Oral care compositions with fluorinated amines

Abstract

This disclosure relates to storage-stable compositions comprising amines and zinc-containing compounds. Related methods of use and preparation are also disclosed.

Description

Technical Field

[0001] This disclosure relates to compositions comprising amines and zinc-containing compounds, and related methods of using said compositions. Background Technology

[0002] Oral hygiene compositions are known to contribute to oral hygiene through their cleaning action and thus help maintain healthy teeth and gums. The cleaning action of these oral hygiene compositions is often supplemented by a mixture of active compounds that prevent or control pathological symptoms in the oral cavity, and in particular, prevent or control the formation of bacterial films (i.e., dental plaque) on teeth.

[0003] These membranes are composed of polysaccharides, primarily dextran. Besides low-molecular-weight sugars, these polysaccharides also serve as a nutrient source for dental plaque bacteria (mainly streptococci and lactobacilli). These bacteria gradually break down the polysaccharides to form acidic degradation products (e.g., pyruvate, lactic acid, etc.). The resulting decrease in pH causes enamel deterioration, a condition known as dental caries. This condition can lead to other complications such as gingivitis and / or periodontitis.

[0004] Therefore, various oral hygiene compositions (e.g., toothpaste, rinsing solutions, or dental gels) have been used to combat the formation of oral pathological symptoms. Known active compounds in the art include N-octadecyl-9-enamine hydrofluoric acid (International Nonproprietary Name "dectaflur") and N'-octadecyl-N',N,N-tris(2-hydroxyethyl)-1,3-propanediamine dihydrofluoric acid (International Nonproprietary Name "olaflur"). When used in oral hygiene compositions, these active compounds form a thin hydrophobic film on the enamel, with the amine hydrofluoric acid groups in contact with the enamel. Thus, on the one hand, the enamel becomes more resistant to acid erosion due to the formation of a CaF2 coating; on the other hand, the long-chain hydrocarbon residues form a hydrophobic layer that prevents the formation of deposits on the enamel and the erosion by acidic degradation products.

[0005] Zinc is also a known antimicrobial agent used in oral care compositions such as toothpaste or mouthwash. Zinc is a known essential mineral for human health and has been reported to help strengthen tooth enamel and promote cell repair. Unfortunately, conventional toothpaste formulations typically require high concentrations of zinc (e.g., 2% by weight or higher) to achieve efficacy. At these concentrations, zinc imparts a noticeable astringent taste to the composition. Therefore, there is a need for improved antibacterial toothpaste formulations that do not suffer from the drawbacks of conventional compositions.

[0006] Therefore, given the drawbacks and disadvantages of using various antimicrobial agents such as zinc, there is a need for oral care compositions that are antibacterial but also palatable and desirable to users. Summary of the Invention

[0007] This article provides a method for the in-situ synthesis of fluorinated amines from amine bases without the use of hydrofluoric acid. Related compositions (e.g., oral care compositions and / or personal care compositions) are also disclosed.

[0008] Therefore, in the first aspect, this disclosure relates to an oral care composition comprising:

[0009] amine base;

[0010] Fluoride source;

[0011] And zinc sources selected from zinc lactate and zinc citrate. Detailed Implementation

[0012] 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, during normal use, is not intended for systemic administration of a particular therapeutic agent, is not intended for swallowing, but is intended for oral activities and remains in the oral cavity for a sufficient period of time to contact substantially all tooth surfaces and / or oral tissues. Examples of such compositions include, but are not limited to, toothpaste or dental cleaning agents, mouthwashes or mouthwashes, topical oral gels, denture cleaners, sprays, toothpaste powders, tablets, etc.

[0013] As used herein, unless otherwise specified, the term "dental cleaning agent" means a paste, gel, or liquid formulation. A dental cleaning agent composition may be in any desired form, such as a deep stripe form, a surface stripe form, a multilayer form, a gel form having a paste surrounding it, or any combination thereof. Alternatively, the oral composition may be a two-phase formulation dispensed from a spaced-apart dispenser.

[0014] As used herein, the term "amine base" can refer to a primary, secondary, or tertiary amine base. A "primary amine base" is a compound comprising at least one amine in which a nitrogen atom is directly bonded to one carbon atom of any hybrid other than the carbonyl carbon. A "secondary amine base" is a compound comprising at least one amine in which a nitrogen atom is directly bonded to two carbons of any hybrid other than the carbonyl carbon. A "tertiary amine base" is a compound comprising at least one amine in which a nitrogen atom is directly bonded to three carbons of any hybrid other than the carbonyl carbon. "Amino base" can also refer to compounds comprising a plurality of primary, secondary, and / or tertiary amine groups (e.g., tertiary polyamines). In particular, the term "amine base" excludes acid addition salts (e.g., hydrochlorides and hydrofluoric acids) and therefore refers to the free base form of the molecule. Hydrofluoric acid derivatives of amines are referred to herein as "fluorinated amines." In methods for producing or manufacturing compositions comprising fluorinated amines, the amine base can be a precursor for the formation of fluorinated amines.

[0015] As used herein, the term "in situ" refers 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 could be a salting reaction by mixing an amine with a fluoride source and an acid to produce a fluorinated amine and a salt. In some embodiments, in situ excludes the possibility of forming the 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).

[0016] The compositions disclosed herein

[0017] In another aspect, this disclosure relates to an oral care composition (composition 1) comprising:

[0018] amine base;

[0019] Fluoride source;

[0020] And zinc sources selected from zinc lactate and zinc citrate.

[0021] For example, this disclosure contemplates any of the following compositions (unless otherwise stated, values ​​are given as a percentage of the total weight of the composition):

[0022] 1.1 Composition 1, wherein the amine base is a primary amine, a secondary amine, a tertiary amine, or a combination thereof.

[0023] 1.2 Any of the aforementioned compositions, wherein the amine base comprises or is composed of a primary amine base.

[0024] 1.3 Any of the aforementioned compositions, wherein the amine base comprises or is composed of a secondary amine base.

[0025] 1.4 Any of the aforementioned compositions, wherein the amine base comprises or is composed of a tertiary amine base.

[0026] 1.5 Any of the foregoing compositions, wherein the amine base is of plant origin.

[0027] 1.6 Any of the methods described above, wherein the amine base is of animal origin.

[0028] 1.7 Any of the methods described above, wherein the amine base is derived from tallow.

[0029] 1.8 Any of the aforementioned compositions, wherein the amine base is derived from rapeseed oil or rice bran oil.

[0030] 1.9 Any of the foregoing compositions, wherein the amine base is a linear or branched aliphatic amine or polyamine, or a mixture thereof.

[0031] 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.

[0032] 1.11 Any of the foregoing compositions, wherein the amine base is myristyl, palmityl, linoleyl, oleyl or stearylamine or polyamine, or a combination thereof.

[0033] 1.12 Any of the aforementioned compositions, wherein the amine base is a polyamine (e.g., a monoamine base, a diamine base, and / or a triamine base).

[0034] 1.13 Any of the aforementioned compositions, wherein the amine base is a monoamine base.

[0035] 1.14 Any of the aforementioned compositions, wherein the amine base is a diamine base.

[0036] 1.15 Any of the aforementioned compositions, wherein the amine base is a triamine base.

[0037] 1.16 Any of the foregoing compositions, wherein the amine base comprises one or more of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol) and / or N-octadec-9-enamine.

[0038] 1.17 Any of the foregoing compositions, wherein the amine base is N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol).

[0039] 1.18 Any of the aforementioned compositions, wherein the amine base is N-octadec-9-enamine.

[0040] 1.19 Any of the foregoing compositions, wherein the amine base and the fluoride ion source form a fluorinated amine in situ. 1.20 Any of the foregoing compositions further comprises an acid.

[0041] 1.21 The aforementioned composition, wherein the acid is an organic acid (e.g., lactic acid, citric acid, tartaric acid, fumaric acid, malic acid), phosphoric acid, or hydrochloric acid.

[0042] 1.22 The aforementioned composition, wherein the organic acid is an aliphatic dicarboxylic acid or tricarboxylic acid in free or salt form.

[0043] 1.23 Any of the aforementioned compositions further comprises malic acid.

[0044] 1.24 Any of the aforementioned compositions further comprises hydrochloric acid.

[0045] 1.25 Any of the foregoing compositions further comprises phosphoric acid.

[0046] 1.26 Any of the aforementioned compositions, wherein the acid is not hydrofluoric acid.

[0047] 1.27 Any of the foregoing compositions, wherein the composition is substantially free of hydrofluoric acid (e.g., less than 0.001% by weight of hydrofluoric acid).

[0048] 1.28 Any of the aforementioned compositions, wherein the amine base, fluoride ion source, and acid are formed in situ into a fluorinated amine.

[0049] 1.29 Any of the aforementioned 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.

[0050] 1.30 Any of the aforementioned compositions, wherein the fluoride is sodium fluoride.

[0051] 1.31 Any of the foregoing compositions, wherein the composition contains less than 0.01% by weight of stannous fluoride.

[0052] 1.32 Any of the foregoing compositions, wherein the composition contains less than 0.001% by weight of stannous fluoride.

[0053] 1.33 Compositions 1.19 or 1.28, wherein the fluorinated amine formed is one or more of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride (Olarflu) or N-octadec-9-enamine hydrofluoride (dectaflur).

[0054] 1.34 Compositions 1.19 or 1.28, wherein the fluorinated amine formed is N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride (Oraflu).

[0055] 1.35 Composition 1.19 or 1.28, wherein the fluorinated amine formed is N-octadecano-9-enamine hydrofluoric acid (dectaflur).

[0056] 1.36 Any of the aforementioned compositions, wherein the zinc source is zinc lactate.

[0057] 1.37 Any of the aforementioned compositions, wherein the zinc source is zinc citrate.

[0058] 1.38 Any of the foregoing compositions, wherein the amine base is present in an amount of about 0.01% by weight to about 5% by weight, about 0.01% by weight to about 3% by weight, or about 0.1% by weight to about 1% by weight, based on the total weight of the composition.

[0059] 1.39 Any of the foregoing compositions, wherein the amine base is present in an amount of about 0.5% by weight to about 2.5% by weight, about 1% by weight to about 2% by weight, about 1.2% by weight to about 1.4% by weight, or about 1.3% by weight, based on the total weight of the composition.

[0060] 1.40 Any of the foregoing compositions, wherein the amine base is present in an amount of about 0.1% by weight to about 0.5% by weight, or about 0.15% by weight to about 0.25% by weight, based on the total weight of the composition.

[0061] 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.

[0062] 1.42 Any of the foregoing compositions, wherein the total fluoride content of the composition is in an amount of 50 ppm to 25,000 ppm (e.g., 750 ppm to 7,000 ppm, e.g., 1,000 ppm to 5,500 ppm, e.g., about 250 ppm, 500 ppm, 1,000 ppm, 1,100 ppm, 1,400 ppm, 1,450 ppm, 2,800 ppm, 5,000 ppm, or 25,000 ppm).

[0063] 1.43 Any of the foregoing compositions, wherein the zinc source is present in an amount of about 0.1% by weight to about 2.5% by weight, for example about 0.5% by weight or about 2.0% by weight, based on the total weight of the composition.

[0064] 1.44 Any of the foregoing compositions, wherein the zinc source is present in an amount of about 0.1% by weight to about 0.2% by weight, for example, about 0.17% by weight to about 0.18% by weight, based on the total weight of the composition. 1.45 Any of the foregoing compositions, wherein the zinc source is zinc lactate present in an amount of about 0.5% by weight based on the total weight of the composition.

[0065] 1.46 Any of the foregoing compositions, wherein the zinc source is zinc lactate present in an amount of about 0.1% by weight to about 0.25% by weight or 0.2% by weight based on the total weight of the composition.

[0066] 1.47 Any of the foregoing compositions, wherein the zinc source is zinc citrate present in an amount of about 2.0% by weight based on the total weight of the composition.

[0067] 1.48 Any of the foregoing compositions further comprises polyvinylpyrrolidone in an amount of about 0.1% by weight to about 1.00% by weight based on the total weight of the composition.

[0068] 1.49 Any of the foregoing compositions contains an acid (e.g., hydrochloric acid) in an amount of about 0.1% to about 1.0% by weight (e.g., about 0.7% to about 0.9% by weight) based on the total weight of the composition. 1.50 Any of the foregoing compositions contains malic acid in an amount of about 0.03% to about 0.07% by weight based on the total weight of the composition.

[0069] 1.51 Any of the foregoing compositions comprises a cellulose derivative (e.g., hydroxyethyl cellulose) in an amount of about 1% to about 2% by weight based on the total weight of the composition.

[0070] 1.52 Any of the foregoing compositions further comprises a basic amino acid (e.g., arginine) present in an amount corresponding to 1% to 15% of the total composition weight, such as 3% to 10% by weight, such as about 1.5%, 4%, 5% or 8%, wherein the weight of the basic amino acid is calculated in free form.

[0071] 1.53 Any of the foregoing compositions, wherein the composition does not contain ethanol.

[0072] 1.54 Any of the aforementioned compositions, wherein the pH is below 7, for example, a pH of about 3 to 6, or a pH of about 4 to 5.

[0073] 1.55 Any of the foregoing compositions further comprises an effective amount of one or more alkali metal phosphates, such as sodium, potassium, or calcium salts, selected from alkali metal dibasic phosphates and alkali metal pyrophosphates, such as alkali metal phosphates selected from: disodium hydrogen phosphate, dipotassium hydrogen phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, disodium orthophosphate, sodium dihydrogen phosphate, pentapotassium triphosphate, and mixtures of two or more thereof, for example, in an amount of 0.01% to 20% by weight of the composition, such as 0.1% to 8%, 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%.

[0074] 1.56 The aforementioned composition, wherein the polyphosphate is tetrasodium pyrophosphate.

[0075] 1.57 The aforementioned composition, wherein the tetrasodium pyrophosphate is 0.1% to 1.0% by weight (e.g., about 0.5% by weight).

[0076] 1.58 Any of the foregoing compositions further comprises abrasives or microparticles (e.g., silica). 1.59 Any of the foregoing compositions further comprises a nonionic surfactant, wherein the amount of the nonionic surfactant is 0.5% to 5%, for example 1% to 2%, selected from poloxamer (e.g., poloxamer 407), polysorbate (e.g., polysorbate 20), polyhydroxy hydrogenated castor oil (e.g., polyhydroxy 40 hydrogenated castor oil), polyglycerol 4-decanoate, and mixtures thereof.

[0077] 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.

[0078] 1.61 Any of the foregoing compositions further comprises a moisturizer selected from glycerin, sorbitol, xylitol, and propylene glycol in an amount of about 10% to 70% by weight based on the total weight of the composition. 1.62 Any of the foregoing compositions comprises a moisturizer selected from glycerin and sorbitol.

[0079] 1.63 Any of the foregoing compositions further comprises a flavoring agent, a flavoring agent, and / or a coloring agent. 1.64 Any of the foregoing compositions comprises one or more flavoring agents selected from saccharin and sucralose (e.g., the amount of saccharin is about 0.02% by weight, and the amount of sucralose is about 0.007% by weight to about 0.01% by weight).

[0080] 1.65 The aforementioned composition further comprises glycerol in an amount of about 2.0% to about 3.5% by weight based on the total weight of the composition.

[0081] 1.66 Any of the foregoing compositions further comprises a thickener selected from: carboxyvinyl polymers, hydroxyethyl cellulose, and water-soluble salts of cellulose ethers (e.g., sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose).

[0082] 1.67 Any of the foregoing compositions further comprises an antimicrobial agent selected from: 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, magnolol, catechin, methyl salicylate, epigallocatechin gallate, epigallocatechin gallate, gallic acid, miswak extract, sea buckthorn extract), biguanide preservatives (e.g., chlorhexidine, alexidine, or octenidine), and quaternary ammonium compounds (e.g., hexadecylpyridine chloride). (CPC), benzalkonium chloride, tetradecylpyridine chloride (TPC), N-Tetradecyl-4-ethylpyridine chloride (TDEPC), phenolic preservatives, hexetidine, octenidine, sanguisorbin, povidone-iodine, delmopinol, salifluor, sanguisorbin, propolis and oxidizing agents (e.g., buffered sodium perborate or sodium percarbonate), phthalic acid and its salts, monoperoxyphthalic acid and its salts and esters, ascorbate stearate, sarcosine oleoyl ester, alkyl sulfate, dioctyl sulfosuccinate, salicylaniline, domiphenbromide, delmopinol, octapinol and other piperidinyl derivatives, nicotinic acid preparations, chlorites; and mixtures of any of the foregoing substances.

[0083] 1.68 Any of the foregoing compositions further comprises an antioxidant, for example, said antioxidant is selected from: coenzyme Q10, PQQ, vitamin C, vitamin E, vitamin A, BHT, anethole-dithiothion and mixtures thereof.

[0084] 1.69 Any of the foregoing compositions further comprises a whitening agent selected from: metal chlorites, perborates, percarbonates, peroxy acids, hypochlorites, and combinations thereof.

[0085] 1.70 Any of the foregoing compositions further comprises an agent that interferes with or prevents bacterial attachment, such as ethyl lauroyl arginine (ELA) or chitosan.

[0086] 1.71 Any of the foregoing compositions, wherein the oral composition may be any of the following oral compositions: toothpaste or dental cleaning agent, mouthwash or mouth rinse liquid, topical oral gel, spray, powder, strip, dental floss and denture cleaner.

[0087] 1.72 Any of the foregoing compositions, wherein the composition is in the form of a cleaning agent, such as a liquid hand soap preparation, shower gel or skin cleanser; or a household care preparation, such as a hard surface cleaner such as dish soap, sunscreen, makeup remover or topical disinfectant.

[0088] 1.73 Any of the foregoing compositions is used to treat periodontitis and / or gingivitis.

[0089] Compositions obtained or available by combining the ingredients described in any of the foregoing compositions.

[0090] In another embodiment, this disclosure covers methods for improving oral health, said methods comprising applying an effective amount of an oral composition of any of the above embodiments to the oral cavity of a subject in need, for example, for the following methods:

[0091] i. Reduce or inhibit the formation of tooth decay,

[0092] ii. To reduce, repair, or inhibit early enamel damage, for example, as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM).

[0093] iii. Reduces or inhibits demineralization and promotes tooth remineralization.

[0094] iv. Reduce tooth hypersensitivity

[0095] v. To reduce or suppress gingivitis

[0096] vi. To promote the healing of oral ulcers or incisions.

[0097] vii. Inhibit the formation of oral microbial biofilms.

[0098] viii. After the sugar challenge, raise and / or maintain the plaque pH at a level of at least pH 5.5.

[0099] ix. Reduce plaque buildup.

[0100] x. Treatment for dry mouth,

[0101] xi. Enhance overall health, including cardiovascular health, for example by reducing the likelihood of systemic infections transmitted through oral tissues.

[0102] xii. Teeth whitening

[0103] xiii. Reduce tooth erosion

[0104] xiv. To make teeth immune to cariogenic bacteria and their effects (or to protect teeth), and / or

[0105] xv. To clean teeth and mouth.

[0106] Fluoride ion source

[0107] Oral care compositions may also contain one or more fluoride ion sources, such as soluble fluoride salts. A wide variety of fluoride-generating substances can be used as soluble fluoride sources in the compositions of the present invention. Examples of suitable fluoride-generating substances are found in U.S. Patent No. 3,535,421 to Briner et al.; U.S. Patent No. 4,885,155 to Parran, Jr. et al.; and U.S. Patent No. 3,678,154 to Widder et al., each of which is incorporated herein by reference. Representative fluoride ion sources used in this disclosure (e.g., Composition 1.0 and below, etc.) include, but are not limited to, sodium fluoride, potassium fluoride, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, and combinations thereof. In some embodiments, the fluoride ion source includes sodium fluoride. When the formulation contains a calcium salt, the fluoride salt is preferably a salt in which the fluoride is covalently bonded to another atom (e.g., as in sodium monofluorophosphate) rather than merely ionicly bonded (e.g., as in sodium fluoride).

[0108] surfactants

[0109] In another embodiment, the cationic surfactants that can be used in this 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 lauryltrimethylammonium chloride and cetylpyridine chloride. Cetyltrimethylammonium bromide, diisobutylphenoxyethyl dimethylbenzylammonium chloride, nitrite-cocoylalkyltrimethylammonium, fluorinated cetylpyridine 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 compositions.

[0110] The illustrative nonionic surfactants that can be used in the compositions of this disclosure, such as Composition 1.0 and the following, can be broadly defined as compounds produced by condensing an alkylene oxide group (which is inherently hydrophilic) with an organic hydrophobic compound that may be inherently aliphatic or alkyl aromatic. 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 substances. In a particular embodiment, the compositions of this disclosure comprise a nonionic surfactant selected from: poloxamer (e.g., poloxamer 407), polysorbates (e.g., polysorbate 20), polyhydroxyl hydrogenated castor oil (e.g., polyhydroxyl 40 hydrogenated castor oil), betaine (e.g., cocamidopropyl betaine), and mixtures thereof.

[0111] Composition 1.0, which can be used in the compositions of this disclosure, and the following illustrative amphoteric surfactants include betaine (e.g., cocamidopropyl betaine); derivatives of aliphatic secondary and tertiary amines, wherein the aliphatic group may be linear or branched, and wherein one of the aliphatic substituents contains about 8 to 18 carbon atoms, and another contains anionic water-soluble groups (e.g., carboxyl, sulfonate, sulfate, phosphate, or phosphonate); and mixtures of such substances.

[0112] The surfactant or mixture of compatible surfactants may be present in the composition of this disclosure at 0.1% to 5% by weight of the total composition, 0.3% to 3% in another embodiment, and 0.5% to 2% in yet another embodiment.

[0113] Flavoring agents

[0114] The oral care compositions of this disclosure may also contain flavoring agents. Flavoring agents used in the practice of this disclosure include, but are not limited to, essential oils and various flavoring aldehydes, esters, alcohols and similar substances, as well as sweeteners such as sodium saccharin. Examples of essential oils include oils of spearmint, peppermint, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange. Chemicals such as menthol, carvone, and anethole are also available. Some embodiments use peppermint and spearmint oils.

[0115] The flavoring agent is incorporated into the oral composition at a concentration of 0.01% to 1.7% by weight.

[0116] Chelating agents and anti-tartar agents

[0117] The oral care compositions disclosed herein may also contain one or more chelating agents capable of complexing with calcium present in bacterial cell walls. This binding to calcium weakens the bacterial cell wall and enhances bacterial lysis.

[0118] Another group of reagents suitable for use as chelating agents or anti-tartar agents in this disclosure are soluble pyrophosphates. The pyrophosphate used in the compositions of the present invention can be any of the alkali metal pyrophosphates. In some 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 and dehydrated forms. The effective amount of pyrophosphate that can be used in the compositions of the present invention is generally sufficient to provide at least 0.1% by weight of pyrophosphate ions, for example, 0.1% to 3% by weight, for example, 0.1% to 2% by weight, for example, 0.1% to 1% by weight, for example, 0.2% to 0.5% by weight. Pyrophosphates also help preserve the composition by reducing water activity.

[0119] polymer

[0120] The oral care compositions of this disclosure optionally also comprise one or more polymers, such as polyethylene glycol, polyvinyl methyl ether maleic acid copolymers, and polysaccharides (e.g., cellulose derivatives, such as carboxymethyl cellulose). Acidic polymers, such as polyacrylate gels, may be provided as their free acid or as partially or completely neutralized water-soluble alkali metals (e.g., potassium and sodium) or ammonium salts. Some embodiments comprise a 1:4 to 4:1 copolymer of maleic anhydride or maleic acid with another polymerizable olefinically unsaturated monomer, such as methyl vinyl ether (methoxyethylene), having a molecular weight (MW) of about 30,000 to about 1,000,000. These copolymers are available, for example, in Gantrez AN 139 (MW 500,000), AN 1 19 (MW 250,000), and S-97 pharmaceutical grade (MW 70,000) from GAF Chemicals Corporation.

[0121] Other active polymers 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, under Monsanto EMA number 1 103, MW 10,000, and EMA class 61; and 1:1 copolymers of acrylic acid with methyl methacrylate or hydroxyethyl methacrylate, methyl acrylate or ethyl acrylate, isobutyl vinyl ether, or N-vinyl-2-pyrrolidone.

[0122] Generally, suitable copolymers are olefinic or olefinically unsaturated carboxylic acids containing an active carbon-carbon olefinic double bond and at least one carboxyl group, i.e., acids containing an olefinic double bond in the monomer molecule that readily functions in polymerization due to its presence at the α-β position relative to the carboxyl group or as part of the terminal methylene group. Examples of such acids include acrylic acid, methacrylic acid, ethacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloyloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid, β-styrylacrylic acid, mucoacrylic acid, itacrylic acid, citraconic acid, methyl fumaric acid, pentenediaic acid, aconitic acid, α-phenylacrylic acid, 2-benzylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbelliferous acid, fumaric acid, maleic acid, and acid anhydrides. Other different olefinic monomers that can copolymerize with such carboxyl monomers include vinyl acetate, vinyl chloride, dimethyl maleate, etc. The copolymer contains a carboxyl group sufficient for water solubility.

[0123] Another class of polymerizers 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 selected from acrylamide-alkyl sulfonic acids (e.g., 2-acrylamido-2-methylpropanesulfonic acid) with a molecular weight of about 1,000 to about 2,000,000, as described in U.S. Patent No. 4,842,847 to Zahid, June 27, 1989, which is incorporated herein by reference.

[0124] Another class of available polymerizers includes polyamino acids, particularly those containing a proportion of anionic surfactant amino acids such as aspartic acid, glutamic acid, and phosphoserine, as disclosed in U.S. Patent No. 4,866,161 to Sikes et al., which is incorporated herein by reference.

[0125] In the preparation of oral care compositions, it is sometimes necessary to add thickening materials to provide a desired consistency or to stabilize or enhance the performance of the formulation. In some embodiments, the thickener is a water-soluble salt of carboxyvinyl polymers, hydroxyethyl cellulose, and cellulose ethers, such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums, such as gum arabic, gum arabic, and gum astragalus, may also be incorporated. Colloidal magnesium aluminum silicate or finely dispersed silica may be used as a component of the thickening composition to further improve the texture of the composition. In some embodiments, a thickener is used in an amount of about 0.5% to about 5.0% by weight of the total composition.

[0126] abrasive

[0127] In some embodiments, this disclosure may include additional silica abrasives, sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite, or other siliceous materials, or combinations thereof. Any silica suitable for oral care compositions may be used, such as precipitated silica or silica gel. For example, synthetic amorphous silica. Silica may also be used as a thickener, such as particulate silica. For example, silica may also be small particulate silica (e.g., Sorbosil AC43 from PQ Corporation, Warrington, UK).

[0128] water

[0129] Water is present in the oral compositions of this disclosure. The water used in the preparation of commercial oral compositions should be deionized and free of organic impurities. Water typically makes up the balance of the composition and constitutes 5% to 99% by weight, for example 10% to 20% by weight, for example 25% to 35% by weight of the oral composition. This amount of water includes the added free water plus the amount of water introduced with other substances such as sorbitol or silica or any component of this disclosure. The Karl Fischer method is one method for calculating free water.

[0130] moisturizer

[0131] In some embodiments of the oral composition, it is also desirable to incorporate a humectant to reduce evaporation and to aid preservation by reducing the activity of water. Some humectants may also impart a desired sweetness or flavor to the composition. As a pure humectant, the humectant typically constitutes 1% to 70% by weight of the composition in one embodiment or 30% to 65% in another embodiment.

[0132] Suitable humectants include edible polyols such as glycerin, sorbitol, xylitol, propylene glycol, and other polyols and mixtures of these humectants. A mixture of glycerin and sorbitol may be used as a humectant component of the compositions herein in some embodiments.

[0133] pH adjuster

[0134] In some embodiments, the compositions of this disclosure comprise 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 buffer is sufficient to provide a pH of about 3 to about 9, preferably about 4 to 5. Typical amounts of buffer are 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.

[0135] This disclosure relates, in terms of its method, to the application of a safe and effective amount of the composition described herein to the oral cavity.

[0136] The compositions and methods according to this disclosure (e.g., composition 1.0 and the following, etc.) can be incorporated into oral compositions for oral and dental care, such as toothpaste, clear paste, gel, mouthwash, mouthwash liquid, spray, toothpaste powder, tablets and chewing gum.

[0137] As used throughout, ranges are used as abbreviations to describe the individual values ​​within a range and for each value. Any value within a range may be chosen as an endpoint of the range. Furthermore, all references cited herein are incorporated herein by reference in their entirety. In the event of any conflict between definitions in this disclosure and those in the cited references, the definitions in this disclosure shall prevail. It should be understood that, in describing formulations, they may be described based on their components, as is common in the art, although these components may react with each other in the actual formulation during preparation, storage, and use, and such products are intended to be covered by the formulation.

[0138] The following embodiments further describe and illustrate exemplary embodiments within the scope of this disclosure. These embodiments are given merely as examples and should not be construed as limiting the scope of this disclosure, as many variations are possible without departing from the spirit and scope of the invention. Various modifications to this disclosure, other than those shown and described herein, will be apparent to those skilled in the art and are intended to fall within the scope of the appended claims.

[0139] Example

[0140] Example 1: Model toothpaste formulation

[0141] Prepare toothpaste formulations according to the following:

[0142] Table 1: Toothpaste formulations based on this disclosure

[0143] Formulation 1 Formulation 2 Formulation 3 surfactants 5.5 5.5 5.5 polymer 1.6 1.6 1.6 Amine base (derived from beef tallow) 1.38 -- -- hydrochloric acid 0.79 0.88 0.89 Sodium saccharin 0.39 0.39 0.39 glycerin 40 40 40 amorphous silica 19 19 19 Thickened 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 Amino bases (of plant origin) -- 1.38 1.38 Fragrances and colorants 1.6 1.6 1.6 water 26.24 26.15 24.64

[0144] Formulations 1 to 3 were subjected to accelerated aging conditions to test storage stability. The results are summarized in Table 2 below.

[0145] Table 2: Stability of toothpaste formulations

[0146]

[0147] As shown above, all formulations exhibited high levels of stability even under accelerated aging conditions.

[0148] Several control toothpaste formulations were designed as comparatives to formulations 1 through 3, and are summarized in Table 2.

[0149] Table 3: Comparison of toothpaste formulations

[0150]

[0151] Example 2: In vitro antibacterial test of toothpaste formulation

[0152] Formulations were designed to test the in vitro antibacterial activity of various toothpaste formulations according to this disclosure. McBain medium was diluted and supplemented with a 1:1000 dilution of heme chloride and menadione. The medium was then inoculated at a concentration of 2 mL / 40 mL. HAP discs were placed in the plate as a substrate for biofilm growth and incubated for 60 hours. 1.5 mL of medium was added every 12 hours.

[0153] Add 1.5 mL of test reagent to each plate. Treat the HAP discs for 2 minutes and incubate on a steady-state shaker at 90 rpm. Determine bacterial viability by ATP fluorescence. The results are summarized in Table 3 below:

[0154] Table 4: Antibacterial Activity

[0155] Composition Fluorescence counting Formulation 1 29712 Formulation 2 33862 Formulation 3 42957 Comparative formulation 1 40756 Comparative formulation 2 155913

[0156] As shown above, compositions containing zinc lactate or zinc citrate with amine bases and sodium fluoride performed at least as well as or better than comparative formulation 1, which did not contain any zinc compounds. Furthermore, each of compositions 1 through 3 performed significantly better than comparative formulation 2, which contained sodium fluoride but no amine bases or zinc compounds. These results indicate that oral care compositions containing amine bases, sodium fluoride, and zinc compounds provide an unexpected enhancement in the antibacterial efficacy of the composition.

[0157] Example 3: In vitro antibacterial test of mouthwash formulation

[0158] The preparation of mouthwash formulations according to this disclosure is summarized in Table 5.

[0159] Table 5: Mouthwash Compositions

[0160] Formulation 4 Formulation 5 Formulation 6 Xylitol 1.5 2.5 2.5 Polyvinylpyrrolidone 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 agents, sweeteners and coloring agents 0.17 0.16 0.16 water Appropriate amount Appropriate amount Appropriate amount

[0161] Several comparative compositions were analyzed in short-term lethality tests. The comparative compositions were prepared according to the summary in Table 6.

[0162] Table 6: Comparison of mouthwash compositions

[0163]

[0164] In the short-interval kill assay, all saliva was mixed 1:1 with mouthwash and exposed for 1 minute. The reaction was terminated with neutralizing broth, and the samples were serially diluted and plated. Data were reported as a reduction in log (colony-forming units) relative to the buffer-treated negative control. Results are summarized below.

[0165] Table 7: SIKT Test Results

[0166] Composition Log reduction of CFU Formulation 4 4.05 Comparative formulation 3 2.91 Comparative formulation 4 0.27

[0167] As these results show, formulation 4, which contains zinc lactate and amine fluoride, performed significantly better than the comparative formulation 3 (which contains amine fluoride and stannous fluoride active material), giving a reduction of one more log than the other samples.

[0168] Based on the PGRM clinical study found in the US FDA's provisional monograph on dental plaque and gingivitis, an additional study was conducted using an in vitro plaque glycolysis model. This model used a saliva-derived biofilm instead of dental plaque and monitored pH changes after treatment with the test mouthwash as a measure of the formulation's ability to limit biofilm metabolic activity.

[0169] Saliva-derived biofilms were cultured on hydroxyapatite discs attached to McBain medium supplemented with 0.4% sucrose at 37°C in an environment containing 5% CO2. The biofilms were cultured for 48 hours, with the medium replaced after the initial 24 hours of growth. The resulting biofilms were treated with undiluted mouthwash for 5 minutes and rinsed twice by immersion in sterile deionized water for 30 seconds each. Each treatment was performed in quadruplicate. 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) for each sample was calculated.

[0170] Table 8: pH changes after exposure to the test formulation

[0171] Composition pH changes Formulation 4 1.75 Comparative formulation 3 1.69 Comparative formulation 4 2.7 Unprocessed 2.75

[0172] Results of in vitro dental plaque glycolysis studies showed that, compared to placebo and positive controls, comparative formulations 5 and 6, containing amine fluoride and stannous fluoride, both exhibited a significant reduction in acid production. The similar performance of these two mouthwashes suggests that the efficacy of the formulations is not affected over time. Formulation 4, containing amine fluoride and zinc lactate, also showed a significant reduction in bacterial activity compared to placebo and positive controls. Without being bound by theory, it is believed that the antibacterial activity observed in formulation 4, as well as comparative formulations 5 and 6, may be due to the presence of amine fluoride in addition to metal ions.

[0173] Further studies were conducted using an aerobic biofilm model, in which saliva-derived biofilms were grown on vertically suspended HAP discs. The biofilms were grown in a selected composite medium (SHI medium) as it has been shown to provide high diversity in saliva-derived biofilms. The biofilms were treated twice daily with 1.5 mL of test mouthwash for 30 seconds each time. After 5 days of growth, the biofilms were harvested and the total biomass (optical density at 610 nm, i.e., OD) was compared. 610 Quantification is performed on ATP activity and metabolic activity (e.g., measured by ATP activity).

[0174] Table 9: Reduction of bacteria (via OD) 610 )

[0175] Composition Bacterial reduction (%) Formulation 4 51.39 Comparative formulation 3 45.78 Comparative formulation 4 5.13

[0176] Table 10: Reduction in bacteria (detected by ATP fluorescence)

[0177] Composition Bacterial reduction (%) Formulation 4 89.90 Comparative formulation 3 77.15 Comparative formulation 4 2.91

[0178] Research experiments were conducted to test the stability of the compositions after exposure to air (i.e., after first use). As shown below, while formulation 3 still exhibited antibacterial effects during the test period, its efficacy decreased significantly over time. On the other hand, formulation 4 did not show the same trend, indicating that the active ingredients in these formulations are more stable and retain their activity over time.

[0179] Table 11: Reduction of bacteria (by OD over time) 610 )

[0180]

[0181] Although this disclosure has been described with reference to embodiments, those skilled in the art will understand that various modifications and changes may be made thereto without departing from the scope of this disclosure as defined by the appended claims.

Claims

1. An oral care composition comprising Amine bases, wherein the amine bases are plant-derived amine bases; Fluoride source; And zinc lactate; The composition contains less than 0.01% by weight of stannous fluoride.

2. The composition according to claim 1, wherein the amine base is a linear or branched aliphatic amine base.

3. The composition according to claim 1, wherein the amine base is a linear or branched fatty polyamine base.

4. The composition according to claim 1, wherein the amine base is a saturated or unsaturated C24-carbon alloy. 12-20 Alkylamine bases.

5. The composition according to claim 1, wherein the amine base is a saturated or unsaturated C24-carbon alloy. 12-20 Alkyl polyamine bases.

6. The composition according to claim 1, wherein the amine base is a myristyl, palmityl, linoleyl, oleyl, or stearyl amine base, or N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol), or N-octadec-9-enamine and combinations thereof.

7. The composition according to claim 6, wherein the myristyl, palmyl, linoleyl, oleyl, or stearylamine base is a myristyl, palmyl, linoleyl, oleyl, or stearyl polyamine base.

8. The composition according to claim 1, wherein the amine base is a monoamine base.

9. The composition according to claim 1, wherein the amine base is a diamine base or a triamine base.

10. The composition according to claim 1, wherein the amine base is present in an amount of 0.01% to 5% by weight based on the total weight of the composition.

11. The composition according to claim 1, wherein the amine base is present in an amount of 0.01% to 3% by weight based on the total weight of the composition.

12. The composition according to claim 1, wherein the amine base is present in an amount of 0.1% to 1% by weight based on the total weight of the composition.

13. The composition according to claim 1, wherein the fluoride source is selected from one or more of sodium fluoride, potassium fluoride, ammonium fluoride, and combinations thereof.

14. The composition of claim 1, wherein the fluoride source is present in an amount of 0.005% by weight to 2.5% by weight based on the total weight of the composition.

15. The composition of claim 1, wherein the fluoride source is present in an amount of 0.025% to 0.145% by weight based on the total weight of the composition.

16. The composition of claim 1, wherein the fluoride source is present in an amount of 0.1% to 0.5% by weight based on the total weight of the composition.

17. The composition of claim 1, wherein the fluoride source is present in an amount of 0.01% to 0.03% by weight based on the total weight of the composition.

18. The composition according to claim 1, wherein the zinc lactate is present in an amount of 0.1% to 2.5% by weight based on the total weight of the composition.

19. The composition of claim 1, wherein the zinc lactate is present in an amount of 0.5% by weight or 2.0% by weight based on the total weight of the composition.

20. The composition according to claim 1 further comprises an acid selected from organic acids, phosphoric acid, or hydrochloric acid.

21. The composition according to claim 1 further comprises an acid selected from lactic acid, citric acid, tartaric acid, fumaric acid, or malic acid.

22. The composition of claim 20, wherein the acid is selected from hydrochloric acid, phosphoric acid, or malic acid.

23. The composition according to claim 22, wherein the acid is hydrochloric acid.

24. The composition of claim 20, wherein the amine base, the fluoride ion source, and the acid form a fluorinated amine in situ.

25. The composition of claim 1, wherein the composition is in the form of toothpaste, mouthwash, topical oral gel, denture cleaner or dental spray.

26. The composition according to claim 1, wherein the composition is in the form of a dental cleaning agent.

27. The composition according to claim 1, wherein the composition is in the form of a mouthwash.

Images