Oral care composition

Abstract

An oral care composition comprising histidine or salts thereof and potassium nitrate.

Description

[0001] P0001204 CPL

[0002] - 1 -

[0003] ORAL CARE COMPOSITION

[0004] The present invention relates to oral care compositions, in particular to oral care compositions 5 comprising histidine and salts thereof.

[0005] Background

[0006] Alkali generation by oral bacteria plays a key role in plaque pH homeostasis and may be a major impediment to the development of dental caries. Ammonia production by oral bacteria is believed to have an impact on oral microbial ecology and to be intimately linked with oral health and diseases.

[0007] Several amino acids can be decarboxylated by dental plaque and converted into amine and carbon oxide thereby neutralizing the acidic plaque environment. In these metabolic systems, 15 many enzymatic reactions, such as deamination and transamination, are involved. However, there is no information available about which amino acids are mainly degraded and how those amino acids are metabolized in dental plaque (Hayes ML and Hyatt AT ,1974).

[0008] Similarly, A study on isolation and characterisation of nitrate reducing bacteria as potential 20 probiotics for oral health showed nitrate prevented acidification by oral bacteria via conversion to ammonium through the dissimilatory nitrated reduction to ammonium (DNRA) pathway and the nitrate reduction capacity of the oral microbiota correlated negatively with caries abundance (Li et al., 2007, Doel et al., 2004).

[0009] 25 The present invention has found synergistic benefits for ammonia production by the oral commensal bacteria Streptococcus sanguinis from histidine and KN03 as the substrate which could play major roles in pH homeostasis in oral biofilms and may moderate initiation and progression of dental caries.

[0010] Description of the Invention

[0011] The present invention relates to an oral care composition comprising histidine or salts thereof and potassium nitrate in which the weight ratio of histidine or salt thereof to potassium nitrate is from 8:1 to 2:3.

[0012] 35P0001204 CPL

[0013] - 2 -

[0014] The invention further relates to an oral care composition comprising histidine or salts thereof and potassium nitrate for use in the treatment and / or mitigation of dental caries.

[0015] Detailed Description of the Invention

[0016] 5 Except in the examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and / or use may optionally be understood as modified by the word “about”.

[0017] All amounts are by weight of the composition, unless otherwise specified.

[0018] It should be noted that in specifying any ranges of values, any upper value can be associated with any particular lower value.

[0019] Where a feature is disclosed with respect to a particular aspect of the invention (for example a 15 composition of the invention), such disclosure is also to be considered to apply to any other aspect of the invention (for example a method of the invention) mutatis mutandis.

[0020] The term “oral care composition" refers to a composition that is delivered to the oral surfaces. The composition may be a product which, during the normal course of usage, is not for the 20 purpose of systemic administration or intentionally swallowed but is rather retained in the oral cavity for a time sufficient to contact substantially all of the dental surfaces and / or oral tissues for the purposes of oral activity.

[0021] Examples of the oral composition include a toothpaste or a dentifrice, a mouthwash or a mouth 25 rinse, powder (e.g., tooth powder), lozenge, mint, cream, strip or gum (e.g., chewing gum), a film a topical oral gel, and a denture cleanser and the like.

[0022] The composition of the invention is used to clean the surfaces of the oral cavity.

[0023] Accordingly, preferred product forms for compositions of the invention are those which are suitable for brushing and / or rinsing the surfaces of the oral cavity.

[0024] The composition of the invention is most preferably in the form of a dentifrice / toothpaste. The term "dentifrice" denotes an oral composition which is used to clean the surfaces of the oral 35 cavity. Such a composition is not intentionally swallowed for purposes of systemic administration of therapeutic agents, but is applied to the oral cavity, used to treat the oral cavityP0001204 CPL

[0025] - 3 -

[0026] and then expectorated. Typically such a composition is used in conjunction with a cleaning implement such as a toothbrush, usually by applying it to the bristles of the toothbrush and then brushing the accessible surfaces of the oral cavity.

[0027] 5 Preferably the dentifrice / toothpaste is in the form of an extrudable semi-solid such as a cream, paste or gel (or mixture thereof).

[0028] Preferably the level of histidine or salt thereof is from 0.1 to 5 wt% of the total composition, more preferably from 0.2wt% to 3 wt%.

[0029] Preferably the level of potassium nitrate is from 0.1 to 5 wt% of the total composition, more preferably from 0.2wt% to 3 wt%.

[0030] The weight ratio of histidine or salt thereof to potassium nitrate is from 8:1 to 2:3, preferably 15 from 5:1 to 1:1, most preferably from 3:1 to 3:2

[0031] It is preferred if the histidine is a sodium salt or is not a salt form.

[0032] A composition according to the invention (such as a dentifrice / toothpaste) will generally contain 20 further ingredients to enhance performance and / or consumer acceptability, in addition to the ingredients specified above.

[0033] Compositions according to the invention, particularly toothpastes, preferably comprise particulate abrasive materials such as silicas, aluminas, calcium carbonates,

[0034] 25 dicalciumphosphates, calcium pyrophosphates, hydroxyapatites, trimetaphosphates, insoluble hexametaphosphates and so on, including agglomerated particulate abrasive materials, usually in amounts between 3 and 60% by weight of the oral care composition.

[0035] In one embodiment of the invention the composition comprises a silica based abrasive. The preferred abrasive silicas used in the present invention is a silica with a low refractive index. It may be used as the sole abrasive silica, or in conjunction with a low level of other abrasive silicas, e.g. those according to EP 236070. The low refractive index silicas, used as abrasives in the present invention are preferably silicas with an apparent refractive index (R.l.) in the range of 1.41 - 1.47, preferably 1.435 - 1.445, preferably having a weight mean particle size of 35 between 5 and 15 mm, a BET (nitrogen) surface area of between 10 and 100 m2 / g and an oil absorption of about 70 - 150 cm3 / 100 g, but abrasive silicas with a lower apparent refractiveP0001204 CPL

[0036] - 4 -

[0037] index may also be used. Typical examples of suitable low refractive index abrasive silicas (e.g. having an R.l. of between 1.435 and 1.445) are Tixosil 63 and 73 ex Rhone Poulenc; Sident 10 ex Degussa; Zeodent 113 exZeofinn; Zeodent 124 ex Evonik, Sorbosil AC 77 ex PQ Corporation (having an R.l. of approximately 1.440). The amount of these silicas in the 5 composition generally ranges from 5-60% by weight, usually 5-20% by weight.

[0038] An alternative suitable abrasive is calcium carbonate. Natural calcium carbonate abrasive is typically a finely ground limestone which may optionally be refined or partially refined to remove impurities. The material preferably has an average particle size of less than 10 microns, e.g., 3-7 microns, e.g., about 5.5 microns. For example, a small particle silica may have an average particle size (D50) of 2.5 -4.5 microns. Because natural calcium carbonate may contain a high proportion of relatively large particles of not carefully controlled, which may unacceptably increase the abrasivity, preferably no more than 0.01 wt%, preferably no more than

[0039] 0.004 percent by weight of particles would not pass through a 325 mesh. The material has 15 strong crystal structure, and is thus much harder and more abrasive than precipitated calcium carbonate. The tapped density for the natural calcium carbonate is for example between 1 and 1.5 g / cc, e.g., about 1.2 for example about 1.19 g / cc. There are different polymorphs of natural calcium carbonate, e.g., calcite, aragonite and vaterite, calcite being preferred for purposes of this invention.

[0040] 20

[0041] Precipitated calcium carbonate has a different crystal structure from natural calcium carbonate. It is generally more friable and more porous, thus having lower abrasivity and higher water absorption. For use in the present invention, the particles are small, e.g., having an average particle size of 1-5 microns, and e.g., no more than 0.1 percent, preferably no more than 25 0.05 percent by weight of particles which would not pass through a 325 mesh. The particles may for example have a D50 of 3-6 microns, for example 3.8-4.9, e.g., about 4.3; a D50 of 1-4 microns, e.g., 2.2-2.6 microns, e.g., about 2.4 microns, and a D10 of 1-2 microns, e.g., 1.2-1.4, e.g., about 1.3 microns. The particles have relatively high water absorption, e.g., at least 25 g / 100 g, e.g., 30-70 g / 100 g.

[0042] In some embodiments, additional calcium-containing abrasives, for example calcium phosphate abrasive, e.g., tricalcium phosphate, hydroxyapatite or dicalcium phosphate dihydrate or calcium pyrophosphate, and / or silica abrasives, sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, or other siliceous materials, or

[0043] 35 combinations thereof are used.P0001204 CPL

[0044] - 5 -

[0045] The composition, particularly if a toothpaste preferably comprises an inorganic or a natural or synthetic thickener or gelling agent in proportions of about 0.10 to about 15% by weight depending on the material chosen. These proportions of thickeners in the dentifrice compositions of the present invention form an extrudable, shape-retaining product which can be 5 squeezed from a tube onto a toothbrush and will not fall between the bristles of the brush but rather, will substantially maintain its shape thereon. Suitable thickeners or gelling agents useful in the practice of the present invention include inorganic thickening silicas such as amorphous silicas available from Huber Corporation under the trade designation Zeodent 165, Irish moss, iota-carrageenan, gum tragacanth, and polyvinylpyrrolidone.

[0046] Further suitable binders and thickeners can be present and include as sodium carboxymethylcellulose, hydroxyethyl cellulose (Natrosol®), xanthan gum, gum arabic etc. as well as synthetic polymers such as polyacrylates and carboxyvinyl polymers such as Carbopol®.

[0047] 15 Compositions according to the invention may comprise a polymeric deposition aid. Preferably the composition comprises acid anhydride polymers, particularly preferred are co-polymers of maleic anhydride with methyl vinylether, in which the anhydride moiety may be in a partially or fully hydrolysed or alcoholysed form. Preferred copolymers include Gantrez(R) polymers such as:

[0048] 20 Gantrez S-95: molecular weight 216,000; free acid;

[0049] Gantrez S-96: molecular weight 700,000; free acid;

[0050] Gantrez S-97: molecular weight 1,500,000; free acid; and

[0051] Gantrez MS-955: molecular weight 1,060,000; calcium / sodium salt.

[0052] Particularly preferred co-polymers of maleic acid and methyl vinylether have a molecular weight 25 of 1 ,000,000 or greater and an especially preferred material is Gantrez S-97.

[0053] Compositions according to the invention may comprise a tooth whitening agent. The whitening agent preferably comprises a green and / or a blue pigment. In the context of the present invention a pigment is generally understood to be a shade / material which is insoluble in the relevant medium, at the relevant temperature. This is in contrast to dyes which are soluble. In the context of this invention, the "relevant medium" is human saliva, the liquid medium in which the composition is used, at the temperature of the oral cavity during brushing of the teeth, i.e. up to 37 Degrees C. As a reasonable approximation, the relevant medium may be considered to be water and the relevant temperature to be 25 Degrees C.P0001204 CPL

[0054] - 6 -

[0055] Preferably the blue pigment is Pigment Blue 15, more preferably Pigment Blue 15:1, 15:2, 15:3, 15:4, 15:5 or 15:6, most preferably 15:1. A preferred pigment is blue pigment is Phthalocyanine Blue Pigment, Cl No. 74160, blue covarine.

[0056] 5 The preferred Green pigment is Phthalocyanine Green, preferably Phthalocyanine Green CI- 74260.

[0057] Preferably the total level of pigment in the composition is from 0.01 wt% to 3 wt, more preferably from 0.02 to 2 wt%.

[0058] If the composition is a toothpaste it may be a dual phase paste, with the whitening pigments present in one phase.

[0059] Compositions according to the invention may comprise water-soluble or sparingly water-soluble 15 sources of metal salts Preferred are zinc ions such as zinc chloride, zinc acetate, zinc gluconate, zinc sulphate, zinc fluoride, zinc citrate, zinc lactate, zinc oxide, zinc monoglycerolate, zinc tartrate, zinc pyrophosphate and zinc maleate; also preferred are stannous ions such as stannous fluoride and stannous chloride.

[0060] 20 Compositions according to the invention may comprise oral care enzyme systems such as hydrogen peroxide producing enzyme systems (e.g. the oxidoreductase enzyme glucose oxidase), amyloglucosidase, dextranase and / or mutanase, (optionally in the presence of zinc ion providing compounds and / or 8- hydroxyquinoline derivatives), lactoperoxidase, lactoferrin, lysozyme and mixtures thereof.

[0061] 25

[0062] Compositions of the invention may comprise fluoride sources such as sodium fluoride, stannous fluoride, sodium monofluorophosphate, zinc ammonium fluoride, tin ammonium fluoride, calcium fluoride, cobalt ammonium fluoride and mixtures thereof. Fluoride ion sources may be added to the compositions at a level of about 0.001 wt. percent to about 10 wt. percent, e.g., from about 0.003 wt. percent to about 5 wt. percent, 0.01 wt. percent to about 1 wt., or about 0.05 wt. percent. In some embodiment, the stannous fluoride is present in an amount of 0.1 wt. percent to 2 wt. percent (0.1 wt percent -0.6 wt. percent) of the total composition weight.

[0063] Fluoride ion sources may be added to the compositions at a level of about 0.001 wt. percent to about 10 wt. percent, e.g., from about 0.003 wt. percent to about 5 wt. percent, 0.01 wt. percent 35 to about 1 wt., or about 0.05 wt. percent. However, it is to be understood that the weights of fluoride salts to provide the appropriate level of fluoride ion will obviously vary based on theP0001204 CPL

[0064] - 7 -

[0065] weight of the counter ion in the salt, and one of skill in the art may readily determine such amounts. In some embodiment, the fluoride source is a fluoride salt present in an amount of 0.1 wt. percent to 2 wt. percent (0.1 wt percent -0.6 wt. percent) of the total composition weight (e.g., sodium fluoride (e.g., about 0.32 wt. percent).

[0066] 5

[0067] Some preferred embodiments of the invention are free from fluoride sources, that is the composition comprises less than 0.05 wt% of the total composition of a fluoride source, more preferably less than 0.01 wt%.

[0068] In one embodiment a preferred class of oral care active for inclusion in the compositions of the invention includes agents for the remineralisation of teeth. The term “remineralisation” in the context of the present invention means the in situ generation of hydroxyapatite on teeth.

[0069] A specific example of a suitable agent for the remineralisation of teeth is a mixture of a calcium 15 source and a phosphate source which, when delivered to the teeth results in the in situ generation of hydroxyapatite on teeth.

[0070] Illustrative examples of the types of calcium source that may be used in this context (hereinafter termed “remineralising calcium sources”) include, for example, calcium phosphate, calcium 20 gluconate, calcium oxide, calcium lactate, calcium glycerophosphate, calcium carbonate, calcium hydroxide, calcium sulphate, calcium carboxymethyl cellulose, calcium alginate, calcium salts of citric acid, calcium silicate and mixtures thereof. Preferably the remineralising calcium source is calcium silicate.

[0071] 25 Calcium salts, particularly calcium carbonate can also be used for enamel remineralization.

[0072] Preferred calcium carbonate has a particle size (D50)) from 0.1 to 3 microns, preferable from 0.5 to 2 microns, more preferably from 0.6 to 1.8 microns.

[0073] The amount of remineralising calcium source(s) (e.g. calcium silicate) in the composition of the invention typically ranges from 1 to 30%, preferably from 5 to 20% by total weight remineralising calcium source based on the total weight of the oral care composition.

[0074] Illustrative examples of the types of phosphate source that may be used in this context (hereinafter termed “remineralising phosphate sources”) include, for example, monosodium 35 dihydrogen phosphate, disodium hydrogen phosphate, sodium pyrophosphate, tetrasodium pyrophosphate, sodium tripolyphosphate, sodium hexametaphosphate, potassiumP0001204 CPL

[0075] - 8 -

[0076] dihydrogenphosphate, trisodium phosphate, tripotassium phosphate and mixtures thereof. Preferably the remineralising phosphate source is a mixture of trisodium phosphate and sodium dihydrogen phosphate.

[0077] 5 The amount of remineralising phosphate source(s) (e.g. trisodium phosphate and sodium dihydrogen phosphate) in the composition of this invention typically ranges from 2 to 15%, preferably from 4 to 10% by total weight remineralising phosphate source based on the total weight of the oral care composition.

[0078] In some embodiments, the oral care compositions comprise an effective amount of one or more antibacterial agents, for example comprising an antibacterial agent selected from halogenated diphenyl ether (e.g. triclosan), triclosan monophosphate, herbal extracts and essential oils (e.g., rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitol, magnolol, ursolic acid, ursic acid, catechol, methyl salicylate, epigallocatechin 15 gallate, epigallocatechin, gallic acid, miswak extract, sea-buckthorn extract), bisguanide antiseptics (e.g., chlorhexidine, alexidine or octenidine), quaternary ammonium compounds (e.g., cetylpyridinium chloride (CPC), CPC-claybenzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic antiseptics, hexetidine furanones, bacteriocins, ethyllauroyl arginate, arginine bicarbonate, a Camellia 20 extract, a flavonoid, a flavan, halogenated diphenyl ether, creatine, sanguinarine, povidone iodine, delmopinol, salifluor, metal ions (e.g., zinc salts, stannous salts, copper salts, iron salts), propolis and oxygenating agents (e.g., hydrogen peroxide, buffered sodium peroxyborate or peroxycarbonate), phthalic acid and its salts, monoperthalic acid and its salts and esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphen 25 bromide, delmopinol, octapinol and other piperidino derivatives, nisin preparations, chlorite salts; parabens such as methylparaben or propylparaben and mixtures of any of the foregoing. One or more additional antibacterial or preservative agents may optionally be present in the composition in a total amount of from about 0.01 wt. percent to about 0.5 wt. percent, optionally about 0.05 wt. percent to about 0.1 wt. percent or about 0.3 percent, by total weight of the composition.

[0079] In some embodiments, the oral care compositions also comprise at least one flavorant, useful for example to enhance taste of the composition. Any orally acceptable natural or synthetic flavorant can be used, including without limitation essential oils and various flavoring aldehydes, 35 esters, alcohols, and similar materials, tea flavors, vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, oil of Wintergreen, peppermint oil, clove oil, bay oil, anise oil,P0001204 CPL

[0080] - 9 -

[0081] eucalyptus oil, citrus oils, fruit oils, sassafras and essences including those derived from lemon, orange, lime, grapefruit, apricot, banana, grape, apple, strawberry, cherry, pineapple, etc., bean-and nut-derived flavors such as coffee, cocoa, cola, peanut, almond, etc., adsorbed and encapsulated flavorants and the like. Also encompassed within flavorants herein are ingredients 5 that provide fragrance and / or other sensory effect in the mouth, including cooling or warming effects. Such ingredients illustratively include menthol, carvone, menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol, anethole, eugenol, cassia, oxanone, a-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 from about 0.01 wt. percent to about 5 wt. percent, for example, from about 0.03 wt. percent to about 2.5 wt. percent, optionally about 0.05 wt. percent to about 1.5 wt. percent, further optionally about 0.1 wt. percent to about 0.3 wt. percent and in some embodiments in various embodiments from about 0.01 wt. percent to about 1 wt. percent, 15 from about 0.05 to about 2 percent, from about 0.1 percent to about 2.5 percent, and from about 0.1 to about 0.5 percent by total weight of the composition.

[0082] In some embodiments, the oral care compositions comprise at least one sweetener, useful for example to enhance taste of the composition. Sweetening agents among those useful herein 20 include dextrose, polydextrose, sucrose, maltose, dextrin, dried invert sugar, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup, partially hydrolyzed starch, hydrogenated starch hydrolysate, ethanol, sorbitol, mannitol, xylitol, maltitol, isomalt, aspartame, neotame, saccharin and salts thereof (e.g. sodium saccharin), sucralose, dipeptide-based intense sweeteners, cyclamates, dihydrochalcones.

[0083] 25

[0084] One or more sweeteners are optionally present in a total amount depending strongly on the particular sweetener (s) selected, but typically 0.005 wt. percent to 5 wt. percent, by total weight of the composition, optionally 0.005 wt. percent to 0.2 wt. percent, further optionally

[0085] 0.05 wt. percent to 0.1 wt. percent by total weight of the composition.

[0086] In some embodiments, the oral care compositions further comprise an agent that interferes with or prevents bacterial attachment, e.g., ethyl lauroyl arginiate (ELA), solbrol or chitosan, as well as plaque dispersing agents such as enzymes (papain, glucoamylase, etc.).

[0087] 35 Mixtures of any of the above described materials may also be used.P0001204 CPL

[0088] - 10 -

[0089] The composition according the invention will comprise further ingredients which are common in the art, such as:

[0090] antimicrobial agents, e.g. chlorhexidine, sanguinarine extract, metronidazole, quaternary ammonium compounds, such as cetylpyridinium chloride; cetylpyridium chloride clay complex 5 bis-guanides, such as chlorhexidine digluconate, hexetidine, octenidine, alexidine; and halogenated bisphenolic compounds, such as 2,2' methylenebis-(4-chloro-6-bromophenol); anti-inflammatory agents such as ibuprofen, flurbiprofen, aspirin, indomethacin etc.;

[0091] anti-caries agents such as sodium- and stannous fluoride, aminefluorides, sodium monofluorophosphate, sodium trimeta phosphate and casein;

[0092] plaque buffers such as urea, calcium lactate, calcium glycerophosphate and strontium polyacrylates;

[0093] vitamins such as Vitamins A, C, D, B (preferably B3) and E;

[0094] plant extracts;

[0095] plant-derivable antioxidants such as flavonoid, catechin, polyphenol, and tannin compounds 15 and mixtures thereof;

[0096] desensitising agents, e.g. potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate and strontium salts;

[0097] anti-calculus agents, e.g. alkali-metal pyrophosphates, hypophosphite-containing polymers, organic phosphonates and phosphocitrates etc.;

[0098] 20 biomolecules, e.g. bacteriocins, antibodies, enzymes, etc.;

[0099] flavours, e.g. peppermint and spearmint oils;

[0100] proteinaceous materials such as collagen;

[0101] preservatives;

[0102] opacifying agents;

[0103] 25 hyaluronic acid;

[0104] amino acids such as arginine;

[0105] colouring agents;

[0106] pH-adjusting agents;

[0107] sweetening agents;

[0108] mouth feel agents

[0109] pharmaceutically acceptable carriers, e.g. starch, sucrose, water or water / alcohol systems etc.; surfactants, such as anionic, nonionic, cationic and zwitterionic or amphoteric surfactants; Humectants such as glycerol, sorbitol, propyleneglycol, xylitol, lactitol etc.;

[0110] polymeric compounds which can enhance the delivery of active ingredients such as

[0111] 35 antimicrobial agents can also be included;

[0112] buffers and salts to buffer the pH and ionic strength of the oral care composition; andP0001204 CPL

[0113] - 11 -

[0114] other optional ingredients that may be included are e.g. bleaching agents such as peroxy compounds e.g. potassium peroxydiphosphate, effervescing systems such as sodium bicarbonate / citric acid systems, colour change systems, and so on.

[0115] 5 Examples according to the invention are illustrated by a number, comparative Examples by a letter.

[0116] Examples

[0117] Actives preparation:

[0118] Actives described below were prepared in a toothpaste chassis (1 in 300 dilution) formulation.

[0119] Table 1 - Toothpaste chassis

[0120]

[0121] 15

[0122] Table 2 - Concentration of active / actives in toothpaste

[0123]

[0124] Protocol and test results:

[0125] 4 ml of solution of toothpaste containing amino acid (as described above) was added to 5.5ml Inoculum (Streptococcus sanguinis) along with 0.5 ml 160 mM glucose and incubated at 37°C anaerobically. Each sample / combination was carried out in triplicates. After 72hrs, an aliquot of 25 1 ml of the resulting mix was centrifuged and the supernatant transferred to a fresh vial for estimating ammonia.P0001204 CPL

[0126] - 12 -

[0127] The level of ammonia present in the solutions were measured using a kit supplied by Megazyme (K-large) following the manufactures instructions.

[0128] 5 Table 3: Ammonia production after 72hours of incubation with Streptococcus sanguinis containing different substrates (mean and St Dev), triplicates per sample.

[0129]

[0130] 10 The above in-vitro study to demonstrates the synergistic production of ammonia by the oral bacterium Streptococcus sanguinis, histidine and potassium nitrate.

Claims

P0001204 CPL- 13 -CLAIMS1. An oral care composition comprising histidine or salt thereof and potassium nitrate in which the weight ratio of histidine or salt thereof to potassium nitrate is from 8:1 to 2:3.

2. An oral care composition according to any preceding claim in which the level of histidine or salt thereof is from 0.1 to 5 wt% of the total composition, preferably from 0.2wt% to 3wt%.

3. An oral care composition according to any preceding claim in which the level of potassium nitrate is from 0.1 to 5 wt% of the total composition, preferably from 0.2wt% to 3 wt%.

4. An oral care composition according to any preceding claim in which weight the ratio of histidine or salt thereof to potassium nitrate is from 5:1 to 1:1.

5. An oral care composition according to any preceding claim in which the weight ratio of histidine or salt thereof to potassium nitrate is from 3:1 to 3:2.

6. An oral care composition according to any preceding claim that is a toothpaste.

7. An oral care composition according to any preceding claim that further comprises a silica and / or calcium carbonate abrasive.

8. An oral care composition according to any preceding claim that further comprises an anionic and / or nonionic cleansing surfactant.

9. An oral care composition according to any preceding claim that comprises less than 0.05 wt% of the total composition of a fluoride containing compound, preferably less than 0.01wt%.

10. An oral care composition comprising histidine or salts thereof and potassium nitrate for use in the treatment and / or mitigation of dental caries.

Images