RU2781408C2 - Composition for topical use and method for treatment and prevention of atopic dermatitis and infections related to bacterium biofilm - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to a composition for topical use, containing an “oil-in-water” nano-emulsion, and a method for destruction or inhibition of bacterium growth in biofilm, including impact on biofilm with the specified nano-emulsion. The nano-emulsion contains a surfactant begentrimonium chloride, while an oil phase contains at least one softener selected from Vaseline, isopropyl palmitate, dimethicon, mineral oil, paraffin waxes, cetyl alcohol, or a mixture thereof; and a water phase. The nano-emulsion contains drops having values of Souter diameter D[3;2] from about 10 nm to about 100 nm.

EFFECT: obtaining a composition for topical use, which has great microbiological activity.

16 cl, 9 tbl, 12 ex

Description

FIELD OF THE INVENTION

The present invention relates to the treatment and prevention of atopic dermatitis and bacterial biofilm infections. More specifically, the invention discloses a topical composition for inhibiting Staphylococcus aureus bacteria associated with biofilm present in atopic dermatitis. Disclosed is a method for treating skin or mucous membranes and using said composition for topical application.

BACKGROUND OF THE INVENTION

Atopic dermatitis, also called eczema syndrome, is a chronic relapsing itch-inflammation of the skin that can impair quality of life. Atopic dermatitis affects 10-20% of children and 1-3% of adults worldwide, and is increasingly prevalent in industrialized countries. Atopic dermatitis is characterized by a weakened epidermal barrier, dysregulation of innate and adaptive immunity, and a high susceptibility to bacterial colonization and infection. Thus, lubricants (ointments and creams) and topical or oral corticosteroids, which act on the immune system to block the production of substances that cause allergic and inflammatory effects, remain the first line of treatment. Similarly, antihistamine drugs can also be administered. If itching does not respond to standard treatments, antibiotics may be considered.

Lubricants are effective in keeping the skin hydrated and repairing the skin barrier. However, the cosmetic perception of these types of formulations can be poor, leading to poor adherence by patients with atopic dermatitis to the instructions for taking the drug. Moreover, such an approach is often not sufficient on its own. On the other hand, corticosteroids are powerful drugs but are known to cause side effects, some of which can be severe if taken long term. While antihistamine medicines can be used to treat the itching associated with atopic dermatitis, they can cause drowsiness and may not help in all cases of atopic dermatitis. Finally, the use of antibiotics is controversial due to increased bacterial resistance.

Since atopic dermatitis is also characterized by an altered skin microflora, some researchers have investigated the role of bacteria in atopic dermatitis. More specifically, nanoemulsions have been found to have strong bactericidal activity and may therefore be of interest in the treatment of atopic dermatitis.

However, the physicochemical correlation has not been studied to understand which parameter is responsible for the activity. The mechanism of action is not yet clear, but it appears that surfactants used to stabilize nanoemulsions may modulate the antimicrobial activity of the nanoemulsion.

US Pat. No. 6,559,189 (Baker) describes the use of nanoemulsions to kill or inhibit the growth of pathogenic agents. Nanoemulsions according to Baker contain surfactants, detergents and cationic halogenated compounds. Baker reveals a long list of possible formulations and quaternary ammonium compounds in formulations. None of the quaternary ammonium compounds has a linear alkyl chain containing more than 18 carbon atoms. The most effective compositions according to Baker contain detergents such as Tween, Triton and Tylxapol. The use of these detergents on damaged skin (atopic dermatitis) can cause irritation and discomfort to the patient. Finally, Baker does not point to biofilms and the possible use of nanoemulsion when using already formed or growing bacterial biofilms.

US Pat. No. 8,747,872 (Baker) describes the use of a nanoemulsion to treat bacteria associated with biofilms, such as lung infections. Among the many embodiments of the described nanoemulsion composition, some may contain Quaternary ammonium salts. None of the quaternary ammonium salts described has a linear alkyl chain having more than 18 carbon atoms. Examples of formulations presented by Baker effective against biofilm include: poloxamer, ethanol and cetylpyridinium chloride (P ₄₀₇ 5EC), or tween80, ethanol and cetylpyridinium chloride (W ₈₀ 5EC). The use of such formulations may cause irritation and discomfort to the patient when used on damaged skin (for atopic dermatitis).

There is a need to find topical compositions for the treatment or prevention of the growth of pathogens on the skin of a patient with dermatitis, which will not have the side effects of solutions already known in the art. There is also a need to prevent or slow the growth of biofilms, including biofilms associated with skin diseases.

Surprisingly, the inventors have found that nanoemulsions of long alkyl chain quaternary ammonium salts can overcome the shortcomings of prior compositions.

SUMMARY OF THE INVENTION

In this document, unless otherwise indicated, all percentages are by weight based on the total weight of the composition referenced. The disclosures of all patents and published applications referenced herein are incorporated herein by reference in their entirety.

In this document, the term "essentially does not contain" in relation to the ingredient means the content of this ingredient is about 5% of the mass. or less. Preferably, the term "substantially free of an ingredient" means a content of about 2% or less, or about 1% or less, or about 0.5% or less, or about 0.1% or less, or about 0.05% or less , or about 0.01% or less by weight of such an ingredient. In some embodiments, the term "substantially free of an ingredient" means "does not contain an ingredient at all", i.e. does not contain that ingredient at all.

For the sake of brevity, the term "about" is not used to clarify some of the quantitative expressions given herein. Whether or not the term "about" is explicitly applied, each numerical value given herein is intended to refer to an actual given value and is also intended to refer to an approximation to that given value which may be reasonably estimated based on the knowledge of one of ordinary skill in the art, including approximations associated with experimental and/or measurement conditions for such a given value.

To provide more brevity of description, some quantitative expressions in this document are specified as a range from about an amount of X to about an amount of Y. It is understood that when a range is indicated, it is not limited to the indicated upper and lower limits, but includes the full range of values from about an amount of X up to about Y, or any number or range within those limits. As used herein, the term “cosmetically/dermatologically acceptable” means that the ingredients to which the term refers are suitable for use in contact with tissues (e.g., skin or hair) without side effects such as non-specific toxicity, incompatibility, instability, irritation, allergic reaction. etc.

The expression "inhibit" or other forms of inhibition such as "inhibitory" or "inhibition" is intended to detect or inhibit a particular event or characteristic, or to reduce the frequency or severity of a particular event or characteristic. It should be understood that this generally refers to some standard or expected value, in other words, it is relative, but it is not always necessary to refer to a standard or relative value. For example, "inhibits the formation of biofilms" means preventing or limiting the formation or further growth of a biofilm, or reducing the severity of biofilm formation compared to a standard or control.

By "prevention" or other forms of prevention such as "preventive" or "prophylaxis" is meant stopping a particular event or characteristic, stabilizing or delaying the development or progression of a particular event or characteristic, or minimizing the likelihood of a particular event or characteristic occurring. Prevention does not need to be compared with a control element, since it is usually more absolute than, for example, reduction or inhibition. In this document, something can be reduced but not inhibited or prevented, but what is reduced can also be inhibited or prevented. Also, something can be inhibited but not reduced or prevented, but what is inhibited can also be reduced or prevented. Likewise, something can be prevented but not inhibited or reduced, but what is prevented can also be inhibited or reduced. It should be understood that where reduction, inhibition, or prevention is used, unless otherwise indicated, the use of the other two words is also clearly described. Thus, while disclosing a method for reducing biofilm formation, a method for inhibiting and preventing biofilm formation and the like is also disclosed.

The present invention relates to a topical composition comprising an oil-in-water nanoemulsion. The nanoemulsion includes a quaternary ammonium salt containing at least one linear alkyl chain of at least 20 carbon atoms, an oil phase containing at least one softener; and the water phase. The quaternary ammonium salt is selected from the group consisting of behentrimonium chloride, behenalkonium chloride, dibegenyldimonium chloride, behenamidopropylethyldimonium ethosulfate, and mixtures of these surfactants. In a preferred embodiment of the invention, the quaternary ammonium salt is behentrimonium chloride. The quaternary ammonium salt may be a trimethyl quaternary ammonium salt.

The surfactant in the nanoemulsion is in an amount of from about 1% to about 7% by weight of the composition, or from about 2% to about 5% by weight of the composition. The nanoemulsion has droplets having Sauter diameter D[3;2] values less than about 120 nm, or droplets having Sauter diameter D[3;2] values from about 10 nm to about 100 nm, or droplets having Sauter diameter values D [3;2] from about 30 nm to about 70 nm

The composition of the present invention may have a viscosity of less than 700 cps or more preferably less than 360 cps at 45 s ^-1 when measured with a Physica MCR 300 (Anton Paar GmbH) at a shear rate of 45 s ^-1 and a viscosity of less than 125 cps when measured in the same way. The composition may contain a softener in an amount of from about 1% to about 15% by weight of the composition, and a rheology modifier in an amount of from about 0.5% to about 5% by weight of the composition. The rheology modifier is selected from the group consisting of cetyl alcohol, stearyl alcohol, carnauba wax, stearic acid, hydroxyethyl cellulose, guar gum, locust bean gum, xanthan gum, gelatin, silica, bentonite, magnesium aluminum silicate, carbomers, and mixtures thereof.

The topical composition further comprises at least one humectant in an amount of from about 5% to about 15% by weight of the composition; and from about 5% to about 15% by weight of water, or from about 50% to about 90% by weight of water. In a preferred embodiment, the composition does not contain additional surfactants and preservative.

The present invention also relates to a method for killing or inhibiting the growth of bacteria in a biofilm, including exposing the biofilm to a nanoemulsion in accordance with the present invention. An example of a biofilm is Staphylococcus aureus .

DETAILED DESCRIPTION OF THE INVENTION

Nanoemulsions

The nanoemulsions of the present invention are water-in-oil emulsions containing a quaternary ammonium salt containing at least one linear alkyl chain having at least 20 carbon atoms.

The oil phase of the nanoemulsion may include hydrocarbon oils such as paraffin oil, purcellin oil, perhydrosqualene, microcrystalline wax, petrolatum, mineral oil (Paraffinum liquidum), polyalkene, cerazine, ozocerite, polyethylene, perhydrosqualene, polyalphaolefin, hydrogenated polyisobutene, beeswax, and mixtures thereof. ; saturated esters such as isopropyl palmitate, alkyl myristates such as isopropyl, butyl and cetyl myristates, hexadecyl stearate, ethyl palmitate, triglycerides of octanoic and decanoic acids and cetylricinoleate, sodium formate, tocopheryl acetate, butyl acetate, ethyl acetate, methoxyisopropyl acetate, glyceryl laurate, PEG-30 glyceryl laurate, potassium laurate , glyceryl myristate, isopropyl myristate, potassium myristate, propylene glycol myristate, zinc myristate, ascorbyl palmitate, cetyl palmitate, isopropyl palmitate, potassium palmitate, retinyl palmitate, acetylated glycol stearate, ethylhexyl stearate, glyceryl isostearate, glyceryl stearate, glyceryl stearate SE, glycol distearate, PEG-3 distearate, distearate , PEG-30 glyceryl stearate, PEG-32 stearate, PEG-6 stearate, polyglyceryl-2 diisostearate, polyglyceryl-3 distearate, potassium stearate, potassium sorbate unsaturated esters, glyceryl oleate, ethyl linoleate, glyceryl linoleate, tocopheryl linoleate; silicone oils such as dimethylpolysiloxane, methylphenylpolysiloxane and silicone glycol polymer; vegetable oils containing triglycerides of linoleic acid, such as Cocos Nucifera (cocoa butter) oil, Elaeis Guineensis (palm oil), Arachis Hypogaea (peanut oil), Argania Spinosa (argan oil), sweet almond oil, avocado oil, butter Calophilum, Lanolin, Castor Oil, Olea Europaea Olive Oil, Triticum Vulgare Germ Oil, Corn Germ Oil, Soybean Oil, Sunflower Oil, Cottonseed Oil, Alfalfa Oil, Poppy Oil, Red Chicken Oil, Sesamum Indicum Sesame Oil, Rapeseed Oil, Evening Oil primrose oil, millet oil, barley oil, quinoa oil, rye oil, safflower oil, candenut oil, passion flower oil, grape seed oil, rapeseed oil, toll seed oil, linseed oil, peanut oil, sea buckthorn oil, black currant seed oil, seed oil Siberian Pine, Primrose Oil, Soy Glycine, Corylus Avellana Oil (Nut Oil), Juglans Regia Oil (Nut Oil), Vitis Vinifera Oil (Grape oil).

The oil phase of the nanoemulsion comprises about 5% to about 40% or about 10% to about 30% or about 10% to about 20% by weight of the nanoemulsion.

The aqueous phase of the nanoemulsion may include from about 60% to about 95% of the nanoemulsion, or from about 70% to about 90%, or from about 80% to about 90% by weight of the nanoemulsion. The preferred ratio of the oil phase to the aqueous phase in the nanoemulsion is 1:9.

The surfactant used in the nanoemulsion is a quaternary ammonium salt containing at least one linear alkyl chain having at least 20 carbon atoms. The quaternary ammonium salt may be selected from a list containing behentrimonium chloride, behenalkonium chloride, dibegenyldimonium chloride, behenamidopropylethyldimonium ethosulfate, and mixtures thereof. In a specific embodiment, the nanoemulsion stabilizing quaternary ammonium surfactant of the present invention may further be characterized by having only one linear alkyl chain containing more than 5 carbon atoms. The quaternary ammonium surfactant used in the present invention is a trimethyl quaternary ammonium salt.

Nanoemulsion in accordance with the present invention may include softeners. The softener may be selected from the group consisting of petrolatum, isopropyl palmitate, vegetable oils, hydrogenated or not, silicone oils, any liquid polymerized siloxane such as dimethicone, cyclomethicone, cyclopentasiloxane, dimethiconol and amodimethicone, mineral oil, waxes such as paraffin, liquid paraffin and petroleum jelly, aloe vera, fatty alcohols such as arachidyl alcohol, batyl alcohol, behenyl alcohol, C12-13 alcohols, cetearyl alcohol, cetyl alcohol, coconut alcohol, isocetyl alcohol, octyldodecanol and palm alcohol, fatty acids and fatty acid esters, such as batyl stearate, cetearyl behenate, cetearyl isononanoate, cetyl esters, coconut acid, ethyl linoleate, ethyl linolinate, ethyl olinate, ethyl hexyl cocoate, ethyl hexyl myristate, glyceryl caprylate, glyceryl laurate/oleate, glyceryl ricinoleate, isocetyl salicylate, isostearyl alcohol, linoleic acid, linolenic acid, , palmitic acid and acid for wheat germ, shea butter (Butyrospermum parkii butter), cocoa butter (Theobroma cacao butter), waxes, glyceride derivatives such as caproic/caprylic acid triglycerides, cocoglycerides and palm glycerides, cholesterol, lanolin and derivatives, PEG derivatives, squalane, squalene, sucrose and glycerol derivatives such as glycerol trioctanoate: tricaprylin, glycerol, tristearate: tristearin and mixtures thereof. The softener may be present in an amount of from about 1% to about 15% by weight of the composition.

Nanoemulsions may include humectants selected from pyrrolidone carboxylic acid (PCA) and derivatives (arginine PCA, chitosan PCA, copper PCA, ethylhexyl PCA, lauryl PCA, magnesium PCA, sodium PCA, zinc PCA) butylene glycol, calcium gluconate, fructose, glucose, isomalt , lactose, maltitol, mannitol, polydextrose, sorbitol, sucrose, xylitol, glycerin, glycyrrhizic acid and derivatives, histidine, hyaluronic acid and its salts (sodium hyaluronate), silk hydrolyzate, keratin or soy, PEG (-7, -8, - 10, -12, -14), phytantriol, propylene glycol, silk (serica), urea and mixtures thereof. At least one humectant may be present in the composition in an amount of from about 5% to about 15% by weight of the composition.

The nanoemulsion may include an enhancer to enhance the antimicrobial activity of the surfactant. Such enhancers may be butyl glycol, propylene glycol and caprylyl glycol in an amount of from about 0.05 to 2.0%.

The nanoemulsion may include a rheology modifier in an amount of from about 0.5% to about 5% by weight of the topical composition. The rheology modifier may be selected from a list consisting of cetyl alcohol, stearyl alcohol, carnauba wax and stearic acid, vegetable gums (hydroxyethyl cellulose, guar gum, locust bean gum, xanthan gum) and gelatin, silicon dioxide, bentonite and magnesium aluminosilicate, carbomers ( polyacrylic acids) their mixtures.

The nanoemulsions of the present invention are prepared by mixing the oil and water phases using high shear mixers known in the art. The nanoemulsion has droplets having Sauter diameters D[3;2] less than 1 µm, preferably less than 200 nm, more preferably less than 150 nm.

Compositions for Topical Application

The topical composition according to the present invention does not include an additional preservative.

Preservatives used in topical formulations include ammonium benzoate, butyl benzoate, calcium benzoate, ethyl benzoate, isobutyl benzoate, isopropyl benzoate, magnesium benzoate, meabenzoate, methyl benzoate, phenyl benzoate, potassium benzoate, propyl benzoate, benzoic acid, sodium benzoate, propionic acid, ammonium propionate, Potassium Propionate, Sodium Propionate, Salicylic Acid, Calcium Salicylate, Magnesium Salicylate, Magnesium Measalicylate, Sodium Salicylate, Potassium Salicylate, Tea Salicylate, Sorbic Acid, Calcium Sorbate, Sodium Sorbate, Potassium Sorbate (Hexa-2,4-Dienoic Acid and its salts), formaldehyde, paraformaldehyde, o-phenylphenol, mea o-phenylphenate, potassium o-phenylphenate, sodium o-phenylphenate, zinc pyrithione, sodium sulfite, ammonium bisulfite, ammonium sulfite, potassium sulfite, potassium hydrosulfite, sodium bisulfite, metabisulfite Sodium Metabisulfite, Chlorobutanol, Butylparaben, Propylparaben, Sodium Propoylparaben, Sodium Butylparaben, Potassium Butylparaben, Potassium Propylparaben (Buti l-4-hydroxybenzoate and its salts) (propyl-4-hydroxybenzoate and its salts), 4-hydroxybenzoic acid, methylparaben, potassium ethylparaben, potassium paraben, sodium methylparaben, sodium ethylparaben, ethylparaben, sidium paraben, potassium methylparaben, calcium paraben, dehydroacetic acid, sodium dehydroacetate (3-acetyl-6-methylpyran-2,4(3H)-dione and its salts), formic acid, sodium formate, dibromohexamidine isethionate (3,3'-dibromo-4,4'-hexamethylenedioxydibenzamidine and its salts (including isethionate)), thimerosal, phenylmercury acetate, phenylmercury benzoate, undecylenic acid, potassium undecylenate, sodium undecylenate, calcium undecylenate, mea-undecylenate, thea-undecylenate, hexetidine (5-pyrimidinamine, 1,3-bis(2- ethylhexyl)hexahydro-5-methyl-), 5-bromo-5-nitro-1,3-dioxane, 2-bromo-2-nitropropane-1,3-diol, dichlorobenzyl alcohol, triclocarban (1-(4-chlorophenyl) -3-(3,4-dichlorophenyl)urea), p-chloro-m-cresol, triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol), chlorooxylenol, imidazolidinyl urea (N, N''-methylenebis [N '-[3-(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl]urea]), polyaminopropyl biguanide (poly(hexamethylene biguanide hydrochloride; poly(iminoimidocarbonyl)iminohexamethylene hydrochloride; poly(iminocarbonimidoyliminocarbonimidoylimino-1,6-hexanediyl)), phenoxyethanol, methenamine, quaternium-15 (methenamine-3-chloroallyl chloride), climbazole (1-(4-chlorophenoxy)-1-(imidazol-1-yl)-3.3 -dimethylbutan-2-one), DMDM hydantoin (1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione), benzyl alcohol, 1-hydroxy-4-methyl-6-(2,4 ,4-trimethylpentyl)-2-pyridone and its monoethanolamine salt, bromochlorophene (2,2'-methylenebis(6-bromo-4-chlorophenol)), o-cymen-5-ol (4-isopropyl-m-cresol), methylchloroisothiazolinone and methylisothiazolinone (a mixture of 5-chloro-2-methylisothiazol-3(2H)-one and 2-methylisothiazol-3(2H)-one with magnesium chloride and magnesium nitrate), chlorphen (2-benzyl-4-chlorophenol), chloroacetamide (2-chloroacetamide), chlorhexidine, chlorhexidine diacetate, chlorhexidine digluconate, chlorhexidine dihydrochloride dihydrochloride), phenoxyisopropanol (1-phenoxypropan-2-ol), cetrimonium bromide, cetrimonium chloride, lautrimonium bromide, chl lautrimonium oride, steartrimonium bromide, steartrimonium chloride (trimethylammonium alkyl (C12-C22) bromide or chloride), dimethyloxazolidine (4,4-dimethyl-1,3-oxazolidine), diazolidinylurea (N-hydroxymethyl)-N-(dihydroxymethyl-1, 3-dioxo-2,5-imidazolidinyl-4)-N'-(hydroxymethyl)urea), hexamidine, hexamidine diisethionate, hexamidine diparaben, hexamidine paraben (benzenecarboximidamide, 4,4'-(1,6-hexanediylbis(oxy)) bis- and its salts (including isothionate and p-hydroxybenzoate)), glutaral (glutaraldehyde (pentane-1,5-dial)), 7-ethylbicyclooxazolidine (5-ethyl-3,7-dioxa-1-azabicyclo[3,3 ,0]octane), chlorphenesin (3-(p-chlorophenoxy)-propane-1,2-diol), sodium hydroxymethylglycinate, silver chloride, benzethonium chloride (benzenemethanamine, N,N-dimethyl-N-[2-[2- [4-(1,1,3,3-tetramethylbutyl)phenoxy]ethoxy]ethyl]-, chloride), benzalkonium chloride, benzalkonium bromide, benzalkonium saccharinate, benzylhemiformal (methanol, (phenylmethoxy)-), iodopropynylbutylcarbamate (3-iodine- 2-propynylbutylcarbamate), methylisothiazolinone (2- methyl-2h-isothiazol-3-one), ethyl lauroyl arginate HCl, citric acid(s) silver citrate (1,2,3-propane tricarboxylic acid, 2-hydroxy-, monohydrate and 1,2,3-propane tricarboxylic acid, salt 2 -hydroxy-silver (1+), monohydrate).

In one embodiment of the present invention, the topical compositions or nanoemulsions of the present invention do not contain an additional detergent or surfactant other than a quaternary ammonium salt surfactant. These additional detergents or surfactants can be characterized by having an HLB value ranging from 13 to 15 when calculated using the method described in A Quantitative Kinetic Theory of Emulsion Type. I. Physical Chemistry of the Emulsifying Agent, Davies, Gas/Liquid and Liquid/Liquid Interfaces Proceedings of 2nd Congress Surface Activity, Butterworths, London 1957, available at ^{citeseerx.ist.psu.edu/viewdoc/download?doi=10.1} .1.473.424&rep=rep1&type=pdf.

In one embodiment, the topical composition contains an active agent for the treatment of psoriasis. By "cosmetically active agent" is meant a compound having a cosmetic or therapeutic effect on the skin, hair or nails, e.g. brightening agents, darkening agents such as self-tanning agents, anti-acne agents, gloss control agents, antimicrobial agents, anti-inflammatory agents, antimycotic agents , antiparasitic agents, topical analgesics, sunscreens, sunscreens, antioxidants, keratolytic agents, detergents/surfactants, humectants, nutrients, vitamins, energy enhancers, antiperspirants, astringents, deodorants, hair removers, firming agents agents, anti-corns and hair, nail and/or skin care products.

In one embodiment, the additional agent is selected without limitation from the group consisting of hydroxy acids, benzoyl peroxide, sulfur resorcinol, ascorbic acid, D-panthenol, hydroquinone, octylmethoxycinnimate, titanium dioxide, octyl salicylate, homosalate, avobenzone, polyphenols, carotenoids, free radical scavengers, ceramides, polyunsaturated fatty acids, essential fatty acids, enzymes, enzyme inhibitors, minerals, hormones such as estrogens, steroids such as hydrocortisone, 2-dimethylaminoethanol, copper salts such as copper chloride, coenzyme Q10, lipoic acid, amino acids such such as proline and tyrosine, vitamins, lactobionic acid, acetyl-coenzyme A, niacin, riboflavin, thiamine, ribose electron carriers such as NADH and FADH2 and other plant extracts such as aloe vera, pyrethrum and soy extracts, as well as their derivatives and their mixtures. The cosmetically active agent may typically be present in the composition of the present invention, in an amount of from about 0.001% to about 20% by weight of the composition, for example from about 0.01% to about 10%, in particular from about 0.1% to about 5%.

Examples of vitamins include, without limitation, vitamin A, B vitamins (such as vitamin B3, vitamin B5, and vitamin B12), vitamin C, vitamin K, vitamin E, and derivatives thereof.

In one embodiment, the composition of the present invention contains one or more surface-active substances (surfactants). Examples of antioxidants include, without limitation, water-soluble antioxidants such as sulfhydryl compositions and their derivatives (e.g., sodium metabisulphite and N-acetylcysteine), lipoic acid and dihydrolipoic acid, resveratrol, lactoferrin, and ascorbic acid and ascorbic acid derivatives (e.g., ascorbyl palmitate). and ascorbyl polypeptide). Fat-soluble antioxidants suitable for use in the compositions of the present invention include, without limitation, butylated hydroxytoluene, tocopherols (eg, tocopherol acetate), tocotrienols, and ubiquinones. Natural extracts containing antioxidants suitable for use in the compositions of the present invention include, without limitation, extracts containing flavonoids and isoflavonoids, as well as their derivatives (for example, genistein and diadzein), extracts containing resveratrol, and the like. Examples of such natural extracts include extracts of grape seed, green tea, pine bark and propolis. Other examples of antioxidants can be found on pages 1612-13 of the ICI Handbook.

Local Application

Topical application of nanoemulsions and compositions of the present invention is intended for the treatment of skin diseases such as eczema, inflammation and skin atrophy. The compositions of the present invention are also useful in stopping, preventing, slowing down or inhibiting the growth of bacterial biofilms associated with skin diseases.

As used in this application, the term "topical application" means direct application to the skin or distribution over the skin, for example, by hand or using an appropriate applicator, such as a tissue.

EXAMPLES

Below are a few examples to further illustrate the essence of the invention and the method of its implementation. However, the invention should not be construed as being limited to the details provided herein.

The following test methods were used in the examples.

1. Methods and Materials

1.1 Recipe

The compositions of the standard basic formulation are presented in Table 1. The surfactant and softener are selected from the list given in paragraph 1.2 below. Each surfactant or softener composition may contain one or a combination of different products in each component category.

Formula 1 Formula 2 Formula 3 Glycerol 5% 12% 12% Surface-active substance one% 5% 2.5% softener eight% 10.75% 9.45% or 10.7% NaCl 0.2% 0.01% 0.01% Water Ven. quantity up to 100% Ven. quantity up to 100% Ven. quantity up to 100%

Table 1: Composition formulations for each component as a percentage by weight of the general formula.

1.2 Recipe Ingredients

1.2.1 Surfactant

INCI name: Potassium cetyl phosphate; hydrogenated palm oil glycerides; Trade name: Emulsiphos 677660; Supplier: Symrise AG

INCI name: Distearyl dimonium chloride, isopropyl alcohol; Trade name: VARISOFT TA100; Supplier: EVONIK GOLDSCHMIT GmbH

INCI name: behentrimonium chloride, dipropylene glycol; Trade name: Genamine BTLF; Supplier: Clariant GmbH

INCI name: Triceteareth-4 phosphate, ceteareth 4, cetearyl alcohol; Trade name: Hostaphat KW 340 D; Supplier: Clariant International Ltd

1.2.2 Softener

INCI name: Microcrystalline wax; Paraffin; Mineral oil; BHT, Trade name: Codex Syntadex 7702 white petrolatum, Supplier: Synteal

INCI name: Isopropyl palmitate, Trade name: Isopropyl palmitate, Supplier: Cognis

INCI name: Dimethicone, Trade name: Element14 PDMS 10 A, Supplier: EIGENMANN & VERONNELLI S.P.A

INCI name: Cetyl alcohol, Trade name: Lanette 16, Supplier: BASF Personal Care & Nutrition GmbH

INCI name: Caprylyl glycol, trade name Dermosoft Octiol, supplier of Oxyrane Chemical co. Ltd.

1.3 Microbiology

1.3.1 Load test

Load tests are carried out in accordance with the ISO11930 (2012) standard. Load tests are based on the inoculation of the formulation with a calibrated inoculum. The number of surviving microorganisms was measured at regular intervals for 28 days. For each time interval and for each strain, the log reduction value is determined using the calculated log stress test (population per gram at starting point) compared to the log recovery value at various time points. Load tests are considered a low success if the log reduction is between 2 and 3; as an obvious success if the log reduction exceeds 3.

Tests are performed using the following strains as test organisms:

- Pseudomonas aeruginosa ATCC®9027TM2;

- Staphylococcus aureus ATCC®6538TM;

- Escherichia coli ATCC®8739TM;

- Candida albicans ATCC®10231TM;

- Aspergillus brasiliensis (formerly A. niger ) ATCC®16404TM.

Tests are carried out in sterile closed bacteriological containers. Transfer at least 20 g of test material into a sterile container. The product is thoroughly mixed for about 1 min immediately after inoculation. Encapsulated samples were stored at 20°C during the test period. Before each selection, the products are thoroughly mixed to ensure uniformity. Serial dilutions to determine the number of microorganisms by inoculation on Petri dishes are performed in a neutralizer to neutralize the preservative system. The minimum sample size is 1 ml/gram for standard products + 9 ml of neutralizer. Microorganisms are grown on agar Petri dishes using TSA or SDA incubation medium for 4 days at 30°C or 20°C. After incubation, count the number of microbial colonies and the average CFU/ml for two plates and multiply by the dilution factor.

1.3.2 Biofilm growth, crystal violet method

Biofilm growth experiments were performed according to the protocol described in GA O'Toole, Microtiter Dish Biofilm Formation Assay, J Vis Exp. 2011; (47) 2437. The protocol described in GA O'Toole for Pseudomonas aeruginosa was used for Staphylococcus Aureus MFP03 and Staphylococcus Epidermis MFP04.

Two conditions were investigated:

- Effect of emulsions on biofilm formation: emulsions were added to the medium from the very beginning of bacterial growth.

- Effect of emulsions on already formed biofilms: emulsions were added to the bacteria after the first 24 hour incubation, which allowed the biofilm to form.

The protocol outlined in G.A. O'Toole is as follows :

Growing Biofilm

1. Grow a culture of the wild type Pseudomonas aeruginosa or mutant strain overnight in enriched medium (i.e., LB);

2. Dilute the overnight culture 1:100 with fresh biofilm assay medium. The standard biofilm medium for P. aeruginosa is M63 minimal medium supplemented with magnesium sulfate, glucose, and casamino acids. As an alternative environment to promote biofilm growth, promote less plankton growth and more stable biofilm formation, glucose and casamino acids can be replaced with arginine as the sole source of carbon and energy.

3. Add 100 µl of the dilution to each well of a 96 well dish. For quantitative analysis, we typically use 4-8 replicate wells for each dose.

4. Incubate the microtiter plate for 4-24 hours at 37°C.

Biofilm staining

1. After incubation, shake out the cells by turning the dish and shaking out the liquid.

2. Gently submerge the dish into a small bath of water (i.e. use the bottom of the P1000 pipette tip box as a bath). Shake out the water. Repeat this procedure a second time. This step helps to remove loose cells and media components that can be stained in the next step and greatly reduces background staining.

3. To each well of a microtiter plate, add 125 µl of a 0.1% solution of crystal violet in water.

4. Incubate the microtiter plate at room temperature for 10-15 minutes.

5. Rinse the plate 3-4 times with water by immersion in the water bath as described above, shake out and pat dry with a stack of paper towels to rid the plate of all excess cells and dye.

6. Invert the microtiter plate and dry for several hours or overnight.

7. For qualitative analysis, wells can be photographed when dry.

Biofilm Quantification

1. Add 125 µl of 30% acetic acid in water to each well of the microtiter plate to dissolve the CV.

2. Incubate the microtiter plate at room temperature for 10-15 minutes.

3. Transfer 125 µl of diluted CV to a new flat-bottomed microtiter plate.

4. Quantify the absorbance of the plate reader at 550 nm using 30% acetic acid in water as a reference.

For biofilm formation conditions: 10% (w/w) emulsions are added to the medium and absorbance is measured after 24 hours of incubation. For already formed biofilms: 24 h after biofilm growth, the culture medium was removed and replaced for 4 h with an emulsion. Then the optical density was measured. The results are expressed as percentage of absorbance compared to the control sample, which is a biofilm. For biofilms that form, the decrease in percent absorbance represents growth inhibition in the presence of the emulsion. In the case of already formed biofilms, the decrease in percentage absorbance represents the effect on the already formed biofilms.

1.3.3 Biofilm Growth Inhibition, Well Method .

Biofilm growth experiments were performed according to the protocol described in Hui Zhang et al., Characterization and antimicrobial activity of a pharmaceutical microemulsion, International Journal of Pharmaceutics 395 (2010) 154-160.

The protocol described by Hui Zhang has been adapted as follows:

a - 100 μl of culture of bacterial strains (DO ₅₈₀ =0.5) were distributed on a culture dish with LB.

b - wells with a diameter of 5 mm were created using a punch on the surface of the culture dish gel. Each well refers to the same composition throughout the test.

c - 50 μl of the test composition was injected into each well.

d - 24 h were incubated at 37 °C.

e wells were cleared of formulations.

f - measured the growth retardation halo.

g - repeated from step c to obtain data for several days (in this case 8 days).

1.4 Nanoemulsions

1.4.1 Instrument

The M110P microfluidizer, hydraulic booster pump, and F12Y interaction chamber were manufactured by Microfluidics (Westwood, Massachusetts, USA).

1.4.2 Getting the emulsion

Emulsions were prepared in the laboratory according to the following procedure:

Purified water is added to the main vessel and heated to 50°C while stirring using a mixer such as the Turbotest from VMI Raynerie. Then sodium chloride is added with stirring. The mixture is heated to 80 °C. Then, surfactants and softeners are successively added with stirring and stirred until complete dissolution. The mixture is cooled to 60 °C. At a temperature of about 60 ° C, glycerin is added to the mixture. The process is completed at 60 °C.

1.4.3 Preparation of nanoemulsions

Nanoemulsions were prepared according to the high pressure microfluidic method. The coarse emulsion at 50°C enters the system through the inlet tank of the Microfluidics M110P machine. The emulsion is then pressurized to 20,000 psi. inch, created by a pump with a hydraulic booster. The M110P advances the product through the F12Y interaction chamber. The product was accelerated to high speed and subjected to intense shear and impact (speed, shear and impact are inherent characteristics of an interaction chamber machine). 6 ml of product passes through the chamber in less than a second, fluids must pass through the chamber at over 300 m/s. After processing, the product was collected in the outlet tank. Unless otherwise indicated, the emulsion was subjected to this process in three passes.

1.4.4 Droplet size

Droplet sizes were measured using a Mastersizer 3000 instrument (Malvern instruments Ltd, UK) using the dynamic light scattering method by measuring the angular change in the intensity of light scattered during the passage of a laser beam through a sample of dispersed particles.

Nanoemulsion droplets were measured according to the following method:

- Demineralized water must be taken the day before receiving tempered and degassed water for the experiment

- The equipment was started 20 min before the analysis

- The circulation circuit was flushed with normal water (this facilitates cleaning), then once with demineralized water.

- Analysis options:

- Refractive index: 1.450

- Absorption coefficient: 0.001

- Mi Theory

- Model: spherical

- Exposure time in red wavelength: 10 s+10 s background

- Exposure time in blue wavelength: 3 s + 3 s background

- 5 measurements

- No waiting time between and before measurement

Stirring speed: 1500 rpm

- Initialization

- Detector 1<100

- Detector 20<20

- The profile of the detection circuit should have a regular decreasing exponential value without bumps

- Food must be in the green zone

- Background until the signal is weak and fluctuates randomly

- Sample preparation:

- A small amount of product (spatula point) was diluted in about 2 drops of purified water until smooth.

- Added about 2 ml of additional water and mixed by hand until a homogeneous mixture.

- When the mixture became homogeneous, this mixture was injected with a pipette directly into the bottom of the sampler until an attenuation of about 5%. When the shading stabilized, the measurement was started. Measurements were repeated until RSD values were below 5% (steady curves for d10, d50 and d90).

- Eligibility criteria:

- Requires 10 points. RSD should be < 5%

- Residual and weighted balance must be < 2%

- A suitable signal should be 3 times the background noise.

Nanoemulsions have small droplets with a larger surface area compared to droplets of conventional emulsions. Decreasing the droplet radius multiplies the surface area. The Sauter diameter [3;2] is the diameter used to characterize these droplets. It is defined as the diameter of a sphere that has the same volume to surface area ratio as the particle of interest and is sensitive to small particles.

1.5 Viscosity

Viscosity measurements were performed on a Physica MCR 300 device (Anton Paar GmbH) at a shear rate of 45 s ^-1 .

Test method:

- Install in accordance with the supplier's recommendations.

- Carry out motor adjustment, initialization and zero clearance.

- Set the thermostat to 20°C. The measurement/sample temperature should be 20°C.

- Use a Microman pipette to obtain a product volume corresponding to the gap between the cone / plate of your equipment + 10%

- Slowly release the product in the center of the plate without moving it. It should create a symmetrical round volume. Avoid bubble formation.

- Move down the cone to the measurement position depending on the truncated viscosity at a shear rate of 45s ^-1

- Then apply the following protocol to obtain the viscosity at 45s ^-1 :

1. Adjust to 20°C for 120 s. No shear rate.

2. 3 measurements every 10s at 5s-1

3. 9 measurements every 4 s increasing from 5s ^-1 to 45s ^-1

4. 2 measurements every 5 s at 45 s ^-1

The value recorded for the viscosity is the second value at 45 s ^-1 .

2. Examples and Test Results

2.1 Load tests

Five compositions (Examples 1-5) were tested for their microbiological stability in accordance with the test protocol described above. None of these compositions were subjected to microfluidization. The goal was to select the most effective surfactant for the load test.

Example 1 (Comparative Example)

The composition of Example 1 was formulated according to formula 1.

The surfactant was potassium cetyl phosphate, 1% of the total weight of the mixture.

Example 2 (Comparative Example)

The composition of Example 2 was formulated according to formula 2.

The surfactant was Triceteareth-4 phosphate, 5% by weight of the mixture; and cetyl alcohol in an amount of 1.25% of the total mass of the mixture.

Example 3 (Comparative Example)

The composition of Example 3 was formulated according to Formula 2.

The surfactant was distearyl dimonium chloride, 5% of the total weight of the mixture; and cetyl alcohol in an amount of 1.25% of the total mass of the mixture.

Example 4 (Comparative Example)

The composition of Example 4 was formulated according to Formula 2.

The surfactant was behentrimonium chloride, 5% of the total weight of the mixture; and cetyl alcohol in an amount of 1.25% of the total mass of the mixture.

Example 5 (Comparative Example)

The composition of Example 5 was formulated according to Formula 2.

The surfactant was behentrimonium chloride, 5% of the total weight of the mixture; and cetyl alcohol in the amount of 2.5% of the total mass of the mixture.

The compositions of Examples 1 and 2 failed the test, with the exception of E. Coli for Example 2. Microorganism growth was not detected. The composition of Example 3 successfully passed the loading test, but failed the test for C. albicans and A. brasiliensis . The compositions of Examples 4 and 5 successfully passed the load test. The formulation of Example 5 barely passed the A. brasiliensis test, while the formulation of Example 4 had little success. Detailed results are presented in Table 2.

28 days E. coli S. aureus Pseudomonas aeruginosa C. albicans A. brasiliensis Example 1 -0.7 1.6 0.2 -0.8 0.3 Example 2 2.1 0.6 1.2 -0.7 0.0 Example 3 3.7 3.8 3.8 -one 1.0 Example 4 3.5 3.6 3.5 3.5 2.4 Example 5 3.7 3.9 3.5 3.5 1.8

Table 2: Load test of Comparative Example formulations after 28 days expressed as log reduction

Begentrimonium chloride was superior to the other three surfactants tested in the stress test.

2.2 Nanoemulsions - load test

Compositions in accordance with Examples 4 and 5 were subjected to microfluidization in accordance with the protocol described above to obtain nanoemulsions (Examples 6 and 7, respectively).

Example 6

The composition of Example 6 was formulated in the same way as in Example 4. Additionally, the composition of Example 6 was subjected to microfluidization.

Sauter drop diameter D [3;2]: 60 nm, at t=0 and after 3 months.

Example 7

The composition of Example 7 was formulated in the same way as in Example 5. Additionally, the composition of Example 7 was subjected to microfluidization.

Both compositions of Examples 6 and 7 successfully passed the load test. The formulation of Example 7 showed even better results than its non-microfluidized counterpart (namely Example 5) against A. brasiliensis .

Detailed results are presented in Table 3.

28 days E. coli S. aureus Pseudomonas aeruginosa C. albicans A. brasiliensis Example 4 3.5 3.6 3.5 3.5 2.4 Example 5 3.7 3.9 3.5 3.5 1.8 Example 6 3.5 3.6 3.5 3.7 2.2 Example 7 3.7 3.9 3.5 3.5 2.1

Table 3: Load test of compositions according to the present invention compared to Comparative Examples after 28 days expressed as log reduction.

Begentrimonium nanoemulsions have proven to be as effective as their non-microfluidized equivalents.

2.3 Direct impact on biofilms

The compositions according to examples 6 and 7 (of the present invention) were tested on biofilms of Staphylococcus aureus in accordance with the procedure for obtaining crystal violet, described in paragraph 1.3.2. The tests were repeated on biofilms in the process of their formation and on already formed biofilms. The compositions according to examples 4 and 5 (comparative examples) were subjected to the same growth inhibition tests to evaluate the effect of microfluidization. A 10% solution of Triton X 100 (Aldrich) was subjected to the same test as a reference. Detailed results are presented in Table 4.

bacterial strain S. aureus biofilm As part of already educated Example 4 298 224 Example 5 219 168 Example 6 one 36 Example 7 22 35 Triton 27 177

Table 4: The effect of microfluidization on the formation of biofilms of bacterial strains in the formation stage and already formed biofilms; expressed as a percentage of absorption relative to the control, which is only a biofilm.

Both compositions according to examples 6 and 7 showed good inhibition of biofilm growth for biofilms during formation on both bacterial strains and showed a strong effect on already formed biofilms of both strains. These results are clearly superior to equivalent compositions not subjected to microfluidization; and the above Triton standard.

2.4 Droplet size

Various microfluidization parameters were tested to evaluate the effect of nanoemulsion droplet size on the inhibition of biofilm growth of bacterial strains, during their formation or on already formed biofilms.

Example 8

The composition of Example 8 was formulated in the same way as in Example 6. The composition of Example 8 was subjected to microfluidization (1 pass, 20,000 psi). Sauter drop diameter D [3;2]: 120 nm, at t=1 month

bacterial strain S. aureus biofilm As part of already educated Example 6 one 36 Example 8 55 208

Table 5: Influence of nanoemulsion droplet diameter on the formation of biofilms of bacterial strains during their formation or on already formed biofilms; in accordance with the procedure for obtaining crystal violet, described in paragraph 1.3.2, expressed as a percentage of absorbance relative to the control, which is only a biofilm.

Example 8 is less effective than Example 6 on biofilms in the process of formation or already formed biofilms. Example 8 shows biofilm inhibitory activity, but is not as effective in targeting already formed biofilms as the other composition of the present invention. Nanoemulsion droplets are more effective at acting on already formed biofilms if their Sauter diameter is below 120 nm.

2.5 Antimicrobial activity on biofilms; Comparison between S. aureus and S. epidermidis

Two compositions (Examples 10 and 12) were tested for their growth inhibitory activity against Staphylococcus Aureus and Staphylococcus Epidermidis biofilms.

Example 9 (comparative example)

The composition of Example 9 was formulated according to Formula 3. The surfactant was begentrimonium chloride, 2.5% of the total mixture weight; Softeners accounted for 10.7% of the total mass, including: cetyl alcohol, 2.5% of the total mass of the mixture; and caprylyl glycol, 0.2% by weight of the mixture.

Example 10

The composition of Example 10 was formulated in the same way as in Example 9. Additionally, the composition of Example 10 was subjected to microfluidization. Sauter drop diameter D [3;2]: 126 nm, at t=0 and after 3 months.

Example 11 (comparative example)

The composition of Example 11 was formulated in accordance with formula 3. The surfactant was begentrimonium chloride, 2.5% of the total weight of the mixture; Softeners accounted for 9.45% of the total mass, including: cetyl alcohol, 1.25% of the total mass of the mixture; and caprylyl glycol, 0.2% by weight of the mixture. Sauter drop diameter D [3;2]: 36 µm, at t=0 and after 3 months.

Example 12

The composition of Example 12 was formulated in the same way as in Example 11. Additionally, the composition of Example 12 was subjected to microfluidization. Sauter drop diameter D [3;2]: 52 nm, at t=0 and after 3 months.

2.5.1 Load test compositions according to examples 9-12

Compositions in accordance with examples 9, 10 and 12 successfully passed the load test. The composition according to example 11 was not stable; tests have not been carried out.

Detailed results are presented in Table 6.

28 days E. coli S. aureus Pseudomonas aeruginosa C. albicans A. brasiliensis Example 9 (comparative) 3.9 3.7 3.4 3.7 3.6 Example 10 3.9 3.7 3.4 3.7 3.6 Example 12 3.6 3.5 3.6 3.3 3.7

Table 6: Load test of compositions according to the present invention in comparison with the composition of comparative examples after 28 days expressed as a logarithmic reduction.

2.5.2 Biofilm treatment, crystal violet method

Compositions according to examples 10 and 12 were tested on Staphylococcus aureus biofilms and Staphylococcus Epidermidis biofilms . The tests were carried out on biofilm in the process of formation and on already formed biofilms in accordance with the procedure described in paragraph 1.3.2 (crystal violet). Detailed results are presented in Table 7.

bacterial strain S. aureus S. epidermidis biofilm As part of already educated As part of already educated Example 10 60.51 83.04 48.96 114.9 Example 12 3.9 14.68 3.72 21.54

Table 7: Effect of nanoemulsions according to examples 10 and 12 on the formation of biofilms of bacterial strains in the formation stage and already formed biofilms; in accordance with the procedure for obtaining crystal violet, described in paragraph 1.3.2, expressed as a percentage of absorbance relative to the control, which is only a biofilm.

Compositions according to examples 10 and 12 demonstrate growth inhibition on S aureus and S. epidermidis biofilm. The composition according to example 12 appears to be more effective than the composition according to example 10. Both are more effective on a biofilm in the process of formation than on an already formed biofilm.

2.5.3 Biofilm treatment, well method

The compositions according to examples 10 and 12 (of the present invention) were tested on biofilms of Staphylococcus aureus and Staphylococcus epidermidis . The tests were carried out on biofilms in accordance with the methodology described in paragraph 1.3.3 (Wells). A 10% solution of Triton X 100 (Aldrich) was added to the same test and the results after 2 days were used as references.

The inhibition halo was measured and compared to the inhibition halo obtained with the Triton X-100 solution after 2 days. Differences in inhibition halo value are expressed as %. Over 100% inhibition was higher than that observed for Triton over 2 days; at concentrations less than 100%, the inhibition was lower than that observed with Triton for 2 days. Inhibition was measured after 2 days and 8 days.

Detailed results are presented in Table 8.

bacterial strain S. aureus S. epidermidis 2 days 8 days 2 days 8 days Example 10 3.6 4.8 0 0 Example 12 47.8 93.3 0 0 Triton X-100 100 198.5 100 231

Table 8: Influence of compositions on the development of biofilms with bacterial strain S. aureus and S epidermidis ; expressed as % growth inhibition compared to Triton X 100 after 2 days.

Surprisingly, it was found that the composition according to example 12 showed inhibition of the growth of S Aureus biofilms, but no inhibition of S Epidermidis biofilms. This selectivity is highly desirable and may help to even out the skin microbiome and improve atopic dermatitis. The difference in inhibition between the formulations according to example 10 and 12, taking into account tables 7 and 8, can be explained by differences in viscosity. The composition according to example 12 is more fluid than the composition according to example 10 (see table 9), which can lead to better penetration through the gel used in the well methodology (see paragraph 1.3.3). In addition, this result can be interpreted taking into account paragraph 2.4; the particle diameter of the nanoemulsion is higher for Example 10 (126 nm) than for Example 12 (52 nm).

2.6 Viscosity

The viscosities of the compositions according to the examples of the present invention were measured using the procedure described in paragraph 1.5.

Emulsion Viscosity (cP) at 45s ^-one Example 1 (comparative example) 2050 Example 2 (comparative example) N/A (liquid) Example 3 (comparative example) 575 Example 4 (comparative example) 502 Example 5 (comparative example) 1320 Example 6 N/A (liquid) Example 7 359 Example 8 123 Example 9 (comparative example) 1050 Example 10 664 Example 12 fifteen

Table 9: Viscosity of compositions according to examples of the present invention.

All Examples 6, 7, 8, 10 and 12 have low viscosities below 700 cP at 45 s ^-1 , even below 360 cP at 45 s ^-1 for Examples 6, 7, 8 and 12. Droplet size appears to correlate with fluidity (see examples 7 and 8). Low viscosity can be used when applying the composition to damaged skin or mucous membranes, avoiding mechanical efforts to spread the composition, for example, the composition can be applied in the form of a spray or roller device.

While the invention has been described above with reference to specific embodiments, it is clear that many changes, modifications and variations are possible without departing from the spirit of the concept having the features of the invention described herein. Thus, the invention is intended to cover all such changes, modifications, and variations that fall within the spirit and scope, broadly, of the appended claims.

Claims (16)

1. Composition for topical application containing an oil-in-water nanoemulsion, said nanoemulsion containing behentrimonium chloride surfactant, wherein the oil phase contains at least one emollient selected from petrolatum, isopropyl palmitate, dimethicone, mineral oil, paraffinic waxes, cetyl alcohol, or mixtures thereof; and an aqueous phase; wherein said nanoemulsion contains droplets having Sauter diameters D[3;2] from about 10 nm to about 100 nm. 2. The topical composition of claim 1 wherein said surfactant is in an amount of about 1% to about 7% by weight of the composition. 3. The topical composition of claim 2, wherein said surfactant is in an amount of about 2% to about 5% by weight of the composition. 4. The topical composition of claim 1, wherein said nanoemulsion contains droplets having Sauter diameters D[3;2] from about 30 nm to about 70 nm. 5. The topical composition of claim 1, wherein said topical composition has a viscosity of less than 360 cP at 45 s ^-1 as measured by a Physica MCR 300 (Anton Paar GmbH) at a shear rate of 45 s ^-1 . 6. The topical composition according to claim 5, wherein said topical composition has a viscosity of less than 125 cP at 45 s ^-1 as measured by a Physica MCR 300 (Anton Paar GmbH) at a shear rate of 45 s ^-1 . 7. The topical composition of claim 1 wherein said emollient is present in an amount of from about 1% to about 15% by weight of the composition. 8. The topical composition of claim 1 further comprising a rheology modifier in an amount of from about 0.5% to about 5% by weight of the composition. 9. The topical composition of claim 8 wherein said rheology modifier is selected from the group consisting of cetyl alcohol, stearyl alcohol, carnauba wax, stearic acid, hydroxyethyl cellulose, guar gum, locust bean gum, xanthan gum, gelatin, silica , bentonite, magnesium aluminum silicate, carbomers and mixtures thereof. 10. The topical composition of claim 1 further comprising at least one humectant in an amount of from about 5% to about 15% by weight of the composition. 11. Composition for topical application according to p. 1, additionally containing from about 5% to about 15% of the mass. water. 12. Composition for topical application according to claim 11, containing from about 50% to about 90% of the mass. water. 13. A topical composition according to claim 1, wherein said composition does not contain additional surfactants. 14. A topical composition according to claim 1, wherein said composition does not contain a preservative. 15. A method for destroying or inhibiting the growth of bacteria in a biofilm, including exposing the biofilm to a nanoemulsion according to claim 1. 16. The method of claim 15 wherein the bacteria in the biofilm is Staphylococcus aureus.