CN116600772A - Aqueous compositions comprising hop-metal complexes - Google Patents

Abstract

The present invention provides hops-metal complexes. The invention also provides aqueous compositions comprising the hops-metal complexes. The invention also provides aqueous compositions comprising hops beta acid-tin and/or hops beta acid-zinc complexes. The present invention also provides aqueous compositions comprising lupulone-tin and/or lupulone-zinc complexes.

Description

Aqueous compositions comprising hop-metal complexes

Technical Field

The present invention relates to hop-metal complexes. The present invention also relates to aqueous compositions comprising hop-metal complexes. The present invention also relates to aqueous compositions comprising hop beta acid-tin and/or hop beta acid-zinc complexes. The present invention also relates to aqueous compositions comprising lupulone-tin and/or lupulone-zinc complexes.

Background Art

Oral care compositions (such as toothpaste and/or dentifrice compositions) can be applied to the oral cavity to clean and/or maintain the beauty and/or health of teeth, gums and/or tongue. In addition, many oral care compositions are used to deliver active ingredients directly to the oral care surface. For example, toothpaste compositions can have a metal ion source (such as tin, copper and/or zinc) as a cationic antimicrobial agent.

Unfortunately, metal ion sources (such as tin, copper and/or zinc) can react with many other oral care components. In many formulations, additional metal ion sources are added to increase antimicrobial activity, but they also suffer from reactivity issues. Therefore, there is a need for antimicrobial agents that do not cause some of the stability issues of metal ion sources. Therefore, there is a need for an aqueous composition containing different antimicrobial agents, which can optionally be combined with a metal ion source, to provide improved metal ion stability.

Summary of the invention

Disclosed herein is a hops-metal complex, such as a hops-tin and/or hops-zinc complex.

Also disclosed herein is an aqueous composition comprising a hops-metal complex, such as a hops-tin complex, a hops-zinc complex, a hops-calcium complex, and/or combinations thereof.

Also disclosed herein is an aqueous composition comprising a lupulone-metal complex, such as a lupulone-tin complex, a lupulone-zinc complex, and/or a lupulone-calcium complex.

DETAILED DESCRIPTION

The present invention relates to aqueous compositions comprising complexes of metal ions with hop beta acids, such as lupulone-tin, lupulone-tin, lupulone-tin, lupulone-zinc, lupulone-zinc, and/or lupulone-zinc. The formation of these complexes can result in increased stability of hops and/or metals in the aqueous composition.

The chelation effect assumes that complexes of polydentate ligands with metals are more stable than metal complexes stabilized by a normalized equivalent of monodentate ligands (e.g., 1 mole of bidentate ligand compared to 2 moles of similarly structured monodentate ligands) because of the reduced molar entropy of bidentate chelates relative to monodentate complexes. This can lead to association and complex formation of polyvalent metal ions in the presence of hop beta acids.

Consider the situation of stannous metal ion in the presence of hop beta acid. ^{Sn 2+} preferably has a tetrahedral bonding geometry with four electron-deficient regions and available bonding orbitals. The two β-position acids on hop beta acid can interact with two of the four coordination sites on stannous. Therefore, the β-position acid of hop beta acid (e.g., lupulone) can form a complex with a metal ion (e.g., Sn, Zn, Cu or Ca). The binding affinity represented by the binding constant _Ka depends on the relative affinity of hop beta acid to the metal ion.

The complex can spontaneously form in solution in the presence of both metal ions and hop beta acids. Once formed, the metal ions can be stabilized in the composition, which can help adjust its reactivity with formulation components. In summary, the formation of hop-metal complexes can lead to increased antimicrobial activity due to improved metal ion stability.

While not wishing to be bound by theory, it is believed that the combination of metal ions and hop acids can result in increased stability of the metal ions and/or hops in an aqueous composition. The increase in stability is evident in an aqueous composition. Additionally, while the presence of other competing metal ligands can affect the amount of complex present in an aqueous composition, it is believed that the increase in stability can occur even when the complex is present at low levels.

definition

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Aqueous composition

The present invention includes hops-metal complexes that can be in an aqueous composition. An aqueous composition is a composition that includes water. The aqueous composition can be an oral care composition, as described herein.

Hops-metal complexes

The aqueous composition of the present invention comprises a hop-metal complex. The aqueous composition may be an oral care composition. The oral care composition of the present invention comprises a hop-metal complex. The hop-metal complex may comprise hops as described herein and a metal as described herein, such as a metal ion source.

Hops may include hop beta acids, hop alpha acids, and/or combinations thereof. Hops may include lupulones, lupulone-like acids, lupulone-adders, and/or combinations thereof. Metals may include tin, zinc, calcium, and/or combinations thereof.

The hops-metal complex may include lupulone-tin, lupulone-tin, lupulone-tin, hops beta acid-tin, hops alpha acid-tin, lupulone-zinc, lupulone-zinc, lupulone-zinc, hops beta acid-zinc, hops alpha acid-zinc, lupulone-calcium, lupulone-calcium, lupulone-calcium, hops beta acid-calcium, hops alpha acid-calcium, and/or combinations thereof.

The hops-metal complex can be preformed and added to the oral care composition as a complex, and/or the hops-metal complex can be formed spontaneously when the hops and metal are added during the preparation of the oral care composition. The hops and metal can be added sequentially, simultaneously, or at any separate time during the preparation of the oral care composition.

The hops of the hops-metal complex can be a monodentate ligand, a bidentate ligand, a polydentate ligand, and/or combinations thereof when complexed with the metal of the hops-metal complex.

The hops-metal complex may have a molar ratio of hops to metal of about 0.003 to about 30, about 0.5 to about 10, about 0.1 to about 5, about 0.5 to about 3, about 1 to about 2, and/or about 1.

The aqueous and/or oral care compositions may contain from about 0.001% to about 10%, from about 0.005% to about 50%, from about 0.005% to about 5%, from about 0.01% to about 2%, from about 0.0001% to about 10%, or from about 0.5% to about 5%, by weight of the composition, of the hops-metal complex.

Hops

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

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

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

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

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

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

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

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

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

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

The oral care composition can include about 0.01% to about 10%, greater than 0.01% to about 10%, about 0.05%, to about 10%, about 0.1% to about 10%, about 0.2% to about 10%, about 0.2% to about 10%, about 0.2% to about 5%, about 0.25% to about 2%, about 0.05% to about 2%, or greater than 0.25% to about 2% of hops, such as hop beta acids, as described herein. Hops such as hop beta acids can be provided by suitable hop extracts, hop plants themselves or synthetically derived compounds. Hops such as hop beta acids can be provided as neutral, acidic compounds and/or as salts with suitable counterions such as sodium, potassium, ammonia or any other suitable counterions.

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

Metal ion source

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

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

The aqueous and/or oral care compositions may contain from about 0.01% to about 10%, from about 1% to about 5%, or from about 0.5% to about 15% of a metal ion source.

Tin ion source

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

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

Zinc ion source

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

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

Ca ion source

The aqueous composition and/or oral care composition of the present invention may include calcium such as from a calcium ion source. The calcium ion source may be any suitable compound or molecule that provides calcium ions in the oral care composition and/or delivers calcium ions to the oral cavity when the oral care composition is applied to the oral cavity. The calcium ion source may include calcium salts, calcium abrasives, and/or combinations thereof. In some cases, calcium salts may also be considered as calcium abrasives, or calcium abrasives may also be considered as calcium salts.

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

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

The aqueous and/or oral care compositions may comprise from about 5% to about 70%, from about 10% to about 50%, from about 10% to about 60%, from about 20% to about 50%, from about 25% to about 40%, or from about 1% to about 50% of a calcium ion source.

Fluoride ion source

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

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

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

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

The aqueous composition and/or oral care composition may include a fluoride ion source capable of providing about 50 ppm to about 5000 ppm and preferably about 500 ppm to about 3000 ppm of free fluoride ions. In order to deliver the desired amount of fluoride ions, the fluoride ion source may be present in the aqueous composition and/or oral care composition in an amount of 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% by weight of the oral care composition. Alternatively, the aqueous composition and/or oral care composition may include less than 0.1%, less than 0.01%, substantially free, essentially free, or free of a fluoride ion source.

Buffer

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

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

The aqueous and/or oral care compositions may contain from about 0.1% to about 30%, from about 1% to about 30%, from about 5% to about 25%, or from about 10% to about 20% of one or more buffering agents.

Biofilm modifiers

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

Polyol is an organic compound with more than one hydroxyl functional group. Polyol can be any suitable compound that can weakly associate, interact or bond with tin ions when storing oral care composition before use. Polyol can be sugar alcohol, which is a type of polyol that can be obtained by hydrogenation of sugar compounds with formula (CHOH) _n H _2. Polyol can be glycerol, erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol and/or their combination. Aqueous composition and/or oral care composition can include 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% polyol by weight of oral care composition.

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

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

Antimicrobial agents

The aqueous composition and/or the oral care composition 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 hops acid, a tin ion source, benzyl alcohol, sodium benzoate, menthyl acetate, menthyl lactate, L-menthol, o-neomenthol, chlorophyllin copper complexes, phenol, hydroxyquinoline and/or combinations thereof.

The aqueous and/or oral care compositions may contain from about 0.01% to about 10%, from about 1% to about 5%, or from about 0.5% to about 15% of the antibacterial agent.

Bioactive substances

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

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

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

The aqueous and/or oral care compositions may comprise from about 0.01% to about 20%, from about 0.1% to about 10%, or from about 1% to about 10%, by weight of the oral care composition, of the bioactive material.

Abrasive

The aqueous composition and/or the oral care composition may contain calcium abrasives, as described herein, and/or non-calcium abrasives, such as bentonite, silica gel (alone, and with any structure), precipitated silica, amorphous precipitated silica (alone, and also with any structure), silica hydrate, perlite, titanium dioxide, calcium pyrophosphate, calcium hydrogen phosphate dihydrate, alumina, alumina hydrate, calcined alumina, aluminum silicate, insoluble sodium metaphosphate, insoluble potassium metaphosphate, insoluble magnesium carbonate, zirconium silicate, particulate thermosetting resins, and other suitable abrasive materials. Such materials may be introduced into the aqueous composition and/or the oral care composition to customize the polishing properties of the target dentifrice formulation. The aqueous composition and/or 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 non-calcium abrasives by weight of the oral care composition.

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

water

The aqueous composition and/or oral care composition of the present invention may contain water. The aqueous composition and/or oral care composition may be a low water formulation or a high water formulation. In general, the oral care composition may contain 0.001% 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.

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

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

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

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

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

pH

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

Polyphosphate

The aqueous composition and/or oral care composition may contain polyphosphates such as from a polyphosphate source. The polyphosphate source may contain one or more polyphosphate molecules. Polyphosphates are a class of substances obtained by 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.

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

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

The aqueous and/or oral care compositions may contain from about 0.01% to about 15%, from about 0.1% to about 10%, from about 0.5% to about 5%, from about 1% to about 20%, or about 10% or less, by weight of the oral care composition, of a polyphosphate source.

Wetting agent

Aqueous composition and/or oral care composition can comprise one or more wetting agents, have low-level wetting agents, are substantially free of, substantially free of or free of wetting agents. Wetting agents are used to increase the consistency or " mouthfeel " of oral care composition or dentifrice and prevent the dentifrice from drying out. Suitable wetting agents include polyethylene glycol (with multiple different molecular weights), propylene glycol, glycerine (glycerin, glycerol), erythritol, xylitol, sorbitol, mannitol, butylene glycol, lactitol, hydrogenated starch hydrolysate and/or their mixture. Aqueous composition and/or oral care composition can comprise one or more wetting agents, and the content of each wetting agent is 0% to about 70%, about 5% to about 50%, about 10% to about 60% or about 20% to about 80% by weight of oral care composition.

Surfactants

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

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

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

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

Wherein R ₁ represents a straight or branched alkyl or alkenyl group having 6 to 22 carbon atoms, which is optionally substituted with one or more phosphate groups; n and m are individually and separately 2 to 4, and a and b are individually and separately 0 to 20; Z and Z may be the same or different, each representing hydrogen, alkali metal, ammonium, protonated alkylamine or protonated functional alkylamine, such as alkanolamine or R—(OCH2)(OCH)-group. Examples of suitable agents include alkyl phosphates and alkyl (poly) alkoxy phosphates such as lauryl phosphate; PPGS cetearyl polyoxyethylene ether-10 phosphate; laureth-1 phosphate; laureth-3 phosphate; laureth-9 phosphate; trilaureth-4 phosphate; C _12-18 PEG 9 phosphate: and dilaureth-10 sodium phosphate. The alkyl phosphate may be polymeric. Examples of polymeric alkyl phosphates include those containing repeating alkoxy groups as polymeric moieties, specifically those containing 3 or more ethoxy, propoxy, isopropoxy or butoxy groups.

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

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

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

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

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

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

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

The aqueous and/or oral care compositions may contain one or more surfactants, each present at a level of from about 0.01% to about 15%, from about 0.3% to about 10%, or from about 0.3% to about 2.5%, by weight of the oral care composition.

Thickener

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

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

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

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

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

The aqueous and/or oral care compositions may contain from 0.01% to about 15%, from 0.1% to about 10%, from about 0.2% to about 5%, or from about 0.5% to about 2% of one or more thickening agents.

Prenylated flavonoids

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

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

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

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

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

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

Other suitable prenylated flavonoids can include psoralea chalcone, psoralea flavonoid, methyl psoralea flavonoid, Corylifol A, epimedin A, epimedin A1, epimedin B, epimedin C, icariin, icariin I, icariin II, icariin, isopsoralea chalcone, isoxanthohumol, neopsoralea isoflavone, 6-isoprenylnaringenin, 8-isoprenylnaringenin, sophanolone G, (-)-soybean root root, xanthohumol, quercetin, macellignan, sophora flavescens chalcone, sophora flavescens flavonoid, mulberry G, mulberry C, Panduratin A, 6-geranylnaringenin, Australone A, 6,8-diisoprenyleucodermocarb, dorsmanin C, dorsmanin F, 8-isoprenylukaempferol, 7-O-methyllupin isoflavone, lupin isoflavone, 6-isoprenylugenistein, isowighteone, yellow lupin weiterenone and/or a combination thereof.

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

Preferably, the prenylated flavonoid has a probabilistic MIC of less than about 10% against Escherichia coli, a gram-negative bacterium. Suitable prenylated flavonoids include methyl psoralen, isoxanthohumol, 8-prenylnaringenin, flavonoid G, matrine, Panduratin A, and/or combinations thereof.

Approximately 1000 prenylated flavonoids have been identified from plants. Based on the number of prenylated flavonoids reported previously, prenylated flavones are the most common subclass and prenylated flavanols are the rarest subclass. Although natural prenylated flavonoids have been detected with a variety of structural characteristics, their distribution range in plants is very narrow, unlike the parent flavonoids, which are present in almost all plants. Most prenylated flavonoids are found in the following families, including Guttiferae, Leguminosae, Moraceae, Rutaceae, and Umbelliferae. Leguminosae and Moraceae, due to their consumption as fruits and vegetables, are the most commonly studied families, and many new prenylated flavonoids have been explored.

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

Suitable prenylated flavonoids can have a specific octanol-water partition coefficient. The octanol-water partition coefficient can be used to predict the lipophilicity of a compound. Without wishing to be bound by theory, it is believed that compounds falling within the scope described herein will be able to enter and/or destroy the predominantly hydrophobic phospholipid bilayer that constitutes the microbial cell membrane. Therefore, the octanol-water partition coefficient can be related to the antimicrobial effect of the prenylated flavonoid. Suitable prenylated flavonoids can have a log P 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.

The aqueous and/or oral care compositions may comprise 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% prenylated flavonoid.

Other ingredients

The aqueous composition and/or the oral care composition may contain various other ingredients, such as flavoring agents, sweeteners, coloring agents, preservatives, buffering agents, or other ingredients suitable for use in oral care compositions, as described below.

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

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

Colorants are added to improve the aesthetic appearance of the product. Suitable colorants include, but are not limited to, those approved by the appropriate regulatory agencies such as the FDA and those listed in the European Food and Drug Directive, and include pigments such as _TiO2 , and colors such as FD&C and D&C dyes.

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

Titanium dioxide may also be added to the compositions of the present invention. Titanium dioxide is a white powder that adds opacity to the composition. Titanium dioxide is generally present in an amount of about 0.25% to about 5% by weight of the aqueous composition and/or oral care composition.

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

combination

A. An aqueous composition comprising a hop-metal complex.

B. An aqueous composition as disclosed in A, wherein the hops-metal complex is preformed, formed in situ, or a combination thereof.

C. An aqueous composition as disclosed in A or B, wherein the metal comprises zinc, tin, calcium, or a combination thereof, preferably zinc, tin, or a combination thereof.

D. An aqueous composition as disclosed in C, wherein the zinc comprises zinc phosphate, zinc citrate, zinc lactate, zinc oxide, zinc gluconate, or a combination thereof.

E. An aqueous composition as disclosed in C or D, wherein the tin comprises stannous chloride, stannous fluoride, or a combination thereof.

F. An aqueous composition as disclosed in any one of C to E, wherein the calcium ion source comprises a calcium abrasive, a calcium salt, or a combination thereof.

G. An aqueous composition as disclosed in F, wherein the calcium abrasive comprises calcium carbonate.

H. An aqueous composition as disclosed in any one of A to G, wherein the hops include hop alpha acids, hop beta acids, or a combination thereof.

I. The aqueous composition as disclosed in H, wherein the hop beta acid comprises lupulone, lupulone-like, lupulone-added, or a combination thereof.

J. An aqueous composition as disclosed in any one of A to I, wherein the hops-metal complex comprises lupulone-tin, lupulone-tin, lupulone-tin, hops beta acid-tin, hops alpha acid-tin, lupulone-zinc, lupulone-zinc, lupulone-zinc, hops beta acid-zinc, hops alpha acid-zinc, lupulone-calcium, lupulone-calcium, lupulone-calcium, hops beta acid-calcium, hops alpha acid-calcium, and/or combinations thereof.

K. An aqueous composition as disclosed in any one of A to J, wherein the aqueous composition further comprises amino acids, preferably wherein the amino acids comprise basic amino acids, acidic amino acids, neutral amino acids, or combinations thereof.

L. An aqueous composition as disclosed in K, wherein the amino acids include glycine, alanine, valine, isoleucine, tryptophan, phenylalanine, proline, methionine, leucine, serine, threonine, tyrosine, asparagine, glutamine, cysteine, citrulline, aspartic acid, glutamic acid, lysine, arginine, histidine, or a combination thereof.

M. An aqueous composition as disclosed in any one of A to L, wherein the hop-metal complex comprises Zn (hop beta acid), Sn (hop beta acid), Ca (hop beta acid), or a combination thereof.

N. An aqueous composition as disclosed in any one of A to M for use as a medicament, preferably for treating dental caries, bacteria, glycolytic process, or a combination thereof.

O. An oral care composition comprising a hops-metal complex.

P. An oral care composition as disclosed in O, wherein the hops-metal complex is preformed, formed in situ, or a combination thereof.

Q. An oral care composition as disclosed in O or P, wherein the metal comprises zinc, tin, calcium, or a combination thereof, preferably zinc, tin, or a combination thereof.

R. An oral care composition as disclosed in Q, wherein the zinc comprises zinc phosphate, zinc citrate, zinc lactate, zinc oxide, zinc gluconate, or a combination thereof.

S. An oral care composition as disclosed in Q or R, wherein the tin comprises stannous chloride, stannous fluoride, or a combination thereof.

T. An oral care composition as disclosed in any one of Q to S, wherein the calcium ion source comprises a calcium abrasive, a calcium salt, or a combination thereof.

U. An oral care composition as disclosed in T, wherein the calcium abrasive comprises calcium carbonate.

V. An oral care composition as disclosed in any one of O to U, wherein the hops include hop alpha acids, hop beta acids, or a combination thereof.

W. An oral care composition as disclosed in V, wherein the hop beta acid comprises lupulone, paralupulone, addululone, or a combination thereof.

X. An oral care composition as disclosed in any one of O to W, wherein the hops-metal complex comprises lupulone-tin, lupulone-tin, lupulone-tin, hops beta acid-tin, hops alpha acid-tin, lupulone-zinc, lupulone-zinc, lupulone-zinc, hops beta acid-zinc, hops alpha acid-zinc, lupulone-calcium, lupulone-calcium, lupulone-calcium, hops beta acid-calcium, hops alpha acid-calcium, and/or combinations thereof.

Y. An oral care composition as disclosed in any one of O to X, wherein the oral care composition further comprises an amino acid, preferably wherein the amino acid comprises a basic amino acid, an acidic amino acid, a neutral amino acid, or a combination thereof.

Z. An oral care composition as disclosed in Y, wherein the amino acid comprises glycine, alanine, valine, isoleucine, tryptophan, phenylalanine, proline, methionine, leucine, serine, threonine, tyrosine, asparagine, glutamine, cysteine, citrulline, aspartic acid, glutamic acid, lysine, arginine, histidine, or a combination thereof.

AA. An oral care composition as disclosed in any one of O to Z, wherein the hops-metal complex comprises Zn (hops beta acid), Sn (hops beta acid), Ca (hops beta acid), or a combination thereof.

BB. An oral care composition as disclosed in any one of O to AA, which is used as a medicament, preferably for treating caries, bacteria, glycolytic process, or a combination thereof.

Example

The present invention is further illustrated by the following examples, which should not be construed in any way as limiting the scope of the present invention. After reading the description herein, various other aspects, modifications and equivalents thereof may be proposed to those of ordinary skill in the art without departing from the spirit of the present invention or the scope of the appended claims.

Determination of binding constants

According to Formula 1, the binding constants obtained experimentally are listed in Table 1. The brackets in Formula 1 indicate the water molar concentration of the substance used in the determination of _Ka .

Table 1: Binding constants of hops-metal complexes

Metal ions Complex _Ka vehicle Zn2 ⁺ Zn(hop beta acid) 10 ^5.86 1NNaCl Ca ²⁺ Ca(hops beta acid) 10 ^3.92 1NNaCl Sn ²⁺ Sn(Hops beta acid) 10 ¹⁸ .6 1NNaCl

Table 2. Oral Care Compositions

Recipe A Recipe B Recipe C glycerin 49.10 47.80 - Sorbitol - - 37.98 water - - 13.00 Sodium monofluorophosphate - 1.15 - Sodium Gluconate 1.00 1.00 1.00 _SnCl2 1.10 1.10 1.10 CaCO ₃ 32.00 32.00 32.00 Xanthan gum 0.50 0.50 0.30 Carboxymethyl cellulose - - 1.00 Carbomer 1.00 1.00 - Sodium lauryl sulfate 1.40 1.40 1.29 Flavoring 1.00 1.00 1.00 Saccharin Sodium 0.40 0.40 0.50 Stevioside 0.30 0.30 - Sodium hydroxide 1.20 1.35 0.33 Hops beta acid extract* 0.50 0.50 0.50 Sodium bicarbonate 10.00 10.00 10.00 Titanium Dioxide 0.50 0.50 -

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

According to the experimental method described above, the formulas A, B and C shown in Table 2 were prepared. Hop beta acid is composed of Available as an extract from hops. The extract is about 45% hop beta acids by weight of the extract, and less than 1% hop alpha acids by weight of the extract. Formulations A and B have hop beta acids without separately added water. Formulation C includes hop beta acids without fluoride in a high water base.

Table 3. Effect of Sn addition on hop stability in Crest Cavity Protection

Effect of Sn on the stability of hops

To demonstrate the effect of Sn on hop complexation and stabilization, a series of products containing different amounts of stannous chloride at a fixed hop concentration of 0.15% were prepared. The samples were then loaded into tubes and placed in a stable state at 40°C. The samples were removed at 2 months and, after allowing to equilibrate to room temperature, dispensed twice to obtain a sample first from the tip area and subsequently a second sample from a sample behind the tip area. The hops of both samples were analyzed by measuring the UV absorbance at 366nm after appropriate dilution in a 1:1 water:methanol mixture. The reason for measuring the hops at the tip of the toothpaste tube was to determine the effect of stannous chloride on the hops, where hop degradation is greatest due to potential oxygen exposure and the corresponding hop oxidation that results.

Table 3 shows the effect of adding Sn to a composition comprising hops. Hop beta acids can be oxidized in portions of the toothpaste exposed to the atmosphere, such as toothpaste in the tip or shoulder of the tube. However, as shown in Table 3, the more Sn present, the more hop beta acids remain in the tip and/or shoulder of the tube. In other words, the added Sn unexpectedly stabilizes the hop beta acids present in the toothpaste, which prevents oxidation of the hop beta acids. The improved stability is also observed by the reduction in color change of the composition with increased amounts of stannous.

Table 4. Specifications of hop beta acid extract

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

Table 4 describes the A hop beta acid extract is provided. Because hop beta acids are provided in an extract form, there may be some variability in the amounts of certain components. However, the extract contains about 45% hop beta acids by weight of the extract and about 0.4% hop alpha acids by weight of the extract. This is significantly different than previous hop extracts, which typically contain more hop alpha acids than hop beta acids. Other trace components may be present in the hop beta acid extract.

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

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

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

Claims (15)

1. An aqueous composition comprising a hops-metal complex.

2. The composition of claim 1, wherein the hops-metal complex is preformed, formed in situ, or a combination thereof.

3. The composition of claim 1 or 2, wherein the metal comprises zinc, tin, calcium, or a combination thereof.

4. The composition of claim 3, wherein the zinc comprises zinc phosphate, zinc citrate, zinc lactate, zinc oxide, zinc gluconate, or a combination thereof.

5. The composition of claim 3 or 4, wherein the tin comprises stannous chloride, stannous fluoride, or a combination thereof.

6. The composition of any one of claims 3 to 5, wherein the calcium comprises a source of calcium ions.

7. The composition of any one of claims 23 to 28, wherein the hops comprise hops alpha acids, hops beta acids, or combinations thereof, preferably wherein hops beta acids comprise lupulones, lupulones-like, lupulones-adding, or combinations thereof.

8. The composition of any one of claims 1 to 7, wherein the oral care composition comprises an amino acid, preferably wherein the amino acid comprises a basic amino acid, an acidic amino acid, a neutral amino acid, or a combination thereof, preferably wherein the amino acid comprises glycine, alanine, valine, isoleucine, tryptophan, phenylalanine, proline, methionine, leucine, serine, threonine, tyrosine, asparagine, glutamine, cysteine, citrulline, aspartic acid, glutamic acid, lysine, arginine, histidine, or a combination thereof.

9. The composition of any one of claims 1 to 8, wherein the hops-metal complex comprises Zn (hops beta acids), sn (hops beta acids), ca (hops beta acids), or a combination thereof.

10. A hop-metal complex.

11. The complex of claim 10, wherein the metal comprises zinc, tin, calcium, or a combination thereof.

12. The complex of claim 11, wherein the zinc comprises zinc phosphate, zinc citrate, zinc lactate, zinc oxide, zinc gluconate, or a combination thereof.

13. The complex of claim 11 or 12, wherein the tin comprises stannous chloride, stannous fluoride, or a combination thereof.

14. The complex of any one of claims 11 to 13, wherein the hops comprise hops alpha acids, hops beta acids, or a combination thereof.

15. The complex of claim 14, wherein the hops beta acids comprise lupulones, lupulones-like, or combinations thereof.