WO2024041910A1 - Inactivation or kill of virus and compositions thereof - Google Patents
Inactivation or kill of virus and compositions thereof Download PDFInfo
- Publication number
- WO2024041910A1 WO2024041910A1 PCT/EP2023/072232 EP2023072232W WO2024041910A1 WO 2024041910 A1 WO2024041910 A1 WO 2024041910A1 EP 2023072232 W EP2023072232 W EP 2023072232W WO 2024041910 A1 WO2024041910 A1 WO 2024041910A1
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- WIPO (PCT)
- Prior art keywords
- composition
- fatty acid
- acid
- ppar
- enveloped virus
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- NEOZOXKVMDBOSG-UHFFFAOYSA-N propan-2-yl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OC(C)C NEOZOXKVMDBOSG-UHFFFAOYSA-N 0.000 description 1
- ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
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- BORJONZPSTVSFP-UHFFFAOYSA-N tetradecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCCCOC(=O)C(C)O BORJONZPSTVSFP-UHFFFAOYSA-N 0.000 description 1
- DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 description 1
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- CUXYLFPMQMFGPL-UYWAGRGNSA-N trichosanic acid Natural products CCCCC=C/C=C/C=CCCCCCCCC(=O)O CUXYLFPMQMFGPL-UYWAGRGNSA-N 0.000 description 1
- ICUTUKXCWQYESQ-UHFFFAOYSA-N triclocarban Chemical compound C1=CC(Cl)=CC=C1NC(=O)NC1=CC=C(Cl)C(Cl)=C1 ICUTUKXCWQYESQ-UHFFFAOYSA-N 0.000 description 1
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- 229940082509 xanthan gum Drugs 0.000 description 1
- 229940043810 zinc pyrithione Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- PICXIOQBANWBIZ-UHFFFAOYSA-N zinc;1-oxidopyridine-2-thione Chemical compound [Zn+2].[O-]N1C=CC=CC1=S.[O-]N1C=CC=CC1=S PICXIOQBANWBIZ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
Definitions
- the present invention relates to use of actives and compositions comprising them for treating a surface for inactivation or killing enveloped virus.
- the present invention also relates to certain liquid cleansing and disinfecting compositions and devices for delivering such antiviral action.
- Respiratory infections are considered to be one of the most prevalent cause of disease, worldwide. Globally, acute lower respiratory infections are an important cause of morbidity and mortality in children below 5 years of age. Scientific studies have identified respiratory syncytial virus (RSV), as the most common viral cause of death due to such infection; other prominent viruses being human metapneumovirus, parainfluenza viruses, influenza viruses A and B, adenoviruses and of recent origin coronavirus. Several tens of millions of such infections are reported every year leading to more than half a million deaths in children below the age of five, largely in low and middle income households.
- RSV respiratory syncytial virus
- Virus as discussed above are known to transmit through respiratory aerosol drops or by touching with infected hands and even through inanimate surfaces.
- hand hygiene is a commonly recommended method of killing such germs and thereby reducing the risk of not only respiratory infection but also gastrointestinal diseases.
- Hand hygiene includes use of soap and running water to wash the hands which makes it not only free of dirt but also in washing away and killing germs including bacteria and virus.
- alcohol-based hand sanitizers which contain very little water may be rubbed on the hands as another effective means of removing virus and bacteria from hands. While such methods are very good in instantaneously killing the germs they are sometimes considered harsh. There is thus a need for actives and compositions that are mild on skin and other external and mucosal surfaces but are sufficiently effective in killing or inactivating virus to prevent or mitigate infection.
- PPAR peroxisome proliferator-activated receptor activating fatty acid which they have now found to kill or inactivate enveloped virus, which heretofore was not known before. Further, they found that it synergizes with a specific vitamin viz. Vitamin B3 or its precursors or analogue thereof to deliver enhanced antiviral activity. Further they also found that vitamin B3 or its precursors or analogues thereof in itself can also deliver such activity.
- PPAR fatty acid as per this invention includes fatty acids which have a PPAR action and also includes their corresponding mono, di and triglyceride forms.
- the first aspect of the present invention relates to use of a peroxisome proliferator-activated receptor (PPAR) activating fatty acid for inactivation or kill of enveloped virus on topical surface of a human or animal body.
- PPAR peroxisome proliferator-activated receptor
- a preferred aspect of the present invention relates to use of a composition
- a composition comprising (i) a vitamin B3 compound or its precursors or analogue thereof and (ii) a peroxisome proliferator- activated receptor (PPAR) activating fatty acid for inactivation or kill of enveloped virus on topical surface of a human or animal body.
- PPAR peroxisome proliferator- activated receptor
- Another aspect of the present invention relates to a mouthwash composition for inactivating enveloped virus comprising
- An even further aspect of the present invention relates to a wash-off composition having a pH in the range of 2.5 to 6.0 preferably 2.5 to 4.5 for providing intimate hygiene in and around the vagina comprising (i) a PPAR activating fatty acid;
- an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulphate, ammonium lauryl sulphate, cocoamidopropyl betaine, fatty acid isethionate, and fatty acyl taurate;
- Yet another aspect of the present invention relates to use of a vitamin B3 compound or its precursors or analogue thereof for inactivation of enveloped virus on topical surface of a human or animal body.
- the present invention may be used to inactivate or kill virus especially enveloped virus on topical surface of a human body or animal body.
- the surface is therefore an animate surface.
- Animate surfaces include the external surfaces of living organisms like plants and animals including humans. Due to the rich availability of nutrients and water on most animate surfaces, germs reside and are capable of multiplying on such surfaces.
- the present invention is used against virus infection on any type of animate surface.
- the invention is especially useful for prevention or kill of virus on topical surface of a human body.
- Topical surfaces as per the present invention includes external surfaces as well as mucosal surfaces.
- External surface as per the present invention includes skin on any external part of the body including scalp and hair.
- Mucosal surface as per the present invention includes surfaces in the oral cavity, and that of the vagina.
- the present invention may be used through a leave-on composition or a wash-off composition.
- a leave-on composition is meant a composition which is applied on the external surface of the human body and allowed to remain thereon till the person goes for a shower or a bath usually after several hours or after a day.
- a wash-off composition is meant that the composition is used to wash the external surface of the body e.g with a soap composition, a body wash, a face wash, a shampoo or a hair conditioning composition with copious amount of water such that substantial amount of dirt and oils are washed off the surface of the body leaving it clean.
- wash off compositions generally contain sufficient amounts of surfactants that enable the wash-off action.
- the present invention relates to use of a vitamin B3 compound, its precursors or analogue thereof for inactivation of enveloped virus on topical surface of a human or animal body.
- the use is preferably non-therapeutic.
- the enveloped virus is preferably SARS-Cov2.
- the present invention relates to use of a PPAR activating fatty acid for inactivation or kill of enveloped virus on topical surface if a human or animal body.
- the use is preferably non- therapeutic.
- the present invention is also capable of preventing reinfection of the topical surface through use of one or more of the actives claimed in the present invention for inactivation or kill of enveloped virus on these surfaces.
- actives claimed in the present invention for inactivation or kill of enveloped virus on these surfaces.
- Enveloped virus as per the present invention includes a coronavirus or an influenza virus.
- Preferred coronavirus which may treated as per the present invention is SARS-Cov2.
- Preferred influenza virus which may be treated as per the present invention is H1 N1.
- Other enveloped virus which may be treated as per the present invention include RSV (respiratory syncytial virus) and HSV (herpes simplex virus).
- Peroxisome proliferator-activated receptors are transcription factors that control lipid metabolism. There are three isotypes PPARa PPARp/8 and PPARYy all of which have been localised in the skin. A range of specific fatty acids activates these factors resulting in anti-inflammatory action to reduce cutaneous irritation responses and pro- differentiation/antiproliferation responses to normalise skin metabolism and provide additional skin-care benefits. It is particularly desirable to select PPAR fatty acids containing a hydroxyl and/or methyl side chain. Many such acids contain from 14 to 30 carbons.
- Examples of PPAR fatty acids with demonstrated PPAR activating activity are cis-parinaric acid, cis-9-trans-11 conjugated linoleic acid, columbinic acid, docosahexaenoic acid, eicosapentanoic acid, hexadecatrienoic acid, linolenelaidic acid (isomer of linolenic acid), petroselinic acid, pinolenic acid, punicic acid, ricinoleic acid, ricinolaidic acid (isomer of ricinoleic acid), stearidonic acid, trans-10-cis-12 conjugated linoleic acid, 7-trans octadecanoic acid, vaccenic acid, octadecene dioic acid and hydroxystearic acids.
- a PPAR fatty acid as per this invention also includes hydrolysable PPAR precursors.
- Potential source of hydrolysable PPAR precursors include triglycerides such as coriander seed oil for petroselinic acid, impatiens balsimina seed oil, parinarium laurinarium kernel fat or sabastiana brasilinensis seed oil for cis-parinaric acid, dehydrated castor seed oil for conjugated linoleic acids, and aquilegia vulgaris oil for columbinic acid.
- a single hydrolysable precursor of a PPAR activating fatty acid is employed, it specifically excludes borage oil, castor oil and sunflower seed oil.
- the PPAR acid contains 16 or 18 carbon atoms.
- An especially preferred PPAR acid is hydroxy stearic acids or esters thereof. Most preferred PPAR acid is hydroxy stearic acids.
- the hydroxystearic acid is 10- hydroxy stearic acid, 12-hydroxystearic acid or trihydoxystearic acid (e.g. 9, 10,13-tri hydroxy stearic acid) or trihydroxy stearin or compounds that yield one or more molecules of hydroxy stearic acid or hydroxystearate on their breakdown like mono, di or tri ester of glycerol with hydroxystearic acid.
- 10-hydroxystearic acid, 12-hydroxystearic acid and 9,10,13-trihydroxystearic acid are more preferred, 12- hydroxystearic acid (12-HSA) being most preferred.
- 12-HSA has the structure as given below: It is preferred that the PPAR activating fatty acid for use in any aspect of the present invention is also a Caspase 8 regulator.
- a composition as per the invention may additionally comprise an antimicrobial peptide (AMP).
- AMP antimicrobial peptide
- a further preferred aspect refers to use of a composition as per the invention which additionally comprises an anti-microbial peptide.
- the preferred AMP is LL37.
- a preferred aspect of the present invention relates to use of a composition
- a composition comprising (i) a vitamin B3 compound, its precursor or analogue thereof and (ii) a peroxisome proliferator- activated receptor (PPAR) activating fatty acid for inactivation or kill of enveloped virus on topical surface of a human or animal body.
- PPAR peroxisome proliferator- activated receptor
- Yet another aspect of the present invention relates to use of a PPAR-activating fatty acid as an enveloped virus killing or inactivating agent in a composition also comprising a vitamin B3 compound, its precursor or analogue thereof.
- Yet another aspect relates to use of a combination of a PPAR-activating fatty acid and a vitamin B3 compound, its precursor or analogue thereof in a topical composition as an enveloped-virus-killing or inactivating system.
- the vitamin B3 compound, its precursor or analogue thereof is selected from one or more of tryptophan, niacin, nicotinic acid, isonicotinamide, picolinamide, and nicotinamide (which is also known as niacinamide). It is preferably niacinamide.
- Niacinamide also known as pyridine- 3-carboxamide is the active, water soluble form of vitamin B3.
- Analogues of vitamin B3, as per this invention also includes derivatives like cyclo alkyl nicotinamide with the cyclo alkyl group having 3 to 6 carbon atoms.
- niacinamide When included in the composition of the present invention comprises an effective amount of niacinamide, typically is in a concentration of 0.05 to 3%, preferably in 0.1 to 2% weight of the composition. In such a composition hydroxystearic acid is preferably included in 0.05 to 3%, more preferably 0.1 to 2%, by weight of the composition.
- the actives claimed in the present invention viz. the PPAR fatty acid e.g. 12-HSA activates host cells to help drive the defense benefit against non-enveloped viruses like SARS-Cov2. They believe that this mode of action is quite different from direct antivirals like low boiling alcohols, bleaches and cationic surfactants like quaternary ammonium compounds which act directly on the virus particle to inactivate them thereby delivering the anti-viral benefit.
- the actives claimed in the present invention viz. the PPAR fatty acid e.g. 12-HSA activates host cells to help drive the defense benefit against non-enveloped viruses like SARS-Cov2. They believe that this mode of action is quite different from direct antivirals like low boiling alcohols, bleaches and cationic surfactants like quaternary ammonium compounds which act directly on the virus particle to inactivate them thereby delivering the anti-viral benefit.
- Yet another aspect of the present invention relates to use of a composition for care of external surface of a body 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, for inactivation or kill of enveloped virus on the external surface of a human or animal body.
- a cosmetically acceptable carrier selected from a powder, a bar/ tablet, a liquid, a gel, an emulsion or an anhydrous phase, for inactivation or kill of enveloped virus on the external surface of a human or animal body.
- the use is preferably non-therapeutic.
- Such a composition may additionally comprise a vitamin B3 compound, its precursor or an analogue thereof.
- Yet another aspect of the present invention relates to use of a skin care composition
- a skin care composition comprising (i) a vitamin B3 compound, its precursors or analogue thereof and (ii) a cosmetically acceptable carrier selected from a liquid, a gel, an emulsion or an anhydrous phase, for inactivation of enveloped virus on a topical surface of a human or animal body.
- the use is preferably non-therapeutic.
- Yet another aspect of the present invention relates to use of a skin cleansing composition
- a skin cleansing composition comprising (i) a vitamin B3 compound, its precursors or analogue thereof and (ii) a cosmetically acceptable carrier comprising 5 to 80% surfactant selected from a synthetic surfactant or soap, for inactivation of enveloped virus on a topical surface of a human or animal body.
- the use is preferably non-therapeutic.
- an oral care composition comprising (i) a vitamin B3 compound, its precursors or analogue thereof and (ii) an orally acceptable carrier selected from water, an abrasive, a humectant, an emulsifier or mixtures thereof, for inactivation of enveloped virus in the oral cavity of a human or animal body.
- the use is preferably non-therapeutic.
- the cosmetically acceptable carrier as per the above aspect of the present composition may preferably be delivered as an emulsion e.g. as a cream or a lotion or in gel form preferably in cream form.
- a preferred format for the solid form of the composition is a cream, further more preferably one which has a vanishing cream base.
- Vanishing cream base is one which comprises 3 to 25 wt% fatty acid.
- the composition may comprise 0.1 to 10 wt% soap.
- the fatty acid is preferably a C10 to C22 fatty acid, more preferably a C16 to C18 fatty acid.
- the fatty acids are stearic acid or palmitic acid or a mixture thereof and the soap is preferably the potassium salt of the fatty acid mixture.
- the fatty acid is often hystric acid which is substantially (generally about 90 to 95 %) a mixture of 45 % stearic acid and 55 % palmitic acid.
- the most preferred cream is one having 3 to 25 wt% fatty acid and 0.1 to 10 wt% soap.
- the cosmetically acceptable carrier in the above composition comprises emollients.
- emollients that may be used in the leave-on composition include stearyl alcohol, glyceryl monoricinoleate, mink oil, isopropyl isostearate, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, din-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cotton seed oil, olive oil, palm kernel oil, rape
- the cosmetically acceptable carrier in above composition comprises solvents.
- solvents that may be used in the composition include ethyl alcohol, isopropanol, acetone, ethylene glycol mono ethyl ether, diethylene glycol mono butyl ether, diethylene glycol mono ethyl ether and mixtures thereof.
- the composition may comprise polyhydric alcohols which may be selected from one or more of glycerine, 1 ,3-butylene glycol, propylene glycol, 1 ,3-propanediol, pentylene glycol, hexylene glycol, and sorbitol.
- the cosmetically acceptable carrier in the above composition comprises powders.
- powders that may be used in the composition include chalk, talc, fullers earth, kaolin, starch, gums, colloidal silica sodium polyacrylate, tetra alkyl and/or trialkyl aryl ammonium smectites, chemically modified magnesium aluminium silicate, organically modified montmorillonite clay, hydrated aluminium silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate and mixtures thereof.
- a composition for cleansing of external surfaces of a body comprising (i) a PPAR activating fatty acid and (ii) a cosmetically acceptable vehicle comprising 0.1% to 80 wt% surfactant selected from a synthetic surfactant or soap, for inactivation or kill of enveloped virus on the external surface of a human or animal body.
- the use is preferably non-therapeutic.
- Such a composition may additionally comprise a vitamin B3 compound, its precursor or an analogue thereof.
- Such a composition is generally known as a cleansing composition.
- a cleansing composition as used herein, is meant to include a composition for topical application to skin, hair and/or scalp of mammals, especially humans. Such a composition is generally applied on to the desired topical surface of the body for a period of time from a few seconds to up to a few minutes generally after diluting with water. After this period of time of application, the composition is generally rinsed off with water or wiped away. It includes any product applied to a human body for also improving appearance, odor control or general aesthetics.
- the composition of the present invention can be in the form of a liquid, lotion, cream, foam, scrub, gel, shampoo, conditioner, handwash, facewash or bodywash product.
- the cosmetically acceptable vehicle generally comprises water in addition to surfactant.
- a particularly preferred surfactant is an anionic surfactant like soap.
- the soap for preparing the cleansing composition of the invention is preferably a C8-C24 soap, more preferably C10-C20 soap and most preferably C12-C18 soap.
- the cation of the soap can be alkali metal, alkaline earth metal or ammonium.
- 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 groundnut, soybean, tallow, palm, palm kernel, etc. may also be used in other desired proportions.
- a cosmetically acceptable vehicle comprising generally forms 80 to 99% by weight of the cleansing composition.
- the anionic surfactant e.g. soap
- the anionic surfactant is preferably present in an amount of 1 to 90%, preferably from 10 to 85%, more preferably 25 to 75% by weight of the cleansing composition.
- the cleansing composition is preferably in the form of a solid or semi solid form, most preferably in a solid form.
- Preferred solid compositions are in the shape of a soap bar.
- anionic surfactants are preferably selected from alkyl ether sulphate, primary alkyl sulphate, secondary alkyl sulphonates, alkyl benzene sulphonates, or ethoxylated alkyl sulphates.
- the anionic surfactant other than soap which is preferred in the cleansing composition is an alkyl ether sulphate preferably those having between 1 and 3 ethylene oxide groups, either from natural or synthetic source and/or sulphonic acid. Especially preferred are sodium lauryl ether sulphates.
- Alkyl polyglucoside may also be present in the composition, preferably those having a carbon chain length between Ce and Ci6.
- Preferred cleansing compositions may include other known ingredients such as perfumes, pigments, preservatives, emollients, sunscreens, gelling agents and thickening agents. Choice of these ingredients will largely depend on the format of the composition.
- Water is a preferred carrier. When water is present, it is preferably present in at least 1 %, more preferably at least 2%, furthermore preferably at least 5% by weight of the composition.
- a preferred cleansing composition comprises 10 to 50%, more preferably 12 to 40%, further more preferably from 12 to 25% by weight water.
- the cleansing composition of the invention may also be delivered through a moisturizing bar or a moisturizing liquid composition.
- Moisturizing bar compositions comprising fatty acyl isethionates (e.g. cocyl isethionate) are especially preferred.
- Fatty acyl isethionates e.g., cocoyl isethionates
- 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.
- fatty acid isethionate surfactant products are produced by esterification of fatty acids or by reaction of fatty acid chloride having carbon chain length of C8 to C20 with isethionate.
- a typical surfactant product containing fatty acyl isethionate contains about 40 to 95 wt.% acid isethionate, and 5 to 50 wt.%, typically 10 to 40 wt.% free fatty acid, in addition to isethionate salts, typically at less than 5%, and trace (less than 2 wt.%) of other additives.
- Such compositions may also include an alkyl taurates, e.g., alkyl taurate amides.
- alkyl taurate amides may be made by reaction of a taurine; methyl taurine; or a corresponding taurate salt (e.g., NH2CH2CH2SO3 M+, where M+ may be sodium or potassium counterion) with the appropriate fatty acid.
- alkyl taurate amides include sodium methyl cocoyl taurate and sodium methyl lauroyl taurate.
- Fatty acid soap may be included in the range of 5 to 15 wt%.
- Other surfactants like betaines may be included in 1 to 5 wt%.
- Water is generally included in 2 to 8 wt% of the composition.
- a composition for care or cleansing of mucosal surfaces comprising (i) PPAR activating fatty acid and (ii) a mucosally acceptable carrier selected from one or more of water, an abrasive, a humectant, and an emulsifier, for inactivation or kill of enveloped virus on mucosal surface of a human or animal body.
- a mucosally acceptable carrier selected from one or more of water, an abrasive, a humectant, and an emulsifier, for inactivation or kill of enveloped virus on mucosal surface of a human or animal body.
- the use is preferably non-therapeutic.
- Such a composition may additionally comprise a vitamin B3 compound, its precursor or an analogue thereof.
- the mucosally acceptable carrier is often termed as a orally acceptable carrier.
- More preferred orally acceptable carrier includes an abrasive, a humectant or mixtures thereof.
- the orally acceptable carrier preferably is included in as much as 99.8%, more preferably at as much as 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.
- the oral care composition of the present invention may be delivered in the form of an ointment, a gel, a dentifrice or a mouthwash.
- Dentifrices include forms like toothpaste and toothpowder.
- a composition is most preferably presented in the form of a toothpaste, a toothpowder or a mouthwash.
- Oral care composition of the present invention preferably comprises an abrasive.
- the abrasive may preferably be calcium carbonate or silica.
- Gels usually contain silica, whereas opaque creams generally contain calcium based abrasives, especially chalk (calcium carbonate).
- opaque toothpastes the compositions have 5 to 60 wt% calcium based abrasive. In more preferred compositions it is 30 to 60 wt% and furthermore preferably from 35 to 55 wt%.
- Optimal compositions have 40 to 55 wt% calcium based abrasive.
- Suitable humectants are preferably used in the oral care composition of the present invention and they include, for example, glycerin, sorbitol, propylene glycol, dipropylene glycol, diglycerol, triacetin, mineral oil, polyethylene glycol (preferably, PEG-400), alkane diols (like butane diol and hexanediol, ethanol, pentylene glycol, or a mixture thereof.
- Glycerin, polyethylene glycol, sorbitol or mixtures thereof are the preferred humectants, most preferred ones being glycerol (also known as glycerine) and sorbitol.
- the humectant may be present in the range of from 10 to 90% by weight of oral care compositions. More preferably, the humectant makes up from 25 to 80%, and most preferably, from 45 to 70% by weight of the composition, based on total weight of the composition and including all ranges subsumed therein.
- an oral care composition comprises a surfactant.
- the composition comprises at least 0.01% surfactant by weight of the composition, more preferably at least 0.1 % and most preferably from 0.5 to 7%.
- Suitable surfactants include anionic surfactants, such as the sodium, magnesium, ammonium or ethanolamine salts of C8 to C18 alkyl sulphates (for example sodium lauryl sulphate), 08 to 018 alkyl sulphosuccinates (for example dioctyl sodium sulphosuccinate), 08 to 018 alkyl sulphoacetates (such as sodium lauryl sulphoacetate), 08 to 018 alkyl sarcosinates (such as sodium lauryl sarcosinate), 08 to 018 alkyl phosphates (which can optionally comprise up to 10 ethylene oxide and/or propylene oxide units) and sulphated monoglycerides.
- anionic surfactants such as the sodium, magnesium, ammonium
- the surfactant comprises or is an anionic surfactant.
- the preferred surfactants are sodium lauryl sulphate and/or sodium dodecylbenzene sulfonate. Most preferably the surfactant is sodium lauryl sulphate.
- 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 sulphobetaines. Mixtures of any of the above described materials may also be used.
- Most preferred surfactants are an alkali metal alkyl sulphate or a betaine.
- the composition comprises a thickener.
- Thickeners that may be used in this invention include, sodium carboxymethyl cellulose (SCMC), hydroxyl ethyl cellulose, methyl cellulose, ethyl cellulose, gum tragacanth, gum arabic, gum karaya, xanthan gum, sodium alginate, carrageenan gum, guar gum, Irish moss, starch, modified starch, silica based thickeners including silica aerogels, magnesium aluminum silicate (e.g., Veegum), Carbomers (cross-linked acrylates) and mixtures thereof.
- thickening silica, sodium carboxymethyl cellulose and/or a Carbomer is/are preferred thickeners for use in the composition of the invention.
- Thickening silica is especially preferred to be used in gel toothpastes.
- Gel toothpastes generally contain upto 8.5 wt% thickening silica whereas opaque toothpastes typically contain 3 to 4 wt% thickening silica.
- Thickener when present, preferably makes up from 0.01 to about 10%, more preferably from 0.1 to 9%, and most preferably, from 1.5 to 8% by weight of the composition.
- Water may preferably be included in 5 to 95%, in particular 10 to 75%, and especially at from 10 to 60%, furthermore preferably 10 to 45% by total weight of the composition.
- the oral care composition of this invention is a toothpaste or gel
- the same typically has a viscosity from about 30,000 to 180,000 centipoise, and preferably, from 60,000 to 170,000 centipoise, and most preferably, from 65,000 to 165,000 centipoise.
- the oral care composition of the present invention may contain a variety of other ingredients which are common in the art to enhance physical properties and performance. These ingredients include antimicrobial, anti-caries agents, plaque buffers, fluoride sources, vitamins, plant extracts, desensitizing agents, anti-calculus agents, biomolecules, flavors, proteinaceous materials, preservatives, opacifying agents, coloring agents, pH-adjusting agents, sweetening agents, particulate abrasive materials, polymeric compounds, buffers and salts to buffer the pH and ionic strength of the compositions, and mixtures thereof. Such ingredients typically and collectively make-up less than 20% by weight of the composition, and preferably, from 0.0 to 15% by weight, and most preferably, from 0.01 to 12% by weight of the composition, including all ranges subsumed therein.
- the present invention also relates to a method of inactivating or killing an enveloped virus on a topical surface of a human or animal body comprising the step of exposing the desired topical surface to a PPAR activating fatty acid; or compositions thereof.
- the method also includes an aspect wherein the composition additionally comprises a vitamin B3 compound, its precursor or analogue thereof.
- the method as per the present invention is for cosmetic use i.e. it is for non-therapeutic applications.
- Yet another aspect of the present invention relates to a method of inactivating an enveloped virus on a topical surface of a human or animal body comprising the step of applying a vitamin B3 compound, its precursors or analogues thereof; or compositions thereof on to the desired topical surface.
- a mouthwash composition for inactivating enveloped virus comprising
- a mouthwash composition of the invention is meant that the composition is used to wash the mouth. It may be in the form of a liquid which is used by a consumer in small quantity say 5 to 30 ml in the mouth and throat to wash the mouth free of germs or used to gargle in the mouth or throat for the same purpose. Such a liquid mouth composition may be used as such i.e without any dilution with water or may be diluted with water in a ratio of 1 :0.5 to 1 :10 before washing the mouth. After the mouthwash composition, with or without dilution, is used to rinse the oral cavity or gargled in the mouth and throat for about 10 second to about two minutes, it is usually spat out.
- Mouth wash as per this invention also includes a liquid spay which is delivered to the mouth from a container fitted with a spray pump.
- the mouthwash composition of the invention is in the form of a liquid mouthwash composition or a spray composition, of which the liquid mouthwash composition is particularly preferred.
- liquid mouthwash composition generally denotes liquid formulations which are used to rinse the surfaces of the oral cavity and provide the user with a sensation of oral cleanliness and refreshment.
- the mouthwash is an oral composition that is not intentionally swallowed for purposes of systemic administration of therapeutic agents, but is applied to the oral cavity, used to treat the oral cavity and then expectorated.
- Mouthwash compositions according to the invention preferably comprise an aqueous base.
- the amount of water generally ranges from 70 to 99% by weight based on the total weight of the mouthwash.
- a mouthwash composition according to the invention will generally contain further ingredients to enhance performance and/or consumer acceptability, such as humectants and surfactants.
- the amount of humectant generally ranges from 1.0 to 20%, more preferably from 1.5 to 5% by weight based on the total weight of the mouthwash.
- Preferred humectants that are present at the above levels include polyols, more preferred is sorbitol and/or glycerol, glycerol is particularly preferred. It is preferable if the level of ethanol in the mouthwash composition is less than 0.1 wt%.
- Mouthwash compositions of the invention may comprise a preservative, preferred preservatives are benzyl alcohol, and phenoxyethanol.
- preferred preservatives are benzyl alcohol, and phenoxyethanol.
- the level of preservative is from 0.1 to 1 wt% of the total composition.
- the mouthwash composition of the invention may comprise a deposition aid.
- deposition aid in the context of this invention generally means a material which aids deposition of anti-bacterial agents from the composition. Suitable deposition aids for use in the invention will generally dissolve or disperse in water at a temperature of 25°C.
- Preferred deposition aids for use in the 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 10g/L at 25°C, and more preferably at least 30g/L at 25°C (where the solubility is determined in un-buffered distilled water). It is particularly preferable that the deposition aid remains water soluble after drying, so that it can be re-dissolved. This prevents undesirable build up of the deposition aid on the teeth after repeated usage of the composition.
- Suitable deposition aids for use in the invention include polymeric materials, preferably polymeric materials which are water soluble as defined above.
- Polymeric materials for use as deposition aids in the invention may be naturally or synthetically-derived, and may be ionic or nonionic in nature.
- polymeric materials are high molecular weight.
- 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 to determine the molecular weight of such polymeric materials is gel permeation chromatography against a polyethylene glycol standard.
- suitable classes of polymeric material for use as deposition aids in the invention include:
- n Water-soluble, high molecular weight linear homopolymers of ethylene oxide characterised by the general formula H(OCH2CH2)n OH. These materials are generally termed polyethyleneoxides (or alternatively, polyoxyethylenes, or polyethylene glycols). In the general formula, n usually has an average value of at least 2000, preferably at least 50,000.
- Water-soluble, high molecular weight cellulose ethers such as methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxybutyl methylcellulose, hydroxyethyl ethylcellulose, sodium carboxymethylcellulose, and sodium carboxymethyl hydroxyethylcellulose.
- a preferred class of polymeric material for use as deposition aids in the invention includes water-soluble, high molecular weight polymers having anionic side groups along the polymer main chain.
- poly(carboxylic acid) polymers include poly(carboxylic acid) polymers.
- Poly (carboxylic acid) polymers are typically polymers which include -COOH groups in their structure, or groups which are derived from -COOH groups such as salt, ester or anhydride groups.
- the poly(carboxylic acid) polymers may include:
- R 1 is selected from hydrogen, C1-3 alkyl, C1-3 alkoxy or C1-3 hydroxyalkyl.
- R 1 is hydrogen.
- a preferred type of poly (carboxylic acid) polymer includes adjacent:
- poly(carboxylic acid) polymers may comprise units with pairs of carboxylic acid groups on adjacent polymer chain carbon atoms, for example polymers comprising:
- R 1 ,R 2 ,R 3 ,R 4 ,R 5 and R 6 are each independently selected from hydrogen, C1-3 alkyl or C1-3 alkoxy.
- R 1 and R 2 are hydrogen
- R 3 is hydrogen
- R 4 is methoxy
- R 5 and R 6 are hydrogen.
- Such a poly(carboxylic acid) polymer may be described as the polymer based on a copolymer of methyl vinyl ether and maleic anhydride, and is commercially available for example under the trade name Gantrez®.
- a particularly preferred example of such a polymer comprises:
- 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 Gantrez® S. Most preferably such a polymer has 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).
- Alternative polymers which may be used comprise the units as described above in anhydride form, i.e. in which the two adjacent -COOH groups are cyclised to form a ring system.
- Such polymers are commercially available under the tradename Gantrez® AN, e.g. Gantrez® AN- 119, Gantrez® AN-903, Gantrez® AN-139 and Gantrez® AN-169.
- Other alternative polymers which may be used comprise the units as described above in partial salt form, for example in which some of the free -COOH groups are converted into a metal salt of a Group I or Group II metal such as either sodium or calcium, or a mixed sodiumcalcium salt.
- Such polymers are commercially available under the tradename Gantrez® MS, e.g. Gantrez® MS-955.
- Such polymers are commercially available under the tradename Gantrez® ES, e.g. Gantrez® ES-225 or Gantrez® ES-425.
- the amount of deposition aid (as defined above) in mouthwash compositions of the invention suitably ranges from 0.001 to 5.0%, preferably from 0.005 to 4.0%, more preferably from 0.01 to 2.0% by total weight deposition aid (as defined above) based on the total weight of the composition.
- the mouthwash composition comprises an acid anhydride polymer, particularly preferred are co-polymers of maleic anhydride with methyl vinylether, in which the anhydride moiety may be in a partially or fully hydrolysed or alcoholysed form.
- 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 levels of less than 3.0 wt% of the total composition, more preferably at levels less than 2.0 wt%, most preferably at levels of less than 1.5 wt%.
- Suitable surfactants for use in the invention comprises 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.
- Other suitable surfactants include amphoteric surfactants, such as betaines or sulphobetaines. Mixtures of any of the above described materials may also be used.
- the mouthwash composition is free of anionic surfactants.
- Mouthwash compositions of the present invention may also contain further optional ingredients customary in the art such as fluoride ion sources, anticalculus agents, buffers, flavouring agents, stability agents such as EDTA, sweetening agents, colouring agents, opacifying agents, antisensitivity agents and antimicrobial agents.
- fluoride ion sources such as fluoride ion sources, anticalculus agents, buffers, flavouring agents, stability agents such as EDTA, sweetening agents, colouring agents, opacifying agents, antisensitivity agents and antimicrobial agents.
- Use of the mouthwash composition in the context of this invention typically involves application of the composition to the oral cavity, for a recommended time period before being expectorated. Preferred application times are from 10 to 50 seconds.
- a wash-off composition having a pH in the range of 2.5 to 6.0 preferably 2.5 to 4.5 for providing intimate hygiene in and around the vagina comprising
- an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulphate, ammonium lauryl sulphate, cocoamidopropyl betaine, sodium cocoyl isethionate, sodium lauroyl isethionate, sodium methyl lauroyl taurate;
- the above wash-off composition of the invention may also be used in intimate hygiene products esp. for use by women for effective, safe and mild wash in and around the vagina.
- Such products are generally available as a liquid with certain amount of surfactants and emollients formulated at a pH which is mild on women when used for obtaining intimate hygiene.
- Such products are also known as feminine hygiene products or menstrual hygiene products.
- Such liquid products generally comprise high amount of water in the range of 40 to 80 wt%, preferably 50 to 70 wt%. They further comprise surfactants e.g. an anionic and/ or amphoteric surfactants.
- surfactants are preferred to be included in 10 to 50 wt% preferably 20 to 40 wt% of the composition.
- surfactant for use in such products is triethanolamine lauryl sulphate, ammonium lauryl sulphate, cocoamidopropyl betaine or mixtures thereof.
- Other surfactants in addition which may be included in such products are generally mild surfactants of the amphoacetate or glucoside types. Especially preferred surfactants of these types are disodium cocoamphodiacetate, alkyl e.g. decyl glucoside and combinations thereof.
- the product may comprise oils, emollients, humectants and thickeners and other additives to aid in giving a mild sensation to the skin.
- Suitable humectant which may be included in such compositions are those disclosed hereinabove for oral care like glycerol, sorbitol or mixtures thereof.
- Carboxylic acids like lactic acid and/or citric acid are generally included in such compositions to provide additional hygiene benefits, preferably lactic acid.
- the pH of such products is generally in the range of 2.5 to 6.0 preferably in the range of 2.5 to 4.5.
- Suitable antimicrobial agent may be selected from one or more of salicylic acid, chloroxylenol, bisbalol, zinc pyrithione, octopirox, climbazole, triclosan, trichlocarban and cationic compounds like benzalkonium chloride, dodecyl dimonium chloride, cetrimonium chloride, and cetyl pyridinium chloride.
- compositions claimed here are free of sulphate surfactants.
- compositions herein that are free of preservatives are free of acrylate polymers.
- the compositions are generally prepared to be packaged and sold in plastic containers.
- the plastic is preferably of the PCR type (post-consumer recycled plastic)
- Example A, 1-3 Effect of 12-HSA on virus kill on skin keratinocyte cell line HaCaT
- Skin keratinocyte cell line HaCaT were differentiated and then treated with 10 .M, 20 .M and 40 .M of 12HSA and treatment was done for 72 hrs, following standard protocols. Post this treatment the secretome that contains the secreted anti-microbial peptides (AMPs) was collected and was incubated with SARS-CoV2 virus for 4hrs. After the 4hrs of incubation, the virus kill was enumerated by using quantitative PCR based methods. The data on the viral gene expression as a percentage of control is shown in table -1 below:
- the data in the table above indicates that the secretome generated in the presence of 12HSA is capable of ki lling/inactivati ng the virus.
- Example B-D,4-6 Effect of 12-HSA and vitamin B3 and a combination on epithelial cells (Calu-3 cells):
- 0.1 MOI SARS-CoV-2 was allowed to adsorb on Calu-3 cells, plated in a 48 well plate with about 120,000 cells/well, for one hour. After washing, fresh media was added along with niacinamide (16.4 mM), 12HSA (10 .M), and their respective vehicle controls. After 48 hrs, the conditioned media (containing the virus particles) were collected and plaque forming unit (pfu/ml) was determined for each treatment by performing plaque formation assay on Vero- E6 cells (48 well plate).
- Example E-G.7-9 Effect of human keratinocytes supernatant on SARS-CoV2 infectivity:
- Differentiated primary human keratinocytes were incubated in serum free Epilife media with the mentioned concentrations of niacinamide and/or 12HSA for 72 hr and conditioned media was harvested.
- the SARS-Cov-2 virus particles were incubated for about 4 hrs with the above mentioned conditioned media.
- the pfu/ml of these treated virus particles was determined using VeroE6 reporter cells through Plaque or TCID50. The % infection with respect to the control is shown in Table - 3 below:
- Table - 3 The data in the above table indicates that effect similar to that in Table -2 could be obtained with primary human keratinocytes also.
- Example H-N Effect of some vitamin B3 compound its precursor or analogue thereof on virus kill on skin keratinocyte cell line
- Skin keratinocyte cell line CRL4048 were differentiated and then treated with various concentrations of vitamin B3 compound its precursor or analogue thereof as shown in Table 4 below and treatment was done for 72 hrs, following standard protocols. Post this treatment the secretome that contains the secreted anti-microbial peptides (AMPs) was collected and was incubated with SARS-CoV2 virus for 4hrs. After the 4hrs of incubation, the virus kill was enumerated by incubating the virus mixture on the VeroE6 reporter cell line, and using quantitative PCR based method for measuring the infection. The data on the viral gene expression as a percentage of control is shown in table -4 below:
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Abstract
The present invention relates to use of actives and compositions comprising them for treating a surface for inactivation or killing enveloped virus. The present invention also relates to certain liquid cleansing and disinfecting compositions for delivering such antiviral action. This is achieved using a PPAR activating fatty acid optionally in combination with a vitamin B3 compound.
Description
J2421 CPL 1
INACTIVATION OR KILL OF VIRUS AND COMPOSITIONS THEREOF
Field of the invention
The present invention relates to use of actives and compositions comprising them for treating a surface for inactivation or killing enveloped virus. The present invention also relates to certain liquid cleansing and disinfecting compositions and devices for delivering such antiviral action.
Background of the invention
Respiratory infections are considered to be one of the most prevalent cause of disease, worldwide. Globally, acute lower respiratory infections are an important cause of morbidity and mortality in children below 5 years of age. Scientific studies have identified respiratory syncytial virus (RSV), as the most common viral cause of death due to such infection; other prominent viruses being human metapneumovirus, parainfluenza viruses, influenza viruses A and B, adenoviruses and of recent origin coronavirus. Several tens of millions of such infections are reported every year leading to more than half a million deaths in children below the age of five, largely in low and middle income households.
Virus as discussed above, are known to transmit through respiratory aerosol drops or by touching with infected hands and even through inanimate surfaces. As a consequence, hand hygiene is a commonly recommended method of killing such germs and thereby reducing the risk of not only respiratory infection but also gastrointestinal diseases. Hand hygiene includes use of soap and running water to wash the hands which makes it not only free of dirt but also in washing away and killing germs including bacteria and virus. Alternately, alcohol-based hand sanitizers which contain very little water may be rubbed on the hands as another effective means of removing virus and bacteria from hands. While such methods are very good in instantaneously killing the germs they are sometimes considered harsh. There is thus a need for actives and compositions that are mild on skin and other external and mucosal surfaces but are sufficiently effective in killing or inactivating virus to prevent or mitigate infection.
The present inventors when looking for such actives hit upon specific type of fatty acid which are known to be PPAR (peroxisome proliferator-activated receptor) activating fatty acid which they have now found to kill or inactivate enveloped virus, which heretofore was not known before. Further, they found that it synergizes with a specific vitamin viz. Vitamin B3 or its
precursors or analogue thereof to deliver enhanced antiviral activity. Further they also found that vitamin B3 or its precursors or analogues thereof in itself can also deliver such activity. PPAR fatty acid as per this invention includes fatty acids which have a PPAR action and also includes their corresponding mono, di and triglyceride forms.
It is thus an object of the present invention to provide for novel actives that kill or inactivate enveloped virus.
It is another object of the present invention to provide for such benefit from using commonly used actives that are mild on external or mucosal surfaces of the body.
Summary of the Invention
The first aspect of the present invention relates to use of a peroxisome proliferator-activated receptor (PPAR) activating fatty acid for inactivation or kill of enveloped virus on topical surface of a human or animal body.
A preferred aspect of the present invention relates to use of a composition comprising (i) a vitamin B3 compound or its precursors or analogue thereof and (ii) a peroxisome proliferator- activated receptor (PPAR) activating fatty acid for inactivation or kill of enveloped virus on topical surface of a human or animal body.
Another aspect of the present invention relates to a mouthwash composition for inactivating enveloped virus comprising
(i) 0 to 5.0 wt% a vitamin B3 compound or its precursors or analogue thereof;
(ii) 0.01 to 5.0 wt% a PPAR activating fatty acid;
(iii) 70 to 99 wt% water;
(iv) 1 to 20 wt% humectant; and
(v) less than 1 .5 wt% surfactant chosen from non-ionic or amphoteric surfactant or mixtures thereof.
An even further aspect of the present invention relates to a wash-off composition having a pH in the range of 2.5 to 6.0 preferably 2.5 to 4.5 for providing intimate hygiene in and around the vagina comprising
(i) a PPAR activating fatty acid;
(ii) 0.1 % to 50 wt% of an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulphate, ammonium lauryl sulphate, cocoamidopropyl betaine, fatty acid isethionate, and fatty acyl taurate;
(iii) a carboxylic acid; and
(iv) 40 to 90 wt% water.
Yet another aspect of the present invention relates to use of a vitamin B3 compound or its precursors or analogue thereof for inactivation of enveloped virus on topical surface of a human or animal body.
Detailed description of the invention
These and other aspects, features and advantages will become apparent to those of ordinary skill in the art from a reading of the following detailed description and the appended claims. For the avoidance of doubt, any feature of one aspect of the present invention may be utilized in any other aspect of the invention. The word “comprising” is intended to mean “including” but not necessarily “consisting of” or “composed of.” In other words, the listed steps or options need not be exhaustive. It is noted that the examples given in the description below are intended to clarify the invention and are not intended to limit the invention to those examples per se. Similarly, all percentages are weight/weight percentages unless otherwise indicated. Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description and claims indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word “about”. Numerical ranges expressed in the format "from x to y" are understood to include x and y. When for a specific feature multiple preferred ranges are described in the format "from x to y", it is understood that all ranges combining the different endpoints are also contemplated.
The present invention may be used to inactivate or kill virus especially enveloped virus on topical surface of a human body or animal body. The surface is therefore an animate surface.
Animate surfaces include the external surfaces of living organisms like plants and animals including humans. Due to the rich availability of nutrients and water on most animate surfaces, germs reside and are capable of multiplying on such surfaces. The present invention is used
against virus infection on any type of animate surface. The invention is especially useful for prevention or kill of virus on topical surface of a human body. Topical surfaces as per the present invention includes external surfaces as well as mucosal surfaces. External surface as per the present invention includes skin on any external part of the body including scalp and hair. Mucosal surface as per the present invention includes surfaces in the oral cavity, and that of the vagina.
The present invention may be used through a leave-on composition or a wash-off composition. By a leave-on composition is meant a composition which is applied on the external surface of the human body and allowed to remain thereon till the person goes for a shower or a bath usually after several hours or after a day. By a wash-off composition is meant that the composition is used to wash the external surface of the body e.g with a soap composition, a body wash, a face wash, a shampoo or a hair conditioning composition with copious amount of water such that substantial amount of dirt and oils are washed off the surface of the body leaving it clean. Such wash off compositions generally contain sufficient amounts of surfactants that enable the wash-off action.
The present invention relates to use of a vitamin B3 compound, its precursors or analogue thereof for inactivation of enveloped virus on topical surface of a human or animal body. The use is preferably non-therapeutic. The enveloped virus is preferably SARS-Cov2.
The present invention relates to use of a PPAR activating fatty acid for inactivation or kill of enveloped virus on topical surface if a human or animal body. The use is preferably non- therapeutic.
The present invention is also capable of preventing reinfection of the topical surface through use of one or more of the actives claimed in the present invention for inactivation or kill of enveloped virus on these surfaces. By this is meant that surfaces treated with such actives will prevent infection of the surface in the future for several hours after such treatment.
Enveloped virus as per the present invention includes a coronavirus or an influenza virus. Preferred coronavirus which may treated as per the present invention is SARS-Cov2. Preferred influenza virus which may be treated as per the present invention is H1 N1. Other enveloped virus which may be treated as per the present invention include RSV (respiratory syncytial virus) and HSV (herpes simplex virus).
Peroxisome proliferator-activated receptors (abbreviated herein to PPAR) are transcription factors that control lipid metabolism. There are three isotypes PPARa PPARp/8 and PPARYy
all of which have been localised in the skin. A range of specific fatty acids activates these factors resulting in anti-inflammatory action to reduce cutaneous irritation responses and pro- differentiation/antiproliferation responses to normalise skin metabolism and provide additional skin-care benefits. It is particularly desirable to select PPAR fatty acids containing a hydroxyl and/or methyl side chain. Many such acids contain from 14 to 30 carbons. Examples of PPAR fatty acids with demonstrated PPAR activating activity are cis-parinaric acid, cis-9-trans-11 conjugated linoleic acid, columbinic acid, docosahexaenoic acid, eicosapentanoic acid, hexadecatrienoic acid, linolenelaidic acid (isomer of linolenic acid), petroselinic acid, pinolenic acid, punicic acid, ricinoleic acid, ricinolaidic acid (isomer of ricinoleic acid), stearidonic acid, trans-10-cis-12 conjugated linoleic acid, 7-trans octadecanoic acid, vaccenic acid, octadecene dioic acid and hydroxystearic acids.
A PPAR fatty acid as per this invention also includes hydrolysable PPAR precursors. Potential source of hydrolysable PPAR precursors include triglycerides such as coriander seed oil for petroselinic acid, impatiens balsimina seed oil, parinarium laurinarium kernel fat or sabastiana brasilinensis seed oil for cis-parinaric acid, dehydrated castor seed oil for conjugated linoleic acids, and aquilegia vulgaris oil for columbinic acid. If a single hydrolysable precursor of a PPAR activating fatty acid is employed, it specifically excludes borage oil, castor oil and sunflower seed oil. Desirably, the PPAR acid contains 16 or 18 carbon atoms.
An especially preferred PPAR acid is hydroxy stearic acids or esters thereof. Most preferred PPAR acid is hydroxy stearic acids.
It is preferred that the hydroxystearic acid is 10- hydroxy stearic acid, 12-hydroxystearic acid or trihydoxystearic acid (e.g. 9, 10,13-tri hydroxy stearic acid) or trihydroxy stearin or compounds that yield one or more molecules of hydroxy stearic acid or hydroxystearate on their breakdown like mono, di or tri ester of glycerol with hydroxystearic acid. Of these, 10-hydroxystearic acid, 12-hydroxystearic acid and 9,10,13-trihydroxystearic acid are more preferred, 12- hydroxystearic acid (12-HSA) being most preferred. 12-HSA has the structure as given below:
It is preferred that the PPAR activating fatty acid for use in any aspect of the present invention is also a Caspase 8 regulator.
As per a preferred aspect, a composition as per the invention may additionally comprise an antimicrobial peptide (AMP). A further preferred aspect refers to use of a composition as per the invention which additionally comprises an anti-microbial peptide. The preferred AMP is LL37.
A preferred aspect of the present invention relates to use of a composition comprising (i) a vitamin B3 compound, its precursor or analogue thereof and (ii) a peroxisome proliferator- activated receptor (PPAR) activating fatty acid for inactivation or kill of enveloped virus on topical surface of a human or animal body. The use is preferably non-therapeutic.
Yet another aspect of the present invention relates to use of a PPAR-activating fatty acid as an enveloped virus killing or inactivating agent in a composition also comprising a vitamin B3 compound, its precursor or analogue thereof.
Yet another aspect relates to use of a combination of a PPAR-activating fatty acid and a vitamin B3 compound, its precursor or analogue thereof in a topical composition as an enveloped-virus-killing or inactivating system.
The vitamin B3 compound, its precursor or analogue thereof is selected from one or more of tryptophan, niacin, nicotinic acid, isonicotinamide, picolinamide, and nicotinamide (which is also known as niacinamide). It is preferably niacinamide. Niacinamide also known as pyridine- 3-carboxamide is the active, water soluble form of vitamin B3. Analogues of vitamin B3, as per this invention, also includes derivatives like cyclo alkyl nicotinamide with the cyclo alkyl group having 3 to 6 carbon atoms.
When included in the composition of the present invention comprises an effective amount of niacinamide, typically is in a concentration of 0.05 to 3%, preferably in 0.1 to 2% weight of the composition. In such a composition hydroxystearic acid is preferably included in 0.05 to 3%, more preferably 0.1 to 2%, by weight of the composition.
Without wishing to be bound by theory the inventors believe that the actives claimed in the present invention viz. the PPAR fatty acid e.g. 12-HSA activates host cells to help drive the
defense benefit against non-enveloped viruses like SARS-Cov2. They believe that this mode of action is quite different from direct antivirals like low boiling alcohols, bleaches and cationic surfactants like quaternary ammonium compounds which act directly on the virus particle to inactivate them thereby delivering the anti-viral benefit.
It is further understood by way of experiments that actives like the PPAR fatty acids deposit in sufficient quantities on to the topical surface even from a wash off composition. Further the actives are seen to move into the skin to activate the AMPs from the cells. The generation of AMPs is a biological process and this takes a long time. It has been seen that maximum amount of AMPs are generated in the order of 48 to 72 hours after the deposition of the active.
Yet another aspect of the present invention relates to use of a composition for care of external surface of a body 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, for inactivation or kill of enveloped virus on the external surface of a human or animal body. The use is preferably non-therapeutic. Such a composition may additionally comprise a vitamin B3 compound, its precursor or an analogue thereof.
Yet another aspect of the present invention relates to use of a skin care composition comprising (i) a vitamin B3 compound, its precursors or analogue thereof and (ii) a cosmetically acceptable carrier selected from a liquid, a gel, an emulsion or an anhydrous phase, for inactivation of enveloped virus on a topical surface of a human or animal body. The use is preferably non-therapeutic.
Yet another aspect of the present invention relates to use of a skin cleansing composition comprising (i) a vitamin B3 compound, its precursors or analogue thereof and (ii) a cosmetically acceptable carrier comprising 5 to 80% surfactant selected from a synthetic surfactant or soap, for inactivation of enveloped virus on a topical surface of a human or animal body. The use is preferably non-therapeutic.
Yet another aspect of the present invention relates to use of an oral care composition comprising (i) a vitamin B3 compound, its precursors or analogue thereof and (ii) an orally acceptable carrier selected from water, an abrasive, a humectant, an emulsifier or mixtures thereof, for inactivation of enveloped virus in the oral cavity of a human or animal body. The use is preferably non-therapeutic.
The cosmetically acceptable carrier as per the above aspect of the present composition may preferably be delivered as an emulsion e.g. as a cream or a lotion or in gel form preferably in cream form. A preferred format for the solid form of the composition is a cream, further more preferably one which has a vanishing cream base. Vanishing cream base is one which comprises 3 to 25 wt% fatty acid. Optionally, the composition may comprise 0.1 to 10 wt% 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 acids are stearic acid or palmitic acid or a mixture thereof and the soap is preferably the potassium salt of the fatty acid mixture. The fatty acid is often hystric acid which is substantially (generally about 90 to 95 %) a mixture of 45 % stearic acid and 55 % palmitic acid. The most preferred cream is one having 3 to 25 wt% fatty acid and 0.1 to 10 wt% soap.
Preferably, the cosmetically acceptable carrier in the above composition comprises emollients. Examples of emollients that may be used in the leave-on composition include stearyl alcohol, glyceryl monoricinoleate, mink oil, isopropyl isostearate, isobutyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as dimethylpolysiloxane, din-butyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, cocoa butter, corn oil, cotton seed oil, olive oil, palm kernel oil, rape seed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, sesame seed oil, coconut oil, arachis oil, acetylated lanolin alcohols, petroleum jelly, mineral oil, butyl myristate, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate and mixtures thereof.
Preferably, the cosmetically acceptable carrier in above composition comprises solvents. Examples of solvents that may be used in the composition include ethyl alcohol, isopropanol, acetone, ethylene glycol mono ethyl ether, diethylene glycol mono butyl ether, diethylene glycol mono ethyl ether and mixtures thereof. The composition may comprise polyhydric alcohols which may be selected from one or more of glycerine, 1 ,3-butylene glycol, propylene glycol, 1 ,3-propanediol, pentylene glycol, hexylene glycol, and sorbitol.
Preferably, the cosmetically acceptable carrier in the above composition comprises powders. Examples of powders that may be used in the composition include chalk, talc, fullers earth, kaolin, starch, gums, colloidal silica sodium polyacrylate, tetra alkyl and/or trialkyl aryl
ammonium smectites, chemically modified magnesium aluminium silicate, organically modified montmorillonite clay, hydrated aluminium silicate, fumed silica, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate and mixtures thereof.
According to yet another aspect of the present invention there is provided use of a composition for cleansing of external surfaces of a body comprising (i) a PPAR activating fatty acid and (ii) a cosmetically acceptable vehicle comprising 0.1% to 80 wt% surfactant selected from a synthetic surfactant or soap, for inactivation or kill of enveloped virus on the external surface of a human or animal body. The use is preferably non-therapeutic. Such a composition may additionally comprise a vitamin B3 compound, its precursor or an analogue thereof. Such a composition is generally known as a cleansing composition.
By ‘a cleansing composition’ as used herein, is meant to include a composition for topical application to skin, hair and/or scalp of mammals, especially humans. Such a composition is generally applied on to the desired topical surface of the body for a period of time from a few seconds to up to a few minutes generally after diluting with water. After this period of time of application, the composition is generally rinsed off with water or wiped away. It includes any product applied to a human body for also improving appearance, odor control or general aesthetics. The composition of the present invention can be in the form of a liquid, lotion, cream, foam, scrub, gel, shampoo, conditioner, handwash, facewash or bodywash product.
The cosmetically acceptable vehicle generally comprises water in addition to surfactant. A particularly preferred surfactant is an anionic surfactant like soap. The soap for preparing the cleansing composition of the invention is preferably a C8-C24 soap, more preferably C10-C20 soap and most preferably C12-C18 soap. The cation of the soap can be alkali metal, 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 groundnut, soybean, tallow, palm, palm kernel, etc. may also be used in other desired proportions. A cosmetically acceptable vehicle comprising generally forms 80 to 99% by weight of the cleansing composition.
When present, the anionic surfactant e.g. soap, is preferably present in an amount of 1 to 90%, preferably from 10 to 85%, more preferably 25 to 75% by weight of the cleansing
composition. The cleansing composition is preferably in the form of a solid or semi solid form, most preferably in a solid form. Preferred solid compositions are in the shape of a soap bar.
Other anionic surfactants are preferably selected from alkyl ether sulphate, primary alkyl sulphate, secondary alkyl sulphonates, alkyl benzene sulphonates, or ethoxylated alkyl sulphates. The anionic surfactant other than soap which is preferred in the cleansing composition is an alkyl ether sulphate preferably those having between 1 and 3 ethylene oxide groups, either from natural or synthetic source and/or sulphonic acid. Especially preferred are sodium lauryl ether sulphates. Alkyl polyglucoside may also be present in the composition, preferably those having a carbon chain length between Ce and Ci6.
Preferred cleansing compositions may include other known ingredients such as perfumes, pigments, preservatives, emollients, sunscreens, gelling agents and thickening agents. Choice of these ingredients will largely depend on the format of the composition. Water is a preferred carrier. When water is present, it is preferably present in at least 1 %, more preferably at least 2%, furthermore preferably at least 5% by weight of the composition. When water is the carrier, a preferred cleansing composition comprises 10 to 50%, more preferably 12 to 40%, further more preferably from 12 to 25% by weight water.
The cleansing composition of the invention may also be delivered through a moisturizing bar or a moisturizing liquid composition. Moisturizing bar compositions comprising fatty acyl isethionates (e.g. cocyl isethionate) are especially preferred.
Fatty acyl isethionates (e.g., cocoyl isethionates) 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 chloride having carbon chain length of C8 to C20 with isethionate. A typical surfactant product containing fatty acyl isethionate contains about 40 to 95 wt.% acid isethionate, and 5 to 50 wt.%, typically 10 to 40 wt.% free fatty acid, in addition to isethionate salts, typically at less than 5%, and trace (less than 2 wt.%) of other additives. Such compositions may also include an alkyl taurates, e.g., alkyl taurate amides. Such alkyl taurate amides may be made by reaction of a taurine; methyl taurine; or a corresponding taurate salt (e.g., NH2CH2CH2SO3 M+, where M+ may be sodium or potassium counterion) with the
appropriate fatty acid. Preferably alkyl taurate amides include sodium methyl cocoyl taurate and sodium methyl lauroyl taurate.
Fatty acid soap may be included in the range of 5 to 15 wt%. Other surfactants like betaines may be included in 1 to 5 wt%. Water is generally included in 2 to 8 wt% of the composition.
According to yet another aspect of the present invention there is provided use of a composition for care or cleansing of mucosal surfaces comprising (i) PPAR activating fatty acid and (ii) a mucosally acceptable carrier selected from one or more of water, an abrasive, a humectant, and an emulsifier, for inactivation or kill of enveloped virus on mucosal surface of a human or animal body. The use is preferably non-therapeutic. Such a composition may additionally comprise a vitamin B3 compound, its precursor or an analogue thereof. When the composition is delivered for care of the oral cavity the mucosally acceptable carrier is often termed as a orally acceptable carrier.
More preferred orally acceptable carrier includes an abrasive, a humectant or mixtures thereof. The orally acceptable carrier preferably is included in as much as 99.8%, more preferably at as much as 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.
The oral care composition of the present invention may be delivered in the form of an ointment, a gel, a dentifrice or a mouthwash. Dentifrices include forms like toothpaste and toothpowder. A composition is most preferably presented in the form of a toothpaste, a toothpowder or a mouthwash.
Oral care composition of the present invention preferably comprises an abrasive. The abrasive may preferably be calcium carbonate or silica. Gels usually contain silica, whereas opaque creams generally contain calcium based abrasives, especially chalk (calcium carbonate). In opaque toothpastes, the compositions have 5 to 60 wt% calcium based abrasive. In more preferred compositions it is 30 to 60 wt% and furthermore preferably from 35 to 55 wt%. Optimal compositions have 40 to 55 wt% calcium based abrasive.
Suitable humectants are preferably used in the oral care composition of the present invention and they include, for example, glycerin, sorbitol, propylene glycol, dipropylene glycol, diglycerol, triacetin, mineral oil, polyethylene glycol (preferably, PEG-400), alkane diols (like
butane diol and hexanediol, ethanol, pentylene glycol, or a mixture thereof. Glycerin, polyethylene glycol, sorbitol or mixtures thereof, are the preferred humectants, most preferred ones being glycerol (also known as glycerine) and sorbitol.
The humectant may be present in the range of from 10 to 90% by weight of oral care compositions. More preferably, the humectant makes up from 25 to 80%, and most preferably, from 45 to 70% by weight of the composition, based on total weight of the composition and including all ranges subsumed therein.
Preferably, an oral care composition comprises a surfactant. Preferably the composition comprises at least 0.01% surfactant by weight of the composition, more preferably at least 0.1 % and most preferably from 0.5 to 7%. Suitable surfactants include anionic surfactants, such as the sodium, magnesium, ammonium or ethanolamine salts of C8 to C18 alkyl sulphates (for example sodium lauryl sulphate), 08 to 018 alkyl sulphosuccinates (for example dioctyl sodium sulphosuccinate), 08 to 018 alkyl sulphoacetates (such as sodium lauryl sulphoacetate), 08 to 018 alkyl sarcosinates (such as sodium lauryl sarcosinate), 08 to 018 alkyl phosphates (which can optionally comprise up to 10 ethylene oxide and/or propylene oxide units) and sulphated monoglycerides. More preferably the surfactant comprises or is an anionic surfactant. The preferred surfactants are sodium lauryl sulphate and/or sodium dodecylbenzene sulfonate. Most preferably the surfactant is sodium lauryl sulphate. 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 sulphobetaines. Mixtures of any of the above described materials may also be used. Most preferred surfactants are an alkali metal alkyl sulphate or a betaine.
In a preferred embodiment, the composition comprises a thickener. Thickeners that may be used in this invention include, sodium carboxymethyl cellulose (SCMC), hydroxyl ethyl cellulose, methyl cellulose, ethyl cellulose, gum tragacanth, gum arabic, gum karaya, xanthan gum, sodium alginate, carrageenan gum, guar gum, Irish moss, starch, modified starch, silica based thickeners including silica aerogels, magnesium aluminum silicate (e.g., Veegum), Carbomers (cross-linked acrylates) and mixtures thereof.
Typically, thickening silica, sodium carboxymethyl cellulose and/or a Carbomer is/are preferred thickeners for use in the composition of the invention.
Thickening silica is especially preferred to be used in gel toothpastes. Gel toothpastes generally contain upto 8.5 wt% thickening silica whereas opaque toothpastes typically contain 3 to 4 wt% thickening silica.
Thickener, when present, preferably makes up from 0.01 to about 10%, more preferably from 0.1 to 9%, and most preferably, from 1.5 to 8% by weight of the composition.
Water may preferably be included in 5 to 95%, in particular 10 to 75%, and especially at from 10 to 60%, furthermore preferably 10 to 45% by total weight of the composition.
When the oral care composition of this invention is a toothpaste or gel, the same typically has a viscosity from about 30,000 to 180,000 centipoise, and preferably, from 60,000 to 170,000 centipoise, and most preferably, from 65,000 to 165,000 centipoise.
The oral care composition of the present invention may contain a variety of other ingredients which are common in the art to enhance physical properties and performance. These ingredients include antimicrobial, anti-caries agents, plaque buffers, fluoride sources, vitamins, plant extracts, desensitizing agents, anti-calculus agents, biomolecules, flavors, proteinaceous materials, preservatives, opacifying agents, coloring agents, pH-adjusting agents, sweetening agents, particulate abrasive materials, polymeric compounds, buffers and salts to buffer the pH and ionic strength of the compositions, and mixtures thereof. Such ingredients typically and collectively make-up less than 20% by weight of the composition, and preferably, from 0.0 to 15% by weight, and most preferably, from 0.01 to 12% by weight of the composition, including all ranges subsumed therein.
The present invention also relates to a method of inactivating or killing an enveloped virus on a topical surface of a human or animal body comprising the step of exposing the desired topical surface to a PPAR activating fatty acid; or compositions thereof. The method also includes an aspect wherein the composition additionally comprises a vitamin B3 compound, its precursor or analogue thereof. The method as per the present invention is for cosmetic use i.e. it is for non-therapeutic applications.
Yet another aspect of the present invention relates to a method of inactivating an enveloped virus on a topical surface of a human or animal body comprising the step of applying a vitamin B3 compound, its precursors or analogues thereof; or compositions thereof on to the desired topical surface.
According to a preferred aspect of the present invention there is provided a mouthwash composition for inactivating enveloped virus comprising
(i) 0.01 to 5.0 wt% a vitamin B3 compound, its precursor or analogue thereof;
(ii) 0.01 to 5.0 wt% a PPAR activating fatty acid;
(iii) 70 to 99 wt% water;
(iv) 1 to 20 wt% humectant; and
(v) less than 1.5 wt% surfactant chosen from non-ionic or amphoteric surfactant or mixtures thereof.
By a mouthwash composition of the invention is meant that the composition is used to wash the mouth. It may be in the form of a liquid which is used by a consumer in small quantity say 5 to 30 ml in the mouth and throat to wash the mouth free of germs or used to gargle in the mouth or throat for the same purpose. Such a liquid mouth composition may be used as such i.e without any dilution with water or may be diluted with water in a ratio of 1 :0.5 to 1 :10 before washing the mouth. After the mouthwash composition, with or without dilution, is used to rinse the oral cavity or gargled in the mouth and throat for about 10 second to about two minutes, it is usually spat out. Mouth wash as per this invention also includes a liquid spay which is delivered to the mouth from a container fitted with a spray pump. Thus the mouthwash composition of the invention is in the form of a liquid mouthwash composition or a spray composition, of which the liquid mouthwash composition is particularly preferred. The term “liquid mouthwash composition” generally denotes liquid formulations which are used to rinse the surfaces of the oral cavity and provide the user with a sensation of oral cleanliness and refreshment. The mouthwash is an oral composition that is not intentionally swallowed for purposes of systemic administration of therapeutic agents, but is applied to the oral cavity, used to treat the oral cavity and then expectorated.
Mouthwash compositions according to the invention preferably comprise an aqueous base. The amount of water generally ranges from 70 to 99% by weight based on the total weight of the mouthwash.
A mouthwash composition according to the invention will generally contain further ingredients to enhance performance and/or consumer acceptability, such as humectants and surfactants. The amount of humectant generally ranges from 1.0 to 20%, more preferably from 1.5 to 5% by weight based on the total weight of the mouthwash. Preferred humectants that are present at the above levels include polyols, more preferred is sorbitol and/or glycerol, glycerol is particularly preferred. It is preferable if the level of ethanol in the mouthwash composition is less than 0.1 wt%.
Mouthwash compositions of the invention may comprise a preservative, preferred preservatives are benzyl alcohol, and phenoxyethanol. Preferably the level of preservative is from 0.1 to 1 wt% of the total composition.
The mouthwash composition of the invention may comprise a deposition aid. The term “deposition aid” in the context of this invention generally means a material which aids deposition of anti-bacterial agents from the composition. Suitable deposition aids for use in the invention will generally dissolve or disperse in water at a temperature of 25°C.
Preferred deposition aids for use in the 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 10g/L at 25°C, and more preferably at least 30g/L at 25°C (where the solubility is determined in un-buffered distilled water). It is particularly preferable that the deposition aid remains water soluble after drying, so that it can be re-dissolved. This prevents undesirable build up of the deposition aid on the teeth after repeated usage of the composition.
Suitable deposition aids for use in the invention include polymeric materials, preferably polymeric materials which are water soluble as defined above.
Polymeric materials for use as deposition aids in the invention may be naturally or synthetically-derived, and may be ionic or nonionic in nature.
Preferably such polymeric materials are 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 to determine the molecular weight of such polymeric materials is gel permeation chromatography against a polyethylene glycol standard.
Specific examples of suitable classes of polymeric material for use as deposition aids in the invention include:
Water-soluble, high molecular weight linear homopolymers of ethylene oxide characterised by the general formula H(OCH2CH2)n OH. These materials are generally termed polyethyleneoxides (or alternatively, polyoxyethylenes, or polyethylene glycols). In the general formula, n usually has an average value of at least 2000, preferably at least 50,000.
Water-soluble, high molecular weight cellulose ethers such as methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose, hydroxybutyl methylcellulose, hydroxyethyl ethylcellulose, sodium carboxymethylcellulose, and sodium carboxymethyl hydroxyethylcellulose.
A preferred class of polymeric material for use as deposition aids in the invention includes water-soluble, high molecular weight polymers having anionic side groups along the polymer main chain.
Specific examples of such materials include poly(carboxylic acid) polymers. Poly (carboxylic acid) polymers are typically polymers which include -COOH groups in their structure, or groups which are derived from -COOH groups such as salt, ester or anhydride groups.
For example, the poly(carboxylic acid) polymers may include:
-[C(R1)(COOH)-]- units in their structure, in which R1 is selected from hydrogen, C1-3 alkyl, C1-3 alkoxy or C1-3 hydroxyalkyl. Preferably R1 is hydrogen.
A preferred type of poly (carboxylic acid) polymer includes adjacent:
-[C(R1)(COOH)-]- units in its structure (where R1 is as defined above), for example polymers based on maleic acid, which typically include:
-{-CH(COOH)-CH(COOH)-]- units, and/or salts or esters of such units, or such units in anhydride form in which -COOH groups on adjacent carbon atoms are cyclised to form a ring system.
For example, the poly(carboxylic acid) polymers may comprise units with pairs of carboxylic acid groups on adjacent polymer chain carbon atoms, for example polymers comprising:
-[-C(R1)(R2)-C(R3)(R4)-C(R5)(COOH)- C(R6)(COOH)-]- units in its structure (and/or salts or esters of such units, or such units in anhydride form in which -COOH groups on adjacent carbon atoms are cyclised to form a ring system); in which R1,R2,R3,R4,R5 and R6 are each independently selected from hydrogen, C1-3 alkyl or C1-3 alkoxy. Preferably R1 and R2 are hydrogen, R3 is hydrogen and R4 is methoxy and R5 and R6 are hydrogen.
Such a poly(carboxylic acid) polymer may be described as the polymer based on a copolymer of methyl vinyl ether and maleic anhydride, and is commercially available for example under the trade name Gantrez®.
A particularly preferred example of such a polymer comprises:
-[-CH2-CH(OCH3)-CH(COOH)-CH(COOH)-]- units in its structure, in which the -COOH groups are in free acid form. 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 Gantrez® S. Most preferably such a polymer has 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).
Alternative polymers which may be used comprise the units as described above in anhydride form, i.e. in which the two adjacent -COOH groups are cyclised to form a ring system. Such polymers are commercially available under the tradename Gantrez® AN, e.g. Gantrez® AN- 119, Gantrez® AN-903, Gantrez® AN-139 and Gantrez® AN-169.
Other alternative polymers which may be used comprise the units as described above in partial salt form, for example in which some of the free -COOH groups are converted into a metal salt of a Group I or Group II metal such as either sodium or calcium, or a mixed sodiumcalcium salt. Such polymers are commercially available under the tradename Gantrez® MS, e.g. Gantrez® MS-955.
Other alternative polymers which may be used comprise the units as described above in partial ester form, for example in which some of the free -COOH groups are esterified with C1-6 alkyl, e.g. ethyl or n-butyl. Such polymers are commercially available under the tradename Gantrez® ES, e.g. Gantrez® ES-225 or Gantrez® ES-425.
Mixtures of any of the above described materials may also be used.
The amount of deposition aid (as defined above) in mouthwash compositions of the invention suitably ranges from 0.001 to 5.0%, preferably from 0.005 to 4.0%, more preferably from 0.01 to 2.0% by total weight deposition aid (as defined above) based on the total weight of the composition.
Preferably the mouthwash composition comprises an acid anhydride polymer, particularly preferred are co-polymers of maleic anhydride with methyl vinylether, in which the anhydride moiety may be in a partially or fully hydrolysed or alcoholysed form.
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 levels of less than 3.0 wt% of the total composition, more preferably at levels less than 2.0 wt%, most preferably at levels of less than 1.5 wt%.
Suitable surfactants for use in the invention comprises 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.
Other suitable surfactants include amphoteric surfactants, such as betaines or sulphobetaines. Mixtures of any of the above described materials may also be used.
Preferably the mouthwash composition is free of anionic surfactants.
Mouthwash compositions of the present invention may also contain further optional ingredients customary in the art such as fluoride ion sources, anticalculus agents, buffers, flavouring agents, stability agents such as EDTA, sweetening agents, colouring agents, opacifying agents, antisensitivity agents and antimicrobial agents.
Use of the mouthwash composition in the context of this invention typically involves application of the composition to the oral cavity, for a recommended time period before being expectorated. Preferred application times are from 10 to 50 seconds.
According to a preferred aspect of the present invention there is provided a wash-off composition having a pH in the range of 2.5 to 6.0 preferably 2.5 to 4.5 for providing intimate hygiene in and around the vagina comprising
(i) a vitamin B3 compound, its precursor or analogue thereof;
(ii) a PPAR activating fatty acid;
(iii) 0.1 %- 50 wt% of an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulphate, ammonium lauryl sulphate, cocoamidopropyl betaine, sodium cocoyl isethionate, sodium lauroyl isethionate, sodium methyl lauroyl taurate;
(iv) a carboxylic acid; and
(v) 40 to 90 wt% water.
The above wash-off composition of the invention may also be used in intimate hygiene products esp. for use by women for effective, safe and mild wash in and around the vagina. Such products are generally available as a liquid with certain amount of surfactants and emollients formulated at a pH which is mild on women when used for obtaining intimate hygiene. Such products are also known as feminine hygiene products or menstrual hygiene products. Such liquid products generally comprise high amount of water in the range of 40 to 80 wt%, preferably 50 to 70 wt%. They further comprise surfactants e.g. an anionic and/ or amphoteric surfactants. Such surfactants are preferred to be included in 10 to 50 wt% preferably 20 to 40 wt% of the composition. As especially preferred surfactant for use in such
products is triethanolamine lauryl sulphate, ammonium lauryl sulphate, cocoamidopropyl betaine or mixtures thereof. Other surfactants in addition which may be included in such products are generally mild surfactants of the amphoacetate or glucoside types. Especially preferred surfactants of these types are disodium cocoamphodiacetate, alkyl e.g. decyl glucoside and combinations thereof. Additionally, the product may comprise oils, emollients, humectants and thickeners and other additives to aid in giving a mild sensation to the skin. Suitable humectant which may be included in such compositions are those disclosed hereinabove for oral care like glycerol, sorbitol or mixtures thereof. Carboxylic acids like lactic acid and/or citric acid are generally included in such compositions to provide additional hygiene benefits, preferably lactic acid. The pH of such products is generally in the range of 2.5 to 6.0 preferably in the range of 2.5 to 4.5.
Depending on the type of topical surface desired to be treated for inactivation or kill of virus an appropriate antimicrobial agent may be included in the composition of the invention. Suitable antimicrobial agent may be selected from one or more of salicylic acid, chloroxylenol, bisbalol, zinc pyrithione, octopirox, climbazole, triclosan, trichlocarban and cationic compounds like benzalkonium chloride, dodecyl dimonium chloride, cetrimonium chloride, and cetyl pyridinium chloride.
It is also within the scope of the present invention that the compositions claimed here are free of sulphate surfactants. Another aspect relates to compositions herein that are free of preservatives. Yet another aspect relates to compositions that are free of acrylate polymers. The compositions are generally prepared to be packaged and sold in plastic containers. The plastic is preferably of the PCR type (post-consumer recycled plastic)
The present invention will now be exemplified by way of the following non-limiting examples.
Examples
Example A, 1-3: Effect of 12-HSA on virus kill on skin keratinocyte cell line HaCaT
Skin keratinocyte cell line HaCaT were differentiated and then treated with 10 .M, 20 .M and 40 .M of 12HSA and treatment was done for 72 hrs, following standard protocols. Post this treatment the secretome that contains the secreted anti-microbial peptides (AMPs) was collected and was incubated with SARS-CoV2 virus for 4hrs. After the 4hrs of incubation, the virus kill was enumerated by using quantitative PCR based methods. The data on the viral gene expression as a percentage of control is shown in table -1 below:
The data in the table above indicates that the secretome generated in the presence of 12HSA is capable of ki lling/inactivati ng the virus.
Example B-D,4-6: Effect of 12-HSA and vitamin B3 and a combination on epithelial cells (Calu-3 cells):
Treatments of compounds and plaque formation assay
0.1 MOI SARS-CoV-2 was allowed to adsorb on Calu-3 cells, plated in a 48 well plate with about 120,000 cells/well, for one hour. After washing, fresh media was added along with niacinamide (16.4 mM), 12HSA (10 .M), and their respective vehicle controls. After 48 hrs, the conditioned media (containing the virus particles) were collected and plaque forming unit (pfu/ml) was determined for each treatment by performing plaque formation assay on Vero- E6 cells (48 well plate).
The data in the above table indicates that 12-HSA and niacinamide are both capable of inhibiting the SARS-CoV-2 as evident from the reduced plaque forming units in the assay used above. The inhibition is significantly improved with a combination of 12-HSA and vitamin B3.
Example E-G.7-9: Effect of human keratinocytes supernatant on SARS-CoV2 infectivity:
Differentiated primary human keratinocytes were incubated in serum free Epilife media with the mentioned concentrations of niacinamide and/or 12HSA for 72 hr and conditioned media was harvested. The SARS-Cov-2 virus particles were incubated for about 4 hrs with the above mentioned conditioned media. The pfu/ml of these treated virus particles was determined using VeroE6 reporter cells through Plaque or TCID50. The % infection with respect to the control is shown in Table - 3 below:
Table - 3
The data in the above table indicates that effect similar to that in Table -2 could be obtained with primary human keratinocytes also.
Example H-N: Effect of some vitamin B3 compound its precursor or analogue thereof on virus kill on skin keratinocyte cell line
Skin keratinocyte cell line CRL4048 were differentiated and then treated with various concentrations of vitamin B3 compound its precursor or analogue thereof as shown in Table 4 below and treatment was done for 72 hrs, following standard protocols. Post this treatment the secretome that contains the secreted anti-microbial peptides (AMPs) was collected and was incubated with SARS-CoV2 virus for 4hrs. After the 4hrs of incubation, the virus kill was enumerated by incubating the virus mixture on the VeroE6 reporter cell line, and using quantitative PCR based method for measuring the infection. The data on the viral gene expression as a percentage of control is shown in table -4 below:
The data in the table -4 together with the data in table - 1 above indicates that 12HSA is vastly superior to niacinamide (example I and J) as it is not effective at similar (micromolar) concentration. When other analogues of vitamin B3 compound are used (Examples K-N) one needs orders of magnitude higher (millimolar instead of micromolar concentrations) to get virus kill as compared to 12 HSA (Example 1-3 of Table -1).
Example P, 10-14: Effect of other PPAR fatty acids on virus kill on skin keratinocyte cell line
Other PPAR fatty acids were used to study the viral gene expression as shown in Table - 5 below. The procedure used to generate the data was similar to the one used for Table - 4. The data is summarized in the table -5 below:
In the table above CLA stands for conjugated linoelic acid
The data in the table -5 above indicates 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
Claims
1 Use of a peroxisome proliferator-activated receptor (PPAR) activating fatty acid for inactivation or kill of enveloped virus on topical surface of a human or animal body.
2 Use of a composition comprising (i) a vitamin B3 compound, its precursor or analogue thereof and (ii) a peroxisome proliferator-activated receptor (PPAR) activating fatty acid for inactivation or kill of enveloped virus on topical surface of a human or animal body.
3 Use as claimed in claim 1 or 2 wherein the enveloped virus is a coronavirus preferably SARS-Cov2; or an influenza virus.
4 Use as claimed in any one of the preceding claims wherein the PPAR activating fatty acid is hydroxystearic acid (HSA) preferably 12-hydroxystearic acid or 10- hydroxy stearic acid.
5 Use of a composition for care of external surface of a body 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, for inactivation or kill of enveloped virus on the external surface of a human or animal body.
6 Use of a composition for cleansing of external surfaces of a body comprising (i) a PPAR activating fatty acid and (ii) a cosmetically acceptable vehicle comprising 0.1 % to 80 wt% surfactant selected from a synthetic surfactant or soap, for inactivation or kill of enveloped virus on the external surface of a human or animal body.
7 Use of a composition for care or cleansing of mucosal surfaces comprising (i) PPAR activating fatty acid and (ii) a mucosally acceptable carrier selected from one or more of water, an abrasive, a humectant, and an emulsifier, for inactivation or kill of enveloped virus on mucosal surface of a human or animal body.
8 Use of a composition as claimed in any one of the preceding claims 5 to 7 additionally comprising a vitamin B3 compound, its precursor or analogue thereof.
A method of inactivating or killing an enveloped virus on a topical surface of a human or animal body comprising the step of exposing the desired topical surface to a PPAR activating fatty acid; or compositions thereof. A method as claimed in claim 9 wherein the composition additionally comprises a vitamin B3 compound, its precursor or analogue thereof. A mouthwash composition for inactivating enveloped virus comprising
(i) 0 to 5.0 wt% a vitamin B3 compound, its precursor or analogue thereof;
(ii) 0.01 to 5.0 wt% a PPAR activating fatty acid;
(iii) 70 to 99 wt% water;
(iv) 1 to 20 wt% humectant; and
(v) less than 1.5 wt% surfactant chosen from non-ionic or amphoteric surfactant or mixtures thereof. A wash-off composition having a pH in the range of 2.5 to 6.0 preferably 2.5 to 4.5 for providing intimate hygiene in and around the vagina comprising
(i) a PPAR activating fatty acid;
(ii) 0.1%- 50 wt% of an anionic or amphoteric surfactant selected from one or more of triethanolamine lauryl sulphate, ammonium lauryl sulphate, cocoamidopropyl betaine, fatty acid isethionate, and fatty acyl taurate;
(iii) a carboxylic acid; and
(iv) 40 to 90 wt% water.
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AU8445998A (en) * | 1997-07-05 | 1999-02-08 | Galderma S.A | Use of petroselinum acid for treating inflammations |
KR20090102035A (en) * | 2008-03-25 | 2009-09-30 | 윤길중 | Mouth-wash including water-soluble vitamins for scaling |
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US20200316050A1 (en) * | 2017-12-18 | 2020-10-08 | Conopco, Inc., D/B/A Unilever | A topical composition based on niacinamide derivative |
WO2022117404A1 (en) * | 2020-12-03 | 2022-06-09 | Unilever Ip Holdings B.V. | Hydroxystearic acid for inducing generation of antimicrobial peptides |
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GB0606872D0 (en) * | 2006-04-04 | 2006-05-17 | Norton Healthcare Ltd | Nasal spray device |
CN101756954B (en) * | 2010-01-05 | 2013-07-31 | 沈阳药科大学 | Schneiderian membrane medication preparation of isosorbide dinitrate and preparation method thereof |
CA3052449C (en) * | 2013-03-11 | 2021-10-19 | Jan Remmereit | Lipid compositions comprising 5, 11, 14-eicosatrienoic acid and conjugated linoleic acids |
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2023
- 2023-08-10 WO PCT/EP2023/072233 patent/WO2024041911A1/en unknown
- 2023-08-10 WO PCT/EP2023/072232 patent/WO2024041910A1/en unknown
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AU8445998A (en) * | 1997-07-05 | 1999-02-08 | Galderma S.A | Use of petroselinum acid for treating inflammations |
KR20090102035A (en) * | 2008-03-25 | 2009-09-30 | 윤길중 | Mouth-wash including water-soluble vitamins for scaling |
WO2015172801A1 (en) * | 2014-05-12 | 2015-11-19 | Unilever N.V. | Niacinamide for inducing generation of antimicrobial peptides |
US20200316050A1 (en) * | 2017-12-18 | 2020-10-08 | Conopco, Inc., D/B/A Unilever | A topical composition based on niacinamide derivative |
CN110448515A (en) * | 2019-08-29 | 2019-11-15 | 上海绿瑞生物科技有限公司 | Oral cavity profitable strain is not destroyed, specificity inhibits helicobacter pylori mouthwash |
WO2022117404A1 (en) * | 2020-12-03 | 2022-06-09 | Unilever Ip Holdings B.V. | Hydroxystearic acid for inducing generation of antimicrobial peptides |
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