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    Summary Aqueous Oral Hygiene Compositions described herein are aqueous oral hygiene compositions comprising (a) an effective amount of a basic amino acid in free form or orally acceptable salt; and (b) a polymer system comprising (i) a cellulosic polymer, (ii) a gum polymer, and (iii) a polyacrylate polymer or copolymer; and methods of preparation and use thereof.
    公开号:BR112014014315B1
    申请号:R112014014315-3
    申请日:2011-12-15
    公开日:2018-07-03
    发明作者:Pimenta Paloma；Miksa Davide；Pilch Shira；Rege Aarti；Sullivan Richard
    申请人:Colgate-Palmolive Company；
    IPC主号:
    专利说明:

    (54) Title: WATER COMPOSITION OF ORAL HYGIENE AND USE OF THE SAME (51) Int.CI .: A61K 8/43; A61K 8/44; A61K 8/73; A61K 8/81; A61K 8/21; A61Q 11/00 (73) Holder (s): COLGATE-PALMOLIVE COMPANY (72) Inventor (s): SHIRA PILCH; PALOMA PEPPER; DAVIDE MIKSA; AARTI REGE; RICHARD SULLIVAN
    1/25
    WATER COMPOSITION OF ORAL HYGIENE AND USE OF THE SAME
    BACKGROUND [001] Conventional mouthwash products may contain antibacterial agents and / or fluoride, but they generally do not prevent or repair acid channels, or improve the release and retention of active agents. Effective protection against such acid attacks on the tooth surface should ideally provide a physical barrier against acid attack, as well as improving the release and retention of an active agent that can neutralize acid and / or reinforce tooth enamel.
    SUMMARY [002] In some embodiments, the present invention provides an aqueous oral hygiene composition comprising an effective amount of a basic amino acid, in the form of a free or orally acceptable salt, and a polymer system comprising (i) a cellulosic polymer , (ii) a gum polymer, and (iii) a polyacrylate polymer or copolymer, for example, where the mouthwash shows (i) a measurable degree of viscoelasticity with an elasticity ratio for viscous components, G '/ G , greater than 0.5 and (ii) The pseudoplasticity behavior with a flow rate index, n, of less than 0.85. In some embodiments, the composition is a viscoelastic mouthwash. In some embodiments, the mouthwash optionally further comprises an effective amount of a fluoride source.
    [003] The high viscoelasticity of the formulation (G '/ G> 0.5) favors the formation of a polymer film on the tooth surface and greater retention of agents
    2/25 active ingredients, such as fluoride, arginine or buffering agents on the enamel surface. The property of pseudoplasticity (n <0.85) further characterizes mouthwash as viscoelastic and non-Newtonian and helps boost consumer acceptability of mouthwash.
    [004] As demonstrated by the following examples, the compositions of the present invention provide better resistance to enamel erosion. Without being limited by theory, it is believed that the use of mucoadhesive polymers in sufficient concentrations for the polymers to significantly overlap and form a solution network results in the deposition of a polymer film on the hard and soft tissues of the oral cavity, in use . This polymer film serves as a physical barrier against erosive acids, as well as a vehicle to improve the release and retention of fluoride and / or basic amino acids, such as arginine on enamel surfaces, which provides superior protection to enamel against erosion. and acid-induced demineralization. In addition, it is believed that the absorption of the basic amino acid, for example, arginine, is enhanced because the basic amino acids such as arginine are positively charged. In the presence of a polymer network that is largely negatively charged, the charge and charge interaction increases the deposition of the basic amino acid to the oral surfaces.
    [005] Other areas of application of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the
    3/25 detailed description and specific examples, while indicating the preferred embodiment of the invention, are for illustrative purposes only and are not intended to limit the scope of the invention.
    DETAILED DESCRIPTION [006] The following description of the preferred embodiment (s) is merely exemplary in nature and is in no way intended to limit the invention, its application or uses.
    [007] Some embodiments of the present invention provide an aqueous oral hygiene composition that comprises an effective amount of a basic amino acid, in free form or orally acceptable salt; a polymer system comprising (i) a cellulosic polymer, (ii) a gum polymer, and (iii) a polyacrylate polymer or copolymer, wherein the composition has a flow rate index of less than 0.85.
    [008] Some modalities still comprise a source of fluoride; where the fluoride source. In some embodiments, the fluoride source is present in an amount effective to provide from about 90 to about 500 ppm of fluoride. In other embodiments, the fluoride source is present in an amount effective to provide about 225 ppm of fluoride.
    [009] In some embodiments, the fluoride source is selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (eg N'octadecyltrimethylendiamine- N, N, N'-tris (2-ethanol) 4/25 difluorohydrate), ammonium fluoride, titanium fluoride, hexafluorosulfate, and a combination of two or more of them.
    [010] In some embodiments, the source of fluoride is selected from sodium fluoride, sodium monofluorophosphate, and a combination thereof. In other embodiments, the fluoride source comprises sodium fluoride.
    [011] In some embodiments, the basic amino acid is composed of L-arginine in the free form or an orally acceptable salt. In some embodiments, the basic amino acid is selected from an arginine-free base, arginine hydrochloride, arginine phosphate, arginine bicarbonate, and combinations thereof. In some embodiments, the effective amount of the basic amino acid in free form or orally acceptable salt comprises 0.05 to 2% by weight of the formulation (measured as the equivalent free base weight, when in orally acceptable salt form).
    [012] Some modalities also include a buffering agent. In some embodiments, the buffering agent is a sodium phosphate buffer (for example, monobasic sodium phosphate and disodium phosphate).
    [013] Other modalities also include a humectant, for example, selected from glycerin, sorbitol, propylene glycol, and a combination of two or more of them.
    [014] In still other embodiments, they still comprise an antibacterial agent, for example, triclosan or cetylpyridinium chloride.
    [015] The composition of any of the claims
    5/25 above in which the cellulosic polymer is selected from a hydroxyalkyl methyl cellulose, a carboxyalkyl methyl cellulose, a hydroxyalkyl cellulose, an alkyl cellulose, a carboxyalkyl cellulose, and a combination of two or more of the same.
    [016] Some modalities provide an aqueous oral hygiene composition containing: between about 0.5% to about 2% by weight, of a basic amino acid, in free form or orally acceptable salt, a polymer system comprising ( i) a cellulosic polymer, (ii) a gum polymer, and (iii) a polyacrylate copolymer polymer; and from about 0.01 to about 0.5% by weight, of a fluoride source; wherein the composition has a flow rate index of less than 0.85; and wherein the composition releases an amount of fluoride effective to provide a step height difference of less than 0.25 microns when evaluated using the Hooper protocol.
    [017] In some embodiments, the fluoride source is present in an amount of about 0.02% to about 0.2% by weight, of the composition. In some embodiments, the fluoride source is present in an amount of about 0.03% to about 0.08% by weight, of the composition. Other embodiments provide a composition in which the fluoride source is present in the amount of about 0.05% by weight of the composition. In some embodiments, the fluoride source is present in the amount of 0.5% by weight of the composition.
    [018] Some embodiments of the present invention provide a method of reducing dental enamel erosion comprising administering any of the compositions described herein to the oral cavity of the tooth.
    6/25 individual with this need. In some embodiments, administration involves rinsing for about 15 to about 60 seconds. In some embodiments, administration involves rinsing for about 30 seconds.
    [019] Some embodiments of the present invention therefore provide a viscoelastic mouthwash (mouthwash 1) comprising (a) an effective amount of a basic amino acid in free form or an orally acceptable salt and (b) a polymer system comprising (i) a cellulosic polymer, (ii) a gum polymer, and (iii) a polyacrylate polymer or copolymer.
    [020] In some embodiments, the cellulosic polymer is selected from hydroxyalkyl methyl cellulose (such as hydroxypropyl methyl cellulose, hydroxybutyl methyl cellulose, hydroxyethyl methyl cellulose, hydroxymethyl methyl cellulose and hydroxyethylpropyl methyl cellulose); carboxyalkyl methyl celluloses (such as carboxypropyl methyl cellulose, carboxybutyl methyl cellulose, carboxyethyl methyl cellulose, carboxy methyl cellulose and carboxyethylpropyl methyl cellulose); hydroxyalkyl celluloses (such as hydroxypropyl cellulose, hydroxybutyl cellulose, hydroxyethyl cellulose, hydroxymethyl cellulose and hydroxyethylpropyl cellulose); alkyl celluloses (such as propyl cellulose, butyl cellulose, ethyl cellulose, methyl cellulose); carboxyalkyl celluloses (such as carboxypropyl cellulose, carboxybutyl cellulose, carboxyethyl cellulose, carboxymethyl cellulose and carboxyethylpropyl cellulose), and combinations thereof.
    [021] In some embodiments, the cellulosic polymer comprises carboxymethyl cellulose.
    [022] In some modalities, the polymer is selected
    7/25 from carrageenan gum, xanthan gum, and their combinations. In some embodiments, the gum polymer comprises xanthan gum. In some embodiments, the polyacrylate polymer or copolymer is a carbomer. In some embodiments, the polyacrylate polymer or copolymer is selected from homo- and copolymers of acrylic acid cross-linked with a polyalkenyl polyether.
    [023] In some embodiments, the compositions comprise the ingredients in the concentration ranges provided in Table 1 (below).
    Table 1
    Ingredient Variation of conc.% weight / weight Water 50.0-90.0 Humectants 1.0-25.0 Surfactant 0.01-10.0 Monobasic sodium phosphate 0.01-5.0 Disodium phosphate 0.01-5.0 Preservative 0.01-1.0 Flavor 0.01-1.0 Cellulosic polymer 0.01-0.5 Gum polymer 0.01-0.5 Polymer or copolymer ofpolyacrylate 0.01-0.5 Sodium fluoride 0-0.05 Arginine (in free or salt form,weight of the free base) 0.05-2.0 Sweetener 0.001-0.5 Cetylpyridinium chloride 0.001-1.0
    8/25 [024] The viscoelastic formulations of mouthwash are described in the following copending patent applications PCT / US2010 / 061962, PCT / US2010 / 061956, and PCT / US2010 / 061959, all filed on December 23, 2010, the contents of which are incorporated herein by reference in their entirety.
    [025] The compositions of the present invention are carefully adapted with the appropriate combination and concentration of polymers to form a low viscosity viscoelastic aqueous solution that has unique rheology, but still resembles the fluidity of a typical mouthwash.
    [026] As used herein, the term viscoelastic fluid refers to a complex fluid that has mechanical properties that are both elastic (solid type, for example, rubber) and viscous (similar to liquid, flowable, for example, water) . The composition of the viscoelastic fluid deforms and flows under the influence of an applied shear stress (eg, shaking or swinging in the mouth), but when the stress is removed the composition will recover from deformation. The elastic part of the viscoelastic behavior is quantified by the modulus of elasticity (G '), while the viscous portion is quantified by the viscous modulus (G).
    [027] As used herein, the term pseudoplastic refers to a property in which viscosity decreases with increasing shear stress rate. Materials that exhibit pseudoplasticity properties are called pseudoplastics.
    [028] As used herein, structured fluid and
    9/25 structured composition can be used interchangeably, and refer to a fluid that has a G 'value greater than the G value (that is, the ratio of G' to G is> 0.5) within the linear viscoelastic region of a voltage sweep measurement. The ratio of G 'to G was identified as the structural parameter.
    [029] The basic amino acids that can be used in the compositions of the present invention include not only the naturally occurring basic amino acids, such as arginine, lysine and histidine, but also all the basic amino acids having a carboxyl group and an amino group in the molecule. Consequently, basic amino acids include, but are not limited to, arginine, lysine, citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminoproprionic acid, their salts or combinations thereof. In a particular embodiment, the basic amino acids are selected from arginine, citrulline, and ornithine, preferably arginine, for example, L-arginine.
    [030] The compositions of the invention are intended for topical use in the mouth and so the salts for use in the present invention must be orally acceptable, that is, safe for topical use in the mouth, in anticipated quantities and concentrations. Suitable salts include salts known in the art to be pharmaceutically acceptable salts, which are generally considered to be orally acceptable for that purpose in anticipated amounts and concentrations. Orally acceptable salts include those derived from pharmaceutically acceptable inorganic or organic acids or bases, for example, addition salts
    10/25 acid formed by acids that form a physiologically acceptable anion, for example, hydrochloride salt, and base addition salts formed by bases that form a physiologically acceptable cation, for example, alkali metal derivatives such as potassium and sodium or alkaline earth metals, such as calcium and magnesium. Physiologically acceptable salts can be obtained using standard procedures known in the art, for example, by reacting a sufficiently basic compound such as an amine with a suitable acid to obtain a physiologically acceptable anion.
    [031] In some embodiments, the compositions additionally comprise one or more components selected from a fluoride ion source, a tartar control agent, a buffering agent, an abrasive, and a combination of two or more of the same. In some embodiments, at least one of the one or more components of a fluoride ion source selected from: stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride , ammonium fluoride, and a combination of two or more of them.
    [032] The high molecular weight synthetic polymers of acrylic acid known as carbomers can be cross-linked acrylic acid homopolymers with a pentaerythritol allyl, sucrose allyl or propylene allyl ether. Carbomer has a USP classification of Type A carbomer homopolymer. Carbomers have the ability to adsorb, retain water and
    11/25 often swell to its original volume. Carbomer codes (910, 934, 940, 941, 971, 974 and 934P) are an indication of molecular weight and the specific components of the polymer. Carbomers are commercially available under the trade name Carbopol® from Lubrizol and other companies.
    [033] Humectants useful for this invention include polyhydric alcohols, such as glycerin, sorbitol, xylitol or low molecular weight PEGs, alkylene glycol such as polyethylene glycol or propylene glycol. In various embodiments, humectants are operable to prevent hardening of the paste or gel compositions with exposure to air. In various modalities, humectants also function as sweeteners. In some embodiments, the humectant is present in an amount of about 1 to about 40% by weight, each. In some embodiments, the humectant is sorbitol. In some embodiments, sorbitol is present in a concentration of about 5 to about 25% by weight. In some modalities, sorbitol present in a
    concentration in fence in 5 to about 15% by weight. In some modalities, O sorbitol is present in concentration in fence in 10% by weight. Reference to sorbitol here if refers to normally available material
    commercially as in 70% aqueous solutions. In some embodiments, the total concentration of humectant ranges from about 1 to about 60% by weight. In some embodiments, the humectant is glycerin. In some embodiments, glycerin is present in a concentration of about 5 to about 15% by weight. In some embodiments, the glycerin present is in a concentration of about 7.5% by weight.
    12/25
    In some embodiments, the humectant is propylene glycol. In some embodiments, propylene glycol is present in a concentration of about 5 to about 15% by weight. In some embodiments, propylene glycol is present in a concentration of about 7% by weight.
    [034] Some modalities provide a composition in which a preservative is present. In some embodiments, the preservative is selected from parabens, potassium sorbate, benzyl alcohol, phenoxyethanol, polyaminopropril biguanide, caprylic acid, sodium benzoate and cetylpyridinium chloride. In some embodiments, the preservative is present in a concentration of about 0.0001 to about 1% by weight. In some embodiments, the preservative is present in a concentration of about 0.01 to about 1% by weight. In some embodiments, the preservative is present in a concentration of about 0.5% by weight.
    [035] Dyes such as dyes can be color additives to foods currently certified under the Food Drug & Cosmetic Act for use in ingested foods and medicines, including dyes like FD & C Red No. 3 (tetraiodofluorescein sodium salt), Food Red 17, disodium salt of 6-hydroxy-5 - {(2-methoxy-5-methyl-4-sulfophenyl) azo} 2-naphthalenesulfonic acid, Food Yellow 13, sodium salt of a mixture of quinophthalone mono and disulfonic acids or 2- (2-quinolyl) indanedione, FD & C Yellow No. 5 (sodium salt of 4-p-sulfophenylazo-lp-sulfophenyl-5hydroxypyrazole-3 carboxylic acid), FD & C Yellow No. 6 (sodium salt p-sulfophenylazo-B-naphthol-6-monosulfonate), FD & C Green No. 3 (disodium salt of 4 - {[4 - (N-ethyl-p13 / 25 sulfobenzylamino) -phenyl] - (4-hydroxy- 2-sulfonium phenyl) methylene} - [1- (N-ethyl-Np-sulfobenzyl) -. DELTA.-3,5-cyclohexadienimine], FD & C Blue No. 1 (disodium dibenzyldiethyl-diamino-anhydride salt) triphenylcarbinol trisulfonic), FD & C Blue No. 2 (salt of only indigotine disulfonic acid) and mixtures of these compounds in various proportions. Typically, colorants if included are present in very small amounts.
    [036] Flavoring agents are known, for example, natural and artificial flavors. These flavorings can be chosen from synthetic and aromatic flavoring oils, and / or oils, oil resins and extracts derived from plants, leaves, flowers, fruits and so on, and their combinations. Representative flavoring oils include: peppermint oil, cinnamon oil, peppermint oil, clove oil, bay oil, thyme oil, cedar leaf oil, nutmeg oil, sage oil, and bitter almonds. These flavoring agents can be used individually or in a mixture. The commonly used flavors include mints, such as peppermint, artificial vanilla, cinnamon derivatives, and various fruit flavors, whether used individually or in a mixture. Generally, any flavoring or food additive, such as those described in Chemicals Used in Food Processing, publication 1274 by the National Academy of Sciences, pages 63-258, can be used. Typically, flavorings, if included, are present at 0.01-1% by weight. In some embodiments, flavoring may be present at about 0.2% by weight.
    14/25 [037] Sweeteners include both natural and artificial sweeteners. Suitable sweetener includes water-soluble sweetening agents such as monosaccharides, disaccharides and polysaccharides such as xylose, ribose, glucose (dextrose), mannose, galactose, fructose (levulose), sucrose (sugar), maltose, water-soluble artificial sweeteners soluble saccharin salts, such as sodium or calcium saccharin salts, sweetener based on cyclamate salts dipeptide, such as sweeteners derived from L-aspartic acid, such as methyl ester of L-aspartyl-L-phenylalaine (aspartame ). In general, the effective amount of sweetener is used to provide the desired level of sweetness for a particular composition, it will vary with the chosen sweetener. This amount will normally be from about 0.001% to about 5% by weight of the composition. In some embodiments, the sweetener is sodium saccharin and present in about 0.01% by weight of the composition.
    [038] Optional breath freshening agents can be provided. Any agent that refreshes orally acceptable breath can be used, including, without limitation, zinc salts, such as zinc gluconate, zinc citrate and zinc chloride, alpha-ionone and mixtures thereof. One or more breath-refreshing agents are optionally present in a total effective amount of breath-cooling.
    [039] Optionally, the composition can include a tartar control agent (anti-calculi). Tartar control agents, among those that are useful in this context include phosphates and polyphosphates (for example,
    15/25 pyrophosphates), polyaminopropane sulfonic acid (AMPS), polyolefin sulfonates, polyolefin phosphates, diphosphonates such as azacycloalkane-2,2-diphosphonates (eg azacycloheptane-2,2-diphosphonic acid), N-methyl- azacyclopentane-2,3-diphosphonic acid, ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) and ethane-1-amino-1,1diphosphonate, phosphonoalkane carboxylic acids and the salts of all these agents, for example, their salts alkali and ammonium metal. Useful inorganic phosphate and polyphosphate salts include monobasic, dibasic and tribasic sodium phosphate, sodium tripolyphosphate, tetrapolyphosphate, mono-, di-, tri- and tetrasodium pyrophosphates, sodium trimetaphosphate, sodium hexametaphosphate and mixtures thereof, and mixtures thereof. sodium can optionally be replaced by potassium or ammonium. Other useful anti-calculating agents include polycarboxylate polymers and copolymers of polyvinyl methyl ether / maleic anhydride (PVME / MA), such as those available under the ISP GantrezTM brand, Wayne, N.J.
    [040] In some embodiments, the tartar control agent is present at a concentration of about 0.01 to 10% by weight. In some embodiments, the tartar control agent is present in a concentration of about 1% by weight. In some embodiments, the tartar control agent also acts as a buffer. For example, in a phosphate buffer system, monobasic sodium phosphate is present in a concentration of about 0.01 to about 5% by weight, and disodium phosphate is present in a concentration of about 0.01 to about 5% by weight, the precise ratio depending on the other excipients in the
    16/25 formulation and the desired pH.
    [041] Other optional additives include antimicrobial agents (eg, (antibacterials). Any acceptable oral antimicrobial agent can be used, including triclosan (5-chloro-2- (2,4dichlorophenoxy) -phenol); tin and zinc compounds, quaternary ammonium compounds such as cetylpyridinium chloride (CPC); bisguanides such as chlorhexidine; and benzalkonium chloride. Another illustrative list of useful antibacterial agents is provided in U.S. Patent No. 5,776,435 to Gaffar et al. In some embodiments, the antimicrobial agent is present in a concentration of about 0.001 to about 1% by weight. In some embodiments, the antimicrobial agent is cetylpyridinium chloride. In some embodiments, cetylpyridinium chloride is present in a concentration of about 0.05% by weight.
    [042] Antioxidants are another class of optional additives. Any orally acceptable antioxidant can be used, including butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin A, carotenoids, vitamin E, flavonoids, polyphenols, ascorbic acid, herbal antioxidants, chlorophyll, melatonin, and mixtures thereof .
    [043] In addition, the optional saliva stimulating agent, useful, for example, in improving dry mouth can be included. Any orally acceptable saliva stimulating agent can be used, including, without limitation, acidic foods such as citric, lactic, malic, succinic, ascorbic, adipic, fumaric, and tartaric acid, and mixtures thereof. One or more agents
    17/25 saliva stimulants are optionally present in a total effective amount of saliva stimulant.
    [044] Optionally, an antiplaque agent (for example, plaque disruption), can be included. Any orally acceptable antiplaque agent may be used, including, without limitation, tin, copper, magnesium and strontium salts, dimethicone copolyols, such as cetyl dimethicone copolyol, papain, glucoamylase, glucose oxidase, urea, calcium lactate, glycerophosphate calcium, strontium polyacrylates and their mixtures.
    [045] Optional desensitizing agents include potassium citrate, potassium chloride, potassium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate, strontium salts and mixtures thereof. In some embodiments, a local or systemic pain reliever, such as aspirin, codeine, acetaminophen, sodium salicylate or triethanolamine salicylate can be used.
    [046] In some embodiments, the methods comprise the rinsing step of the oral cavity with a composition as described herein. In some embodiments, the composition's pseudoplasticity properties increase the flow and thus the covered area when agitated within the oral cavity. In some embodiments, a polymer film forms on the surface of the oral cavity following the discharge of the composition which results in the relief of dry mouth symptoms. In some embodiments, 5 ml or more of the composition is gargled. In some embodiments, 10 ml or more is used. In some embodiments, 10 to 50 ml is used. In some embodiments, 15 to 25 ml or more is used. In some embodiments, 15 ml or more is used. In some
    18/25 modalities, the individual garages with the composition several times a day. In some modalities, the individual garages with the composition in several days. In some modalities, the individual gargles with the composition every 4 to 6 hours, up to 6 times a day.
    [047] As used throughout, ranges are used as an abbreviation to describe each and all values that fall within the range. Any value within the range can be selected as the end of the range. In addition, all references cited herein are hereby incorporated by reference in their entirety.
    [048] In the event of a conflict in a definition in this disclosure and that of a cited reference, this disclosure controls.
    [049] Unless otherwise specified, all percentages and quantities here and elsewhere expressed in the specification should be understood as referring to percentages by weight. The quantities indicated are based on the weight of the active material.
    EXAMPLES
    Example 1 [050] The goal is to provide a viscoelastic mouthwash that contains a polymer system plus an active one (arginine, preferably with fluoride), for superior enamel protection against acid-induced demineralization. Oral antiseptic formulations are prepared with the following ingredients:
    Table 2
    Mouthwash 1: Ingredients Concentration (%
    19/25
    weight / weight) Water 71.05 Humectants 17.5 Surfactant 1 Monobasic sodium phosphate 1 Disodium phosphate 0.15 Preservative 0.5 Flavor 0.2 Carboxymethyl cellulose 0.083 Xanthan gum 0.083 Acrylate copolymer 0.05 Sodium fluoride 0.02 Arginine (ArgHCO 3 ) 1.3 Sweetener 0.01 Cetylpriridinium chloride 0.05
    Table 3
    Mouthwash 2: Ingredients Concentration (%weight / weight) Water 71.35 Humectants 17.5 Surfactant 1 Monobasic sodium phosphate 1 Disodium phosphate 0.15 Preservative 0.5 Flavor 0.2 Carboxymethyl cellulose 0.083 Xanthan gum 0.083 Acrylate copolymer 0.05 Sodium fluoride 0.05
    20/25
    Arginine (ArgHCO 3 ) 0.8 Sweetener 0.01 Cetylpriridinium chloride 0.05
    Table 4
    Mouthwash 3: Ingredients Theoretical weight (%) Water 71.22 Sorbitol (Sol. 70%) 10 Glycerin 7.5 Propylene glycol 7 L-Arginine 0.8 Poloxamer 407 1 Monobasic sodium phosphate 1 FD&C Green N ° 3 0.000375 Cetylpriridinium chloride 0.05 Sodium benzoate 0.5 Flavor 0.2 Dibasic sodium phosphate 0.15 Sodium saccharin 0.01 Xanthan gum 0.083 Sodium CMC 0.083 Polyacrylate copolymer 0.05 Trimethyl glycine 0.3 Sodium fluoride 0.05
    Example 2 [051] As examples of compositions of the present invention, they can be prepared according to the following procedure:
    Add approximately 1/3 of the water to a small container and add slowly to the acrylate copolymer with a strong mixture.
    21/25
    Add the remaining water to the main mixing tank.
    Add Poloxomer 407 and mix until completely dissolved.
    Add the appropriate amount of sorbitol.
    Add monobasic sodium phosphate, sodium benzoate, anhydrous dibasic sodium phosphate, sodium saccharin, Betafin BP20, and L-Arginine and mix each before adding to the next.
    Add the CPC and dye. Mix for 10 minutes to ensure the entire batch is completely solubilized.
    Suspend xanthan gum and CMC in propylene glycol.
    Add acrylate copolymer and aqueous mixture to the main mixing tank.
    Add the xanthan gum and CMC suspension to the mixing tank and mix for 15 minutes.
    Add flavor and mix for 5 minutes.
    Example 3 [052] The tripolymer mouthwash formulations of Example 1 are evaluated for their rheological properties, compared to water, saliva and three commercial mouthwashes. The three commercial mouthwashes are a simple fluoride rinse mouthwash (comparative formulation 1), a high fluoride polymer based mouthwash (comparative formulation 2), and a mouthwash having a different conventional polymer system described in this case (mouthwash 3). The rheological properties of formulations are quantified using a
    22/25 AR2000ex controlled voltage rheometer (TA Instruments) and cuette geometry. The flow curve is generated and suitable for a power law model to quantify the flow rate index, n. A stress scan is conducted to quantify the modulus of elasticity, G 'and the loss modulus, G. The results are described in table 5 (below).
    Table 5
    Name ofsample Ingredientskey G '(din /cm2) G(din /cm2) G '/ G K(cps) n Example of Water 0.02 0.23 0.09 1.1 1.0 fluid Newtonian Example of Spittle 21.24 4.79 4.43 88.30 0.41 fluid Natural viscoelastic- tico Antiseptic Network in 8.25 5.57 1.48 163.5 0.50 oral co 1 polymer + tripolymer fluoride 90 ppm + Arginine Antiseptic Network in 3.38 5.04 0.67 153.7 0.60 oral co 2 polymer +tripolymer fluoride 225 ppm + Arginine Example Fluoride 225 0.06 0.69 0.09 5.35 1.00 comparative PP m
    23/25
    1 Example Polymer + 0.22 1.62 0.14 20.84 0.92 comparative fluoride 400 2 pp m Example Polymer + 0.52 3.16 0.17 19.92 1.00 comparative fluoride 225 3 ppm + Arginine
    [053] The data described in table 5 (above) demonstrate that the compositions of the present invention are viscoelastic (more like saliva), while the comparative examples are Newtonian (more like water).
    Example 4 [054] Tripolymer mouthwashes are then compared to commercial mouthwashes for their ability to protect against enamel loss. Enamel loss for tripolymer mouthwash prototypes are compared with water and the three commercial examples using an in vitro methodology, based on the protocol published by S.M. Hooper, RG Newcomb, R. Faller,
    S. Eversole, M. Addy, N.X. West, Journal of Dentistry, 35 (2007), 476-481. Each formulation is tested with 4 to 6 repetitions to obtain statistically significant results.
    [055] Bovine incisors are cleaned and sterilized with 70% alcohol. Each sample is embedded in the epoxy resin using a Teflon mold to form a 20 mm x 10 mm x 5 mm block. The enamel surface is ground using 600 and 1200 grain silicon carbide paper consecutively to achieve a shiny, smooth surface. Each surface
    24/25 of the enamel is masked with tape, leaving only the center area (~ 0.5 mm wide) exposed. The masked enamel blocks are preconditioned with a 5% citric acid solution for 30 seconds to create a pre-existing (incipient) lesion. All enamel samples are kept in artificial saliva, at 37 ° C for at least 12 hours before experimentation. Artificial saliva contained the following ingredients in 1000 ml of deionized water: 25 g porcine stomach mucin, 466 mg NH 4 C1, 420 mg CaCl 2 .H 2 O, 86 mg MgCl 2 .6H 2 O, 2314 mg KC1, 708 mg KH2PO4, 444 mg KCNS, 1070 mg NaHCO3, 750 mg NaH2PO4, 26 mg sodium citrate.2H2O, 50 mg albumin (BSA), 346 mg urea and 900 mg urea glycine.
    [056] The study of erosion is carried out through a demineralization and cyclic remineralization procedure. Each enamel substrate is treated with the formulation assigned MW or H2O control without treatment for 1 min in the morning, and then demineralized twice for 2 minutes using a 1% citric acid solution titrated to pH 3.8 with NaOH. The same procedure is repeated in the afternoon and this treatment regimen is repeated daily for 5 days. Except during demineralisations and MW treatments, enamel substrates are always stored in artificial saliva at 37 ° C. Profilometry is used to quantify the enamel loss induced by acid exposure by measuring the heights of the unmasked center step relative to the masked regions. Enamel loss is calculated using the step height difference before and after studying the cycle.
    25/25 [057] The use of prototypes based on viscoelastic tripolymer results in a substantial and surprising decrease in enamel loss compared to that observed using commercial comparison formulations, as can be seen in Table 6 (below).
    Table 6
    Sample name Key ingredients Loss of enamel Water Water 0.4443 Mouthwash Polymer mesh + 0.2258 1 tripolymer fluoride 90 ppm +Arginine Mouthwash Polymer mesh + 0.2165 3 tripolymer fluoride 225 ppm +Arginine Examplecomparative 1 Fluoride 225 ppm 0.3885 Example Polymer + 0.4969 comparative 2 fluoride 400 ppm Example Polymer + 0.3877 comparative 3 fluoride 225 ppm +Arginine
    [058] The data described in table 6 (above) demonstrates that the compositions of the present invention unexpectedly provide a step height difference of less than 0.25 microns, when evaluated using the Hooper protocol described herein; while similar formulated compositions that do not contain the inventive combinations described herein are unable to provide the same level of protection against enamel loss.
    1/3
    权利要求:
    Claims (16)
    [1]
    1. Aqueous composition of oral hygiene, characterized by the fact that it comprises:
    a) an effective amount of a basic amino acid in free form or an orally acceptable salt; and
    b) a polymer system comprising (i) a cellulosic polymer, (ii) a gum polymer, and (iii) a polyacrylate polymer or copolymer;
    c) a fluoride source, in which the effective amount of basic amino acid in free form or orally acceptable salt comprises 0.05 to 2% by weight of the formulation, measured as the weight of the equivalent free base when it is in the form of oral salt acceptable, and the fluoride source is present in an amount of 0.02% to 0.2% by weight, of the composition, and in which the polyacrylate polymer or copolymer is a carbomer, and / or in which the polymer or copolymer polyacrylate is selected from homo- and copolymers of acrylic acid cross-linked with a polyalkenyl polyether.
    [2]
    2. Composition according to claim 1, characterized in that the fluoride source is present in an amount effective to supply 90 to 500 ppm of fluoride, preferably in which the fluoride source is present in an amount effective for supply 225 ppm of fluoride.
    [3]
    3. Composition according to claim 2, characterized by the fact that the source of fluoride is selected from sodium fluoride, sodium monofluorophosphate, and a combination thereof.
    Petition 870180025108, of 03/28/2018, p. 42/44
    2/3
    [4]
    Composition according to claim 2 or 3, characterized in that the source of fluoride comprises sodium fluoride.
    [5]
    Composition according to any one of claims 1 to 4, characterized in that the basic amino acid comprises L-arginine in the free form or in an orally acceptable salt.
    [6]
    Composition according to any one of claims 1 to 5, characterized in that it further comprises a buffering agent.
    [7]
    Composition according to any one of claims 1 to 6, characterized in that it further comprises a humectant.
    [8]
    Composition according to any one of claims 1 to 7, characterized in that it further comprises an antibacterial agent.
    [9]
    Composition according to any one of claims 1 to 8, characterized in that the cellulosic polymer is selected from a hydroxyalkyl methyl cellulose, a carboxyalkyl methyl cellulose, a hydroxyalkyl cellulose, an alkyl cellulose, a carboxyalkyl cellulose, and a combination of two or more of them.
    [10]
    Composition according to any one of claims 1 to 9, characterized in that the cellulosic polymer comprises carboxymethyl cellulose.
    [11]
    Composition according to any one of claims 1 to 10, characterized in that the gum polymer is selected from carrageen gum, xanthan gum, and combinations thereof.
    Petition 870180025108, of 03/28/2018, p. 43/44
    3/3
    [12]
    12. Composition according to claim 1, characterized by the fact that the fluoride source is present in the amount of 0.05% by weight of the composition.
    [13]
    13. Composition according to any one of claims 1 to 12, characterized in that the composition has a flow rate index of less than 0.85; and has a G '/ G ratio greater than or equal to 0.5.
    [14]
    14. Use of the composition as defined in any of claims 1 to 13, characterized in that it is for preparing a mouthwash to reduce dental erosion of the enamel.
    [15]
    15. Use, according to claim 14, characterized by the fact that the administration comprises the rinse of 15 to 60 seconds.
    [16]
    16. Composition according to any one of claims 1 to 13, characterized in that it is for use in a method of reducing dental enamel erosion.
    Petition 870180025108, of 03/28/2018, p. 44/44
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    同族专利:
    公开号 | 公开日
    EP2790656B1|2016-11-02|
    AU2011383326A1|2014-05-22|
    TW201338798A|2013-10-01|
    RU2609862C2|2017-02-06|
    US10722446B2|2020-07-28|
    EP2790656A1|2014-10-22|
    CN107648070A|2018-02-02|
    PH12014501213A1|2014-09-08|
    HK1200706A1|2015-08-14|
    CN103974691A|2014-08-06|
    AR089268A1|2014-08-13|
    MX2014007143A|2014-09-22|
    AU2011383326B2|2016-01-28|
    CA2855732A1|2013-06-20|
    RU2014128848A|2016-02-10|
    PH12014501213B1|2014-09-08|
    JP2015504040A|2015-02-05|
    US20140305461A1|2014-10-16|
    MX342833B|2016-10-14|
    BR112014014315A2|2017-06-13|
    CA2855732C|2016-06-28|
    SG11201402061UA|2014-06-27|
    WO2013089734A1|2013-06-20|
    TWI478728B|2015-04-01|
    ZA201404188B|2017-09-27|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    JPS528795B2|1971-12-30|1977-03-11|
    DE3102359A1|1981-01-24|1982-08-19|Basf Ag, 6700 Ludwigshafen|METHOD FOR PRODUCING OXAZOLIDINE-2,4-DIONES|
    US5288480A|1987-01-30|1994-02-22|Colgate-Palmolive Co.|Antiplaque antibacterial oral composition|
    JP2656338B2|1989-01-31|1997-09-24|日東電工株式会社|Oral mucosa patch preparation|
    US5284648A|1989-03-17|1994-02-08|White Robert D|Alcohol-free, oral rinse and pre-rinse emulsions method of prepration and method of use|
    SE512333C2|1989-08-25|2000-02-28|Colgate Palmolive Co|Antibacterial oral composition with plaque- and tartar-limiting action|
    US5202112A|1991-08-01|1993-04-13|Colgate-Palmolive Company|Viscoelastic dentifrice composition|
    US5562939A|1995-01-27|1996-10-08|Bush Boake Allen Inc.|Method of suspending inclusions and compositions produced thereby|
    US6106883A|1995-01-27|2000-08-22|Bush Boake Allen, Inc.|Method of suspending inclusions|
    KR20010013377A|1997-06-04|2001-02-26|데이비드 엠 모이어|Mild, leave-on antimicrobial compositions|
    US6153210A|1997-08-14|2000-11-28|Periodontix, Inc.|Use of locally delivered metal ions for treatment of periodontal disease|
    AT344313T|1997-12-20|2006-11-15|Genencor Int|GRANULATE CONTAINS HYDRATED BARRIER MATERIAL|
    US20010016577A1|1998-08-24|2001-08-23|Douglas Joseph Dobrozsi|Oral mucoadhesive compositions containing gastrointestinal actives|
    US6596298B2|1998-09-25|2003-07-22|Warner-Lambert Company|Fast dissolving orally comsumable films|
    AU3239000A|1999-02-23|2000-09-14|Den Mat Corporation|An aqueous non-alcoholic oral rinse containing benzocaine and carbomer|
    US6946118B1|1999-09-14|2005-09-20|Orapharma, Inc.|Formulations for treating or preventing mucositis|
    US20030158111A1|1999-10-01|2003-08-21|David Bar-Or|Methods and products for oral care|
    AT421894T|2000-03-17|2009-02-15|Lg Household & Health Care Ltd|PUNCH TO KNOW THE TEETH|
    US6595997B2|2001-02-28|2003-07-22|Howmedica Osteonics Corp.|Methods used in performing femoral and tibial resection in knee surgery|
    US7008979B2|2002-04-30|2006-03-07|Hydromer, Inc.|Coating composition for multiple hydrophilic applications|
    US20040101494A1|2002-11-26|2004-05-27|Scott Douglas Craig|Chewable solid unit dosage forms and methods for delivery of active agents into occlusal surfaces of teeth|
    CA2540869C|2003-10-28|2013-04-30|Taro Pharmaceuticals U.S.A., Inc.|Spill resistant formulations containing clays|
    EP2263644A2|2004-08-02|2010-12-22|Glaxo Group Limited|Novel composition for treating xerostomia|
    US7618615B2|2004-08-13|2009-11-17|Healthpartners Research Foundation|Methods for providing neuroprotection for the animal central nervous system against neurodegeneration caused by ischemia|
    WO2006138552A2|2005-06-15|2006-12-28|Government Of The Usa, As Represented By The Secretary, Dept. Of Health & Human Services|Tissue engineered cartilage, method of making same, therapeutic and cosmetic surgical applications using same|
    FR2887448B1|2005-06-23|2009-04-17|Rhodia Chimie Sa|COSMETIC COMPOSITION COMPRISING AN AMPHOLYTE COPOLYMER|
    US8119162B2|2005-11-10|2012-02-21|Colgate-Palmolive Company|Particles that disrupt or impede bacterial adhesion, related compositions and methods|
    US20070122358A1|2005-11-29|2007-05-31|The Procter & Gamble Company|Dentifrice composition free of abrasive material|
    US20070122359A1|2005-11-29|2007-05-31|The Procter & Gamble Company|Dentifrice composition comprising binder system comprising hydrophilic clay material|
    US20080267891A1|2007-04-30|2008-10-30|Colgate-Palmolive Company|Oral Care Composition To Reduce Or Eliminate Dental Sensitivity|
    CA2705298C|2008-02-08|2013-10-01|Rajnish Kohli|Oral care product and methods of use thereof|
    MY160687A|2008-02-08|2017-03-15|Colgate Palmolive Co|Oral care product and methods of use and manufacture thereof|
    CN105362087A|2008-02-08|2016-03-02|高露洁-棕榄公司|Compositions and devices|
    JP2011515332A|2008-02-08|2011-05-19|コルゲート・パーモリブ・カンパニー|Oral care products and methods of using and manufacturing the same|
    CN101938978A|2008-02-08|2011-01-05|高露洁-棕榄公司|Oral care product and methods of use and manufacture thereof|
    CL2008000897A1|2008-02-08|2009-08-14|Colgate Palmolive Co|Arginine salt and one or more conjugated acids; oral care composition comprising said salt; use to reduce or inhibit caries formation, demineralization of teeth; reduce hypersensitivity of teeth, reduce or inhibit gingivites among others.|
    US8568697B2|2008-03-21|2013-10-29|Colgate-Palmolive Company|High fluoride ion recovery compositions|
    DE102008019339A1|2008-04-16|2009-10-22|Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh|Composition for medical use, in particular antacids|
    WO2010068428A1|2008-11-25|2010-06-17|The Procter & Gamble Company|Oral care compositions with improved aesthetics and fused silica|
    GB0822434D0|2008-12-09|2009-01-14|Glaxo Group Ltd|Novel use|
    BR112013016214A2|2010-12-23|2018-05-15|Colgate Palmolive Co|polymer systems|
    JP2014501257A|2010-12-23|2014-01-20|コルゲート・パーモリブ・カンパニー|Aqueous oral care composition|
    BR112013016210A2|2010-12-23|2019-09-24|Colgate Palmolive Co|fluid compositions comprising a structuring agent.|
    JP2014501256A|2010-12-23|2014-01-20|コルゲート・パーモリブ・カンパニー|Oral care fluid composition|
    BR112013016223A2|2010-12-23|2016-08-09|Colgate Palmolive Co|films and compositions comprising the same|JP2014501257A|2010-12-23|2014-01-20|コルゲート・パーモリブ・カンパニー|Aqueous oral care composition|
    CN104053458B|2011-07-20|2016-07-20|布莱阿姆青年大学|Comprise eluting plug and draw the hydrogel material of Jining compound|
    US20140363780A1|2011-12-21|2014-12-11|Brigham Young University|Oral care compositions|
    EP2846634A2|2012-05-02|2015-03-18|Brigham Young University|Ceragenin particulate materials and methods for making same|
    US10568893B2|2013-03-15|2020-02-25|Brigham Young University|Methods for treating inflammation, autoimmune disorders and pain|
    AU2013406790B2|2013-12-03|2017-09-28|Colgate-Palmolive Company|Oral care compositions|
    CA2844321C|2014-02-27|2021-03-16|Brigham Young University|Cationic steroidal antimicrobial compounds|
    US10220045B2|2014-03-13|2019-03-05|Brigham Young University|Compositions and methods for forming stabilized compositions with reduced CSA agglomeration|
    US10238665B2|2014-06-26|2019-03-26|Brigham Young University|Methods for treating fungal infections|
    US10441595B2|2014-06-26|2019-10-15|Brigham Young University|Methods for treating fungal infections|
    US10227376B2|2014-08-22|2019-03-12|Brigham Young University|Radiolabeled cationic steroid antimicrobials and diagnostic methods|
    US10155788B2|2014-10-07|2018-12-18|Brigham Young University|Cationic steroidal antimicrobial prodrug compositions and uses thereof|
    WO2016094054A1|2014-12-10|2016-06-16|Elevate Oral Care, Llc|Composition for the relief of dry mouth|
    BR112017012629B1|2014-12-23|2021-06-08|Colgate-Palmolive Company|composition for oral hygiene and its use|
    US10370403B2|2015-04-22|2019-08-06|Brigham Young University|Methods for the synthesis of ceragenins|
    US10226550B2|2016-03-11|2019-03-12|Brigham Young University|Cationic steroidal antimicrobial compositions for the treatment of dermal tissue|
    WO2017219339A1|2016-06-24|2017-12-28|Colgate-Palmolive Company|Oral care compositions and methods of use|
    CA3039225A1|2016-11-08|2018-05-17|Colgate-Palmolive Company|Oral care compositions|
    US10959433B2|2017-03-21|2021-03-30|Brigham Young University|Use of cationic steroidal antimicrobials for sporicidal activity|
    GB2562800A|2017-05-26|2018-11-28|Biofilm Ltd|Oral care composition, process for preparation and method of use thereof|
    AU2018445788A1|2018-10-16|2021-05-06|Colgate-Palmolive Company|Oral care compositions and methods for the same|
    US11154487B2|2018-10-16|2021-10-26|Colgate-Palmolive Company|Oral care compositions and methods for the same|
    WO2021195110A1|2020-03-24|2021-09-30|Colgate-Palmolive Company|Improved methods for manufacturing arginine dentifrice|
    法律状态:
    2017-09-26| B15K| Others concerning applications: alteration of classification|Ipc: A61K 8/43 (2006.01), A61K 8/44 (2006.01), A61K 8/7 |
    2018-01-02| B07A| Application suspended after technical examination (opinion) [chapter 7.1 patent gazette]|
    2018-05-02| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2018-07-03| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|
    优先权:
    申请号 | 申请日 | 专利标题
    PCT/US2011/065125|WO2013089734A1|2011-12-15|2011-12-15|Aqueous oral care compositions|
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