GB2552261A

GB2552261A - Hygiene products

Info

Publication number: GB2552261A
Application number: GB1710763.2A
Authority: GB
Inventors: Siva Kumar; Nowell Peter
Original assignee: BIOCILLIN THERAPEUTICS Ltd
Current assignee: BIOCILLIN THERAPEUTICS Ltd
Priority date: 2016-07-05
Filing date: 2017-07-04
Publication date: 2018-01-17
Also published as: GB201710763D0; WO2018007805A1; GB201611745D0

Abstract

An aqueous antimicrobial and antiviral composition comprising a quaternary ammonium compound, non-ionic surfactant, alkaline agent, chelating agent, pH controller and at least 10% amine oxide is provided. The composition has a pH of at least pH 11. Preferably the quaternary ammonium compound is dodecyl dimethyl ammonium chloride and the amine oxide comprises C12 to C18 (even-numbered) alkyldimethyl, N-oxide. The composition may further comprise a secondary surfactant or co-surfactant, humectant, solubiliser and fragrance. Personal care products comprising the same and use of the composition in disinfecting is described, and they may not cause primary skin irritation potential and/or existing allergic sensitisation.

Description

(54) Title ofthe Invention: Hygiene products

Abstract Title: Aqueous antimicrobial and antiviral composition comprising quaternary ammonium compound (57) An aqueous antimicrobial and antiviral composition comprising a quaternary ammonium compound, non-ionic surfactant, alkaline agent, chelating agent, pH controller and at least 10% amine oxide is provided. The composition has a pH of at least pH 11. Preferably the quaternary ammonium compound is dodecyl dimethyl ammonium chloride and the amine oxide comprises C12 to C18 (even-numbered) alkyldimethyl, N-oxide. The composition may further comprise a secondary surfactant or co-surfactant, humectant, solubiliser and fragrance. Personal care products comprising the same and use ofthe composition in disinfecting is described, and they may not cause primary skin irritation potential and/or existing allergic sensitisation.

1/3

Reduction factor

5,22

4,22

Virus titre (LVP) (logio TCID50/ml)

2,84

Total nunber of positive wells after titration with the LVP

o

Number of positive wells after titration with the LVP/96 well plate

o

n.d.

o

0Titre virus control (logio TCIDjjO/ml)

8,06

7,06

Exposure time

2 min

5 min

Soil load

dirty

Cone

50,0%

97,0%

Product

Additive 1 (2% DDAC), Amine oxide 10% Lauryl betaine

Additive 1, (2% DDAC) Amine oxide 10%

Additive 1, (2%DDAC) Amine oxide 10%, Fragrance

Additive 1, (3% DDAC) Amine oxide 10%

Additive 1, (4% DDAC) Amine oxide 10%

Additive 1, (4.5% DDAC) Amine oxide 10%

Figure 1

2/3

Comparative Testing within Example 7

*r 120s	3,38	0,00	0,00	0,00
Factoraftc 60s	d d	d d	d d	d d
[eduction 1 30 s	oo co co	co o'	o o o~	co o'
F 15s	d d	d d	d d	d d
after 120s	4,50	o o co^-'	oo oo r<	o o co
ξ ω ZS o Q CO P	d d	d d	d d	d d
o S’ w o g) CO	4,50	LO l·-. r<	LO CM OO	m r-. K
w ϊ> LO	d d	d d	d d	d d
£ ¥ P II 2 g> jS £	oo oo r<	oo oo r<	oo oo r<	oo oo K
'g < § S’	4,50	2,50	o LO cd	o in co
Soil load	£ d	£ d	£ d	£ d
Cone	50,0%	50,0%	50,0%	50,0%
Product	Test	Example 2	Example 11	Example 6

Figure 2

3/3

Figure 3

Reduction factor	5,16	5,16
si φ LJ ~ P 'w o 5 σ> 5 έ	2,84	2,84
Total nimber of positive wells after titration with theLVP	o	o
Number of positivewellsafter titration with the LVP/96well plate	o	o	o	o	o	o
o	o	o	o	o	o
0Titre virus control (log™ TCIDs/ml)	8,00	8,00
Exposure time	30s	120s
Soil load	dirty	dirty
Cone	50,0%	50,0%
Product	c £	c £

HYGIENE PRODUCTS

Products useful in controlling infectious agents, such as bacteria and viruses, are disclosed which are suitable for preparing personal care products and sanitary cleaning products for example. In particular compositions are provided which do not show primary skin irritation potential and I or existing allergic sensitisation.

Background to the Disclosure

Quaternary ammonium compounds (hereinafter QAC) have antimicrobial activity and are widely used for the control of bacterial growth in clinical and industrial environments, and as adjuncts to hygiene in domestic cleaning products. It has been considered that QAC containing products can be suitable for antiseptic or disinfectant purposes. However, QAC containing products typically do not have antiviral activity.

Summary of Invention

Whilst the inventors had developed a composition comprising QAC which was effective in showing virucidal efficacy to both adenovirus-5 and polovirus-1, this composition comprising

QAC (say didecyldimethylammonium chloride (hereinafter DDAC)) 4% to 10%, Non-ionic surfactant (Synperonic 916™, and / or MEA/ MELA) 2% to 8%,

Alkaline agent (potassium carbonate) 2% to 8%,

Chelating agent (Caflon™ EDTA) 2% to 8%, pH controller 5% to 10%, and

Demineralised water (q.s. - balance to 100%)) required longer (greater than 5 minutes) contact time with a surface to provide such anti-viral activity.

It was also determined by the inventors that in the case of providing a handwash or bodywash, where a surfactant is provided to assist in the washing and lathering process, the efficacy of the active substance of this composition, which is a QAC, is reduced.

Typically, it is understood by the inventors that the QAC and the surfactant react with one another, reducing the efficacy of the QAC, and therefore the efficacy of the composition, for example a hand-wash or surface spray itself.

The anti-microbial activity of the composition can be tested using the European standard chemical disinfectant bactericidal activity EN1276 test which requires products to demonstrate a bacteria kill rate of 99.999% within 5 minutes. The EN 1276 Standard describes a Quantitative suspension test for the assessment of the bactericidal activity of chemical antiseptics and disinfectants. This test method evaluates how effectively the product causes a reduction in the number of viable bacterial cells of a relevant test microorganism(s). As would be understood by those of skill in the art, in such a test a test organism, for example Staphylococcus Aureus, is exposed to sample of the product (the product can be provided in a diluted form). Following exposure, the test system is neutralized and a quantitative assay is undertaken to determine survivors. For example plates provided with the survivors may be incubated, enumerated, and a reduction in viability or microbiocidal effect is determined as compared to a population control.

EN 14476 is a quantitative assay developed by the European Committee for Standardization) for the evaluation of virucidal activity. In such a test a suspension of virus is added to a solution comprising the product to be tested and maintained at a controlled temperature for an exposure time. At the end of the exposure time, viral infectivity can be assessed of aliquots of the solution and suspended virus.

Reduction of virus infectivity is calculated with reference to appropriate controls and is calculated from differences in the log of virus titers before and after treatment with the product to be tested. Suitable test organisms can be for example adenovirus, poliovirus, or parvovirus.

It has been observed that the efficacy of the QAC to ‘kill’ 4 bacterial strains in the test is reduced when a surfactant is introduced. Most significantly efficacy is diminished with Staphylococcus Aureus.

Previously the decrease in effectiveness of the QAC has been overcome by including a prodigious amount of ethyl alcohol (“alcohol”), to supplement the efficacy of the QAC, or producing a leave-on product in the form of a hand sanitiser, using ethyl alcohol as a drying agent. The difficulty with using alcohol in this context is that it not only dries the skin, but renders the QAC ineffective before it has sufficient time to do its job. The World Health Organisation recommends that the hand-wash process should take a minimum of 20 seconds for the process to be effective; alcohol based hand-washes and sanitisers usually dry after about 7 seconds, after which they cease to be effective.

The inventors have now developed an antimicrobial composition with both a surfactant “soap” and a QAC, which provides for antibacterial and virucidal activity over a short contact time.

Surprisingly, it is now found that it is possible to provide an antimicrobial composition in which the anti-bacterial and anti-viral properties of the composition are provided at improved effective levels. The disclosed compositions have been found to demonstrate a broad spectrum of performance on a range of pathogens. Therefore an antimicrobial composition exhibiting excellent anti-viral and anti-bacterial properties is accessible.

It has been found that presence of an amine oxide, for example Ammonyx CSO™ (Available from STEPAN), in the antimicrobial composition minimises the loss of efficacy of the QAC previously observed. Therefore use of an amine oxide, in particular Ammonyx CSO™ as an ingredient to be added in a formulation method to produce an antimicrobial composition reliant on the QAC for principal antimicrobial effect is disclosed herein.

The amine oxide can be introduced at any formulation stage, for example added with other ingredients such as solubilisers or surfactants, or added separately, mixed with the QAC initially or added subsequently.

Further, it has been determined that the pH of the composition is important in enabling the composition to provide improved anti-viral and anti-bacterial effects. In embodiments a pH of at least 11.5, suitably of at least pH 12, suitably of at least pH 13 may be provided. Suitably pH 13.15 may be used.

Accordingly, there is provided an antimicrobial and antiviral composition comprising at least 1% QAC and at least 10% amine oxide, for example Ammonyx CSO™, wherein the composition has a pH of at least 11, suitably 11.5 is provided.

Suitably, QAC may be provided at at least 2% QAC, suitably 4% QAC.

Suitably the composition may be provided with a pH of at least pH 11, at least pH 11.5, at least pH 12, suitably of at least pH 13. Suitably a composition with a pH of at least pH 13.15 may be provided.

In use a composition comprising at least 2% QAC, suitably at least 10% amine oxide (for example Ammonyx CSO™) wherein the composition has a pH of at least 11, suitably at least 11.5 may be provided.

Suitably amine oxide may be provided in the range 10% to 15%, suitably 10% to 20%, suitably 10% to 25%, suitably 10% to 30%. Suitably amine oxide may be provided at equal to or greater than 11 %, equal to or greater than 12%, equal to or greater than 13%, equal to or greater than 14%, equal to or greater than 15%.

Suitably a composition with a pH of at least pH 11, at least pH 11.5, at least pH 12, suitably of at least pH 13 may be provided. Suitably a composition with a pH of at least pH 13.15 is provided. Suitably an antimicrobial composition can be diluted in use, for example when used it can be provided in combination with water, for example at a 50% dilution. Suitably it may diluted to provide a composition of 25% concentration.

It is advantageous, to provide for lathering, that the composition further comprises a surfactant.

In embodiments a composition can be provided comprising at least 1%, suitably in the range 2% to 4% QAC, at least 2%, suitably in the range 2% to 10%, for example

10% Amine oxide and at least 3% surfactant, in particular a non-ionic surfactant or amphoteric surfactant, in particular Lauryl Betaine.

Suitably in use, such a composition can be provided with water in a diluted form, wherein the composition has a pH of at least 11, at least pH 11.5, suitably at least pH 12, suitably at least pH 13, suitably at least pH 13.15.

An amine oxide may be Ammonyx CSO™ (Ammonyx CSO ™ as available from Stepan™ Europe). This comprises C12-18 (even numbered) - alkyldimethyl, Noxides. This differs from, for example, Ammonyx LSO™ (Available from Stepan™) that comprises Lauramine oxide (C14 H31 NO) and Dimethyltetradeeylamine oxide. Ammonyx CSO™ may be particularly advantageous.

The antimicrobial composition of the present invention can be introduced to topical skin products and surface cleaners to provide improved topical skin product formulations and surface cleanser compositions. In embodiments, the present disclosure provides products capable of delivering a >log6 reduction in 30 seconds under the European Standard EN1276 test.

Broadly, the disclosure provides an aqueous antimicrobial composition comprising:

- a quaternary ammonium compound (QAC), and

- an amine oxide, suitably Ammonyx CSO (Ammonyx CSO™ as available from Stepan ™ Europe) comprising C12-18 (even numbered) - alkyldimethyl, N-oxides.

The composition may suitably be provided at a pH greater or equal to pH 11, pH 11.5, suitably greater or equal to pH 12, suitably greater or equal to pH 13. Suitably a pH of 13.15 or greater, for example pH 13.5 is provided.

As will be appreciated by those in the art, concentrated forms of the composition which can be suitably diluted with water may be provided, for example the composition may be provided at 2% QAC and 10% Ammonyx CSO™ and may be used at up to 50% dilution with water.

The composition may further comprise at least one surfactant selected from a nonionic surfactant, or an amphoteric surfactant in the presence of a pH modifier or controller to maintain pH of the composition within the alkaline range, in particular a pH greater than or equal to pH 11, greater than or equal to pH 11.5, suitably pH 12, suitably pH 12.5, suitably pH 13, more suitably greater or equal to a pH level of 13.15.

In embodiments the aqueous antimicrobial composition has a biocidal activity such that it can kill viruses, suitably, non-enveloped viruses, for example such that it can kill polio virus.

In embodiments of the aqueous antimicrobial composition, before addition of an amine oxide, the composition may comprise or consist of the following ingredients:

QAC (say DDAC)

Non-ionic surfactant (Synperonic 916™, and I or MEA/ MELA) Alkaline agent (potassium carbonate)

Chelating agent (Caflon™ EDTA) pH controller

Demineralised water

4% to 10%

2% to 8%

5% to 10% (q.s. - balance to 100%)

This composition is referred to as Biocillin™ in the examples provided herein.

Such an aqueous antimicrobial composition can be used as an additive to provide antimicrobial activity in a topical formulation for use upon the body. It may be added in an amount of from 20% to 80% (providing an equivalent active concentration of QAC of 1.0% to 4.0% in a finished product (topical formulation). The aqueous antimicrobial composition can be added to other compositions intended for use for personal hygiene purposes or for sanitary purposes e.g. surface cleansers and sanitizers. For illustrative purposes the use of the disclosed antimicrobial composition is described in topical formulations intended for use upon the human or animal body without limitation. Suitably, for use in surface cleaning, the QAC may be provided at equal or greater than 3%, equal or greater than 4%, equal or greater than 4.5%.

A topical formulation for use on the human body may in addition to the QAC and amine oxide, suitably Ammonyx CSO™ comprise the following formulation ingredients:

Surfactant (for example Lauryl betaine)

0.5% to 12.0%

Humectant

Solubiliser

Fragrance

0.5% to 10.0%

0.5% to 3.0%

0.25% to 3.0%

Ingredients such as surfactant, humectant, solubiliser and / or fragrance can be used together with from 20.0% to 80.0% of an antimicrobial composition comprising QAC, for example DDAC, prior to addition of the amine oxide suitably Ammonyx CSO™, such that when the final aqueous solution is made up with a sufficient quantity of water to 100% it provides an active concentration of antimicrobial composition (QAC) in the topical formulation in the range of from 1.0% to 4.0% and at least 5% amine oxide, suitably at least 10 % amine oxide for example Ammonyx CSO™, suitably 10% to 15%, suitably 10% to 20% Ammonyx CSO™.

A topical formulation for use on the human hand may comprise the following formulation ingredients:

Surfactant (Lauryl betaine) 0.5% to 12.0%

Solubiliser 0.5% to 3.0%

Fragrance 0.25% to 3.0%

Such ingredients are used together with from 20.0% to 80.0% antimicrobial composition comprising QAC as disclosed herein, for example Biocillin™ composition and made up with a sufficient quantity of water to “100%” to provide an active concentration of antimicrobial composition in the topical formulation with an amine oxide, suitably Ammonyx CSO™ at a concentration of at least 10%.

An additional, at least a second surfactant may be provided, for example, at least a second non-ionic surfactant or amphoteric surfactant. Suitably, an amphoteric surfactant may be an alkyl betaine for example where the alkyl group is predominantly C12/C14 (“lauryl betaine” or N-dodecyl-N,N-dimethylbetaine).

Testing of compositions as disclosed herein under conditions of European Standard tests demonstrated efficacy against the following bacterial strains:

Staphylococcus aureus ATCC 6538

Pseudomonas aeruginosa ATCC 15442

Escherichia coli ATCC 10536

Enterococcus hirae ATCC 10541

Embodiments of personal care products or hygiene products include an aqueous antimicrobial composition comprising an antiseptic quaternary ammonium compound (QAC), an amine oxide for example selected from Ammonyx CSO™ and at least one other surfactant in an aqueous vehicle together with additional formulation aids selected from further surfactants, solubilisers, spreading agents, humectants, thickeners, pH regulators, and fragrances or other additives such as those used typically in the field of personal care products. The pH can be suitably regulated to ensure the pH of the aqueous composition or any subsequent diluted solution therefore is alkaline, in particular greater than pH 11, greater than pH 11.5, greater than pH 12, greater than pH 13.

In embodiments the QAC may be a long chain alkyl ammonium compound. Didecyl dimethyl ammonium chloride (DDAC) is an example of a quaternary ammonium based antimicrobial agent providing the antiseptic or disinfecting activity required of the disclosed aqueous antimicrobial composition.

The aqueous antimicrobial composition disclosed herein may be presented as “concentrate” additive to be diluted with water and combined with formulation components at a point of use or in a separate manufacturing facility to form a product such as a topical formulation or a surface cleanser. The concentrate for such use may consist of the antimicrobial composition (QAC, non-ionic surfactant, alkaline agent, chelating agent and pH controller) in sufficient water to allow metered dispensing of a flowable substantially consistent composition. The amine oxide may be provided to an additive composition comprising the QAC such that it is included in the aqueous antimicrobial composition before dilution and combination with formulation components or added at the final product formulation stage.

In embodiments the amount of QAC may be up to 10% or more by weight with respect to the aqueous antimicrobial composition when the sole disinfecting ingredient is DDAC. DDAC is soluble in water and can be made up in water at differing concentrations. DDAC is obtainable commercially at 50% or 80% by weight in aqueous solution.

In embodiments the amount of QAC may be at least about 4% by weight with respect to the aqueous antimicrobial composition.

In embodiments surfactants may be selected from non-ionic and amphoteric surfactants. At least one surfactant may be selected from alkyl betaines such as a C12/C14 alkyl betaine, or from alkoxylated fatty alcohols, for example ceto-stearyl (CwCw) alcohol ethoxylated. The base aqueous antimicrobial composition before formulation into product may comprise a non-ionic surfactant such as an alcohol ethoxylate, for example cetostearilic alcohol/ethylene oxide (Cie-ie ethoxylate).

The composition may include other ingredients such as thickeners, solubilisers, humectants, pH regulators or stabilisers, or buffering aids.

Typically the aqueous antimicrobial composition may be made up in demineralised water.

The presently disclosed aqueous antimicrobial composition requires no alcohol (ethanol) for efficacy. Accordingly in embodiments, the aqueous antimicrobial composition and a formulated product containing the same would be substantially alcohol-free. A residual or negligible amount of alcohol may be found in one or more ofthe additives, but no alcohol need be specifically added for improving efficacy.

The aqueous antimicrobial composition comprising the QAC can be used as a concentrate or additive to be further formulated into a final aqueous product formulation to provide a personal care product. Suitably the final aqueous product formulation may comprise from 20% to 80% by weight of the aqueous antimicrobial composition including the QAC. The “final aqueous product formulation” may be a mixture of ingredients suitable for use in a personal care or hygiene product but lacking an antiseptic or antimicrobial or biocidal component, i.e. an incomplete formulation for a personal care or hygiene product.

In an embodiment a first aqueous solution providing an antimicrobial composition concentrate or additive comprises:

about 10% QAC about 5% non-ionic surfactant about 5% alkaline agent about 6% chelating agent about 8% pH controller balance demineralised water to 100%.

In embodiments there is provided a final topical formulation comprising about 40% (suitably 40.5%) of the following additive

Ingredient %w/w

Demineralised water 66.1

QAC (Bardac 2250™) 9.9

Alcohol C9-11 ethoxylate (Synperonic 916™) 5.0

Alkaline agent (Potassium Carbonate) 5.0

Chelating agent (Caflon™ EDTA) 6.0

Monoethanolamine (MELA) 8.0 in combination with water and amine oxide ((suitably Ammonyx CSO™ for example added at 10%) wherein the amine oxide is provided at a final concentration in the range at least 2 to 6 % amine oxide in use, suitably at least 10% and the formulation is at a pH of at least 11, at least pH 11.5, suitably in the range pH 11 to 13.5, suitably 11.5 to 13.5.

In embodiments there is provided a formulation (surface cleaner) comprising about 90% of the following additive

Ingredient %w/w

Demineralised water

QAC (Bardac 2250™)

Alcohol C9-11 ethoxylate (Synperonic 916™)

Alkaline agent (Potassium Carbonate)

Chelating agent (Cation™ EDTA)

Monoethanoloamine (MELA)

66.1

9.9

5.0

6.0

8.0 in combination with water and amine oxide wherein the amine oxide is provided at a final concentration in the range at least 2 to 6 % amine oxide in use (suitably Ammonyx CSO™), suitably at least 10% amine oxide and the formulation is at a pH of at least 11, at least pH 11.5, suitably in the range pH 11 to 13.5 suitably pH 11.5 to 13.5.

In embodiments there is provide a personal care product comprising 20.0% to 80% of an aqueous antimicrobial composition comprising of

Quaternary ammonium compound 4% to 10%,

Non-ionic surfactant 2% to 8%

Alkaline agent 2% to 8%

Chelating agent 2% to 8% pH controller 5% to 10%

C12 to C18 (even-numbered)-alkyldimethyl, N oxides at least 3% a secondary surfactant or co-surfactant 0.5% - 8.0% humectant (optional) 0.5% -10.0% solubiliser 0.5% - 3.0%, and fragrance 0.25% - 3.0%.

Demineralised water (balance to 100%)at least 3%

As will be appreciated the composition of the present invention may be provided in a wipe, in particular a hand wipe, or in a gel, foam or spray.

A wipe, spray, gel, or other aqueous composition comprising the composition of the present invention is provided as separate aspects of the invention.

In a further aspect of the present invention there is provided the use of a composition of the present invention for disinfecting. Disinfecting is an ability of a substance to reduce or eliminate a microorganism population.

Preferred features and embodiments of each aspect of the invention are as for each of the other aspects mutatis mutandis unless context demands otherwise.

As used herein, the articles “a” and “an” refer to one or to more than one (for example to at least one) of the grammatical object of the article.

“About” shall generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements.

Throughout the specification, unless the context demands otherwise, the terms ‘comprise’ or ‘include’, or variations such as ‘comprises’ or ‘comprising’, ‘includes’ or ‘including’ will be understood to imply the includes of a stated integer or group of integers, but not the exclusion of any other integer or group of integers.

Embodiments of the present invention will now be described by way of example only with reference to the accompany figures in which

Figure 1 illustrates screening of formulations against poliovirus type 1 wherein the additive is Demineralised water (66.1%), QAC (Bardac 2250™) (9.9%), Alcohol C911 ethoxylate (Synperonic 916™) (5.0%), Alkaline agent (Potassium Carbonate) (5.0%), Chelating agent (Caflon™ EDTA) (6.0%), Monoethanoloamine (MELA) (8.0%) plus other components as shown.

Figure 2 illustrates screening of 4 compositions against poliovirus type 1 based on EN 14476 wherein a reduction factor of at least or greater than 4 logw (inactivation of greater than or equal to 99.99%) is demonstrative of virus-inactivating efficacy.

Figure 3 illustrates the screening of the composition of the present invention against poliovirus type 1 with large volume plating (LVP) where a reduction factor of greater than 4 logw (inactivation of greater than or equal to 99.99%) is demonstrative of virus-inactivating efficacy.

In an example an Aqueous Antimicrobial Composition Additive of the formulation may comprise

Example 1

Ingredient_%w/w

Demineralised water 64-68

Antiseptic QAC (DDAC) 9-11

Non-ionic surfactant (fatty alcohol type*) 4-6

Alkaline agent (potassium carbonate FG) 4-6

Chelating agent (EDTA) 5-7 pH controller (monoethanolamine) 7-9 *cetostearilic alcohol/ethylene oxide (Cie-18 ethoxylate) or a long chain fatty alcohol surfactant as would be known in the art.

The above provides an antimicrobial formulation which can be diluted for use, or added to fluids and compositions suitable for use as personal care or hygiene products and also added to surface cleaning products. In embodiments the product formulation is a fluid such as a handwash, lotion or cream.

In embodiments of a topical product formulation for use on the human body the components may include:

Antimicrobial composition additive (eg as set out in Ex 1) 20.0% to 80.0%* Amine oxide at least 10%

A primary surfactant or co-surfactant	0.5%	to	8.0%
Humectant (optional)	0.5%	to	10.0%
Solubiliser	0.5%	to	3.0%
Fragrance	0.25% to	3.0%

Water

q.s. to 100% *equivalent to a range of active concentration QAC in the finished topical product formulation of between 1.0% and 4.0%

In an embodiment, an aqueous personal care or hygiene product formulation comprises about 40% by weight of the aqueous antimicrobial composition concentrate or additive (as described by Example 1), suitably at least 10% by weight of amine oxide, with the balance being water, optionally at least one secondary surfactant and formulation ingredients. The secondary surfactant may be a C12/C14 alkyl betaine, and the secondary surfactant may be present at about 3% by weight.

Suitably the antibacterial effect of the formulations can be tested against strains of bacteria, as specified in EN 1276 and EN1499 and also according to EN14476 against viral pathogens (Polio Type I).

In this disclosure all percentages mentioned are by weight unless otherwise stated.

The antimicrobial formulation is suitable for inhibiting proliferation of contact viruses and bacteria as indicated in the results shown in Table 1 below.

Table 1

Antibacterial Standards

EN 1276:2009 standard using Staphyloccus aureus ATCC 6538 at 20 degrees C for a contact time of 30 S was used to test formulations of the present invention.

The test was used to demonstrate at least a 5 decimal log (Ig) reduction with either a 5 minute or 1 minute contact time.

Results

Test suspension (N &No)

Staphyloccocus	N	Vc1	Vc2	x = 2.40x108 IgN = 8.38
aureus				NO = 2.40x107 Ig NO =

ATCC 6538	10-7	20	24	7.38
	10-6	253	232	7.18 <7.38 <7.70

Test (N_a and IgR)

Na is the number of survivors per ml in the test mixture at the end of the contact time and before neutralisation.

IgR is the log reduction.

Organism	Cone, of product %	Vc Test 1	Vc Test 2	Na xx 10	Ig Na	IgR
Staphyloccocus aureus	100% (80%)	0-1	0-1	<140	<2.15	>5.23
-	-	-	-	-	-

The test product met the requirements (with a 30s contact time) as specified in EN1276 (5 log reduction) for the test organism.

Antiviral testing

As shown in figure 1 Screening of 6 formulations against poliovirus type 1 determined a reduction factor greater than 5. Such testing was provided in accordance with EN 14476 quantitative suspension test wherein the product under test was provided to suspension of virus (Polio virus) and at the end of the exposure times indicated, aliquots were taken and viral infectivity was assessed in combination with controls and reduction of virus infectivity is calculated. Suitably the virus infectivity may be calculated from differences in log virus titers before and after treatment with the product.

The following product formulation examples utilise the above antimicrobial composition additive example as discussed above.

Example 2: Topical Product Formulation (human body)

Water 43.5%

Antimicrobial Additive (Ex.1) 40.50%

Amine oxide 10.00%

Surfactant (C12/C14 alkyl betaine) 3.00%

Humectant (glycerine) 0.50%

Solubiliser (cocamide diethanolamine) 1.50%

Fragrance 1.00%

The above provides a formulation suitable for application to the body providing an alcohol-free protection against viruses including HIV, HSV and Polio, and 99.9% of known bacteria.

Example 3: Topical Product Formulation (human hand)

Water 44.00%

Antimicrobial Additive (Ex.1) 40.50%

Amine oxide 10.00%

Surfactant (C12/C14 alkyl betaine) (suitably Lauryl Betaine) 3.00%

Solubiliser (cocamide diethanolamine) 1.50%

Fragrance 1.00%

The above provides an alcohol-free formulation suitable for application to the hand providing an effective way of protecting hands from contact viruses and 99.99% of known bacteria.

In alternative embodiments the antimicrobial additive is formulated in the first instance with an amine oxide present, and the formulation into a topical product is completed by later addition of other ingredients required for the intended complete topical product.

Example 4: Method

A cold process preparation of a topical formulation for the body is described.

A suitable clean vessel is provided for the purpose of mixing, and into the clean vessel is added the following formulation amount of ingredients:

Water (q.s.)

Antimicrobial Composition Additive (as per Example. 1)

Mixing is conducted thoroughly to ensure complete solubility and provide an appropriate aqueous antimicrobial composition solution.

Into the clean vessel containing the aqueous antimicrobial composition solution is added the following formulation amount of ingredients, mixing thoroughly to ensure complete solubility after each addition

Amine oxide - Ammonyx CSO™

A humectant

Thereby is prepared an aqueous antimicrobial composition for use as a main batch solution.

A second suitable clean vessel is provided for the purpose of mixing to prepare a premix, and into the second clean vessel is added additional formulation components including at least:

Solubiliser

Fragrance

Once completely solubilised, the thus prepared premix is added to the main batch and mixing is carried out thoroughly to prepare a final batch of the target topical formulation for the body.

Appropriate quality control (QC) tests are carried and the final batch approved for filling into packaging for the product.

As will be understood, the % of amine oxide provided in the main batch solution is provided such that a final in use concentration of amine oxide of 5%, suitably 10 % is provided.

Example 5: Method

A cold process preparation of topical formulation for the hand is described.

Water (q.s.)

Antimicrobial Additive (as per Ex.1)

Mixing is conducted thoroughly to ensure complete solubility and provide an appropriate aqueous antimicrobial solution.

A primary surfactant

Amine oxide - Ammonyx CSO™

Thereby is prepared an aqueous antimicrobial composition solution main batch.

Solubiliser

Fragrance

Once completely solubilised, the thus prepared premix is added to the main batch and mixing is carried out thoroughly to prepare a final batch of the target topical formulation for the hand.

Similar methods can be used for preparation of other hygiene products.

Example 6 - Dermatological testing

A test to determine whether the composition of the present invention caused primary skin irritation potential and I or existing allergic sensitisation was conducted wherein the product to be tested was applied to the skin of a subject via an occulsive patch at concentration as desired.

The product under test was

Water 46.50%

Antibacterial derivative 40.50%

AmmonyxCSO 10.00%

Lauryl Betaine 3.00%

Wherein the antibacterial derivative is

Ingredient_%w/w

Demineralised water 64-68

Antiseptic QAC (DDAC) 9-11

Non-ionic surfactant (fatty alcohol type*) 4-6

Alkaline agent (potassium carbonate FG) 4-6

Chelating agent (EDTA) 5-7 pH controller (monoethanolamine) 7-9 *cetostearilic alcohol/ethylene oxide (Cie-18 ethoxylate)

5mg /15μΙ of the undiluted composition was applied to an adhesive plaster and the plaster was affixed to clinically healthy skin on a subject’s back. After 20 minutes exposure, the plaster was removed and the exposed skin dermatologically assessed and graded. Second and third assessments were performed after 30 and 60 minutes respectively. The test panel included 30 male and female subjects.

A negative reaction was determined for all subjects at 20, 30, and 60 minutes. There was no evidence of any skin disorder detected in the test area of any of the 30 subjects. Thus, the composition is not considered to have primary skin irritation potential and / or cause existing allergic sensitisation.

Example 7 - Comparative testing

Comparative testing of other compositions was undertaken.

Comparative test composition 1 (Example 2 of GB2391234)

Water 89.530%

Versene 100LN 9.579

Alfonic 0.090

NaOH 0.426

BTC 818 0.230

Sodium molybdate crystals 0.100

Ammonium hydroxide 0.045

Comparative test composition 2 (Example 11 of GB2391234)

Water 78.629%

Dissolvine EDG 16.300%

Ammonyx CDO special 1.720%

Ammonyx LO 0.300%

Na CO anhydrous 2.250%

NaOH 0.426%

BTC818 0.230%

Sodium molybdate crystals 0.100%

Ammonium hydroxide' 0.045%

Comparative test composition 3 (Example 23 of GB2391234)

Water 89.320%

Versene 100LN 9.579%

Ammonyx LO 0.300%

NaOH 0.426%

BTC818 0.230%

Sodium molybdate crystals 0.100%

Ammonium hydroxide 0.045%

Comparative test composition 4 (Example 6 of WO02/072748)

Water 96.130%

EDTA tetra sodium salt (40%) 0.400%

Ammonyx DO 40 C10 dimethyl amine oxide 0.750%

Tergitol 15-S-7 (alcohol ethoxylate) 0.300%

Glucopon 425N (Alkyl Glucoside) 0.563%

BTC 2125 M (quarternary ammonium disinfectant) 0.413% Butyl Cellosolve (ethylene glycol monobutyl ether) 0.751% Polymer S2 0.225%

Sodium Hydroxide (30%) 0.218%

Fragrance IFF 4641 HBD 0.250%

Against a composition of the present invention (TEST)

Antibacterial derivative 40.5%

Ammonyx CSO 10.0%

Lauryl Betaine 3.0%

Wherein the antibacterial derivative is

Ingredient_%w/w

Demineralised water 66.1

Antiseptic QAC (DDAC)

9.9

Non-ionic surfactant (fatty alcohol type*) Alkaline agent (potassium carbonate FG) Chelating agent (EDTA) pH controller (monoethanolamine) *cetostearilic alcohol/ethylene oxide (Cie-18 ethoxylate)

Each of the compositions were provided under EN 1276:2009 testing conditions for a contact time of 30 seconds, under dirty conditions (wherein 3.0g/l Bovine Albumin is provided) wherein membrane filtration is provided to neutralise the bacteria (Staphylococcus aureus ATCC 6538) after the test.

Each of the compositions tested except comparative test composition 2 (Example 11 of GB2391234) passed the anti-bacterial screening.

The same compositions were tested for antiviral activity. Only the composition of the present invention demonstrated virus-inactivating activity. The results of such testing are provided by figures 2 and 3 which demonstrate a reduction factor greater than 4 was provided for the present composition.

Example 8

Testing of compositions including the Aqueous Antimicrobial Composition Additive of the formulation of Example 1 provided above was undertaken to determine the ability of such compositions to act as an anti-viral composition.

Ingredient_%w/w

Demineralised water 64-68

Antiseptic QAC (DDAC) 9-11

Non-ionic surfactant (fatty alcohol type*) 4-6

Alkaline agent (potassium carbonate FG) 4-6

Composition 053

This composition only comprised

40.50% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 59.50% Water and was provided at pH 13.15

An EN 14476 quantitative assay for the evaluation of virucidal activity against Poliovirus type 1 was conducted where a test suspension of virus was added to a solution comprising the product to be tested and maintained at a controlled temperature for an exposure time of 60s and 120s.

The composition was able to provide reduction factors of 2.38 at both exposure points and thus failed the test.

Composition 056

The composition comprised

40.50% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 48.50% Water 3.00% Lauryl Betaine 8.00% Ammonyx CSO and was provided at pH 13.15

The composition did not show reduction at either exposure points and thus failed the test.

Composition 057

The composition comprised

40.50% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 50.50% Water 1.00% Fragrance 8.00% Ammonyx CSO and was provided at pH 13.15

Composition 058

The composition comprised

40.50% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 55.50% Water 3.00% Lauryl Betaine 1.00% Fragrance and was provided at pH 13.15

An EN 14476 quantitative assay for the evaluation of virucidal activity against

Poliovirus type 1 was conducted where a test suspension of virus was added to a solution comprising the product to be tested and maintained at a controlled temperature for an exposure time of 60s and 120s.

Composition 059

This composition only comprised

60.75% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 39.25% Water and was provided at pH 13.15

Composition 061

This composition comprised

40.50% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 46.50% Water 3.00% Lauryl Betaine 10.00% Ammonyx CSO and was provided at pH 13.15

An EN 14476 quantitative assay for the evaluation of virucidal activity against

Poliovirus type 1 was conducted where a test suspension of virus was added to a solution comprising the product to be tested and maintained at a controlled temperature for an exposure time of 30s and 120s.

The composition was able to provide reduction factors of 4.91 and 5.22 and thus passed the test.

Composition 062

This composition comprised

40.50% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 49.50% Water 10.00% Ammonyx CSO and was provided at pH 13.15

An EN 14476 quantitative assay for the evaluation of virucidal activity against Poliovirus type 1 was conducted where a test suspension of virus was added to a solution comprising the product to be tested and maintained at a controlled temperature for an exposure time of 120s.

The composition was able to provide a reduction factor of 5.22 and thus passed the test.

Composition 063

This composition comprised

40.50% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 48.50% Water 10.00% Ammonyx CSO 1.00% Fragrance and was provided at pH 13.15

An EN 14476 quantitative assay for the evaluation of virucidal activity against

Poliovirus type 1 was conducted where a test suspension of virus was added to a solution comprising the product to be tested and maintained at a controlled temperature for an exposure time of 120s.

Composition 064

This composition comprised

60.50% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 29.50% Water 10.00% Ammonyx CSO and was provided at pH 13.15

Composition 065

This composition comprised

81.00% Aqueous Antimicrobial Composition Additive of the formulation of Example 1

9.00% Water

10.00% Ammonyx CSO and was provided at pH 13.15

An EN 14476 quantitative assay for the evaluation of virucidal activity against

Poliovirus type 1 was conducted where a test suspension of virus was added to a solution comprising the product to be tested and maintained at a controlled temperature for an exposure time of 300s.

The composition was able to provide a reduction factor of 4.22 and thus passed the test.

Composition 066 5

This composition comprised

90.00% Aqueous Antimicrobial Composition Additive of the formulation of Example 1 10.00% Ammonyx CSO and was provided at pH 13.15

An EN 14476 quantitative assay for the evaluation of virucidal activity against Poliovirus type 1 was conducted where a test suspension of virus was added to a solution comprising the product to be tested and maintained at a controlled temperature for an exposure time of 300s.

Although the invention has been particularly shown and described with reference to particular examples, it will be understood by those skilled in the art that various changes in the form and details may be made therein without departing from the scope of the present invention.

Claims

Claims: 1. An aqueous antimicrobial and antiviral composition comprising Quaternary ammonium compound Non-ionic surfactant Alkaline agent Chelating agent pH controller and at least 10% amine oxide

1% to 10% 0.5% to 8% 0.5% to 8% 0.5% to 8% 1%to 10% wherein the composition has a pH of at least pH 11.

2. An aqueous antimicrobial and antiviral composition comprising 20.0% to 80% of %w/w

Demineralised water 64-68 Quaternary ammonium compound 9-11 Non-ionic surfactant 4-6 Alkaline agent 4-6 Chelating agent 5-7 pH controller 7-9

and at least 10% amine oxide wherein the composition has a pH of at least pH 11.

3. The aqueous antimicrobial and antiviral composition of claim 2 comprising at least 40.50% of %w/w

and at least 10% amine oxide.

4. The aqueous antimicrobial and antiviral composition of any preceding claim wherein the composition has a pH of at least pH 11.5.

5. The aqueous antimicrobial and antiviral composition of any preceding claim wherein the composition has a pH of at least 13.15.

6. The aqueous antimicrobial and antiviral composition as claimed in any previous claim, wherein the quaternary ammonium compound is a long chain alkyl ammonium compound.

7. The aqueous antimicrobial and antiviral composition as claimed in any previous claim, wherein the quaternary ammonium compound is didecyl dimethyl ammonium chloride.

8. The aqueous antimicrobial and antiviral composition as claimed in any previous claim, wherein the amine oxide comprises C12 to C18 (evennumbered) - alkyldimethyl, N-oxide (Ammonyx CSO™).

9. The aqueous antimicrobial and antiviral composition as claimed in any previous claim, wherein the non-surfactant is a fatty alcohol/alkylene oxide.

10. The aqueous antimicrobial and antiviral composition as claimed in claim 9 wherein the surfactant is Lauryl betaine.

11. The aqueous antimicrobial and antiviral composition as claimed in any one of claims 1 to 10 for use as a surface cleaner.

12. The aqueous antimicrobial and antiviral composition as claimed in claim 11 further diluted with water to provide a composition of 25% concentration.

13. The aqueous antimicrobial and antiviral composition as claimed in claim 11 further diluted with water to provide a composition of 50% concentration.

14. A personal care product comprising a composition as claimed in any one of claims 1 to 10, additionally comprising formulation aids selected from pH modifiers or controllers, buffering agents, chelating agents, solubilisers, spreading agents, thickeners, a humectant, and additional surfactants wherein amine oxide is at least 10%.

15. A personal care product as claimed in claim 14, formulated as a topical composition such as a handwash, body wash, or lotion.

16. A personal care product as claimed in claim 14 or claim 15, comprising

20.0% to 80% of an aqueous antimicrobial composition consisting of Quaternary ammonium compound 4% to 10%

Non-ionic surfactant 2% to 8%

Alkaline agent 2% to 8%

Chelating agent 2% to 8% pH controller 5% to 10%

Demineralised water (balance to 100%) with the balance of the personal care product comprising of at least 10% amine oxide, and water q.s. to 100%.

17. A personal care product as claimed in claim 16 further comprising at least one of a secondary surfactant or co-surfactant humectant (optional) solubiliser fragrance

0.5% - 8.0%,

0.5% -10.0%, 0.5% - 3.0%, 0.25%-3.0%, and wherein the amine oxide is at least 10%.

18. Use of an antimicrobial and and antiviral composition as claimed in any one of claims 1 to 13, or a personal care product of any one of claims 14 to 17, for disinfecting.

19. Use as claimed in claim 18 for killing polio virus.

10

20. A wipe comprising an antimicrobial and and antiviral composition as claimed in any one of claims 1 to 13, or a personal care product of any one of claims 14 to 17.

21. An antimicrobial and and antiviral composition as claimed in any one of claims 1 to 13, or a personal care product of any one of claims 14 to 17

15 which, in use, does not cause primary skin irritation potential and / or existing allergic sensitisation.

Intellectual

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Application No: GB1710763.2 Examiner: Helen Yard