Oral Care Products and Methods

Abstract

Provided herein are oral care compositions comprising partially hydrolyzed plant protein, which are useful in methods of repairing or inhibiting dental erosion, promoting dental remineralization, and/or enhancing the anti-cavity effects of fluoride.

Claims

1. An oral care composition comprising: a. partially hydrolyzed plant protein, wherein the partially hydrolyzed plant protein comprises oligo- and polypeptide molecules having a molecular weight distribution of about 500 D to about 10000 D; and b. an orally acceptable carrier, wherein the partially hydrolyzed plant protein is present in the composition in an amount of from 3.05 weight % to 10.5 weight % by total weight of the composition.

2. The oral care composition of claim 1 wherein the partially hydrolyzed plant protein is obtained from grains of the family Poaceae.

3. The oral care composition of claim 1, wherein the partially hydrolyzed plant protein is partially hydrolyzed wheat protein or hydrolyzed rice protein.

4. The oral care composition of claim 1, wherein the partially hydrolyzed plant protein is obtained from wheat, rice, almond, potato, pea, soya or combinations thereof.

5. The oral care composition of claim 1, wherein the oral care composition comprises fluoride.

6. The oral care composition of claim 1, wherein the composition is free of any fluoride source.

7. The oral care composition of claim 1, wherein the partially hydrolyzed plant protein is present in the composition in an amount of from 3.5 weight %-10.5 weight % by total weight of the composition.

8. The oral care composition of claim 1, wherein the partially hydrolyzed plant protein is present in the composition in an amount of from 3.05 weight % to 30.5 weight % by total weight of the composition.

9. The oral care composition of claim 1, wherein the partially hydrolyzed plant protein is present in the composition from 3.5 weight %-4.5% weight % by total weight of the composition.

10. The oral care composition of claim 1, wherein the composition is in a form selected from a mouthrinse, a toothpaste, a tooth gel, a tooth powder, a non-abrasive gel, a mousse, a foam, a mouth spray, chewing gum, and a tablet.

11. The oral care composition of claim 1, wherein the composition is in the form of a gel.

12. A method of repairing or inhibiting dental erosion, promoting dental remineralization, and/or enhancing the anti-cavity effects of fluoride comprising applying to the teeth a composition comprising: a) partially hydrolyzed plant protein, comprising oligo- and polypeptide molecules having a molecular weight distribution of about 500 to about 10000 D; b) an orally acceptable carrier, wherein the partially hydrolyzed plant protein is present in the composition in an amount of from 3.5 weight %-10 weight % by total weight of the composition.

13. The method of claim 12, wherein the partially hydrolyzed plant protein is partially hydrolyzed wheat protein or hydrolyzed rice protein.

14. The method of claim 12, wherein the partially hydrolyzed plant protein is obtained from almond, potato or soya.

15. The method of claim 12, wherein the oral care composition comprises fluoride.

16. The method of claim 12, wherein the oral composition is free of any source of fluoride.

17. A method of making an oral care product useful for repairing or inhibiting dental erosion, promoting dental remineralization, and/or enhancing the anti-cavity effects of fluoride, comprising: a) a partially hydrolyzed plant protein, comprising oligo- and polypeptide molecules having a molecular weight distribution of about 500 to about 10000 D, adjusting the pH by dilution with an aqueous buffer solution, to obtain a solution having the desired pH; b) filtering and centrifuging the solution product of a) to obtain a filtrate comprising the partially hydrolyzed plant protein; c) optionally adding fluoride and optionally a biocide; d) admixing the product of c) to components of an orally acceptable carrier to obtain an oral care composition comprising the partially hydrolyzed plant protein in an amount of from 3.1 weight % to 10 weight % by total weight of the composition.

Description

DETAILED DESCRIPTION

[0111] The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.

[0112] As used throughout, ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range. In addition, all references cited herein are hereby incorporated by referenced in their entireties. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls.

[0113] Unless otherwise specified, all percentages and amounts expressed herein and elsewhere in the specification should be understood to refer to percentages by weight. The amounts given are based on the active weight of the material.

Hydrolyzed Plant Proteins

[0114] Hydrolyzed plant proteins are proteins from plants, for example, from edible plant parts, for example from wheat, rice, almond, potato, pea, soya or combinations thereof, e.g., from cereal grains such as maize, wheat, rice, barley, oats, and millet. In particular embodiments, the hydrolyzed plant proteins are from wheat or rice.

[0115] Hydrolyzed wheat protein, also referred to as hydrolyzed wheat gluten, is typically obtained by enzymatically hydrolyzing wheat gluten using endoproteases and exoproteases. Hydrolyzed wheat protein may also be obtained through acid or alkaline hydrolysis. Methods of preparing hydrolyzed wheat protein would be known to the person skilled in the art of protein chemistry. However, hydrolyzed wheat protein is also commercially available as Gluadin® W20, Gluadin W40 from BASF, and as Wheatpro® from IKEDA. Gluadin W20 is a partial hydrolysate obtained through enzymatic hydrolysis of wheat gluten. It contains at least 20.0% of dry substance. Gluadin W40 is a partial hydrolysate obtained through enzymatic hydrolysis of wheat gluten. It contains at least 40.0% of dry substance.

[0116] In another embodiment, the hydrolyzed plant protein is made from processed wheat protein which is free of gluten.

[0117] Hydrolyzed rice protein is typically obtained by enzymatically hydrolyzing rice protein using endoproteases and exoproteases. Hydrolyzed rice protein may also be obtained through acid or alkaline hydrolysis. Methods of preparing hydrolyzed rice protein would be known to the person skilled in the art of protein chemistry. However, hydrolyzed rice protein is also commercially available as Gluadin® R from BASF, and as Rice Pro-Tein BK-S® from TRI-K Industries

[0118] The hydrolyzed plant protein used in the compositions and methods herein is not fully hydrolyzed and thus is sometimes referred to as “partially hydrolyzed” to emphasize this point. By “partially hydrolyzed” it is meant that at least some, but not all, of the peptide bonds are hydrolyzed. Thus, the hydrolyzed plant protein typically comprises a mixture of amino acids and peptides of varying size. MW of relevant active ingredient is in the range of about 500-about 10,000 D, for example about 1000 to about 5000 D.

[0119] In some embodiments, the hydrolyzed plant protein is present in the composition in an amount of from 3.1 weight % to 10 weight % by total weight of the composition. In some embodiments, the hydrolyzed plant protein is present in the composition in an amount of from 3.1 weight % to 10.5 weight % by total weight of the composition, e.g., from 3.5 weight %-10 weight % by total weight of the composition, e.g., 3.5 weight %-4.5% weight % by total weight of the composition, e.g., 4.5 weight %-5.5% weight % by total weight of the composition, e.g., 9.5 weight %-10.5% weight % by total weight of the composition, or e.g., e.g., 5.5 weight %-10.5 weight % by total weight of the composition, or about 4 weight %, or about 5 weight %, or about 6 weight %, or about 7 weight %, or about 8 weight %, or about 9 weight %, or about 10 weight % by total weight of the composition.

[0120] In one arrangement, the compositions of the present invention comprise both hydrolyzed wheat protein and hydrolyzed rice protein. In this arrangement, the hydrolyzed wheat protein and the hydrolyzed rice protein may be present in the composition in the amounts defined above. Optionally, the total amount of hydrolyzed wheat protein and hydrolyzed rice protein in the composition is from 3.1 weight % to 10 weight %, or from 3.1 weight % to 9 weight %, or from 3.1 weight % to 8 weight %, or from 3.1 weight % to 7 weight %, or from 3.1 weight % to 6 weight %, or 3.1 weight % to 5 weight % by total weight of the composition.

[0121] In some embodiments, the hydrolyzed plant protein is present in the composition in an amount of from 10.5 weight % to 30.5 weight % by total weight of the composition. In some embodiments, the hydrolyzed plant protein (e.g., hydrolyzed wheat protein) is present in the composition in an amount of about 15 weight %, or about 20 weight %, or about 25 weight %, or about 30 weight %, by total weight of the composition.

Orally Acceptable Carrier and Optional Ingredients

[0122] The expression “orally acceptable carrier” as used herein denotes a carrier made from materials that are safe and acceptable for oral use in the amounts and concentrations intended, for example materials as would be found in conventional toothpaste and mouthwash. Such materials include water or other solvents that may contain a humectant such as glycerin, sorbitol, xylitol and the like. In some aspects, the term “orally acceptable carrier” encompasses all of the components of the oral care composition except for the hydrolyzed plant protein and the fluoride. In other aspects, the term refers to inert or inactive ingredients that serve to deliver the hydrolyzed plant protein, and/or any other functional ingredients, to the oral cavity.

[0123] Orally acceptable carriers for use in the invention include conventional and known carriers used in making mouth rinses or mouthwashes, toothpastes, tooth gels, tooth powder, lozenges, gums, beads, edible strips, tablets and the like. Carriers should be selected for compatibility with each other and with other ingredients of the composition.

[0124] The following non-limiting examples are provided. In a toothpaste composition, the carrier is typically a water/humectant system that provides a major fraction by weight of the composition. Alternatively, the carrier component of a toothpaste composition may comprise water, one or more humectants, and other functional components other than the hydrolyzed wheat protein or hydrolyzed rice protein. In a mouth rinse or a mouthwash formulation, the carrier is typically a water/alcohol liquid mixture in which the hydrolyzed wheat protein or hydrolyzed rice protein is dissolved or dispersed. In a dissolvable lozenge, the carrier typically comprises a solid matrix material that dissolves slowly in the oral cavity. In chewing gums, the carrier typically comprises a gum base, while in an edible strip, the carrier typically comprises one or more film forming polymers.

[0125] The oral care compositions provided herein may further comprise one or more additional ingredients selected from abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, anti-calculus or tartar control agents, sweeteners, flavorants, colorants and preservatives. These ingredients may also be regarded as carrier materials. Non-limiting examples are provided below.

[0126] In one embodiment a composition of the invention comprises at least one abrasive, useful, for example, as a polishing agent. Any orally acceptable abrasive can be used, but the type, fineness (particle size) and amount of abrasive should be selected so that tooth enamel is not excessively abraded during normal use of the composition. Suitable abrasives include, without limitation, silica, for example in the form of silica gel, hydrated silica or precipitated silica, alumina, insoluble phosphates, calcium carbonate, resinous abrasives such as urea-formaldehyde condensation products and the like. Among insoluble phosphates useful as abrasives are orthophosphates, polymetaphosphates and pyrophosphates. Illustrative examples are dicalcium orthophosphate dihydrate, calcium pyrophosphate, [beta]-calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate and insoluble sodium polymetaphosphate. One or more abrasives are optionally present in the oral care compositions of the present invention in an amount of 1 weight % to 5 weight % by total weight of the composition. The average particle size of an abrasive, if present, is generally 0.1 to 30 μm, and preferably, 5 to 15 μm.

[0127] In a further embodiment an oral care composition of the invention comprises at least one bicarbonate salt, useful, for example, to impart a “clean feel” to teeth and gums due to effervescence and release of carbon dioxide. Any orally acceptable bicarbonate can be used, including, without limitation, alkali metal bicarbonates such as sodium and potassium bicarbonates, ammonium bicarbonate and the like. One or more bicarbonate salts are optionally present in a total amount of 1 weight % to 10% by weight of the composition.

[0128] In a still further embodiment, an oral care composition of the invention comprises at least one pH modifying agent. Such agents include acidifying agents to lower pH, basifying agents to raise pH and buffering agents to control pH within a desired range. For example, one or more compounds selected from acidifying, basifying and buffering agents can be included to provide a pH of 2 to 10, or in various illustrative embodiments a pH of 2 to 8, 3 to 9, 4 to 8, 5 to 7, 6 to 10, or 7 to 9. Any orally acceptable pH modifying agent can be used, including, without limitation, carboxylic, phosphoric and sulfonic acids, acid salts (for example, monosodium citrate, disodium citrate, monosodium malate), alkali metal hydroxides such as sodium hydroxide, carbonates such as sodium carbonate, bicarbonates, borates, silicates, phosphates (for example, monosodium phosphate, trisodium phosphate, pyrophosphate salts) imidazole and the like. One or more pH modifying agents are optionally present in a total amount effective to maintain the composition in an orally acceptable pH range.

[0129] In a still further embodiment a composition of the invention comprises at least one surfactant, useful, for example, to provide enhanced stability to the composition and the components contained therein, to aid in cleaning a dental surface through detergent action, and to provide foam upon agitation (for example, during brushing with a dentifrice composition of the invention). Any orally acceptable surfactant, including those which are anionic, nonionic or amphoteric, can be used. Suitable anionic surfactants include, without limitation, water-soluble salts of C.sub.8-20 alkyl sulfates, sulfonated monoglycerides of C.sub.8-20 fatty acids, sarcosinates, taurates and the like. Suitable nonionic surfactants include, without limitation, poloxamers, polyoxyethylene sorbitan esters, fatty alcohol ethoxylates, alkylphenol ethoxylates, tertiary amine oxides, tertiary phosphine oxides, dialkyl sulfoxides and the like. Suitable amphoteric surfactants, without limitation, derivatives of C.sub.8-20 aliphatic secondary and tertiary amines having an anionic group such as carboxylate, sulfate, sulfonate, phosphate or phosphonate. A suitable example is cocoamidopropyl betaine. One or more surfactants are optionally present in a total amount of 0.01 weight % to 10 weight %, for example, from 0.05 weight % to 5 weight % or from 0.1 weight % to 2 weight % by total weight of the composition.

[0130] In a still further embodiment, an oral care composition of the invention comprises at least one foam modulator, useful, for example, to increase the amount, thickness or stability of foam generated by the composition upon agitation. Any orally acceptable foam modulator can be used including, without limitation, polyethylene glycols (PEGs). One or more PEGs are optionally present in a total amount of from 0.1 weight % to 10 weight by total weight of the composition.

[0131] In a still further embodiment, an oral care composition of the invention comprises at least one thickening agent, useful, for example, to impart a desired consistency and/or mouth feel to the composition. Any orally acceptable thickening agent can be used including, without limitation, carbomers (carboxyvinyl polymers), carrageenans, cellulosic polymers such as hydroxyethylcellulose, carboxymethylcellulose (CMC) and salts thereof, natural gums such as karaya, xanthan, gum arabic and tragacanth, colloidal magnesium aluminum silicate, colloidal silica and the like. One or more thickening agents are optionally present in a total amount of 0.01 weight % to 15 weight %, by total weight of the composition.

[0132] In a still further embodiment a composition of the invention comprises at least one viscosity modifier, useful, for example, to inhibit settling or separation of ingredients or to promote re-dispersion of ingredients upon agitation of a liquid composition. Any orally acceptable viscosity modifier can be used including, without limitation, mineral oil, petrolatum, clays, silica and the like. One or more viscosity modifiers are optionally present in a total amount of 0.01 weight % to 10 weight %, by total weight of the composition.

[0133] In a still further embodiment, an oral care composition of the invention comprises at least one humectant which may be used to prevent hardening of a toothpaste upon exposure to air. Any orally acceptable humectant can be used, including, without limitation, polyhydric alcohols such as glycerin, sorbitol, xylitol or low molecular weight PEGs. Most humectants also function as sweeteners. One or more humectants are optionally present in a total amount of 1 weight % to 50 weight % by total weight of the composition.

[0134] In a still further embodiment, an oral care composition of the invention comprises at least one sweetener which enhances taste of the composition. Any orally acceptable natural or artificial sweetener can be used including, without limitation, dextrose, sucrose, maltose, dextrin, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup, partially hydrolyzed starch, hydrogenated starch hydrolysate, sorbitol, mannitol, xylitol, maltitol, isomalt, aspartame, neotame, saccharin and salts thereof, dipeptide-based intense sweeteners, cyclamates and the like. One or more sweeteners are optionally present in a total amount of 0.005 weight % to 5 weight % by total weight of the composition.

[0135] In a still further embodiment, an oral care composition of the invention comprises at least one flavorant which enhances the taste of the composition. Any orally acceptable natural or synthetic flavorant can be used including, without limitation, vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, oil of wintergreen (methylsalicylate), peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, citrus oils, fruit oils and essences, and the like. Also encompassed within flavorants are ingredients that provide fragrance and/or other sensory effects in the mouth, including cooling or warming effects. Such ingredients illustratively include menthol, menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol, eugenol, cassia, oxanone, α-irisone, thymol, linalool, benzaldehyde, cinnamaldehyde, N-ethyl-p-menthan-3-carboxamine, N,2,3-trimethyl-2-isopropylbutanamide, 3-(1-menthoxy)-propane-1,2-diol, cinnamaldehyde glycerol acetal (CGA), menthone glycerol acetal (MGA) and the like. One or more flavorants are optionally present in a total amount of 0.01 weight % to 5 weight %, by total weight of the composition.

[0136] In a still further embodiment, an oral care composition of the invention comprises at least one colorant. A colorant can serve a number of functions. These include providing a white or light-colored coating on a dental surface, indicating locations on a dental surface that have been effectively contacted by the composition, and/or modifying the appearance of the composition to enhance attractiveness to the consumer. Any orally acceptable colorant can be used including, without limitation, talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, magnesium aluminum silicate, silica, titanium dioxide, zinc oxide, iron oxide, ferric ammonium ferrocyanide, manganese violet, titaniated mica, bismuth oxychloride and the like. One or more colorants are optionally present in a total amount of 0.001 weight % to 20 weight % by total weight of the composition.

[0137] In a still further embodiment, an oral care composition of the invention comprises a preservative. The preservative may be selected from parabens, potassium sorbate, benzyl alcohol, phenoxyethanol, polyaminopropryl biguanide, caprylic acid, sodium benzoate and cetylpyridinium chloride. In some embodiments, the preservative is present at a concentration of from about 0.001 to about 1 weight %, by total weight of the composition.

[0138] The following examples illustrate compositions of the invention and their uses. The exemplified compositions are illustrative and do not limit the scope of the invention.

EXAMPLES

Example 1—Microhardness

[0139] Bovine teeth are cut, ground and polished to obtain enamel blocks having approximate dimensions of 3 mm×3 mm×2 mm. The thickness of the enamel is approximately 1 to 2 mm, and the thickness of dentin is approximately 1 mm. All measurements are taken on the enamel surface.

[0140] Microhardness is measured using a Micromet 6020 Micro-hardness Tester with a Knoop Diamond Indenter and a 50 g load (Buehler, Lake Bluff, Ill., USA). Blocks with a Knoop hardness (KH) of at least 300 are selected. The blocks are etched by immersing in 30% phosphoric acid for 15 seconds. Then blocks are washed with DI water @5 minutes, 500 RPM and air dried overnight. Microhardness for each etched block is measured. Subsequently, the blocks are treated with 2 ml of corresponding weight concentration solution of hydrolyzed wheat protein (Gluadin W20 from BASF), for 30 minutes. The blocks are washed twice with DI water @ 5 minutes, 500 PRM after the treatment. Subsequently, the blocks are incubated in AS solution (0.2 mM MgCl.sub.2, 1 mM CaCl.sub.2).H.sub.2O, 20 mM HEPES buffer, 4 mM KH.sub.2PO.sub.4, 16 mM KCl, 4.5 mM NH.sub.4Cl at pH 7 (adjusted with 1M NaOH)) overnight. After rinsing the enamel blocks with DI water and air-drying the rinsed blocks, microhardness is measured again. Surface microhardness regain (SMHL, Remin %) as a percent is calculated as

[00001]$\%\mathrm{remineralization}=\frac{\left({\mathrm{MH}}_{\mathrm{Repaired}}-{\mathrm{MH}}_{\mathrm{Etched}}\right)}{\left({\mathrm{MH}}_{\mathrm{Baseline}}-{\mathrm{MH}}_{\mathrm{Etched}}\right)}\times 100$

[0141] The results of the microhardness assay are illustrated in Table 1.

TABLE-US-00001 TABLE 1 Results of microhardness assay Protein % remineralization (mean) S.D. 3% Hydrolyzed wheat protein 27.8% 5.9% 4% Hydrolyzed wheat protein 38.8% 8.2% 5% Hydrolyzed wheat protein 42.0% 0.7% 10% Hydrolyzed wheat protein 49.4% 5.8% Control (0% Hydrolyzed wheat 9.32% 6.37% protein)

[0142] It can be seen from Table 1 that hydrolyzed wheat protein is effective in remineralizing the enamel surface of acid-etched enamel blocks. In particular, higher concentrations of hydrolyzed wheat protein appear to increase the remineralization effect. The only differences in the formulations are the amounts (or presence) of hydrolyzed wheat protein. The test formulations in Table 1 as simple solutions (using deionized water) corresponding to the weight percentages of hydrolyzed wheat protein.

[0143] Formulations with the hydrolyzed wheat protein are also effective in remineralizing the enamel surface of acid-etched enamel blocks when compared to oral care composition formulations containing fluoride. The results of such a comparison, using the microhardness assay illustrated above, is illustrated in Table 2.

TABLE-US-00002 TABLE 2 Results of microhardness assay (Comparison w./Fluoride formulations) Protein % remineralization (mean) S.D. 4% Hydrolyzed wheat protein 42.1 3.6% 225 ppm F 26.0% 2.8% Control - Water (0% 11.4% 3.94% Hydrolyzed wheat protein)

Example 2

[0144] An exemplary gel formulation (e.g., tooth gel) is prepared comprising the following ingredients:

TABLE-US-00003 Ingredients Amounts (by wt %) Demineralized water q.s. Poloxamer 338 0.5 Sodium Saccharin 0.02 Hydrolyzed Wheat Protein 4.0 Cetylpyridinium Chloride 0.04 Potassium Sorbate 0.05 Glycerin - USP, EP VEG 7.5 Sorbitol - Non Crystal - 5.5 70% Solution USP, EP Propylene Glycol 7 Benzyl Alcohol 0.20 Xanthan Gum 1.6 Flavoring 0.14 Total Components 100%

Example 3

[0145] An exemplary gel formulation (e.g., tooth gel) is prepared comprising the following ingredients:

TABLE-US-00004 Ingredients Amounts (by wt %) Demineralized water q.s. Poloxamer 338 0.5 Sodium Saccharin 0.02 Hydrolyzed Wheat Protein 4.0 Cetylpyridinium Chloride 0.04 Potassium Sorbate 0.05 Glycerin - USP, EP VEG 7.5 Sorbitol - Non Crystal - 5.5 70% Solution USP, EP Propylene Glycol 7 Benzyl Alcohol 0.20 Hydroxyethylcellulose 4.0 Flavoring 0.14 Total Components 100%

[0146] The above exemplary formulation provides a fluoride-free alternative oral gel. For example, the above formulation can be used as an in-office dental preparation.

[0147] While particular embodiments of the invention have been illustrated and described, it will be obvious to those skilled in the art that various changes and modifications may be made without departing from the scope of the invention as defined in the appended claims.