Virus inactivation or killing and compositions thereof

Abstract

The present invention relates to the use of active agents and compositions containing them to treat surfaces to inactivate or kill enveloped viruses. The present invention also relates to specific liquid cleansing and disinfecting compositions for exerting such antiviral activity. This is achieved using PPAR-activating fatty acids, optionally in combination with vitamin B3 compounds.

Description

[Technical Field]

[0001] The present invention relates to the use of active agents and compositions containing same for treating surfaces to inactivate or kill enveloped viruses. The invention also relates to certain liquid cleansing and disinfecting compositions and devices for exerting such antiviral action. [Background technology]

[0002] Respiratory infections are considered one of the most prevalent causes of illness worldwide. Globally, acute lower respiratory tract infections are a significant cause of morbidity and mortality among children under the age of five. Scientific studies have identified respiratory syncytial virus (RSV) as the most common viral cause of death from such infections. Other major viruses include human metapneumovirus, parainfluenza viruses, influenza viruses A and B, adenoviruses, and recently emerged coronaviruses. Tens of millions of such infections are reported each year, resulting in over 500,000 deaths among children under the age of five, primarily from low- and middle-income households.

[0003] The aforementioned viruses are known to be transmitted through respiratory aerosol droplets, by contact with infected hands, and even through inanimate surfaces. As a result, hand hygiene is a commonly recommended method for killing such germs and thereby reducing the risk of not only respiratory infections but also gastrointestinal illnesses. Hand hygiene involves using soap and running water to wash hands, which not only removes dirt but also washes away and kills germs such as bacteria and viruses. Alternatively, rubbing alcohol-based hand sanitizer with a very small amount of water on hands is another effective means for removing viruses and germs from hands. While such methods are very effective at instantly killing germs, they are sometimes considered too harsh. Therefore, there is a need for active substances and compositions that are gentle on skin and other external and mucosal surfaces, yet are sufficiently effective to kill or inactivate viruses to prevent or mitigate infection. Summary of the Invention

[0004] In their search for such active substances, the inventors have come across a specific type of fatty acid known as PPAR (peroxisome proliferator-activated receptor)-activating fatty acids, which they have discovered kill or inactivate enveloped viruses, a previously unknown activity. Furthermore, the inventors have discovered that it exerts a synergistic effect with a specific vitamin, namely, vitamin B3, or its precursor or analog, to enhance antiviral activity. Furthermore, the inventors have discovered that vitamin B3, or its precursor or analog itself, can also exert such activity.

[0005] PPAR fatty acids according to the present invention include fatty acids that have PPAR activity, and also include their corresponding mono-, di-, and triglyceride forms.

[0006] It is therefore an object of the present invention to provide novel active substances that kill or inactivate enveloped viruses.

[0007] Another object of the present invention is to provide such benefits using commonly used active agents that are gentle on external or mucosal body surfaces.

[0008] A first aspect of the present invention relates to the use of peroxisome proliferator-activated receptor (PPAR)-activating fatty acids to inactivate or kill enveloped viruses on topical surfaces of the human or animal body.

[0009] A preferred embodiment of the present invention relates to the use of a composition comprising (i) a vitamin B3 compound or a precursor or analog thereof, and (ii) a peroxisome proliferator-activated receptor (PPAR)-activating fatty acid to inactivate or kill enveloped viruses on topical surfaces of the human or animal body.

[0010] Another aspect of the present invention is a method for producing a semiconductor device comprising: (i) 0 to 5.0% by weight of a vitamin B3 compound, a precursor thereof, or an analog thereof; (ii) 0.01 to 5.0 wt % of a PPAR-activating fatty acid; (iii) 70–99 wt % water; (iv) 1 to 20 wt. % of a humectant; and (v) less than 1.5% by weight of a surfactant selected from nonionic or amphoteric surfactants or mixtures thereof The present invention relates to a mouthwash composition for inactivating enveloped viruses, comprising:

[0011] A further aspect of the present invention is (i) PPAR-activated fatty acids; (ii) 0.1% to 50% by weight of an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulfate, ammonium lauryl sulfate, cocoamidopropyl betaine, fatty acid isethionates, and fatty acid acyltaurates; (iii) a carboxylic acid; and (iv) 40 to 90% by weight of water The present invention relates to a wash-off composition which provides intimate hygiene in or around the vagina and has a pH in the range of 2.5 to 6.0, preferably 2.5 to 4.5.

[0012] Yet another aspect of the present invention relates to the use of a vitamin B3 compound or a precursor thereof or an analog thereof to inactivate enveloped viruses on topical surfaces of the human or animal body. DETAILED DESCRIPTION OF THE INVENTION

[0013] These and other aspects, features, and advantages will become apparent to those skilled in the art upon reading the following detailed description and the appended claims. For the avoidance of doubt, any feature of one aspect of the present invention can be utilized in any other aspect of the present invention. The term "comprising" is intended to mean "including," but not necessarily "consisting of" or "consisting of." In other words, the steps or options described need not be all-inclusive. It should be noted that the examples described below are intended to clarify the invention but are not intended to limit the invention to the examples themselves. Similarly, unless otherwise indicated, all percentages are weight / weight percent. Except in the examples and comparative examples, or unless explicitly stated, all numbers in this "Detailed Description" and "Claims" describing quantities of materials or reaction conditions, physical properties of materials, and / or uses should be understood to be modified by the word "about." Numerical ranges expressed in the format "from x to y" are understood to include both x and y. When multiple preferred ranges for a particular feature are stated in the format "from x to y," it is understood that all ranges combining the different endpoints are also contemplated.

[0014] The present invention may be used to inactivate or kill viruses, particularly enveloped viruses, on topical surfaces of the human or animal body, whereby the surface is a biological surface.

[0015] Biological surfaces include the external surfaces of living organisms, such as plants and animals, including humans. The abundant availability of nutrients and water on most biological surfaces allows bacteria to live and grow on such surfaces. The present invention is useful for viral infections on all types of biological surfaces. The present invention is particularly useful for preventing or killing viruses on topical surfaces of the human body. Topical surfaces according to the present invention include external surfaces as well as mucosal surfaces. External surfaces according to the present invention include skin on any external part of the body, including the scalp and hair. Mucosal surfaces according to the present invention include surfaces within the oral cavity and vaginal surfaces.

[0016] The present invention can be used with leave-on compositions or wash-off compositions. A leave-on composition is a composition that is applied to the outer surface of the human body and left on the surface until the person showers or bathes, usually after a few hours or a day. A wash-off composition is a composition that is used to wash the outer surface of the body with a large amount of water, such as a soap composition, body wash, facial cleanser, shampoo, or hair conditioning composition, so that a significant amount of dirt and oil is washed away from the surface of the body, leaving it clean. Such wash-off compositions usually contain a sufficient amount of surfactant to enable the wash-off action.

[0017] The present invention relates to the use of vitamin B3 compounds, their precursors, or analogs thereof for inactivating enveloped viruses on localized surfaces of the human or animal body. This use is preferably non-therapeutic. The enveloped virus is preferably SARS-CoV-2.

[0018] The present invention relates to the use of PPAR-activating fatty acids to inactivate or kill enveloped viruses on topical surfaces of the human or animal body, the use being preferably non-therapeutic.

[0019] The present invention can also prevent reinfection of topical surfaces by using one or more of the active agents claimed in the present invention to inactivate or kill enveloped viruses on these surfaces, meaning that surfaces treated with such active agents will prevent future infection of the surface for several hours after such treatment.

[0020] Enveloped viruses according to the present invention include coronaviruses and influenza viruses. A preferred coronavirus that can be treated according to the present invention is SARS-Cov2. A preferred influenza virus that can be treated according to the present invention is H1N1. Other enveloped viruses that can be treated according to the present invention include RSV (respiratory syncytial virus) and HSV (herpes simplex virus).

[0021] Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate lipid metabolism. There are three isotypes: PPARα, PPARβ / δ, and PPARγ, all of which are localized in the skin. A wide range of specific fatty acids activate these factors, resulting in anti-inflammatory effects that reduce inflammatory responses in the skin, and suppress pro-differentiation / anti-proliferative responses that normalize skin metabolism, providing additional skin care benefits. Selecting PPAR fatty acids containing hydroxyl and / or methyl side chains is particularly desirable. Many of these acids contain 14 to 30 carbon atoms. Examples of PPAR fatty acids with demonstrated PPAR-activating activity include cis-parinaric acid, cis-9-trans-11 conjugated linoleic acid, columbic acid, docosahexaenoic acid, eicosapentaenoic acid, hexadecatrienoic acid, linoleniclaidic acid (an isomer of linolenic acid), petroselinic acid, pinolenic acid, punicic acid, ricinoleic acid, ricinoleiclaidic acid (an isomer of ricinoleic acid), stearidonic acid, trans-10-cis-12 conjugated linoleic acid, 7-trans octadecanoic acid, vaccenic acid, octadecenedioic acid, and hydroxystearic acid.

[0022] The PPAR fatty acids of the present invention also include hydrolyzable PPAR precursors. Potential sources of hydrolyzable PPAR precursors include triglycerides such as coriander seed oil for petroselinic acid, Impatiens balsimina seed oil for cis-parinaric acid, Parinarium laurinarium kernel oil or Sabastiana brasilinensis seed oil, dehydrated castor seed oil for conjugated linoleic acid, and columbine oil for columbic acid. When a single hydrolyzable precursor of PPAR-activating fatty acid is used, borage oil, castor oil, and sunflower seed oil are specifically excluded. Preferably, the PPAR acid contains 16 or 18 carbon atoms.

[0023] A particularly preferred PPAR acid is hydroxystearic acid or an ester thereof. The most preferred PPAR acid is hydroxystearic acid.

[0024] The hydroxystearic acid is preferably 10-hydroxystearic acid, 12-hydroxystearic acid, trihydroxystearic acid (e.g., 9,10,13-trihydroxystearic acid), trihydroxystearin, or a compound that generates one or more molecules of hydroxystearic acid or hydroxystearate upon decomposition, such as a mono-, di-, or triester of glycerol and hydroxystearic acid. Of these, 10-hydroxystearic acid, 12-hydroxystearic acid, and 9,10,13-trihydroxystearic acid are more preferred, with 12-hydroxystearic acid (12-HSA) being most preferred. 12-HSA has the following structure:

[0025] [ka]

[0026] Preferably, the PPAR-activating fatty acids used in any aspect of the invention are also caspase-8 modulators.

[0027] According to a preferred embodiment, the composition according to the invention may further comprise an antimicrobial peptide (AMP). A further preferred embodiment refers to the use of a composition according to the invention further comprising an antimicrobial peptide. A preferred AMP is LL37.

[0028] A preferred embodiment of the present invention relates to the use of a composition comprising (i) a vitamin B3 compound, a precursor thereof, or an analog thereof, and (ii) a peroxisome proliferator-activated receptor (PPAR)-activating fatty acid for the inactivation or killing of enveloped viruses on a topical surface of the human or animal body, the use being preferably non-therapeutic.

[0029] Yet another aspect of the present invention relates to the use of PPAR-activating fatty acids as killers or inactivators of enveloped viruses in compositions that also contain a vitamin B3 compound, its precursors, or its analogs.

[0030] Yet another aspect relates to the use of a combination of a PPAR-activating fatty acid and a vitamin B3 compound, a precursor thereof, or an analog thereof in a topical composition as an enveloped virus killing or inactivation system.

[0031] The vitamin B3 compound, its precursor, or its analog is selected from one or more of tryptophan, niacin, nicotinic acid, isonicotinamide, picolinamide, and nicotinamide (also known as niacinamide). It is preferably niacinamide. Niacinamide, also known as pyridine-3-carboxamide, is the active, water-soluble form of vitamin B3. Vitamin B3 analogs according to the present invention also include derivatives such as cycloalkylnicotinamides having 3 to 6 carbon atoms.

[0032] When included in the compositions of the present invention, an effective amount of niacinamide is typically present at a concentration of 0.05-3%, preferably 0.1-2% by weight of the composition. In such compositions, hydroxystearic acid is preferably present at 0.05-3%, more preferably 0.1-2% by weight of the composition.

[0033] Without wishing to be bound by theory, the inventors believe that the active agents claimed in the present invention, i.e., PPAR fatty acids, such as 12-HSA, activate host cells to promote defense against non-enveloped viruses such as SARS-CoV 2. The inventors believe that this mechanism of action is distinct from direct antiviral agents, such as low-boiling alcohols, bleach, and cationic surfactants, such as quaternary ammonium compounds, which exert their antiviral effect by directly acting on and inactivating viral particles.

[0034] Furthermore, experiments have shown that actives such as PPAR fatty acids can be deposited on topical surfaces in sufficient quantities even from wash compositions. Furthermore, the actives have been shown to migrate into the skin and activate AMP from cells. AMP production is a biological process that takes a long time. It has been shown that maximum amounts of AMP are produced approximately 48-72 hours after active deposition.

[0035] Yet another aspect of the present invention relates to the use of a composition for caring for the external surface of the human or animal body, comprising (i) a PPAR-activating fatty acid and (ii) a cosmetically acceptable carrier selected from a powder, bar / doublet, liquid, gel, emulsion, or anhydrous phase, for inactivating or killing enveloped viruses on the external surface of the human or animal body. This use is preferably non-therapeutic. Such a composition may further comprise a vitamin B3 compound, its precursor, or its analog.

[0036] Yet another aspect of the present invention relates to the use of a skin care composition comprising (i) a vitamin B3 compound, a precursor thereof or an analog thereof, and (ii) a cosmetically acceptable carrier selected from a liquid, a gel, an emulsion or an anhydrous phase, for the inactivation of enveloped viruses on topical surfaces of the human or animal body, said use being preferably non-therapeutic.

[0037] Yet another aspect of the present invention relates to the use of a skin cleansing composition comprising (i) a vitamin B3 compound, a precursor thereof, or an analog thereof, and (ii) a cosmetically acceptable carrier containing 5 to 80% of a surfactant selected from synthetic surfactants or soaps, for the inactivation of enveloped viruses on topical surfaces of the human or animal body, the use being preferably non-therapeutic.

[0038] Yet another aspect of the present invention relates to the use of an oral care composition comprising (i) a vitamin B3 compound, a precursor thereof, or an analog thereof, and (ii) an orally acceptable carrier selected from water, an abrasive, a humectant, an emulsifier, or a mixture thereof, for inactivating enveloped viruses in the oral cavity of a human or animal, the use being preferably non-therapeutic.

[0039] The cosmetically acceptable carrier according to the above embodiment of the composition of the present invention can be preferably delivered as an emulsion, e.g., a cream or lotion, or in gel form, preferably a cream. A preferred solid form of the composition is a cream, even more preferably one having a vanishing cream base. The vanishing cream base contains 3-25% by weight of a fatty acid. Optionally, the composition can contain 0.1-10% by weight of soap. When a fatty acid is included, it is preferably a C10-C22 fatty acid, more preferably a C16-C18 fatty acid. Most preferably, the fatty acid is stearic acid or palmitic acid, or a mixture thereof, and the soap is preferably a potassium salt of the fatty acid mixture. The fatty acid is often substantially (generally about 90-95%) hystric acid, which is a mixture of 45% stearic acid and 55% palmitic acid. The most preferred cream contains 3-25% by weight of a fatty acid and 0.1-10% by weight of soap.

[0040] Preferably, the cosmetically acceptable carrier in the above composition comprises an emollient. Examples of emollients that may be used in leave-on compositions include stearyl alcohol, glyceryl monoricinoleate, mink oil, isopropyl isostearate, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecane-2-ol, isocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, dibutyl sebacate, isopropyl myristate, palmitate, palm oil ... Isopropyl myristate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cottonseed oil, olive oil, palm kernel oil, rapeseed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, sesame oil, coconut oil, peanut oil, acetylated lanolin alcohol, petrolatum, mineral oil, butyl myristate, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate, and mixtures thereof.

[0041] Preferably, the cosmetically acceptable carrier in the composition comprises a solvent. Examples of solvents that can be used in the composition include ethyl alcohol, isopropanol, acetone, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, and mixtures thereof. The composition may comprise a polyhydric alcohol, which may be selected from one or more of glycerin, 1,3-butylene glycol, propylene glycol, 1,3-propanediol, pentylene glycol, hexylene glycol, and sorbitol.

[0042] Preferably, the cosmetically acceptable carrier in the composition comprises a powder, examples of which include chalk, talc, fuller's earth, kaolin, starch, gum, colloidal silica, sodium polyacrylate, tetraalkyl and / or trialkylarylammonium smectite, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethylcellulose, ethylene glycol monostearate, and mixtures thereof.

[0043] According to yet another aspect of the present invention, there is provided a use of a composition for cleansing the external surface of the human or animal body, comprising (i) a PPAR-activating fatty acid and (ii) a cosmetically acceptable vehicle containing 0.1% to 80% by weight of a surfactant selected from synthetic surfactants or soaps, for inactivating or killing enveloped viruses on the external surface of the human or animal body. This use is preferably non-therapeutic. Such a composition may further comprise a vitamin B3 compound, its precursor, or its analog. Such a composition is generally known as a cleansing composition.

[0044] As used herein, the term "cleansing composition" is intended to include compositions for topical application to the skin, hair, and / or scalp of mammals, particularly humans. Such compositions are typically diluted with water and then applied to the desired topical surface of the body for a period of from a few seconds up to several minutes. After this application period, the composition is typically rinsed off with water or wiped off. This includes any product applied to the human body to improve appearance, odor control, or general aesthetics. The compositions of the present invention may be in the form of a liquid, lotion, cream, foam, scrub, gel, shampoo, conditioner, hand wash, face wash, or body wash product.

[0045] A cosmetically acceptable vehicle generally contains water in addition to a surfactant. Particularly preferred surfactants are anionic surfactants such as soap. The soap used to prepare the cleansing composition of the present invention is preferably a C8 to C9 24 Soap, preferably C 10 ~C 20 Soap, most preferably C 12 ~C 18 The cleansing composition is preferably a soap. The cation of the soap can be an alkali metal, an alkaline earth metal, or ammonium. Preferably, the cation of the soap is selected from sodium, potassium, or ammonium. More preferably, the cation of the soap is sodium or potassium. Fatty acids derived from other suitable oils / fats, such as peanut, soybean, tallow, palm, palm kernel, etc., can also be used in other desired proportions. The cosmetically acceptable vehicle generally forms 80-99% by weight of the cleansing composition.

[0046] When present, the anionic surfactant, e.g., soap, is present in an amount of 1 to 90% by weight of the cleansing composition, preferably 10 to 85% by weight, more preferably 25 to 75% by weight. The cleansing composition is preferably in solid or semi-solid form, most preferably in solid form. A preferred solid composition is in the form of a soap bar.

[0047] The other anionic surfactants are preferably selected from alkyl ether sulfates, primary alkyl sulfates, secondary alkyl sulfonates, alkyl benzene sulfonates, or ethoxylated alkyl sulfates. Preferred non-soap anionic surfactants in the cleansing composition are alkyl ether sulfates, preferably those having 1 to 3 ethylene oxide groups from natural or synthetic sources and / or sulfonic acids. Particularly preferred is sodium lauryl ether sulfate. Alkyl polyglucosides may also be present in the composition, preferably C6-C8. 16 The carbon chain length is

[0048] Preferred cleansing compositions may also contain other known ingredients, such as fragrances, pigments, preservatives, emollients, sunscreens, gelling agents, and thickeners. The selection of these ingredients will depend largely on the composition's format. Water is a preferred carrier. When water is present, it is preferably present in an amount of at least 1% by weight of the composition, more preferably at least 2% by weight, and even more preferably at least 5% by weight. When water is the carrier, preferred cleansing compositions contain 10-50% by weight, more preferably 12-40% by weight, and even more preferably 12-25% by weight of water.

[0049] The cleansing compositions of the present invention can also be delivered via moisturizing bars or moisturizing liquid compositions. Moisturizing bar compositions comprising fatty acyl isethionates (e.g., cocyl isethionate) are particularly preferred.

[0050] Fatty acyl isethionate (e.g., cocoyl isethionate) surfactant "products" are defined as mixtures of anionic acyl isethionate surfactants and fatty acids / fatty acid soaps. They are highly desirable in personal care, particularly skin or hair cleansing products, due to their high lathering, gentleness, and good emollient properties. Typically, fatty acid isethionate surfactant products are prepared by esterification of fatty acids, or by the addition of C8-C 20 The fatty acyl isethionate is prepared by reacting a fatty acid chloride having a carbon chain length of 1000 with an isethionate salt. Typical surfactant products containing fatty acyl isethionate salts contain, in addition to the isethionate salt, about 40-95% by weight of the acid isethionate salt, and 5-50%, typically 10-40%, by weight of free fatty acid, in addition to the isethionate salt, typically less than 5% and trace amounts (less than 2% by weight) of other additives. Such compositions may also contain alkyl taurates, such as alkyl taurate amides. Such alkyl taurate amides may be prepared from taurine; methyl taurine; or the corresponding taurate salts (e.g., NH2CH2CH2SO3M). + , where M +The alkyl taurate amides can be prepared by reacting alkyl taurate amides (wherein the counterion can be sodium or potassium) with an appropriate fatty acid. Preferred alkyl taurate amides include sodium methyl cocoyl taurate and sodium methyl lauroyl taurate.

[0051] Fatty acid soaps may be present in the range of 5-15% by weight. Other surfactants such as betaines may be present in the range of 1-5% by weight. Water typically comprises 2-8% by weight of the composition.

[0052] According to yet another aspect of the present invention, there is provided a use of a mucosal surface care or cleansing composition comprising (i) a PPAR-activating fatty acid and (ii) a mucosally acceptable carrier selected from one or more of water, abrasives, moisturizers, and emulsifiers for inactivating or killing enveloped viruses on mucosal surfaces of the human or animal body. This use is preferably non-therapeutic. Such a composition may further comprise a vitamin B3 compound, its precursor, or its analog. When the composition is delivered for oral care, the mucosally acceptable carrier is often referred to as an orally acceptable carrier.

[0053] More preferred orally acceptable carriers include abrasives, moisturizers, or mixtures thereof. The orally acceptable carrier preferably comprises about 99.8% by weight, more preferably about 96% by weight, of the composition. The orally acceptable carrier preferably comprises at least 80% by weight, more preferably at least 90% by weight of the composition.

[0054] The oral care compositions of the present invention can be provided in the form of an ointment, gel, dentifrice, or mouthwash. Dentifrice includes forms such as toothpaste and tooth powder. The compositions are most preferably provided in the form of toothpaste, tooth powder, or mouthwash.

[0055] The oral care compositions of the present invention preferably contain an abrasive. The abrasive is preferably calcium carbonate or silica. Gels usually contain silica, while opaque creams usually contain a calcium-based abrasive, especially chalk (calcium carbonate). In opaque toothpastes, the composition contains 5-60% by weight of calcium-based abrasive. In more preferred compositions, it is 30-60% by weight, and even more preferably 35-55% by weight. The optimal composition contains 40-55% by weight of calcium-based abrasive.

[0056] Suitable humectants are preferably used in the oral care compositions of the present invention, such as glycerin, sorbitol, propylene glycol, dipropylene glycol, diglycerol, triacetin, mineral oil, polyethylene glycol (preferably PEG-400), alkanediols (such as butanediol and hexanediol), ethanol, pentylene glycol, or mixtures thereof. Glycerin, polyethylene glycol, sorbitol, or mixtures thereof are preferred humectants, with glycerol (also known as glycerin) and sorbitol being most preferred.

[0057] The humectant may be present in the range of 10 to 90% by weight of the oral care composition. More preferably, the humectant comprises 25 to 80% by weight of the composition, and most preferably 45 to 70% by weight, based on the total weight of the composition, including all ranges subsumed therein.

[0058] Preferably, the oral care composition comprises a surfactant. Preferably, the composition comprises at least 0.01%, more preferably at least 0.1%, and most preferably 0.5-7% of a surfactant by weight of the composition. Suitable surfactants include anionic surfactants such as C8-C18 alkyl sulfates (e.g., sodium lauryl sulfate), C8-C18 alkyl sulfosuccinates (e.g., dioctyl sodium sulfosuccinate), C8-C18 alkyl sulfoacetates (e.g., sodium lauryl sulfoacetate), C8-C18 alkyl sarcosinates (e.g., sodium lauryl sarcosinate), C8-C18 alkyl phosphates (optionally containing up to 10 ethylene oxide and / or propylene oxide units), and sulfated monoglycerides. More preferably, the surfactant comprises or is an anionic surfactant. Preferred surfactants are sodium lauryl sulfate and / or sodium dodecylbenzenesulfonate. Most preferably, the surfactant is sodium lauryl sulfate. Other suitable surfactants include nonionic surfactants such as optionally polyethoxylated fatty acid sorbitan esters, ethoxylated fatty acids, esters of polyethylene glycol, ethoxylates of fatty acid monoglycerides and diglycerides, and ethylene oxide / propylene oxide block polymers. Other suitable surfactants include amphoteric surfactants such as betaines or sulfobetaines. Mixtures of any of the above materials can also be used. The most preferred surfactants are alkali metal alkyl sulfates or betaines.

[0059] In a preferred embodiment, the composition comprises a thickener, such as sodium carboxymethylcellulose (SCMC), hydroxyethylcellulose, methylcellulose, ethylcellulose, tragacanth gum, gum arabic, karaya gum, xanthan gum, sodium alginate, carrageenan gum, guar gum, Irish moss, starch, modified starch, silica-based thickeners such as silica aerogel, magnesium aluminum silicate (e.g., Veegum), carbomers (crosslinked acrylates), and mixtures thereof.

[0060] Typically, thickening silica, sodium carboxymethylcellulose and / or carbomer are preferred thickening agents for use in the compositions of the present invention.

[0061] Thickening silicas are particularly preferred for use in gel toothpastes.

[0062] Gel toothpastes generally contain up to 8.5% by weight of thickening silica, while opaque toothpastes typically contain 3-4% by weight of thickening silica.

[0063] When present, thickeners preferably comprise from 0.01 to about 10% by weight of the composition, more preferably from 0.1 to 9% by weight, and most preferably from 1.5 to 8% by weight.

[0064] Water may be contained preferably in an amount of 5 to 95%, particularly 10 to 75%, especially 10 to 60%, and more preferably 10 to 45% of the total weight of the composition.

[0065] When the oral care composition of the present invention is a toothpaste or gel, it typically has a viscosity of about 30,000 to 180,000 centipoise, preferably 60,000 to 170,000 centipoise, and most preferably 65,000 to 165,000 centipoise.

[0066] The oral care compositions of the present invention may contain various other ingredients common in the art to enhance their physical properties and performance. These ingredients include antimicrobial agents, anticaries agents, plaque buffers, fluoride sources, vitamins, botanical extracts, desensitizing agents, anti-tartar agents, biomolecules, flavoring agents, proteinaceous materials, preservatives, opacifiers, colorants, pH adjusters, sweeteners, particulate abrasive materials, polymeric compounds, buffers and salts for buffering the pH and ionic strength of the composition, and mixtures thereof. Such ingredients typically and collectively comprise less than 20% by weight of the composition, including all ranges included, preferably 0.0-15% by weight, and most preferably 0.01-12% by weight of the composition.

[0067] The present invention also relates to a method for inactivating or killing enveloped viruses on a topical surface of the human or animal body, comprising exposing the desired topical surface to a PPAR-activating fatty acid or a composition thereof. The method also includes an embodiment in which the composition further comprises a vitamin B3 compound, a precursor thereof, or an analog thereof. The method according to the present invention is for cosmetic use, i.e., non-therapeutic use.

[0068] Yet another aspect of the present invention relates to a method for inactivating enveloped viruses on a topical surface of the human or animal body, comprising applying a vitamin B3 compound, a precursor thereof, an analog thereof, or a composition thereof to the desired topical surface.

[0069] According to a preferred embodiment of the present invention, (i) 0.01 to 5.0% by weight of a vitamin B3 compound, a precursor thereof, or an analog thereof; (ii) 0.01 to 5.0 wt % of a PPAR-activating fatty acid; (iii) 70–99 wt % water; (iv) 1 to 20 wt. % of a humectant; and (v) less than 1.5% by weight of a surfactant selected from nonionic or amphoteric surfactants or mixtures thereof A mouthwash composition for inactivating enveloped viruses is provided, comprising:

[0070] The mouthwash composition of the present invention refers to a composition used for rinsing the mouth. It may be in the form of a liquid that consumers use to rinse their mouths or throats with a small amount, e.g., 5 to 30 mL, to remove bacteria or to gargle for the same purpose. Such liquid mouthwash compositions may be used as is, i.e., without dilution with water, or may be diluted with water at a ratio of 1:0.5 to 1:10 before rinsing the mouth. Whether diluted or not, the mouthwash composition is used to rinse the mouth or gargle in the mouth or throat for about 10 seconds to about 2 minutes, after which it is typically expectorated. Mouthwashes of the present invention also include liquid sprays delivered to the mouth from a container equipped with a spray pump. Thus, the mouthwash composition of the present invention may be in the form of a liquid mouthwash composition or a spray composition, of which liquid mouthwash compositions are particularly preferred. The term "liquid mouthwash composition" generally refers to a liquid preparation used to cleanse the surfaces of the oral cavity and provide the user with a clean and refreshing feeling. Mouthwashes are oral compositions that are not intentionally swallowed for the purpose of systemic administration of a therapeutic agent, but are instead applied to the oral cavity, used to treat the oral cavity, and then expectorated.

[0071] Mouthwash compositions according to the present invention preferably comprise an aqueous base, the amount of water generally ranging from 70 to 99% by weight, based on the total weight of the mouthwash.

[0072] Mouthwash compositions according to the present invention typically include additional ingredients to enhance performance and / or consumer acceptability, such as humectants and surfactants. The amount of humectant typically ranges from 1.0 to 20% by weight, more preferably 1.5 to 5% by weight, based on the total weight of the mouthwash. Preferred humectants present at these levels include polyols, more preferably sorbitol and / or glycerol, with glycerol being particularly preferred. Preferably, the level of ethanol in the mouthwash composition is less than 0.1% by weight.

[0073] The mouthwash composition of the present invention may contain a preservative, and preferred preservatives are benzyl alcohol and phenoxyethanol. The content of the preservative is preferably 0.1 to 1% by weight of the total composition.

[0074] The mouthwash compositions of the present invention may also include a deposition aid. The term "deposition aid" in the context of the present invention generally refers to a substance that aids in the deposition of the antimicrobial agent from the composition. Deposition aids suitable for use in the present invention are generally soluble or dispersible in water at a temperature of 25°C.

[0075] Preferred deposition aids for use in the present invention are water-soluble. The term "water-soluble" in this particular context generally means that the deposition aid has an aqueous solubility of at least 10 g / L at 25°C, more preferably at least 30 g / L at 25°C (wherein the solubility is measured in unbuffered distilled water). It is particularly preferred that the deposition aid remain water-soluble after drying, thereby allowing it to be redissolved. This prevents undesirable buildup of the deposition aid on the teeth after repeated use of the composition.

[0076] Deposition aids suitable for use in the present invention include polymeric materials, preferably water-soluble polymeric materials as defined above.

[0077] The polymeric materials used as deposition aids in the present invention can be of natural or synthetic origin and can be ionic or non-ionic in nature.

[0078] Preferably, such polymeric materials are of high molecular weight. The term "high molecular weight" in this particular context generally means that the polymeric material has a molecular weight of at least 50,000, more preferably at least 500,000 g / mol. A suitable method for determining the molecular weight of such polymeric materials is gel permeation chromatography against polyethylene glycol standards.

[0079] Specific examples of suitable classes of polymeric materials for use as deposition aids in the present invention include:

[0080] Water-soluble high molecular weight ethylene oxide linear homopolymers have the general formula H(OCH2CH2) n These materials are commonly called polyethylene oxides (or polyoxyethylenes, or polyethylene glycols). In the general formula, the average value of n is usually at least 2000, preferably at least 50,000.

[0081] Water-soluble polymeric cellulose ethers such as methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxybutyl methyl cellulose, hydroxyethyl ethyl cellulose, sodium carboxymethyl cellulose, and sodium carboxymethyl hydroxyethyl cellulose.

[0082] A preferred class of polymeric materials for use as deposition aids in the present invention includes water-soluble, high molecular weight polymers having anionic side groups along the polymer backbone.

[0083] Specific examples of such materials include poly(carboxylic acid) polymers, which are typically polymers that contain -COOH groups or groups derived from -COOH groups, such as salt, ester, or anhydride groups, within their structure.

[0084] For example, a poly(carboxylic acid) polymer may contain in its structure the following units: [ka] wherein R 1 is hydrogen, C 1-3 alkyl, C alkoxy or C hydroxyalkyl. Preferably R 1 is hydrogen.

[0085] A preferred class of poly(carboxylic acid) polymers has in its structure the following adjacent units: [ka] Including (R 1 is as defined above), for example, typically the following units: [ka] and / or salts or esters of such units, or maleic acid-based polymers containing such units in anhydrous form (wherein the -COOH groups on adjacent carbon atoms are cyclized to form a ring system).

[0086] For example, a poly(carboxylic acid) polymer can include units having pairs of carboxylic acid groups on adjacent polymer chain carbon atoms, such as the following units in the structure: [ka] (and / or salts or esters of such units, or anhydride forms of such units in which —COOH groups on adjacent carbon atoms have cyclized to form a ring system), wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are independently hydrogen, C 1-3 Alkyl or C 1-3 Preferably, R is selected from alkoxy. 1 and R 2 is hydrogen and R 3 is hydrogen and R 4 is methoxy and R 5 and R 6 is hydrogen.

[0087] Such poly(carboxylic acid) polymers can be described as polymers based on copolymers of methyl vinyl ether and maleic anhydride, and are available commercially, for example, under the trade name Gantrez®.

[0088] Particularly preferred examples of such polymers include those containing in their structure the following units: [ka] wherein the -COOH group is in the free acid form. Such polymers may be linear or crosslinked. More preferably, the polymer is linear. Polymers of this type are commercially available, for example, under the trade name Gantrez® S. Most preferably, such polymers have a molecular weight of at least 500,000 g / mol (e.g., Gantrez® S-96), ideally at least 1,000,000 g / mol (e.g., Gantrez® S-97).

[0089] Alternative polymers that can be used are those that contain the above units in the anhydride form, i.e., two adjacent -COOH groups cyclized to form a ring system. Such polymers are commercially available under the trade name Gantrez® AN, such as Gantrez® AN-119, Gantrez® AN-903, Gantrez® AN-139, and Gantrez® AN-169.

[0090] Other alternative polymers that can be used are those that contain the units described above in the form of partial salts, for example, those in which some of the free -COOH groups have been converted to metal salts of Group I or Group II metals such as sodium or calcium, or mixed sodium-calcium salts. Such polymers are commercially available under the trade name Gantrez® MS, e.g., Gantrez® MS-955.

[0091] Other alternative polymers that can be used include the above units in partial ester form, e.g., where some of the free -COOH groups are C 1-6It is esterified with an alkyl, such as ethyl or n-butyl. Such polymers are commercially available under the trade name Gantrez® ES, for example Gantrez® ES-225 or Gantrez® ES-425.

[0092] Mixtures of the above materials may also be used.

[0093] The amount of deposition aid (as defined above) in the mouthwash composition of the present invention is in the range of 0.001 to 5.0%, preferably 0.005 to 4.0%, more preferably 0.01 to 2.0%, of the total weight of the deposition aid (as defined above), based on the total weight of the composition.

[0094] Preferably, the mouthwash composition comprises an acid anhydride polymer, particularly preferred is a copolymer of maleic anhydride and methyl vinyl ether, the anhydride portion of which may be in a partially or fully hydrolyzed or alcoholyzed form.

[0095] The mouthwash composition may contain low levels of surfactant, based on the total weight of the composition. If present, the surfactant is preferably present at a level of less than 3.0% by weight of the total composition, more preferably less than 2.0% by weight, and most preferably less than 1.5% by weight.

[0096] Surfactants suitable for use in the present invention include nonionic surfactants such as polyethoxylated fatty acid sorbitan esters, ethoxylated fatty acids, esters of polyethylene glycol, ethoxylates of fatty acid mono- and diglycerides, and ethylene oxide / propylene oxide block polymers. A preferred nonionic surfactant is the ethoxylated polyethylene glycol ester of castor oil, particularly PEG40 hydrogenated castor oil.

[0097] Other suitable surfactants include amphoteric surfactants such as betaines and sulfobetaines. Mixtures of any of the above materials may also be used.

[0098] Preferably, the mouthwash composition is free of anionic surfactants.

[0099] The mouthwash compositions of the present invention may also include additional optional ingredients conventional in the art, such as a fluoride ion source, anticalculus agents, buffers, flavoring agents, stabilizers such as EDTA, sweeteners, coloring agents, opacifiers, anti-hypersensitivity agents, and antibacterial agents.

[0100] Use of a mouthwash composition in the context of the present invention typically involves applying the composition to the oral cavity for a recommended period of time before expectoration, with a preferred application period being 10 to 50 seconds.

[0101] According to a preferred embodiment of the present invention, there is provided a wash-off composition for providing delicate hygiene in and around the vagina, having a pH in the range of 2.5 to 6.0, preferably 2.5 to 4.5, comprising: (i) Vitamin B3 compounds, their precursors or analogs thereof; (ii) PPAR-activated fatty acids; (iii) 0.1% to 50% by weight of an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulfate, ammonium lauryl sulfate, cocoamidopropyl betaine, sodium cocoyl isethionate, sodium lauroyl isethionate, and sodium methyl lauroyl taurate; (iv) a carboxylic acid; and (v) 40 to 90% by weight of water A composition comprising:

[0102] The wash-off compositions of the present invention can also be used in intimate hygiene products, particularly those used by women for effective, safe, and gentle cleansing in and around the vagina. Such products, when used for intimate hygiene, are commonly available as liquids containing a certain amount of surfactant and emollient, formulated at a feminine-friendly pH. These products are also known as feminine hygiene products or menstrual hygiene products. Such liquid products typically contain a large amount of water, typically in the range of 40-80% by weight, and preferably 50-70% by weight. They also contain a surfactant, such as an anionic and / or amphoteric surfactant. Such surfactants preferably comprise 10-50% by weight, and preferably 20-40% by weight, of the composition. Particularly preferred surfactants for use in such products include triethanolamine lauryl sulfate, ammonium lauryl sulfate, cocoamidopropyl betaine, or mixtures thereof. Additional surfactants that may be included in such products are generally mild surfactants of the amphoacetate or glucoside type. Particularly preferred among these types of surfactants are disodium cocoamphodiacetate, alkyl esters such as decyl glucoside, and combinations thereof. Additionally, the product may contain oils, emollients, moisturizers, thickeners, and other additives that help provide a mild feel to the skin. Suitable moisturizers that can be included in such compositions are those disclosed above for oral care, such as glycerol, sorbitol, or mixtures thereof. Carboxylic acids, such as lactic acid and / or citric acid, are typically included in such compositions to provide additional hygiene benefits, with lactic acid being preferred. The pH of such products is generally in the range of 2.5 to 6.0, preferably 2.5 to 4.5.

[0103] Depending on the type of topical surface desired to be treated for viral inactivation or killing, the compositions of the present invention may include a suitable antimicrobial agent selected from one or more of salicylic acid, chloroxylenol, bisvalol, zinc pyrithione, octopirox, climbazole, triclosan, triclocarban, and cationic compounds such as benzalkonium chloride, dodecyldimonium chloride, cetrimonium chloride, and cetylpyridinium chloride.

[0104] It is also within the scope of the present invention that the compositions claimed herein are free of sulfate surfactants. Another embodiment relates to compositions of the present invention that are free of preservatives. Yet another embodiment relates to compositions that are free of acrylate polymers. The compositions are typically prepared for sale in plastic containers, which are preferably of the PCR type (post-consumer recycled plastic).

[0105] The invention will now be illustrated by the following non-limiting examples. [Example]

[0106] Examples A, 1-3: Virucidal effect of 12-HSA on the skin keratinocyte line HaCaT The skin keratinocyte cell line HaCaT was differentiated and treated with 10 μM, 20 μM, or 40 μM 12HSA for 72 hours according to standard protocols. After this treatment, secretomes containing secreted antimicrobial peptides (AMPs) were harvested and incubated with SARS-CoV2 virus for 4 hours. After 4 hours of incubation, virus killing was measured using a quantitative PCR-based method. Data on viral gene expression as a percentage of the control are shown in Table 1 below.

[0107] Table-1 [Table 1]

[0108] The data in the table above demonstrate that secretomes produced in the presence of 12HSA have the ability to kill / inactivate viruses.

[0109] Examples B-D, 4-6: Effects of 12-HSA and Vitamin B3 and Combinations on Epithelial Cells (Calu-3 Cells): Compound treatment and plaque formation assay SARS-CoV-2 was adsorbed to Calu-3 cells at 0.1 MOI and plated at approximately 120,000 cells / well in 48-well plates for 1 hour. After washing, fresh medium was added along with niacinamide (16.4 mM), 12HSA (10 mM), and individual solvent controls. After 48 hours, conditioned medium (containing viral particles) was collected and a plaque-forming assay was performed on Vero-E6 cells (48-well plates) to measure plaque-forming units (pfu / ml) for each treatment.

[0110] The data is summarized in Table 2 below. Table-2 [Table 2]

[0111] The data in the table above demonstrate that both 12-HSA and niacinamide have the ability to inhibit SARS-CoV-2, as evidenced by the reduction in plaque-forming units in the assays used above, and that inhibition is significantly improved by the combination of 12-HSA and vitamin B3.

[0112] Examples E-G, 7-9: Effect of human keratinocyte supernatant on SARS-CoV2 infectivity Differentiated primary human keratinocytes were cultured in serum-free Epilife medium containing the above concentrations of niacinamide and / or 12HSA for 72 hours, and the conditioned medium was collected. SARS-CoV-2 viral particles were cultured in the above conditioned medium for approximately 4 hours. The pfu / mL of these treated viral particles was measured using VeroE6 reporter cells via Plaque or TCID50. The % infection rate relative to the control is shown in Table 3 below.

[0113] Table-3 [Table 3]

[0114] The data in the above table indicate that effects similar to those in Table 2 may also be obtained with primary human keratinocytes.

[0115] Examples HN: Effects of Vitamin B3 Compounds, Their Precursors, or Their Analogs on Virus Killing in Skin Keratinocyte Cell Lines The skin keratinocyte cell line CRL4048 was differentiated and treated with various concentrations of vitamin B3 compounds, their precursors, or their analogs, as shown in Table 4 below, for 72 hours according to standard protocols. After this treatment, secretomes containing secreted antimicrobial peptides (AMPs) were harvested and incubated with SARS-CoV2 virus for 4 hours. After the 4-hour incubation, the virus mixture was incubated on the VeroE6 reporter cell line, and virus killing was enumerated using a quantitative PCR-based infectivity assay. Data on viral gene expression as a percentage of control are shown in Table 4 below.

[0116] Table-4 [Table 4]

[0117] The data in Table 4, combined with the data in Table 1 above, show that 12HSA is far superior to niacinamide (Examples I and J), as it is not effective at similar (micromolar) concentrations. When other analogs of vitamin B3 compounds (Examples K-N) are used, orders of magnitude higher concentrations (millimolar rather than micromolar) are required to kill the virus compared to 12HSA (Examples 1-3 in Table 1).

[0118] Examples P, 10-14: Effect of other PPAR fatty acids on virus killing in skin keratinocyte cell lines Viral gene expression was examined using other PPAR fatty acids, as shown in Table 5 below. The procedures used to generate the data were similar to those used in Table 4. The data are summarized in Table 5 below.

[0119] Table-5 [Table 5]

[0120] In the table above, CLA stands for conjugated linoleic acid.

[0121] The data in Table 5 above show that other PPAR fatty acids (Examples 10-14) are as effective as 12HSA (Examples 1-3 in Table 1) in viral gene expression at similar (micromolar) concentrations.

Claims

1. Use of peroxisome proliferator-activated receptor (PPAR)-activating fatty acids to inactivate or kill enveloped viruses on topical surfaces of the human or animal body.

2. Use of a composition comprising (i) a vitamin B3 compound, a precursor thereof, or an analog thereof, and (ii) a peroxisome proliferator-activated receptor (PPAR)-activating fatty acid to inactivate or kill enveloped viruses on a topical surface of the human or animal body.

3. The use according to claim 1 or 2, wherein the enveloped virus is a coronavirus, preferably SARS-Cov2; or an influenza virus.

4. Use according to any one of the preceding claims, wherein the PPAR-activating fatty acid is hydroxystearic acid (HSA), preferably 12-hydroxystearic acid or 10-hydroxystearic acid.

5. Use of a composition for caring for the external body surface, comprising (i) a PPAR-activating fatty acid and (ii) a cosmetically acceptable carrier selected from a powder, bar / tablet, liquid, gel, emulsion or anhydrous phase, for inactivating or killing enveloped viruses on the external surface of the human or animal body.

6. Use of a composition for cleansing the external body surface, comprising (i) a PPAR-activating fatty acid and (ii) a cosmetically acceptable vehicle containing 0.1% to 80% by weight of a surfactant selected from synthetic surfactants or soaps, for inactivating or killing enveloped viruses on the external body surface of a human or animal.

7. Use of a composition for caring for or cleansing mucosal surfaces, comprising (i) a PPAR-activating fatty acid and (ii) a mucosally acceptable carrier selected from one or more of water, abrasives, moisturizers, and emulsifiers, for inactivating or killing enveloped viruses on mucosal surfaces of the human or animal body.

8. Use of the composition according to any one of claims 5 to 7, further comprising a vitamin B3 compound, a precursor thereof or an analog thereof.

9. A method for inactivating or killing enveloped viruses on a topical surface of the human or animal body, the method comprising exposing the desired topical surface to a PPAR-activating fatty acid or composition thereof.

10. 10. The method of claim 9, wherein the composition further comprises a vitamin B3 compound, a precursor thereof, or an analog thereof.

11. (i) 0 to 5.0% by weight of a vitamin B3 compound, a precursor thereof, or an analog thereof; (ii) 0.01 to 5.0 wt. % of a PPAR-activating fatty acid; (iii) 70 to 99 wt. % water; (iv) 1 to 20% by weight of a humectant; and (v) less than 1.5% by weight of a surfactant selected from nonionic or amphoteric surfactants or mixtures thereof 1. A mouthwash composition for inactivating enveloped viruses, comprising:

12. (i) PPAR activated fatty acids; (ii) 0.1% to 50% by weight of an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulfate, ammonium lauryl sulfate, cocoamidopropyl betaine, fatty acid isethionates, and fatty acid acyltaurates; (iii) a carboxylic acid; and (iv) 40 to 90% by weight of water 1. A wash-off composition which provides intimate hygiene in or around the vagina, having a pH in the range of 2.5 to 6.0, preferably 2.5 to 4.5.

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