Inactivation or killing of viruses and compositions thereof

Abstract

The present invention relates to the use of active substances and compositions comprising them for treating surfaces to inactivate or kill enveloped viruses. The invention also relates to certain liquid cleaning and disinfecting compositions for delivering such antiviral effects. This is accomplished by using a PPAR-activated fatty acid, optionally in combination with a vitamin B3 compound.

Description

Field of the Invention

[0001] The present invention relates to the use of active substances and compositions containing them for treating surfaces to inactivate or kill enveloped viruses. The present invention also relates to certain liquid cleaning and disinfecting compositions and devices for delivering such antiviral effects. Background of the Invention

[0003] Respiratory tract infections are considered one of the most prevalent causes of illness in the world. Globally, acute lower respiratory tract infections are a significant cause of morbidity and mortality in children under five years of age. Scientific studies have identified respiratory syncytial virus (RSV) as the most common viral cause of death due to this infection; other important viruses are human metapneumovirus, parainfluenza virus, influenza viruses A and B, adenovirus, and coronaviruses of emerging origin. Tens of millions of cases of these infections are reported each year, resulting in more than 500,000 deaths in children under five years of age, mostly in low- and middle-income families.

[0004] Viruses as described above are known to spread through respiratory aerosol droplets or through contact with infected hands and even through inanimate surfaces. Therefore, hand hygiene is a generally recommended method for killing these germs, which not only reduces the risk of respiratory infections, but also reduces the risk of gastrointestinal diseases. Hand hygiene includes washing hands with soap and running water, which not only removes dirt, but also washes off and kills germs including bacteria and viruses. Alternatively, an alcohol-based hand sanitizer containing a very small amount of water can be rubbed on the hands as another effective way to remove viruses and bacteria from the hands. Although these methods are very good in killing germs in an instant, they are sometimes considered to be caustic. Therefore, it is necessary to be gentle to the skin and other external and mucosal surfaces but sufficient to effectively kill or inactivate viruses to prevent or alleviate infection. Active substances and compositions.

[0005] In the search for such active substances, the inventors have stumbled upon a specific type of fatty acid known as a PPAR (peroxisome proliferator activated receptor) activating fatty acid, which has now been found to kill or inactivate enveloped viruses, which was previously unknown. In addition, it has been found to synergize with a specific vitamin (i.e., vitamin B3 or its precursor or analog thereof) to provide enhanced antiviral activity. In addition, it has been found that vitamin B3 or its precursor or analog itself can also deliver this activity.

[0006] The PPAR fatty acids according to the present invention include fatty acids having PPAR effects, and also include their corresponding mono-, di- and tri-glyceride forms.

[0007] It was therefore an object of the present invention to provide novel active substances which kill or inactivate enveloped viruses.

[0008] It is another object of the present invention to provide this benefit by using commonly available active ingredients that are mild to the external body or mucosal surfaces. Summary of the invention

[0009] A first aspect of the present invention relates to the use of peroxisome proliferator-activated receptor (PPAR) activating fatty acids for inactivating or killing enveloped viruses on a topical surface of the human or animal body.

[0010] A preferred aspect 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 for inactivating or killing enveloped viruses on a topical surface of the human or animal body.

[0011] Another aspect of the present invention relates to a mouthwash composition for inactivating enveloped viruses, comprising

[0012] (i) 0 to 5.0% by weight of a vitamin B3 compound, a precursor thereof, or an analog thereof;

[0013] (ii) 0.01 to 5.0 wt % of a PPAR-activating fatty acid;

[0014] (iii) 70 to 99% by weight of water;

[0015] (iv) 1 to 20 wt % of a wetting agent; and

[0016] (v) less than 1.5% by weight of a surfactant selected from nonionic or amphoteric surfactants or mixtures thereof.

[0017] A further aspect of the present invention relates to a rinse-off composition for providing intimate hygiene in and around the vagina having a pH value in the range of 2.5 to 6.0, preferably 2.5 to 4.5, comprising

[0018] (i) PPAR activation fatty acids;

[0019] (ii) 0.1 wt % to 50 wt % of an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulfate, ammonium lauryl sulfate, cocamidopropyl betaine, fatty acid isethionate and fatty acyl taurate;

[0020] (iii) carboxylic acid; and

[0021] (iv) 40 to 90% by weight of water.

[0022] Another aspect of the present invention relates to the use of a vitamin B3 compound or its precursor or analogue for inactivating enveloped viruses on the local surface of the human or animal body. DETAILED DESCRIPTION OF THE INVENTION

[0024] By reading the following detailed description and the appended claims, these and other aspects, features and advantages will become apparent to those of ordinary skill in the art. For the avoidance of doubt, any feature of one aspect of the present invention may be used in any other aspect of the present invention. The word "comprising" is intended to mean "including", but not necessarily "consisting of" or "consisting of". In other words, the steps or options listed do not have to be exhaustive. It should be noted that the examples given in the following description are intended to illustrate the present invention, but are not intended to limit the present invention to these examples themselves. Similarly, unless otherwise indicated, all percentages are weight / weight percentages. Except in the operating and comparative examples, or where otherwise clearly indicated, all numbers representing the amount of material or reaction conditions, the physical properties of the material and / or the use in this specification and claims should be understood to be modified by the word "about". Numerical ranges expressed in the form of "from x to y" are understood to include x and y. When multiple preferred ranges are described in the form of "from x to y" for a particular feature, it should be understood that all ranges combining different endpoints are also considered.

[0025] The present invention can be used to inactivate or kill viruses, particularly enveloped viruses, on the local surface of the human or animal body. Therefore, the surface is a living surface.

[0026] Animate surfaces include the outer surfaces of living organisms like plants and animals (including humans). Due to the high availability of nutrients and water on most animate surfaces, germs reside and can multiply on these surfaces. The present invention is useful for combating viral infections on any type of animate surface. The present invention is particularly useful for preventing or killing viruses on local surfaces of the human body. Local surfaces according to the present invention include outer 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 in the oral cavity and surfaces of the vagina.

[0027] The present invention can be used with a leave-on composition or a rinse-off composition. A "leave-on composition" refers to a composition that is applied to the outer surface of the human body and allowed to remain thereon until the person takes a shower or bath, usually a few hours later or a day later. A rinse-off composition refers to a composition that is used to wash the outer surface of the body, such as with a soap composition, shower gel, facial cleanser, shampoo or hair conditioning composition and a large amount of water, so that a significant amount of dirt and oil is washed off the body surface to keep it clean. Such rinse-off compositions typically contain a sufficient amount of surfactant to achieve the rinse-off effect.

[0028] The present invention relates to the use of vitamin B3 compounds, their precursors or analogs thereof for inactivating enveloped viruses on the local surface of the human or animal body. The use is preferably non-therapeutic. The enveloped virus is preferably SARS-Cov2.

[0029] The present invention relates to the use of PPAR activating fatty acids for inactivating or killing enveloped viruses on localized surfaces of the human or animal body. The use is preferably non-therapeutic.

[0030] The present invention also enables the prevention of reinfection of these surfaces by inactivating or killing enveloped viruses on local surfaces using one or more of the active substances claimed herein. This means that surfaces treated with these active substances are protected against future surface infection within a few hours after such treatment.

[0031] Envelope viruses according to the present invention include coronaviruses or 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 envelope viruses that can be treated according to the present invention include RSV (respiratory syncytial virus) and HSV (herpes simplex virus).

[0032] Peroxisome proliferator-activated receptor (abbreviated as PPAR herein) is a transcription factor that controls lipid metabolism. There are three subtypes, PPARα, PPARβ / δ and PPARγ, which are all located in the skin. A series of specific fatty acids activate these factors, thereby leading to anti-inflammatory effects to reduce skin irritation reactions and promote differentiation / anti-proliferation reactions so that skin metabolism is normalized and additional skin care benefits are provided. It is particularly desirable to select PPAR fatty acids containing hydroxyl and / or methyl side chains. Many such acids contain 14 to 30 carbons. Examples of PPAR fatty acids with demonstrated PPAR activating activity are cis-octadecatetraenoic acid, cis-9-trans-11 conjugated linoleic acid, columbinic acid, docosahexaenoic acid, eicosapentaenoic acid, hexadecatrienoic acid, trans-linolenic acid (an isomer of linolenic acid), petroselinic acid, pinene acid, punicic acid, ricinoleic acid, trans-ricinoleic acid (an isomer of ricinoleic acid), stearidonic acid, trans-10-cis-12 conjugated linoleic acid, 7-trans-octadecanoic acid, trans-vaccenic acid, octadecenedioic acid, and hydroxystearic acid.

[0033] PPAR fatty acids according to 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 seed oil, parinarium laurinarium kernel fat or sabastiana brasilinensis seed oil for cis-octadecatetraenoic acid, dehydrated castor oil for conjugated linoleic acid, and aquilegia oil for gulombic acid. If a single hydrolyzable precursor of a PPAR activating fatty acid is used, it specifically excludes borage oil, castor oil and sunflower seed oil. Ideally, the PPAR acid contains 16 or 18 carbon atoms.

[0034] A particularly preferred PPAR acid is hydroxystearic acid or an ester thereof. The most preferred PPAR acid is hydroxystearic acid.

[0035] It is preferred that the hydroxystearic acid is 10-hydroxystearic acid, 12-hydroxystearic acid or trihydroxystearic acid (e.g. 9,10,13-trihydroxystearic acid) or trihydroxystearin or a compound that produces one or more hydroxystearic acid or hydroxystearic acid ester molecules when it decomposes, such as a monoester, diester or triester of glycerol and hydroxystearic acid. Among them, 10-hydroxystearic acid, 12-hydroxystearic acid and 9,10,13-trihydroxystearic acid are more preferred, and 12-hydroxystearic acid (12-HSA) is most preferred. 12-HSA has the structure given below:

[0036]

[0037] Preferably, the PPAR activating fatty acid for use in any aspect of the invention is also a caspase 8 modulator.

[0038] According to a preferred aspect, the composition according to the invention may additionally comprise an antimicrobial peptide (AMP). A further preferred aspect relates to the use of a composition according to the invention (which additionally comprises an antimicrobial peptide). A preferred AMP is LL37.

[0039] A preferred aspect 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 inactivating or killing enveloped viruses on a topical surface of the human or animal body. The use is preferably non-therapeutic.

[0040] Yet another aspect of the present invention relates to the use of PPAR activating fatty acids as enveloped virus killing or inactivating agents in a composition further comprising a vitamin B3 compound, a precursor thereof, or an analog thereof.

[0041] 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 inactivating system.

[0042] The vitamin B3 compound, its precursor or its analogue is selected from one or more of tryptophan, niacin, nicotinic acid, isonicotinamide, pyridine amide and nicotinamide (also known as nicotinamide). Preferably it is nicotinamide. Nicotinamide, also known as pyridine-3-carboxamide, is an active, water-soluble form of vitamin B3. According to the present invention, analogues of vitamin B3 also include derivatives such as cycloalkyl nicotinamide, whose cycloalkyl group has 3 to 6 carbon atoms.

[0043] When included in the composition of the present invention, niacinamide is included in an effective amount, typically at a concentration of 0.05 to 3%, preferably 0.1 to 2%, by weight of the composition. In such a composition, hydroxystearic acid preferably comprises 0.05 to 3%, more preferably 0.1 to 2%, by weight of the composition.

[0044] Without wishing to be bound by theory, the inventors believe that the active substances claimed in the present invention, namely PPAR fatty acids, such as 12-HSA, activate host cells to help drive the defense benefit against non-enveloped viruses such as SARS-Cov 2. This mode of action is believed to be very different from direct antiviral agents such as low boiling alcohols, bleaching agents and cationic surfactants such as quaternary ammonium compounds, which act directly on viral particles to inactivate them and exert their antiviral effects.

[0045] It can be further understood experimentally that active substances such as PPAR fatty acids are deposited on the topical surface in sufficient amounts even from rinse-off compositions. In addition, it can be observed that the active substances move into the skin to activate AMP of the cells. The production of AMP is a biological process, and this takes a long time. It has been observed that the maximum amount of AMP is produced about 48 to 72 hours after the active substance is deposited.

[0046] Yet another aspect of the invention relates to the use of a composition for the care of the external surface of the body for inactivating or killing enveloped viruses on the external surface of the human or animal body, the composition comprising (i) a PPAR activating fatty acid and (ii) a cosmetically acceptable carrier selected from a powder, a bar / tablet, a liquid, a gel, an emulsion or an anhydrous phase. The use is preferably non-therapeutic. Such a composition may additionally comprise a vitamin B3 compound, a precursor thereof or an analog thereof.

[0047] Yet another aspect of the present invention relates to the use of a skin care composition for inactivating enveloped viruses on a topical surface of the human or animal body, the 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. The use is preferably non-therapeutic.

[0048] Yet another aspect of the present invention relates to the use of a skin cleansing composition for inactivating enveloped viruses on a topical surface of the human or animal body, the skin cleansing composition comprising (i) a vitamin B3 compound, a precursor thereof or an analog thereof and (ii) a cosmetically acceptable carrier comprising 5 to 80% of a surfactant selected from a synthetic surfactant or a soap. The use is preferably non-therapeutic.

[0049] Yet another aspect of the present invention relates to the use of an oral care composition for inactivating enveloped viruses in the oral cavity of a human or animal body, the 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. The use is preferably non-therapeutic.

[0050] The cosmetically acceptable carrier according to the aspect of the above-mentioned composition of the present invention can be preferably delivered in an emulsion, for example, as a cream or lotion or gel form, preferably in the form of a cream. The preferred form of the solid form composition is a cream, further more preferably a cream with a vanishing cream base. The vanishing cream base is a base containing 3 to 25% by weight of fatty acids. Optionally, the composition can include 0.1 to 10% by weight of soap. When included, the fatty acid is preferably a C10 to C22 fatty acid, more preferably a C16 to 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 a fatty acid mixture. The fatty acid is generally hystric acid, which is essentially (usually about 90 to 95%) a mixture of 45% stearic acid and 55% palmitic acid. The most preferred cream is a cream containing 3 to 25% by weight of fatty acids and 0.1 to 10% by weight of soap.

[0051] Preferably, the cosmetically acceptable carrier in the above composition comprises an emollient. Examples of emollients that can be used in leave-on compositions include stearyl alcohol, glyceryl monoricinoleate, mink oil, isopropyl isostearate, isobutyl palmitate, isooctyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecane-2-ol, isocetyl alcohol, eicosanol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, di-n-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, and the like. Esters, 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.

[0052] Preferably, the cosmetically acceptable carrier in the above composition comprises a solvent. Examples of solvents that can be used in the composition include ethanol, isopropanol, acetone, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether and mixtures thereof. The composition may comprise a polyol, which may be selected from one or more of glycerol, 1,3-butylene glycol, propylene glycol, 1,3-propanediol, pentanediol, hexylene glycol and sorbitol.

[0053] Preferably, the cosmetically acceptable carrier in the above composition comprises a powder. Examples of powders that can be used in the composition include chalk, talc, fuller's earth, kaolin, starch, gum, colloidal silica sodium polyacrylate, tetraalkyl and / or trialkyl aryl ammonium montmorillonite, chemically modified magnesium aluminum silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, carboxyvinyl polymers, sodium carboxymethylcellulose, ethylene glycol monostearate, and mixtures thereof.

[0054] According to another aspect of the present invention, there is provided a composition for cleaning the external surface of the body for inactivating or killing enveloped viruses on the external surface of the human or animal body, the composition comprising (i) a PPAR activating fatty acid and (ii) a cosmetically acceptable vehicle comprising 0.1 wt % to 80 wt % of a surfactant selected from a synthetic surfactant or soap. The use is preferably non-therapeutic. Such a composition may additionally comprise a vitamin B3 compound, a precursor thereof or an analog thereof. Such a composition is generally referred to as a cleaning composition.

[0055] As used herein, "cleaning compositions" are meant to include compositions that are topically applied to the skin, hair and / or scalp of mammals, especially humans. Such compositions are generally applied to the desired local surface of the body for a period of a few seconds to a maximum of a few minutes, usually after dilution with water. After this application period, the composition is usually rinsed off or wiped off with water. It includes any product that is applied to the human body and is also used to improve appearance, odor control or overall aesthetics. The composition of the present invention can be in the form of a liquid, lotion, cream, foam, scrub, gel, shampoo, conditioner, hand soap, facial cleanser or shower gel product.

[0056] In addition to the surfactant, the cosmetically acceptable medium generally comprises water. Particularly preferred surfactants are anionic surfactants, such as soap. The soap used to prepare the cleaning composition of the present invention is preferably C8-C 24 Soap, more preferably C 10 -C 20 Soap, most preferably C 12 -C 18 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 oil, soybean oil, tallow, palm oil, palm kernel, etc. can also be used in other desired proportions. The cosmetically acceptable vehicle generally accounts for 80 to 99% by weight of the cleansing composition.

[0057] When present, anionic surfactants (e.g., soap) are preferably present in an amount of 1 to 90%, preferably 10 to 85%, more preferably 25 to 75% by weight of the cleaning composition. The cleaning composition is preferably in solid or semi-solid form, most preferably in solid form. Preferred solid compositions are in the shape of soap bars.

[0058] The other anionic surfactants are preferably selected from alkyl ether sulfates, primary alkyl sulfates, secondary alkyl sulfonates, alkylbenzene sulfonates or ethoxylated alkyl sulfates. Preferred anionic surfactants other than soaps in the cleaning composition are alkyl ether sulfates, preferably those having 1 to 3 ethylene oxide groups, which are 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 with a carbon chain length between C6 and C 16 Those alkyl polyglucosides between.

[0059] Preferred cleaning compositions may include other known ingredients, such as perfumes, pigments, preservatives, emollients, sunscreens, gelling agents and thickeners. The selection of these ingredients depends largely on the form of the composition. Water is a preferred carrier. When water is present, it is preferably present in at least 1% by weight of the composition, more preferably at least 2%, and further preferably at least 5%. When water is a carrier, preferred cleaning compositions contain 10 to 50% by weight, more preferably 12 to 40% by weight, and further more preferably 12 to 25% by weight of water.

[0060] The cleansing compositions of the present invention may also be delivered via moisturizing bars or moisturizing liquid compositions. Moisturizing bar compositions comprising fatty acyl isethionate (eg, cocoyl isethionate) are particularly preferred.

[0061] 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 skin or hair cleansing products, particularly in personal care products, because they lather well, are mild to the skin and have good emollient properties. Typically, fatty acid isethionate surfactant products are produced by esterification of fatty acids or by reaction of fatty acid chlorides having a carbon chain length of C8-C20 with isethionates. Typical surfactant products containing fatty acyl isethionates contain, in addition to isethionates (usually less than 5%), about 40 to 95% by weight of acidic isethionic acid and 5 to 50%, typically 10 to 40%, of free fatty acids, and trace amounts (less than 2% by weight) of other additives. Such compositions may also include alkyl taurates, for example, alkyl tauramides. Such alkyl taurine amides may be prepared by taurine; methyl taurine; or the corresponding taurate (e.g., NH2CH2CH2SO3 M + , where M + The alkyl taurine amides are prepared by reacting sodium methyl cocoyl taurate (which may be a sodium or potassium counterion) with an appropriate fatty acid. Preferred alkyl taurine amides include sodium methyl cocoyl taurate and sodium methyl lauroyl taurate.

[0062] The fatty acid soap content may range from 5 to 15 wt%. Other surfactants such as betaines may be included at 1 to 5 wt%. Water is typically included at 2 to 8 wt% of the composition.

[0063] According to another aspect of the present invention, there is provided a composition for nursing or cleaning mucosal surfaces for inactivating or killing enveloped viruses on mucosal surfaces of human or animal bodies, the composition comprising (i) PPAR activating fatty acids and (ii) a mucosal acceptable carrier, the carrier being selected from one or more of water, abrasives, wetting agents and emulsifiers. The use is preferably non-therapeutic. This composition may additionally comprise a vitamin B3 compound, a precursor thereof or an analog thereof. When the composition is delivered for oral care, the mucosal acceptable carrier is generally referred to as an oral acceptable carrier.

[0064] More preferred orally acceptable carriers include abrasives, humectants or mixtures thereof. The orally acceptable carrier is preferably included in up to 99.8%, more preferably up to 96% by weight of the composition. The orally acceptable carrier is included in at least 80%, more preferably at least 90% by weight of the composition.

[0065] The oral care composition of the present invention can be delivered in the form of a paste, gel, dentifrice or mouthwash. Dentifrice includes forms such as toothpaste and tooth powder. The composition is most preferably in the form of toothpaste, tooth powder or mouthwash.

[0066] The oral care composition of the present invention preferably comprises an abrasive. The abrasive may preferably be calcium carbonate or silicon dioxide. Gels typically contain silicon dioxide, while opaque creams typically contain calcium-based abrasives, especially chalk (calcium carbonate). In opaque toothpastes, the composition contains 5 to 60% by weight of calcium-based abrasive. In more preferred compositions, it is 30 to 60% by weight, further preferably 35 to 55% by weight. The best composition has 40 to 55% by weight of calcium-based abrasive.

[0067] Suitable humectants are preferably used in the oral care composition of the present invention, and they include, for example, glycerol, sorbitol, propylene glycol, dipropylene glycol, diglycerol, triacetin, mineral oil, polyethylene glycol (preferably PEG-400), alkane diols (such as butylene glycol and hexylene glycol), ethanol, pentylene glycol or mixtures thereof. Glycerol, polyethylene glycol, sorbitol or mixtures thereof are preferred humectants, and glycerol (also known as glycerol) and sorbitol are most preferred.

[0068] 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, most preferably 45 to 70% by weight, based on the total weight of the composition, including all ranges subsumed therein.

[0069] Preferably, the oral care composition comprises a surfactant. Preferably, the composition comprises at least 0.01% by weight of the surfactant of the composition, more preferably at least 0.1% by weight, most preferably 0.5 to 7% by weight. Suitable surfactants include anionic surfactants, such as C8 to C18 alkyl sulfates (e.g., sodium lauryl sulfate), C8-C18 alkyl sulfosuccinic acid (e.g., dioctyl sodium sulfosuccinate), C8-C18 alkyl sulfoacetic acid (e.g., sodium lauryl sulfoacetate), C8-C18 alkyl sarcosine (e.g., sodium lauryl sarcosinate), C8-C18 alkyl phosphoric acid (which may optionally contain up to 10 ethylene oxide and / or propylene oxide units) and sodium, magnesium, ammonium or ethanolamine salts of sulfated monoglycerides. More preferably, the surfactant comprises or is an anionic surfactant. Preferred surfactants are sodium lauryl sulfate and / or sodium dodecylbenzene sulfonate. 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 may also be used. The most preferred surfactant is an alkali metal alkyl sulfate or a betaine.

[0070] In a preferred embodiment, the composition comprises a thickener. Thickeners useful in the present invention include sodium carboxymethylcellulose (SCMC), hydroxyethylcellulose, methylcellulose, ethylcellulose, tragacanth, gum arabic, gum karaya, xanthan gum, sodium alginate, carrageenan, guar gum, Irish moss, starch, modified starch, silica-based thickeners (including silica aerogels), magnesium aluminum silicate (e.g., Veegum), carbomer (cross-linked acrylates), and mixtures thereof.

[0071] Generally, thickening silica, sodium carboxymethylcellulose and / or carbomer are preferred thickening agents for use in the compositions of the present invention.

[0072] Thickening silicas are particularly preferred for use in gel toothpastes.

[0073] Gel toothpastes typically contain up to 8.5% by weight thickening silica, while opaque toothpastes typically contain 3 to 4% by weight thickening silica.

[0074] Thickeners, when present, preferably comprise from 0.01 to about 10%, more preferably from 0.1 to 9%, most preferably from 1.5 to 8% by weight of the composition.

[0075] Water may preferably be contained in an amount of 5 to 95%, particularly 10 to 75%, especially 10 to 60%, further preferably 10 to 45%, based on the total weight of the composition.

[0076] When the oral care composition of the present invention is a toothpaste or a gel, its viscosity is generally from about 30,000 to 180,000 centipoise, preferably from 60,000 to 170,000 centipoise, and most preferably from 65,000 to 165,000 centipoise.

[0077] The oral care compositions of the present invention may include a variety of other ingredients common in the art to enhance physical properties and performance. These ingredients include antibacterial agents, anti-caries agents, plaque buffers, fluoride sources, vitamins, plant extracts, desensitizers, anticalculus agents, biomolecules, flavoring agents, proteinaceous materials, preservatives, opacifiers, colorants, pH regulators, sweeteners, granular abrasives, polymeric compounds, buffers and salts that buffer the pH and ionic strength of the composition, and mixtures thereof. These ingredients typically and collectively account for less than 20% by weight of the composition, preferably 0.0 to 15% by weight of the composition, and most preferably 0.01 to 12% by weight, including all ranges contained therein.

[0078] 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 the step of exposing the desired topical surface to a PPAR activating fatty acid; or a composition thereof. The method also includes aspects wherein the composition additionally 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. it is for non-therapeutic applications.

[0079] Yet another aspect of the present invention relates to a method for inactivating enveloped viruses on a topical surface of a human or animal body, comprising the step of applying a vitamin B3 compound, a precursor thereof or an analog thereof; or a composition thereof to a desired topical surface.

[0080] According to a preferred aspect of the present invention, there is provided a mouthwash composition for inactivating enveloped viruses, comprising

[0081] (i) 0.01 to 5.0% by weight of a vitamin B3 compound, a precursor thereof or an analog thereof;

[0082] (ii) 0.01 to 5.0 wt % of a PPAR-activating fatty acid;

[0083] (iii) 70 to 99% by weight of water;

[0084] (iv) 1 to 20 wt % of a wetting agent; and

[0085] (v) less than 1.5% by weight of a surfactant selected from nonionic or amphoteric surfactants or mixtures thereof.

[0086] The mouthwash composition of the present invention means that the composition is used to clean the oral cavity. It can be used by the consumer in a small amount (i.e., 5 to 30 ml) to clean the oral cavity to remove germs, or for gargling in the oral cavity or throat to achieve the same purpose in the form of a liquid. This liquid oral composition can be used as is, i.e., without any dilution with water, or can be diluted with water at a ratio of 1:0.5 to 1:10 before cleaning the oral cavity. After rinsing the oral cavity with the mouthwash composition (diluted or undiluted) or gargling in the oral cavity and throat for about 10 seconds to about 2 minutes, it is usually spit out. The mouthwash according to the present invention also includes a liquid spray delivered to the oral cavity from a container equipped with a spray pump. Therefore, the mouthwash composition of the present invention is in the form of a liquid mouthwash composition or a spray composition, wherein a liquid mouthwash composition is particularly preferred. The term "liquid mouthwash composition" generally refers to a liquid preparation for rinsing the oral surface and providing the user with a clean and fresh feeling in the oral cavity. A mouthwash is an oral composition that is not intentionally swallowed for the purpose of systemic administration of a therapeutic agent, but is applied to the oral cavity for treating the oral cavity and then spitting out.

[0087] The mouthwash composition according to the present invention preferably comprises an aqueous base. The amount of water is generally in the range of 70 to 99 wt %, based on the total weight of the mouthwash.

[0088] Mouthwash compositions according to the present invention typically contain other ingredients to enhance performance and / or consumer acceptance, 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 the above levels include polyols, more preferably sorbitol and / or glycerol, particularly preferably glycerol. It is preferred that the ethanol content of the mouthwash composition is less than 0.1% by weight.

[0089] The mouthwash composition of the present invention may contain a preservative, preferably benzyl alcohol and phenoxyethanol. Preferably, the content of the preservative is 0.1 to 1% by weight of the total composition.

[0090] The mouthwash composition of the present invention may contain a deposition aid. The term "deposition aid" in the context of the present invention generally refers to a substance that aids the deposition of the antibacterial agent from the composition. Deposition aids suitable for use in the present invention are generally soluble or dispersed in water at 25°C.

[0091] 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 a water 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 retains water solubility after drying so that it can be redissolved. This prevents undesirable accumulation of the deposition aid on the teeth after repeated use of the composition.

[0092] Deposition aids suitable for use in the present invention include polymeric materials, preferably water-soluble polymeric materials as defined above.

[0093] The polymeric materials used as deposition aids in the present invention may be of natural or synthetic origin and may be ionic or non-ionic in nature.

[0094] Preferably, the polymeric material is of high molecular weight. The term "high molecular weight" in this particular context generally refers to a polymeric material having a molecular weight of at least 50,000, more preferably at least 500,000 g / mole. A suitable method for determining the molecular weight of the polymeric material is gel permeation chromatography against a polyethylene glycol standard.

[0095] Specific examples of suitable classes of polymeric materials for use as deposition aids in the present invention include:

[0096] Water-soluble high molecular weight linear ethylene oxide homopolymer characterized by the general formula H(OCH2CH2) n OH. These materials are often referred to as polyethylene oxides (or polyoxyethylenes or polyethylene glycols). In the general formula, n generally has an average value of at least 2000, preferably at least 50,000.

[0097] Water-soluble high molecular weight cellulose ethers such as methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, hydroxyethylethylcellulose, sodium carboxymethylcellulose and sodium carboxymethylhydroxyethylcellulose.

[0098] One preferred class of polymeric materials for use as deposition aids in the present invention comprises water-soluble high molecular weight polymers having anionic pendant groups along the polymer backbone.

[0099] Specific examples of such materials include poly(carboxylic acid) polymers.Poly(carboxylic acid) polymers are generally polymers that include -COOH groups or groups derived from -COOH groups (such as salt, ester or anhydride groups) in their structure.

[0100] For example, a poly(carboxylic acid) polymer may include in its structure:

[0101] -[C(R 1)(COOH)-]-unit,

[0102] Where R 1 Selected from hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy or C 1-3 Preferably, R 1 It's hydrogen.

[0103] A preferred type of poly(carboxylic acid) polymer comprises in its structure adjacent:

[0104] -[C(R 1 )(COOH)-]-unit (where R 1 as defined above),

[0105] For example, maleic acid based polymers, which typically include:

[0106] -{-CH(COOH)-CH(COOH)-]- units, and / or salts or esters of such units, or such units in anhydride form,

[0107] wherein the -COOH groups on adjacent carbon atoms are cyclized to form a ring system.

[0108] For example, a poly(carboxylic acid) polymer may comprise units having pairs of carboxylic acid groups on adjacent polymer chain carbon atoms, for example, a polymer comprising in its structure:

[0109] -[-C(R 1 )(R 2 )-C(R 3 )(R 4 )-C(R 5 )(COOH)-C(R 6 )(COOH)-]- units (and / or salts or esters of such units, or such units in anhydride form in which the -COOH groups on adjacent carbon atoms are cyclized to form a ring system);

[0110] Where R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently selected from hydrogen, C 1-3 Alkyl or C 1-3 Preferably, R 1 and R 2 is hydrogen, R 3 is hydrogen, R 4 is a methoxy group, and R 5 and R 6 It's hydrogen.

[0111] Such poly(carboxylic acid) polymers can be described as polymers based on copolymers of methyl vinyl ether and maleic anhydride and are marketed, for example, under the trade name Commercially available.

[0112] Particularly preferred examples of such polymers comprise in their structure:

[0113] -[-CH2-CH(OCH3)-CH(COOH)-CH(COOH)-]- unit,

[0114] wherein the -COOH groups are in the form of free acids. Such polymers may be linear or cross-linked. More preferably, the polymer is linear. Polymers of this type are commercially available, for example, under the trade name Most preferably, the molecular weight of such polymers is at least 500,000 g / mole (e.g. S-96), desirably at least 1,000,000 g / mole (e.g., S-97).

[0115] An alternative polymer that can be used comprises the above described units in anhydride form, i.e. wherein two adjacent -COOH groups are cyclized to form a ring system. Such polymers are available under the trade name AN is commercially available, for example, AN-119, AN-903, AN-139 and AN-169.

[0116] Other alternative polymers that can be used contain the above described units in partial salt form, for example where some of the free -COOH groups are converted into metal salts of Group I or Group II metals such as sodium or calcium, or mixed sodium-calcium salts. Such polymers are available under the trade name MS is commercially available, e.g. MS-955.

[0117] Other alternative polymers that can be used contain the above-described units in the form of partial esters, for example, in which some of the free -COOH groups are replaced by C 1-6 Alkyl (e.g., ethyl or n-butyl) esterification. This polymer is available under the trade name ES is commercially available, for example, ES-225 or ES-425.

[0118] Mixtures of any of the above materials may also be used.

[0119] The amount of deposition aid (as defined above) in the mouthwash composition of the present invention suitably ranges from 0.001 to 5.0%, preferably 0.005 to 4.0%, more preferably 0.01 to 2.0% by total weight of deposition aid (as defined above), based on the total weight of the composition.

[0120] Preferably, the mouthwash composition comprises an anhydride polymer, particularly preferably a copolymer of maleic anhydride and methyl vinyl ether, wherein the anhydride portion may be in a partially or fully hydrolyzed or alcoholyzed form.

[0121] The mouthwash composition may contain low levels of surfactants based on the total weight of the composition. If present, the surfactant is preferably present at a level of less than 3.0 wt %, more preferably at a level of less than 2.0 wt %, most preferably at a level of less than 1.5 wt % of the total composition.

[0122] 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 monoglycerides and diglycerides, and ethylene oxide / propylene oxide block polymers. Preferred nonionic surfactants are ethoxylated polyethylene glycol esters of castor oil, particularly PEG 40 hydrogenated castor oil.

[0123] Other suitable surfactants include amphoteric surfactants such as betaines or sultaines. Mixtures of any of the above materials may also be used.

[0124] Preferably, the mouthwash composition contains no anionic surfactants.

[0125] The mouthwash composition of the present invention may also contain other optional ingredients commonly used in the art, such as fluoride ion sources, antitartar agents, buffers, flavoring agents, stabilizers such as EDTA, sweeteners, colorants, opacifiers, antiallergic agents and antimicrobial agents.

[0126] In the context of the present invention, use of a mouthwash composition typically involves applying the composition to the oral cavity for a recommended period of time before being expectorated. The preferred application time is from 10 to 50 seconds.

[0127] According to a preferred aspect of the present invention, there is provided a rinse-off composition for providing intimate hygiene in and around the vagina, the pH being in the range of 2.5 to 6.0, preferably 2.5 to 4.5, comprising

[0128] (i) Vitamin B3 compounds, their precursors or their analogs;

[0129] (ii) PPAR activation fatty acids;

[0130] (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, cocamidopropyl betaine, sodium cocoyl isethionate, sodium lauroyl isethionate, and sodium methyl lauroyl taurate;

[0131] (iv) carboxylic acid; and

[0132] (v) 40 to 90% by weight of water.

[0133] The above-mentioned wash-off composition of the present invention can also be used in private hygiene products, especially for women to effectively, safely and gently clean the vagina and the vaginal periphery. Such products are usually obtained as liquids prepared at a pH that is gentle to women (when used to obtain private hygiene) containing a certain amount of surfactants and emollients. Such products are also referred to as feminine hygiene products or menstrual hygiene products. Such liquid products usually contain a high water content of 40 to 80% by weight, preferably 50 to 70% by weight. They also contain surfactants, such as anionic and / or amphoteric surfactants. Such surfactants are preferably included in 10 to 50% by weight of the composition, preferably 20 to 40% by weight. The particularly preferred surfactants for such products are triethanolamine lauryl sulfate, ammonium lauryl sulfate, cocamidopropyl betaine or mixtures thereof. Other surfactants that can be additionally included in such products are usually mild surfactants of the type of amphoteric acetate or glucoside. Particularly preferred surfactants of these types are coconut oil amphoteric diacetate disodium, alkyl (e.g., decyl) glucoside and combinations thereof. In addition, the product may include oils, emollients, humectants and thickeners and other additives to help impart a gentle feel to the skin. Suitable humectants that may be included in such compositions are those disclosed above for oral care, such as glycerol, sorbitol or a mixture thereof. Carboxylic acids such as lactic acid and / or citric acid are typically included in such compositions to provide additional hygienic benefits, preferably lactic acid. The pH of such products is typically in the range of 2.5 to 6.0, preferably in the range of 2.5 to 4.5.

[0134] Depending on the type of topical surface to be treated for inactivation or killing of viruses, a suitable antimicrobial agent may be included in the composition of the present invention. Suitable antimicrobial agents may be selected from one or more of the following: salicylic acid, chloroxylenol, bisbalol, zinc pyrithione, octopirox, climbazole, triclosan, triclocarban and cationic compounds such as benzalkonium chloride, dodecyldimethylammonium chloride, cetrimonium chloride and cetylpyridinium chloride.

[0135] It is also within the scope of the invention that the compositions claimed herein do not contain sulfate surfactants. Another aspect relates to the compositions herein that do not contain preservatives. Yet another aspect relates to compositions that do not contain acrylate polymers. The compositions are typically prepared to be packaged and sold in plastic containers. The plastic is preferably of the PCR (post-consumer recycled plastic) type.

[0136] The invention will now be illustrated by the following non-limiting examples. Example

[0137] Example A, 1-3: Effect of 12-HSA on Virus Killing in Skin Keratinocyte Cell Line HaCaT

[0138] The skin keratinocyte cell line HaCaT was differentiated and then treated with 10 μM, 20 μM and 40 μM 12HSA according to a standard experimental protocol, and the treatment was performed for 72 hours. After this treatment, the secretome containing secreted antimicrobial peptides (AMPs) was collected and incubated with the SARS-CoV2 virus for 4 hours. After 4 hours of incubation, the virus killing was counted by using a quantitative PCR-based method. Table 1 below shows the data of viral gene expression as a percentage of the control:

[0139] Table 1

[0140]

[0141] The data in the above table indicate that the secretome produced in the presence of 12HSA is capable of killing / inactivating viruses.

[0142] Examples BD, 4-6: Effects of 12-HSA and Vitamin B3 and Combinations on Epithelial Cells (Calu-3 Cells):

[0143] Compound treatment and plaque formation assay

[0144] SARS-CoV-2 was adsorbed at 0.1 MOI on Calu-3 cells seeded at approximately 120,000 cells / well in 48-well plates for one hour. After washing, fresh medium was added along with nicotinamide (16.4 mM), 12HSA (10 μM), and their respective vehicle controls. After 48 hours, the conditioned medium (containing viral particles) was collected and the plaque forming units (pfu / ml) of each treatment were determined by plaque formation assay on Vero-E6 cells (48-well plates).

[0145] The data are summarized in Table 2 below:

[0146] Table 2

[0147]

[0148] The data in the table above demonstrate that both 12-HSA and nicotinamide are able to inhibit SARS-CoV-2, as evident from the reduction in plaque forming units in the assay used above. The combination of 12-HSA and vitamin B3 significantly improved the inhibition.

[0149] Examples EG, 7-9: Effect of human keratinocyte supernatant on SARS-CoV2 infectivity:

[0150] Differentiated primary human keratinocytes were incubated with the concentrations of nicotinamide and / or 12HSA in serum-free Epilife medium for 72 hours, and the conditioned medium was collected. SARS-Cov-2 virus particles were incubated with the above conditioned medium for about 4 hours. The pfu / ml of these treated virus particles were determined by Plaque or TCID50 using VeroE6 reporter cells. The % infection relative to the control group is shown in Table 3 below:

[0151] Table 3

[0152]

[0153] The data in the above table indicate that similar effects as those in Table 2 can be obtained using primary human keratinocytes.

[0154] Example HN: Effects of some vitamin B3 compounds, their precursors or their analogs on the growth of viruses on skin keratinocytes The impact of killing

[0155] Skin keratinocytes CRL4048 differentiation, then according to standard experimental scheme with various concentrations of vitamin B3 compounds, its precursor or its analog (as shown in Table 4 below) treatment, and treatment for 72 hours.After this treatment, collect the secretion group containing secreted antimicrobial peptides (AMP), and incubate with SARS-CoV2 virus for 4 hours.After incubation for 4 hours, by incubating virus mixture on VeroE6 reporter cell line, and using quantitative PCR-based method to measure infection to count virus killing.Table-4 below shows the data of percentage of viral gene expression as control:

[0156] Table 4

[0157]

[0158]

[0159] The data in Table-4, together with the data in Table-1 above, show that 12HSA is far superior to nicotinamide (Examples I and J), as nicotinamide is ineffective at similar (micromolar) concentrations. When other analogs of vitamin B3 compounds are used (Examples KN), orders of magnitude higher (millimolar rather than micromolar) concentrations are required to kill the virus compared to 12HSA (Examples 1-3 of Table 1).

[0160] Examples P, 10-14: Effects of other PPAR fatty acids on killing viruses in skin keratinocytes

[0161] Other PPAR fatty acids were used to study viral gene expression as shown in Table 5 below. The procedure used to generate the data was similar to that used in Table 4. The data are summarized in Table 5 below:

[0162] Table 5

[0163]

[0164] In the table above, CLA stands for conjugated linoleic acid.

[0165] The data in Table-5 above demonstrate that other PPAR fatty acids (Examples 10-14) are as effective as 12HSA (Examples 1-3 in Table-1) at similar (micromolar) concentrations in viral gene expression.

Claims

1. Use of peroxisome proliferator-activated receptor (PPAR) activating fatty acids for inactivating or killing enveloped viruses on the localized surface 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 for inactivating or killing enveloped viruses on a localized surface of a 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 the care of external body surfaces for inactivating or killing enveloped viruses on the external surfaces of the human or animal body, the composition comprising (i) a PPAR-activating fatty acid and (ii) a cosmetically acceptable carrier selected from a powder, a bar / tablet, a liquid, a gel, an emulsion or a non-aqueous phase.

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

7. Use of a composition for caring for or cleaning mucosal surfaces for inactivating or killing enveloped viruses on mucosal surfaces of the human or animal body, the composition comprising (i) a PPAR-activating fatty acid and (ii) a mucosal acceptable carrier selected from one or more of water, an abrasive, a wetting agent and an emulsifier.

8. Use of a composition as claimed in any one of the preceding claims 5 to 7, further comprising a vitamin B3 compound, a precursor thereof or an analogue thereof.

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

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

11. A mouthwash composition for inactivating enveloped viruses, 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 to 99% by weight of water; (iv) 1 to 20 wt % of a wetting agent; and (v) less than 1.5% by weight of a surfactant selected from nonionic or amphoteric surfactants or mixtures thereof.

12. A rinse-off composition for providing intimate hygiene in and around the vagina having a pH range of 2.5 to 6.0, preferably 2.5 to 4.5, comprising (i) PPAR activation fatty acids; (ii) 0.1 wt% to 50 wt% of an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulfate, ammonium lauryl sulfate, cocamidopropyl betaine, fatty acid isethionate and fatty acyl taurate; (iii) carboxylic acid; and (iv) 40 to 90% by weight of water.

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