Oral compositions and related methods

Abstract

The present disclosure relates to storage stable compositions comprising an amine, a zinc-containing compound, and one or more quaternary ammonium surfactants. Related methods of use and preparation are also disclosed.

Description

Technical Field

[0001] The present disclosure relates to a novel quaternary ammonium surfactant comprising an amine, a zinc-containing compound, and one or more quaternary ammonium surfactants (e.g., pyridine Surfactants) (e.g. cetylpyridinium chloride (CPC)) and related methods of using the same. Background Art

[0002] Oral hygiene compositions are known which contribute to oral hygiene and thus to the maintenance of healthy teeth and gums through their cleaning action. The cleaning action of these oral hygiene compositions is usually supplemented by admixture of active compounds which prevent or control pathological conditions in the oral cavity, in particular also prevent or control the formation of bacterial films (i.e., dental plaque) on the teeth.

[0003] These films are composed of polysaccharides, mainly composed of glucan. In addition to low molecular weight sugars, these polysaccharides also form a nutrient source for dental plaque bacteria (which are mainly streptococci and lactobacilli). Dental plaque bacteria gradually decompose polysaccharides to form acidic degradation products (e.g., pyruvic acid, lactic acid, etc.). The pH reduction caused thereby causes the deterioration of the tooth enamel known as caries. This condition may cause other complications, such as gingivitis and / or periodontitis.

[0004] Therefore, attempts have been made to take measures against the formation of pathological symptoms in the oral cavity using various oral hygiene compositions (e.g., toothpastes, rinsing solutions or tooth gels). Active compounds known in the prior art include N-octadec-9-enamine hydrofluoride (international nonproprietary name "dectaflur") and N'-octadecyl-N',N,N-tris(2-hydroxyethyl)-1,3-propylenediamine dihydrofluoride (international nonproprietary name "olaflur"). When the hygiene composition is used in the oral cavity, these active compounds form a thin hydrophobic film on the tooth enamel, with the amine hydrofluoride groups in contact with the tooth enamel. Thus, on the one hand, due to the formation of the CaF2 coating, the tooth enamel becomes more resistant to acid attack, and on the other hand, the long-chain hydrocarbon residues form a hydrophobic layer that prevents the formation of deposits on the tooth enamel and the attack of acidic degradation products.

[0005] Zinc is also a known antimicrobial agent for oral care compositions such as toothpaste or mouthwash. Zinc is a known essential mineral for human health and is reported to help strengthen tooth enamel and promote cell repair. Unfortunately, conventional toothpaste formulations typically require high concentrations of zinc (e.g., 2 wt % or more) to achieve efficacy. At this concentration, zinc imparts a noticeable astringency to the composition. There is therefore a need for improved antibacterial toothpaste formulations that do not have the disadvantages of conventional compositions.

[0006]

[0006] Therefore, in view of the drawbacks and disadvantages of using various antimicrobial agents such as zinc, there exists a need for oral care compositions that have antimicrobial efficacy but are also palatable and desirable to the user. Summary of the invention

[0007] Provided herein are methods for the in situ synthesis of fluorinated amines from amine bases, e.g., without the use of hydrofluoric acid, wherein the resulting composition is stable and further comprises one or more quaternary ammonium surfactants (e.g., pyridine Surfactants) (e.g., cetylpyridinium chloride (CPC)). Related compositions (eg, oral care compositions and / or personal care compositions) are also disclosed.

[0008] Accordingly, in a first aspect, the present disclosure relates to an oral care composition comprising:

[0009] Amine bases;

[0010] Fluoride sources;

[0011] a zinc source selected from zinc lactate and zinc citrate; and

[0012] One or more quaternary ammonium surfactants (e.g., pyridinium Surfactants) (e.g., cetylpyridinium chloride (CPC)). DETAILED DESCRIPTION

[0013] As used herein, the term "oral care composition" means the total composition delivered to the oral cavity surface. The composition is also defined as a product that is not intended for systemic administration of a specific therapeutic agent, is not intended to be swallowed, but is maintained in the oral cavity for a sufficient time to contact substantially all tooth surfaces and / or oral tissues for the purpose of oral activities during the normal course of use. Examples of such compositions include, but are not limited to, toothpaste or dentifrice, mouthwash or mouthwash, topical oral gel, denture cleanser, spray, toothpaste powder, tablet, mousse, foam, lozenge, ribbon, chewing gum, etc.

[0014] As used herein, unless otherwise specified, the term "dentifrice" means a paste, gel or liquid formulation. The dentifrice composition can be in any desired form, such as a deep stripe form, a surface stripe form, a multi-layer form, a form with a gel surrounding a paste, or any combination thereof. Alternatively, the oral composition can be two phases dispensed from a separate chamber dispenser.

[0015] As used herein, the term "amine base" may refer to a primary amine base, a secondary amine base or a tertiary amine base. "Primary amine base" refers to a compound comprising at least one amine of one carbon of any hybridization except the carbonyl carbon to which a nitrogen atom is directly bonded. "Secondary amine base" refers to a compound comprising at least one amine of two carbons of any hybridization except the carbonyl carbon to which a nitrogen atom is directly bonded. "Tertiary amine base" refers to a compound comprising at least one amine of three carbons of any hybridization except the carbonyl carbon to which a nitrogen atom is directly bonded. "Amine base" may be used to refer to a compound (e.g., tertiary polyamine) comprising a plurality of primary amine groups, secondary amine groups and / or tertiary amine groups. In particular, the term "amine base" excludes acid addition salts (e.g., hydrochloride and hydrofluoride), and therefore refers to the free base form of the molecule. The hydrofluoride derivative of an amine is referred to as "fluorinated amine" in this article. In a method for producing or manufacturing a composition comprising fluorinated amine, an amine base may be a precursor for forming fluorinated amine.

[0016] As used herein, the term "in situ" is used to refer to the formation of a chemical product (e.g., a fluorinated amine) in an oral care composition or personal care composition. For example, the reaction can be a salification reaction performed by mixing an amine with a fluoride source and an acid, thereby producing a fluorinated amine and a salt. In some embodiments, in situ eliminates the possibility of forming a reaction product in a first reaction vessel (e.g., at a first location) and subsequently adding the reaction product to a mixture, blend, or solution containing other ingredients of the oral care composition or personal care composition in a second vessel (e.g., at a second location).

[0017] Compositions of the Disclosure

[0018] In another aspect, the present disclosure relates to an oral care composition (Composition 1) comprising:

[0019] Amine bases;

[0020] Fluoride sources;

[0021] a zinc source selected from zinc lactate and zinc citrate; and

[0022] One or more quaternary ammonium surfactants (e.g., pyridinium Surfactants) (e.g., cetylpyridinium chloride (CPC)).

[0023] For example, the present disclosure contemplates any of the following compositions (unless otherwise indicated, values ​​are given as a percentage of the total weight of the composition):

[0024] 1.1 Composition 1, wherein the amine base is a primary amine, a secondary amine, a tertiary amine or a combination thereof.

[0025] 1.2 Any of the preceding compositions, wherein the amine base comprises or consists of a primary amine base.

[0026] 1.3 Any of the preceding compositions, wherein the amine base comprises or consists of a secondary amine base.

[0027] 1.4 Any of the preceding compositions, wherein the amine base comprises or consists of a tertiary amine base.

[0028] 1.5 Any of the preceding compositions, wherein the amine base is of plant origin.

[0029] 1.6 Any of the preceding compositions wherein the amine base is of animal origin.

[0030] 1.7 Any of the preceding compositions wherein the amine base is derived from tallow.

[0031] 1.8 Any of the preceding compositions, wherein the amine base is derived from rapeseed oil or from rice bran oil.

[0032] 1.9 Any of the preceding compositions wherein the amine base is a linear or branched fatty amine or polyamine, or a mixture thereof.

[0033] 1.10 The aforementioned composition, wherein the amine base is a saturated or unsaturated C 12-20 Alkylamine bases or saturated or unsaturated C 12-20 Alkyl polyamine bases, or mixtures thereof.

[0034] 1.11 Any of the preceding compositions wherein the amine base is a myristyl, palmityl, linoleyl, oleyl or stearyl amine or polyamine, or a combination thereof.

[0035] 1.12 Any of the preceding compositions wherein the amine base is a polyamine (eg, a monoamine base, a diamine base, and / or a triamine base).

[0036] 1.13 Any of the preceding compositions wherein the amine base is a monoamine base.

[0037] 1.14 Any of the preceding compositions wherein the amine base is a diamine base.

[0038] 1.15 Any of the preceding compositions wherein the amine base is a triamine base.

[0039] 1.16 Any of the preceding compositions wherein the amine base comprises one or more of N'-octadecyltrimethylenediamine-N,N,N'-tri(2-ethanol) and / or N-octadeca-9-enamine.

[0040] 1.17 Any of the preceding compositions wherein the amine base is N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol).

[0041] 1.18 Any of the preceding compositions wherein the amine base is N-octadeca-9-enamine.

[0042] 1.19 Any of the preceding compositions wherein the amine base and the fluoride ion source form the fluorinated amine in situ.

[0043] 1.20 Any of the preceding compositions, further comprising an acid.

[0044] 1.21 The aforementioned composition, wherein the acid is an organic acid (eg, lactic acid, citric acid, tartaric acid, fumaric acid, malic acid), phosphoric acid or hydrochloric acid.

[0045] 1.22 The aforementioned composition wherein the organic acid is an aliphatic dicarboxylic acid or tricarboxylic acid in free form or in salt form.

[0046] 1.23 Any of the preceding compositions, further comprising malic acid.

[0047] 1.24 Any of the preceding compositions, further comprising hydrochloric acid.

[0048] 1.25 Any of the preceding compositions, further comprising phosphoric acid.

[0049] 1.26 Any of the preceding compositions wherein the acid is not hydrofluoric acid.

[0050] 1.27 Any of the preceding compositions, wherein the composition is substantially free of hydrofluoric acid (e.g., less than 0.001 wt. % hydrofluoric acid).

[0051] 1.28 Any of the preceding compositions wherein the amine base, fluoride ion source, and acid form the fluorinated amine in situ.

[0052] 1.29 Any of the preceding compositions wherein the fluoride source is selected from one or more of sodium fluoride, potassium fluoride, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, and combinations thereof.

[0053] 1.30 Any of the preceding compositions wherein the fluoride is sodium fluoride.

[0054] 1.31 Any of the preceding compositions wherein the composition comprises less than 0.01 wt. % stannous fluoride.

[0055] 1.32 Any of the preceding compositions wherein the composition comprises less than 0.001 wt. % stannous fluoride.

[0056] 1.33 Composition 1.19 or 1.28 wherein the fluorinated amine formed is one or more of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride (olaflu) or N-octadec-9-enamine hydrofluoride (deketafur).

[0057] 1.34 Composition 1.19 or 1.28 wherein the fluorinated amine formed is N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride (olafluor).

[0058] 1.35 Composition 1.19 or 1.28 wherein the fluorinated amine formed is N-octadec-9-enamine hydrofluoride (diketafur).

[0059] 1.36 Any of the preceding compositions wherein the zinc source is zinc lactate.

[0060] 1.37 Any of the preceding compositions wherein the zinc source is zinc citrate.

[0061] 1.38 Any of the preceding compositions wherein the amine base is present in an amount of about 0.01 wt % to about 5 wt %, about 0.01 wt % to about 3 wt %, or about 0.1 wt % to about 1 wt %, based on the total weight of the composition.

[0062] 1.39 Any of the preceding compositions, wherein the amine base is present in an amount of about 0.5 wt % to about 2.5 wt %, about 1 wt % to about 2 wt %, about 1.2 wt % to about 1.4 wt %, or about 1.3 wt %, based on the total weight of the composition.

[0063] 1.40 Any of the preceding compositions wherein the amine base is present in an amount of about 0.1 wt % to about 0.5 wt %, or about 0.15 wt % to about 0.25 wt %, based on the total weight of the composition.

[0064] 1.41 The aforementioned composition wherein the fluoride ion source is present in an amount of 0.005 wt % to 2.5 wt % (e.g., about 0.025 wt % to about 0.145 wt %), about 0.1 wt % to about 0.5 wt %, or about 0.01 wt % to about 0.03 wt %, based on the total weight of the composition.

[0065] 1.42 Any of the preceding compositions, wherein the total fluoride content of the composition is in an amount from 50 ppm to 25,000 ppm (e.g., from 750 ppm to 7000 ppm, for example, from 1000 ppm to 5500 ppm, for example, about 250 ppm, 500 ppm, 1000 ppm, 1100 ppm, 1400 ppm, 1450 ppm, 2800 ppm, 5000 ppm, or 25000 ppm).

[0066] 1.43 Any of the preceding compositions wherein the zinc source is present in an amount of about 0.1 wt % to about 2.5 wt %, e.g., about 0.5 wt % or about 2.0 wt %, based on the total weight of the composition.

[0067] 1.44 Any of the preceding compositions wherein the zinc source is present in an amount from about 0.1 wt % to about 0.2 wt %, e.g., from about 0.17 wt % to about 0.18 wt %, based on the total weight of the composition.

[0068] 1.45 Any of the preceding compositions wherein the zinc source is zinc lactate present in an amount of about 0.5 weight percent based on the total weight of the composition.

[0069] 1.46 Any of the preceding compositions wherein the zinc source is zinc lactate present in an amount from about 0.1 wt % to about 0.25 wt %, or 0.2 wt %, based on the total weight of the composition.

[0070] 1.47 Any of the preceding compositions wherein the zinc source is zinc citrate present in an amount of about 2.0 weight percent based on the total weight of the composition.

[0071] 1.48 Any of the preceding compositions, further comprising polyvinylpyrrolidone in an amount of about 0.1 wt % to about 1.00 wt % based on the total weight of the composition.

[0072] 1.49 Any of the preceding compositions, comprising an acid (eg, hydrochloric acid) in an amount of about 0.1 wt % to about 1.0 wt % (eg, about 0.7 wt % to about 0.9 wt %) based on the total weight of the composition.

[0073] 1.50 Any of the preceding compositions, comprising malic acid in an amount from about 0.03 wt % to about 0.07 wt % based on the total weight of the composition.

[0074] 1.51 Any of the preceding compositions, comprising a cellulose derivative (eg, hydroxyethyl cellulose) in an amount of about 1 wt % to about 2 wt % based on the total weight of the composition.

[0075] 1.52 Any of the aforementioned compositions, further comprising an amino acid (e.g., basic amino acid) (e.g., arginine) present in an amount corresponding to 1% to 15% by weight of the total composition, such as 3% to 10% by weight, such as about 1.5%, 4%, 5% or 8%, wherein the weight of the amino acid (e.g., basic amino acid) is calculated in free form.

[0076] 1.53 Any of the preceding compositions, wherein the composition does not contain ethanol.

[0077] 1.54 Any of the preceding compositions wherein the pH is below 7, such as a pH of about 3 to 6, such as a pH of about 4 to 5.

[0078] 1.55 Any of the aforementioned compositions, further comprising an effective amount of one or more alkali metal phosphates, such as sodium, potassium or calcium salts, for example selected from alkali metal dibasic phosphates and alkali metal pyrophosphates, for example selected from the following alkali metal phosphates: disodium hydrogen phosphate, dipotassium hydrogen phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium hydrogen orthophosphate, sodium dihydrogen phosphate, pentapotassium triphosphate and mixtures of any two or more thereof, for example, based on the weight of the composition, its amount is 0.01% to 20%, such as 0.1% to 8%, for example, such as 0.1% to 5%, such as 0.3% to 2%, such as 0.3% to 1%, such as about 0.01%, about 0.1%, about 0.5%, about 1%, about 2%, about 5%, about 6%.

[0079] 1.56 The aforementioned composition wherein the polyphosphate is tetrasodium pyrophosphate.

[0080] 1.57 The foregoing composition wherein tetrasodium pyrophosphate is present at 0.1 wt % to 1.0 wt % (e.g., about 0.5 wt %).

[0081] 1.58 Any of the preceding compositions further comprising an abrasive or particulate material (eg, silica).

[0082] 1.59 Any of the aforementioned compositions, further comprising a nonionic surfactant, wherein the amount of the nonionic surfactant is 0.5% to 5%, for example 1% to 2%, selected from poloxamers (e.g., poloxamer 407), polysorbates (e.g., polysorbate 20), polyoxyl hydrogenated castor oil (e.g., polyoxyl 40 hydrogenated castor oil), polyglycerol 4-caprate and mixtures thereof.

[0083] 1.60 The aforementioned composition, wherein the poloxamer nonionic surfactant has a polyoxypropylene molecular weight of 3000 g / mol to 5000 g / mol and a polyoxyethylene content of 60 mol % to 80 mol %, for example, the poloxamer nonionic surfactant comprises poloxamer 407.

[0084] 1.61 Any of the preceding compositions, further comprising a humectant selected from glycerin, sorbitol, xylitol, propylene glycol in an amount of about 10 wt % to 70 wt % based on the total weight of the composition.

[0085] 1.62 Any of the preceding compositions comprising a humectant selected from glycerin and sorbitol.

[0086] 1.63 Any of the preceding compositions, further comprising a flavoring agent, an aromatic agent and / or a coloring agent.

[0087] 1.64 Any of the preceding compositions comprising one or more flavoring agents selected from saccharin and sucralose (e.g., saccharin in an amount of about 0.02 wt % and sucralose in an amount of about 0.007 wt % to about 0.01 wt %).

[0088] 1.65 The aforementioned composition further comprises glycerin in an amount of about 2.0 wt % to about 3.5 wt % based on the total weight of the composition.

[0089] 1.66 Any of the preceding compositions further comprising a thickener selected from the group consisting of carboxyvinyl polymers, hydroxyethyl cellulose, and water-soluble salts of cellulose ethers (eg, sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose).

[0090] 1.67 Any of the foregoing compositions, further comprising an antimicrobial agent selected from the group consisting of halogenated diphenyl ethers (e.g., triclosan), herbal extracts and essential oils (e.g., rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, honokiol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak extract, sea buckthorn extract), biguanide preservatives (e.g., chlorhexidine, alexidine or octenidine), quaternary ammonium compounds (e.g., cetylpyridinium chloride (CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-Tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic preservatives, hexetidine, octenidine, sanguinarine, povidone iodine, delmopinol, salifluor, sanguinarine, propolis and oxidizing agents (e.g., buffered sodium peroxyborate or sodium peroxycarbonate), phthalic acid and its salts, monoperoxyphthalic acid and its salts and esters, ascorbyl stearate, oleyl sarcosinate, alkyl sulfates, dioctyl sulfosuccinate, salicylanilide, domiphen bromide, delmopinol, octapinol and other piperidinyl derivatives, nicin preparations, chlorites; and mixtures of any of the foregoing. 1.68 Any of the aforementioned compositions, further comprising an antioxidant, for example, the antioxidant is selected from: coenzyme Q10, PQQ, vitamin C, vitamin E, vitamin A, BHT, anethole-dithiothione and mixtures thereof.

[0091] 1.69 Any of the preceding compositions, further comprising a whitening agent selected from the group consisting of metal chlorites, perborates, percarbonates, peroxyacids, hypochlorites, and combinations thereof.

[0092] 1.70 Any of the preceding compositions further comprising an agent that interferes with or prevents bacterial attachment, such as ethyl lauroyl arginate (ELA) or chitosan.

[0093] 1.71 Any of the preceding compositions, wherein the oral composition can be any of the following oral compositions selected from: toothpaste or dentifrice, mouthwash or mouthwash, topical oral gel, spray, powder, strip, chewing gum, ribbon, foam, mousse, dental floss and denture cleanser.

[0094] 1.72 Any of the preceding compositions wherein the quaternary ammonium surfactant comprises pyridine Surfactant.

[0095] 1.73 1.72 Composition of which pyridine Surfactant selected from: cetylpyridinium chloride Tetradecylpyridinium chloride N-Tetradecyl-4-ethylpyridinium chloride Domiphene bromide, or a mixture thereof.

[0096] 1.74 1.73 Compositions in which pyridine Cetylpyridinium chloride (CPC).

[0097] 1.75 Any of the preceding compositions, wherein the composition comprises:

[0098] Amine fluoride (e.g., 0.05 wt % to 1 wt %);

[0099] Zinc lactate (e.g., 0.05 wt % to 2 wt %) (e.g., about 0.2 wt %); and

[0100] ·Cetylpyridinium chloride (e.g., 0.05 wt % to 1 wt %) (e.g., about 0.075 wt %).

[0101] 1.76 The oral care composition of 1.75, wherein the composition is a mouthwash.

[0102] 1.77 Any of the preceding compositions wherein the oral care composition is free of stannous fluoride.

[0103] 1.78 Any of the preceding compositions, wherein the composition comprises:

[0104] Amine fluoride (e.g., 0.05 wt % to 1 wt %);

[0105] Zinc lactate (e.g., 0.05 wt % to 2 wt %) (e.g., about 0.2 wt %);

[0106] Sodium fluoride (e.g., 0.01 wt % to 1 wt %); and

[0107] ·Cetylpyridinium chloride (e.g., 0.05 wt % to 1 wt %) (e.g., about 0.075 wt %).

[0108] 1.79 The oral care composition of 1.78, wherein the composition is a mouthwash.

[0109] 1.80 Any of the preceding compositions, wherein the oral care composition comprises:

[0110] Amine fluoride (e.g., 0.05 wt % to 1 wt %);

[0111] Zinc lactate (e.g., 0.05 wt % to 2 wt %) (e.g., about 0.2 wt %); and

[0112] ·Cetylpyridinium chloride (e.g., 0.05 wt % to 1 wt %) (e.g., about 0.075 wt %);

[0113] xylitol (e.g., 0.5 wt % to 7.5 wt %);

[0114] Polyvinyl pyrrolidone (e.g., 0.05 wt % to 1 wt %)

[0115] 1.81 Any of the preceding compositions, wherein the composition comprises:

[0116] Amine fluoride (e.g., 0.05 wt % to 1 wt %);

[0117] Zinc lactate (e.g., 0.05 wt % to 2 wt %) (e.g., about 0.2 wt %); and

[0118] ·Cetylpyridinium chloride (e.g., 0.05 wt % to 1 wt %) (e.g., about 0.075 wt %)

[0119] The total fluoride content of the composition is in an amount of 50 ppm to 5,000 ppm (eg, about 250 ppm).

[0120] 1.82 Any of the preceding compositions, wherein the composition comprises:

[0121] Amine fluoride (e.g., 0.05 wt % to 1 wt %);

[0122] Zinc lactate (e.g., 0.05 wt % to 2 wt %) (e.g., about 0.2 wt %);

[0123] Sodium fluoride (e.g., 0.01 wt % to 1 wt %); and

[0124] ·Cetylpyridinium chloride (e.g., 0.05 wt % to 1 wt %) (e.g., about 0.075 wt %).

[0125] The total fluoride content of the composition is in an amount of 50 ppm to 5,000 ppm (eg, about 250 ppm).

[0126] 1.83 An oral care composition as described in any one of 1.80 to 1.82 wherein the composition is a mouthwash.

[0127] 1.84 Any of the preceding compositions, wherein the composition is in the form of a cleanser, for example a liquid hand soap formulation, a shower gel or a skin cleanser; or a home care formulation, for example a hard surface cleaner such as a dish soap, a sunscreen, a make-up remover or a topical disinfectant.

[0128] 1.85 Any of the preceding compositions for use in treating periodontitis and / or gingivitis.

[0129] A composition obtained or obtainable by combining the ingredients as set out in any of the preceding compositions.

[0130] In another embodiment, the present disclosure encompasses a method of improving oral health, comprising applying an effective amount of the oral composition of any one of the above embodiments to the oral cavity of a subject in need thereof, for example, for the following methods:

[0131] i. Reduce or inhibit the formation of dental caries,

[0132] ii. reducing, repairing or inhibiting early enamel damage, for example, as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM),

[0133] iii. Reduce or inhibit tooth demineralization and promote tooth remineralization,

[0134] iv. Reduce tooth hypersensitivity,

[0135] v. Reduce or inhibit gingivitis,

[0136] vi. Promote the healing of oral ulcers or cuts,

[0137] vii. Inhibit the formation of microbial biofilm in the oral cavity,

[0138] viii. Raising and / or maintaining dental plaque pH at a level of at least pH 5.5 following a sugar challenge,

[0139] ix. Reduce plaque accumulation,

[0140] x.Treatment of dry mouth,

[0141] xi. Enhance systemic health, including cardiovascular health, for example by reducing the likelihood of systemic infection via oral tissues,

[0142] xii. Whiten teeth,

[0143] xiii. Reduce tooth erosion,

[0144] xiv. Immunize teeth against (or protect teeth from) cariogenic bacteria and their effects, and / or

[0145] xv. Clean teeth and mouth.

[0146] Fluoride ion source

[0147] The oral care composition may also include one or more fluoride ion sources, such as soluble fluoride salts. A variety of fluoride ion-generating materials can be used as soluble fluoride sources in the compositions of the present invention. Examples of suitable fluoride ion-generating materials are found in U.S. Pat. No. 3,535,421 to Briner et al.; U.S. Pat. No. 4,885,155 to Parran, Jr. et al. and U.S. Pat. No. 3,678,154 to Widder et al., each of which is incorporated herein by reference. Representative fluoride ion sources for the present disclosure (e.g., composition 1.0 et al.) include, but are not limited to, sodium fluoride, potassium fluoride, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, and combinations thereof. In certain embodiments, the fluoride ion source includes sodium fluoride. When the formulation includes a calcium salt, the fluoride salt is preferably a salt in which fluoride is covalently bound to another atom (e.g., as in sodium monofluorophosphate) rather than merely ionically bound (e.g., as in sodium fluoride).

[0148] Surfactants

[0149] In another embodiment, cationic surfactants useful in the present disclosure can be broadly defined as derivatives of aliphatic quaternary ammonium compounds having a long alkyl chain containing 8 to 18 carbon atoms, such as lauryl trimethyl ammonium chloride, cetyl pyridinium chloride, Cetyltrimethylammonium bromide, diisobutylphenoxyethyldimethylbenzyl ammonium chloride, coconut oil alkyltrimethylammonium nitrite, cetylpyridinium fluoride and mixtures thereof. Illustrative cationic surfactants are the quaternary ammonium fluorides described in U.S. Patent No. 3,535,421 to Briner et al., which is incorporated herein by reference. Certain cationic surfactants may also act as bactericides in the composition.

[0150] Illustrative nonionic surfactants that can be used in the compositions of the present disclosure, such as any of Compositions 1.0 et seq., can be broadly defined as compounds produced by condensing alkylene oxide groups (hydrophilic in nature) with organic hydrophobic compounds that can be aliphatic or alkyl aromatic in nature. Examples of suitable nonionic surfactants include, but are not limited to, Pluronics, polyethylene oxide condensates of alkylphenols, products derived from the condensation of ethylene oxide with the reaction products of propylene oxide and ethylenediamine, ethylene oxide condensates of aliphatic alcohols, long chain tertiary amine oxides, long chain tertiary phosphine oxides, long chain dialkyl sulfoxides, and mixtures of such materials. In a specific embodiment, the compositions of the present disclosure comprise a nonionic surfactant selected from the group consisting of poloxamers (e.g., poloxamer 407), polysorbates (e.g., polysorbate 20), polyoxyl hydrogenated castor oils (e.g., polyoxyl 40 hydrogenated castor oil), betaines (e.g., cocamidopropyl betaine), and mixtures thereof.

[0151] Illustrative amphoteric surfactants that can be used in the compositions of the present disclosure, such as composition 1.0, et seq., include betaines (e.g., cocamidopropyl betaine); derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and in which one of the aliphatic substituents contains from about 8 to 18 carbon atoms and one contains an anionic water-solubilizing group (e.g., carboxylate, sulfonate, sulfate, phosphate, or phosphonate); and mixtures of such materials.

[0152] The surfactant or mixture of compatible surfactants may be present in the compositions of the present disclosure at 0.1% to 5%, in another embodiment 0.3% to 3%, and in another embodiment 0.5% to 2% by weight of the total composition.

[0153] Flavoring agents

[0154] The oral care composition of the present disclosure, for example, composition 1.0 and any of the following or the like, can also include flavoring agents. The flavoring agents used in the practice of the present disclosure include, but are not limited to, essential oils and various flavoring aldehydes, esters, alcohols and similar substances, and sweeteners, for example sodium saccharin. The example of essential oil comprises the oil of spearmint, peppermint, holly, sassafras, cloves, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit and orange. Also available are chemicals such as menthol, carvone and anethole. Some embodiments use the oil of peppermint and spearmint.

[0155] Flavoring agents are incorporated into the oral composition at a concentration of 0.01% to 1.7% by weight.

[0156] Chelating and anti-tartar agents

[0157] The oral care compositions of the present disclosure, such as any of Composition 1.0 et seq., may also contain one or more chelating agents capable of complexing with calcium present in bacterial cell walls. Binding of this calcium weakens the bacterial cell wall and enhances bacterial lysis.

[0158] Another group of reagents suitable for use as chelating agents or anticalculus agents in the present disclosure is soluble pyrophosphate. The pyrophosphate used in the composition of the present invention can be any of the alkali metal pyrophosphates. In certain embodiments, the salt includes tetraalkali metal pyrophosphates, dialkali metal dihydrogen pyrophosphates, trialkali metal monohydrogen pyrophosphates and mixtures thereof, wherein the alkali metal is sodium or potassium. The salt can be used in both its hydrated form and non-hydrated form. The effective amount of the pyrophosphate that can be used in the composition of the present invention is usually enough to provide at least 0.1% by weight of pyrophosphate ions, such as 0.1% by weight to 3% by weight, such as 0.1% by weight to 2% by weight, such as 0.1% by weight to 1% by weight, such as 0.2% by weight to 0.5% by weight. Pyrophosphate also helps to preserve the composition by reducing water activity.

[0159] polymer

[0160] Oral care compositions of the present disclosure, such as composition 1.0 and any of the following, etc., optionally also include one or more polymers, such as polyethylene glycol, polyvinyl methyl ether maleic acid copolymer, polysaccharide (e.g., cellulose derivatives, such as carboxymethyl cellulose). Acidic polymers such as polyacrylate gels can be provided in the form of their free acids or partially or completely neutralized water-soluble alkali metals (e.g., potassium and sodium) or ammonium salts. Certain embodiments include maleic anhydride or maleic acid and another polymerizable ethylenically unsaturated monomer such as methyl vinyl ether (methoxyethylene) having a molecular weight (MW) of about 30,000 to about 1,000,000 1:4 to 4:1 copolymers. These copolymers can be obtained, for example, as Gantrez AN 139 (MW 500,000), AN 1 19 (MW 250,000) and S-97 pharmaceutical grade (MW 70,000) of GAF Chemicals Corporation.

[0161] Other polymers that work include those such as 1:1 copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available, for example, as Monsanto EMA No. 1 103, MW 10,000, and EMA Grade 61; and 1:1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl ether, or N-vinyl-2-pyrrolidone.

[0162] Generally, suitable are polymeric olefinic or ethylenically unsaturated carboxylic acids containing an active carbon-carbon olefinic double bond and at least one carboxyl group, i.e., an acid containing an olefinic double bond that readily functions in the polymerization due to being present in the monomer molecule in the α-β position relative to the carboxyl group or as part of a terminal methylene group. Exemplary of such acids are acrylic acid, methacrylic acid, ethacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid, β-styryl acrylic acid, muconic acid, itaconic acid, citraconic acid, methylfumaric acid, glutaconic acid, aconitic acid, α-phenylacrylic acid, 2-benzylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbelliferous acid, fumaric acid, maleic acid, and anhydrides. Other different olefinic monomers copolymerizable with such carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate, and the like. The copolymer contains sufficient carboxylate groups for water solubility.

[0163] Another class of polymerizing agents includes compositions containing homopolymers of substituted acrylamides and / or homopolymers of unsaturated sulfonic acids and their salts, particularly wherein the polymer is based on an unsaturated sulfonic acid having a molecular weight of about 1,000 to about 2,000,000 selected from acrylamidoalkylsulfonic acids (e.g., 2-acrylamido-2-methylpropanesulfonic acid) as described in U.S. Pat. No. 4,842,847 to Zahid, June 27, 1989, which is incorporated herein by reference.

[0164] Another class of useful polymerizing agents includes polyamino acids, particularly those containing a proportion of anionic surface active amino acids such as aspartic acid, glutamic acid and phosphoserine, as disclosed in US Pat. No. 4,866,161 to Sikes et al., which is incorporated herein by reference.

[0165] When preparing oral care compositions, it is sometimes necessary to add some thickening materials to provide the desired consistency or to stabilize or enhance the performance of the formulation. In certain embodiments, the thickening agent is a water-soluble salt of carboxyvinyl polymers, hydroxyethylcellulose, and cellulose ethers, such as sodium carboxymethylcellulose and sodium carboxymethylhydroxyethylcellulose. Natural gums, such as gum karaya, gum arabic, and gum tragacanth may also be incorporated. Colloidal magnesium aluminum silicate or finely dispersed silicon dioxide may be used as a component of the thickening composition to further improve the texture of the composition. In certain embodiments, a thickening agent in an amount of about 0.5% to about 5.0% by weight of the total composition is used.

[0166] Abrasive

[0167] In certain embodiments, any of the present disclosure, such as composition 1.0 and the following, etc., can include additional silica abrasives, sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite or other siliceous materials, or a combination thereof. Any silica suitable for oral care compositions can be used, such as precipitated silica or silica gel. For example, synthetic amorphous silica. Silica can also be used as a thickener, such as granular silica. For example, silica can also be small particle silica (e.g., SorbosilAC43 from PQ Corporation in Warrington, UK).

[0168] water

[0169] Water is present in any of the oral compositions of the present disclosure, such as composition 1.0 and the following, etc. The water used in the preparation of commercial oral compositions should be deionized and free of organic impurities. Water generally makes up the balance of the composition and accounts for 5% to 99% by weight of the oral composition, such as 10% to 20% by weight, such as 25% to 35% by weight, such as 40% to 95% by weight, such as 60% to 95% by weight. This amount of water includes the added free water plus the amount of water introduced with other substances such as sorbitol or silicon dioxide or any component of the present disclosure. The Karl Fischer method is a measure to calculate free water.

[0170] Moisturizer

[0171] In certain embodiments of the oral composition, it is also desirable to incorporate a humectant to reduce evaporation and also aid in preservation by reducing the activity of water. Certain humectants may also impart a desired sweetness or flavor to the composition. As pure humectant, the humectant typically comprises 1% to 70% in one embodiment or 30% to 65% in another embodiment by weight of the composition.

[0172] Suitable humectants include edible polyols such as glycerin, sorbitol, xylitol, propylene glycol and other polyols and mixtures of these humectants. Mixtures of glycerin and sorbitol may be used as the humectant component of the compositions herein in certain embodiments.

[0173] pH Adjusters

[0174] In some embodiments, the composition of the present disclosure includes a buffer. Examples of buffers include anhydrous carbonates such as sodium carbonate, sesquicarbonates, bicarbonates such as sodium bicarbonate, silicates, bisulfates, phosphates (e.g., potassium dihydrogen phosphate, dipotassium hydrogen phosphate, trisodium phosphate, sodium tripolyphosphate, phosphoric acid), citrates (e.g., citric acid, dehydrated trisodium citrate), pyrophosphates (sodium and potassium salts) and combinations thereof. When the composition is dissolved in water, a mouthwash base or a toothpaste base, the amount of the buffer is sufficient to provide a pH of about 3 to about 9, preferably about 4 to about 5. The typical amount of the buffer is about 5% to about 35% by weight of the total composition, about 10% to about 30% in one embodiment, and about 15% to about 25% in another embodiment.

[0175] The present disclosure, in its method aspects, relates to applying to the oral cavity a safe and effective amount of a composition described herein.

[0176] The compositions and methods according to the present disclosure (e.g., Composition 1.0 et seq.) can be incorporated into oral compositions for oral and dental care, such as toothpastes, clear pastes, gels, mouthwashes, mouth rinses, sprays, foams, lozenges, mousses, toothpaste powders, tablets, and chewing gums.

[0177] As used throughout, ranges are used as shorthand for describing individual values ​​and each value within a range. Any value within a range may be selected as the endpoint of a range. In addition, all references cited herein are incorporated herein by reference as a whole. In the event that the definition in the present disclosure conflicts with the definition of the cited references, the present disclosure shall prevail. It should be understood that when describing a preparation, it may be described according to its composition, as is common in the art, although these compositions may react with each other in actual preparations when prepared, stored, and used, and such products are intended to be covered by the preparations.

[0178] The following examples further describe and demonstrate exemplary embodiments within the scope of the present disclosure. These examples are provided merely for illustration and should not be construed as limitations on the present disclosure, as many variations are possible without departing from the spirit and scope of the present invention. In addition to those shown and described herein, various changes to the present disclosure should be apparent to those skilled in the art and are intended to fall within the scope of the appended claims.

[0179] Example

[0180] Example 1: Model toothpaste formulation

[0181] Prepare toothpaste formulation as follows:

[0182] Table 1: Toothpaste formulations according to the present disclosure

[0183] Preparation 1 Preparation 2 Preparation 3 Surfactants 5.5 5.5 5.5 polymer 1.6 1.6 1.6 Amine base (from beef tallow) 1.38 -- -- hydrochloric acid 0.79 0.88 0.89 Saccharin Sodium 0.39 0.39 0.39 glycerin 40 40 40 Amorphous Silica 19 19 19 Thickening Silica 2.7 2.7 2.7 Zinc lactate 0.5 0.5 -- Zinc Citrate -- -- 2.0 Sodium fluoride 0.31 0.31 0.31 Amine base (plant source) -- 1.38 1.38 Fragrance and coloring agents 1.6 1.6 1.6 water 26.24 26.15 24.64

[0184] Formulations 1 to 3 were subjected to accelerated aging conditions to test storage stability. The results are summarized in Table 2 below.

[0185] Table 2: Stability of toothpaste formulations

[0186]

[0187] As shown above, each formulation exhibited a high level of stability even under accelerated aging conditions.

[0188] Several control toothpaste formulations were designed as comparators for Formulations 1 to 3 and are summarized in Table 2.

[0189] Table 3: Control toothpaste formulations

[0190]

[0191] Example 2: In vitro antibacterial test of toothpaste preparation

[0192] The formulations were designed to test the in vitro antimicrobial activity of various toothpaste formulations according to the present disclosure. McBain's medium was diluted and supplemented with a 1:1000 dilution of hemin and menadione. The medium was then inoculated at a concentration of 2 mL / 40 mL of medium. HAP disks were placed in the plates as a substrate for biofilm growth and allowed to incubate for 60 hours. 1.5 mL of medium was supplemented every 12 hours.

[0193] 1.5 mL of the test formulation was added to each plate. The HAP disks were treated for 2 minutes and incubated at 90 rpm in an orbital shaker. Bacterial viability was determined by ATP fluorescence. The results are summarized in Table 3 below:

[0194] Table 4: Antimicrobial activity

[0195] Composition Fluorescence counting Preparation 1 29712 Preparation 2 33862 Preparation 3 42957 Comparative Preparation 1 40756 Comparative Preparation 2 155913

[0196] As shown above, the compositions containing zinc lactate or zinc citrate with an amine base and sodium fluoride performed at least as well as or better than Comparative Formulation 1, which did not contain any zinc compound. In addition, each of Compositions 1 to 3 performed much better than Comparative Formulation 2, which contained sodium fluoride but no amine base or zinc compound. These results show that oral care compositions containing an amine base, sodium fluoride, and a zinc compound provide an unexpected enhancement in the antibacterial efficacy of the composition.

[0197] Example 3: In vitro antibacterial test of mouthwash preparations

[0198] Mouthwash formulations according to the present disclosure were prepared as summarized in Table 5.

[0199] Table 5: Mouthwash composition

[0200] Preparation 4 Preparation 5 Preparation 6 Xylitol 1.5 2.5 2.5 Polyvinyl pyrrolidone 0.2 0.8 0.8 castor oil 0.25 -- 0.25 Zinc lactate 0.2 0.2 0.2 Amine base 0.16 0.15 0.16 Hydrofluoric acid 0.03 0.03 0.03 Polyglycerol 4-decanoate -- 0.25 -- Sodium fluoride 0.03 0.03 0.03 glycerin -- 2.0 2.0 Flavoring, sweetening and coloring agents 0.17 0.16 0.16 water Moderate Moderate Moderate

[0201] The above compositions were analyzed in a short term kill test against several comparative compositions. The comparative compositions were prepared as summarized in Table 6.

[0202] Table 6: Comparative Mouthwash Compositions

[0203]

[0204] In the short interval killing test, all saliva was mixed with the mouthwash 1:1 for a 1 minute contact time. The reaction was terminated with neutralizing broth, and the samples were serially diluted and plated. Data are reported as the reduction in log (colony forming units) relative to the buffer-treated negative control. The results are summarized below.

[0205] Table 7: SIKT test results

[0206] Composition Log reduction of CFU Preparation 4 4.05 Comparative Preparation 3 2.91 Comparative Preparation 4 0.27

[0207] As shown in these results, Formulation 4, which contained zinc lactate and amine fluoride, performed significantly better than Comparative Formulation 3 (containing amine fluoride and stannous fluoride actives), giving a 1 log reduction over the other samples.

[0208] Based on the clinical studies of PGRM found in the US FDA tentative monograph on dental plaque and gingivitis, additional studies were conducted using an in vitro dental plaque glycolysis model. This model uses salivary-derived biofilm in place of dental plaque and monitors pH changes after treatment with the test mouthwash as a measure of the formulation's ability to limit the metabolic activity of the biofilm.

[0209] Saliva-derived biofilms were grown on hydroxyapatite disks in McBain medium supplemented with 0.4% sucrose at 37°C in a 5% CO 2 The biofilms were cultured under an environment of . The biofilms were cultured for 48 hours, with the culture medium replaced after an initial growth of 24 hours. The resulting biofilms were treated with an undiluted mouthwash for 5 minutes and rinsed by immersing in sterile deionized water for 30 seconds twice in a row. Four replicates were performed for each treatment. All treated biofilms were then incubated for 6.5 hours in 0.3% TSB (pH 7.2) supplemented with 0.5% sucrose. The final pH of each biofilm sample was measured, and the pH change (initial pH-final pH) of each sample was calculated.

[0210] Table 8: pH changes after exposure to test formulations

[0211] Composition Changes in pH Preparation 4 1.75 Comparative Preparation 3 1.69 Comparative Preparation 4 2.7 Untreated 2.75

[0212] The results of the in vitro plaque glycolysis study showed that both comparative formulations 5 and 6, which contained amine fluoride and stannous fluoride, showed a substantial reduction in acid production compared to the placebo treatment and the positive control. The two mouthwashes performed similarly, indicating that the efficacy of the formulations was not affected over time. Formulation 4, which contained amine fluoride and zinc lactate, also showed a significant reduction in bacterial activity compared to the placebo treatment and the positive control. Without being bound by theory, it is believed that the resulting antibacterial activity of formulation 4 and comparative formulations 5 and 6 may be due to the presence of amine fluoride in addition to the metal ions.

[0213] Additional studies were performed using an aerobic biofilm model in which salivary-derived biofilms were grown on vertically suspended HAP disks. Biofilms were grown in a selected complex medium (SHI medium) because it has been shown to provide a high degree of diversity in salivary-derived biofilms. Biofilms were treated twice daily with 1.5 mL of the test mouthwash for 30 seconds each time. After 5 days of growth, biofilms were harvested and analyzed for total biomass (optical density at 610 nm, OD 610 ) and metabolic activity (as measured by ATP activity) were quantified.

[0214] Table 9: Bacterial reduction (by OD 610 )

[0215] Composition Bacteria reduction (%) Preparation 4 51.39 Comparative Preparation 3 45.78 Comparative Preparation 4 5.13

[0216] Table 10: Bacterial reduction (by ATP fluorescence detection)

[0217] Composition Bacteria reduction (%) Preparation 4 89.90 Comparative Preparation 3 77.15 Comparative Preparation 4 2.91

[0218] Research trials were conducted to test the stability of the compositions after they were exposed to air (i.e., after first use). As shown below, while Comparative Formulation 3 still exhibited an antimicrobial effect over the test period, the efficacy decreased significantly over time. Formulation 4, on the other hand, did not exhibit the same trend, indicating that the active ingredients in these formulations are more stable and remain active over time.

[0219] Table 11: Bacterial reduction over time (by OD 610 )

[0220]

[0221] Example 4: Representative Mouthwash Formulations

[0222] Mouthwash formulations according to the present disclosure were prepared as summarized in Table 12.

[0223] Table 12: Mouthwash composition (wt % of total composition)

[0224]

[0225] Example 5: Additional in vitro antibacterial testing of mouthwash formulations

[0226] Formulation 10 described in Table 12 was compared to the following formulations:

[0227]

[0228] In the short interval killing assay, whole saliva was mixed 1:1 with the mouthwash for a contact time of 1 minute. The reaction was terminated with neutralizing broth, and the samples were serially diluted and plated. Data are reported as log (colony forming units) reduction relative to the buffer-treated negative control.

[0229] Table 13: SIKT test results

[0230] Composition pH changes Preparation 10 1.90 Preparation A 0.04 Preparation B 1.81 Preparation C 0.18 Preparation D 1.71 Preparation E 1.69 Formulation F 1.54 Formulation G 1.92

[0231] Overall, all rinses tested, except for the zinc lactate alone rinse (Formulation C), gave > 1 log reduction in total salivary bacterial counts. Without being bound by theory, this result may be due to the fact that this method only considers the effects of a very short single treatment, whereas zinc lactate is considered a slower acting antimicrobial agent that requires repeated exposures to show a significant effect.

[0232] In addition, an important function of any mouthwash formulation is to help prevent the acidification of dental plaque after sugar intake. Formulas that can block the glycolytic pathway of oral bacteria are believed to be able to reduce or prevent the pH drop of dental plaque that causes caries development. The in vitro dental plaque glycolysis model uses saliva-derived biofilms to measure the ability of formulas to prevent this pH change in response to sucrose challenge. The biofilm was grown in McBain medium for 48 hours. The biofilm was then treated once with the test formula and incubated for 4 to 6 hours under sucrose challenge. The pH change of the final culture medium was used as an indicator of the test formula's inhibition of dental plaque glycolysis. The final pH of each biofilm sample was measured, and the pH change (initial pH-final pH) of each sample was calculated. The results are summarized in Tables 14 and 15 below. Because some of these formulas significantly reduce the total biomass present in a single biofilm. In order to understand the ability of these formulas to resist the rapid changes in pH that may be caused by sucrose challenges, the OD of the biofilm after being removed from the disc was also measured. 610 The data were normalized (Table 15). This measurement was considered to give an approximation of the total biomass of the community.

[0233] Table 14

[0234] Composition pH changes Preparation 10 1.02 Preparation A 2.59 Preparation B 2.66 Preparation C 0.97 Preparation D 2.67 Preparation E 1.07 Formulation F 1.12 Formulation G 1.19

[0235] Table 15

[0236] Composition Normalized pH change Preparation 10 2.68 Preparation A 7.39 Preparation B 6.31 Preparation C 2.94 Preparation D 6.76 Preparation E 3.36 Formulation F 3.39 Formulation G 3.36

[0237] Many of these formulations had an effect on biofilm accumulation as shown by normalized plaque glycolysis data.

[0238] Additional studies were performed using an aerobic biofilm model. The dental plaque glycolysis method used salivary derived biofilms that survived for 48 hours, treated once. To enhance the effect of the mouthwash treatment, a 108 hour biofilm model was implemented, where the biofilms were treated twice per 24 hour period, separated by at least 5 hours. This model is considered particularly useful for illustrating the effects of active substances that require more time and exposure to exert their full effect, such as metal ions.

[0239] The first measure of the biofilm model is the total biomass as measured by OD at 610 nm. It measures the total amount of material in each biofilm, reflecting not only the bacteria present, but also the extracellular matrix material. The data are shown in Table 16:

[0240] Table 16: Bacterial reduction (by OD 610 )

[0241] Composition Reduction in optical density % Preparation 10 71.12 Preparation A 6.46 Preparation B 24.59 Preparation C 26.28 Preparation E 37.76 Formulation F 42.06 Formulation G 65.36

[0242] The metabolic activity of the final biofilm community was measured by evaluating ATP production of biofilm bacterial samples. The data are shown in Table 17.

[0243] Table 17: Bacterial reduction (by ATP fluorescence detection)

[0244] Composition ATP reduction % Preparation 10 55.59 Preparation A 5.14 Preparation B 5.22 Preparation C 5.58 Preparation E 26.01 Formulation F 34.59 Formulation G 68.84

[0245] Research trials were conducted to test the stability of the compositions after they were exposed to air (i.e., after first use). As shown below, while Comparative Formulation 3 still exhibited an antimicrobial effect over the test period, the efficacy decreased significantly over time. Formulation 4, on the other hand, did not exhibit the same trend, indicating that the active ingredients in these formulations are more stable and remain active over time.

[0246] While the present disclosure has been described with reference to embodiments, it will be appreciated by those skilled in the art that various modifications and changes may be made thereto without departing from the scope of the present disclosure as defined in the appended claims.

Claims

1. An oral care composition comprising Amine bases; Fluoride sources; a zinc source selected from zinc lactate and zinc citrate; and One or more quaternary ammonium surfactants.

2. The composition of claim 1, wherein the amine base is a linear or branched fatty amine or a polyamine.

3. A composition according to any one of the preceding claims, wherein the amine base is a saturated or unsaturated C 12-20 Alkylamine bases or saturated or unsaturated C 12-20 Alkylpolyamine bases.

4. A composition according to any one of the preceding claims, wherein the amine base is a myristyl, palmityl, linoleyl, oleyl or stearyl amine or polyamine, or N'-octadecyltrimethylenediamine-N,N,N'-tri(2-ethanol), or N-octadec-9-enamine, and combinations thereof.

5. The composition of any one of the preceding claims, wherein the amine base is a polyamine (eg, a monoamine base, a diamine base, or a triamine base).

6. The composition of any of the preceding claims, wherein the amine base is present in an amount of about 0.01 wt % to about 5 wt %, about 0.01 wt % to about 3 wt %, or about 0.1 wt % to about 1 wt %, based on the total weight of the composition.

7. The composition of any one of the preceding claims, wherein the fluoride source is selected from one or more of sodium fluoride, potassium fluoride, ammonium fluoride, and combinations thereof.

8. The composition of any of the preceding claims, wherein the fluoride source is present in an amount of 0.005 wt % to 2.5 wt % (e.g., about 0.025 wt % to about 0.145 wt %), about 0.1 wt % to about 0.5 wt %, or about 0.01 wt % to about 0.03 wt %, based on the total weight of the composition.

9. A composition according to any one of the preceding claims, wherein the zinc source is zinc lactate.

10. The composition of any one of the preceding claims, wherein the zinc source is present in an amount of about 0.1 wt% to about 2.5 wt%, such as about 0.5 wt% or about 2.0 wt%, based on the total weight of the composition.

11. A composition according to any one of the preceding claims, further comprising an acid selected from an organic acid (eg lactic acid, citric acid, tartaric acid, fumaric acid, malic acid), phosphoric acid or hydrochloric acid.

12. The composition of claim 11, wherein the acid is hydrochloric acid, phosphoric acid or malic acid.

13. The composition of claim 12, wherein the acid is hydrochloric acid.

14. The composition of any one of the preceding claims, wherein the amine base, fluoride ion source and the acid form a fluorinated amine in situ.

15. A composition according to any one of the preceding claims, wherein the quaternary ammonium surfactant comprises a pyridine Surfactant.

16. The composition according to claim 15, wherein pyridine Surfactant selected from: cetylpyridinium chloride Tetradecylpyridinium chloride N-Tetradecyl-4-ethylpyridinium chloride Domiphene bromide, or a mixture thereof.

17. The composition according to claim 16, wherein the pyridine Cetylpyridinium chloride (CPC).

18. A composition according to any one of the preceding claims, wherein the composition comprises: Amine fluoride; Zinc lactate; and ·Cetylpyridinium chloride 19. An oral care composition according to claim 18, wherein the composition is a mouthwash.

20. A composition according to any preceding claim, wherein the oral care composition is free of stannous fluoride.

21. A composition according to any one of the preceding claims, wherein the composition comprises: 0.05 to 1% by weight of a fluorinated amine; 0.05% to 2% by weight of zinc lactate; 0.01 wt % to 1 wt % sodium fluoride; and 0.05 to 1 wt% cetylpyridinium chloride Wherein weights are relative to the total composition.

22. An oral care composition according to claim 21, wherein the composition is a mouthwash.

23. A composition according to any one of the preceding claims, wherein the oral care composition comprises: 0.05 to 1% by weight of a fluorinated amine; 0.05 wt % to 2 wt % zinc lactate; and 0.05 to 1 wt% cetylpyridinium chloride 0.5 to 7.5 wt % xylitol; · 0.05 to 1 wt% polyvinylpyrrolidone.

24. An oral care composition according to claim 23, wherein the composition is a mouthwash.

25. A composition according to any one of the preceding claims, wherein the composition is in the form of a toothpaste or dentifrice, a mouthwash or rinse, a topical oral gel, a denture cleanser or a tooth spray.

Images