Topical antimicrobial formulation

Abstract

It relates to a topical antimicrobial formulation comprising an acidic substance comprising at least one organic acid diluted in an aqueous solvent while having an action deleterious against microbes, said acidic substance having an acidity constant pKa that is less than 6, as well as: between 1% and 10% by weight of acidic substance in the INCI base; a basic substance the quantity of which in the formulation is such that the pH is comprised between the pKa of the acidic substance and 8; between 0.1% and 15% by weight of a booster substance capable of biochemically interacting with the membrane of the microbes to facilitate the deleterious action of the acidic substance, said booster substance comprising at least one compound in the INCI base selected from amphiphilic compounds, chelating compounds having an ability to associate with divalent ions or sterols, or polyphenolic compounds.

Description

[0001] DESCRIPTION

[0002] Title: Topical antimicrobial formulation

[0003] The invention relates to a topical antimicrobial formulation.

[0004] It applies in particular to a formulation intended to be applied to the skin and in particular to the hands, for hygiene purposes and / or to prevent the spread of diseases. Such formulations are generally used without rinsing, in addition to and / or as a replacement for washing with soap and water, and may more particularly be used by healthcare personnel in the context of health care or during travel, both personal and professional, as well as by children, particularly in schools, and more generally in the event of a risk of skin exposure to a possibly contaminated surface.

[0005] These formulations are intended to kill, deactivate or slow the growth of microbes harmful to human health, such as bacteria, yeasts, fungi and / or viruses.

[0006] Antimicrobial formulations, called hydroalcoholic solutions, are known which contain an alcohol, in particular ethanol and / or isopropanol, mixed with an antimicrobial agent, for example a positively charged surfactant, of the quaternary ammonium type.

[0007] Antimicrobial formulations are also known which comprise an acidic substance comprising at least one organic acid diluted in an aqueous solvent and exhibiting a deleterious action against microbes, said acidic substance having an acidity constant pKa which is less than 6. These formulations prove to be particularly effective because, in addition to being easily bio-sourced and biodegradable, they exhibit low volatility in air and low dermal absorption, which increases the effectiveness of their antimicrobial action when applied to the skin of a user. However, the known formulations are not entirely satisfactory, due to their low dermo-compatibility induced by their acidic pH, in particular lower than the pKa of the acid, which is necessary for their effectiveness.In particular, in the case of repeated applications, they can lead to the appearance of undesirable effects on the skin, in particular drying, redness and / or irritation of the epidermis.

[0008] The invention aims to improve the prior art by proposing in particular a formulation which comprises an antimicrobial organic acid substance, in order to benefit from the advantages relating to biosourceability, biodegradability and persistence on the epidermis, while presenting improved dermo-compatibility.

[0009] For this purpose, the invention provides an antimicrobial topical formulation comprising an acidic substance comprising at least one organic acid diluted in an aqueous solvent exhibiting a deleterious action against microbes, said acidic substance having an acidity constant pKa which is less than 6, said formulation further comprising:

[0010] - between 1% and 10% by weight of acidic substance in which at least one organic acid used is referenced in the INCI database;

[0011] - a basic substance comprising at least one base, the quantity of basic substance in the formulation being such that the pH of said formulation is between the pKa of the acidic substance and 8;

[0012] - between 0.1% and 15% by weight of a booster substance which is capable of interacting biochemically with the membrane of the microbes to facilitate the deleterious action of the acid substance on said microbes, said booster substance comprising at least one compound referenced in the INCI base chosen from amphiphilic compounds, chelating compounds having a capacity for association with divalent ions or sterols, polyphenolic compounds. Other features and advantages of the invention will appear in the following description of different particular embodiments.

[0013] The invention relates to a topical antimicrobial formulation, in particular intended to be applied to the skin and in particular to the hands of a user for hygiene purposes and / or to combat the spread of diseases.

[0014] The formulation comprises an acidic substance comprising at least one organic acid diluted in an aqueous solvent and having a deleterious action against microbes. For optimal antimicrobial efficacy, the acidic substance has an acidity constant pKa which is less than 6. In the case of a polyacid, the pKa considered is that of the weakest acid.

[0015] The acidic substance may in particular exhibit virucidal activity, for example against viruses such as:

[0016] - herpes, in particular HVE1 (for “Equine Herpes Virus Type 1”);

[0017] - adenoviruses, notably AdV5 (for “Adenovirus 5”);

[0018] - coronaviruses, notably SARS-COV-2 (for Severe Acute Respiratory Syndrome Coronavirus 2).

[0019] The acidic substance may also exhibit other antimicrobial functions, including against bacteria (antibacterial), yeasts (yeasticidal), and / or fungi (antimycotic).

[0020] The organic acid is chosen in particular from carboxylic acids, that is to say acids having a carboxyl group.These acids include, but are not limited to, the following components: lactic acid, citric acid, tartaric acid, acetic acid, adipic acid, anisic acid, malic acid, succinic acid, benzoic acid, cholic acid, ascorbic acid, dehydroacetic acid, deoxycholic acid, glucuronic acid, glycolic acid, fumaric acid, formic acid, gluconic acid, glutamic acid, guanylic acid, folic acid, fulvic acid, sorbic acid, glycyrrhizic acid, kojic acid, itaconic acid, mellisic acid, hyaluronic acid, amino acids, glutaric acid, glyoxylic acid, humic acids, hippuric acid, inosic acid, levulinic acid, perillic acid, quinic acid, tauric acid, ribonic acid, salicylic acid, shikimic acid, trenaxamic acid, thujic acid, tiglic acid, ursolic acid, usnic acid, vanillic acid, valproic acid.

[0021] The organic acid may also be chosen from acids derived from vegetable oils, such as: safflower acids, rapeseed acids, coconut and copra acids, jojoba acids, palm acids, corn acids, soybean acids, uric acid, as well as fatty acids, in particular fatty acids comprising between 3 and 24 carbon atoms (C3 to C24), including unsaturated and functionalized fatty acids.

[0022] To ensure dermatological compatibility, the formulation comprises between 1% and 10% by weight, and preferably between 1% and 5% by weight, of acidic substance in which the at least one organic acid used is referenced in the INCI database (for the English “International Nomenclature of Cosmetic Ingredients”).

[0023] In particular, the acidic substance comprises an organic acid or a mixture of organic acids whose individual concentrations are arranged to give the formulation a margin of safety (MOS) greater than 100. This MOS margin is calculated according to standard methods in the field of toxicology, from the dermal absorption and the NOAEL (No Observable Adverse Effect Level) value of each component of the formulation, as well as the exposure scenario.

[0024] In advantageous examples, the acidic substance comprises at least one organic acid selected from lactic acid, lauric acid, citric acid, oleic acid, or a mixture of at least two of these compounds. The formulation further comprises a basic substance comprising at least one base, the amount of basic substance in said formulation being such that the pH of said formulation is between the pKa of the acidic substance and 8.

[0025] The addition of a basic substance makes it possible to limit the total acidity of the formulation, in order to improve its dermo-compatibility, and thus to limit the risk of irritation and / or redness, in particular after several applications on a user's skin. In particular, the formulation may comprise a quantity of basic substance adapted to give it a pH of around 5, which corresponds approximately to the minimum pH value of healthy human skin.

[0026] The basic substance comprises at least one base chosen from salts of organic acids, in particular sodium lactate and / or potassium lactate, clays, in particular bentonite and / or montmorillonite, sodium hydroxide, potassium hydroxide, triethanolamine, butylethanolamine, disodium carbonates, dipotassium carbonates, disodium phosphates, dipotassium phosphates, or a mixture of at least two of these compounds.

[0027] Advantageously, the basic substance comprises sodium hydroxide, optionally mixed with a clay, in particular based on bentonite and / or montmorillonite.

[0028] When mixed in a formulation at a pH above their respective pKa constants, organic acids react chemically to produce salts, e.g., sodium salt or potassium salt, depending on the acid(s) used, which greatly attenuates or even deactivates their antimicrobial properties, and thus reduces the effectiveness of the formulation.

[0029] In particular, for each organic acid present in the formulation, the concentration of its organic form decreases as the pH value of said formulation increases. Thus, for a pH value between the pKa of a given organic acid and a pKa+1 value, the concentration of its acid form is greater than 5% of the total concentration of said organic acid, while this percentage drops to 0.5% for a pH between pKa+1 and pKa+2.

[0030] To overcome these drawbacks, the formulation further comprises between 0.1% and 15% by weight, and preferably between 1% and 10% by weight, of a booster substance which is capable of interacting biochemically with the membrane of the microbes to facilitate the deleterious action of the acidic substance on said microbes. In particular, the booster substance makes it possible to stimulate the deleterious action of the acidic substance.

[0031] The booster substance comprises at least one compound referenced in the INCI database chosen from:

[0032] - amphiphilic compounds;

[0033] - chelating compounds having the capacity to associate with divalent ions or sterols;

[0034] - polyphenolic compounds.

[0035] Thus, the addition of a booster substance to the formulation allows the antimicrobial action of the acidic substance to be benefited from, despite a lower concentration of acid forms due to the presence of the basic substance. This results in a formulation that has both good antimicrobial properties and good compatibility with human skin.

[0036] The booster substance may comprise at least one amphiphilic compound having a critical micelle concentration (CMC) value of between 1 mM and 400 mM, in particular between 10 mM and 100 mM.

[0037] In particular, the booster substance comprises at least one amphiphilic compound chosen from glyceryl laurate, glyceryl caprate, glyceryl caprylate, glyceryl palmitate, glyceryl stearate, quaternary ammoniums, saponins or a mixture of at least two of these compounds. The amphiphilic compound may also be chosen in the INCI base from fatty alcohols, ethoxylated alcohols, an amphiphilic compound with betaine, phosphate, sulfate group, alkylated sugars, polylyglyceryl, polysorbate or a mixture of at least two of these compounds.

[0038] Advantageously, the formulation may in particular include:

[0039] - between 5% and 7% by weight of glyceryl stearate;

[0040] - between 0.5% and 3.5% by weight of glyceryl laurate;

[0041] - between 0.2% and 0.7% by weight of xanthan.

[0042] Amphiphilic compounds have a molecular structure with a hydrophobic part having an affinity for membrane lipids and a hydrophilic part having an affinity for aqueous media. They can interact with the membrane lipid bilayer of microbes, in order to destabilize the membrane. Indeed, since this lipid bilayer is mainly composed of phospholipids, certain amphiphilic compounds can reduce its coherence, and thus facilitate the penetration of the antimicrobial acid substance with the membrane.

[0043] The booster substance may also comprise at least one chelating compound which has a LogK constant of interaction with divalent ions or sterols greater than 4, and in particular greater than 8. This chelating compound may be chosen from EDTA (ethylenediaminetetraacetic acid) or one of its salts, cyclodextrin or one of its derivatives, phytic acid or one of its salts, oxalic acid or one of its salts, or a mixture of at least two of these compounds.

[0044] In fact, some microbial membranes contain divalent ions, such as magnesium and calcium, or sterols, which increase their stability. Therefore, the use of chelating compounds with appropriate LogK constants can annihilate the effect of divalent ions and / or sterols and decrease the stability of the membrane, facilitating the penetration of the membrane by the antimicrobial acid substance.

[0045] The booster substance may also comprise at least one polyphenolic compound, notably chosen from quercetin, oleuropein, caffeic acid, gallic acid, epigallocatechin, epigallocatechin gallate, tannins, tannic acids, fulvic acids, humic acids, plant extracts, notably based on olive, tea, cocoa, coffee, cassia, or a mixture of at least two of these compounds.

[0046] As is known, the presence of phenolic and / or polyphenolic compounds can contribute to the destabilization of microbial membranes, through interaction between the hydroxyl / benzoic groups of said compounds and the proteins of said membranes.

[0047] As with the acid substance, the booster substance comprises compounds whose individual concentrations are arranged to give the formulation a MOS margin greater than 100 MOS, in order to guarantee the said formulation good compatibility with the epidermis even in the case of repeated applications.

[0048] Advantageously, the booster substance comprises a mixture based on glyceryl stearate, glyceryl laurate and xanthan, optionally mixed with benzalkonium chloride, cetrimonium chloride and / or methyl cyclodextrin.

[0049] The formulation may further comprise at least one additional compound having a dermo-compatible function, and in particular a dermo-cosmetic function, in order to provide an additional beneficial effect for the maintenance of the epidermis.

[0050] In particular, the formulation may comprise at least one additional compound which has at least one dermo-cosmetic function chosen from: - moisturizing and / or humectant functions, in order to increase the water content of the skin, in particular of the upper layers (for humectant functions); and / or

[0051] - emollient functions, in order to lubricate the surface of the skin to improve its appearance and feel; and / or

[0052] - lipid-replenishing functions, in order to replenish the lipids in the upper layers of the skin.

[0053] For this purpose, the formulation may comprise at least one dermo-cosmetic compound chosen from an oil, shea butter, glycerol, triheptanoin, p-mentanediol, dibutyl adipate, a fatty alcohol or a mixture of at least two of these compounds.

[0054] Advantageously, the formulation may in particular include:

[0055] - between 1% and 5% by weight of glycerol;

[0056] - between 1% and 6% by weight of almond oil.

[0057] The formulation may also comprise an additional compound having a homogenizing function, in particular based on microcrystalline cellulose, in order to improve the distribution in the aqueous solvent of the different compounds of the formulation, in particular the compounds which have lipophilic groups.

[0058] The solvent of the formulation consists mainly of water, the weight percentage of which is adjusted according to the desired weight percentage for the other compounds of said formulation. Such a solvent has advantages in terms of dermo-compatibility, in that it reduces the risks of allergies and / or irritation to the skin, particularly in the context of repeated applications.

[0059] The formulation may also include an additional organic solvent, in particular based on hexanediol. Such additional compounds are referenced in the NCI database, and are also chosen to satisfy the toxicological criterion relating to the MOS margin described above.

[0060] Experimental examples

[0061] For each test formulation example presented below, the weight percentages refer to the total weight of said formulation.

[0062] Example 1

[0063] A first series of tests were conducted in the laboratory to evaluate the effectiveness of two different formulations against the HVE1 virus (Equine Herpes Virus Type 1).

[0064] To do this, a first “test” formulation, called CMV42, was prepared, which contains the following ingredients:

[0065] - as an antimicrobial organic acid: o 2% by weight of lactic acid;

[0066] - as booster compounds: o 6.5% by weight of glyceryl stearate (amphiphilic); o 3% by weight of glyceryl laurate (amphiphilic); o 0.4% by weight of xanthan (amphiphilic).

[0067] A second "control" formulation, called CMV40, was also prepared, which differed from the CMV42 formulation in that it did not contain lactic acid or glyceryl laurate, and also included the other compounds listed above in the same percentages.

[0068] These two formulations also contain the following compounds, in the same percentages:

[0069] - as a base: o 0.05% by weight of a clay; o sodium hydroxide, at a rate sufficient to give the formulation a pH of 5;

[0070] - as dermo-cosmetic compounds: o 2% by weight of almond oil (moisturizer); o 0.1% by weight of shea butter (moisturizer); o 2% by weight of glycerol (humectant);

[0071] - 0.05% by weight of microcrystalline cellulose;

[0072] - 1.4% by weight of hexanediol-based solvent;

[0073] - the water supplement.

[0074] These two formulations were each mixed at a percentage of 97% and following four different dilution rates (10 3 , 10 4 , 10 5 , 10 6 ), in a solution comprising cells from a rabbit kidney cell line (RK13) infected with an HVE1 virus carrying a green fluorescent protein (GFP), with a viral load of 5.5.10 8 ffu / ml. For each test sample, the exposure time of the formulation to the virus was 5 minutes.

[0075] Then, a well was formed for each sample obtained on an examination plate, in order to be able to observe under the microscope the number of infected cells per well after this 5-minute time, compared to control wells containing only infected cells, without antimicrobial formulation.

[0076] For the “control” CMV40 formulation, very small decreases in viral load were observed, ranging from 0.3 log (for a 10 dilution 4 ) at only 0.56 log (for a 10 dilution 3 ). In particular, the most dilute sample (10 6 ) showed a negligible decrease in his viral load.

[0077] On the other hand, for the CMV42 “test” formulation according to the invention, much greater reductions in viral load were observed, ranging from 1.56 log (for a 10 dilution 6 ) to 4.25 (for a dilution of 10 3). Thus, this formulation has a virucidal efficacy greater than 99.99% against the HVE1 virus, and proves effective even at high dilution rates.

[0078] This first series of tests made it possible to highlight the effectiveness of a formulation according to the invention comprising an organic acid, in particular based on lactic acid, compared to a similar formulation not containing organic acid.

[0079] Example 2

[0080] Another "control" CMVTA formulation was prepared containing only the following ingredients:

[0081] - 2% by weight of lactic acid as an antimicrobial organic acid;

[0082] - a basic substance based on sodium hydroxide, at a rate suitable for giving this formulation a pH of 5;

[0083] - the water supplement.

[0084] This formulation was then tested in contact with a solution of cells infected with the HVE1 virus identical to that prepared for example 1, and following an experimental protocol similar to this example 1, with the exception of the following parameters:

[0085] - the contact time of the formulation with the virus was only 60 seconds; and

[0086] - only one dilution rate was carried out (10 3 ).

[0087] Considering the very small decrease observed for the viral load (only 0.28 log), it was concluded that a formulation containing only organic acid shows no efficacy against the HVE1 virus.

[0088] Thus, the series of tests carried out in examples 1 and 2 presented above made it possible to highlight the effectiveness against the HVE1 virus of a formulation according to the invention comprising both an organic acid and a booster substance, in particular in the following proportions: - 2% by weight of lactic acid;

[0089] - 6.5% by weight of glyceryl stearate;

[0090] - 3% by weight of glyceryl laurate;

[0091] - 0.4% by weight of xanthan.

[0092] Example 3.1

[0093] For this series of tests, a solution of cells infected with the HVE1 virus similar to that used in previous examples 1 and 2 was prepared.

[0094] A CMV42 formulation as described in Example 1 was also prepared, as well as three other "test" formulations CMV41, CMV43 and CMV44 according to the invention, which differ from the CMV42 formulation by the addition of additional ingredients, namely:

[0095] - for the CMV41 formulation: o 2% by weight of lauric acid as an antimicrobial organic acid; o 0.5% by weight of methyl cyclodextrin as a chelating booster compound;

[0096] - for the CMV43 formulation: o 2% by weight of lauric acid as an antimicrobial organic acid;

[0097] - for the CMV44 formulation: o 0.5% by weight of methyl cyclodextrin as a chelating booster compound.

[0098] Then, each of these formulations was tested following a protocol similar to that of examples 1 and 2, with a single dilution rate (10 3 ) and a contact time of 30 seconds between each formulation and the virus.

[0099] Observation of the samples under a microscope revealed a reduction in viral load of more than 99% for each of the formulations tested, and more particularly: - for the CMV43 formulation, containing both lactic acid and lauric acid, but without the addition of methyl cyclodextrin: a reduction in viral load of around 2.14 log; and

[0100] - for the other formulations CMV41, CMV42 and CMV44, a reduction in viral load of around 4.08 log, almost twice the reduction in viral load obtained with the CMV43 formulation.

[0101] This series of tests has made it possible to highlight an increased and very rapid virucidal efficacy against the HVE1 virus (from 30 seconds of contact), for formulations comprising the combination of the following compounds:

[0102] - 6.5% by weight of glyceryl stearate;

[0103] - 3% by weight of glyceryl laurate;

[0104] - 0.4% by weight of xanthan; and

[0105] - 2% by weight of lactic acid, in particular: o alone (formulations CMV42, CMV44); or o in combination with (formulation CMV43):

[0106] ■ 2% by weight of lauric acid; and

[0107] ■ 0.5% by weight of methyl cyclodextrin as a chelating booster compound.

[0108] Example 3.2

[0109] Another “test” formulation CMV910 according to the invention was prepared which comprises:

[0110] - as antimicrobial organic acids: o 1% by weight of lactic acid; o 1% by weight of citric acid;

[0111] - as booster compounds: o 6% by weight of glyceryl stearate (amphiphilic); o 1% by weight of glyceryl laurate (amphiphilic); o 0.5% by weight of xanthan (amphiphilic); o 0.13% by weight of benzalkonium chloride (amphiphilic);

[0112] - as bases: o sodium hydroxide, at a rate sufficient to give the formulation a pH of 5;

[0113] - as dermo-cosmetic compounds: o 7% by weight of almond oil (moisturizer); o 2.5% by weight of glycerol (humectant); o 1% by weight of triheptanoin (humectant); o 2% by weight of dibutyl adipate (emollient); o 1.5% by weight of shea butter (emollient); o 5% by weight of a fatty alcohol (emollient);

[0114] - the water supplement.

[0115] This formulation was then tested in contact with a solution of cells infected with the HVE1 virus identical to those prepared for the previous examples, and following a similar experimental protocol, with the exception of a contact time with the virus of 60 seconds and a single dilution rate of 10- 3 .

[0116] Microscopic observation of the tested sample revealed a decrease in viral load of more than 99%, and notably of 2.44 log, after a contact time of 60 seconds, so that the CMV910 formulation also proves to be very effective against the HVE1 virus.

[0117] Example 4

[0118] For this test, a CMV910 formulation was prepared as described in Example 3.2, and mixed at a percentage of 97% in a solution comprising cells from an African green monkey kidney epithelial cell line (Vero-E6) infected with the SARS-CoV-2 virus, with a viral load of 6.10 7 TCID50 / ml. The formulation was exposed to the virus for 60 seconds. Following this exposure, a reduction in viral load of over 99.99% was observed, demonstrating increased and rapid virucidal efficacy of the CMV910 formulation against the SARS-CoV-2 virus.

[0119] Example 5

[0120] For this series of tests, formulations CMV40, CMV42, CMV43, CMV44 identical to those used in Example 3 were prepared, as well as a fifth formulation CMV45 according to the invention, the composition of which differs from that of formulation CMV42 by the addition of 2% by weight of p-menthanediol as a humectant compound.

[0121] These five formulations were each mixed, at a percentage of 97%, in a solution comprising cells from a human embryonic kidney (HEK) cell line infected with an ADV5 adenovirus carrying a fluorescent protein. For each test sample, the exposure time of the formulation to the virus was 60 seconds.

[0122] Then, a well was formed for each sample obtained on an examination plate, in order to be able to observe under the microscope the number of infected cells per well after this time of 60 seconds, compared to control wells containing only infected cells, without antimicrobial formulation.

[0123] Microscopic observation revealed, after 60 seconds of contact with the ADV5 virus:

[0124] - for the “control” CMV40 formulation not containing organic acid, no reduction in viral load;

[0125] - for the CMV43 and CMV45 “test” formulations, a reduction in viral load of the order of 34% and 35% respectively; and

[0126] - for the CMV42 and CMV44 “test” formulations, a reduction in viral load close to 70%, or 69% and 68% respectively. Thus, this series of tests revealed increased and rapid virucidal efficacy against the ADV5 virus of formulations comprising the following combination:

[0127] - as an antimicrobial organic acid: o 2% by weight of lactic acid;

[0128] - as booster compounds: o 6.5% by weight of glyceryl stearate (amphiphilic); o 3% by weight of glyceryl laurate (amphiphilic); o 0.4% by weight of xanthan (amphiphilic).

[0129] - as bases: o 0.05% by weight of a clay; o sodium hydroxide, at a rate sufficient to give the formulation a pH of 5;

[0130] - as dermo-cosmetic compounds: o 2% by weight of almond oil (moisturizer); o 0.1% by weight of shea butter (moisturizer); o 2% by weight of glycerol (humectant);

[0131] - 0.05% by weight of microcrystalline cellulose;

[0132] - 1.4% by weight of hexanediol-based solvent;

[0133] - the water supplement.

[0134] Example 6.1

[0135] For this series of tests, a “control” formulation CMVT and four “test” formulations CMV2, CMV3, CMV4 and CMV5 according to the invention were prepared, all of which contained:

[0136] - 5% by weight of glyceryl stearate;

[0137] - 0.5% by weight of xanthan;

[0138] - 5% by weight of almond oil;

[0139] - 4.5% by weight of glycerol;

[0140] - a sodium hydroxide base at a level suitable for giving said formulation a pH of 5;

[0141] - the water supplement. If the CMVT “control” formulation contained only the above-mentioned compounds, and no organic acids, the following compounds were added to each test formulation:

[0142] - in common: o 2% by weight of lauric acid; o 1% by weight of oleic acid; o 2% by weight of glyceryl laurate;

[0143] - as specific ingredients: o for the CMV3 formulation:

[0144] ■ 2% by weight of p-menthanediol; or o for CMV2, CMV4, CMV5 formulations:

[0145] ■ 2% by weight of lactic acid; in particular with

[0146] • 0.08% cetrimonium chloride (CMV5); or

[0147] • 1% by weight of methyl cyclodextrin (CMV4).

[0148] With each of these five formulations, two Textite StreriIWip type fabrics were surface impregnated with an amount of 60 mg / 2.25 cm 2 , following a pause time of 3 minutes and 3 hours respectively for each of these two fabrics.

[0149] These pre-impregnated fabrics were then coated with a solution containing Vero-E6 cells infected with the SARS-CoV-2 virus, with a viral load of 10 μl to 10 5 TCID50 / 2.25 cm 2 , counting a formulation / virus contact time of 5 minutes.

[0150] After this 5-minute contact time, the tissues were observed and the following was noted:

[0151] - for the tissue treated with the “control” CMVT formulation, no decrease in viral load, both after 3 minutes and after 3 hours of impregnation;

[0152] - for fabrics treated with the "test" formulations, a reduction in viral load greater than 81.3% after 3 minutes of impregnation, and greater than 96.4% after three hours of impregnation. Thus, this series of tests made it possible to demonstrate the effectiveness against the SARS-COV-2 virus of a textile treatment with a formulation comprising at least the following ingredients:

[0153] - as antimicrobial organic acids: o 2% by weight of lauric acid; o 1% by weight of oleic acid;

[0154] - as a base: o sodium hydroxide at a rate suitable for giving said formulation a pH of 5;

[0155] - as booster compounds: o 5% by weight of glyceryl stearate; o 2% by weight of glyceryl laurate; o 0.5% by weight of xanthan;

[0156] - as additional dermo-cosmetic ingredients: o 5% by weight of almond oil; o 4.5% by weight of glycerol;

[0157] - the water supplement.

[0158] Example 6.2

[0159] For this series of tests, a CMV910 "test" formulation was prepared as described in Examples 3.2 and 4, which was applied to a Textile StreriIWip fabric with a setting time of 3 hours and in an amount of 60 mg / 2.25 cm 2 .

[0160] A solution of infected cells identical to that used in example 6.1 was then applied to this textile, allowing a 5-minute exposure time, at the end of which we observed the results, which revealed a reduction in the viral load greater than 98% after 3 hours of impregnation with the tested formulation, a result slightly higher than that observed with the “test” formulations of example 6.1.

Claims

DEMANDS 1. Topical antimicrobial formulation comprising an acidic substance comprising at least one organic acid diluted in an aqueous solvent and exhibiting deleterious action against microbes, said acidic substance having an acidity constant pKa which is less than 6, said formulation being characterized in that it comprises: - between 1% and 10% by weight of acidic substance in which at least one organic acid used is referenced in the INCI database; - a basic substance comprising at least one base, the quantity of basic substance in the formulation being such that the pH of said formulation is between the pKa of the acidic substance and 8; - between 0.1% and 15% by weight of a booster substance which is capable of interacting biochemically with the membrane of microbes to facilitate the deleterious action of the acidic substance on said microbes, said booster substance comprising at least one compound referenced in the INCI database chosen from among amphiphilic compounds, chelating compounds having an association capacity with divalent ions or sterols, polyphenolic compounds.

2. Topical antimicrobial formulation according to claim 1, characterized in that the acidic substance comprises at least one organic acid selected from lactic acid, citric acid, tartaric acid, acetic acid, adipic acid, anisic acid, malic acid, succinic acid, benzoic acid, cholic acid, ascorbic acid, dehydroacetic acid, deoxycholic acid, glucuronic acid, glycolic acid, fumaric acid, formic acid, gluconic acid, glutamic acid, guanylic acid, folic acid, fulvic acid, sorbic acid, glycyrrhizic acid, kojic acid, itaconic acid, mellic acid, hyaluronic acid, amino acids, glutaric acid, acid glyoxylic acid, humic acids, hippuric acid, inosic acid, levulinic acid, perillic acid, quinic acid, tauric acid, ribonic acid, salicylic acid, shikimic acid, trenaxamic acid, thujic acid,tiglic acid, ursolic acid, usnic acid, Vanillic acid, valproic acid, or a mixture of at least two of these compounds.

3. Topical antimicrobial formulation according to any one of claims 1 or 2, characterized in that the basic substance comprises at least one base selected from organic acid salts, clays, sodium hydroxide, potassium hydroxide, triethanolamine, butylethanolamine, disodium carbonates, dipotassium carbonates, disodium phosphates, dipotassium phosphates, or a mixture of at least two of these compounds.

4. Topical antimicrobial formulation according to any one of claims 1 to 3, characterized in that it comprises an amount of basic substance suitable for giving said formulation a pH of the order of 5.

5. Topical antimicrobial formulation according to any one of claims 1 to 4, characterized in that the booster substance comprises at least one amphiphilic compound having a critical micellar concentration (CMC) value between 1 mM and 400 mM, in particular between 10 mM and 100 mM.

6. Topical antimicrobial formulation according to claim 5, characterized in that the booster substance comprises at least one amphiphilic compound selected from glyceryl laurate, glyceryl caprate, glyceryl caprylate, glyceryl palmitate, glyceryl stearate, quaternary ammonium compounds, saponins or a mixture of at least two of these compounds.

7. Topical antimicrobial formulation according to claim 5, characterized the booster substance comprises at least one amphiphilic compound selected from the INCI base from fatty alcohols, ethoxylated alcohols, an amphiphilic compound with betaine, phosphate, sulfate, alkylated sugars, polyglyceryl, polysorbate or a mixture of at least two of these compounds.

8. Topical antimicrobial formulation according to any one of claims 1 to 7, characterized in that the booster substance comprises at least one chelating compound which has a LogK interaction constant with divalent ions or sterols greater than 4, and in particular greater than 8.

9. Topical antimicrobial formulation according to claim 8, characterized in that the booster substance comprises at least one chelating compound selected from EDTA (ethylenediaminetetraacetic acid) or one of its salts, cyclodextrin or one of its derivatives, phytic acid or one of its salts, oxalic acid or one of its salts, or a mixture of at least two of these compounds.

10. Topical antimicrobial formulation according to any one of claims 1 to 9, characterized in that the booster substance comprises at least one polyphenolic compound selected from quercetin, oleuropein, caffeic acid, gallic acid, epigallocatechin, epigallocatechin-gallate, tannins, tannic acids, fulvic acids, humic acids, plant extracts, in particular based on olive, tea, cocoa, coffee, cassia, or a mixture of at least two of these compounds.

11. Topical antimicrobial formulation according to any one of claims 1 to 10, characterized in that it further comprises at least one additional compound having a skin-compatible function.

12. Topical antimicrobial formulation according to claim 11, characterized in that it comprises at least one additional compound which has at least one dermocosmetic function selected from moisturizing functions, emollient functions, humectant functions and / or lipid-replenishing functions.

13. Topical antimicrobial formulation according to claim 12, characterized in that it comprises at least one dermocosmetic compound selected from almond oil, shea butter, glycerol, triheptanoin, p- mentanediol, dibutyl adipate, a fatty alcohol or a mixture of at least two of these compounds.

14. Topical antimicrobial formulation according to any one of claims 1 to 13, characterized in that it further comprises an additional component having a homogenizing function, in particular based on microcrystalline cellulose.

15. Topical antimicrobial formulation according to any one of claims 1 to 14, characterized in that it comprises an additional organic solvent.