Oral care compositions with fluorinated amines

Abstract

The present disclosure relates to amine hydrofluorides and mixtures of these amine hydrofluorides, and to processes for preparing these amine hydrofluorides and their use in oral hygiene compositions.

Description

Technical Field

[0001] This invention relates to compositions containing tertiary amines, and to methods for preparing amine hydrofluorides and their use in said compositions. Background Technology

[0002] Oral hygiene compositions are known to contribute to oral hygiene and thus protect the health of teeth and gums through their cleaning action. The cleaning action of these compositions is typically supplemented by a mixture of active compounds that prevent or control pathological symptoms in the oral cavity, and particularly the formation of bacterial films (plaque) on teeth. These films are composed of polysaccharides, primarily dextran. In addition to low molecular weight sugars, these polysaccharides serve as a nutrient source for plaque bacteria (mainly Streptococci and Lactobacilli). Plaque bacteria gradually break down the polysaccharides to form acid degradation products (e.g., pyruvate, lactic acid, etc.). The resulting decrease in pH causes enamel deterioration, a condition known as dental caries.

[0003] Therefore, steps have been taken to combat the formation of oral pathological symptoms using various oral hygiene compositions (e.g., toothpaste, mouthwash, or dental gel). Known active compounds in the art include N-octadecyl-9-enylamine hydrofluoride (International Nonproprietary Name "Dicotalfluoride") and N′-octadecyl-N′,N,N-tris(2-hydroxyethyl)-1,3-propanediamine dihydrofluoride (International Nonproprietary Name "Olafluoride"). In the oral application of these hygiene compositions, these active compounds form a thin hydrophobic film on the enamel, with the amine hydrofluoride groups in contact with the enamel. Thus, on the one hand, the enamel becomes more resistant to acid erosion due to the formed CaF2 coating; on the other hand, the long-chain hydrocarbon residues form a hydrophobic layer that prevents the formation of deposits and acid degradation products that erode the enamel.

[0004] However, while such compounds are effective when used in oral care compositions, their use can be expensive due to their limited physical properties. For example, olaflu has very low water solubility. Therefore, the production and transportation of the compound require large quantities of solution to carry relatively small amounts of the active agent, resulting in high processing costs. Therefore, increasing the solubility of tertiary amines would be beneficial for production and transportation. Summary of the Invention

[0005] The production of compositions containing fluorinated amines, such as N′-octadecyl-N′,N,N-tris(2-hydroxyethyl)-1,3-propanediamine dihydrofluoride (Oraflu), typically involves dissolving a solid fluorinated amine in water to produce a fluorinated amine stock solution. This stock solution can then be used directly in the formulation of compositions containing fluorinated amines (e.g., Oraflu). However, this stock solution contains only a moderate concentration of fluorinated amine, which can typically only be increased slightly further. Attempting to increase the concentration of fluorinated amine beyond this point results in incomplete dissolution, precipitation, or the solution transforming into a gel-like structure, each of which is undesirable and unusable in a standardized production process.

[0006] The inventors unexpectedly discovered that adding an alkali metal salt to a solution could result in significantly higher concentrations of fluorinated amines and / or tertiary amines dissolving in water. When an alkali metal salt (e.g., sodium chloride) is added to a stock solution, the solubility of fluorinated amines and / or their non-hydrofluoride salt counterparts (referred to as "tertiary amines") in water can increase by at least 45%. This property is thought to result in proportional savings in the transportation costs of the active agent (i.e., the tertiary amine) and also simplifies the synthesis of such tertiary amines (e.g., fluorinated amines) and compositions containing said tertiary amines.

[0007] Therefore, in a first aspect, this disclosure relates to oral care compositions comprising a tertiary amine (e.g., an amine fluoride) and an alkali metal salt in an amount sufficient to increase the solubility of the tertiary amine. In several embodiments, the tertiary amine is a tertiary polyamine or an amine fluoride (e.g., olafluridine or diketamine), and the alkali metal salt is sodium chloride.

[0008] In a second aspect, this disclosure relates to a method of manufacturing an oral care composition, comprising the steps of: mixing a tertiary amine (e.g., an amine fluoride) in water; and increasing the solubility of the tertiary amine by adding an alkali metal salt. In several embodiments, the step of mixing the tertiary amine in water further includes mixing a pH adjuster and a fluoride source. In some embodiments, the tertiary amine is a tertiary polyamine or an amine fluoride (e.g., olafluridine or decitabine) and the alkali metal salt is sodium chloride. Detailed Implementation

[0009] As used herein, the term "oral composition" means the entire composition delivered to the oral cavity surface. This composition is also defined as a product intended for oral activity during normal use, not for systemic administration of a particular therapeutic agent, not intended for ingestion, but for the purpose of maintaining contact with substantially all tooth surfaces and / or oral tissues for a sufficient period of time. Examples of such compositions include, but are not limited to, toothpaste or dental cleaning agents, mouthwash or mouthwash liquid, topical oral gels, denture cleaners, sprays, etc.

[0010] 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 paste surrounded by a gel, or any combination thereof. Alternatively, the oral composition may be a two-phase formulation dispensed from a spaced-apart dispenser.

[0011] The compositions disclosed herein

[0012] In one aspect, the present invention is an intermediate composition (composition 1) for formulating oral care or personal care compositions, wherein the composition comprises a tertiary amine (e.g., a tertiary polyamine) and an alkali metal salt in an amount sufficient to increase the solubility of the tertiary amine. For example, the present invention contemplates any of the following compositions (unless otherwise indicated, values ​​are given as a percentage of the total weight of the composition):

[0013] 1.1 Composition 1, wherein the tertiary amine comprises a tertiary polyamine or a fluorinated amine.

[0014] 1.2 Any of the foregoing compositions, wherein the tertiary amine comprises one or more of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol), N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride (oraflu), N-octadec-9-enylamine hydrofluoride (diketofur), and / or N-octadec-9-enylamine.

[0015] 1.3 Any of the foregoing compositions, wherein the tertiary amine is a tertiary polyamine.

[0016] 1.4 Any of the foregoing compositions, wherein the tertiary amine comprises at least one of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol) and N-octadec-9-enylamine.

[0017] 1.5 Any of the foregoing compositions, wherein the tertiary amine comprises N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol) or is composed of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol).

[0018] 1.6 Any of the foregoing compositions, wherein the tertiary amine comprises a fluorinated amine (e.g., octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride, N-octadec-9-enylamine hydrofluoride).

[0019] 1.7 Any of the foregoing compositions, wherein the tertiary amine is present in an amount of about 10% by weight to about 80% by weight based on the total weight of the composition.

[0020] 1.8 Any of the foregoing compositions, wherein the tertiary amine is present in an amount of about 20% to about 70% by weight based on the total weight of the composition.

[0021] 1.9 Any of the foregoing compositions, wherein the tertiary amine is present in an amount of about 20% to about 40% by weight based on the total weight of the composition.

[0022] 1.10 Any of the foregoing compositions, wherein the tertiary amine is present in an amount of about 25% to about 35% by weight based on the total weight of the composition.

[0023] 1.11 Any of the foregoing compositions, wherein the alkali metal salt is an alkali metal halide and / or an alkali metal salt of an organic acid.

[0024] 1.12 Any of the foregoing compositions, wherein the alkali metal salt is an alkali metal halide.

[0025] 1.13 Any of the foregoing compositions, wherein the alkali metal salt is a sodium halide or a potassium halide.

[0026] 1.14 Any of the foregoing compositions, wherein the alkali metal salt is sodium chloride or potassium chloride.

[0027] 1.15 Any of the foregoing compositions, wherein the alkali metal salt is sodium chloride.

[0028] 1.16 Any of the foregoing compositions, wherein the alkali metal salt is an alkali metal salt of an organic acid.

[0029] 1.17 Any of the foregoing compositions, wherein the alkali metal salt is trisodium citrate.

[0030] 1.18 Any of the foregoing compositions, wherein the alkali metal salt is trisodium citrate dihydrate.

[0031] 1.19 Any of the foregoing compositions, wherein the alkali metal salt is present in an amount of about 0.01% by weight to about 15% by weight based on the total weight of the composition.

[0032] 1.20 Any of the foregoing compositions, wherein the alkali metal salt is present in an amount of about 0.05% by weight to about 5% by weight based on the total weight of the composition.

[0033] 1.21 Any of the foregoing compositions, wherein the alkali metal salt is present in an amount of about 1% to about 2.5% by weight based on the total weight of the composition.

[0034] 1.22 Any of the foregoing compositions, wherein, based on the total weight of the composition, the alkali metal salt comprises sodium chloride in an amount of about 1.0 wt% to about 2.0 wt%, or is composed of sodium chloride in an amount of about 1.0 wt% to about 2.0 wt%.

[0035] 1.23 Any of the foregoing compositions, wherein, based on the total weight of the composition, the alkali metal salt comprises potassium chloride present in an amount of about 1.0 wt% to about 2.5 wt%, for example, about 1.0 wt% to about 2.0 wt%, or is composed of potassium chloride present in an amount of about 1.0 wt% to about 2.5 wt%, for example, about 1.0 wt% to about 2.0 wt%.

[0036] 1.24 Any of the foregoing compositions, wherein, based on the total weight of the composition, the alkali metal salt comprises trisodium citrate dihydrate present in an amount of about 1.0 wt% to about 4.0 wt%, for example, about 1.0 wt% to about 3.5 wt%, or is composed of trisodium citrate dihydrate present in an amount of about 1.0 wt% to about 4.0 wt%, for example, about 1.0 wt% to about 3.5 wt%.

[0037] 1.25 Any of the foregoing compositions, wherein the composition is an aqueous solution.

[0038] 1.26 Any of the foregoing compositions further comprises an organic acid.

[0039] 1.27 Any of the foregoing compositions further comprises, based on the total weight of the compositions, an aliphatic dicarboxylic acid or tricarboxylic acid in a free or salt form in an amount of about 1% to about 10% by weight.

[0040] 1.28 The aforementioned composition, wherein the aliphatic dicarboxylic acid or tricarboxylic acid is malic acid.

[0041] 1.29 Any of the aforementioned compositions further comprises an organic acid selected from lactic acid, citric acid, tartaric acid and fumaric acid.

[0042] 1.30 Any of the foregoing compositions further comprises an inorganic acid.

[0043] 1.31 Any of the foregoing compositions further comprises hydrochloric acid.

[0044] 1.32 Any of the foregoing compositions further comprises hydrochloric acid in an amount of about 1% to about 10% by weight based on the total weight of the compositions.

[0045] 1.33 Any of the foregoing compositions, wherein the composition is a stock solution.

[0046] 1.34 Any of the foregoing compositions, wherein the composition is a stock solution for producing an oral care composition containing fluorinated amine.

[0047] 1.35 Any of the foregoing compositions, wherein the composition is a stock solution for producing a personal care composition containing fluorinated amines.

[0048] 1.36 Any of the aforementioned compositions further comprises a stannous ion source.

[0049] 1.37 The aforementioned composition, wherein the stannous source is selected from stannous fluoride, stannous chloride, stannous fluoride, stannous chloride, stannous acetate, stannous acetate, and combinations thereof.

[0050] 1.38 Either of the first two aforementioned compositions, wherein the tin subion source is present in an amount of about 0.01% by weight to about 0.10% by weight based on the total weight of the composition.

[0051] 1.39 Any of the foregoing compositions further comprises a fluoride source selected from: sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.

[0052] 1.40 The aforementioned composition, wherein the fluoride source is present in an amount of 0.1% to 7% by weight (e.g., about 3% to about 6% by weight) of the total composition.

[0053] 1.41 Any of the foregoing compositions, wherein the total fluoride content of the composition is from 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 500 ppm, 1,000 ppm, 1,100 ppm, 2,800 ppm, 5,000 ppm, or 25,000 ppm).

[0054] 1.42 Any of the foregoing compositions further comprises a polyvinylpyrrolidone in an amount of about 2.20% to about 3.00% by weight based on the total weight of the compositions.

[0055] 1.43 Any of the foregoing compositions further comprises a basic amino acid (e.g., arginine) present in an amount corresponding to 1% to 15%, for example 3% to 10% by weight, or about 1.5%, 4%, 5% or 8% of the total composition, wherein the weight of the basic amino acid is calculated in free form.

[0056] 1.44 Any of the foregoing compositions, wherein the composition is ethanol-free.

[0057] 1.45 Any of the foregoing compositions, wherein the pH is 4.0 to 10.0, for example 5.0 to 8.0, for example 7.0 to 8.0.

[0058] 1.46 Any of the foregoing compositions further comprises calcium carbonate.

[0059] 1.47 The aforementioned composition, wherein the calcium carbonate is highly absorbent precipitated calcium carbonate (e.g., 20% to 30% by weight of the composition) (e.g., 25% highly absorbent precipitated calcium carbonate).

[0060] 1.48 Any of the foregoing compositions further comprises light precipitated calcium carbonate (e.g., about 10% light precipitated calcium carbonate) (e.g., about 10% natural calcium carbonate).

[0061] 1.49 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 dialkali metal hydrogen phosphate and alkali metal pyrophosphate, 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 hydrogen orthophosphate, sodium dihydrogen phosphate, pentapotassium triphosphate, and mixtures of any two or more of these, 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%.

[0062] 1.50 The aforementioned composition, wherein the polyphosphate is tetrasodium pyrophosphate.

[0063] 1.51 The aforementioned composition, wherein the tetrasodium pyrophosphate is 0.1% to 1.0% by weight (e.g., about 0.5% by weight).

[0064] 1.52 Any of the foregoing compositions further comprises abrasives or microparticles (e.g., silicon dioxide).

[0065] 1.53 Any of the foregoing compositions further comprises a nonionic surfactant, wherein the amount of said nonionic surfactant is 0.5% to 5% (e.g., 1% to 2%), selected from poloxamer (e.g., poloxamer 407), polysorbate (e.g., polysorbate 20), polyoxyethylene hydrogenated castor oil (e.g., polyoxyethylene 40 hydrogenated castor oil), and mixtures thereof.

[0066] 1.54 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 includes poloxamer 407.

[0067] 1.55 Any of the foregoing compositions further comprises sorbitol, wherein the total amount of said sorbitol is 10% to 40% (e.g., about 23%).

[0068] 1.56 Any of the foregoing compositions further comprises a zinc ion source selected from zinc oxide, zinc citrate, zinc lactate, zinc phosphate, and combinations thereof.

[0069] 1.57 Any of the foregoing compositions further comprises a zinc ion source consisting of a combination of zinc oxide and zinc citrate or a combination of zinc oxide and zinc citrate.

[0070] 1.58 The aforementioned composition, wherein the ratio of the amount of zinc oxide (e.g., wt%) to the amount of zinc citrate (e.g., wt%) is 1.5:1 to 4.5:1 (e.g., 2:1, 2.5:1, 3:1, 3.5:1 or 4:1).

[0071] 1.59 Either of the first two aforementioned compositions, wherein the amount of zinc citrate is from 0.25% to 1.0% by weight (e.g., 0.5% by weight) based on the weight of the oral care composition, and zinc oxide may be present in an amount from 0.75% to 1.25% by weight (e.g., 1.0% by weight).

[0072] 1.60 Any of the foregoing compositions contains zinc citrate in an amount of about 0.5% by weight.

[0073] 1.61 Any of the foregoing compositions contains zinc oxide in an amount of about 1.0% by weight.

[0074] 1.62 Any of the foregoing compositions further comprises an additional ingredient selected from: benzyl alcohol, methylisothiazolinone (“MIT”), sodium bicarbonate, sodium methyl cocoyl tauranol, lauryl alcohol, and polyphosphate.

[0075] 1.63 Any of the foregoing compositions further comprises a flavoring agent, a fragrance agent, and / or a coloring agent.

[0076] 1.64 Any of the foregoing compositions, wherein the composition further comprises a copolymer.

[0077] 1.65 The aforementioned composition, wherein the copolymer is a PVM / MA copolymer.

[0078] 1.66 The aforementioned composition, wherein the PVM / MA copolymer comprises maleic anhydride or maleic acid in a 1:4 to 4:1 ratio with another polymerizable olefinically unsaturated monomer; for example, a 1:4 to 4:1 ratio, such as about 1:1 copolymer.

[0079] 1.67 The aforementioned composition, wherein the additional polymerizable olefinic unsaturated monomer comprises methyl vinyl ether (methoxyethylene).

[0080] 1.68 Composition 1.50 to 1.52, wherein the PVM / MA copolymer comprises a copolymer of methyl vinyl ether / maleic anhydride, wherein the anhydride is hydrolyzed after copolymerization to yield the corresponding acid.

[0081] 1.69 Composition 1.50 to 1.53, wherein the PVM / MA copolymer comprises polymers (e.g., S-97 polymer).

[0082] 1.70 Any of the foregoing compositions further comprises a thickener selected from: carboxyvinyl polymers, carrageenan, xanthan gum, hydroxyethyl cellulose, and water-soluble salts of cellulose ethers (e.g., sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose).

[0083] 1.71 Any of the foregoing compositions further comprises an additional 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, alexiconidine, or oteninidine), and quaternary ammonium compounds (e.g., hexadecylpyridine chloride). (CPC), benzalkonium chloride, tetradecylpyridine chloride (TPC), N-Tetradecyl-4-ethylpyridine chloride (TDEPC), phenolic preservatives, hexetine, ostinidine, sanguisorbin, povidone-iodine, dimopistol, 5-octanoyl-3'-trifluoromethylphenyl salicylate (salifluor), metal ions (e.g., copper salts, iron salts), sanguisorbin, propolis and oxidizing agents (e.g., hydrogen peroxide, buffered sodium perborate or sodium percarbonate), phthalic acid and its salts, monoperoxyphthalic acid and its salts and esters, ascorbic acid stearate, oleoyl sarcosine, alkyl sulfates / esters, dioctyl sulfosuccinate, salicylaniline, domiphen bromide, dimopistol, octopiol and other piperidinyl derivatives, nicotinic acid preparations, chlorites; and any mixtures of the foregoing.

[0084] 1.72 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.

[0085] 1.73 Any of the foregoing compositions further comprises a whitening agent.

[0086] 1.74 The aforementioned composition, wherein the whitening agent is selected from peroxides, metal chlorites, perborates, percarbonates, peroxy acids, hypochlorites, and combinations thereof.

[0087] 1.75 Any of the foregoing compositions further comprises an agent that interferes with or prevents bacterial attachment, such as ethyl lauroyl arginine (ELA) or chitosan.

[0088] 1.76 Any of the foregoing compositions, wherein the oral composition may be selected from 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.

[0089] 1.77 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 household care preparation, such as a hard surface cleaner, such as a dishwashing liquid, sunscreen, makeup remover, or topical disinfectant.

[0090] 1.78 A composition obtained or obtainable by combining the ingredients described in any one of the foregoing compositions.

[0091] A composition obtained or obtainable by combining any of the ingredients described in the foregoing composition.

[0092] In another embodiment, the invention covers a method for improving oral health, the method 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:

[0093] i. Reduce or inhibit the formation of tooth decay,

[0094] ii. To reduce, repair, or inhibit early enamel damage, for example, as detected by quantitative light-induced fluorescence (QLF) or electrical caries measurement (ECM).

[0095] iii. Reduces or inhibits tooth demineralization and promotes tooth remineralization.

[0096] iv. Reduce the hypersensitivity of the teeth,

[0097] v. To reduce or suppress gingivitis

[0098] vi. To promote the healing of ulcers or wounds in the mouth.

[0099] vii. Inhibit the formation of the oral microbial biofilm.

[0100] viii. After the sugar challenge, raise and / or maintain the pH of the plaque at a level of at least pH 5.5.

[0101] ix. Reduce plaque buildup.

[0102] x. Treatment for dry mouth,

[0103] xi. Enhance overall health, including cardiovascular health, for example by reducing the potential for systemic infections originating from oral tissues.

[0104] xii. Teeth whitening

[0105] xiii. Reduce the erosion of the teeth.

[0106] xiv. To make the teeth immune (or protect) against cariogenic bacteria and their effects, and / or

[0107] or

[0108] xv. Clean the teeth and the oral cavity.

[0109] As used herein, the term "tertiary amine" refers to a compound containing at least one amine in which a nitrogen atom is directly bonded to three carbon atoms of any hybridization other than a carbonyl carbon. Tertiary amine can also be used to refer to compounds containing a plurality of tertiary amine groups (i.e., tertiary polyamines). In particular, tertiary amines are contemplated to be salts with added acids or may not be salts with added acids (e.g., hydrochloride salts and hydrofluoride salts). Hydrofluoride derivatives of tertiary amines are referred to as "fluorinated amines." In methods for producing or manufacturing compositions containing fluorinated amines, tertiary amines can be precursors for the formation of fluorinated amines.

[0110] basic amino acids

[0111] The basic amino acids that can be used in the compositions and methods of the present invention include not only naturally occurring basic amino acids such as arginine, but also any basic amino acids having a carboxyl group and an amino group in their molecules, said basic amino acids being water-soluble and provided in an aqueous solution with a pH of 7 or greater.

[0112] Therefore, basic amino acids include, but are not limited to, arginine, serine, citrulline, ornithine, creatine, diaminobutyric acid, diaminopropionic acid, their salts, or combinations thereof. In one particular embodiment, the basic amino acid is selected from arginine, citrulline, and ornithine.

[0113] In some embodiments, the basic amino acid is arginine, such as L-arginine or a salt thereof.

[0114] The compositions of the present invention are intended for topical use in the mouth, and therefore the salts used in the present invention should be safe for such use at the provided amounts and concentrations. Suitable salts include salts of pharmaceutically acceptable salts known in the art, which are generally considered physiologically acceptable at the provided amounts and concentrations. Physiologically acceptable salts include those derived from pharmaceutically acceptable inorganic or organic acids or inorganic or organic bases, such as salts of added acids formed by acids that form physiologically acceptable anions, such as hydrochloride or bromide salts, and salts of added bases formed by bases that form physiologically acceptable cations, such as those derived from alkali metals such as potassium and sodium or alkaline earth metals such as calcium and magnesium. Physiologically acceptable salts can be obtained using standard processes known in the art, for example by reacting a sufficiently basic compound, such as an amine, with a suitable acid that provides a physiologically acceptable anion.

[0115] Fluoride ion source

[0116] Oral care compositions may also contain one or more fluoride ion sources, such as soluble fluoride salts. Various fluoride-generating materials can be used as soluble fluoride sources in the compositions of the present invention. Examples of suitable fluoride-generating materials 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 the present invention (e.g., composition 1.0 and below, etc.) include, but are not limited to, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, and combinations thereof. In some embodiments, the fluoride ion source includes sodium fluoride, sodium monofluorophosphate, and mixtures thereof. In the case where the formulation contains a calcium salt, the fluoride salt is preferably a salt in which the fluoride is covalently bonded to another atom, such as in sodium monofluorophosphate, rather than merely ionicly bonded, such as in sodium fluoride.

[0117] surfactants

[0118] In some embodiments of the present invention (e.g., composition 1.0 and compositions thereof), anionic surfactants may be included, such as water-soluble salts of monoglycerides of higher fatty acids, such as sodium salts of monosulfated monoglycerides of hydrogenated coconut oil fatty acids, such as sodium N-methyl-N-cocoyl taurate or sodium cocoyl monoglyceride sulfate; higher alkyl sulfates, such as sodium lauryl sulfate; and higher alkyl ether sulfates, such as those of the formula CH3(CH2). m CH2(OCH2CH2) n OS03X, where m is 6 to 16, for example 10, n is 1 to 6, for example 2, 3 or 4, and X is Na, or for example sodium lauryl ether-2-sulfate (CH3(CH2)). 10 CH2(OCH2CH2)2OSO3Na); higher alkyl aryl sulfonates, such as sodium dodecylbenzenesulfonate (sodium laurylbenzenesulfonate); higher alkyl sulfonates, such as sodium lauryl sulfonate (sodium dodecyl sulfonate), higher fatty acid esters of 1,2-dihydroxypropane sulfonate, sulfocolaurate (N-2-ethyllaurate potassium sulfoacetamide), and sodium lauryl sarcosinate. "Higher alkyl" means, for example, C 6-3 O-alkyl. In a particular embodiment, the anionic surfactant (when present) is selected from sodium lauryl sulfate and sodium lauryl ether sulfate. When present, the anionic surfactant is present in an effective amount (e.g., greater than 0.001 wt% of the formulation), but not at a concentration that would irritate oral tissues (e.g., 1%), and the optimal concentration depends on the specific formulation and the specific surfactant. In one embodiment, the anionic surfactant is present from 0.03 wt% to 5 wt% (e.g., 1.5 wt%).

[0119] In another embodiment, the cationic surfactant used in this invention can be broadly defined as a derivative of an aliphatic quaternary ammonium compound having a long alkyl chain containing 8 to 18 carbon atoms, such as lauryltrimethylammonium chloride or cetylpyridine chloride. Cetyltrimethylammonium bromide, diisobutylphenoxyethyl dimethylbenzylammonium chloride, nitrite coconutylalkyltrimethylammonium, fluorinated cetylpyridine and mixtures thereof. Exemplary cationic surfactants are quaternary ammonium fluorides as described in U.S. Patent No. 3,535,421 to Briner et al., which is incorporated herein by reference. Some cationic surfactants may also act as bactericides in compositions.

[0120] Composition 1.0 and exemplary nonionic surfactants that can be used in the compositions of the present invention, and the like, can be broadly defined as compounds produced by condensing an oxidized alkenyl group (which is inherently hydrophilic) with an organic hydrophobic compound that can be inherently aliphatic or alkyl aromatic compounds. Examples of suitable nonionic surfactants include, but are not limited to, pluronics, polyoxyethylene 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 particular embodiment, the compositions of the present invention comprise a nonionic surfactant selected from poloxamer (e.g., poloxamer 407), polysorbates (e.g., polysorbate 20), polyoxyethylene hydrogenated castor oil (e.g., polyoxyethylene 40 hydrogenated castor oil), betaine (e.g., cocamidopropyl betaine), and mixtures thereof.

[0121] Composition 1.0, which can be used in the compositions of the present invention, and exemplary amphoteric surfactants such as the following 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 comprises about 8 to 18 carbon atoms and another comprises anionic water-solubilizing groups (e.g., carboxyl, sulfonate, sulfate, phosphate, or phosphonate); and mixtures of such materials.

[0122] The surfactant or mixture of compatible surfactants may be present in the composition of the invention 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.

[0123] Flavoring agents

[0124] The oral care compositions of the present invention may also contain flavoring agents. Flavoring agents used in the practice of the present invention include, but are not limited to, essential oils and various flavor aldehydes, esters, alcohols and similar materials, 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 employ peppermint and spearmint oils.

[0125] The flavoring agent is incorporated into the oral composition at a concentration of 0.01% to 1% by weight.

[0126] Chelating agents and anti-tartar agents

[0127] The oral care composition of the present invention may also contain one or more chelating agents capable of complexing calcium present in bacterial cell walls. This calcium binding weakens the bacterial cell walls and enhances bacterial lysis.

[0128] Another group of reagents suitable for use as chelating agents and anti-tartar agents in the present invention are soluble pyrophosphates. The pyrophosphates used in the compositions of the present invention can be any of the alkali metal pyrophosphates. In some embodiments, the salts include tetraalkali metal pyrophosphates, dialkali metal dihydrogen pyrophosphates, trialkali metal monohydrogen pyrophosphates, and mixtures thereof, wherein the alkali metal is sodium or potassium. The salts are useful in both their hydrated and unhydrated 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% to 5% 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 the activity of water.

[0129] polymer

[0130] The oral care compositions of the present invention optionally also comprise one or more polymers, such as polyethylene glycol, polyethylene methyl ether maleic acid copolymers, polysaccharides (e.g., cellulose derivatives, such as carboxymethyl cellulose; or polysaccharide gums, such as xanthan gum or carrageenan). Acidic polymers (e.g., polyacrylate gels) may be provided in the form of their free acid or partially or completely neutralized water-soluble alkali metals (e.g., potassium and sodium) or ammonium salts. Some embodiments comprise maleic anhydride or maleic acid in a 1:4 to 4:1 copolymer 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, as GAF Chemicals' Gantrez AN 139 (MW 500,000), AN 1 19 (MW 250,000), and S-97 pharmaceutical grade (MW 70,000).

[0131] Other active polymers include 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 those of acrylic acid with methyl methacrylate or hydroxyethyl methacrylate, methyl acrylate or ethyl acrylate, isobutyl vinyl ether, or N-vinyl-2-pyrrolidone.

[0132] 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 that readily functions in polymerization due to its presence in the monomer molecule 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, ethylacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloyloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid, β-styrylacrylic acid, mucilage acid, itaconic acid, citraconic acid, mesocarboxylic acid, pentenepic acid, aconitic acid, α-phenylacrylic acid, 2-phenylmethylacrylic acid, 2-cyclohexylacrylic acid, angelic acid, umbelliferous acid, fumaric acid, maleic acid, and acid anhydrides. Other different olefinic monomers that can copolymerize with such carboxylic acid monomers include vinyl acetate, vinyl chloride, dimethyl maleate, etc. The copolymer contains a sufficient number of carboxyl groups for water solubility.

[0133] 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 an unsaturated sulfonic acid based on an acrylamide-alkyl sulfonic acid (e.g., 2-acrylamide-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, issued June 27, 1989, which is incorporated herein by reference.

[0134] Another class of available polymerizers includes polyamino acids, particularly those containing proportionate amounts 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.

[0135] In the preparation of oral care compositions, it is sometimes necessary to add thickening materials to provide a desired consistency or to stabilize or improve the performance of the formulation. In some embodiments, the thickener is a carboxyvinyl polymer, carrageenan, xanthan gum, hydroxyethyl cellulose, and water-soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums, such as gum arabic, gum arabic, and astragalus gum, may also be incorporated. Colloidal magnesium aluminum silicate or finely crushed 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.

[0136] abrasive

[0137] Natural calcium carbonate is found in rocks such as chalk, limestone, marble, and travertine. It is also a major component of eggshells and mollusk shells. The natural calcium carbonate abrasive of the present invention is typically finely ground limestone, which may optionally be refined or partially refined to remove impurities. For use in the present invention, the material has an average particle size of less than 10 micrometers, for example, 3 to 7 micrometers, such as about 5.5 micrometers. For example, small-particle silica can have an average particle size (D50) of 2.5 to 4.5 micrometers. Since natural calcium carbonate can contain a high proportion of relatively large, uncontrolled particles, which can unacceptably increase abrasiveness, preferably no more than 0.01% by weight, preferably no more than 0.004% by weight, of particles will not pass through a 325-mesh sieve. The material has a strong crystalline structure and is therefore much harder and more abrasive than precipitated calcium carbonate. The tap density of natural calcium carbonate is, for example, 1 g / cc to 1.5 g / cc, such as about 1.2 g / cc, such as about 1.19 g / cc. Natural calcium carbonate exists in various polymorphs, such as calcite, aragonite, and spherulite, with calcite being preferred for the purposes of this invention. Examples of commercially available products suitable for use in this invention include those from GMZ. 25-11FG.

[0138] Precipitated calcium carbonate is typically prepared by calcining limestone to produce calcium oxide (lime), which can then be converted back to calcium carbonate by reacting with carbon dioxide in water. Precipitated calcium carbonate has a different crystal structure than natural calcium carbonate. It is generally more brittle and porous, thus exhibiting lower abrasiveness and higher water absorption. For use in this invention, the particles are small, for example, having an average particle size of 1 to 5 micrometers, and, for example, no more than 0.1% by weight, preferably no more than 0.05% by weight, of the particles will not pass through a 325-mesh sieve. The particles may, for example, have a D50 of 3 to 6 micrometers, for example 3.8 = 4.9, for example about 4.3; 1 to 4 micrometers, for example 2.2 to 2.6 micrometers, for example about 2.4 micrometers; and 1 to 2 micrometers, for example 1.2 to 1.4, for example about 1.3 micrometers. The particles have relatively high water absorption, for example at least 25 g / 100g, for example 30 g / 100g to 70 g / 100g. Examples of commercially available products suitable for use in this invention include, for example, those from LagosIndustria Quimica. 15Plus.

[0139] In some embodiments, the present invention may include additional calcium-containing abrasives, such as calcium phosphate abrasives, such as tricalcium phosphate (Ca3(PO4)2) and hydroxyapatite (Ca2PO4). 10(PO4)6(OH)2) or dicalcium phosphate dihydrate (CaHPO4·2H2O, sometimes referred to herein as DiCal) or calcium pyrophosphate, and / or 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 obtained as a thickener, such as particulate silica. For example, silica may also be small particulate silica (e.g., Sorbosil AC43 from PQ Corporation, Warrington, United Kingdom). However, this additional abrasive is preferably not present in a type or amount that increases the RDA of the dental cleaning agent to levels that could potentially damage sensitive teeth (e.g., greater than 130).

[0140] water

[0141] Water is present in the oral compositions of the present invention. 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 45% by weight of the oral composition, for example 10% to 20%, for example 25% to 35%. This amount of water includes the added free water plus the amount introduced with other materials such as sorbitol or silica or any component of the present invention. The Karl Fischer method is one measure for calculating free water.

[0142] Moisturizer

[0143] 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 15% to 70% by weight of the composition in one embodiment or 30% to 65% in another embodiment.

[0144] 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 in certain embodiments as a humectant component of the compositions described herein.

[0145] pH adjuster

[0146] 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, trisodium dehydrated 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 5 to about 9, preferably about 6 to about 8, and more preferably about 7. The typical amount of buffer by weight of the total composition is about 5% to about 35%, in one embodiment about 10% to about 30%, and in another embodiment about 15% to about 25%.

[0147] The present invention relates, in its method aspect, to applying a safe and effective amount of the composition described herein to the oral cavity.

[0148] The compositions and methods according to the invention (e.g., composition 1.0 and the like below) can be incorporated into oral compositions for mouth and teeth care, such as toothpaste, clear paste, gel, mouthwash, spray and chewing gum.

[0149] The ranges used throughout are used as a concise way to describe the individual values ​​within that range and each value. Any value within the 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 definitions 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 prepared, stored, and used, and such products are intended to be covered by said formulation.

[0150] The following examples further describe and demonstrate exemplary embodiments within the scope of the present invention. The examples are given for illustrative purposes only and should not be construed as limiting the invention, as many variations can be made without departing from its spirit and scope. Various modifications to the invention 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.

[0151] The method of this public content

[0152] In another aspect, the present invention is a method for manufacturing an oral care or personal care composition [Method 1], comprising the steps of: mixing a tertiary amine (e.g., fluorinated amine) in water; and increasing the solubility of said tertiary amine by adding an effective amount of an alkali metal salt. For example, the present invention conceives of any of the following compositions (unless otherwise stated, values ​​are given as a percentage of the total weight of the composition).

[0153] 1.1 Method 1, wherein the step of mixing the tertiary amine in water further includes mixing an acid (e.g., an organic acid and / or an inorganic acid).

[0154] 1.2 The aforementioned method, wherein the acid is lactic acid, citric acid, tartaric acid, fumaric acid, malic acid or hydrochloric acid.

[0155] 1.3 The aforementioned method, wherein the acid is hydrochloric acid.

[0156] 1.4 Any of the foregoing methods, wherein the step of mixing the tertiary amine in water further includes mixing a fluoride source.

[0157] 1.5 Any of the foregoing methods, wherein the solubility of the tertiary amine is increased by at least 25%.

[0158] 1.6 Any of the foregoing methods, wherein the solubility of the tertiary amine is increased by at least 30%.

[0159] 1.7 Any of the foregoing methods, wherein the solubility of the tertiary amine is increased by at least 40%.

[0160] 1.8 Any of the foregoing methods, wherein the solubility of the tertiary amine is increased by at least 50%.

[0161] 1.9 Any of the foregoing methods, wherein the solubility of the tertiary amine is increased by at least 60%.

[0162] 1.10 Any of the foregoing methods, wherein the solubility of the tertiary amine is increased by at least 70%.

[0163] 1.11 Any of the foregoing methods, wherein the solubility of the tertiary amine is increased by at least 80%.

[0164] 1.12 Composition 1, wherein the tertiary amine comprises a tertiary polyamine or a fluorinated amine.

[0165] 1.13 Any of the foregoing compositions, wherein the tertiary amine comprises one or more of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol), N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride (oraflu), N-octadec-9-enylamine hydrofluoride (diketofur), and / or N-octadec-9-enylamine.

[0166] 1.14 Any of the foregoing compositions, wherein the tertiary amine is a tertiary polyamine.

[0167] 1.15 Any of the foregoing compositions, wherein the tertiary amine comprises at least one of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol) and N-octadec-9-enylamine.

[0168] 1.16 Any of the foregoing compositions, wherein the tertiary amine comprises N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol) or is composed of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol).

[0169] 1.17 Any of the foregoing compositions, wherein the tertiary amine comprises a fluorinated amine (e.g., octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride, N-octadec-9-enylamine hydrofluoride).

[0170] 1.18 Any of the foregoing methods, wherein the tertiary amine is present in the resulting mixture in an amount of about 10% by weight to about 80% by weight, based on the total weight of the composition.

[0171] 1.19 Any of the foregoing methods, wherein the tertiary amine is present in the resulting mixture in an amount of about 20% to about 70% by weight, based on the total weight of the composition.

[0172] 1.20 Any of the foregoing methods, wherein the tertiary amine is present in the resulting mixture in an amount of about 20% to about 40% by weight, based on the total weight of the composition.

[0173] 1.21 Any of the foregoing methods, wherein the tertiary amine is present in the resulting mixture in an amount of about 25% to about 35% by weight, based on the total weight of the composition.

[0174] 1.22 Any of the foregoing methods, wherein the alkali metal salt is an alkali metal halide or an alkali metal salt of an organic acid.

[0175] 1.23 Any of the foregoing methods, wherein the alkali metal salt is an alkali metal halide.

[0176] 1.24 Any of the foregoing methods, wherein the alkali metal salt is a sodium halide or a potassium halide.

[0177] 1.25 Any of the foregoing methods, wherein the alkali metal salt is sodium chloride or potassium chloride.

[0178] 1.26 Any of the methods described above, wherein the alkali metal salt is sodium chloride.

[0179] 1.27 Any of the foregoing methods, wherein the alkali metal salt is an alkali metal salt of an organic acid.

[0180] 1.28 Any of the methods described above, wherein the alkali metal salt is trisodium citrate.

[0181] 1.29 Any of the methods described above, wherein the alkali metal salt is trisodium citrate dihydrate.

[0182] 1.30 Any of the foregoing methods, wherein the alkali metal salt is present in the resulting mixture in an amount of about 0.01% by weight to about 15% by weight, based on the total weight of the composition.

[0183] 1.31 Any of the foregoing methods, wherein the alkali metal salt is present in the resulting mixture in an amount of about 0.05% by weight to about 5% by weight, based on the total weight of the composition.

[0184] 1.32 Any of the foregoing methods, wherein the alkali metal salt is present in the resulting mixture in an amount of about 1% to about 2.5% by weight, based on the total weight of the composition.

[0185] 1.33 Any of the foregoing methods, wherein, based on the total weight of the composition, the alkali metal salt comprises sodium chloride present in an amount of about 1.0 wt% to about 2.0 wt%, or is composed of sodium chloride present in an amount of about 1.0 wt% to about 2.0 wt%.

[0186] 1.34 Any of the foregoing methods, wherein, based on the total weight of the composition, the alkali metal salt comprises potassium chloride present in an amount of about 1.0 wt% to about 2.5 wt%, for example, about 1.0 wt% to about 2.0 wt%, or is composed of potassium chloride present in an amount of about 1.0 wt% to about 2.5 wt%, for example, about 1.0 wt% to about 2.0 wt%.

[0187] 1.35 Any of the foregoing methods, wherein, based on the total weight of the composition, the alkali metal salt comprises trisodium citrate dihydrate present in an amount of about 1.0 wt% to about 4.0 wt%, for example, about 1.0 wt% to about 3.5 wt%, or consists of trisodium citrate dihydrate present in an amount of about 1.0 wt% to about 4.0 wt%, for example, about 1.0 wt% to about 3.5 wt%.

[0188] 1.36 Any of the foregoing methods, wherein the composition is an aqueous solution.

[0189] 1.37 Any of the foregoing methods, wherein the composition is an oral care composition.

[0190] 1.38 Any of the foregoing methods, wherein the composition is in the form of mouthwash or dental cleaning agent.

[0191] In another aspect, this disclosure relates to compositions (e.g., composition 1 or composition 1.1 and so on) obtained or obtainable by the methods described above (e.g., method 1 or method 1.1 and so on).

[0192] Example

[0193] Example 1 - Effect of Alkali Metal Salts on the Solubility of Amine Fluoride in Solution

[0194] A test solution containing fluorinated amine (N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride) and water was prepared. The fluorinated amine was added in increasing amounts to determine its saturation concentration, as shown in Table 1A below. All values ​​reported in the table below are by weight percentage.

[0195] Table 1A: Solubility characteristics of amine fluoride in water in the absence of additional inorganic salts

[0196]

[0197] Therefore, the maximum solubility of fluorinated amine in water was determined to be approximately 24% by weight, which corresponds to a concentration of approximately 440 mM tertiary amine when the fluorinated amine is completely separated from the hydrofluoride.

[0198] Similar formulations containing one or more alkali metal salts selected from sodium chloride, potassium chloride, and trisodium citrate dihydrate were also prepared to investigate the effect of the presence of salts on the solubility of fluorinated amines. The results are summarized in Table 1B below.

[0199] Table 1B: Solubility characteristics of amine fluoride in water with the addition of alkali metal salts

[0200]

[0201]

[0202] When sodium chloride is added, it is shown that the addition of an alkali metal salt increases the solubility of fluorinated amines in water by slightly more than 35% by weight (i.e., corresponding to a tertiary amine concentration of about 640 mM), as demonstrated with composition 10. Sodium chloride concentrations as low as about 0.7% are shown to increase the solubility of fluorinated amines in water. Similar effects were observed with potassium chloride and trisodium citrate. On the other hand, a 2.5% concentration of sodium chloride did not increase the solubility of fluorinated amines, as determined in composition 8, and caused incomplete dissolution of the formulation component.

[0203] Example 2 - Effect of Alkali Metal Salts on the Solubility of Tertiary Amines in Solution

[0204] Compositions similar to those listed in Table 1A were produced, but using tertiary amines instead of fluorinated amines. Without pH adjustment, the solubility of the tertiary amine in water was shown to be approximately 70% by weight (approximately 1520 mM tertiary amine). However, when hydrochloric acid was added to the solution at a concentration calculated corresponding to the level of hydrated hydrogen ions present in an equivalent amount of fluorinated amine (compositions 21 to 23), the solubility of the tertiary amine became slightly greater than 24%, corresponding to a concentration of approximately 530 mM. The results are summarized below in Table 2A.

[0205] Table 2A: Solubility properties of tertiary amines without the addition of inorganic salts

[0206]

[0207] Another composition containing a tertiary amine and hydrochloric acid was produced. Different amounts of alkali metal salts were added to these solutions to evaluate their effect on the solubility of the tertiary amine. The results are summarized in Table 2B below.

[0208] Table 2B: Solubility properties of tertiary amines with the addition of inorganic salts

[0209]

[0210]

[0211] When hydrochloric acid is added to a tertiary amine solution at a concentration corresponding to the level of hydrated hydrogen ions present in an equal volume of fluorinated amine, and an alkali metal salt is additionally added, the solubility of the tertiary amine in water increases to approximately 40% by weight (approximately 870 mM tertiary amine), requiring the addition of approximately 5% alkali metal salt to completely dissolve the tertiary amine (composition 34). For complete dissolution of 34% tertiary amine, the minimum amount of sodium chloride added is approximately 1%.

[0212] A new batch of solutions similar to those shown in Table 2B is produced, but with sodium fluoride added.

[0213] Table 2C: Solubility properties of tertiary amines with and without the addition of inorganic salts and sodium fluoride.

[0214]

[0215] When hydrochloric acid and sodium fluoride, along with an additional alkali metal salt, are added to a solution containing a tertiary amine at concentrations corresponding to the levels of hydrated hydrogen ions and fluoride ions present in an equal volume of fluorinated amine, the solubility of the tertiary amine does not increase further compared to the solubility of the tertiary amine (composition 24) without the presence of the additional inorganic salt. Unbound from theoretical constraints, this may be due to the fact that hydrochloric acid and sodium fluoride promote a high loading of the additional ions in the solution, preventing the dissolution of the additional tertiary amine.

[0216] Although the invention has been described with reference to embodiments, those skilled in the art will understand that various modifications and variations may be made therein without departing from the scope of the invention as defined by the appended claims.

Claims

1. A method for manufacturing an oral care composition, comprising the following steps: a. A tertiary amine and an acid are mixed in water to form an aqueous solution, wherein the tertiary amine comprises one or more of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol), N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride, N-octadec-9-enylamine, and / or N-octadec-9-enylamine hydrofluoride; and b. The solubility of the tertiary amine is increased by adding an effective amount of an alkali metal salt to the aqueous solution, wherein the alkali metal salt is sodium chloride, potassium chloride, or trisodium citrate dihydrate, and the alkali metal salt is present in the aqueous solution in an amount of 1% to 2.0% by weight based on the total weight of the composition.

2. A method for manufacturing a personal care composition, comprising the following steps: a. A tertiary amine and an acid are mixed in water to form an aqueous solution, wherein the tertiary amine comprises one or more of N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol), N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol)-dihydrofluoride, N-octadec-9-enylamine, and / or N-octadec-9-enylamine hydrofluoride; and b. The solubility of the tertiary amine is increased by adding an effective amount of an alkali metal salt to the aqueous solution, wherein the alkali metal salt is sodium chloride, potassium chloride, or trisodium citrate dihydrate, and the alkali metal salt is present in the aqueous solution in an amount of 1% to 2.0% by weight based on the total weight of the composition.

3. The method according to claim 1 or 2, wherein the acid is lactic acid, citric acid, tartaric acid, fumaric acid, malic acid, or hydrochloric acid.

4. The method according to claim 3, wherein the acid is hydrochloric acid.

5. The method of claim 4, wherein the hydrochloric acid is present in an amount of 1% to 10% by weight based on the total weight of the composition.

6. The method according to claim 1 or 2, wherein the step of mixing the tertiary amine and the acid in water further comprises mixing a fluoride source.

7. The method according to claim 6, wherein the fluoride source is selected from: sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.

8. The method according to claim 1 or 2, wherein the solubility of the tertiary amine is increased by 25% to 40% compared to the solubility of the tertiary amine before the addition of the alkali metal salt.

9. The method according to claim 1 or 2, wherein the tertiary amine comprises N'-octadecyltrimethylenediamine-N,N,N'-tris(2-ethanol) and / or N-octadec-9-enylamine.

10. The method according to claim 1 or 2, wherein the tertiary amine is present in the aqueous solution in an amount of 10% to 35% by weight, based on the total weight of the composition.

11. The method according to claim 1 or 2, wherein the alkali metal salt is sodium chloride.

12. The method according to claim 1 or 2, wherein the alkali metal salt is potassium chloride.

13. The method according to claim 1 or 2, wherein the alkali metal salt is trisodium citrate dihydrate.

14. The method according to claim 1 or 2, wherein the composition is an aqueous solution.

15. A composition obtained by the method according to any one of claims 1 to 14.

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