Methods of using oral care compositions comprising hops

Abstract

Methods of using oral care compositions comprising hops are disclosed. Methods of using non-fluoride anti-cavity oral care compositions. Methods of using anti-cavity toothpaste comprising hops. Methods of using anti-cavity toothpaste comprising hops but not containing fluoride. Methods of using oral care compositions comprising hops and optionally not containing fluoride to treat, reduce, and / or prevent dental caries.

Description

Technical Field

[0001] This invention relates to methods of using oral care compositions containing hops. This invention also relates to methods of using fluoride-free anti-cavity oral care compositions. Background Technology

[0002] Oral care compositions (such as toothpaste and / or dental cleaning compositions) are applied to the oral cavity to clean and / or maintain the aesthetics and / or health of teeth, gums, and / or tongue. Additionally, many oral care compositions are designed to deliver active ingredients directly to oral care surfaces. For example, toothpaste compositions may contain fluoride sources such as sodium fluoride, sodium monofluorophosphate, and / or stannous fluoride as caries-preventing agents. While the effectiveness and safety of fluoride as a caries-preventing agent are well-known, many consumers require other options for cavity protection.

[0003] Unfortunately, due to the acid produced by bacteria found on the tooth surface, current fluoride-free oral care compositions cannot provide sufficient or any protection against tooth decay. Therefore, there is a need for methods that use fluoride-free oral care compositions that provide beneficial anti-cavity effects. Summary of the Invention

[0004] This article discloses a method for treating, reducing, or preventing tooth decay, the method comprising (a) dispensing a toothpaste composition onto a toothbrush, (b) applying the toothpaste composition to the oral cavity for at least 1 minute, and (c) spitting out the toothpaste from the oral cavity, wherein the toothpaste composition comprises hops and abrasives.

[0005] This article also discloses a method for treating, reducing or preventing tooth decay, the method comprising: (a) instructing a user to apply a toothpaste composition to a toothbrush, and (b) instructing a user to apply the toothpaste composition to the user's oral cavity, wherein the toothpaste composition comprises hops and abrasive.

[0006] This article also discloses a method for treating, reducing or preventing dental caries, the method comprising: (a) applying an oral care composition to the oral cavity, the oral care composition comprising hops, and (b) spitting out the oral care composition from the oral cavity.

[0007] This article also discloses hop β-acid as a medicine, preferably wherein the medicine is an oral care composition.

[0008] This article also discloses hops used in the treatment of tooth decay.

[0009] This article also discloses the use of hops to reduce white spots in the oral cavity, preferably where the white spots in the oral cavity are on teeth and can be attributed to dental caries, cavities and / or a combination thereof. Detailed Implementation

[0010] This invention relates to methods for treating tooth decay, dental caries, gingivitis, and / or combinations thereof using compositions containing hops. The disclosed hop-containing compositions can be used to treat, reduce, or prevent dental caries.

[0011] Tooth decay, or cavities, is the breakdown of teeth caused by acids produced by bacteria. Cavities are created by acids produced when bacteria dissolve the hard tissues of the tooth, such as enamel, dentin, and / or cementum. Acids are produced by bacteria as they break down food debris or sugars on the tooth surface.

[0012] Fluoride works by reducing the solubility of tooth enamel in the acid produced by bacteria, known as plaque acid. Tooth enamel is made of hydroxyapatite (Ca5(PO4)3(OH)). Hydroxyapatite can dissolve from enamel at pH below 5.5 (demineralization). If hydroxyapatite is demineralized in the presence of fluoride ions, fluorapatite (Ca5(PO4)3(F)) can remineralize on the surface of the enamel. In short, this process involves the substitution of hydroxyl (OH) ions with fluoride (F) ions. Even under acidic conditions, fluorapatite is inherently less soluble than hydroxyapatite. Therefore, fluoride is used as an anti-caries agent to make the tooth surface more resistant and less soluble in plaque acid.

[0013] While not wishing to be bound by theory, the disclosed oral care compositions are believed to have a mechanism of action different from fluoride therapy. In contrast to the single-symptom treatment of fluoride (i.e., the result of treating plaque acid), the disclosed compositions are believed to have anti-cavity activity through a combination of effects that collectively lead to anti-cavity action. While not wishing to be bound by theory, the disclosed oral care compositions are believed to have anti-cavity action 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 on hard tissue surfaces.

[0014] Inhibition of pectin production can be achieved by providing one or more antimicrobial agents to kill the source of pectin (i.e., the bacteria themselves) and / or by providing one or more biofilm modifiers to disrupt and encapsulate the antimicrobial agents within the biofilm matrix.

[0015] Neutralizing dental plaque acid can be achieved by providing one or more biofilm modifiers to disrupt the biofilm matrix and / or by providing one or more buffers to buffer the generated dental plaque acid and / or by providing one or more calcium ion sources to increase the calcium ion saturation on the enamel surface.

[0016] Reducing the solubility of hydroxyapatite on hard surfaces can be achieved by providing one or more calcium ion sources. This creates a supersaturated environment of calcium and / or phosphate ions around the hydroxyapatite surface, which, according to the Le Chatelier principle, shifts the equilibrium of Equation I to facilitate the remineralization of hydroxyapatite.

[0017]

[0018] Reducing the solubility of hard hydroxyapatite surfaces can also be achieved through surface adsorption of metal ions, which slows 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.

[0019] While each of these mechanisms on its own may not be sufficient to provide the cavity-preventing benefits equivalent to a therapeutic dose of fluoride, the combination of these mechanisms can provide cavity-preventing benefits. Therefore, the present invention relates to compositions and methods of using compositions that may be fluoride-free but still provide cavity-preventing and / or caries-preventing benefits.

[0020] definition

[0021] To more clearly define the terms used herein, the following definitions are provided. Unless otherwise indicated, the following definitions apply to this disclosure. If a term is used in this disclosure but is not specifically defined herein, the definition from IUPAC Compendium of Chemical Terminology, 2nd Edition (1997) may be applied, provided that the definition does not conflict with any other disclosure or definition applied herein, or render any claim to which the definition is applied uncertain or unenforceable.

[0022] As used herein, the term "oral care composition" includes products that, during ordinary use, are not intended for swallowing for the purpose of systemic administration of a particular therapeutic agent, but rather remain in the oral cavity for a sufficient duration to contact the tooth surface or oral tissues. Examples of oral care compositions include dental floss, toothpaste, teeth whitening gel, subgingival gel, mouthwash, mousse, foam, mouth spray, lozenges, chewing tablets, chewing gum, teeth whitening strips, dental floss and floss coatings, breath freshening soluble strips, or denture care or adhesive products. Oral care compositions may also be incorporated into strips or films for direct application or attachment to oral surfaces.

[0023] The active ingredients and other ingredients used herein may be classified or described in accordance with their cosmetic and / or therapeutic benefits or their assumed mode of action or function. However, it should be understood that in some cases, the active substances and other ingredients used herein may provide more than one cosmetic and / or therapeutic benefit, or act or function 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 functions or activities listed.

[0024] 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 a composition can be mixed but do not interact with each other in a way that would significantly reduce the stability and / or efficacy of the composition.

[0025] As used herein, the term “substantially free” means that the composition contains no more than 0.05%, preferably no more than 0.01%, and more preferably no more than 0.001% of the specified material on a total weight basis.

[0026] As used herein, the term "substantially free of" means that the indicated material is not intentionally added to the composition, or preferably is not present at an analytically detectable level. This means that the composition in which the indicated material is included exists only as an impurity among other intentionally added materials.

[0027] Although the compositions and methods described herein are “comprising” various components or steps, unless otherwise indicated, the compositions and methods may also consist “substantially” or “composed of” various components or steps.

[0028] As used herein, the word “or” when used as a conjunction for two or more elements means including either the individual element or a combination of the elements; for example, X or Y means X or Y or both.

[0029] As used herein, the articles “an” and “a” are understood to refer to one or more materials protected or described in the claims, such as “oral care composition” or “bleaching agent”.

[0030] Unless otherwise specified, all measurements mentioned herein were performed at approximately 23°C (i.e., room temperature).

[0031] Generally, the numbering scheme shown in the version of the periodic table published in Chemical and Engineering News, 63(5), 27, 1985, is used to indicate element groups. In some cases, the common name assigned to the group may be used to indicate the element group; for example, for alkali metals in group 1, for alkaline earth metals in group 2, and so on.

[0032] This invention discloses several types of scopes. When any type of scope is disclosed or protected by claims, the purpose is to disclose or protect by claims every possible value that such scope can reasonably cover, including the endpoints of the scope and any sub-scopes and combinations thereof covered therein.

[0033] The term "about" means that quantities, dimensions, formulations, parameters, and other quantities and characteristics are not and need not be precise, but may be approximate and / or larger or smaller as required, reflecting tolerances, conversion factors, rounding, measurement errors, and other factors known to those skilled in the art. Generally, whether or not such an explicit statement is made, quantities, dimensions, formulations, parameters, or other quantities or characteristics are "about" or "approximate." The term "about" also covers amounts that differ due to different equilibrium conditions of the composition resulting from a particular initial mixture. Claims include equivalent quantities, whether or not modified by the term "about." The term "about" may mean a value within 10% of the reported value, preferably within 5% of the reported value.

[0034] Oral care compositions may be in any suitable form, such as solid, liquid, powder, paste, or combinations thereof. Oral care compositions may be dental cleaning agents, teething gels, subgingival gels, mouthwashes, mousses, foams, mouth sprays, lozenges, chewing tablets, chewing gum, teeth whitening strips, dental floss and floss coatings, breath freshening soluble strips, or denture care or adhesive products. Components of dental cleaning agent compositions may be incorporated into film, strip, foam, or fiber-based dental cleaning agent compositions. Oral care compositions may contain a variety of active and inactive ingredients, such as, but not limited to, hops extract, tin ion sources, calcium ion sources, water, fluoride ion sources, zinc ion sources, one or more polyphosphates, humectants, surfactants, other ingredients, and any combinations thereof, as described below.

[0035] The section headings provided below are for organization and convenience only. Section headings do not imply 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 can fit into multiple categories and / or sections.

[0036] Hops

[0037] The oral care compositions of the present invention may comprise hops. The hops may comprise at least one hop compound of Formula I and / or Formula IV. The compounds of Formula I and / or Formula IV may be provided from any suitable source, such as extracts from hops or hops, hops themselves, their synthetic derivatives and / or salts, prodrugs, or other similar substances. The hop extract may comprise one or more hop α-acids, one or more hop iso-α-acids, one or more hop β-acids, one or more hop oils, one or more flavonoids, one or more solvents, and / or water. Suitable hop α-acids (generally represented by Formula I) may include humulone (Formula II), polyhumulone, humulone-like humulone, post-humulone, pro-humulone, and / or mixtures thereof. Suitable hop iso-α-acids may include cis-isohumulone and / or trans-isohumulone. Humulone isomerization to cis-isohumulone and trans-isohumulone may be represented by Formula III.

[0038]

[0039] Formula I. Hops iso-α acid A is an acidic hydroxyl functional group at the α-position, B is an acidic hydroxyl functional group at the β-position, and R is an alkyl functional group.

[0040]

[0041]

[0042] Suitable hop β-acids may include humulone, humulone-like compounds, humulone-added compounds, and / or mixtures thereof. Suitable hop β-acids may include compounds described in formulas IV, V, VI, and / or VII.

[0043]

[0044]

[0045] While hop alpha acids exhibit some antibacterial activity, they also possess a bitter taste. The bitterness provided by hop alpha acids is suitable for beer but not for oral care compositions. In contrast, hop β acids can be associated with higher antibacterial and / or anti-caries activity, but are less bitter. Therefore, hop extracts with a higher ratio of β to alpha acids than typically found in nature could be suitable for use in oral care compositions as antibacterial and / or anti-caries agents.

[0046] Depending on the type of hops, natural hop sources may contain about 2% to about 12% hop β-acid by weight of the hop source. Hop extracts used in other applications, such as in beer brewing, may contain about 15% to about 35% hop β-acid by weight of the extract. The hop extracts desired herein may contain 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 β-acid. Hop β-acids may be in acidic form (i.e., having hydrogen atoms attached to hydroxyl functional groups) or in salt form.

[0047] Suitable hop extracts are described in detail in U.S. Patent No. 7,910,140, ​​the entire contents of which are incorporated herein by reference. The desired hop β-acids may be non-hydrogenated, partially hydrogenated by a non-naturally occurring chemical reaction, or hydrogenated by a non-naturally occurring chemical reaction. Hop β-acids may be substantially free of or substantially free of hydrogenated hop β-acids and / or hop acids. Non-naturally occurring chemical reactions are those involving compounds not present in hops, such as chemical hydrogenation reactions carried out at high temperatures and / or with metal catalysts that are not typically experienced in wild hops.

[0048] Natural hop sources may contain about 2% to about 12% hop alpha acid by weight of the hop source. Hop extracts used in other applications, such as in beer brewing, may contain about 15% to about 35% hop alpha acid by weight of the extract. The hop extracts used herein may contain less than about 10%, less than about 5%, less than about 1%, or less than about 0.5% hop alpha acid by weight of the extract.

[0049] Hop oil may contain terpenes such as myrcene, humulene, caryophyllene, and / or mixtures thereof. The hop extract desired herein may contain less than 5%, less than 2.5%, or less than 2% by weight of the extract of one or more hop oils.

[0050] Flavonoids present in hop extracts may include xanthohumol, 8-isoprene naringenin, isoxanthohumol, and / or mixtures thereof. Hop extracts may be substantially free of, substantially free of, contain no, or have less than 250 ppm, less than 150 ppm, and / or less than 100 ppm of one or more flavonoids.

[0051] As described in U.S. Patent No. 5,370,863, hop acid has previously been added to oral care compositions. However, the oral care compositions taught in U.S. Patent No. 5,370,863 contain only up to 0.01% by weight of the oral care composition. While not wishing to be bound by theory, it is believed that only small amounts of hop acid can be incorporated into U.S. Patent No. 5,370,863 because hop alpha acid has a bitter taste. Hop extracts with low levels of hop alpha acid do not have this problem.

[0052] Hop compounds can be combined with extracts from another plant, such as species of the genus Magnolia, or without extracts from another plant. Hop compounds can be combined with triclosan or without triclosan.

[0053] Oral care compositions may contain about 0.01% to about 10%, greater than 0.01% to about 10%, about 0.05%, 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 hops, such as hop β-acid, as described herein. Hop, such as hop β-acid, may be provided from suitable hop extracts, the hop plant itself, or synthetic derivatives. Hop, such as hop β-acid, may be provided as a neutral, acidic compound and / or as a salt having a suitable counterion such as sodium, potassium, ammonia, or any other suitable counterion.

[0054] Hops may be provided by hop extracts, such as extracts derived from hops, having at least 35% hop β-acid and less than 1% hop α-acid by weight of the extract. Oral care compositions may contain 0.01% to about 10%, greater than 0.01% to about 10%, about 0.05%, 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%, as described herein.

[0055] Fluoride ion source

[0056] Oral care compositions may contain fluorides, such as those derived from fluoride ion sources. Fluoride ion sources 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.

[0057] The fluoride ion source and the tin ion source can be the same compound, such as stannous fluoride, which can generate tin ions and fluoride ions. Alternatively, 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.

[0058] The fluoride ion source and the zinc ion source can be the same compound, such as zinc fluoride, which can generate both zinc and fluoride ions. Alternatively, 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.

[0059] The fluoride ion source may be substantially free of stannous fluoride or not. Therefore, oral care compositions may contain sodium fluoride, potassium fluoride, amine fluoride, sodium monofluorophosphate, zinc fluoride, and / or mixtures thereof.

[0060] The oral care composition may contain 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 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 contain less than 0.1%, less than 0.01%, substantially none, substantially none, or no fluoride ion source.

[0061] Tin ion source

[0062] The oral care composition of the present invention may contain tin, such as from a tin ion source. The tin ion source may be any suitable compound that, when the dental cleaning composition is applied to the oral cavity, provides tin ions in the oral care composition and / or delivers tin ions to the oral cavity. The tin ion source may contain one or more tin-containing compounds, such as stannous fluoride, stannous chloride, stannous bromide, stannous iodide, stannous oxide, stannous oxalate, stannous sulfate, stannous sulfide, tin fluoride, stannous chloride, stannous bromide, stannous iodide, stannous sulfide, and / or mixtures thereof. The tin ion source may contain stannous fluoride, stannous chloride, and / or mixtures thereof. The tin ion source may also be a fluorine-free tin ion source, such as stannous chloride.

[0063] The oral care composition may contain about 0.0025% to about 5%, about 0.01% to about 10%, about 0.2% to about 1%, about 0.5% to about 1.5% or about 0.3% to about 0.6% of a tin ion source based on the weight of the oral care composition.

[0064] Ca ion source

[0065] 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, when the oral care composition is applied to the oral cavity, provides calcium ions in the oral care composition and / or delivers calcium ions into the oral cavity. The calcium ion source may comprise calcium salts, calcium abrasives, and / or combinations thereof. In some cases, calcium salts may also be considered calcium abrasives, or calcium abrasives may also be considered calcium salts.

[0066] The calcium ion source may comprise calcium abrasives. The calcium abrasives may be any suitable abrasive compound that, when applied to the oral care composition, provides calcium ions into the oral care composition and / or delivers calcium ions into the oral cavity. The calcium abrasives 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.

[0067] The calcium ion source may comprise a calcium salt, or, when the oral care composition is applied to the oral cavity, may provide calcium ions in the oral care composition and / or a non-abrasive compound that delivers calcium ions into the oral cavity. The calcium salt may include 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.

[0068] The oral care composition may contain 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 a calcium ion source.

[0069] buffer

[0070] Oral care compositions may contain buffers. Buffers may be weak acids or weak bases that maintain a specific pH at selected sites in the oral cavity. For example, a buffer may maintain the pH of the tooth surface to mitigate the effects of plaque acid produced by bacteria. Buffers may contain conjugate acids of ions also present in the oral care composition. For example, if the calcium ion source contains calcium carbonate, the buffer may contain bicarbonate anions (-HCO3-). - Buffers may contain conjugate acid / base pairs, such as citric acid and sodium citrate.

[0071] Suitable buffer systems may contain phosphates, citrates, carbonates / bicarbonates, tris(hydroxymethyl)aminomethane buffers, imidazoles, ureas, borates, and / or combinations thereof. Suitable buffers include bicarbonates, such as sodium bicarbonate, glycine, orthophosphates, arginine, ureas, and / or combinations thereof.

[0072] Oral care compositions may contain one or more buffers, ranging from about 1% to about 30%, from about 5% to about 25%, or from about 10% to about 20%.

[0073] Biofilm modifier

[0074] Oral care compositions may contain one or more biofilm modifiers. Biofilm modifiers may include polyols, ammonia-generating compounds, and / or glucosyltransferase inhibitors.

[0075] Polyols are organic compounds having more than one hydroxyl functional group. A polyol can be any suitable compound that can weakly associate, interact, or bond with tin ions when storing oral care compositions prior to use. Polyols can be sugar alcohols, which are a class of compounds that can be converted into tin ions by having the formula (CHOH). n Polyols obtained by hydrogenation of sugar compounds of H2. The polyols may be glycerol, erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol, and / or combinations thereof. Oral care compositions 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.

[0076] The ammonia-generating compound can be any suitable compound that can generate ammonia upon delivery to the oral cavity. Suitable ammonia-generating compounds include arginine, urea, and / or combinations thereof. The oral care composition may contain about 0.01% to about 10%, about 1% to about 5%, or about 1% to about 25% of one or more ammonia-generating compounds.

[0077] Glucosyltransferase inhibitors can be any suitable compound that can inhibit glucosyltransferases. Glucosyltransferases are enzymes that can form natural glycosidic bonds. Specifically, these enzymes partially break down polysaccharides or oligosaccharides into monosaccharides for use by bacteria associated with tooth decay. Therefore, any compound that can inhibit this process can help prevent tooth decay. Suitable glucosyltransferase inhibitors include oleic acid, epicatechin, tannins, tannic acid, menofamycin, caspofungin, ethambutol, clofenuron, and / or combinations thereof. Oral care compositions may contain about 0.001% to about 5%, about 0.01% to about 2%, or about 1% of one or more glucosyltransferase inhibitors.

[0078] Metal ion source

[0079] Oral care compositions may contain metals, such as those from a metal ion source comprising one or more metal ions. As described herein, the metal ion source may comprise a tin ion source and / or a zinc ion source, or other than 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. Trace metal sources may be any compound having a suitable metal and any associated ligands and / or anions.

[0080] Suitable ligands and / or anions that can pair with a metal ion source include, but are not limited to, acetate, ammonium sulfate, benzoate, bromide, borate, carbonate, chloride, citrate, gluconate, glycerophosphate, hydroxide, iodide, oxides, propionate, D-lactate, DL-lactate, orthophosphate, pyrophosphate, sulfate, nitrate, tartrate, and / or mixtures thereof.

[0081] Oral care compositions may contain about 0.01% to about 10%, about 1% to about 5%, or about 0.5% to about 15% of a metal ion source.

[0082] Antibacterial agents

[0083] Oral care compositions may contain one or more antimicrobial agents. Suitable antimicrobial agents include any molecule that provides antimicrobial activity in the oral cavity. Suitable antimicrobial agents include hop acid, tin ion source, benzyl alcohol, sodium benzoate, menthyl acetate, menthyl lactate, L-menthol, o-menthol, copper chlorophyllin complex, phenol, hydroxyquinoline, and / or combinations thereof.

[0084] Oral care compositions may contain about 0.01% to about 10%, about 1% to about 5%, or about 0.5% to about 15% of an antimicrobial agent.

[0085] Bioactive substances

[0086] Oral care compositions may also contain bioactive substances suitable for tooth remineralization. Suitable bioactive substances include bioactive glass and Novamin. TM Recaldent TM Hydroxyapatite, one or more amino acids (e.g., arginine, citrulline, glycine, lysine, or histidine), or combinations thereof. Suitable examples of compositions containing arginine can be found in U.S. Patent Nos. 4,154,813 and 5,762,911, the entire contents of which are incorporated herein by reference. Other suitable bioactive substances include any calcium phosphate compound. Other suitable bioactive substances include compounds comprising both a calcium source and a phosphate source.

[0087] Amino acids are organic compounds 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.

[0088] Bioactive glasses contain calcium and / or phosphates, which may be present in proportions similar to hydroxyapatite. These glasses are tissue-adhesive and biocompatible. Bioactive glasses may contain phosphopeptides, calcium sources, phosphate sources, silica sources, sodium sources, and / or combinations thereof.

[0089] The oral care composition may contain about 0.01% to about 20%, about 0.1% to about 10%, or about 1% to about 10% of a bioactive substance by weight of the oral care composition.

[0090] abrasive

[0091] Oral care compositions may contain 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 incorporated into oral care compositions to tailor the polishing properties of the targeted dental cleaning formulation. Oral care compositions may contain approximately 5% to approximately 70%, approximately 10% to approximately 50%, approximately 10% to approximately 60%, approximately 20% to approximately 50%, approximately 25% to approximately 40%, or approximately 1% to approximately 50% of non-calcium abrasives by weight of the oral care composition.

[0092] Alternatively, the oral care composition may be substantially free of, substantially free of, 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 abrasive, such as silica and / or alumina.

[0093] water

[0094] The oral care composition of the present invention may be an anhydrous, low-water, or high-water formulation. Generally, the oral care composition 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.

[0095] In high-water oral care compositions and / or toothpaste formulations, the oral care composition comprises about 45% to about 75% water by weight of the composition. The high-water oral care composition and / or toothpaste formulation may comprise about 45% to about 65%, about 45% to about 55%, or about 46% to about 54% water by weight of the composition. Water may be added to the high-water formulation, and / or water may be incorporated into the composition due to the inclusion of other ingredients.

[0096] In low-water oral care compositions and / or toothpaste formulations, the oral care composition contains about 5% to about 45% water by weight of the composition. The low-water oral care composition may contain about 5% to about 35%, about 10% to about 25%, or 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 due to the inclusion of other ingredients.

[0097] In anhydrous oral care compositions and / or toothpaste formulations, the oral care composition contains less than about 10% water by weight of the composition. The anhydrous composition contains less than about 5%, less than about 1%, or 0% water by weight of the composition. Water may be added to the anhydrous formulation, and / or water may enter the composition due to the inclusion of other ingredients.

[0098] Mouthwash formulations contain about 75% to about 99%, about 75% to about 95%, or about 80% to about 95% water.

[0099] The composition may also contain other orally acceptable carrier materials, such as alcohols, humectants, polymers, surfactants, and acceptability improvers (such as flavoring agents, sweeteners, coloring agents, and / or cooling agents).

[0100] pH

[0101] The pH of the disclosed composition may 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.

[0102] Zinc ion source

[0103] Oral care compositions 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.

[0104] The zinc ion source may be present in the total dental cleaning composition in an amount of about 0.01% to about 10%, about 0.2% to about 1%, about 0.5% to about 1.5%, or about 0.3% to about 0.6% by weight of the oral care composition.

[0105] Polyphosphate

[0106] Oral care compositions may contain polyphosphates, such as those derived from polyphosphate sources. A polyphosphate source may contain one or more polyphosphate molecules. Polyphosphates are a class of substances obtained by the dehydration and condensation of orthophosphates to form 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.

[0107] Preferred polyphosphates are those having an average of two or more phosphate groups, so that sufficient unbound phosphate functional groups are generated for effective surface adsorption, which enhances the anionic surface charge and the surface's hydrophilic properties. In this invention, a linear polyphosphate having the following formula is preferred: XO(XPO3). n X, where X is sodium, potassium, ammonium, or any other alkali metal cation, and n on average is 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. Therefore, the oral care compositions disclosed herein may be free of, substantially free of, or substantially free of calcium pyrophosphate.

[0108] 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. polyphosphate, and may include those polyphosphate compounds produced by FMC Corporation, ICL Performance Products and / or Astaris.

[0109] The oral care composition may contain about 0.01% to about 15%, about 0.1% to about 10%, about 0.5% to about 5%, about 1% to about 20%, or about 10% or less of a polyphosphate source based on the weight of the oral care composition.

[0110] wetting agent

[0111] Oral care compositions may contain one or more humectants, have a low content of humectants, be substantially free of, substantially free of, or contain no humectants. Humectants are used to increase the consistency or "texture" of oral care compositions or dental cleanings and to prevent dental cleanings from drying out. Suitable humectants include polyethylene glycol (having a variety of different molecular weights), propylene glycol, glycerin, erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol, hydrogenated starch hydrolysate, and / or mixtures thereof. Oral care compositions may contain one or more humectants, each humectant in an amount of 0% to about 70%, about 5% to about 50%, about 10% to about 60%, or about 20% to about 80% by weight of the oral care composition.

[0112] surfactants

[0113] Oral care compositions may contain one or more surfactants. Surfactants can be used to make the composition more cosmetically acceptable. Surfactants are preferably detergency agents that impart detergency and foaming properties to the composition. Suitable surfactants are anionic, cationic, nonionic, amphoteric, amphoteric, and betaine surfactants in safe and effective amounts.

[0114] 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 sulfonate. Other suitable anionic surfactants include sarcosine salts such as sodium lauroyl sarcosinate, taurine, sodium lauryl sulfoacetate, sodium lauroyl hydroxyethyl sulfonate, sodium lauryl polyoxyethylene ether carboxylate, and sodium dodecylbenzene sulfonate. Combinations of anionic surfactants may also be used.

[0115] Another suitable class of anionic surfactants are alkyl phosphates. These surface-active organophosphate reagents can have a strong affinity for enamel surfaces and a strong tendency to surface bind, causing desorption of membrane proteins and maintaining their attachment to the enamel surface. Suitable examples of organophosphate compounds include monoesters, diesters, or tripesters represented by the following general formulas, wherein Z1, Z2, or Z3 may be the same or different, and at least one of them is an organic moiety. Z1, Z2, or Z3 may be selected from a straight-chain or branched alkyl or alkenyl group of 1 to 22 carbon atoms, optionally substituted with one or more phosphate groups; alkoxylated alkyl or alkenyl, (poly)saccharide, polyol, or polyether groups.

[0116]

[0117] Some other reagents include alkyl or alkenyl phosphates represented by the following structures:

[0118]

[0119] Wherein R1 represents a straight-chain or branched alkyl or alkenyl group having 6 to 22 carbon atoms, 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, protonated alkylamine or protonated functionalized alkylamine, such as alkanolamine or R-(OCH2)(OCH)- group. Examples of suitable reagents include alkyl phosphates and alkyl (poly)alkoxy phosphates such as lauryl phosphate; PPGS cetearyl polyoxyethylene ether-10 phosphate; lauryl polyoxyethylene ether-1 phosphate; lauryl polyoxyethylene ether-3 phosphate; lauryl polyoxyethylene ether-9 phosphate; trilauryl polyoxyethylene ether-4 phosphate; C 12-18 PEG 9 phosphate ester: and dilauryl polyoxyethylene ether-10 sodium phosphate. Alkyl phosphates can be polymeric. Examples of polymeric alkyl phosphate esters include those containing repeating alkoxy groups as polymeric moieties, specifically those containing three or more ethoxy, propoxy, isopropoxy, or butoxy groups.

[0120] Other suitable anionic surfactants are sarcosinates, hydroxyethyl sulfonates, and taurines, especially their alkali metal or ammonium salts. Examples include lauroyl sarcosinate, myristoyl sarcosinate, palmitoyl sarcosinate, stearoyl sarcosinate, oleoyl sarcosinate, or combinations thereof.

[0121] Other suitable anionic surfactants include sodium or potassium alkyl sulfates, such as sodium lauryl sulfate, acyl hydroxyethyl sulfonate, acyl methyl hydroxyethyl sulfonate, alkyl ether carboxylates, acyl alanine salts, acyl glutamate salts, acyl glycinate salts, acyl sarcosine salts, sodium methyl acyl taurate, sodium lauryl ether sulfosuccinate, α-olefin sulfonate, alkylbenzene sulfonate, sodium lauroyl lactate, sodium lauryl glucoside hydroxypropyl sulfonate, and / or combinations thereof.

[0122] The zwitterionic surfactants or amphoteric surfactants that can be used herein include derivatives of aliphatic quaternary ammonium, phosphonium, and sulfonium compounds, wherein the aliphatic group can be straight-chain 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, such as a carboxyl, sulfonate, sulfate, phosphate, or phosphonate group. Suitable betaine surfactants are disclosed in U.S. Patent 5,180,577. Typical alkyl dimethyl betaines include decyl betaine or 2-(N-decyl-N,N-dimethylamine) acetate, cocoyl betaine or 2-(N-cocoyl-N,N-dimethylamine) acetate, tetradecyl betaine, palmityl betaine, lauryl betaine, hexadecyl betaine, hexadecyl betaine, stearyl betaine, etc. Amide betaines can be exemplified by cocamidoethyl betaine, cocamidopropyl betaine (CADB), and lauramidopropyl betaine. Other suitable amphoteric surfactants include betaine, sulfobetaine, sodium lauryl amphoteric acetate, alkyl amphoteric diacetates, and / or combinations thereof.

[0123] The cationic surfactants that can be used in this 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; hexadecyltrimethylammonium bromide; hexadecylpyridinium fluoride or combinations thereof.

[0124] Nonionic surfactants that can be used in the compositions of the present invention include, for example, compounds formed by the condensation of an epoxy alkyl group (which is itself hydrophilic) with an organic hydrophobic compound that may be aliphatic or alkyl aromatic. Examples of suitable nonionic surfactants may include (i.e., poloxamer), alkylphenol polyoxyethylene condensates, products derived from the condensation of ethylene oxide with propylene oxide and ethylenediamine, fatty alcohol ethylene oxide condensates, long-chain tertiary amine oxides, long-chain tertiary phosphine oxides, long-chain dialkyl sulfoxides, and combinations thereof. Other suitable nonionic surfactants include alkyl glucosamides, alkyl glucosides, and / or combinations thereof.

[0125] 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, plant oils, passion fruit oil, candelilla wax, cocoyl caprylate, caprylate, dioctyl ether, lauryl alcohol, tetradecyl myristate, dioctyl ether, caprylic acid, octyl ester, octyl caprylate, octyl caprylate, undecane, tridecane, decyl oleate, decyl oleate, hexadecyl palmitate, stearic acid, palmitic acid, glyceryl stearate, hydrogenated, non-hydrogenated or partially hydrogenated vegetable glycerides, polyglycerol-2 dihydroxystearate, hexadecyl / octadecanol, sucrose polystearate, glycerin, octadecyl alcohol, hydrolyzed, partially water-soluble... Hydrolyzed or unhydrolyzed plant proteins, hydrolyzed, partially hydrolyzed or unhydrolyzed wheat protein hydrolysates, polyglycerol-3 diisostearate, glyceryl oleate, myristyl alcohol, hexadecyl alcohol, sodium hexadecylstearyl sulfate, hexadecylstearyl alcohol, glyceryl laurate, triglycerides caprylate, cocoglycerol, lecithin, dioctyl ether, xanthan gum, sodium cocosulfate, ammonium lauryl sulfate, sodium cocosulfate, sodium cocoglutamate, polyalkyl glucosides such as decyl glucoside, hexadecylstearyl glucoside, hexadecylstearyl polyglucoside, cocoglycoside and lauryl glucoside and / or combinations thereof. Natural surfactants may include any of the natural ingredients sold by BASF, such as and / or combinations thereof.

[0126] Other specific examples of surfactants include sodium lauryl sulfate, sodium lauryl hydroxyethyl sulfonate, sodium lauroyl methyl hydroxyethyl sulfonate, sodium cocoyl glutamate, sodium dodecylbenzene sulfonate, alkali metal 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; polyoxyethylene condensates of alkylphenols; cocoaminopropyl betaine, lauroaminopropyl betaine, palmitoyl betaine, sodium cocoyl glutamate, etc. Additional surfactants desired include fatty acid salts of glutamate, alkyl glucosides, taurine, betaine, caprylate, and / or mixtures thereof. Oral care compositions may also be sulfate-free.

[0127] The oral care composition may contain one or more surfactants, each surfactant being present in a concentration of about 0.01% to about 15%, about 0.3% to about 10%, or about 0.3% to about 2.5% by weight of the oral care composition.

[0128] Thickener

[0129] Oral care compositions may contain one or more thickeners. Thickeners may be used in oral care compositions to provide a gel-like structure to stabilize dental floss and / or toothpaste and prevent phase separation. Suitable thickeners include polysaccharides, polymers, and / or silica thickeners.

[0130] Thickeners may contain one or more polysaccharides. Some non-limiting examples of polysaccharides include starch; starch glycerol; gums such as carrageenan gum, tragacanth gum, gum arabic, solanum, xanthan gum, guar gum, and cellulose gum; magnesium aluminum silicate (colloidal magnesium aluminum silicate); carrageenan; sodium alginate; agar; pectin; gelatin; cellulose 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 lithium montmorillonite clay; and mixtures thereof.

[0131] Other polysaccharides applicable to this document include carrageenan, gellan gum, locust bean gum, xanthan gum, carbomer, poloxamer, modified cellulose, and mixtures thereof. Carrageenan is a polysaccharide derived from seaweed. Several types of carrageenan exist, which can be distinguished by their seaweed origin and / or by their degree and position of sulfation. Thickeners may include κ-carrageenan, modified κ-carrageenan, ι-carrageenan, modified ι-carrageenan, λ-carrageenan, and mixtures thereof. Carrageenan applicable to this document includes those commercially available under the series name "Viscarin" from FMC Company, including but not limited to Viscarin TP329, Viscarin TP 388, and Viscarin TP 389.

[0132] The thickener may comprise one or more polymers. The polymer may be polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), polyacrylic acid, a polymer derived from at least one acrylic acid monomer, a copolymer of maleic anhydride and methyl vinyl ether, or a cross-linked polyacrylic acid polymer, having various weight percentages and a wide range of average molecular ranges in the oral care composition. Alternatively, the oral care composition may be free of, substantially free of, or substantially free of copolymers of maleic anhydride and methyl vinyl ether.

[0133] Thickeners may include one or more inorganic thickeners. Some non-limiting examples of suitable inorganic thickeners include colloidal magnesium aluminum silicate and silica thickeners. Non-limiting examples of silica thickeners that may be used 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 purchased from Evonik Corporation), and Pyrolysis of silicon dioxide.

[0134] Oral care compositions may contain 0.01% to about 15%, 0.1% to about 10%, about 0.2% to about 5%, or about 0.5% to about 2% of one or more thickeners.

[0135] Isoprene-modified flavonoids

[0136] Oral care compositions may contain isoprene-modified flavonoids. Flavonoids are a group of natural substances widely found in fruits, vegetables, grains, bark, roots, stems, flowers, tea, and wine. Flavonoids can have a variety of beneficial effects on health, such as antioxidant, anti-inflammatory, antimutagenic, anticancer, and antibacterial effects. Isoprene-modified flavonoids are flavonoids that include at least one isoprene functional group (3-methylbut-2-en-1-yl, as shown in Formula VIII), which has previously been identified as promoting binding to cell membranes. Therefore, while not wishing to be bound by theory, it is believed that the addition of an isoprene group (i.e., isoprene modification) to flavonoids can enhance the activity of the original flavonoid by increasing the lipophilicity of the parent molecule and improving the permeability of the isoprene molecule to bacterial cell membranes. Increasing lipophilicity to increase permeability to cell membranes may be a double-edged sword, as isoprene-modified flavonoids tend to be insoluble at high Log P values ​​(high lipophilicity). Log P can be an important indicator of antibacterial efficacy.

[0137] Therefore, the term isoprene flavonoids may include naturally occurring flavonoids having one or more isoprene functional groups, flavonoids having synthetically added isoprene functional groups, and / or isoprene flavonoids having synthetically added additional isoprene functional groups.

[0138]

[0139] Formula VIII. Isoprene functional group, where R represents other parts of the molecule.

[0140] Other suitable functional groups of the parent molecule that improve the structure-activity relationship (e.g., structure-MIC relationship) of the isoprene molecule include additional heterocycles containing nitrogen or oxygen, alkyl amino chains, or alkyl chains substituted to one or more aromatic rings of the parent flavonoid.

[0141] Flavonoids may have a 15-carbon backbone having at least two benzene rings and at least one heterocycle. Some suitable flavonoid backbones may be shown in formula IX (flavonoid backbone), formula X (isoflavone backbone), and / or formula XI (neoflavonoid backbone).

[0142]

[0143]

[0144] Other suitable flavonoid subgroups include anthocyanins, flavonoids, flavanones, flavanols, flavans, isoflavones, chalcones, and / or combinations thereof.

[0145] Isoprene flavonoids may include naturally isolated isoprene flavonoids or naturally isolated flavonoids, which are synthetically modified by a variety of synthetic methods known to those skilled in the art of synthetic organic chemistry to add one or more isoprene functional groups.

[0146] Other suitable isoprene-based flavonoids may include psoralen chalcone, psoralen dihydroflavonoid, methyl psoralen chalcone, Corylifol A, icariin A, icariin A1, icariin B, icariin C, icariin, icariin I, icariin II, icariin, isopsoralen chalcone, isoflavone, neopsoralen isoflavone, 6-isoprene naringenin, 8-isoprene naringenin, sophoranone G, (-)-stigmocarpin, flavol, quercetin, myristoyl phenol, sophora flavescens chalcone, sophoraecin, morinone G, morinone C, panduratin A, 6-geranyl naringenin, Australone A, 6,8-diisoprene sennaol, dorsmanin C, dorsmanin F, 8-isoprene kaempferol, 7-O-methyl lupin isoflavone, lupin isoflavone, 6-isoprene genistein, isowighteone, yellow lupin veneterone, and / or combinations thereof. Other suitable isoprene-based flavonoids include cannabinoids, such as cannabinoid A, cannabinoid B, and / or cannabinoid C.

[0147] Preferably, isoprene flavonoids are highly likely to have a MIC of less than about 25 ppm against Staphylococcus aureus (a Gram-positive bacterium). Suitable isoprene flavonoids include psoralen dihydroflavonoids, methyl psoralen, Corylifol A, icariin, isoflavone, neopsoralen isoflavone, 6-isoprene naringenin, 8-isoprene naringenin, sophoranone G, (-)-stigmosiderin, matrine, morinone C, pandanatin A and / or combinations thereof.

[0148] Preferably, isoprene flavonoids are highly likely to have a MIC of less than about 25 ppm against *Escherichia coli* (a Gram-negative bacterium). Suitable isoprene flavonoids include methyl psoralen, isoxoflavone, 8-isoprene naringenin, sophoranone G, matrine, pandanatin A, and / or combinations thereof.

[0149] Approximately 1000 isoprene flavonoids have been identified from plants. Based on previously reported numbers of isoprene flavonoids, isoprene flavonoids are the most common subclass, while isoprene flavanols are the rarest. Although naturally occurring isoprene flavonoids have been detected with diverse structural characteristics, their distribution in plants is narrow, unlike their parent flavonoid counterparts which are present in almost all plants. Most isoprene flavonoids are found in the following families: Cannabaceae, Guttiferae, Leguminosae, Moraceae, Rutaceae, and Umbelliferae. Leguminosae and Moraceae, due to their consumption as fruits and vegetables, are the most frequently studied families, and many novel isoprene flavonoids have been explored. Hops from the Cannabaceae family contain 8-isoprene naringenin and isoxalohumol, which may contribute to the health benefits of beer.

[0150] Isoprene flavonoids can be incorporated into hop extract, added to a standalone extract, or added as a standalone component of the oral care compositions disclosed herein.

[0151] Suitable isoprene-modified flavonoids can possess specific octanol-water partition coefficients. Octanol-water partition coefficients can be used to predict the lipophilicity of compounds. Without wishing to be bound by theory, compounds falling within the scope described herein are believed to be able to enter and / or disrupt the major hydrophobic phospholipid bilayer that constitutes the microbial cell membrane. Therefore, octanol-water partition coefficients can be correlated with the antibacterial activity of isoprene-modified flavonoids. Suitable isoprene-modified flavonoids may have log P values ​​of at least about 2, at least about 4, about 2 to about 10, about 4 to about 10, about 4 to about 7, or about 4 to about 7.

[0152] Oral care compositions may contain at least about 0.001%, about 0.001% to about 5%, about 0.01% to about 2%, about 0.0001% to about 2%, or at least about 0.05% of isoprene flavonoids.

[0153] Other ingredients

[0154] Oral care compositions may contain a variety of other ingredients, such as flavoring agents, sweeteners, coloring agents, preservatives, buffers, or other ingredients suitable for use in oral care compositions, as described below.

[0155] Flavoring agents can also be added to oral care compositions. Suitable flavoring agents include wintergreen oil, peppermint oil, spearmint oil, clove bud oil, menthol, p-propenyl anisole, methyl salicylate, eucalyptol, cinnamon, 1-menthol acetate, sage, eugenol, parsley oil, hydroxyphenyl ethyl ketone, α-ionone, oregano, lemon, orange, propenyl ethyl guaiacol, cinnamon, vanillin, ethyl vanillin, heliotrope, 4-cis-heptenal, dimethyl butyl ketone, methyl p-tert-butylphenylacetate, and mixtures thereof. Cooling agents can also be part of the flavoring agent system. Preferred cooling agents in the compositions of the present invention are p-menthanecarbamoyl reagents, 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. Flavoring systems are typically used in compositions at a concentration of about 0.001% to about 5% by weight of the oral care composition. These flavorings typically contain aldehydes, ketones, esters, phenols, acids, and mixtures of aliphatic, aromatic, and other alcohols.

[0156] Sweeteners can be added to oral care compositions to give the product a pleasant taste. Suitable sweeteners include saccharin (such as sodium saccharin, potassium saccharin, or calcium saccharin), cyclosulfonates (such as sodium, potassium, or calcium salts), acesulfame K, arbutin, neohesperidin dihydrochalcone, aminoglycoside, dextrose, levulose, sucrose, mannose, sucralose, stevia, and glucose.

[0157] Colorants are added to improve the aesthetic appearance of products. Suitable colorants include, but are not limited to, those approved by the relevant regulatory agencies such as the FDA and those listed in the European Food and Drug Directive, and include pigments such as TiO2, as well as colors such as FD&C and D&C dyes.

[0158] Preservatives can also be added to oral care compositions to prevent bacterial growth. Suitable preservatives approved for use in oral compositions, such as methylparaben, propylparaben, benzoic acid, and sodium benzoate, can be added in safe and effective amounts.

[0159] Titanium dioxide may also be added to the compositions of the present invention. Titanium dioxide is a white powder that increases the opacity of the composition. Titanium dioxide typically comprises about 0.25% to about 5% by weight of the oral care composition.

[0160] Other ingredients may be used in oral care compositions, such as desensitizers, rehabilitative agents, other caries prevention agents, chelating agents / polyvalent chelating agents, vitamins, amino acids, proteins, other anti-plaque / anti-tartar agents, light-blocking agents, antibiotics, anti-enzymes, enzymes, pH control agents, oxidants, antioxidants, etc.

[0161] How to use

[0162] The oral care composition of the present invention can be used to treat, reduce and / or prevent dental caries, cavities, gingivitis and / or combinations thereof.

[0163] Oral care compositions that can be used in the method include hops as described above, such as hops provided by hop extracts and / or hop (Humulus lupulus) extracts. As described herein, hop β-acids can be used as anti-cavity agents. Therefore, adding hops to any oral care composition can provide anti-cavity protection.

[0164] Oral care compositions may include primary packaging, such as tubes, bottles, and / or drums. The primary packaging may be placed within secondary packaging, such as cartons, shrink wrap, etc. Instructions for use of the oral care composition may be printed on the primary and / or secondary packaging. The scope of this method is intended to include instructions provided by the manufacturer, distributor, and / or producer of the oral care composition.

[0165] If the oral care composition is toothpaste, the user can be instructed to dispense the toothpaste from the tube.

[0166] The user may be instructed to apply a portion of toothpaste to the toothbrush. This portion of toothpaste may be in any suitable shape, such as a strip, a pea-sized amount, or various other shapes that will fit onto any mechanical and / or manual brush head. The user may be instructed to apply a strip of toothpaste at least about 1 inch, at least about 0.5 inches, at least 1 inch, and / or at least 0.5 inches to the bristles of the toothbrush (such as a soft-bristled toothbrush).

[0167] Users can be instructed to apply a pea-sized or rice-grain-sized amount of toothpaste to the bristles of the toothbrush, such as when used by children under 6 years of age and / or under 2 years of age.

[0168] Users can be instructed to brush their teeth for at least approximately 30 seconds, at least approximately 1 minute, at least approximately 90 seconds, at least approximately 2 minutes, at least 30 seconds, at least 1 minute, at least 90 seconds, and / or at least 2 minutes.

[0169] It can instruct users to brush their teeth thoroughly and / or as directed by a doctor and / or dentist.

[0170] Users can be instructed to brush their teeth after each meal. Users can be instructed to brush their teeth at least once, at least twice, and / or at least three times a day. Users can be instructed to brush their teeth no more than three times a day, for example, to prevent Sn staining. Users can be instructed to brush their teeth in the morning and / or before going to bed at night.

[0171] Because the toothpaste composition contains ingredients that are not suitable for ingestion, such as fluoride, the user may be instructed not to swallow it. However, in the case of oral care compositions that contain hops but not fluoride, it may not be necessary to instruct the user not to swallow the toothpaste. The user may be instructed to spit out (or cough up) the toothpaste composition after stopping the brushing cycle.

[0172] If the oral care composition is mouthwash, the user can be instructed to dispense the mouthwash from the bottle containing the mouthwash.

[0173] Users may be instructed to use mouthwash at least once a day, at least twice a day, and / or at least three times a day.

[0174] Users can be instructed to use the mouthwash composition after using toothpaste and / or dental floss.

[0175] The user can be instructed to rinse their mouth with a portion of mouthwash for a period of time, such as between their teeth. The user can also be instructed to rinse vigorously with a portion of mouthwash.

[0176] Users can be instructed to use mouthwash in doses of approximately 5 mL to approximately 50 mL, approximately 10 mL to approximately 40 mL, 10 mL, 20 mL, 25 mL, 30 mL, 40 mL, 2 teaspoons, and / or 4 teaspoons.

[0177] Users may be instructed to rinse their mouths with mouthwash for at least approximately 30 seconds, at least approximately 1 minute, at least approximately 90 seconds, at least approximately 2 minutes, at least 30 seconds, at least 1 minute, at least 90 seconds, and / or at least 2 minutes.

[0178] Because the mouthwash composition contains ingredients that are not suitable for ingestion, such as fluoride, the user may be instructed not to swallow it. However, in the case of oral care compositions that contain hops but not fluoride, it may not be necessary to instruct the user not to swallow the mouthwash. The user may be instructed to spit out (or cough up) the mouthwash composition after stopping the rinsing cycle.

[0179] Instructions for use of oral care compositions such as toothpaste compositions and / or mouthwashes may vary based on age. For example, one set of instructions may be provided for adults and children aged at least 6 years or at least 2 years, while a second set of instructions may be provided for children aged 6 years or less.

[0180] As described herein, oral care compositions containing hops can be used as medicines, such as the cavity treatments described herein. Suitable medicines include oral care compositions, toothpaste compositions, mouthwash compositions, dental floss coatings, chewing gum, and / or other suitable compositions to be applied to the oral cavity.

[0181] Additionally, as described herein, oral care compositions can be used to reduce the number and / or intensity of white spots on teeth that may be attributable to dental caries.

[0182] As described herein, the methods described above can be used in any oral care composition containing hops. Oral care compositions containing hops may also contain other ingredients described above, such as metals, tin, zinc, fluoride, calcium, biofilm modifiers, polyphosphates, abrasives, humectants, flavorings, sweeteners, isoprene-modified flavonoids, thickeners, buffers, and / or water. Additionally, oral care compositions that can be used in the disclosed methods may be substantially free of, substantially free of, or free of fluoride.

[0183] Composition

[0184] A. A hop β-acid used as a medicine, preferably said medicine being an oral care composition, more preferably being a toothpaste, mouthwash, dental floss coating, or a combination thereof.

[0185] B. Hops β-acid as disclosed in A, wherein the hops β-acid contains less than about 1% hops α-acid by weight of the hops β-acid, preferably wherein the hops β-acid is substantially free of, substantially free of, or more preferably free of hops α-acid.

[0186] C. Hops β-acid as disclosed in A or B, wherein the drug comprises a metal, preferably wherein the metal comprises tin, zinc, calcium or a combination thereof, more preferably wherein the tin comprises stannous fluoride, stannous chloride or a combination thereof.

[0187] D. Hops β-acid as disclosed in any one of A to C, wherein the drug comprises an abrasive, preferably wherein the abrasive comprises a silica abrasive, a calcium abrasive, or a combination thereof, more preferably wherein the calcium abrasive comprises calcium carbonate, calcium pyrophosphate, calcium phosphate, or a combination thereof.

[0188] E. Hops β-acid as disclosed in any one of A to D, wherein the drug is substantially free of, substantially free of, or preferably free of fluoride.

[0189] F. Hops β-acid as disclosed in any one of A to E, for the prevention, reduction and treatment of gingivitis, leukoplakia, cavities, dental caries or combinations thereof in the oral cavity, preferably wherein the leukoplakia in the oral cavity is on teeth and can be attributed to dental caries, cavities and / or combinations thereof.

[0190] G. A type of hop for the prevention, reduction and treatment of gingivitis, leukoplakia, cavities, dental caries, or combinations thereof in the oral cavity, preferably wherein the leukoplakia in the oral cavity is on teeth and can be attributed to dental caries, cavities, and / or combinations thereof.

[0191] H. Hops as disclosed in G, wherein the hops comprise hops extract, preferably wherein the hops extract comprises hops β acid, hops α acid or a combination thereof, more preferably wherein the hops β acid comprises less than about 1% hops α acid by weight of the extract, and even more preferably wherein the hops are substantially free of, substantially free of or contain no hops α acid.

[0192] I. Hops as disclosed in G or H, wherein the hops are provided in an oral care composition, preferably wherein the oral care composition is toothpaste, mouthwash, dental floss coating, or a combination thereof.

[0193] J. Hops as disclosed in I, wherein the oral care composition further comprises an abrasive, preferably wherein the abrasive comprises silica abrasive, calcium abrasive or a combination thereof, more preferably wherein the calcium abrasive comprises calcium carbonate, calcium pyrophosphate, calcium phosphate or a combination thereof.

[0194] K. Hops disclosed in I or J, wherein the oral care composition further comprises a metal, preferably wherein the metal comprises tin, zinc, calcium or a combination thereof, more preferably wherein the tin comprises stannous fluoride, stannous chloride or a combination thereof.

[0195] L. Hops disclosed in any of I to K, wherein the oral care composition is substantially free of, substantially free of, or preferably free of fluoride.

[0196] M. Hops disclosed in any one of I to L; wherein:

[0197] Instructing the user to use the oral care composition, preferably toothpaste; wherein the instructions for use include:

[0198] (a) Dispensing the oral care composition, preferably the toothpaste, onto a toothbrush;

[0199] (b) Applying the oral care composition, preferably the toothpaste, to the oral cavity for at least 1 minute; and

[0200] (c) Spitting out the oral care composition, preferably the toothpaste, from the oral cavity.

[0201] N. Hops as disclosed in M; wherein the description also includes not swallowing the oral composition.

[0202] Example

[0203] The following embodiments further illustrate the invention, and these embodiments should not be construed in any way as limiting the scope of the invention. After reading this specification, various other aspects, modifications, and equivalents thereof may be proposed to those skilled in the art without departing from the spirit of the invention or the scope of the appended claims.

[0204] Toothpaste Composition Description Example 1

[0205] The oral care compositions described herein may include the following:

[0206] Adults and children 12 years and older: Brush thoroughly, preferably after each meal or at least twice a day, or as directed by your dentist or doctor.

[0207] Children under 12: Consult a dentist

[0208] The instructions are placed on the cardboard box containing the toothpaste composition containing hops and / or on the toothpaste tube containing the toothpaste composition containing hops. The instructions may also include "Do not swallow".

[0209] Therefore, in general, users will perform these steps, and the manufacturers, distributors, and / or producers of the toothpaste composition will guide users to perform these steps by placing instructions on the carton, tube, and / or combinations thereof.

[0210] Toothpaste Composition Description Example 2

[0211] The oral care compositions described herein may include the following:

[0212] Adults and children aged 12 and over:

[0213] Apply at least a 1-inch strip of product to the soft-bristled toothbrush.

[0214] Brush thoroughly, twice a day (morning and evening) for at least one minute, and no more than three times a day, or as advised by your dentist or doctor. Make sure to brush all areas of your teeth. Swallow as little as possible. Spit out your brush after brushing.

[0215] Children under 12: Consult a dentist or doctor.

[0216] The instructions are placed on a cardboard box containing a toothpaste composition containing hops and / or on a toothpaste tube containing a toothpaste composition containing hops.

[0217] Therefore, in general, users will perform these steps, and the manufacturers, distributors, and / or producers of the toothpaste composition will guide users to perform these steps by placing instructions on the carton, tube, and / or combinations thereof.

[0218] Toothpaste Composition Description Example 3

[0219] The oral care compositions described herein may include the following:

[0220] Adults and children aged 2 and above:

[0221] Brush your teeth thoroughly, preferably after each meal or at least twice a day, or as directed by your dentist or doctor.

[0222] Children aged 2 to 6:

[0223] • Use only a pea-sized amount and supervise children as they brush and rinse (to minimize swallowing).

[0224] Children under 2 years old:

[0225] Consult a dentist or doctor.

[0226] The instructions are placed on the cardboard box containing the toothpaste composition containing hops and / or on the toothpaste tube containing the toothpaste composition containing hops. The instructions may also include "Do not swallow".

[0227] Therefore, in general, users will perform these steps, and the manufacturers, distributors, and / or producers of the toothpaste composition will guide users to perform these steps by placing instructions on the carton, tube, and / or combinations thereof.

[0228] Toothpaste Composition Description Example 4

[0229] The oral care compositions described herein may include the following:

[0230] Adults and children aged 2 and above:

[0231] • Brush your teeth thoroughly after each meal or at least twice a day, or use a dental product as directed by your dentist.

[0232] To minimize swallowing, use a pea-sized amount for children under 6 years old.

[0233] Supervise children as they brush their teeth until they develop good habits.

[0234] • Use only a pea-sized amount and supervise children as they brush and rinse.

[0235] Children under 2 years old:

[0236] Consult a dentist or doctor.

[0237] The instructions are placed on the cardboard box containing the toothpaste composition containing hops and / or on the toothpaste tube containing the toothpaste composition containing hops. The instructions may also include "Do not swallow".

[0238] Therefore, in general, users will perform these steps, and the manufacturers, distributors, and / or producers of the toothpaste composition will guide users to perform these steps by placing instructions on the carton, tube, and / or combinations thereof.

[0239] Toothpaste Composition Description Example 5

[0240] The oral care compositions described herein may include the following:

[0241] Adults and children aged 12 and over:

[0242] Apply at least a 1-inch strip of product to a soft-bristled toothbrush. Brush thoroughly, twice a day (morning and evening) for at least 1 minute, or as directed by your dentist.

[0243] Children under 12 years old: Consult a dentist

[0244] The instructions are placed on the cardboard box containing the toothpaste composition containing hops and / or on the toothpaste tube containing the toothpaste composition containing hops. The instructions may also include "Do not swallow".

[0245] Therefore, in general, users will perform these steps, and the manufacturers, distributors, and / or producers of the toothpaste composition will guide users to perform these steps by placing instructions on the carton, tube, and / or combinations thereof.

[0246] Mouthwash Composition Description Example 1

[0247] The oral care compositions described herein may include the following:

[0248] Adults and children aged 12 and over:

[0249] Use after brushing your teeth with toothpaste, twice a day.

[0250] • Rinse your mouth vigorously between your teeth for 1 minute with 10mL (2 teaspoons), then spit it out.

[0251] Do not eat or drink for 30 minutes after rinsing.

[0252] • Supervise children as needed until they are able to use it without supervision.

[0253] The instructions are placed on the cardboard box containing the mouthwash composition containing hops and / or on the mouthwash bottle containing the mouthwash composition containing hops. The instructions may also include "Do not swallow".

[0254] Therefore, in general, users will perform these steps, and the manufacturers, distributors, and / or producers of the mouthwash composition will guide users to perform these steps by placing instructions on the carton, bottle, and / or combinations thereof.

[0255] Mouthwash Composition Description Example 2

[0256] The oral care compositions described herein may include the following:

[0257] Adults and children 6 years and older: Use after brushing with toothpaste, twice daily. Rinse vigorously between teeth for 1 minute with 10 ml (2 teaspoons), then spit out. Do not eat or drink for 30 minutes after rinsing. Instruct children under 12 years of age to develop good rinsing habits (to minimize swallowing). Supervise children as needed until they are able to use without supervision.

[0258] Children under 6 years old: Consult a dentist or doctor.

[0259] The instructions are placed on the cardboard box containing the mouthwash composition containing hops and / or on the mouthwash bottle containing the mouthwash composition containing hops. The instructions may also include "Do not swallow".

[0260] Therefore, in general, users will perform these steps, and the manufacturers, distributors, and / or producers of the mouthwash composition will guide users to perform these steps by placing instructions on the carton, bottle, and / or combinations thereof.

[0261] Mouthwash Composition Description Example 3

[0262] The oral care compositions described herein may include the following:

[0263] Use after normal brushing and flossing; rinse toothpaste from the mouth before use. Adults and children 6 years and older: Rinse for 30 seconds with 20 mL (4 teaspoons) twice daily. Children 6 to 12 years: Use under supervision. Children under 6 years: Do not use.

[0264] The instructions are placed on the cardboard box containing the mouthwash composition containing hops and / or on the mouthwash bottle containing the mouthwash composition containing hops. The instructions may also include "Do not swallow".

[0265] Therefore, in general, users will perform these steps, and the manufacturers, distributors, and / or producers of the mouthwash composition will guide users to perform these steps by placing instructions on the carton, bottle, and / or combinations thereof.

[0266] Experimental methods

[0267] Acid production and acid inhibition [%)

[0268] Acid production and inhibition were determined using an in vitro dental plaque glycolysis model (iPGRM). The aim of this technique is to provide a simple and rapid method for determining whether compounds affect metabolic pathways used by dental plaque microorganisms to produce toxins that adversely affect gingival health.

[0269] The in vitro plaque glycolysis model (iPGRM) is a technique in which dental plaque is grown from human saliva and treated with various reagents to determine the anti-glycolytic activity of the treatment. When bacteria convert sugars into energy using enzymes, acids are formed. These acids demineralize and damage tooth enamel. The aim of this technique is to provide a simple and rapid method for determining whether a therapeutic compound inhibits the metabolic pathways used by plaque microorganisms to produce acids or toxins and / or inhibit their growth. For the purposes of this work, if the therapeutic composition being tested contains Sn, a Sn placebo should be tested. Additionally, the antimicrobial composition should be tested relative to its placebo to determine the iPGRM value of the antimicrobial composition alone. It is important if a buffer solution, such as bicarbonate, orthophosphate, or calcium carbonate, is present in the composition in addition to the antimicrobial composition.

[0270] Dental plaque biofilms derived from freshly collected human saliva and trypsin-hydrolyzed casein soy broth (TSB) were grown on glass rods at 37°C for 2 days by repeatedly immersing and removing them from the culture medium. Treatments consisted of a 2-minute dip in a dental cleaning agent slurry (1:5) or a diluted solution (1:5) in water. Following treatment, the biofilms were incubated with TSB and sucrose until a 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.

[0271] On Day 1, new glass rods (5mm × 90mm) are polished on a lathe, approximately 25mm from the blunt end, using silicon carbide paper of grit sizes 240, 320, 400, and 600. After the initial polishing, the rods should be polished with 600-grit paper before each test. After polishing, the rods are stored until ready for test runs. Sufficient rods should be polished for the entire rack process. The rack can handle 12 compositions, each repeated 4 times, resulting in a rack with 48 rods.

[0272] On day 2, saliva was collected daily from groups of 5-10 people via paraffin stimulation and refrigerated at 4°C until saliva was needed throughout the day. The saliva was carefully collected (without pouring in the wax / mucus) and thoroughly mixed before use. The sticks were removed from the storage device, rinsed with deionized water to remove any sanding residue, sterilized in 70% ethanol / water solution, and allowed to dry on a sterile surface. The sticks were then loaded into the hanging rack of a support for continuously immersing the sticks in vials containing growth medium. The height of the sticks was adjusted and each stick was secured in place using rubber O-rings. In the early afternoon, 7 mL of growth medium (160 g of 3% TSB solution containing 3% sucrose) was mixed with 240 g of collected human saliva. This TSB / sucrose solution should be autoclaved and then combined with the collected human saliva into the vials. The vials were then arranged under the hanging sticks on a support in an incubator. The incubator had been modified to allow the immersion motor to dip the rod into the culture medium vial at a frequency of once per minute, immersing the 1.5 cm rod into the growth medium without the rod touching the wall of the vial. The rod was then immersed overnight using this method.

[0273] On day 3, prepare enriched growth medium (mix 500g of a solution of 3% TSB and 10% sucrose with 33g of pooled human saliva. This TSB / sucrose solution should be autoclaved before being combined with the pooled human saliva). Pipe the enriched growth medium into a new set of vials (7mL each) and replace the overnight growth medium from day 1. Immerse the sticks in the enriched growth medium for 5 hours at 37°C in an incubator. At the end of the day, prepare a new overnight growth medium (mix 40g of a solution of 3% TSB with 360g of pooled human saliva and 0.5g of sucrose), pipette it into a new set of vials, and replace the enriched growth medium. Immerse the sticks overnight in the same manner as day 1.

[0274] On day 4, a glycolysis medium was prepared by mixing 0.15 g TSB, 25 g sucrose, and 500 mL 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 0.1 M HCl and pipetteed into new culture vials (7 mL). Two additional vials were filled, compared to the number needed for the pH blank. Two drops of chlorophenol red solution were added to each of the four tubes containing the negative control (caries-protecting slurry). Three drops of bromocresol purple solution were added to the two tubes containing the positive control (1% chlorhexidine solution). The racks were set aside until the treatment was complete. A vial containing 12 mL of deionized water was prepared to rinse away the treatment. A vial containing the homogenized treatment and water was prepared (7 mL). Immerse the bar in the treatment vials for 2 minutes, rinse 10 times in the first set of rinse vials, rinse 10 times in the second set of rinse vials, and rinse 10 times in the third set of rinse vials before returning it to the incubator rack. Treat and rinse the entire biofilm. Once all treatments are complete, the biofilm on the bar is fully immersed in the glycolysis medium in the incubator for 2 hours without soaking. After two hours, the soaking device is activated. The total incubation time is between 3 and 7 hours. Incubation is terminated when the pH of the negative control glycolysis medium is between 4.8 and 5.6, ideally 4.9 and 5.2, and when the pH of the positive control glycolysis medium is higher than that of the negative control. If the indicator dye in the positive control turns yellow, i.e., the pH drops below 5.2, the incubation time is too long and the test needs to be repeated.

[0275] After terminating incubation on day 4, remove the bars from the glycolysis medium and allow them to dry in an oven. Remove the glycolysis medium from the incubation oven and allow it to return to room temperature. Measure the pH in each vial and the blank vial to determine the average pH change of the medium after treatment. Determine the pH change relative to the blank vial. If the final pH of the blank is less than 6.6, the test needs to be repeated. If the difference between the positive and negative controls in the Student's t-test is not significant, the test needs to be repeated. If the pH change of the negative control relative to the blank is less than 1, the test needs to be repeated.

[0276] 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. The glycolysis inhibitory efficacy was determined by the following formula. The average ΔpH of the treatment was determined by averaging the results from four replicates of each treatment.

[0277]

[0278] If the efficacy of the positive control (1% chlorhexidine solution) is not between about 65% and about 85% relative to the negative control (Crest Cavity Protection, Procter & Gamble, Cincinnati, OH), the test should be repeated.

[0279] Anti-caries activity

[0280] The test design used in this study is similar to those found in FDA method #37 of the OTC monograph on fluoride caries prevention. The main 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 conducted in accordance with FDA Regulation Part 58.

[0281] Using litter size as a covariate, each treatment group used 50 to 58 animals (depending on the type of fluoride) to meet the ADA’s most stringent power requirement of the Dental Treatment Committee, namely a 20% clinical difference between treatments at 80% power. However, we routinely used 40 animals per treatment group, and these tests are consistently accepted by the ADA’s CDT and FDA. This required starting the study with 40 animals per group. Twenty-three (23) litters of these animals were provided. When the study was set up this way, approximately 16% treatment differences were found to be sometimes significant and are therefore often considered a clinically significant inflection point.

[0282] Before receiving animals, all programs must be reviewed and approved by the agency’s animal care and use committee.

[0283] The animals were weaned, mixed-sex Sprague Dawley rats, weighing 29 g–53 g. The mother rats and all their litters were received due to the supplier’s shipping schedule. Litters were received when the pups were 6 days old and litter sizes were reduced to ten (10) pups per litter at 8 days old. Twenty-five (25) litters were purchased. The additional five litters were to account for any mortality prior to stratification. Any unused animals were euthanized after the study stratification.

[0284] Keep littermates in large, solid-bottom (box-type) cages with their mothers until the littermates are weaned at 18 days of age. Starting when the littermates are 9 days old, rotate the placement of the mother in the litter daily until the littermates are weaned at 18 days of age. The littermates are then kept in the box-type cages until 21 days of age. At this point, the littermates are placed in pairs and stratified in suspended wire-bottom cages that have been cleaned and sterilized before use. Cage arrangements are necessary to prevent artificially increased caries rates due to direct contact with the bedding. Arrange the cages so that all animals in a single group are together, and label the cages with the group name and treatment (treatment code) to which the animal is receiving.

[0285] When the pups were 21 days old, they were given unique numbers through ear piercing, and records of littermates were kept. Animals were grouped by balancing littermates, weight, and sex within each group. Each group consisted of 40 animals.

[0286] Upon receipt, mother mice and littermates were fed a rodent laboratory diet until the pups were 8 days old. On day 8 (juvenile stage), mother mice and littermates were fed a diet of MIT 305. On day 18 (juvenile stage) and throughout the experiment, mother mice and littermates were fed a diet of MIT 200 freely. Deionized water was provided freely to all animals.

[0287] Change cages on days 13 and 18 of instar. After inoculation, sterilize cages and bedding by autoclaving before disinfection. Change cage boards three times a week when fresh food and water are provided (Mondays, Wednesdays, and Fridays). Provide clean and sterilized water bottles and food containers weekly. Sterilize cages and containers every two weeks. Observe animals daily by staff and weekly by the attending veterinarian for any signs of health problems. Keep animals in AAALAC-approved facilities. Maintain room temperature at 72℉ (±6℉), with 10-15 air changes per hour and 12-hour light circulation.

[0288] On day 15 (juvenile stage), animals were orally inoculated with a culture of streptomycin-resistant distant streptococcus 6715 (ATCC strain #27352). This involved injecting 0.2 ml of culture per animal into the oral cavity. On day 18 (juvenile stage), animals were inoculated with distant streptococcus for three consecutive days (days 18, 19, and 20). This involved placing 0.1 ml of distant streptococcus culture on the occlusal surface of each mandibular molar quadrant, adding 10 cc of this concentration-adjusted culture to each sterilized and filled water bottle, and gently spraying no more than 10 cc of the remaining culture onto the bedding. Twenty-four hours after adding the inoculum, all water bottles were removed and sterilized. The inoculum was administered to the animals using a 200 micropipette.

[0289] Treatment phases began on day 22 of the infant. Each treatment used a labeled plastic beaker, which was only for that treatment. Fresh material (i.e., obtained from the raw material supplier) was used for each treatment. The dental cleaning agent was mixed with deionized water at a 1:1 ratio (by weight). Specifically, 10 grams of dental cleaning agent was weighed into a 30 ml beaker; then 10 grams of deionized water was added to the dental cleaning agent. 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 rod was placed on a magnetic stirrer set to the lowest speed and stirred for four (4) minutes prior to each treatment. The slurry was prepared immediately before each treatment.

[0290] Dip the cotton applicator into the paste (for 2 seconds) and apply it to half of the rat's oral cavity, with the side of the applicator in contact with the mandibular and maxillary molars on one side of the mouth. Complete the treatment by rolling the applicator along the side of the mandibular and maxillary molars for 15 seconds. Dip the applicator into the paste a second time (again, for 2 seconds), and treat the other side of the rat's oral cavity similarly for 15 seconds. Use a fresh applicator for each animal.

[0291] Treatment was administered twice daily for five days, with one treatment per day on weekends. The first treatment each day began at approximately the same time, and the second treatment began no earlier than six hours after the first. 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.

[0292] One week after the start of the inoculation protocol and at the end of the study, oral swabs were obtained from each rat using sterile swabs (six-inch, single-headed applicators). Microbes were sampled from the mandibular and maxillary molars by rolling the swab on one side of the mouth for 15 seconds, on the tongue, and on the molars on the other side of the mouth for another 15 seconds. Immediately after removing the applicator from the animal's mouth, it was run across half of a 100 mm Piper dish containing agar containing *Streptococcus salivarius*, with 200 units / ml of streptomycin sulfate added. The culture plates were incubated at 37°C and 10% CO2 for 48 hours. Colony counts collected after 48 hours of incubation were recorded in a log.

[0293] The rat caries study lasted for three weeks. Immediately before termination, all animals were observed for any visual signs of poor health or pathology, weighed individually, and oral swabs were collected to confirm distant streptococcal infestation. Animals were euthanized by inhaling carbon dioxide. Each animal was assigned a code number, and its head was removed, placed in a separate container along with the code number, and pressure-cooked (10 PSI for 12 minutes). The jaw was then removed, and all soft tissue was excised.

[0294] Place the cleaned half-jaw (four quadrants) into plastic vials, affixing a code number to each vial. Add ammonium purpurate solution (0.3g ammonium purpurate; 300ml DI H2O and 700ml ethanol) to each vial and allow the jawbone to stain overnight. Then rinse the jawbone and allow it to air dry.

[0295] Smooth-surface caries in the hemimaxilla were examined under a microscope, sections were prepared, and then fissure caries and interdental caries were examined under a microscope using the Keyes method. The scoring method is detailed 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). Analysis of variance (ANOVA) was used to compare groups, with a fixed effect on groups and a random effect on littermates. The littermate effect was included in the model to reduce known factors affecting the variability of the measurement. Paired comparisons between groups were performed using Tukey's multiple comparisons procedure to control for the overall significance level of the comparisons (α = 0.05).

[0296] Specific data types for tabulation and statistical analysis may include:

[0297] 1) Mortality data experimental phase

[0298] a. Initial number of animals

[0299] b. The final number of animals

[0300] c. Mortality rate percentage

[0301] 2) Growth data experimental stage

[0302] a. Initial body weight (mean ± SEM)

[0303] b. Final body weight (mean ± SEM)

[0304] 3) Caries test

[0305] a. Enamel and dentin involvement in lesions on smooth surfaces (buccal and lingual surfaces) (mean ± SEM)

[0306] b. Enamel and dentin involvement in interdental lesions (mean ± SEM)

[0307] c. Enamel and dentin involvement in lesions on all smooth surfaces (buccal, lingual, and interdental) (mean ± SEM)

[0308] d. Enamel and dentin involvement in gingival sulcus lesions (mean ± SEM)

[0309] e. Scoring of all caries-affected areas, including smooth surfaces, interdental spaces, and fissures, using the Keyes scoring method (mean ± SEM).

[0310] Preparation of oral care compositions

[0311] The oral care compositions of Table 1A are prepared by combining one or more humectants, water, sweeteners, tin ion sources, sodium gluconate, and / or flavoring agents to produce a liquid mixture. The liquid mixture is homogenized at 25°C for 2 minutes. Then, sodium hydroxide (50% solution) is added to the liquid mixture, and the liquid mixture is homogenized at 25°C for 2 minutes. A separate powder mixture is prepared by mixing a portion of a calcium ion source with any thickener such as xanthan gum and / or sodium carboxymethyl cellulose. The powder mixture is then mixed with the liquid mixture. Next, a surfactant such as sodium lauryl sulfate is added to the mixture. The contents are homogenized at 25°C for 2 minutes. Then, hop extract is mixed with the mixture and homogenized at 25°C for 2 minutes. Finally, the remaining portion of the calcium ion source and buffer is mixed with the mixture and homogenized at 25°C for 2 minutes.

[0312] Table 1A. Oral Care Compositions

[0313] Formula A Formula B Formula 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[SnCl2]]> 1.10 1.10 1.10 <![CDATA[CaCO3]]> 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 agent 1.00 1.00 1.00 Sodium saccharin 0.40 0.40 0.50 Steviosides 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 -

[0314] *Hops beta-acid extract, from It contains 45% hop β-acid and less than 1% hop α-acid.

[0315] Formulas A, B, and C, as shown in Table 1A, were prepared according to the experimental methods described above. Hop β-acid was obtained from... It is provided in the form of an extract derived from hops. The extract contains approximately 45% hop β-acid by weight and less than 1% hop α-acid by weight. Formulas A and B contain hop β-acid without separately added water. The only difference between Formulas A and B is that Formula B includes a fluoride ion source (sodium monofluorophosphate, NaMFP), which is used in the total enamel caries test shown in Table 4. Formula C contains fluoride-free hop β-acid in a high-water pan.

[0316] Table 1B. Specifications of Hops β-Acid Extract

[0317] Element Quantity (by weight) hop β-acid 45±2 hop alpha acid 0.4±0.3 Hops oil 1.5±0.5 Propylene glycol 20±15 water <8％ pH 11±0.5

[0318] Table 1B describes the... The provided product is a hop beta-acid extract. Because hop beta-acid is provided as an extract, the amounts of certain components may vary. However, the extract contains approximately 45% hop beta-acid and approximately 0.4% hop alpha-acid by weight of the extract. This is significantly different from previous hop extracts, which typically contained more hop alpha-acid than hop beta-acid. Other trace components may be present in the hop beta-acid extract.

[0319] Table 2. Acid production and glycolysis inhibition after 3 days of biofilm treatment [%)

[0320]

[0321]

[0322] Table 2 shows the changes in acid production in the biofilm over 3 days using the iPGRM test described herein. Commercially available sodium fluoride was used. After toothpaste treatment, the average acid product concentration was 1.55, and the average inhibition rate was 3.43%. Using toothpaste containing stannous fluoride... Toothpaste treatment for 3 days resulted in a reduction in acid production due to biofilm formation, with a net average acid inhibition of 43.14%. Pro-Health TM ) and 68.49% Gum Care). This is the expected result because stannous ions are known to act as antibacterial agents, reducing the number of acid-producing bacteria in biofilms. Due to the extra amount of stannous ions (i.e., SnCl2), Gum Care performed slightly better than Pro-Health TM Chlorhexidine is an antibacterial agent that can be prescribed for the treatment of gingivitis. Treatment with chlorhexidine resulted in an average acid inhibition of 75.12%, which is not surprising, as chlorhexidine is known as an extremely effective antibacterial agent.

[0323] Table 2 also shows that formulas A and C exhibit virtually zero acid production, with an average acid inhibition of approximately 100%. Surprisingly, in the absence of fluorides and / or chlorhexidine (two of the most common and effective antimicrobial agents), formulas A and C (without fluoride ion sources) are virtually 100% effective in preventing acid production.

[0324] Table 3. Total enamel caries

[0325]

[0326] a The silica placebo is a negative control that does not contain any fluoride ion source.

[0327] b NaMFP at 1000ppm

[0328] c NaF 1100ppm + silica is a positive control compared with silica and fluoride ion sources.

[0329] Table 3 shows the results of the rat caries test, FDA number 37. The rat caries test is a biological testing method required by the US FDA monograph to demonstrate the efficacy of anti-caries drugs, and currently only includes a fluoride ion source. As shown in Table 3, the negative control and silica placebo are toothpastes containing silica abrasives but without any fluoride ion source. Silica + NaMFP is USP NaMFP toothpaste containing sodium monofluorophosphate and silica abrasives. Cavity Protection is a toothpaste containing sodium fluoride and silica abrasives. In contrast, Formula A does not contain a fluoride ion source or silica abrasive, but does contain hop β-acid and stannous chloride. Surprisingly, Formula A (26.23) behaves similarly to [other toothpastes] without any fluoride ion source. Cavity Protection (25.28) is a toothpaste containing 1100 ppm sodium fluoride. Furthermore, Formula A outperforms toothpastes containing sodium monofluorophosphate and silica abrasives (Formula A is 26.23, while NaMFP is 31.55). The only caries-preventing agents listed by the US FDA are stannous fluoride, sodium fluoride, and sodium monofluorophosphate. In other words, Formula A is a fluoride-free anti-cavity toothpaste.

[0330] The dimensions and values ​​disclosed herein should not be construed as strictly limited to the precise numerical values ​​cited. Rather, unless otherwise specified, each such dimension is intended to represent the stated value and a range around which it is functionally equivalent. For example, a dimension disclosed as “40 mm” is intended to represent “approximately 40 mm”.

[0331] Unless expressly excluded or otherwise limited, every reference cited herein, including any cross-references or related patents or patent applications, and any patent application or patent claiming priority to or benefiting from it, is incorporated herein by reference in its entirety. Reference to any reference is not an endorsement of it as prior art to any disclosed or protected art herein, nor is it an endorsement of any such invention, either on its own or in combination with any one or more references. Furthermore, where any meaning or definition of a term in this invention conflicts with any meaning or definition of the same term in referenced documents, the meaning or definition given to that term in this invention shall prevail.

[0332] While specific embodiments of the invention have been illustrated and described by way of example, it will be apparent to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. Therefore, it is intended that all such changes and modifications falling within the scope of the invention be covered by the appended claims.

Claims

1. Use of an oral care composition in the preparation of a medicament for the prevention, relief and treatment of gingivitis, white spots on teeth and in the oral cavity attributable to caries, cavities and / or combinations thereof, wherein the oral care composition comprises hops extract and stannous chloride, wherein the medicament is fluoride-free, and wherein the composition has a pH of 7 to 10, wherein the hops extract comprises 35% to 99% by weight of hops β-acid and less than 1% by weight of hops α-acid.

2. The use according to claim 1, wherein the hop extract is free of hop α-acid.

3. The use according to claim 1 or claim 2, wherein the drug comprises an abrasive.

4. The use according to claim 3, wherein the abrasive comprises silica abrasive, calcium abrasive, or a combination thereof.

5. The use according to claim 4, wherein the calcium abrasive comprises calcium carbonate, calcium pyrophosphate, calcium phosphate, or a combination thereof.

6. The use according to claim 1 or claim 2, wherein the oral care composition is toothpaste, mouthwash, dental floss coating, or a combination thereof.

7. The use according to claim 6, wherein: Instruct the user to use the oral care composition; The instructions for use include: (a) Dispensing the oral care composition onto a toothbrush; (b) Applying the oral care composition to the oral cavity for at least 1 minute; and (c) Discard the oral care composition from the oral cavity.

8. The use according to claim 7, wherein the description further includes not swallowing the oral composition.

9. The use according to claim 7, wherein the oral care composition is toothpaste.

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