Fluoride-free detergent oral care

Abstract

The invention discloses a fluoride-free oral care composition with an anti-caries or anti-tooth decay effect. Oral care compositions that are fluoride-free and contain an extract from a species of the family Humuliaceae are disclosed. Oral care compositions free of fluoride and containing an extract from hop are disclosed. Oral care compositions free of fluoride and containing hop beta acids are disclosed.

Description

[0001] This application is a divisional application of the invention patent application with application date September 30, 2020, application number 202080068676.8 (PCT / US2020 / 070598), and invention name “Fluoride-free anti-caries oral care composition”. Technical Field

[0002] The present invention relates to a composition having anticaries activity. The present invention also relates to a fluoride-free composition having anticaries activity. The present invention also relates to a fluoride-free composition comprising hop beta acids, such as an extract from hops (Humulus lupulus). Background Art

[0003] Oral care compositions (such as toothpaste and / or dentifrice compositions) can be applied to the oral cavity to clean and / or keep the attractive appearance and / or health of teeth, gums and / or tongue. In addition, many oral care compositions are used for direct delivery of active ingredients to the oral care surface. For example, toothpaste compositions can contain fluoride from such as sodium fluoride, sodium monofluorophosphate and / or stannous fluoride as anticaries medicine. Although the effectiveness and safety of fluoride as anticaries medicine are well-known, many consumers need oral care compositions without fluoride.

[0004] However, current oral care compositions that do not contain fluoride do not provide adequate or any protection against dental caries due to acids produced by bacteria found on the tooth surface.Therefore, there is a need for oral care compositions that do not contain fluoride and provide anti-caries benefits. Summary of the invention

[0005] Disclosed herein is an oral care composition comprising (a) from about 0.01% to about 10%, by weight of the composition, of hops beta acid; and (b) an abrasive, wherein the oral care composition is fluoride-free.

[0006] Also disclosed herein is an oral care composition comprising (a) from about 0.01% to about 10%, by weight of the composition, of hops beta acid; and (b) from about 10% to about 50%, by weight of the composition, of calcium, wherein the oral care composition is free of silica.

[0007] Also disclosed herein is an oral care composition comprising (a) from about 0.01% to about 10% of an antibacterial agent, by weight of the composition; and (b) from about 10% to about 50% of calcium, by weight of the composition, wherein the oral care composition is free of silica abrasive and has a glycolysis inhibition percentage of at least 60% in an in vitro dental plaque glycolysis and regrowth model.

[0008] Also disclosed herein is an oral care composition comprising (a) from about 0.01% to about 10%, by weight of the composition, of hops beta acid; (d) from about 0.01% to about 10%, by weight of the composition, of a metal ion source; (c) from about 10% to about 50%, by weight of the composition, of calcium; and (d) from about 1% to about 20%, by weight of the composition, of a buffer, wherein the oral care composition does not contain fluoride.

[0009] Also disclosed herein is an oral care composition comprising (a) from about 0.01% to about 10% lupulone, by weight of the composition; (b) from about 0.01% to about 10% tin, by weight of the composition; (c) from about 10% to about 50% calcium carbonate, by weight of the composition; and (d) from about 1% to about 20% buffer, by weight of the composition, wherein the oral care composition is fluoride-free.

[0010] Also disclosed herein is an oral care composition comprising (a) from about 0.01% to about 10%, by weight of the composition, of hops beta acid; (b) from about 0.01% to about 10%, by weight of the composition, of stannous chloride; (c) from about 10% to about 50%, by weight of the composition, of calcium carbonate; and (d) from about 1% to about 20%, by weight of the composition, of a buffer, wherein the oral care composition does not contain fluoride.

[0011] Also disclosed herein is a method for preventing dental caries comprising (a) providing a fluoride-free toothpaste composition comprising one or more hops beta acids; and (b) applying the fluoride-free toothpaste composition to the oral cavity.

[0012] Also disclosed herein is an oral care composition comprising (a) from about 0.01% to about 10%, by weight of the composition, of hops beta acid; and (b) from about 0.01% to about 10%, by weight of the composition, of a sweetener.

[0013] Also disclosed herein is a method of preventing dental caries, the method comprising (a) providing any one of the oral care compositions disclosed herein, and (b) applying the selected oral care composition to the oral cavity.

[0014] Also disclosed is an oral care composition comprising: (a) from about 0.01% to about 10%, by weight of the composition, of hops beta acid; and (b) from about 0.01% to about 10%, by weight of the composition, of an antibacterial agent, wherein the oral care composition is fluoride-free. DETAILED DESCRIPTION

[0015] The present invention relates to oral care compositions that do not contain fluoride but still provide anti-caries and / or anti-dental caries benefits. Dental caries or tooth decay is the breakdown of teeth caused by acids produced by bacteria. Cavities are caused by acids produced by bacteria that dissolve tooth hard tissues such as enamel, dentin and / or cementum. Acids are produced by bacteria as they break down food debris or sugars on the surface of the teeth.

[0016] The role of fluoride is to make the tooth surface less soluble to the acid produced by bacteria, the "plaque acid". Tooth enamel is composed of hydroxyapatite (Ca 5 (PO 4 ) 3 (OH)). Hydroxyapatite can be dissolved (demineralized) from enamel at a pH below 5.5. If hydroxyapatite is demineralized in the presence of fluoride ions, then fluorapatite (Ca 5 (PO 4 ) 3 Fluoride (F) can remineralize on the surface of tooth enamel. In short, this process replaces hydroxyl (OH) ions with fluoride (F) ions. Fluorapatite is inherently less soluble than hydroxyapatite, even under acidic conditions. Therefore, fluoride is used as an anticaries agent to make the tooth surface more resistant and less soluble in plaque acids.

[0017] While not wishing to be bound by theory, it is believed that the disclosed oral care compositions have a different mechanism of action than fluoride ion therapy. In contrast to the single symptomatic treatment of fluoride (i.e., the result of treating plaque acid), it is believed that the disclosed compositions have anti-caries activity through a combination of effects that together result in an anti-caries effect. While not wishing to be bound by theory, it is believed that the disclosed oral care compositions have an anti-caries effect by providing one or more of the following results: (1) inhibiting plaque acid production, (2) neutralizing produced plaque acid, and / or (3) reducing the solubility of hydroxyapatite hard tissue surfaces.

[0018] Inhibition of plaque acid production can be achieved by providing one or more antimicrobial agents to kill the source of plaque acid (ie, the bacteria themselves) and / or providing one or more biofilm modifying agents to disrupt and entrap the antimicrobial agents within the biofilm matrix.

[0019] Neutralization of plaque acid may be accomplished by providing one or more biofilm modifying agents to disrupt the biofilm matrix and / or providing one or more buffering agents to buffer generated plaque acid and / or by providing one or more calcium ion sources to increase calcium ion saturation on the enamel surface.

[0020] Reducing the solubility of hydroxyapatite at hard tissue surfaces can be achieved by providing one or more calcium ion sources. This can create a supersaturated environment of calcium and / or phosphate ions around the hydroxyapatite surface, which can shift the equilibrium of formula I to favor the remineralization of hydroxyapatite according to the LeChatelier principle.

[0021]

[0022] Formula I. Hydroxyapatite

[0023] Reducing the solubility of hydroxyapatite hard tissue surfaces can also be achieved by surface adsorption of metal ions, which slow down the dissolution of the enamel by forming an acid-resistant surface layer. This can be achieved, for example, by depositing stannous ions on the enamel surface.

[0024] While each of these mechanisms by itself may not be sufficient to provide anticaries benefits equivalent to therapeutic doses of fluoride, the combination of these mechanisms can provide anticaries benefits. Thus, the present invention is directed to compositions and methods of using compositions that do not contain fluoride but still provide anticaries and / or anticaries benefits.

[0025] definition

[0026] In order to more clearly define the terms used herein, the following definitions are provided. Unless otherwise indicated, the following definitions all apply to the present disclosure. If a term is used in the present disclosure but is not specifically defined herein, the definition from IUPAC Compendium of Chemical Terminology 2nd edition (1997) may be applied, as long as the definition does not conflict with any other disclosure or definition used herein, or does not make any claim to which the definition is applied uncertain or incapable of being realized.

[0027] As used herein, the term "oral care composition" includes products that are not intended to be swallowed for the purpose of systemic administration of a particular therapeutic agent during ordinary use, but are retained in the oral cavity for a sufficient period of time to contact tooth surfaces or oral tissues. Examples of oral care compositions include dentifrices, toothpastes, tooth gels, subgingival gels, mouthwashes, mousses, foams, mouth sprays, lozenges, chewable tablets, chewing gums, tooth whitening strips, dental floss and dental floss coatings, breath freshening soluble strips, or denture care or adhesive products. Oral care compositions can also be incorporated into strips or films for direct application or attachment to oral surfaces.

[0028] The "active ingredients and other ingredients" useful herein may be classified or described herein according to their cosmetic and / or therapeutic benefits or their postulated modes of action or operation. However, it should be understood that in some cases, the active substances and other ingredients useful herein may provide more than one cosmetic and / or therapeutic benefit, or function or operate via more than one mode of action. Therefore, the classification herein is for convenience only and is not intended to limit the ingredients to the specific specified functions or activities listed.

[0029] The term "orally acceptable carrier" includes one or more compatible solid or liquid excipients or diluents suitable for topical oral administration. As used herein, "compatible" means that the components of the composition can be mixed but do not interact, which would significantly reduce the stability and / or efficacy of the composition.

[0030] As used herein, the term "substantially free" means that no more than 0.05%, preferably no more than 0.01% and more preferably no more than 0.001% of a specified material is present in the composition, based on the total weight of such composition.

[0031] As used herein, the term "substantially free" means that the indicated material is not intentionally added to the composition, or preferably is not present at an analytically detectable level. This is meant to include compositions in which the indicated material is present only as an impurity in one of the other materials that are intentionally added.

[0032] Although compositions and methods are described herein as "comprising" various components or steps, unless otherwise specified, the compositions and methods may also "consist essentially of" or "consist of" the various components or steps.

[0033] As used herein, the word “or” when used as a conjunction of two or more elements is meant to include the elements individually or in combination; for example, X or Y means X or Y or both.

[0034] As used herein, the articles "a" and "an" are understood to refer to one or more materials being claimed or described, for example, "an oral care composition" or "a bleaching agent."

[0035] Unless otherwise indicated, all measurements mentioned herein were made at about 23°C (ie, room temperature).

[0036] Generally, element groups are indicated using the numbering scheme shown in the version of the periodic table published in Chemical and Engineering News, 63(5), 27, 1985. In some cases, element groups may be indicated using the common name assigned to the group; for example, alkali metal elements for Group 1, alkaline earth metal elements for Group 2, and so on.

[0037] Several types of ranges are disclosed herein. When any type of range is disclosed or claimed, it is intended to disclose or claim individually every possible value that such range can reasonably cover, including the endpoints of the range and any subranges and combinations of subranges contained therein.

[0038] The term "about" means that quantities, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and / or larger or smaller as needed, reflecting tolerances, conversion factors, rounding, measurement errors, etc., as well as other factors known to those skilled in the art. In general, whether or not such explicit statements are made, quantities, sizes, formulations, parameters, or other quantities or characteristics are "about" or "approximately". The term "about" also encompasses quantities that differ due to different equilibrium conditions for a composition resulting from a particular initial mixture. Whether or not modified by the term "about", the claims include equivalent amounts of the quantities. The term "about" may mean values ​​within 10% of the reported value, preferably values ​​within 5% of the reported value.

[0039] Oral care composition can be any suitable form, such as solid, liquid, powder, paste or their combination. Oral care composition can be dentifrice, tooth gel, subgingival gel, mouthwash, mousse, foam, mouth spray, lozenge, chewable tablet, chewing gum, teeth whitening strip, dental floss and dental floss coating, breath freshening soluble strip or denture care or adhesive product. The component of dentifrice composition can be incorporated in film, strip, foam or fiber-based dentifrice composition. Oral care composition can comprise multiple active and inactive ingredients, such as, but not limited to hop extract, tin ion source, calcium ion source, water, fluoride ion source, zinc ion source, one or more polyphosphates, wetting agent, surfactant, other ingredients etc. and any combination thereof, as described below.

[0040] The section headings provided below are only for organization and convenience. Section headings do not mean that a compound cannot be in multiple sections. In fact, a compound can fall into more than one section. For example, stannous chloride can be both a tin ion source and a biofilm modifier, stannous fluoride can be both a tin ion source and a fluoride ion source, glycine can be an amino acid, a buffer and / or a biofilm modifier, and many other compounds that can fit into multiple categories and / or sections.

[0041] Hops

[0042] The oral care composition of the present invention comprises at least one hop compound of formula I and / or formula IV. The compound of formula I and / or formula IV can be provided by any suitable source, such as extracts from hops or hops, hops itself, its synthetic derivative compounds and / or salts, prodrugs or other analogs. Hop extracts can include one or more hop alpha acids, one or more hop iso-alpha acids, one or more hop beta acids, one or more hop oils, one or more flavonoids, one or more solvents and / or water. Suitable hop alpha acids (generally represented by formula I) can include humulones (formula II), polyhumulones, class humulones, rear humulones, front humulones and / or mixtures thereof. Suitable hop iso-alpha acids can include cis-isohumulones and / or trans-isohumulones. Humulones isomerized to cis-isohumulones and trans-isohumulones and can be represented by formula III.

[0043]

[0044] Formula I. Hop isoalpha acid A is the acidic hydroxyl functional group in the alpha position, B is the acidic hydroxyl functional group in the beta position, and R is an alkyl functional group.

[0045]

[0046] Formula II. Humulone

[0047]

[0048] Formula III. Humulone isomerizes to isohumulone.

[0049] Suitable hop beta acids may include lupulones, lupulones, addululones and / or mixtures thereof. Suitable hop beta acids may include compounds described in Formula IV, V, VI and / or VII.

[0050]

[0051] Formula IV. Hop beta acid. B is an acidic hydroxyl functional group in the beta position, and R is an alkyl functional group.

[0052]

[0053] Formula V. Lupulone

[0054]

[0055] Formula VI. Lupulone

[0056]

[0057] Formula VII. Lupulone

[0058] Although hop alpha acids can exhibit some antibacterial activity, hop alpha acids also have a bitter taste. The bitter taste provided by hop alpha acids may be suitable for use in beer, but not in oral care compositions. In contrast, hop beta acids may be associated with higher antibacterial and / or anticaries activity, but the taste is less bitter. Therefore, hop extracts having a higher ratio of beta acids to alpha acids than is typically found in nature may be suitable for use in oral care compositions as antibacterial and / or anticaries agents.

[0059] Depending on the type of hops, the natural hop source can include about 2% to about 12% hop beta acids by weight of the hop source. Hop extracts used in other cases, such as in the brewing of beer, can include about 15% to about 35% hop beta acids by weight of the extract. Hop extracts required herein can include at least about 35%, at least about 40%, at least about 45%, about 35% to about 95%, about 40% to about 90%, or about 45% to about 99% hop beta acids. Hop beta acids can be in acidic form (that is, with a hydrogen atom connected to a hydroxyl functional group) or in salt form.

[0060] Suitable hop extracts are described in detail in U.S. Pat. No. 7,910,140, ​​which is incorporated herein by reference in its entirety. The desired hop beta acids may be non-hydrogenated, partially hydrogenated by a non-naturally occurring chemical reaction, or hydrogenated by a non-naturally occurring chemical reaction. Hop beta acids may be substantially free of or essentially free of hydrogenated hop beta acids and / or hop acids. Non-naturally occurring chemical reactions are chemical reactions performed with the aid of compounds not present in hops, such as chemical hydrogenation reactions performed at high temperatures and / or metal catalysts that wild hops would not normally experience.

[0061] Natural hop sources may contain about 2% to about 12% hop alpha acids by weight of the hop source. Hop extracts used in other situations, such as in the brewing of beer, may contain about 15% to about 35% hop alpha acids by weight of the extract. Hop extracts desired herein may contain less than about 10%, less than about 5%, less than about 1%, or less than about 0.5% hop alpha acids by weight of the extract.

[0062] Hop oils may contain terpene hydrocarbons such as myrcene, humulene, caryophyllene and / or mixtures thereof. Hop extracts desired herein may contain less than 5%, less than 2.5%, or less than 2% of one or more hop oils by weight of the extract.

[0063] The flavonoids present in the hop extract may include xanthohumol, 8-prenylnaringenin, isoxanthohumol and / or mixtures thereof. The hop extract may be substantially free, essentially free, free or have less than 250 ppm, less than 150 ppm and / or less than 100 ppm of one or more flavonoids.

[0064] Hops acids have previously been added to oral care compositions as described in U.S. Pat. No. 5,370,863. However, the oral care compositions taught in U.S. Pat. No. 5,370,863 contain only up to 0.01% by weight of the oral care composition. Although not wishing to be bound by theory, it is believed that U.S. Pat. No. 5,370,863 can only incorporate small amounts of hop acids because hop alpha acids have a bitter taste. Hops extracts with low levels of hop alpha acids do not have this problem.

[0065] The hops compounds may be combined with or without an extract of another plant, such as a Magnolia species. The hops compounds may be combined with or without triclosan.

[0066] The oral care composition may include from about 0.01% to about 10%, greater than 0.01% to about 10%, about 0.05%, to about 10%, about 0.1% to about 10%, about 0.2% to about 10%, about 0.2% to about 10%, about 0.2% to about 5%, about 0.25% to about 2%, about 0.05% to about 2%, or greater than 0.25% to about 2% of hop beta acids, as described herein. Hop beta acids may be provided by suitable hop extracts, the hop plant itself, or synthetically derived compounds. Hop beta acids may be provided as neutral, acidic compounds, and / or as salts with suitable counterions such as sodium, potassium, ammonia, or any other suitable counterions.

[0067] Hop beta acids can be provided by a hop extract, such as an extract from hops having at least 35% hop beta acids by weight of the extract and less than 1% hop alpha acids by weight of the hop extract. The oral care composition can include 0.01% to about 10%, greater than 0.01% to about 10%, about 0.05%, to about 10%, about 0.1% to about 10%, about 0.2% to about 10%, about 0.2% to about 10%, about 0.2% to about 5%, about 0.25% to about 2%, about 0.05% to about 2%, or greater than 0.25% to about 2% of a hop extract, as described herein.

[0068] Fluoride ion source

[0069] The oral care composition may contain fluoride, such as from a fluoride ion source. The fluoride ion source may contain one or more fluoride-containing compounds such as stannous fluoride, sodium fluoride, titanium fluoride, calcium fluoride, calcium phosphate silicate fluoride, potassium fluoride, amine fluoride, sodium monofluorophosphate, zinc fluoride, and / or mixtures thereof.

[0070] The fluoride ion source and the tin ion source can be the same compound, for example, stannous fluoride, which can generate tin ions and fluoride ions. In addition, the fluoride ion source and the tin ion source can be separate compounds, such as when the tin ion source is stannous chloride and the fluoride ion source is sodium monofluorophosphate or sodium fluoride.

[0071] The fluoride ion source and the zinc ion source can be the same compound, for example, zinc fluoride, which can generate zinc ions and fluoride ions. In addition, the fluoride ion source and the zinc ion source can be separate compounds, such as when the zinc ion source is zinc phosphate and the fluoride ion source is stannous fluoride.

[0072] The fluoride ion source may be substantially free or free of stannous fluoride.Thus, the oral care composition may comprise sodium fluoride, potassium fluoride, amine fluoride, sodium monofluorophosphate, zinc fluoride and / or mixtures thereof.

[0073] The oral care composition may include a fluoride ion source capable of providing from about 50 ppm to about 5000 ppm and preferably from about 500 ppm to about 3000 ppm of free fluoride ions. To deliver the desired amount of fluoride ions, the fluoride ion source may be present in the oral care composition in an amount of from about 0.0025% to about 5%, from about 0.01% to about 10%, from about 0.2% to about 1%, from about 0.5% to about 1.5%, or from about 0.3% to about 0.6% by weight of the oral care composition. Alternatively, the oral care composition may include less than 0.1%, less than 0.01%, substantially free, essentially free, or free of a fluoride ion source.

[0074] Tin ion source

[0075] The oral care composition of the present invention may include tin, such as from a tin ion source. The tin ion source may be any suitable compound that provides tin ions in the oral care composition and / or delivers tin ions to the oral cavity when the dentifrice composition is applied to the oral cavity. The tin ion source may include one or more tin-containing compounds, such as stannous fluoride, stannous chloride, stannous bromide, stannous iodide, stannous oxide, stannous oxalate, stannous sulfate, stannous sulfide, stannous fluoride, stannous chloride, stannous bromide, stannous iodide, stannous sulfide and / or mixtures thereof. The tin ion source may include stannous fluoride, stannous chloride and / or mixtures thereof. The tin ion source may also be a tin ion source that does not contain fluorine, such as stannous chloride.

[0076] The oral care composition may comprise from about 0.0025% to about 5%, from about 0.01% to about 10%, from about 0.2% to about 1%, from about 0.5% to about 1.5%, or from about 0.3% to about 0.6%, by weight of the oral care composition, of a tin ion source.

[0077] Ca ion source

[0078] The oral care composition of the present invention may contain calcium, such as from a calcium ion source. The calcium ion source may be any suitable compound or molecule that provides calcium ions in the oral care composition and / or delivers calcium ions to the oral cavity when the oral care composition is applied to the oral cavity. The calcium ion source may include a calcium salt, a calcium abrasive, and / or a combination thereof. In some cases, a calcium salt may also be considered a calcium abrasive, or a calcium abrasive may also be considered a calcium salt.

[0079] The calcium ion source may comprise a calcium abrasive. The calcium abrasive may be any suitable abrasive compound that can provide calcium ions in the oral care composition and / or deliver calcium ions to the oral cavity when the oral care composition is applied to the oral cavity. The calcium abrasive may comprise one or more calcium abrasive compounds such as calcium carbonate, precipitated calcium carbonate (PCC), ground calcium carbonate (GCC), chalk, dicalcium phosphate, calcium pyrophosphate and / or mixtures thereof.

[0080] The calcium ion source may comprise a calcium salt, or a compound that can provide calcium ions in the oral care composition and / or deliver calcium ions to the oral cavity when the oral care composition is applied to the oral cavity and that cannot act as an abrasive. The calcium salt may comprise one or more calcium compounds such as calcium chloride, calcium nitrate, calcium phosphate, calcium lactate, calcium oxalate, calcium oxide, calcium gluconate, calcium citrate, calcium bromide, calcium iodate, calcium iodide, hydroxyapatite, fluorapatite, calcium sulfate, calcium glycerophosphate, and / or combinations thereof.

[0081] The oral care composition may comprise from about 5% to about 70%, from about 10% to about 50%, from about 10% to about 60%, from about 20% to about 50%, from about 25% to about 40%, or from about 1% to about 50% of a calcium ion source.

[0082] Buffer

[0083] The oral care composition may include a buffer. The buffer may be a weak acid or a weak base that can maintain a specific pH at a selected location in the oral cavity. For example, the buffer can maintain the pH of the tooth surface to mitigate the effects of bacterially produced plaque acids. The buffer may include a conjugate acid of an ion that is also present in the oral care composition. For example, if the calcium ion source includes calcium carbonate, the buffer may include a bicarbonate anion (-HCO 3 -). The buffer may comprise a conjugate acid / base pair such as citric acid and sodium citrate.

[0084] Suitable buffer systems may include phosphate, citrate, carbonate / bicarbonate, Tris buffer, imidazole, urea, borate and / or combinations thereof. Suitable buffers include bicarbonates such as sodium bicarbonate, glycine, orthophosphate, arginine, urea and / or combinations thereof.

[0085] The oral care composition may comprise from about 1% to about 30%, from about 5% to about 25%, or from about 10% to about 20% of one or more buffering agents.

[0086] Biofilm modifiers

[0087] The oral care composition may include one or more biofilm modifiers. The biofilm modifiers may include polyols, ammonia generating compounds and / or glucosyltransferase inhibitors.

[0088] A polyol is an organic compound having more than one hydroxyl functional group. The polyol may be any suitable compound that can weakly associate, interact or bond with the tin ions when the oral care composition is stored prior to use. The polyol may be a sugar alcohol, which is a class of organic compounds that can be represented by having the formula (CHOH) n H 2 The polyol may be glycerol, erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol and / or a combination thereof. The oral care composition may contain 0.01% to about 70%, about 5% to about 70%, about 5% to about 50%, about 10% to about 60%, about 10% to about 25%, or about 20% to about 80% of the polyol by weight of the oral care composition.

[0089] The ammonia generating compound can be any suitable compound that can generate ammonia when delivered to the oral cavity. Suitable ammonia generating compounds include arginine, urea, and / or combinations thereof. The oral care composition may contain from about 0.01% to about 10%, from about 1% to about 5%, or from about 1% to about 25% of one or more ammonia generating compounds.

[0090] Glucosyltransferase inhibitors can be any suitable compound that can inhibit glucosyltransferase. Glucosyltransferase is an enzyme that can establish natural glycosidic bonds. Specifically, these enzymes partially decompose polysaccharides or oligosaccharides into monosaccharides for bacteria associated with dental caries. Therefore, any compound that can inhibit this process can help prevent dental caries. Suitable glucosyltransferase inhibitors include oleic acid, epicatechin, tannin, tannic acid, mennomycin, caspofungin, ethambutol, chlorfenuron and / or combinations thereof. The oral care composition may contain about 0.001% to about 5%, about 0.01% to about 2%, or about 1% of one or more glucosyltransferase inhibitors.

[0091] Metal ion source

[0092] The oral care composition may include a metal such as from a metal ion source comprising one or more metal ions. As described herein, the metal ion source may include or be in addition to a tin ion source and / or a zinc ion source. Suitable metal ion sources include compounds having metal ions such as, but not limited to, Sn, Zn, Cu, Mn, Mg, Sr, Ti, Fe, Mo, B, Ba, Ce, Al, In, and / or mixtures thereof. The trace metal source may be any compound having a suitable metal and any associated ligands and / or anions.

[0093] Suitable ligands and / or anions that may be paired with a metal ion source include, but are not limited to, acetate, ammonium sulfate, benzoate, bromide, borate, carbonate, chloride, citrate, gluconate, glycerophosphate, hydroxide, iodide, oxide, propionate, D-lactate, DL-lactate, orthophosphate, pyrophosphate, sulfate, nitrate, tartrate, and / or mixtures thereof.

[0094] The oral care composition may comprise from about 0.01% to about 10%, from about 1% to about 5%, or from about 0.5% to about 15% of a metal ion source.

[0095] Antimicrobial agents

[0096] The oral care composition may contain one or more antibacterial agents. Suitable antibacterial agents include any molecule that provides antibacterial activity in the oral cavity. Suitable antibacterial agents include hops acid, a tin ion source, benzyl alcohol, sodium benzoate, menthyl acetate, menthyl lactate, L-menthol, o-neomenthol, chlorophyllin copper complex, phenol, hydroxyquinoline and / or combinations thereof.

[0097] The oral care composition may comprise from about 0.01% to about 10%, from about 1% to about 5%, or from about 0.5% to about 15% of an antibacterial agent.

[0098] Bioactive substances

[0099] The oral care composition may also contain a bioactive material suitable for tooth remineralization. Suitable bioactive materials include bioactive glass, Novamin TM 、Recaldent TM , hydroxyapatite, one or more amino acids (e.g., arginine, citrulline, glycine, lysine or histidine) or a combination thereof. Suitable examples of compositions comprising arginine can be found in U.S. Patent Nos. 4,154,813 and 5,762,911, both of which are incorporated herein by reference in their entirety. Other suitable bioactive substances include any calcium phosphate compound. Other suitable bioactive substances include compounds comprising a calcium source and a phosphate source.

[0100] Amino acid is an organic compound containing an amine functional group, a carboxyl functional group and a side chain unique to each amino acid. Suitable amino acids include, for example, amino acids with positive or negative side chains, amino acids with acidic or basic side chains, amino acids with polar uncharged side chains, amino acids with hydrophobic side chains and / or combinations thereof. Suitable amino acids also include, for example, arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, tryptophan, citrulline, ornithine, creatine, diaminobutyric acid, diaminopropionic acid, their salts and / or combinations thereof.

[0101] Bioactive glasses contain calcium and / or phosphate, which may be present in proportions similar to hydroxyapatite. These glasses can bond to tissue and are biocompatible. Bioactive glasses may contain phosphopeptides, a calcium source, a phosphate source, a silica source, a sodium source, and / or combinations thereof.

[0102] The oral care composition may comprise from about 0.01% to about 20%, from about 0.1% to about 10%, or from about 1% to about 10%, by weight of the oral care composition, of a biologically active material.

[0103] Abrasive

[0104] The oral care composition may include calcium abrasives, as described herein, and / or non-calcium abrasives, such as bentonite, silica gel (alone, and of any structure), precipitated silica, amorphous precipitated silica (alone, and also of any structure), silica hydrate, perlite, titanium dioxide, calcium pyrophosphate, calcium hydrogen phosphate dihydrate, alumina, alumina hydrate, calcined alumina, aluminum silicate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, insoluble magnesium carbonate, zirconium silicate, particulate thermosetting resins, and other suitable abrasive materials. Such materials may be introduced into the oral care composition to customize the polishing properties of the target dentifrice formulation. The oral care composition may include about 5% to about 70%, about 10% to about 50%, about 10% to about 60%, about 20% to about 50%, about 25% to about 40%, or about 1% to about 50% of non-calcium abrasives by weight of the oral care composition.

[0105] Alternatively, the oral care composition may be substantially free, essentially free, or free of silica, alumina, or any other non-calcium abrasive. The oral care composition may contain less than about 5%, less than about 1%, less than about 0.5%, less than about 0.1%, or 0% of non-calcium abrasives, such as silica and / or alumina.

[0106] water

[0107] The oral care compositions of the present invention may be anhydrous, low-water, or high-water formulations. In general, the oral care compositions may contain 0% to about 99%, about 5% to about 75%, about 20% or more, about 30% or more, or about 50% or more water by weight of the composition. Preferably, the water is USP water.

[0108] In a high water oral care composition and / or toothpaste formulation, the oral care composition comprises from about 45% to about 75% water by weight of the composition. The high water oral care composition and / or toothpaste formulation may comprise from about 45% to about 65%, from about 45% to about 55%, or from about 46% to about 54% water by weight of the composition. Water may be added to the high water formulation and / or water may enter the composition as a result of the inclusion of other ingredients.

[0109] In low water oral care compositions and / or toothpaste formulations, the oral care composition comprises from about 5% to about 45% water by weight of the composition. The low water oral care composition may comprise from about 5% to about 35%, from about 10% to about 25%, or from about 20% to about 25% water by weight of the composition. Water may be added to the low water formulation and / or water may enter the composition as a result of the inclusion of other ingredients.

[0110] In an anhydrous oral care composition and / or toothpaste formulation, the oral care composition comprises less than about 10% water by weight of the composition. An anhydrous composition comprises less than about 5%, less than about 1%, or 0% water by weight of the composition. Water may be added to an anhydrous formulation and / or may enter the composition as a result of the inclusion of other ingredients.

[0111] Mouthwash formulations comprise from about 75% to about 99%, from about 75% to about 95%, or from about 80% to about 95% water.

[0112] The composition may also contain other orally acceptable carrier materials, such as alcohols, humectants, polymers, surfactants, and acceptance-enhancing agents (such as flavorings, sweeteners, colorings, and / or cooling agents).

[0113] pH

[0114] The pH of the disclosed compositions can be from about 4 to about 10, from about 7 to about 10, greater than 7 to about 10, greater than 8 to about 10, greater than 7, greater than 7.5, greater than 8, greater than 9, or from about 8.5 to about 10.

[0115] Zinc ion source

[0116] The oral care composition may contain zinc, such as from a zinc ion source. The zinc ion source may contain one or more zinc-containing compounds, such as zinc fluoride, zinc lactate, zinc oxide, zinc phosphate, zinc chloride, zinc acetate, zinc hexafluorozirconate, zinc sulfate, zinc tartrate, zinc gluconate, zinc citrate, zinc malate, zinc glycinate, zinc pyrophosphate, zinc metaphosphate, zinc oxalate and / or zinc carbonate. The zinc ion source may be a fluoride-free zinc ion source, such as zinc phosphate, zinc oxide and / or zinc citrate.

[0117] The zinc ion source may be present in the total dentifrice composition in an amount from about 0.01% to about 10%, from about 0.2% to about 1%, from about 0.5% to about 1.5%, or from about 0.3% to about 0.6% by weight of the oral care composition.

[0118] Polyphosphate

[0119] Oral care compositions may include polyphosphates, such as from a polyphosphate source. The polyphosphate source may include one or more polyphosphate molecules. Polyphosphates are a class of substances obtained by dehydrating and condensing orthophosphates to generate linear and cyclic polyphosphates of varying chain lengths. Therefore, polyphosphate molecules are typically identified by the average number (n) of polyphosphate molecules, as described below. Although some cyclic derivatives may exist, polyphosphates are generally considered to consist of two or more phosphate molecules arranged primarily in a linear configuration.

[0120] Preferred polyphosphates are those having an average of two or more phosphate groups so that surface adsorption at an effective concentration produces sufficient unbound phosphate functional groups, which enhances the anionic surface charge and the hydrophilic nature of the surface. Preferred in the present invention are linear polyphosphates having the formula: XO(XPO 3 ) n X, wherein X is sodium, potassium, ammonium or any other alkali metal cation, and n is, on average, from about 2 to about 21. Alkaline earth metal cations, such as calcium, are not preferred because they tend to form insoluble fluoride salts from aqueous solutions containing fluoride ions and alkaline earth metal cations. Thus, the oral care compositions disclosed herein may be free, substantially free, or essentially free of calcium pyrophosphate.

[0121] Some examples of suitable polyphosphate molecules include, for example, pyrophosphate (n=2), tripolyphosphate (n=3), tetrapolyphosphate (n=4), sodium polyphosphate (n=6), hexapolyphosphate (n=13), benzene polyphosphate (n=14), hexametaphosphate (n=21), which is also known as Glass H. Polyphosphates may include those polyphosphate compounds produced by FMC Corporation, ICL Performance Products and / or Astaris.

[0122] The oral care composition may comprise from about 0.01% to about 15%, from about 0.1% to about 10%, from about 0.5% to about 5%, from about 1% to about 20%, or about 10% or less, by weight of the oral care composition, of a polyphosphate source.

[0123] Wetting agent

[0124] Oral care composition can comprise one or more humectants, have low content of humectant, substantially do not contain, substantially do not contain or do not contain humectant.Humitant is used to increase the consistency or " mouthfeel " of oral care composition or dentifrice and prevent dentifrice from drying out.Suitable humectant comprises polyethylene glycol (having multiple different molecular weight), propylene glycol, glycerine (glycerin, glycerol), erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol, hydrogenated starch hydrolysate and / or their mixture.Oral care composition can comprise one or more humectants, and the content of each humectant is by the weight of this oral care composition 0% to about 70%, about 5% to about 50%, about 10% to about 60% or about 20% to about 80%.

[0125] Surfactants

[0126] The oral care composition may contain one or more surfactants. Surfactants can be used to make the composition more cosmetically acceptable. The surfactant is preferably a detersive material that imparts detersive and foaming properties to the composition. Suitable surfactants are safe and effective amounts of anionic, cationic, nonionic, zwitterionic, amphoteric and betaine surfactants.

[0127] Suitable anionic surfactants include, for example, water-soluble salts of alkyl sulfates having 8 to 20 carbon atoms in the alkyl group and water-soluble salts of sulfonated monoglycerides of fatty acids having 8 to 20 carbon atoms. Examples of such anionic surfactants are sodium lauryl sulfate (SLS) and sodium coconut monoglyceride sulfonates. Other suitable anionic surfactants include sarcosinates such as sodium lauroyl sarcosinate, taurates, sodium lauryl sulfoacetate, sodium lauroyl isethionate, sodium laureth carboxylate, and sodium dodecylbenzene sulfonate. Combinations of anionic surfactants may also be used.

[0128] Another class of suitable anionic surfactants are alkyl phosphates. These surface active organophosphate agents can have a strong affinity for enamel surfaces and have sufficient surface binding propensity to desorb surface membrane proteins and remain attached to the enamel surface. Suitable examples of organophosphate compounds include monoesters, diesters, or triesters represented by the following general structure, wherein Z 1 , Z 2 or Z 3 may be the same or different, at least one of which is an organic moiety. 1 , Z 2 or Z 3 It may be selected from a linear or branched alkyl or alkenyl group having 1 to 22 carbon atoms, optionally substituted by one or more phosphate groups; an alkoxylated alkyl or alkenyl group, a (poly)saccharide, a polyol or a polyether group.

[0129]

[0130] Some other reagents include alkyl or alkenyl phosphates represented by the following structures:

[0131]

[0132] Where R 1represents a straight or branched alkyl or alkenyl group having 6 to 22 carbon atoms, which is optionally substituted with one or more phosphate groups; n and m are independently and individually 2 to 4, and a and b are independently and individually 0 to 20; Z and Z may be the same or different, each representing hydrogen, alkali metal, ammonium, a protonated alkylamine or a protonated functional alkylamine such as an alkanolamine or an R—(OCH2)(OCH)─ group. Examples of suitable agents include alkyl phosphates and alkyl (poly) alkoxy phosphates such as lauryl phosphate; PPGS cetearyl polyoxyethylene eth-10 phosphate; laureth-1 phosphate; laureth-3 phosphate; laureth-9 phosphate; trilaureth-4 phosphate; C 12-18 PEG 9 phosphate: and sodium laureth-10 phosphate. The alkyl phosphates may be polymeric. Examples of polymeric alkyl phosphates include those containing repeating alkoxy groups as polymeric moieties, specifically those containing 3 or more ethoxy, propoxy, isopropoxy or butoxy groups.

[0133] Other suitable anionic surfactants are sarcosinates, isethionates and taurates, especially the alkali metal or ammonium salts thereof. Examples include: lauroyl sarcosinate, myristoyl sarcosinate, palmitoyl sarcosinate, stearoyl sarcosinate, oleoyl sarcosinate or combinations thereof.

[0134] Other suitable anionic surfactants include sodium or potassium alkyl sulfates such as sodium lauryl sulfate, acyl isethionates, acyl methyl isethionates, alkyl ether carboxylates, acyl alaninates, acyl glutamates, acyl glycinates, acyl sarcosinates, sodium methyl acyl taurate, sodium lauryl ether sulfosuccinate, alpha-olefin sulfonates, alkyl benzene sulfonates, sodium lauroyl lactylate, sodium lauryl glucoside hydroxypropyl sulfonate, and / or combinations.

[0135] Zwitterionic surfactants or amphoteric surfactants useful herein include derivatives of aliphatic quaternary ammonium, phosphonium and sulfonium compounds, wherein the aliphatic group may be linear or branched, and one of the aliphatic substituents contains 8 to 18 carbon atoms, and one of the aliphatic substituents contains an anionic water-solubilizing group, for example, carboxyl, sulfonate, sulfate, phosphate or phosphonate. Suitable betaine surfactants are disclosed in U.S. Pat. No. 5,180,577. Typical alkyl dimethyl betaines include decyl betaine or 2-(N-decyl-N,N-dimethylamine) acetate, coconut betaine or 2-(N-cocoyl-N,N-dimethylamine) acetate, tetradecyl betaine, palmityl betaine, lauryl betaine, hexadecyl betaine, hexadecyl betaine, stearyl betaine, etc. Amidobetaines can be exemplified by cocamidoethyl betaine, cocamidopropyl betaine (CADB) and lauramidopropyl betaine.Other suitable amphoteric surfactants include betaines, sulfobetaines, sodium lauroamphoacetate, alkyl amphodiacetates and / or combinations thereof.

[0136] Cationic surfactants useful in the present invention include, for example, quaternary ammonium compound derivatives having a long alkyl chain containing 8 to 18 carbon atoms, such as lauryltrimethylammonium chloride; cetylpyridinium chloride; cetyltrimethylammonium bromide; cetylpyridinium fluoride or combinations thereof.

[0137] Nonionic surfactants useful in the compositions of the present invention include, for example, compounds formed by the condensation of alkylene oxide groups (hydrophilic in nature) with an organic hydrophobic compound which may be aliphatic or alkyl aromatic in nature. Examples of suitable nonionic surfactants may include (i.e., poloxamer), polyethylene oxide condensates of alkylphenols, products derived from the condensation of ethylene oxide with the reaction product of propylene oxide and ethylenediamine, ethylene oxide condensates of fatty alcohols, long-chain tertiary amine oxides, long-chain tertiary phosphine oxides, long-chain dialkyl sulfoxides, and combinations of these substances. Other suitable nonionic surfactants include alkyl glucamides, alkyl glucosides, and / or combinations thereof.

[0138] One or more surfactants may also include one or more natural and / or naturally derived surfactants. Natural surfactants may include surfactants derived from natural products and / or minimally processed or unprocessed surfactants. Natural surfactants may include: hydrogenated, non-hydrogenated or partially hydrogenated vegetable oils, vegetable oils, passionflower oil, candelilla wax, coconut oil base caprylate, caprate, dioctyl ether, lauryl alcohol, myristate tetradecyl ester, dioctyl ether, caprylic acid, caprylate, caprylate, caprylate, undecane, tridecane, decyl oleate, decyl oleate, palmitic acid hexadecyl ester, stearic acid, palmitic acid, stearyl glyceride, hydrogenated, non-hydrogenated or partially hydrogenated vegetable glycerides, polyglyceryl-2 dipolyhydroxystearate, sixteen / octadecanol, sucrose polystearate, glycerol, stearyl alcohol, hydrolyzed, partially water The surfactants may include any of the natural ingredients sold by BASF, such as glyceryl stearate, glyceryl laurate, capric triglyceride, cocoyl glycerides, lecithin, dicaprylyl ether, xanthan gum, sodium coco sulfate, ammonium lauryl sulfate, sodium coco sulfate, sodium cocoyl glutamate, polyalkyl glucosides such as decyl glucoside, hexadecyl stearyl glucoside, hexadecyl stearyl polyglucoside, cocoyl glucoside and lauryl glucoside and / or combinations thereof.

[0139] and / or a combination thereof.

[0140] Other specific examples of surfactants include sodium lauryl sulfate, sodium lauryl isethionate, sodium lauroyl methyl isethionate, sodium cocoyl glutamate, sodium dodecylbenzene sulfonate, alkali metal salts or ammonium salts of lauroyl sarcosine, myristoyl sarcosine, palmitoyl sarcosine, stearoyl sarcosine and oleoyl sarcosine, polyoxyethylene sorbitan monostearate, isostearate and laurate, sodium lauryl sulfoacetate, sodium, potassium and ethanolamine salts of N-lauroyl sarcosine, N-lauroyl, N-myristoyl or N-palmitoyl sarcosine, polyethylene oxide condensates of alkylphenols, cocoamidopropyl betaine, lauroylamidopropyl betaine, palmityl betaine, sodium cocoyl glutamate, etc. Desired additional surfactants include fatty acid salts of glutamic acid, alkyl glucosides, taurates, betaines, caprylates and / or mixtures thereof. The oral care composition may also be sulfate-free.

[0141] The oral care composition may include one or more surfactants, each present at a level of from about 0.01% to about 15%, from about 0.3% to about 10%, or from about 0.3% to about 2.5%, by weight of the oral care composition.

[0142] Thickener

[0143] The oral care composition may include one or more thickeners. Thickeners may be used in oral care compositions to provide a gel-like structure to stabilize the dentifrice and / or toothpaste to prevent phase separation. Suitable thickeners include polysaccharides, polymers and / or silica thickeners.

[0144] The thickener may comprise one or more polysaccharides. Some non-limiting examples of polysaccharides include starch; starch glycerol; gums such as gum karaya (gum karaya), gum tragacanth, gum arabic, gum ghatti, gum arabic, xanthan gum, guar gum, and cellulose gum; magnesium aluminum silicate (colloidal magnesium aluminum silicate); carrageenan; sodium alginate; agar; pectin; gelatin; cellulosic compounds such as cellulose, microcrystalline cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, hydroxymethyl carboxypropyl cellulose, methyl cellulose, ethyl cellulose, and sulfated cellulose; natural and synthetic clays such as hectorite clay; and mixtures thereof.

[0145] Other polysaccharides suitable for use herein include carrageenan, gellan gum, locust bean gum, xanthan gum, carbomer, poloxamer, modified cellulose and mixtures thereof. Carrageenan is a polysaccharide derived from seaweed. There are several types of carrageenan, which can be distinguished by their seaweed sources and / or by their degree of sulfation and position. Thickeners may include kappa-carrageenan, modified kappa-carrageenan, iota-carrageenan, modified iota-carrageenan, lambda-carrageenan and mixtures thereof. Carrageenan suitable for use herein includes those commercially available from FMC Company (FMC Company) under the serial name "Viscarin", including but not limited to Viscarin TP 329, Viscarin TP 388 and Viscarin TP 389.

[0146] The thickener may comprise one or more polymers. The polymer may be polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP), polyacrylic acid, a polymer derived from at least one acrylic acid monomer, a copolymer of maleic anhydride and methyl vinyl ether, a cross-linked polyacrylic acid polymer, with various weight percentages of the oral care composition and various ranges of average molecular weight ranges. Alternatively, the oral care composition may be free of, substantially free of, or essentially free of a copolymer of maleic anhydride and methyl vinyl ether.

[0147] The thickener may include one or more inorganic thickeners. Some non-limiting examples of suitable inorganic thickeners include colloidal magnesium aluminum silicate, silica thickeners. Non-limiting examples of useful silica thickeners include, for example, amorphous precipitated silica, such as 165 silica. Other non-limiting silica thickeners include 153, 163 and 167 and 177 and 265 silica products (both available from Evonik Corporation), and Fumed silica.

[0148] The oral care composition may comprise from 0.01% to about 15%, from 0.1% to about 10%, from about 0.2% to about 5%, or from about 0.5% to about 2% of one or more thickening agents.

[0149] Prenylated flavonoids

[0150] The oral care composition of the present invention may include isoprenyl flavonoids. Flavonoid compounds are a group of natural substances widely present in fruits, vegetables, cereals, bark, roots, stems, flowers, tea and wine. Flavonoids can have a variety of beneficial effects on health, such as anti-oxidation, anti-inflammatory, anti-mutagenic, anti-cancer and antibacterial beneficial effects. Isoprenyl flavonoids are flavonoids including at least one isoprenyl functional group (3-methylbut-2-ene-1-yl, as shown in formula VIII), which have previously been identified as promoting connection with cell membranes. Therefore, although it is not desired to be bound by theory, it is believed that adding isoprenyl groups (i.e., isoprenylation) to flavonoids can increase the activity of the original flavonoids by increasing the lipophilicity of the parent molecule and improving the permeability of the isoprenyl molecule to the bacterial cell membrane. Increasing lipophilicity to increase the permeability to the cell membrane may be a double-edged sword, because isoprenyl flavonoids tend to be insoluble under high Log P values ​​(high lipophilicity). Log P can be an important indicator of antimicrobial efficacy.

[0151] Thus, the term prenylated flavonoid may include naturally occurring flavonoids having one or more prenyl functional groups, flavonoids having synthetically added prenyl functional groups, and / or prenylated flavonoids having additional synthetically added prenyl functional groups.

[0152]

[0153] Formula VIII. Isoprenyl functional group, R represents the other part of the molecule

[0154] Other suitable functional groups of the parent molecule that improve the structure-activity relationship (e.g., structure-MIC relationship) of the prenylated molecule include additional heterocycles containing nitrogen or oxygen, alkylamino chains, or alkyl chains substituted onto one or more aromatic rings of the parent flavonoid.

[0155] Flavonoids may have a 15-carbon backbone having at least two benzene rings and at least one heterocyclic ring. Some suitable flavonoid backbones may be shown in Formula IX (flavonoid backbone), Formula X (isoflavanoid backbone), and / or Formula XI (neoflavone backbone).

[0156]

[0157] Formula IX. Flavonoid backbone

[0158]

[0159] Formula X. Isoflavone Main Chain

[0160]

[0161] Formula XI. New flavonoid backbone

[0162] Other suitable flavonoid subgroups include anthocyanidins, anthocyanins, flavanones, flavanols, flavans, isoflavones, chalcones and / or combinations thereof.

[0163] The prenylated flavonoids may include naturally isolated prenylated flavonoids or naturally isolated flavonoids that have been synthetically altered to add one or more prenyl functional groups by a variety of synthetic methods known to those of ordinary skill in the art of synthetic organic chemistry.

[0164] Other suitable prenylated flavonoids can include psoralea chalcone, psoralea flavonoid, methyl psoralea flavonoid, Corylifol A, Epimedin A, Epimedin A1, Epimedin B, Epimedin C, Icariin, Icariin I, Icariin II, Icariin, Isopsoralea chalcone, Isoxanthohumol, Neopsoralea isoflavone, 6-isoprenylnaringenin, 8-isoprenylnaringenin, Sophora flavanone G, (-)-Sophora flavanone, Xanthohumol, Quercetin, Myristolamine, Sophora flavanone, Sophora flavanone, Mulberone G, Mulberone C, Panduratin A, 6-geranylnaringenin, Australone A, 6,8-diisoprenyleucodermol, dorsmanin C, dorsmanin F, 8-isoprenylated kaempferol, 7-O-methyl lupin isoflavone, lupin isoflavone, 6-isoprenylated genistein, isowighteone, yellow lupin weite ketone and / or combinations thereof. Other suitable prenylated flavonoids include cannaflavonoids, such as cannaflavonoid A, cannaflavonoid B and / or cannaflavonoid C.

[0165] Preferably, the prenylated flavonoid has a high probability of having an MIC of less than about 25 ppm against Staphylococcus aureus, a gram-positive bacterium. Suitable prenylated flavonoids include psoralen, methyl psoralen, Corylifol A, icariin, isoxanthohumol, neopsoralen, 6-prenylnaringenin, 8-prenylnaringenin, flavonoid G, (-)-soybean root root, matrine, mulberry root C, Panduratin A and / or combinations thereof.

[0166] Preferably, the prenylated flavonoid has a high probability of having a MIC of less than about 25 ppm against Escherichia coli, a gram-negative bacterium. Suitable prenylated flavonoids include methyl psoralen, isoxanthohumol, 8-isoprenylnaringenin, flavonoid G, matrine, Panduratin A, and / or combinations thereof.

[0167] Approximately 1000 prenylated flavonoids have been identified from plants. Based on the number of prenylated flavonoids reported previously, prenylated flavonoids are the most common subclass and prenylated flavanols are the rarest subclass. Although natural prenylated flavonoids have been detected with a variety of structural characteristics, their distribution range in plants is narrow, unlike the parent flavonoids, which are present in almost all plants. Most prenylated flavonoids are found in the following families, including Cannabaceae, Guttiferae, Leguminosae, Moraceae, Rutaceae, and Umbelliferae. Leguminosae and Moraceae, due to their consumption as fruits and vegetables, are the most commonly studied families, and many novel prenylated flavonoids have been explored. Hops from the Cannabaceae family include 8-prenylnaringenin and isoxanthohumol, which play an important role in the health benefits of beer.

[0168] The prenylated flavonoids can be incorporated via the hops extract, incorporated into a separately added extract, or added as a separate component of the oral care compositions disclosed herein.

[0169] Other Ingredients

[0170] The oral care composition may contain a variety of other ingredients, such as flavoring agents, sweetening agents, coloring agents, preservatives, buffering agents, or other ingredients suitable for use in oral care compositions, as described below.

[0171] Flavoring agents can also be added to the oral care composition. Suitable flavoring agents include wintergreen oil, peppermint oil, spearmint oil, clove bud oil, menthol, p-propenylanisole, methyl salicylate, eucalyptol, cinnamon, 1-menthyl acetate, sage, eugenol, parsley oil, hydroxyphenyl butanone, α-ionone, sweet oregano, lemon, orange, propenyl ethyl guaiacol, cassia bark, vanillin, ethyl vanillin, heliotropin, 4-cis-heptenal, diacetyl, methyl p-tert-butylphenyl acetate, and mixtures thereof. Coolants can also be part of the flavoring system. Preferred coolants in the compositions of the present invention are p-menthanecarbamoyl agents, such as N-ethyl-p-menthane-3-carboxamide (commercially known as "WS-3") or N-(ethoxycarbonylmethyl)-3-p-menthanecarboxamide (commercially known as "WS-5") and mixtures thereof. Flavor systems are typically used in the composition at levels of from about 0.001% to about 5% by weight of the oral care composition.These flavoring agents typically comprise mixtures of aldehydes, ketones, esters, phenols, acids, and aliphatic, aromatic and other alcohols.

[0172] Sweeteners can be added to the oral care composition to impart a pleasant taste to the product. Suitable sweeteners include saccharin (e.g., sodium saccharin, potassium saccharin, or calcium saccharin), cyclamate (e.g., sodium, potassium, or calcium salts), acesulfame-K, afritosin, neohesperidin dihydrochalcone, aminated glycyrrhizin, dextrose, levulose, sucrose, mannose, sucralose, stevioside, and glucose.

[0173] Colorants are added to improve the aesthetic appearance of the product. Suitable colorants include, but are not limited to, those approved by the appropriate regulatory agencies such as the FDA and those listed in the European Food and Drug Directive, and include pigments such as TiO 2 , and colors such as FD&C and D&C dyes.

[0174] Preservatives may also be added to the oral care composition to prevent bacterial growth. Suitable preservatives approved for use in oral compositions, such as methylparaben, propylparaben, benzoic acid, and sodium benzoate, may be added in safe and effective amounts.

[0175] Titanium dioxide may also be added to the compositions of the present invention. Titanium dioxide is a white powder that adds opacity to the composition. Titanium dioxide generally comprises from about 0.25% to about 5% by weight of the oral care composition.

[0176] Other ingredients may be used in the oral care composition, such as desensitizing agents, healing agents, other anticaries agents, chelating / sequestering agents, vitamins, amino acids, proteins, other anti-plaque / anticarctic agents, sunscreens, antibiotics, anti-enzymes, enzymes, pH control agents, oxidants, antioxidants, and the like.

[0177] Example

[0178] The following examples further illustrate the present invention, and these examples should not be understood in any way to limit the scope of the present invention. After reading the description herein, various other aspects, modifications and equivalents thereof can be proposed to those of ordinary skill in the art without departing from the spirit of the present invention or the scope of the appended claims.

[0179] Experimental methods

[0180] Acid production and acid inhibition [%]

[0181] Acid production and acid inhibition were measured using the in vitro dental plaque glycolysis model (iPGRM). The purpose of this technique is to provide a simple and rapid method for determining whether a compound has an effect on the metabolic pathways used by dental plaque microorganisms to produce toxins that adversely affect gum health.

[0182] In vitro dental plaque glycolysis model (iPGRM) is a technique in which dental plaque is grown from human saliva and treated with various reagents to determine the antiglycolytic activity of the treatment. When bacteria convert sugars into energy with the help of enzymes, acids are formed. These acids demineralize and damage tooth enamel. The purpose of this technology is to provide a simple and rapid method for determining whether a therapeutic compound has an inhibitory effect on the metabolic pathways used by dental plaque microorganisms to produce acids or toxins and / or inhibit their growth. For the purpose of this work, if the test treatment composition contains Sn, a Sn placebo should be tested. In addition, the antibacterial composition should be tested relative to its placebo to determine the iPGRM value of the antibacterial composition alone. This is important if a buffer, such as bicarbonate, orthophosphate, calcium carbonate, is present in the composition in addition to the antibacterial composition.

[0183] Dental plaque biofilms from freshly pooled human saliva and trypticase soy broth (TSB) were grown on glass rods at 37°C for 2 days by dipping the rods into and out of the culture medium in a reciprocating motion. Treatments were either 2-minute dentifrice slurries in water (1:5) or treatments diluted in water (1:5). After treatment, the biofilms were incubated with TSB and sucrose until the pH indicator showed a color change (approximately 6 hours). The pH of the culture medium solution was then measured to determine the amount of glycolysis inhibition relative to the negative control.

[0184] On day 1, new glass rods (5 mm x 90 mm) were polished on a lathe approximately 25 mm from the untipped end using 240 grit, 320 grit, 400 grit, and 600 grit silicon carbide papers, in sequence. After the initial polish, the rods should be polished with 600 grit paper before each test. After polishing, the rods are stored until the test is ready to be run. Enough rods should be polished for a full rack treatment. A rack can process 12 compositions with 4 replicates of each composition, resulting in a rack with 48 rods.

[0185] On the second day, saliva was collected from a group of 5-10 people by paraffin stimulation every day during the test and refrigerated at 4°C until saliva was needed throughout the day. Carefully concentrate the saliva (do not pour wax / mucus) and mix thoroughly before use. The rod is taken out of the storage device, rinsed with deionized water to remove any sanding residue, disinfected in a 70% ethanol / water solution, and dried on a sterile surface. Subsequently, the rod is loaded into the hanging rack of the support, which is used to continuously immerse the rod in a culture medium bottle containing a growth medium. Adjust the rod height and use a rubber o-ring to fix each rod in place. In the early afternoon, 7mL of growth medium (160g of 3% TSB solution containing 3% sucrose) was mixed with 240g of collected human saliva. This TSB / sucrose solution should be sterilized by autoclave, and then merged with the collected human saliva. ) In a culture medium bottle. The culture medium bottle is arranged under the hanging rod on the support in the incubation oven. The incubator had been previously modified so that the dipping motor could dip the rod into the medium vial, dipping 1.5 cm of the rod into the growth medium at a frequency of 1 dip per minute without the rod touching the wall of the medium vial. The rod was immersed in this manner overnight.

[0186] On day 3, prepare enriched growth medium (mix 500 g of a solution of 3% TSB and 10% sucrose with 33 g of pooled human saliva. This TSB / sucrose solution should be sterilized by autoclave and then combined with the pooled human saliva.). Pipette this enriched growth medium into a new set of media vials (7 mL per vial) and replace the overnight growth medium from day 1. Immerse the rods in this enriched growth medium for 5 hours throughout the day in an incubation oven at 37°C. At the end of the day, prepare new overnight growth medium (mix 40 g of a solution of 3% TSB with 360 g of pooled human saliva and 0.5 g sucrose), pipette into a new set of media vials, and replace the enriched growth medium. Immerse the rods overnight in the same manner as on day 1.

[0187] On the 4th day, glycolysis medium was prepared by mixing 0.15g TSB, 25g sucrose and 500mL deionized water to obtain an aqueous solution of 0.03% TSB and 0.5% sucrose. This solution was mixed and then sterilized in an autoclave. The pH was then adjusted to 6.5 using 0.1M HCl and pipetted into a new culture medium vial (7mL). Two additional vials were filled compared to what was required for the stick holder as a pH blank. Two drops of chlorophenol red solution were added to each of the 4 test tubes containing the negative control (caries protection slurry). Three drops of bromocresol purple solution were added to the 2 test tubes containing the positive control (1% chlorhexidine solution). The support was set aside before the treatment was completed. A vial containing 12mL deionized water was prepared to rinse off the treated material. A vial containing a treatment slurry / solution (7mL) of homogenized treated material and water was prepared. The rod is immersed in the treatment vial for 2 minutes, rinsed 10 times in the first set of rinse vials, 10 times in the second set of rinse vials, 10 times in the third set of rinse vials, and returned to the incubator rack. The entire biofilm is treated and rinsed. Once all treatments are completed, the biofilm on the rod is completely immersed in the glycolysis medium in the incubation oven without immersion for 2 hours. After two hours, the immersion device is activated. The total incubation time is between 3 hours and 7 hours. The incubation is terminated when the pH in the glycolysis medium of the negative control is between 4.8-5.6, more ideally 4.9-5.2, and when the pH in the glycolysis medium of the positive control is higher than that of the negative control. If the indicator dye in the positive control turns yellow, that is, the pH drops below 5.2, the incubation time is too long and the test needs to be repeated.

[0188] After the incubation was terminated on day 4, the sticks were removed from the glycolysis medium and allowed to dry in an oven. The glycolysis medium was removed from the incubation oven, allowed to return to room temperature, and the pH was measured in each vial and the blank vial to determine the average pH change of the medium after treatment. The change in pH was determined relative to the blank vial. If the final pH of the blank was less than 6.6, the test should be repeated. If the difference between the positive and negative controls in the Student's t-test was not significant, the test should be repeated. If the pH change of the negative control relative to the blank was less than 1, the test should be repeated.

[0189] After measuring the pH of all vials, the ΔpH of each vial was determined by subtracting its pH from the average pH of the blank. Glycolysis inhibition efficacy was determined by the following formula. The average ΔpH of the treatments was determined by averaging the results of four replicate vials per treatment.

[0190]

[0191] If the efficacy of the positive control (1% chlorhexidine solution) was not between about 65% and about 85% relative to the negative control (Crest Cavity Protection, Procter & Gamble, Cincinnati, OH), the test was repeated.

[0192] Anti-caries activity

[0193] The test design used herein is similar to those found in FDA Method #37 for the Fluoride Anti-caries OTC Monograph. The major changes are the diet used (MIT 200 instead of #469), the caries scoring method (keyer method instead of HMA), and the treatment frequency. The experimental procedures were performed in accordance with Part 58 of the FDA regulations.

[0194] Using litter size as a covariate, 50 to 58 animals per treatment group (depending on the type of fluoride) were used to meet the ADA's Board of Dental Therapeutics' most stringent power requirement of a 20% clinical difference between treatments at 80% power. However, we routinely use 40 animals per treatment group, and the ADA's CDT and FDA have consistently accepted these tests. This requires starting the study with 40 animals per group. Twenty-three (23) litters provided these animals. When studies are set up like this, it has been found that treatment differences of approximately 16% are sometimes significant and are therefore generally considered the tipping point for clinical significance.

[0195] All protocols were reviewed and approved by the Institutional Animal Care and Use Committee prior to receipt of animals.

[0196] Animals were weaned mixed-sex Sprague Dawley rats; weighing 29 g-53 g. Due to the supplier's shipping schedule, dams and their entire litters were received. Littermates were received when pups were 6 days old and litter size was reduced to ten (10) pups per litter at 8 days of age. Twenty-five (25) litters were purchased. The additional five litters were to account for any mortality prior to stratification. After study stratification, any unused animals were euthanized.

[0197] The same litter pups are kept in large solid bottom (box type) cages with mother mice until the pups are weaned at 18 days old. Starting from the 9th day of the pups, the mother mice are placed in rotation in the nest every day until the pups are weaned at 18 days old. The pups are kept in box cages until 21 days old. At this point, the pups are layered and placed in pairs in a hanging wire bottom cage, which has been cleaned and disinfected before use. It is necessary to change the cages to prevent the artificial increase of dental caries rate due to direct contact with bedding. The cages are arranged so that all animals of a single group are together, and the cages are marked with the group name and treatment (treatment code) received by the animals.

[0198] When the pups were 21 days old, they were given unique numbers by ear punching and a record of littermates was kept. The animals were divided into groups in a way that littermates, weight and sex were balanced across groups. There were 40 animals per group.

[0199] Dams and littermates were provided with a rodent laboratory diet upon receipt until pups were 8 days old. On day 8 (young), dams and littermates were provided with diet MIT 305. Dams and littermates were provided with diet MIT 200 ad libitum on day 18 (young) and throughout the experimental period. Deionized water was provided ad libitum to all animals.

[0200] Cages were changed on the 13th and 18th day of age. After the inoculum was applied, cages and bedding were decontaminated by autoclaving before disinfection. Cage plates were changed three times a week when fresh food and water were given (Monday, Wednesday and Friday). Clean and disinfected water bottles and food cans were provided weekly. Cages and storage tanks were disinfected every two weeks. Animals were observed daily by staff and weekly by the attending veterinarian for any signs of health problems. Animals were housed in a facility accredited by AAALAC. Room temperature was maintained at 72°F (± 6°F), with 10-15 air changes per hour and a 12-hour light cycle.

[0201] On day 15 (young), animals received an oral inoculation of a streptomycin-resistant S. sobrinus 6715 (ATCC strain #27352) culture. This consisted of injecting 0.2 ml of culture / animal into the oral cavity. On day 18 (young), animals were inoculated with S. sobrinus for three consecutive days (18, 19, and 20 days of age). This consisted of placing 0.1 ml of S. sobrinus culture on the occlusal surface of each mandibular molar quadrant, placing 10 cc of this concentration-adjusted culture into each sterilized and filled water bottle, and lightly spraying no more than 10 cc of the remaining culture on the litter. 24 hours after the addition of the inoculum, all water bottles were removed and sterilized. The inoculum was administered to the animals using a 200 micropipette.

[0202] The treatment phase began on the 22nd day of infancy. Each treatment used a labeled plastic beaker that was only suitable for that treatment. Fresh materials (i.e., obtained from the raw material supply) were used for each treatment. Dentifrice was mixed with deionized water at a 1:1 ratio (by weight). Specifically, 10 grams of dentifrice was weighed into a 30 ml beaker; 10 grams of deionized water was then added to the dentifrice. The mixture was then manually stirred (30 seconds) with a clean micro-scraper to produce a smooth mixture. The beaker containing the slurry and a small magnetic stirring bar was placed on a magnetic stirrer, which was set to the lowest speed and stirred for four (4) minutes before treatment. The slurry was prepared immediately before each treatment.

[0203] A cotton-tipped applicator was dipped into the slurry (for 2 seconds) and applied to half of the rat's mouth in such a way that the side of the applicator was in contact with the mandibular and maxillary molars on one side of the mouth. The treatment was completed by using a rolling motion of the side of the applicator on the mandibular and maxillary molars for 15 seconds. The applicator was dipped into the slurry a second time (again, for 2 seconds), and the other side of the rat's mouth was similarly treated for 15 seconds. A new applicator was used for each animal.

[0204] Treatments were administered twice daily for five days, with one treatment daily on weekends. The first treatment of each day began at approximately the same time each day, and the second treatment began no earlier than six hours after the first treatment. Single treatments were administered at 24-hour intervals on weekends. Treatment materials were stored at room temperature. All treatment products were returned to the Sponsor upon completion of the study.

[0205] One week after the start of the vaccination regimen and at the termination of the study, oral swabs were obtained from each rat using a sterile cotton swab (six-inch, single-ended applicator). Microorganisms on the mandibular and maxillary molars were sampled by rolling the swab on one side of the oral cavity for 15 seconds, on the tongue, and on the molar on the other side of the oral cavity for another 15 seconds. Immediately after the applicator was removed from the animal's oral cavity, it was streaked across half of a 100 mm Petri dish containing S. salivarius agar, to which 200 units / ml of streptomycin sulfate had been added. The plates were incubated at 37°C and 10% CO. 2 Incubate at 40 °C for 48 h. Record the colony counts collected after 48 h of incubation in the log.

[0206] The experimental duration of the rat caries study was three weeks. Immediately prior to termination, all animals were observed for any visual signs of poor health or pathology, weighed individually, and oral swabs were collected to confirm S. sobrinus implantation. The animals were euthanized by carbon dioxide inhalation. A code number was assigned to each animal, and the head was then removed, placed in a separate tank along with the code number, and steamed under pressure (10 PSI for 12 minutes). The half jaws were then removed and all soft tissues removed.

[0207] The cleaned half jaws (four quadrants) were placed in plastic vials with code numbers taped to the vials. Murexide solution (0.3 g Murexide; 300 ml DI H20 and 700 ml ethanol) was added to each vial and the jaws were stained overnight. The jaws were then rinsed and air dried.

[0208] The smooth surface caries of the hemi-jaws were examined under a microscope, sections were taken, and then examined under a microscope for groove caries and interdental caries using the Keyes method. The scoring method is described in detail in Navia, JN, Animal Models in Dental Research, pp. 287-290, 1977; and Keyes, PH, J.Dent.Res .37:1088-1099,1958. All analyses were performed using SAS statistical software (version 9.4). Groups were compared using analysis of variance (ANOVA) with a fixed effect for group and a random effect for littermates. Littermate effects were included in the model to reduce known factors that affect the variability of the measurements. Paired comparisons between groups were performed using Tukey's multiple comparison procedure to control the overall significance level of the comparisons (α=0.05).

[0209] Specific types of data for tabulation and statistical analysis can include:

[0210] 1) Experimental phase of mortality data

[0211] a. Initial number of animals

[0212] b. Final number of animals

[0213] c. Mortality rate percentage

[0214] 2) Growth data experiment phase

[0215] a. Initial body weight (mean ± SEM)

[0216] b. Final body weight (mean ± SEM)

[0217] 3) Tooth decay experiment

[0218] a. Smooth surface (buccal and lingual) lesions involving enamel and dentin (mean

[0219] ±SEM)

[0220] b. Enamel and dentin involvement in interdental lesions (mean ± SEM)

[0221] c. Total smooth surface (buccal, lingual, and interdental) lesions involving enamel and dentin

[0222] (mean ± SEM)

[0223] d. Enamel and dentin involvement in gingival sulcus lesions (mean ± SEM)

[0224] e. Total caries involvement combined with Keyes scoring for smooth surface, interdental and groove caries

[0225] (mean ± SEM)

[0226] Preparation of oral care compositions

[0227] The oral care composition of Table 1A is prepared by combining one or more wetting agents, water, sweeteners, tin ion sources, sodium gluconate and / or flavoring agents to produce a liquid mixture. The liquid mixture is homogenized for 2 minutes at 25°C. Then, sodium hydroxide (50% solution) is added to the liquid mixture, and the liquid mixture is homogenized for 2 minutes at 25°C. A separate powder mixture is prepared by mixing a portion of a calcium ion source and any thickener such as xanthan gum and / or sodium carboxymethyl cellulose. The powder mixture is then mixed with the liquid mixture. Then, a surfactant such as sodium lauryl sulfate is added to the mixture. The contents are homogenized for 2 minutes at 25°C. Then the hop extract is mixed with the mixture and homogenized for 2 minutes at 25°C. Finally, the remainder of the calcium ion source and buffer are mixed with the mixture and homogenized for 2 minutes at 25°C.

[0228] Preparation of commercial oral care compositions using hop beta acid

[0229] The commercial oral care composition was mixed with the hop beta acid extract or total hop extract by weighing out a portion of the commercial oral care composition and mixing in an appropriate amount of hop extract. The mixed oral care composition was homogenized at 25°C for at least 2 minutes.

[0230] Table 1A. Oral Care Compositions

[0231] Recipe A Recipe B Recipe C glycerin 49.10 47.80 - Sorbitol - - 37.98 water - - 13.00 Sodium monofluorophosphate - 1.15 - Sodium Gluconate 1.00 1.00 1.00 <![CDATA[SnCl 2 ]]> 1.10 1.10 1.10 <![CDATA[CaCO 3 ]]> 32.00 32.00 32.00 Xanthan gum 0.50 0.50 0.30 Carboxymethyl cellulose - - 1.00 Carbomer 1.00 1.00 - Sodium lauryl sulfate 1.40 1.40 1.29 Flavoring 1.00 1.00 1.00 Saccharin Sodium 0.40 0.40 0.50 Stevioside 0.30 0.30 - Sodium hydroxide 1.20 1.35 0.33 Hops beta acid extract* 0.50 0.50 0.50 Sodium bicarbonate 10.00 10.00 10.00 Titanium Dioxide 0.50 0.50 -

[0232] * Hops beta acid extract, from Provided with 45% hop beta acids and less than 1% hop alpha acids

[0233] According to the experimental method described above, the formulations A, B and C shown in Table 1A were prepared. Hop beta acid was Available as an extract from hops. The extract was about 45% hop beta acids by weight of the extract, and less than 1% hop alpha acids by weight of the extract. Formulations A and B had hop beta acids without separately added water. Formulations A and B differed only in that Formulation B included a fluoride ion source (sodium monofluorophosphate, NaMFP) which was used in the total enamel caries test shown in Table 4. Formulation C included hop beta acids without fluoride in a high water base.

[0234] Table 1B. Specifications of hop beta acid extract

[0235] Element Amount (weight %) Hops beta acid 45±2 Hops alpha acid 0.4±0.3 Hops Oil 1.5±0.5 Propylene glycol 20±15 water <8％ pH 11±0.5

[0236] Table 1B describes the A hop beta acid extract is provided. Because hop beta acids are provided in an extract form, there may be some variability in the amounts of certain components. However, the extract contains about 45% hop beta acids by weight of the extract and about 0.4% hop alpha acids by weight of the extract. This is significantly different than previous hop extracts, which typically contain more hop alpha acids than hop beta acids. Other trace components may be present in the hop beta acid extract.

[0237] Table 2. Acid production and glycolysis inhibition after 3-day biofilm treatment [%]

[0238]

[0239] Table 2 shows the changes in acid production in 3-day biofilms using the iPGRM assay described herein. After toothpaste treatment, the average acid product was 1.55 and the average inhibition rate was 3.43%. Toothpaste treatment of biofilm for 3 days resulted in a reduction in acid production, and a net average acid inhibition of 43.14% ( Pro-Health TM ) and 68.49%( Gum Care). This is an expected result since stannous ions are known to act as antimicrobial agents, which can reduce the number of acid-producing bacteria in the biofilm. 2 ), GumCare performed slightly better than Pro-Health TM Chlorhexidine is an antibacterial agent that may be prescribed for the treatment of gingivitis. Treatment with chlorhexidine resulted in an average acid inhibition of 75.12%, which is not unexpected since chlorhexidine is known as an extremely effective antibacterial agent.

[0240] Table 2 also shows that Formulations A and C showed essentially zero acid production, with an average acid inhibition of approximately 100%. Unexpectedly, in the absence of fluoride and / or chlorhexidine (two of the most common and effective antimicrobial agents), Formulations A and C (without a fluoride ion source) would be essentially 100% effective in preventing acid production.

[0241] Table 3. Total enamel caries

[0242]

[0243] aSilica placebo is a negative control that does not contain any fluoride ion source

[0244] b NaMFPc at 1000ppm NaF 1100ppm + silica is a positive control with silica and fluoride ion source

[0245] Table 3 shows the results of the rat caries test, FDA No. 37. The rat caries test is a biological test method required by the U.S. FDA monograph to show the efficacy of anticaries drugs, which currently only includes fluoride ion sources. As shown in Table 3, the negative control, silica placebo, is a toothpaste containing silica abrasive but without any fluoride ion source. Silica + NaMFP is USP NaMFP toothpaste containing sodium monofluorophosphate and silica abrasive. Cavity Protection is a toothpaste containing sodium fluoride and silica abrasive. In contrast, Formulation A does not contain a fluoride ion source or silica abrasive, but does contain hops beta acid and stannous chloride. Unexpectedly, Formulation A (26.23) behaved similarly to Cavity Protection in the absence of any fluoride ion source. Cavity Protection (25.28), a dentifrice containing 1100 ppm sodium fluoride. In addition, Formula A outperformed the dentifrice containing sodium monofluorophosphate and silica abrasive (Formula A was 26.23 and NaMFP was 31.55). The only anti-caries drugs listed by the US FDA are stannous fluoride, sodium fluoride, and sodium monofluorophosphate. In other words, Formula A is a fluoride-free anti-caries toothpaste.

[0246] Table 4. Final pH, acid production and glycolysis inhibition [%] after 3 days of biofilm treatment

[0247]

[0248] Table 4 shows that hop beta acid can be added to non-fluoride toothpaste and provide additional benefits, including toothpastes with a variety of active agents, abrasives, water content, polyphosphates, etc. As shown in Table 4, the addition of hop beta acid improves the antibacterial performance of the non-fluoride oral care composition by the iPGRM test method. Importantly, the antibacterial performance is not improved by adding a hop extract including both hop alpha acid and hop beta acid. In fact, the extract including hop alpha extract and hop beta extract, "total hop extract", reduces the antibacterial performance in many cases.

[0249] The hop extract used was the hop beta extract of Table 1B. The total hop extract included hop alpha acids and hop beta acids. Hops alcohol-free liquid extract ("total hop extract") was purchased from Hawaii Pharm and used as is. Hops beta acid extract was added at 0.5% by weight and hops total extract was added at 0.64% by weight. Different amounts of extract were used to balance the different concentrations of extracted hop acids in either composition. In all cases, the amount of hop acids (hop alpha acids + hop beta acids or essentially only hop beta acids) was essentially equal to about 0.23%.

[0250] For example, hop beta acid extract and total hop extract were added to Tom's of Maine Rapid Relief, which did not contain fluoride but included arginine, calcium carbonate, and silica, as shown in Table 4. Adding hop beta acid extract to Tom's of Maine increased acid inhibition from 9.8% to 94.0%. Adding total hop extract to Tom's of Maine only slightly increased acid inhibition from 9.8% to 11.6%.

[0251] In other formulas where hops were added at the same level as used here (0.5 wt % solution), the average effect of hops was an additional 60% acid inhibition. However, in the Tom's of Maine Rapid Relief formula containing hops, the additional benefit was about 84%, with an increase of 25% in acid inhibition. The Tom's of Maine Rapid Relief formula has a basic amino acid, arginine. It is well known that arginine-decomposing bacteria that can consume arginine still prefer to consume sugars and acids in the presence of a sugar source and at low pH (i.e., the conditions of the iPGRM used here). Therefore, in order for bacteria to effectively use arginine to produce ammonia and neutralize acids to form biofilms, the biofilm pH is required to be maintained at a fairly high level. This tends to hinder the effectiveness of arginine in biofilms where sugars are present and the pH is low. As shown in Table 4, hops activate the arginine-decomposing bacterial pathway by preventing the pH from dropping in the presence of sugars. Unexpectedly, this produces a synergistic effect and produces a more effective stable biofilm pH than either ingredient can achieve on its own.

[0252] Therefore, hop beta acid is a very effective antibacterial agent, regardless of the chassis, and can also improve existing dentifrice formulations. Hop beta acid can improve the antibacterial activity in dentifrice compositions containing sodium fluoride, sodium monofluorophosphate and / or stannous fluoride. In addition, hop beta acid can improve the antibacterial properties in dentifrice compositions that do not contain fluoride. Hop beta acid can improve the antibacterial activity in dentifrice compositions of anhydrous, low water, medium water or high water formulations. Hop beta acid can improve the antibacterial activity in dentifrice compositions containing silica abrasives and / or calcium abrasives such as calcium carbonate. Hop beta acid can improve the antibacterial activity in dentifrice compositions containing basic amino acids such as arginine. Hop beta acid can improve the antibacterial activity in dentifrice compositions containing tin ion sources, zinc ion sources or a combination of tin and zinc ions. Importantly, these benefits were not found when using total extracts (i.e., extracts containing hop alpha acid and hop beta acid).

[0253] Thus, described herein are oral care compositions having an average acid inhibition of at least 50%, at least 55%, at least 60%, at least 70%, or at least 80% when hop beta acids are added via a hop beta acid extract, direct addition of one or more hop beta acids, or any other suitable source of hop beta acids.

[0254] The dimensions and values ​​disclosed herein are not to be understood as being strictly limited to the exact numerical values ​​cited. Instead, unless otherwise indicated, each such dimension is intended to represent the stated value and a functionally equivalent range around that value. For example, a dimension disclosed as "40 mm" is intended to mean "about 40 mm".

[0255] Unless expressly excluded or otherwise limited, each document cited herein, including any cross-referenced or related patent or patent application and any patent application or patent to which this application claims priority or the benefit of, is hereby incorporated by reference in its entirety. The citation of any document is not an admission that it is prior art to any of the present invention disclosed or claimed herein, or an admission that it, by itself or in combination with any one or more of the references, proposes, suggests, or discloses any such invention. In addition, to the extent that any meaning or definition of a term in this invention conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this invention shall govern.

[0256] Although specific embodiments of the present invention have been illustrated and described, it will be apparent to those skilled in the art that various other changes and modifications may be made without departing from the spirit and scope of the present invention. Therefore, it is intended that all such changes and modifications within the scope of the present invention be covered in the appended claims.

Claims

1. An oral care composition comprising: (a) from 0.01% to 10%, by weight of the composition, of hop beta acids, the hop beta acids being provided in the form of a hop extract, wherein the hop extract comprises greater than 0% and less than 2.5% hop oils, by weight of the hop extract, and wherein the hop extract comprises a ratio of hop beta acids to hop alpha acids, by weight of the hop extract, of greater than 5 and less than 1000; (b) 0.01% to 10%, by weight of the composition, of a source of tin ions; (c) abrasives; The oral care composition is free of fluoride.

2. The oral care composition of claim 1, wherein the hop beta acid comprises lupulone, paralupulone, addaluplupulone, or a combination thereof.

3. The oral care composition of claim 1, wherein the abrasive is a calcium abrasive.

4. The oral care composition of claim 1, wherein the abrasive comprises calcium carbonate.

5. The oral care composition of claim 1, wherein the oral care composition is a toothpaste.

6. An oral care composition according to any one of claims 1 to 5, wherein the oral care composition comprises from 0.2% to 1%, by weight of the composition, of a source of tin ions.

7. The oral care composition of any one of claims 1-5, wherein the oral care composition further comprises a zinc ion source.

8. The oral care composition of any one of claims 1-5, wherein the tin ion source comprises stannous chloride.

9. The oral care composition of any one of claims 1-5, wherein the oral care composition has at least 60% acid inhibition in an in vitro dental plaque glycolysis and regrowth model.

10. The oral care composition of any one of claims 1-5, wherein the oral care composition comprises from 1% to 20%, by weight of the composition, of a buffering agent.

11. The oral care composition of claim 10, wherein the buffering agent comprises bicarbonate.

12. An oral care composition comprising: (a) from 0.01% to 10%, by weight of the composition, of hop beta acids, the hop beta acids being provided in the form of a hop extract, wherein the hop extract comprises greater than 0% and less than 2.5% hop oils, by weight of the hop extract, and wherein the hop extract comprises a ratio of hop beta acids to hop alpha acids, by weight of the hop extract, of greater than 5 and less than 1000; (b) from 0.01% to 10%, by weight of the composition, of a source of tin ions; and (c) 10% to 50% by weight of the composition of calcium, The oral care composition is free of fluoride.

13. The oral care composition of claim 12, wherein the oral care composition is free of silicon dioxide.

14. The oral care composition of claim 12, wherein the hop beta acids comprise lupulones, paralupulones, addaluplupulones, or combinations thereof.

15. The oral care composition of claim 12, wherein the calcium comprises calcium carbonate.

16. The oral care composition of claim 12, wherein the oral care composition is a toothpaste.

17. An oral care composition according to any one of claims 12 to 16, wherein the oral care composition comprises from 0.01% to 10% by weight of the composition of an antibacterial agent.

18. An oral care composition according to any one of claims 12-16, wherein the oral care composition comprises from 0.2% to 1%, by weight of the composition, of a source of tin ions.

19. The oral care composition of any one of claims 12-16, wherein the oral care composition further comprises a zinc ion source.

20. The oral care composition of any one of claims 12-16, wherein the source of tin ions comprises stannous chloride.

21. The oral care composition of any one of claims 12-16, wherein the oral care composition has a glycolysis inhibition percentage of at least 60% in an in vitro dental plaque glycolysis and regrowth model.

22. An oral care composition according to any one of claims 12-16, wherein the oral care composition comprises from 1% to 20%, by weight of the composition, of a buffering agent.

23. The oral care composition of claim 22, wherein the buffering agent comprises bicarbonate.

24. An oral care composition comprising: (a) from 0.01% to 10%, by weight of the composition, of hop beta acids, the hop beta acids being provided in the form of a hop extract, wherein the hop extract comprises greater than 0% and less than 2.5% hop oils, by weight of the hop extract, and wherein the hop extract comprises a ratio of hop beta acids to hop alpha acids, by weight of the hop extract, of greater than 5 and less than 1000; (b) arginine; The oral care composition is free of fluoride.

25. The oral care composition of claim 24, wherein the hop beta acids comprise lupulones, paralupulones, addaluplupulones, or combinations thereof.

26. The oral care composition of claim 24, wherein the oral care composition further comprises lysine.

27. An oral care composition according to any one of claims 24-26, wherein the oral care composition is a toothpaste.

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