 4% wt .

The pH modifiers, where used, will preferably serve to bring the pH of the aqueous phase to 5 to 7.5, especially 5.5 to 6.5. pH modifiers conventionally used in topical pharmaceutical, cosmetic and disinfectant products may be used.

The cartridge containing the compositions of the invention will typically have a liquid content (i.e. an emulsion content) of 10 to 10000 mL, especially 100 to 4000 mL. The cartridges may be of glass, metal, plastic or less preferably plastic or foil lined paper and may be rigid or, more preferably, flexible. Besides having an outlet port through which the emulsion may be expelled, they may also be provided with an inlet port for gas or air to replace expelled emulsion or to expel the emulsion. Numerous liquid dispenser cartridges are known from the prior art and cartridge design need not be explained in detail herein.

The invention will now be described with reference to the following non-limiting Examples and the accompanying drawing in which:

Figure 1 is a schematic cross-sectional drawing of one embodiment of a cartridge according to the invention.

Referring to Figure 1 there is shown a cartridge 1 comprising a reservoir 2 containing a emulsion disinfectant composition 3. The cartridge has a neck 4 adapted for snap fitting into a dispenser (not shown) and providing an outlet port 5 sealed by membrane 6.

Example 1

Emulsion

A mixture of Amygdalae Oleum (10 g) and hexadecane (0,1 g) was emulsified in distilled water (10 g) containing cetyl pyridinium chloride (CPC) (0,03g) using an ultrasonic device, LabSonic 2000 (head diameter 2 cm) at 200W for 2 min. The mean emulsion droplet size (by number) was 0.263 μm (CV: 63%) measured in a' COULTER LS 230. Example 2

Nano Emulsion

Thymol (0,2g) and Stepantex VK90 (0.2g) were mixed in Aracidis Oleum (1.6Og). The resulting solution was emulsified in distilled water (17.8Ig) containing CTAC (O.lδg) and PEDAC (P-141) (0.009g) . The emulsification was performed using an ultrasonic device, LabSonic 2000 (head diameter 2 cm) at 200W for 2 min. The mean emulsion droplet size (by number) was 78 nm (CV: 58%) measured in a COULTER LS 230.

Example 3

Activity against Gram-positive and Gram-negative bacteria

The antimicrobial effect of oil-in-water emulsions against Gram-negative (E.coli) and Gram-positive (S. aureus) bacteria was investigated for a range of emulsions according to the invention, the details of which are set forth in Table 1 below. In all cases the oil phase was 10 %vol of the total volume and used peanut oil as the oil base. Unless indicated otherwise, the emulsions were prepared by emulsification at 200 W for 2 minutes using ultrasound. The efficacy was determined in terms of the log reduction in the bacterial count after 5 minutes contact. A log ≥4 reduction was rated +++, ≥2 as + and <2 as 0. The results are set out in Table 1. Table 1

* repeated with same results with emulsification for 4 minutes in an Ultraturax T-25 set at strength 4.

+ emulsified for 4 minutes in an Ultraturax T-25 set at strength 4 using twice the quantity of oil

Components :

A: CTAC

B: CPC

C: PEDAC - low molecular weight poly DADMAC (100-200 kDa) , P-141 from Sigma-Aldrich D: PEDAC - high molecular weight poly DADMAC (400-500 kDa) , P-142 from Sigma-Aldrich E: Stepantex VK90, from Stepan Ltd F : Thymol

To test antibacterial efficacy, the emulsion was added to a suspension of bacteria in water. After the test time, a sample was removed and diluted with a neutralizing reagent. The solution and a control was put in stripes on agar plates at a series of log ^• dilutions and after incubation for a couple of days the number of bacterial colonies was counted.

Example 4

Emulsion comprising ethanol, benzalkonium chloride and thymol

Benzalkonium chloride (50 mg) and Thymol (50 mg) were added to a mixture of ClinOleic® (6 ml) and ethanol (4 ml, 96%) . The mixture was stirred for 5 minutes using an IKA Ultra Turrax at 24 000 rpm. The product obtained was a white emulsion. The product was stable on standing at room temperature for days. The emulsion was also stable during centrifugation using an Eppendorf MiniSpin Plus centrifuge (1 minute, 2000 rpm) .

ClinOleic® is a commercial product from Baxter for parenteral administration. 1000 ml ClinOleic® contains: purified olive oil and purified soya bean oil (4:1) 200 grams; phospholipids from egg 12 grams; glycerol 22.5 grams; sodium hydroxide q.s. ad pH 6-8; and water to 1000 ml.

Example 5

Emulsions comprising benzalkonium chloride and various phenols based on soya bean oil/olive oil/phospholipids

Benzalkonium chloride and various phenols (thymol, linalool, eugenol and carvacrol) were added to ClinOleic® emulsion and mixed for 5 minutes using IKA Ultra Turrax at 24 000 rpm. The amounts of components in the emulsions are shown in Table 2 below.

Table 2

Emulsion ClinOleic® Benzalkonium T L E C

No ml mg mg mg mg mg

1 10 10 100

2 10 50. 100

3 10 100 100

4 10 200 100

5 10 100 100

6 10 100 100

7 10 100 100

8 10 100 50 50

9 10 100 50 50

10 10 100 50 50

11 10 100 50 50 50

T : Thymol

L : Linalool

E : Eugenol

C : Carvacrol

Example 6

Stability testing of emulsions prepared in Example 5

All emulsions prepared in Example 5 were stable on standing at room temperature for days. For extended evaluation of stability, the emulsions were centrifugated using an Eppendorf MiniSpin Plus centrifuge (3 minutes, 4000 rpm) . All emulsions were stable. More extensive centrifugation (3 minutes, 8000 rpm) destroyed all emulsions including pure ClinOleic®.

Example 7

Emulsions comprising cetylpyridinium chloride and various phenols based on soya bean oil/olive oil/phospholipids

Cetylpyridinium chloride and various phenols or alcohols (thymol, linalool, eugenol and carvacrol) were added to ClinOleic® emulsion and mixed for 5 minutes using IKA. Ultra Turrax at 24 000 rpm. The amounts of the components in each of the emulsions are shown in Table 3 below.

Table 3

Emulsion ClinOleic® Cetylpyridinium T L E C

No. chloride ml mg mg mg mg mg

1 10 10 100

2 10 50 100

3 10 100 100

4 10 200 100

5 10 100 100 100

6 10 100 100

7 10 100 100

8 10 50 50 50

9 10 50 50 50

10 10 50 50 50

11 10 50 50 50 50

T . Thymol

L : Linalool

E : Eugenol

C : Carvacrol Example 8

Stability testing of emulsions prepared in Example 7

All emulsions prepared in Example 7 were stable on standing at room temperature for days. Centrifugation studies, as described in Example 6, showed that all emulsions were stable.

Example 9

Emulsions comprising thymol and cetylpyridinium chloride based on peanut oil

Cetylpyridinium chloride and thymol were added to a mixture of peanut oil and water. The amount of components in each mixture are shown in Table 4 below. The mixtures were shaken for 1 minute using a SM ESPE CapMix shaker. The emulsions were stable at room temperature for days .

Table 4

Emulsion no. Peanut oil Water Thymol Cetylpyridinium chloride mg mg mg mg

1 50 950 5 5 2 100 900 5 5 3 200 800 5 5 4 300 700 5 5

Intermediate 1

Emulsions comprising thymol and 1, 2-dipalmitoyl-sn- glycero-3-phosphomethanol based on peanut oil

Thymol and the sodium salt of 1, 2-dipalmitoyl-sπ- glycero-3-phosphomethanol were added to a mixture of peanut oil and water. The amounts of the components in each emulsion are shown in Table 5 below. The mixtures were shaken using a SM ESPE CapMix shaker for 1 minute. The mixtures were stable at room temperature for days .

Table 5

Emulsion Peanut oil Water Thymol Phosphomethanol No. mg mg mg mg

1 50 950 5 10

2 100 900 5 10

3 200 800 5 10

4 300 700 5 10

Example 10

Emulsions comprising thymol and benzalkonium chloride based on peanut oil/phosphomethanol derivative

Benzalkonium chloride (5 mg) was added to the emulsions of Intermediate 1, and the mixtures were shaken for 1 minute using 3M ESPE CapMix shaker.

Intermediate 2

Emulsions comprising thymol and 1, 2-distearoyl-sn- glycero-3-phosphate based on peanut oil

Four different emulsions were prepared as in Intermediate 1 using 1, 2-glycero-3-phosphate instead of the phosphomethanol derivative used in Intermediate 1. The emulsions were stable at room temperature.

Example 11

Emulsions comprising thymol and cetylpyridinium chloride based on peanut oil/ phospholipids

Cetyl pyridinium chloride (5 mg) was added to the emulsions of Intermediate 2, and the mixtures were shaken for 1 minute using a 3M ESPE CapMix shaker.

Example 12

Emulsions comprising cetylpyridinium chloride/benzalkonium chloride and hexachlorophene/chlorhexidine based on soya bean oil/olive oil/phospholipids

Emulsions comprising two antimicrobial agents were prepared by shaking a mixture of the agents with CinOleic® for 1 minute using a 3M ESPE CapMix shaker. The compositions of the various emulsions are shown in Table 6 below.

Table 6

Emulsion ClinOleic® Cetyl Hexochlor. Benzalkon. Chlor. No ml mg mg mg mg

1 1 50 50

2 1 50 50

3 1 50 50

4 1 50 50 Cetyl : Cetylpyridinium chloride Hexachlor . : Hexachlorophene Benzalkon. : Benzalkonium chloride Chlor. : Chlorhexidine

Claims

1. A disinfectant emulsion composition having a continuous phase having dissolved therein a first antimicrobial agent and a discontinuous phase having dissolved therein a second antimicrobial agent.

2. A composition as claimed in claim 1 further comprising a phospholipid stabilizer.

3. A composition as claimed in either of claims 1 and

2 comprising a cationic surfactant.

4. A composition as claimed in any one of claims 1 to

3 having an aqueous phase with dissolved therein a polycationic species.

5. A composition as claimed in claim 4 wherein said polycationic species is poly-dialIyIdialkyl ammonium salt.

6. A composition as claimed in any one of claims 1 to

5 having an oil phase which contains an oil-soluble, water-immiscible antimicrobial agent and an aqueous phase which comprises an alcohol and a disinfectant polymeric polycationic species .

7. A composition as claimed in any one of claims 1 to

6 in the form of an oil-in-water emulsion the oil phase of which constitutes 10 to 30% vol. of the emulsion.

8. A composition as claimed in any one of claims 1 to

7 having an aqueous phase comprising an alcohol water mixture in a volume ratio of 35:65 to 50:50.

9. A composition as claimed in any one of claims 1 to

8 having an oil phase with dissolved therein a phenolic antimicrobial agent.

10. A method of cleansing the hands of a human subject, which method comprises spraying an emulsion according to any one of claims 1 to 9 over the hands of said subject, rubbing said emulsion onto said hands, optionally rinsing said emulsion from said hands, and optionally drying said hands .

11. A sealed cartridge having a fluid reservoir with an outlet port adapted to engage with a disinfectant dispenser, said reservoir containing a disinfectant composition.

12. A cartridge as claimed in claim 11 wherein said composition is a disinfectant emulsion.

13. A cartridge as claimed in claim 12 wherein said composition is a composition according to any one of claims 1 to 9.