Oral care composition comprising an amino acid-zinc halide complex and uses thereof

专利摘要:
Summary Oral Hygiene Compositions Containing Zinc Amino Acid Halides The invention discloses oral hygiene compositions comprising a zinc amino acid halide. Also provided are methods for making and using the compositions.
公开号:BR112015014502B1
申请号:R112015014502-7
申请日:2012-12-19
公开日:2019-04-09
发明作者:Long Pan；Shaotang Yuan；Shira Pilch；James G. Masters；Zhiqiang Liu
申请人:Colgate-Palmolive Company；
IPC主号:

专利说明:

COMPOSITION FOR ORAL CARE UNDERSTANDING A COMPLEX
ZINO AMINO ACID HALIDE AND USES OF THE SAME
BACKGROUND [0001] Dental erosion involves demineralization and damage to the dental structure due to acid attack from non-bacterial sources. Erosion is found initially in the enamel and, if left unchecked, can progress to the dentin. Dental erosion can be caused or aggravated by acidic foods and drinks, exposure to chlorinated pool water and gastric acid regurgitation. Tooth enamel is a negatively charged surface, which naturally tends to attract positively charged ions, such as hydrogen and calcium ions, while resisting negatively charged ions, such as fluoride ions.
[0002] Dentin hypersensitivity is an acute and localized toothache in response to physical stimulation of the dentin surface such as thermal osmotic (hot or cold), tactile combination of thermal, osmotic and tactile stimulation of exposed dentin. Dentin exposure, which is usually due to receding gums, or loss of enamel, often leads to hypersensitivity. Dentin tubules open to the surface have a high correlation with dentin hypersensitivity. The dentinal tubules lead from the pulp to the cementum. When the superficial cementation of the tooth root is eroded, the dentinal tubules are exposed to the external environment. The exposed dentinal tubules provide a path for the transmission of
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2/60 fluid to the pulp nerves, the transmission induced by changes in temperature, pressure and ionic gradients.
[0003] Although the prior art describes the use of various oral compositions for the treatment of dentin hypersensitivity, dental caries, enamel erosion and demineralization, there is still a need for additional compositions and methods that provide improved performance in such treatments.
SUMMARY [0004] It has now been discovered that zinc ions can form a soluble complex with an amino acid. The complex comprising zinc and amino acid and optionally an anion and / or oxygen forms a soluble cationic fraction which in turn can form a salt with a halide or another anion. When placed in the formulation, this complex has an effective concentration of zinc ions for the enamel, thus protecting against erosion, reducing bacterial colonization and the development of biofilm, in addition to providing better shine to the teeth. In addition, when used, the formulation provides a precipitate that can obstruct the dentinal tubules, thus reducing the sensitivity of the teeth. While providing effective zinc release compared to formulations with insoluble zinc salts, formulations that comprise the zinc-amino acid complex have no degradable taste or sensation in the mouth, poor fluoride release and low foaming, and the cleanliness associated with care products oral zinc based products using soluble zinc salts.
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3/60 [0005] In a particular embodiment, the zinc-amino acid complex is a zinc-lysine-HCl complex, for example, the new complex called ZLC, which can be formed from a mixture of zinc oxide and hydrochloride of lysine. ZLC has the chemical structure [Zn (C6H14N2O2) 2Cl] ⁺ Cl ^- and can exist in the cationic cation solution ([Zn (C6H14N2O2) 2Cl] ⁺ and the chloride anion or it can be a solid salt, for example, a crystal, optionally in mono- or dihydrate form.
[0006] The invention thus provides compositions for oral care, for example, compositions for mouthwash, compositions for toothpastes or gels, which comprise a zinc-amino acid complex, for example, a lysine-zinc chloride complex, for example, ZLC. The compositions can optionally comprise a fluoride source and an additional phosphate source. The compositions can be formulated in a formulation suitable for oral care, for example, conventional toothpaste, oral gel or mouthwash, for example, comprising one or more abrasives, surfactants, foaming agents, vitamins, polymers, enzymes , humectants, thickeners, antimicrobial agents, preservatives, flavorings and / or dyes.
[0007] The invention further provides methods of using the compositions of the invention to reduce and inhibit acid enamel erosion, cleaning teeth, reducing the generated bacterial biofilm and plaque, reducing gingivitis, inhibiting tooth decay and forming cavities, besides reducing the hypersensitivity of
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4/60 dentin, comprising applying a composition of the invention to teeth.
[0008] The invention further provides methods of preparing the compositions of the invention which comprise the combination of a source of zinc ion (for example, ZnO), an amino acid (for example, a basic amino acid, for example, arginine or lysine), and, optionally, a halide source, for example, combination of zinc oxide and lysine hydrochloride in aqueous solution, for example, at a molar ratio of Zn: amino acid from 1: 1 to 1: 3, for example, 1: 2 and Zn: halide, where present, from 1: 1 to 1: 3, for example, 1: 2; optionally, isolating the ionic complex thus formed as a solid; and mixing with a base for oral care, for example, a toothpaste, oral gel, or mouthwash base.
[0009] Other areas of applicability of the present invention will be evident from the detailed description provided hereinafter. It should be understood that the detailed description and the specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and do not limit the scope of the invention.
DETAILED DESCRIPTION [00010] The following description of the preferred mode (s) is of an exemplary nature only and in no way intended to limit the invention, its application or uses.
[00011] The invention, therefore, provides in a first modality, a composition for oral care
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5/60 (Composition 1), which comprises zinc in complex with an amino acid, for example:
1.1 ^. Composition 1, where the amino acid is selected The from lysine , glycine and arginine, at form of salt addition of free acid orally acceptable, per example, way of hydrochloride ^.1.2 . Composition 1 or 1.1 wherein amino acid is one amino acid basic, for example, arginine or lysine, at
free or orally acceptable salt form.
1.3. Any of the preceding compositions further comprising a halide in ionic association with zinc and amio acids.
1.4. Any of the preceding compositions in which the molar ratio of Zn: amino acid is 3: 1 to 1: 5, for example, about 1: 2 and the molar ratio of Zn: halide, when present is from 3: 1 to 1 : 3, for example, about
1: 2.
1.5. Any of them of the compositions precedents, in what O zinc-amino acid complex is formed, in its entirety or in part, in situ, after the composition be applied. 1.6. Any of them of the compositions precedents, in what O zinc-amino acid complex is formed, in its entirety or in part, in situ, after the composition be formulated. 1.7. Any of them of the compositions precedents, in what O amino acid is lysine.1.8. Any of them of the compositions precedents, in what O zinc is present in an amount of 0.05 to 10%
by weight of the composition, optionally at least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5,
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6/60 at least 1, at least 2, at least 3, or at least 4 to 10% by weight of the composition, for example, about 1-3%, for example, about 2-2.7% by weight .
1.9. Any of the preceding compositions, wherein the amino acid is present in an amount of 0.05 to 30% by weight of the composition, optionally at least 0.1, at least 0.2, at least 0.3, at least 0 , 4, at least 0.5, at least 1, at least 2, at least 3, at least 4, at least 5, at least 10, at least 15, at least 20 to 30% by weight, for example, about 1-10% by weight.
1.10 Any of the preceding compositions, in which a molar ratio of zinc to amino acid is 2: 1 to
1: 4, optionally 1: 1 to 1: 4, 1: 2 to 1: 4, 1: 3 to 1: 4, 2: 1 to 1: 3, 2: 1 to 1: 2, or 2: 1 to 1: 1, for example, about 1: 2 or 1: 3.1.11 Any one of compositions precedent
comprising a halide in ionic association with zinc and amino acid, in which the halide is selected from the group consisting of fluorine, chlorine and their mixtures.
1.12 Any of the foregoing compositions in which the amino acid and zinc complex is a lysine-zinc chloride complex (for example, (ZnLys2Cl) ⁺ Cl ^- or ZnLys3) ²⁺ Cl2) or an arginine-zinc chloride complex.
1.13 Any of the preceding compositions, in which the amino acid and zinc complex is a lysine-zinc chloride complex, for example, ZLC, for example, a lysine-zinc chloride complex that has the chemical structure [Zn (C6H14N2O2) 2Cl ] ⁺ Cl ^- either in the cationic cation solution (for example, [Zn (CóH14N2O2) 2Cl] ⁺ ) and the chloride anion, or in
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7/60 solid salt form, for example, crystal form, optionally in mono- or dihydrate form.
1.14 Any of the preceding compositions in the form of a toothpaste, gel, mouthwash, powder, cream, strip, or gum.
1.15 Any of the preceding compositions on an acceptable oral basis, for example, a mouthwash, gel or toothpaste base.
1.16 Any of the preceding compositions in the form of toothpaste, for example, in which the amino acid and zinc complex is present in an effective amount, for example, in an amount of 0.5-4% by weight of zinc, for example example, about 1-3% by weight of zinc in a toothpaste base.
1.17 Any of the preceding compositions in the form of a toothpaste, wherein the base of the toothpaste comprises an abrasive, for example, an effective amount of a silica abrasive, for example, 10-30%, for example, about 20 %.
1.18 Any of the preceding compositions in the form of a mouthwash, for example, in which the complex of amino acid and zinc is present in an effective amount, for example, in an amount of 0.5-4% by weight of zinc, for example , about 1-3% by weight of zinc.
1.19 Any of the preceding compositions further comprising an effective amount of fluoride ion source, for example, providing 50 to 3,000 ppm of fluorine.
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8/60
1.20 Any of the preceding compositions further comprising an effective amount of fluoride, for example, where fluoride is a salt selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorsilicate, sodium fluorosilicate , amine fluoride (for example, N'-octadecyltrimethylendiamine-Ν, Ν, Ν'-tris (2-ethanol) -dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorsulfate and combinations thereof.
1.21 Any of the preceding compositions comprising an effective amount of one or more alkaline phosphate salts, for example, sodium, potassium or calcium salts, for example, selected from alkaline dibasic phosphate and alkaline pyrophosphate salts, for example, salts alkaline phosphate selected from dibasic sodium phosphate, dibasic potassium, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and mixtures of any two or more of these, for example, in an amount of 20 %, for example, 2-8%, for example, about 5%, by weight of the composition.
1.22 Any of the foregoing compositions comprising buffering agents, for example, sodium phosphate buffer (for example, monobasic sodium phosphate and disodium phosphate).
1.23 Any of the preceding compositions comprising a humectant, for example, selected from glycerin, sorbitol, propylene glycol, polyethylene glycol, xylitol, and mixtures thereof, by
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9/60 example, comprising at least 20%, for example, 2040%, for example, 25-35% glycerin.
1.24 Any of the preceding compositions comprising one or more surfactants, for example, selected from anionic, cationic, zwitterionic, and non-ionic surfactants and mixtures thereof, for example, comprising an anionic surfactant, for example, a selected surfactant from sodium lauryl sulfate, sodium lauryl sulfate ether and mixtures thereof, for example, in an amount from about 0.3% to about 4.5% by weight, for example 1-2% of sodium lauryl sulfate (SLS); and / or a zwitterionic surfactant, for example, a betaine surfactant, for example, cocamidopropyl betaine, for example, in an amount comprised from about 0.1% to about 4.5% by weight, for example, 0, 5-2% cocamidopropyl betaine.
1.25 Any of the preceding compositions further comprising a viscosity modifying amount of one or more of the polysaccharide gums, for example, xanthan or carrageen gum, silica thickener and combinations thereof.
1.26 Any of the preceding compositions comprising strips of gum or fragments.
1.27 Any of the preceding compositions further comprising flavorings, perfumes and / or dyes.
1.28 Any of the preceding compositions comprising an effective amount of one or more antibacterial agents, for example, comprising an antibacterial agent selected from diphenyl ether
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10/60 halogenated (for example, triclosan), herbal extracts and essential oils (for example, rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitol, catechol, methyl salicylate, epigallocatechin gallate, gallate, gallic acid, miswak extract, sea thorn extract), bisguanide antiseptics (eg chlorhexidine, alexidine or octenidine), quaternary ammonium compounds (eg cetylpyridinium (CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic antiseptics, hexetidine, octenidine, sanguinarine, iodine povidone, delmopinol, metho example, zinc salts, for example, zinc citrate, stannous salts, copper salts, iron salts), blood, propolis and oxygenation agents (eg, hydrogen peroxide, buffered sodium peroxyborate or perox icarbonate), phthalic acid and its salts, monopertalic acid and its salts and esters, ascorbyl stearate, oleoyl sarcosine, alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphen bromide, delmopinol, octapinol and other piperidine derivatives, preparations of piperidine, chloride salts; and mixtures of any of the foregoing; for example, comprising triclosan or cetylpyridinium chloride.
1.29 Any of the preceding compositions comprising an effective antibacterial amount of triclosan, for example, 0.1-0.5%, for example, about
,% ,%
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11/60
1.30 Any of the preceding compositions additionally comprising a bleaching agent, for example, one selected from the group consisting of peroxides, metal chlorites, perborates, percarbonates, peracids, hypochlorites, and combinations thereof.
1.31 Any of the compositions additionally comprising hydrogen peroxide or a source of hydrogen peroxide, for example, urea peroxide or a peroxide salt or complex (for example, such as peroxyphosphate, peroxycarbonate, perborate, peroxysilicate, or salts of persulfate, for example calcium peroxyphosphate, sodium perborate, sodium carbonate peroxide, sodium peroxyphosphate and potassium persulfate).
1.32 Any of the foregoing compositions additionally comprising an agent that interferes with or prevents bacterial adhesion, for example, sorbrol or chitosan.
1.33 Any of the compositions further comprising a source of calcium and phosphate selected from (i) vitreous calcium complexes, for example, sodium and calcium phosphosilicates and (ii) calcium and protein complexes, for example, casein phosphopeptide-amorphous calcium phosphate.
1.34 Any of the compositions additionally comprising a soluble calcium salt, for example, selected from calcium sulfate, calcium chloride, calcium nitrate, calcium acetate, calcium lactate and combinations thereof.
1.35 Any of the compositions additionally comprising an acceptable physiological or potassium salt
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12/60 orally, for example, potassium nitrate or potassium chloride, in an amount effective to reduce dentin sensitivity.
1.36 Any of the preceding compositions additionally comprising an anionic polymer, for example, a synthetic anionic polymeric polycarboxylate, for example, in which the anionic polymer is selected from 1: 4 to 4: 1 of anhydride or maleic acid with another polymerizable monomer ethylenically unsaturated; for example, where the anionic polymer is a methyl vinyl ether / maleic anhydride (PVM / MA) copolymer, copolymer having a weight
molecular average (M.W.) in about 30,000 about in 1,000,000, for example, in about 300,000 about in 800,000, for example, in what the polymer anionic is about in 1-5%, for example, about of 2 %, weight composition.1.37 Any an of the compositions precedent further comprising a refreshing oral, perfume or
breath flavoring.
1.38 Any of the preceding compositions, wherein the pH of the composition is approximately neutral, for example from pH 6 to pH 8, for example, from about pH 7.
1.39 Any of the preceding compositions in the form of a mouthwash, in which the amino acid is lysine and zinc and lysine form a lysine-zinc chloride complex and which has the chemical structure [Zn (C6H14N2O2) 2Cl] ⁺ Cl ^- in a amount providing 0.5-2%, for example, about 1% by weight of zinc, the composition further comprising humectant,
for example, sorbitol, propylene glycol and mixtures From themselves, per example, in an amount 10-25%, per example, about 15-20%, surfactant non-ionic, per
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13/60 example, poloxamer, for example, in an amount of 0.11%, and sweetener, flavorings, and water, for example, a mouthwash comprising:
Ingredients % by weight Sorbitol3-7% for example, about 4% ZLCTo provide 0.5-2% Zn, for example, about 1% Zn Propylene glycol5-10%, for example, about 7% Poloxamer, per 0.1-1% by weight, for example, about 0.4% example, Poloxamer 407Glycerin5-10% by weight, for example, about 7.5% Flavoringsweetener and / or 0.01% -1% for example, about 0.1% Deionized water70-85%, for example, about 80%
1.40 Any of the preceding compositions in the form of an oral gel, in which the amino acid is lysine and zinc and lysine form a lysine-zinc chloride complex that has the chemical structure [Zn (C6H14N2O2) 2Cl] ⁺ Cl ^- in a amount to provide 0.1-2%, for example, about 0.5% by weight of zinc, and further comprises humectant, for example, sorbitol, propylene glycol and mixtures thereof, for example, in an amount of 45- 65%, for example, about 50-60%, thickeners, for example cellulose derivatives, for example, selected from carboxymethylcellulose (CMC), trimethyl cellulose (TMC) and mixtures thereof, for example, in an amount of 0.1-2%, sweetener and / or flavorings and water, for example, an oral gel comprising:
Ingredients % by weight
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14/60
Sorbitol 40-60%, for example, 50-55% ZLC To provide 0.1-2% Zn, forexample, 0.5% Zn Carboxymethyl cellulose(CMC) and trimethylcellulose (TMC) 0.5-1%, for example, about 0.7% Flavoring and / orsweetener 0.01-1% Propylene glycol 1-5%, for example, about 3.00%
1.41 Any of the preceding compositions for use in reducing and inhibiting acidic enamel erosion, cleaning teeth, reducing biofilm and plaques generated by bacteria, reducing gingivitis, inhibiting tooth decay and forming cavities, and reducing dentin hypersensitivity .
[00012] The invention additionally provides methods for reducing and inhibiting acidic enamel erosion, cleaning teeth, reducing biofilm and plaques generated by bacteria, reducing gingivitis, inhibiting tooth decay and forming cavities, and reducing hypersensitivity of dentin comprising applying an effective amount of a composition of the invention, for example, of Composition 1 and sequences to the teeth and optionally rinsing with sufficient water or aqueous solution to trigger precipitation of the zinc oxide of the composition.
[00013] The invention further provides a method for obtaining a composition for oral care, comprising a complex of amino acid and zinc, for example, any of Composition 1 and sequences comprising the combination of a
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15/60 source of zinc ions with an amino acid, in free or salt form (for example, combining zinc oxide with lysine hydrochloride), in an aqueous medium, optionally isolating the complex thus formed as a solid salt , and combining the complex with an oral base, for example, a base of toothpaste or mouthwash.
[00014] For example, in various modalities, The invention provides methods Stop) reduce The hypersensitivity of teeth, (ii) reduce the accumulation gives bacterial plaque, (iii) reduce or inhibit The
demineralization and promote remineralization of the teeth, (iv) inhibit the formation of microbial biofilms in the oral cavity, (v) reduce or inhibit gingivitis, (vi) promote the healing of wounds or cuts in the mouth, (vii) reduce levels of acid-producing bacteria, (viii) increase the relative levels of non-cariogenic and / or non-plaque forming bacteria, (ix) reduce or inhibit the formation of dental caries, (x), reduce, or inhibit the repair of pre- enamel caries, for example, as detected by quantitative light-induced fluorescence (QLF) or electrical measurement of caries (ECM), (xi) treating, relieving or reducing dry mouth, (xii) cleaning teeth and oral cavity, ( xiii) reduce erosion, (xiv) whiten teeth; (xv) reduce the formation of tartar, and / or (xvi) promote systemic health, including cardiovascular health, for example, by reducing the potential for systemic infection through oral tissues, including the application of any of the compositions 1 , and sequences, as described above, to the oral cavity of a person in
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16/60 need, for example, one or more times a day. The invention further provides compositions 1, and sequences for use in any of these methods.
[00015] The invention further provides the use of zinc and an amino acid to obtain an oral care composition comprising an amino acid and zinc complex.
[00016] The invention further provides the use of an amino acid and zinc complex, for example, an amino acid and zinc halide, for example, a lysine-zinc chloride complex to reduce and inhibit acid and enamel erosion, clean the teeth, reduce biofilm and plaque generated by bacteria, reduce gingivitis, inhibit tooth loss and cavity formation, and / or reduce dentin hypersensitivity.
[00017] Without claiming to be limited by theory, it is believed that the formation of the amino acid halide proceeds through the formation of the zinc halide, then the coordination of the amino acid residues around a central zinc. When reacting ZnO with lysine hydrochloride in water, as an example, zinc can react with lysine and / or lysine HCl to form a clear solution of the Zn-lysine-chloride complex (ZnLys3Cl2), where Zn ⁺⁺ located in an octahedral center coordinated with two oxygen atoms and two nitrogen atoms in the equatorial plane from two lysine carboxylic acids and the amine groups, respectively. Zinc is also coordinated with the third lysine through its nitrogen and carboxylic oxygen, at the apical position of the metal's geometry.
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17/60 [00018] In another embodiment, a complex zinc cation with two amino acid residues and two chloride residues. For example, when the amino acid is lysine, the complex has the formula [Zn (C6H14N2O2) 2Cl] ⁺ Cl ^- . In this complex, the Zn cation is coordinated by two lysine ligands with two N atoms of the NH2 groups and O atoms of the carboxylic groups in an equatorial plane. It reveals a distorted geometry of pyramidal squares with the apical position occupied by a Cl ^- atom. This new structure gives rise to a positive cation fraction, to which a Cl ^- anion is combined to form the ionic salt.
[00019] Other zinc and amino acid complexes are possible, and their exact shape depends, in part, on the molar ratios of the precursor compounds, for example, if there is limited halide, halide-free complexes can form, for example, ZnOLys2 , having a pyramid geometry, with the equatorial plane, which is the same as the compound above (Zn is linked to two oxygen atoms and two nitrogen atoms from different lysines), in which the top of the pyramid is occupied by an O atom.
[00020] Mixtures of complexes and / or additional complex structures, for example, involving multiple zinc ions based on the zinc structure, are possible and contemplated within the scope of the invention. When complexes are in solid form, they can form crystals, for example, in hydrated form.
[00021] Regardless of the exact structure of the complex or complexes, however, the interaction of zinc and amino acid converts zinc salts or zinc oxide
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18/60 insoluble in a highly soluble complex at approximately neutral pH. With the increase in water dilution, however, the complex dissociates and the zinc ion converts to insoluble zinc oxide. This dynamic is unexpected - typically ionic compositions become more soluble at greater dilution, not less - and this facilitates the deposition of zinc precipitate on teeth after administration, in the presence of saliva and with a rinse. This precipitation occludes the dentinal tubules, thus reducing hypersensitivity, and also providing zinc to the enamel, which reduces acid erosion and the formation of biofilm plaques.
[00022] Must be understood what other amino acids can be used in place in lysine in scheme previous. It will also be understood what, although the zinc, amino acids and optionally the halide can be
mainly in the form of precursor materials or in the form of an ionic complex, there may be some degree of equilibrium, so that the proportion of material that is actually in the complex compared to the proportion in the form of precursor may vary depending on conditions you need formulation, material concentration, pH, presence or absence of water, presence or absence of other charged molecules, and so on.
[00023] The active agents can be distributed in the form of any oral care formulations, for example, a toothpaste, gel, elixir, powder, cream, strip, gum, or any other known in the art.
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19/60 [00024]
If the active ingredients are distributed in the form of a mouthwash, a person who wants the benefits rinses with the master solution and the natural dilution of the master solution by saliva will initiate zinc precipitation. Alternatively, the person can mix the concentrated solution with an appropriate amount of aqueous diluent and rinse with the mixture.
[00025] In another embodiment, the mixture is prepared and immediately transferred to a holding tray, such as that used with bleaching gels and for an effective period of time.
with the mixture will be retention, the mixture of low viscosity or using the person tray can
The teeth what They are in treated. For use with The Can be in the shape of one
liquid tray contact a gel.
[00026] In another embodiment, the master solution, or a mixture of master solution with water is applied to the teeth in a gel formulation, for example, in which the gel can remain on the tooth for a long period of time for an effective treatment .
[00027] In another modality, the asset is provided in a toothpaste. After brushing, the active substance is diluted by saliva and water, leading to precipitation and the formation of deposits and particles of occlusion.
[00028] The rate of precipitation from the formulation can be modulated by adjusting the concentration of the complex in the master solution and changing the ratio of the master solution to water. A more diluted formula leads to
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20/60 faster precipitation and is therefore preferred when rapid treatment is desired.
[00029] The advantages of the oral care compositions of the invention are numerous. By providing zinc ions and zinc-containing compounds that can release zinc ions into oral cavities, the oral care compositions of the present invention provide antimicrobial, anti-plaque, anti-gingivitis benefits, combat unpleasant odors, cavities, and have anticalculation advantages. Occlusion particles and surface deposits are zinc-containing compounds (specifically ZnO), as well as other zinc derivatives that can release zinc ions into the oral cavities and provide the various benefits recognized as above. Additional advantages include, but are not limited to, antifixation, antiperiodontitis and bone loss, as well as promoting wound healing.
[00030] A second benefit consists of the anti-erosion properties of zinc ions, which form anti-erosion deposits on the surfaces of teeth through oxidation and hydrolysis. Surface deposits, as well as occlusion particles, can react and neutralize acids, thus protecting the tooth surface from the erosive effects of acids. In this regard, the more surface / occlusion depositions the treatments lead to, the more effective the treatments will be and therefore zinc arginine and zinc lysine are preferred. It is also observed that when surface deposits and occlusion particles neutralize acids, beneficial zinc ions and
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21/60 amino acids (infra) can be released, providing advantages for oral care and others besides anti-erosion.
[00031] A third benefit is anti-sensitivity benefit as a result of occlusion. Occlusion of dentinal tubules leads to relief of sensitivity.
[00032] A fourth advantage is the benefit associated with amino acids. The occlusion particles and surface deposits contain the corresponding amino acids, such as arginine and lysine. These amino acids provide several benefits. For example, basic amino acids lead to a higher pH of plaque and can provide anti-caries benefits.
[00033] The composition may include the amino acid and zinc halide and / or its precursors. Precursors, which can react in situ with water, to form the amino acid and zinc halide, include (i) zinc and an amino acid hydrohalide, or (ii) zinc chloride and amino acid, or (iii) a source of zinc ions , an amino acid and a halogen acid, or (iv) combinations of (i), (ii), and / or (iii). In one embodiment, the amino acid and zinc halide can be prepared at room temperature by mixing the precursors in a solution, such as water. In situ training provides ease of formulation. Precursors can be used instead of first having to form the amino acid and zinc halide. In another modality, water, allowing the formation of the amino acid and zinc halide from the precursor, arrives from saliva and / or rinse water that comes into contact with the composition after application.
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22/60 [00034] The amino acid and zinc halide is a water soluble complex formed from the addition salt of zinc halide acid (eg, zinc chloride) and an amino acid, or from the addition salt halide acid of an amino acid (eg, lysine hydrochloride) and a source of zinc ions, and / or from the combination of all three of a halogen acid, an amino acid, and a source of zinc ion .
[00035] Examples of amino acids include, but are not limited to, common natural amino acids, for example: lysine, arginine, histidine, glycine, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, tryptophan, aspartic acid and glutamic acid. In some embodiments, the amino acid is a neutral amino acid or acidic amino acid, for example, glycine.
[00036] As can be seen from the examples below, the precipitation of zinc from the complex, when diluted with water is most noticeable when the complex is formed from a basic amino acid. Thus, when dilution precipitation is desired, a basic amino acid may be preferred. In some embodiments, therefore, the amino acid is a basic amino acid. The term basic amino acid means the naturally occurring basic amino acids, such as arginine, lysine and histidine, as well as any basic amino acid having a carboxyl group and an amino group in the molecule, which is soluble in water and provides a solution
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Aqueous 23/60 with a pH of about 7 or higher. Consequently, basic amino acids include, but are not limited to, arginine, lysine, citrulline, ornithine, creatine, histidine, diaminobutanoic acid, diaminoproprionic acid, its salts or combinations thereof. In certain embodiments, the amino acid is lysine. In other embodiments, the amino acid is arginine.
[00037] The halide can be chlorine, bromine, or iodine, more typically chlorine. The acid addition salt of an amino acid and a halogen acid (for example, HCl, HBr, or HI) is sometimes referred to herein as an amino acid hydrochloride. Thus an example of amino acid hydrochloride is lysine hydrochloride. Another is glycine hydrochloride.
[00038] The source of zinc ion for the combination with an amino acid halide or an amino acid, optionally plus the halogen acid in this case can be, for example, zinc oxide or zinc chloride.
[00039] In certain embodiments, the amount of amino acid and zinc halide in the composition is 0.05 to 10% by weight of the composition. In certain embodiments, precursors, for example, amino acid and zinc hydrohalide, are present in amounts such that, when combined in the amino acid and zinc halide, the amino acid and zinc halide would be present in an amount of 0.05 to 10% in weight of the composition. In either of these embodiments, the amount of the amino acid and zinc halide can be varied for the desired purpose, such as a toothpaste or mouthwash. In other embodiments, the amount of the halide
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24/60 amino acid and zinc is at least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least 3, at least 4 to 10% by weight of the composition. In other embodiments, the amount of amino acid and zinc halide is less than 9, less than 8, less than 7, less than 6, less than 5, less than 4, less than 3, less than 2, less than 1, less than 0, 5 to 0.05% by weight of the composition. In other modalities, the quantities are
0.05 to 5%, from 0.05 to 4%, from 0.05 to 3%, from 0.05 to 2%, from 0.1 to 5%, from 0.1 to 4%,4%, from 0.1 to 3%,3%, from 0.1 to 2%, from 0.5 to 5%, from 0.5 to 4%, in 0.5 to 3% or of 0.5 to 2% by weight gives composition. [00040] In certain modalities, O zinc is present in a amount in 0.05 to 10% by weight gives
composition. In other embodiments, the amount of zinc is at least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least 3, or at least 4 to 10% by weight of the composition. In other embodiments, the amount of zinc is less than 9, less than 8, less than 7, less 6, less than 5, less than 4, less than 3, less than 2, less than 1, less than 0.5 to 0.05% by weight of the composition. In other modalities, the quantities are from 0.05 to 5%, from 0.05 to 4%, from 0.05 to 3%, from 0.05 to 2%, from 0.1 to 5%, from 0, 1 to 4%, 0.1 to 3%, 0.1 to 2%, 0.5 to 5%, 0.5 to 4%, 0.5 to 3% or 0.5 to 2% by weight of the composition.
[00041] In certain embodiments, amino acid hydrohalide is present in an amount of 0.05 to 30% by weight. In other modalities, the quantity is at least
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25/60
0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, at least 1, at least 2, at least 3, at least 4, at least 5, at least 10, at least 15, at least 20 to 30% by weight. In other embodiments, the quantity is less than 30, less than 25, less than 20, less than 15, less than 10, less than 5, less than 4, less than 3, less than 2, or less than 1 to 0, 05% by weight of the composition.
[00042] When precursor materials are present, they are preferably present in molar proportions approximately as necessary to produce the desired amino acid and zinc halide, although an excess of one material or another may be desirable, in certain formulations, for example. example, to balance the pH against other components of the formulation, to provide additional antibacterial zinc, or to provide amino acid buffer. Preferably, however, the amount of halide is limited, as restricting the level of halide does little to encourage interaction between zinc and the amino acid.
[00043] In some embodiments, the total amount of zinc in the composition is 0.05 to 8% by weight of the composition. In other embodiments, the total amount of zinc is at least 0.1, at least 0.2, at least 0.3, at least 0.4, at least 0.5, or at least 1 to 8% by weight of the composition. In other embodiments, the total amount of zinc in the composition is less than 5, less than 4, less than 3, less than 2, or less than 1 to 0.05% by weight of the composition.
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26/60 [00044] In certain embodiments, a molar ratio of zinc to amino acids is at least 2: 1. In other embodiments, the molar ratio is at least 1: 1, at least 1: 2, at least 1: 3, at least 1: 4, 2: 1 to 1: 4, 1: 1 to 1: 4, 1: 2 to 1: 4, 1: 3 to 1: 4, 2: 1 to 1: 3, 2: 1 to 1: 2, 2: 1 to 1: 1, or 1: 3. Above 1: 4, zinc is expected to be fully dissolved.
[00045] In certain embodiments, the composition is anhydrous. The term anhydrous (o), means that there is less than 5% by weight of water, optionally less than 4, less than 3, less than 2, less than 1, less than 0.5, less than 0.1 to 0 % by weight of water.
[00046] When provided in an anhydrous composition, precursors, for example, TBZC and amino acid hydrohalide, will not react significantly to form the amino acid and zinc halide. When placed in contact with a sufficient amount of water, which may be in the form of saliva and / or the water used to rinse the mouth, during or after applying the composition, the precursors will then react to form the amino acid and zinc halide, then, after further dilution, they will provide the precipitate containing zinc to the teeth.
[00047] The vehicle represents all other materials in the composition other than the amino acid-zinc halide complex or its precursors. The vehicle amount is then the amount to reach 100%, adding to the weight of the amino acid and zinc halide, including any precursors.
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27/60 [00048] Active Agents: The compositions of the invention can comprise various agents that are active to protect and increase the strength and integrity of the enamel and teeth structure and / or to reduce tooth decay and associated bacteria and / or diseases gingival. The effective concentration of the active ingredients used in this document will depend on the particular agent and the delivery system used. It is understood that a toothpaste, for example, will typically be diluted with water upon use, while a mouthwash will typically not be. Thus, an effective concentration of active ingredient in a toothpaste will normally be 5 to 15 times greater than that required for a mouthwash. The concentration will also depend on the exact salt or polymer selected. For example, when the active agent is supplied in the form of salt, the counterion will affect the weight of the salt, so that if the counterion is heavier, more salt by weight will be needed to provide the same concentration of active ion in the final product. . Arginine, when present, can be present at levels, for example, from about 0.1 to about 20% by weight (expressed as free base weight), for example, about 1 to about 10% by weight of a consumer toothpaste or about 7 to about 20% by weight for a professional treatment product or prescription. Fluoride when present can be present at levels, for example, from about 25 to about 25,000 ppm, for example, from about 750 to about 2,000 ppm for a consumer toothpaste, or from about 2,000 to about 25,000 ppm of a professional treatment product or prescription. Levels of antibacterial agents will vary
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28/60 in the same way, with levels used in toothpaste being, for example, from about 5 to about 15 times higher than those used in mouthwashes. For example, a triclosan toothpaste can contain about 0.3% by weight of triclosan.
[00049] Source of fluoride ions: Oral care compositions may also include one or more sources of fluoride ions, for example, soluble fluoride salts. A wide variety of materials that yield fluoride ions can be used as a source of soluble fluoride in the present compositions. Examples of suitable materials that yield fluoride ions are found in US Patent No. 3,535,421 to Briner and others; 4,885,155 by Parran, Jr. and others and 3,678,154 by Widder and others. Representative sources of fluoride ions include, but are not limited to stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorphosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride and combinations thereof.
In certain embodiments, the fluoride ion source includes stannous fluoride, sodium fluoride, sodium monofluorophosphate, as well as mixtures thereof. In certain embodiments, the oral care composition of the invention may also contain a source of fluoride ions or fluoride-providing ingredient in sufficient quantities to supply from about 25 ppm to about 25,000 ppm of fluoride ions, generally at least about 500 ppm , for example, from about 500 to about 2,000 ppm, for example, from about 1,000 to about 1,600 ppm, for example, about 1,450 ppm. The appropriate level of fluoride will depend on the particular application. A toothpaste
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29/60 for general use in general typically ranges from about 1,000 to about 1,500 ppm, with pediatric toothpaste showing slightly less. A toothpaste or coating for professional application could have as much as about 5,000 or even about 25,000 ppm of fluoride. Fluoride ion sources can be added to the compositions of the invention at a level of about 0.01% by weight to about 10% by weight. In one embodiment, from about 0.03% by weight to about 5% by weight and in another embodiment from about 0.1% by weight to about 1% by weight of the composition, in another embodiment. The weights of the fluoride salts to provide the appropriate level of fluoride ion will, of course, vary according to the weight of the counterion in the salt.
[00050] Amino acids: In some embodiments, the compositions of the present invention comprise an amino acid. In particular embodiments, the amino acid can be a basic amino acid. The term basic amino acid means naturally occurring basic amino acids, such as arginine, lysine and histidine, as well as any basic amino acid having a carboxyl group and an amino group in the molecule, which is soluble in water and provides an aqueous solution with a pH of about 7 or higher. 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. In
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30/60 certain modalities, the basic amino acid is arginine, for example, l-arginine or a salt thereof.
[00051] In various embodiments, the amino acid is present in an amount of about 0.5% by weight to about 20% by weight of the total weight of the composition, from about 0.5% by weight to about 10% by weight of the total weight of the composition, for example, from about 1.5% by weight to about 3.75% by weight, about 5% by weight or about 7.5% by weight of the total weight of the composition in the case of a toothpaste, or for example, about 0.5-2% by weight, for example, about 1% in the case of a mouthwash.
[00052] Abrasives: The compositions of the invention, for example, Composition 1 and sequences can comprise silica abrasives and can comprise additional abrasives, for example, a calcium phosphate abrasive, tricalcium phosphate (Ca3 (PO4) 2), hydroxyapatite ( Ca10 (PO4) 6 (OH) 2), or dicalcium phosphate dihydrate (CaHPO4.
2H2O, also sometimes referred to in this document as DiCal) or calcium pyrophosphate, abrasive calcium carbonate; or abrasives, such as sodium metaphosphate, potassium metaphosphate, aluminum silicate, calcined alumina, bentonite or other silica materials or combinations thereof.
[00053] Other abrasive silica polishing materials useful herein, as well as other abrasives generally have an average particle size ranging between about 0.1 and about 30 microns, between about 5 and about 15 microns. The silica abrasives can be precipitated silica or silica gels, such as the silica xerogels described in US Patents.
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31/60 numbers 3,538,230 to Pader et al. And US Patent number 3,862,307 to Digiulio. Private silica Xerogels are marketed under the trade name Syloid® by WR Grace & Co., Davison Chemical Division. Precipitated silica materials include those marketed by JM Huber Corp. under the trade name Zeodent®, including silica with the designation Zeodent 115 and 119. These silica abrasives are described in US Patent No. 4,340,583, issued to Wason. In certain embodiments, useful abrasive materials for practicing the compositions for oral care according to the invention include precipitated and silica , amorphous silica gels having a value of less oil absorption of about 100 ^cm3 / 100 g silica and range of about 45 cm3 / 100 g to about 70 cm3 / 100 g of silica. Oil absorption values are measured using the ASTA Rub-Out D281 method. In certain embodiments, silicas are colloidal particles with an average particle size of about 3 microns to about 12 microns and about 5 to about 10 microns. Low oil absorption silica abrasives particularly useful in the practice of the invention are marketed under the trade name Sylodent XWA® by Davison Chemical Division of WR Grace & Co., Baltimore, Md. 21203. Sylodent 650 XWA®, a silica hydrogel, composed of colloidal silica particles having a water content of 29% by weight, on average about 7 to about 10 microns in diameter, and an oil absorption of less than about 70 cm3 / 100 g of silica is an example of a low oil absorption silica abrasive useful in the practice of the present invention.
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[00054] Foaming agents: The oral care compositions of this invention may also include an agent for increasing the amount of foam that is produced when the oral cavity is brushed. Illustrative examples of agents that increase the amount of foam include, but are not limited to, polyoxyethylene and certain polymers including, but not limited to, alginate polymers. Polyoxyethylene can increase the amount of foam and the foam thickness generated by the oral care vehicle component of the present invention. Polyoxyethylene is also commonly known as polyethylene glycol (PEG), or polyethylene oxide. The polyoxyethylenes suitable for this invention will have a molecular weight of about 200,000 to about 7,000,000. In one embodiment, the molecular weight will be about 600,000 to about 2,000,000 and in another mode from about 800,000 to about 1,000,000. Polyox® is the trade name for high molecular weight polyoxyethylene produced by Union Carbide. Polyoxyethylene can be present in
an amount of fence in 1 9-1% about in 90% , in a modality of fence in 5% The fence in 50% and in another modality of fence in 10% The fence in 20% in weight
carrier component of the oral care compositions of the present invention. When present, the amount of foaming agent in the oral care composition (i.e., a single dose) is about 0.01 to about 0.9%, by weight, about 0.05 to about 0.5% by weight, and in another embodiment from about 0.1 to about 0.2% by weight.
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33/60 [00055] Surfactants: Compositions useful in the invention may contain anionic surfactants, for example:
i. water-soluble salts of higher fatty acid monoglyceride monosulfates, such as the sodium salt of the coconut oil fatty acid monoglyceride, such as sodium N-methyl N-cocoyl taurate, sodium cocomonoglyceride sulphate, ii . higher alkyl sulfates, such as sodium lauryl sulfate, iii. higher alkyl ether sulfates, for example, of the formula CH3 (CH2) mCH2 (OCH2CH2) nOSO3X, where m is 6-16, for example, 10, n is 1-6, for example, 2, 3 or 4, and X is Na or K, for example, sodium laureth-2 sulfate (CH3 (CH2) 10CH2 (OCH2CH2) 2OSO3Na), iv. higher alkylarylsulfonates, such as sodium dodecyl benzene sulfonate (sodium lauryl benzene sulfonate).
v. higher alkyl sulfoacetates, such as sodium lauryl sulfoacetate (sodium dodecyl sulfoacetate), higher fatty acid esters of 1,2 dihydroxypropane sulfonate, sulfocolaurate (potassium laurate sulfoacetamide N-2-ethyl)) and sodium lauryl sarcocinate.
[00056] The term upper alkyl means, for example, C6-30 alkyl. In the specific embodiments, the anionic surfactant is selected from sodium lauryl sulfate and sodium lauryl sulfate ether. The anionic surfactant may be present in an amount that is effective, for example,> 0.01% by weight of the formulation,
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34/60 but not at a concentration that is irritating to oral tissue, as they depend on the example, <10%, and the optimal concentrations of the specific formulation and the specific surfactant.
For example, the concentrations used or mouthwash are typically on the order of one tenth of those used for toothpaste. In one embodiment, the anionic surfactant is present in the toothpaste of about 0.3%, about 4.5% by weight, for example, about 1.5%.
The compositions of the invention may optionally contain mixtures of surfactants, for example, comprising anionic surfactants and other surfactants which can be anionic, cationic, zwitterionic or non-ionic. Generally, surfactants are those that are reasonably stable over a wide pH range. Surfactants are described more fully, for example, in the Patent
US 3,959,458 to Agricola and others;
US patent 3,937,807 to Haefele; and US patent number
4,051,234 by Gieske et al., Which are incorporated herein by reference. In certain embodiments, the anionic surfactants useful for this invention include the water-soluble salts of alkyl sulfates having about 10 to about 18 carbon atoms in the alkyl radical and the water-soluble salts of sulfonated fatty acid monoglycerides with about of about 18 carbon atoms. Sodium lauryl sulfate, sodium lauroyl sarcosinate and sodium monoglyceride sulfonates are examples of anionic surfactants of this type.
In a particular embodiment, the composition of the invention, for example, the
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35/60
Composition 1 and sequences comprise sodium lauryl sulfate.
[00057] The surfactant or mixtures of compatible surfactants can be present in the compositions of the present invention in about 0.1% to about 5.0%, in another embodiment, about 0.3% to about 3, 0% and in another embodiment from about 0.5% to about 2.0% by weight of the total composition.
[00058] Tartar control agents: In the various embodiments of the present invention, the compositions comprise an anti-calculating agent (tartar control). Suitable anti-calculating agents include, without limitation, phosphates and polyphosphates (eg, pyrophosphates), polyamino propane sulfonic acid (AMPS)], hexametaphosphate salts, zinc citrate trihydrate, polypeptides, polyolefin sulfonates, polyolefin phosphates, diphosphonates. The invention thus can comprise phosphate salts in addition to zinc phosphate. In particular embodiments, these salts are alkaline phosphate salts, that is, salts of alkali metal hydroxides or alkaline earth hydroxides, for example, sodium, potassium or calcium salts. Phosphate, as used herein, encompasses orally acceptable mono- and polyphosphates, for example, P1-6 phosphates, for example, monomeric phosphates, such as monobasic, dibasic or tribasic phosphate; dimeric phosphates, such as pyrophosphates; and multimeric phosphates, for example, sodium hexametaphosphate. In the particular examples, the selected phosphate is that obtained from alkaline dibasic phosphate and alkaline pyrophosphate salts, for example,
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36/60 selected from dibasic sodium phosphate, dibasic potassium phosphate, dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, sodium tripolyphosphate, and
mixtures of any two or more of these. In a modality specific, per example, at compositions understand a mix in pyrophosphate in tetrasodium
(Na4P2O7), calcium pyrophosphate (Ca2P2O7) and dibasic sodium phosphate (Na2HPO4), for example, in quantities of about
3-4% of the dibasic sodium phosphate and about 0.2-1% of each of the pyrophosphates. In another embodiment, the compositions comprise a mixture of tetrasodium pyrophosphate (TSPP) and sodium tripolyphosphate (STPP) (Na5P3O10), for example, in ratios of about 1-2% TSPP and about 7% about STPP 10%. Such phosphates are supplied in an amount effective to reduce enamel erosion, to aid teeth cleaning, and / or to reduce the accumulation of tartar on the teeth, for example, in an amount of 2-20%, for example, about 5-15%, by weight of the composition.
[00059] Flavoring agents: The oral care compositions of this invention can also include a flavoring agent. Flavoring agents that are used in the practice of the present invention include, but are not limited to, essential oils as well as the various aldehydes, flavoring esters, alcohols and the like. Examples of essential oils include mint, peppermint, wintergreen, sassafras, cloves, sage, eucalyptus, marjoram, cinnamon, lemon, grapefruit and orange oils. Chemicals such as
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37/60 menthol, carvone and anethole. Certain modalities use peppermint and peppermint oils. The flavoring agent can be incorporated into the oral composition at a concentration of about 0.1 to about 5% by weight, for example, from about 0.5 to about 1.5% by weight.
[00060] Polymers: The oral care compositions of the invention also include polymers, additional in order to adjust the viscosity of the formulation or improve the solubility of other ingredients. Such additional polymers include polyethylene glycols, polysaccharides (for example, cellulose derivatives, for example, carboxymethyl cellulose, or polysaccharide gums, for example, xanthan gum or carrageenan gum). Acid polymers, for example, polyacrylate gels can be supplied in the form of their free acids or partially or completely neutralized water-soluble alkali metal (eg, potassium and sodium) or ammonium salts.
[00061] Silica thickeners, which form polymeric or gel structures in aqueous media may be present. It should be noted that these silica thickeners are physically and functionally distinct from the particulate silica abrasives also present in the compositions, as the silica thickeners are very finely divided and offer little or no abrasive action. Other thickening agents are carboxyvinyl polymers, carrageenan, hydroxyethyl cellulose and water soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose. Natural gums such as gum caraia, gum arabic, and tragacanth gum can also be incorporated. Silicate
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38/60 colloidal magnesium aluminum can be used as a component of the thickener composition to further improve the texture of the composition. In certain embodiments, thickening agents are used in an amount of about 0.5% to about 5.0% by weight, of the total composition.
[00062] The compositions of the invention can include an anionic polymer, for example, in an amount of about 0.05 to about 5%. Such agents that are generally known for use in toothpaste, although not for that specific application, and useful in the present invention are disclosed in US Patent numbers 5,188,821 and 5,192,531; and include synthetic anionic polymeric polycarboxylates, such as 1: 4 to 4: 1 copolymers of maleic anhydride or acid with another ethylenically unsaturated, polymerizable monomer, preferably methyl vinyl ether / maleic anhydride having a molecular weight (MW) of about 30,000 to about 1,000,000, more preferably about 300,000 to about 800,000. These copolymers are available, for example, as Gantrez, for example, AN 139 (M.W. 500,000), AN 119 (M.W. 250,000) and preferably S-97 Pharmaceutical Grade (M.W 700,000) available from ISP Technologies,
Inc., Bound Brook, NJ 08805. The reinforcing agents, when present, are present in amounts ranging from about 0.05 to about 3% by weight. Other operative polymers include those, such as 1: 1 maleic anhydride copolymers with ethyl acrylate, hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, or ethylene, the latter being available, for example, as Monsanto EMA number 1103 , MW 10,000 and EMA Grade 61, and 1: 1 acrylic acid copolymers with methyl or hydroxyethyl methacrylate,
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39/60 methyl or ethyl acrylate, isobutyl vinyl ether or Nvinyl-2-pyrrolidone. Generally suitable are olefinically polymerized or ethylenically unsaturated carboxylic acids containing an olefinic carbonocarbon double bond and at least one carboxyl group, that is, an acid containing an olefinic double bond that works readily in polymerization due to its presence in the monomer molecule, either in alpha-beta position relative to a carboxyl group or as part of a terminal methylene group. Illustrative of such acids are acrylic, methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxy-propionic, sorbic, alpha-chlorocorbic, cinnamic, beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic, alpha-phenacyl, alpha-phenacyl, alpha-phenolic , 2-benzyl acrylic, 2cyclohexylacrylic, angelic, umbelic, fumaric, maleic and anhydrides. Other different olefinic monomers copolymerizable with these carboxylic monomers include vinyl acetate, vinyl chloride, dimethyl maleate and the like. Copolymers contain sufficient carboxylic salt groups for water solubility. Another class of polymeric agents includes a composition that contains the acrylamide homopolymers and / or unsaturated sulfonic acid homopolymers and substituted salts thereof, in particular, where the polymers are based on unsaturated sulfonic acids selected from sulfonic acrylamide acids, such such as 2-acrylamide2-methylpropane acid having a molecular weight of about 1,000 to about 2,000,000, described in US Patent No. 4,842,847, June 27, 1989 to Zahid, incorporated into
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40/60 this document as a reference. Another useful class of polymeric agents includes polyamino acids containing proportions of anionic surface active amino acids, such as aspartic acid, glutamic acid and phosphoserine, as disclosed in US Patent No. 4,866,161 to Sikes et al.
[00063] Water: Oral compositions can comprise significant levels of water. The water used in the preparation of commercial oral compositions must be deionized and free from organic impurities. The amount of water in the compositions includes free water that is added plus that amount that is introduced with other materials.
[00064] Humectants: Within certain modalities of oral compositions, it is also desirable to incorporate a humectant to prevent the composition from becoming stiff upon exposure to air. Certain humectants can also impart sweetness or desirable flavor to toothpaste compositions. Suitable humidifiers include edible polyhydric alcohols, such as glycerin, sorbitol, xylitol, propylene glycol, as well as other polyols and mixtures of these humectants. In one embodiment of the invention the main humectant is glycerin, which can be present in levels of more than 25%, for example, 25-35%, about 30% with 5% or less of other humectants.
[00065] Other optional ingredients: In addition to the components described above, the embodiments of this invention may contain a variety of optional ingredients for toothpaste, some of which are described below. Optional ingredients include, for example, but not
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41/60 are limited to adhesives, foaming agents, flavoring agents, sweetening agents, additional anti-plaque agents, abrasives and coloring agents. These and other optional components are further described in US Patent No. 5,004,597 to Majeti; US Patent 3,959,458 to Agricola et al. And US Patent 3,937,807 to Haefele, all of which are incorporated herein by reference.
[00066] Unless otherwise specified, all percentages of the components of the composition provided quantities in the specification are by weight based on the weight of the composition or 100% total formulation.
[00067] Unless otherwise all ingredients for use have been identified, in the compositions and formulations of the present invention are preferably cosmetically acceptable.
The term cosmetically acceptable means suitable for use in a formulation for topical application to human skin.
A cosmetically acceptable excipient, for example, is an excipient that is suitable for external application, in amounts and concentrations contemplated in the formulations of the present invention, and includes, for example, excipients that are generally recognized as safe (GRAS) by United States Food and Drug Administration.
[00068] The compositions and formulations as provided in the present invention are described and claimed with reference to their ingredients, as is customary in the art. As will be evident to a person skilled in the art, the ingredients may in some cases react with each other, so that the true composition of the final formulation
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42/60 may not correspond exactly to the listed ingredients. Thus, it should be understood that the invention extends to the product of the combination of the listed ingredients.
[00069] As used throughout the document, bands are used as an abbreviation to describe each and every value that is within the range. Any value within the range can be selected as the end of the range. In addition, all references cited in this document are incorporated by reference in their entirety. In the event of a conflict between a definition in the present disclosure and that of a cited reference, the present invention will prevail.
[00070] Unless otherwise specified, all percentages and quantities here and elsewhere expressed in this document and elsewhere in the specification should be understood as referring to percentages by weight. The quantities supplied are based on the weight of the active material.
EXAMPLES
Example 1 [00071] The general reaction for the formation of ZLC is as follows:
ZnO + 2 (Lysine. HCl) -> [Zn (Lysine) 2Cl] Cl.2H2O (ZLC)
A molar ratio of
2: 1 of the suspension of
ZnO: Lisina.HCl is prepared with stirring at room temperature for about hours.
The mixture is centrifuged. A volume of mL of supernatant is transferred to a
NMR.
The NMR tube is then placed in a closed test tube, filled with
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43/60 ethanol for crystal development. Several colorless cubic crystals are formed after one week. The crystal structure of the ZLC crystal is determined by single crystal X-ray diffraction. The size of this complex molecule is 1.7 nm * 7.8 nm * 4.3 nm. In this complex, the Zn cation is coordinated by two lysine ligands with two N atoms of the NH2 groups and O atoms of the carboxylic groups in an equatorial plane. It shows a distorted square-pyramidal geometry with the apical position occupied by a Cl atom. This new structure gives rise to a positive radical cation, to which a and an Cl anion is combined to form an ionic salt.
[00072] Synthesis of laboratory stepwise increase of pure ZLC powder: An amount of 2 mol of Lysine HCl is dissolved in 1,000 ml of deionized water with stirring at room temperature, 1 mol of solid ZnO is added slowly to the Lysine HCl solution with stirring and stirring continues at room temperature overnight (about 12 hours). The suspension solution is centrifuged at high speed for 15 min. The supernatant is slowly poured into EtOH. A precipitate is formed immediately. Approximately 5-8 mL of EtOH is required to obtain 1 g of powder. The powdered EtOH solvent is filtered, and an off-white powder is obtained. The powder is placed in an oven at 50 ° C for drying and a yield of 88% of the product is obtained. PXRD confirms the purity of the ZLC powder compared to ZLC crystal.
Example 2
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44/60 [00073] Four batches of mouthwash containing 500 g of NaF, ZLC, ZnCl2 and ZnO as an active ingredient are formulated with the ingredients shown in Table 1. The purpose of this study is to compare the clarity of samples with different actives. Turbidity is assessed by the percentage of light transmission through the solution, as measured by a TurbiScan® dispersion stability analyzer. The higher the percentage of transmission, the more transparent it will be. Thus, a lower percentage of transmission suggests that the solution is more turbid. The concentration of zinc ions in the ZLC solution 25,300 ppm, obtained by analysis of ICP (inductively coupled plasma), which corresponds to approximately 17% by weight of ZLC active ingredients in the solution. The concentration of zinc ions in all batches is controlled to the same level, that is, 1.01% by weight. Among the four batches, the one with ZnO as active has a milk-white appearance, with 0% transmission, while the other three samples are as clear as deionized water (Table 2).
Table 1
Mouthwash containing NaF Ingredients % Load (g) Actual (g) 70% Sorbitol sun 5.5 27.5 27.51 Sodium fluoride 0.05 0.25 0.25 Saccharin 0.02 0.1 0.1 Propylene Glycol 7 35 35 Poloxamer 407 0.4 2 2.01 Citric acid 0.02 0.1 0.1
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Potassium sorbitol 0.05 0.25 0.25 Glycerin 7.5 37.5 37.5 Mint flavoringchili 0.1 0.5 0.5 Deionized water 79.36 396.8 396.8 Total 100 500 500.02
Mouthwash containing ZnCl ₂ Ingredients % Load (g) Actual (g) 70% Sorbitol sun 5.5 27.5 27.5 ZnCl2 47.97% Zn 2.11 10.55 10.56 Saccharin 0.02 0.1 0.1 Propylene Glycol 7 35 34.98 Poloxamer 407 0.4 2 2 Citric acid 0.02 0.1 0.1 Potassium sorbitol 0.05 0.25 0.25 Glycerin 7.5 37.5 37.48 Mint flavoringchili 0.1 0.5 0.48 Deionized water 77.3 386.5 386.88 Total 100 500 500.33 Zn% 1.01
Mouthwash containing ZnO Ingredients % Load (g) Actual (g) 70% Sorbitol sun 5.50 27.5 27.55 ZnCl2 80.34% Zn 1.26 6.3 6.28 Saccharin 0.02 0.1 0.1
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Propylene Glycol 7 35 34.98 Poloxamer 407 0.4 2 2.02 Citric acid 0.02 0.1 0.1 Potassium sorbitol 0.05 0.25 0.25 Glycerin 7.5 37.5 37.52 Mint flavoringchili 0.1 0.5 0.52 Deionized water 78.15 390.75 390.62 Total 100 500 499.94 Zn% 1.01
Mouthwash with ZLC Sorbitol sol 70% 5.5 27.5 27.49 ZLC 2.53% Zn 40 200 200 Saccharin 0.02 0.1 0.1 Propylene glycol 7 35 35.01 Poloxamer 407 0.4 2 2 Citric acid 0.02 0.1 0.1 Potassium sorbitol 0.05 0.25 0.25 Glycerin 7.5 37.5 37.5 Flavoring Mintchili 0.1 0.5 0.5 Deionized water 39.41 197.05 196.98 Total 100 500 499.93 Zn% 1.01
Table 2
Waterdeionized NaF MW ZLC MW ZnCl2 MW ZnO MW pH 5.89 4.79 7.18 3.49 7.03
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Turbidity (% 88.68% 88.40% 86.23% 89.03 0.0016% Streaming)
[00074] All batches of original mouthwash are diluted 2 times, 4 times, 8 times, 16 times and 32 times. Turbidity measurements were performed after all solutions were prepared and thoroughly stirred. The turbidity data of the samples are shown in Table 3, 4, 5 and 6, for the mouthwash dilutions containing NaF, ZLC, ZnCl2 and ZnO, respectively. Precipitation is observed as the ZLC mouthwash sample is diluted, but the turbidity of the other samples is unchanged.
Table 3
2X 4X 8X 16X 32X Turbidity 89.85% 88.90% 88.44% 88.77% 88.61% (% streaming)
Table 4
2X 4X 8X 16X 32X pH 7.46 7.67 7.86 7.80 7.94 Turbidity (% transmission) 86.73% 85.99% 60.50% 59.61% 23.21%
Table 5
2X 4X 8X 16X 32X Turbidity (% transmission) 88.63% 88.04% 87.77% 87.42% 87.99%
Table 6
2X 4X 8X 16X 32X Turbidity (% transmission) 0% 0% 0% 0% 0%
[00075] The diluted ZLC mouthwash samples are placed in a 37 ° C oven over the weekend (about 60 hours) for a stability study. The results are shown in Table 7. Precipitation
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48/60 can be observed and started from the 4-fold dilution. The greatest amount of precipitation is found in the dilution of 16 times. The original batch, however, is still stable and shows no precipitation, even though it is left to stand for 60 hours.
Table 7
0X 2X 4X 8X 16X 32X pH 7.16 7.48 7.65 7.82 7.85 7.95 Turbidity (% in 86.16% 86.15% 8.33% 6.37% 0.14% 9.91% streaming)
[00076] Compared to the batches of mouthwash formulated using ZnCl ₂ and ZnO, only the formulation with ZLC as active can form a clear, stable solution, but generate the precipitate when diluted. This ZLC mouthwash formulation has a neutral pH and is stable at 37 ° C. The ZLC provides a mouthwash formulation that is stable when stored, but that precipitates in the diluted solution. This formation of insoluble precipitate by dilution allows the formation of buffers in the dentinal tubules, providing benefits for hypersensitivity.
Example 3 [00077] The mouthwash formulation of the previous example using ZLC as an active ingredient not only shows competitive clarity with the current commercial mouthwash product containing NaF as an active ingredient, but also has the ability to precipitate when diluted with water. This unique property facilitates anti-sensitivity and anti-cavity effects, and it is therefore of interest to employ ZLC in a toothpaste product.
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49/60 [00078] A toothpaste in the form of an oral gel with ZLC as an active ingredient is formulated and compared to other formulations containing ZnCl2, ZnO, and NaF. Only the ZLC formulation shows competitive clarity as a current gel phase containing NaF. The ZLC gel phase precipitation property is also investigated by the hydrolysis reaction study, providing evidence that when teeth are brushed with toothpaste containing ZLC actives, insoluble particles formed during brushing can penetrate the dentinal tubules and block teeth. tubules resulting in anti-sensitivity and signal effect for the consumer.
[00079] Four batches of 500 g of gel phase containing NaF (control), ZLC, ZnCl2 and ZnO as an active ingredient are formulated with the ingredients shown in Table 8. The clarity of the samples with different active ingredients is compared, and the characteristic precipitation of the ZLC gel phase by dilution is evaluated. The concentration of zinc ions in solution is 25,300 ppm ZLC obtained by ICP, which in terms of weight provides about 17% of ZLC assets in the solution. Zinc ion concentrations in the batches that follow are all prepared at 0.5% (weight / weight) of the zinc level.
Table 8
Oral gel with ZLC (2.53% Zn) Ingredients % Load (g) Actual (g) 70% Sorbitol sun 76, 03 380.15 380.14 Aqueous solution of 20.00 100 100 ZLC 2.53% Zn
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Carboxymethyl 0.70 3.5 3.51 celluloseTrimethyl(TMC) (CMC) andcellulose Saccharin At 0.27 1.35 1.35 Propylene glycol 3.00 15 15 Total100.00 500 500 % Zn0.5060.5060%
Oral Gel with ZnCl2 (47.97% Zn) Ingredients % Load (g) Actual (g) Sorbitol sol 70% 80 400 399.99 ZnC12 47.97% Zn 1.06 5.275 5.27 CMC TMC 0.70 3.5 3.5 Saccharin 0.27 1.35 1.35 Propylene glycol 3 15 14.98 Deionized water 14.98 74,875 74.91 Total 100 500 500 % Zn 0.5080.5056
Oral Gel with ZnO (80.34% Zn) Ingredients % Load (g) Actual (g) Sorbitol sol 70% 80.2 401 400.99 ZnO 80.34% Zn 0.63 3.15 3.15 CMC TMC 0.70 3.5 3.5 Saccharin 0.27 1.35 1.35 Propylene glycol 3 15 15 Deionized water 15.2 76 75.99 Total 100 500 499.98
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% Zn 0.5500.5062%
Oral gel with NaF Ingredients % Load (g) Actual (g) Sorbitol sol 70% 80.2 401 401 In F 0.76 3.8 3.79 CMC TMC 0.70 3.5 3.51 Saccharin 0.27 1.35 1.35 Propylene glycol 3 15 15.01 Deionized water 15.07 75.35 75.36 Total 100 500 500.02
[00080] Lambda 25 UV / VIS spectrometer (Perkin
Elmer) is used to obtain absorbance information for all samples, in order to compare the clarity of the gel phase between the different active agents. Absorbance is a logarithmic measure of the amount of light that is absorbed when it passes through a substance. Since the particles in the gel absorb light, the more particles there are in the solution, the more light will be absorbed by the gel. Thus, a lower absorbance number of a gel indicates greater clarity. Absorbance is corrected using deionized water (DI) as the blank solution under the 610 nm wavelength light source. ZnO is not dissolved and is suspended in the gel phase resulting in high absorbance. Even though ZnCl2 is soluble in water, the gel phase containing ZnCl2 appears cloudy. Only the gel phase formulated by ZLC forms a homogeneous solution and shows competitive clarity as the gel phase formulated by NaF. The absorbance and pH of all samples are shown in Table 9.
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Table 9
In F ZLC ZnCl2 ZnO Absorbance 0.0344 0.1765 0.9204 2.4626 pH 7, 63 7.37 5, 25 8.30
[00081] Dilution Experiment: All original gel phase batches are diluted 2 times, 4 times, 8 times, 16 times and 32 times. There is a decrease in absorbance as the NaF gel, ZnCl2 gel, and ZnO gel are further diluted, and an increase in absorbance in the additionally diluted ZLC gel solution. This observation confirms the formation of precipitate when ZLC gel is being diluted with water. The pH values of the ZLC gel solutions diluted 2 times, 4 times, 8 times, 16 times, and 32 times are 7.71, 7.91, 8.03, 8.12, and 8.14, respectively.
Table 10
Active ingredient 2-fold dilution 4-fold dilution 8-fold dilution 16-fold dilution 32-fold dilution In F 0.0106 0.0104 0.0107 0.0075 0.0137 ZLC 0.1436 0.1887 0.1860 0.1336 0.2998 ZnCl2 0.7315 0.3700 0.1701 0.0570 0.0280 ZnO 2.4630 2.5340 2.1883 1.8638 1.0492
[00082] The above gels can be used alone or in a toothpaste that has a gel phase and an abrasive paste phase. ZLC is an active ingredient in the gel phase of toothpaste formulation. In comparison with the gel phase batches formulated by ZnCl2 and ZnO, only the formulation with ZLC shows competitive clarity and pH according to those of a commercial product (NaF as active ingredient). The dilution experiment shows that
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53/60 only the ZLC gel phase can form insoluble precipitate from the clear gel when it is diluted. The formation of an insoluble precipitate by dilution facilitates the formation of buffers in the dentin tubules after using this type of toothpaste and, in addition, provides a white precipitate signal during use by the consumer.
Example 4 [00083] Dental occlusion by an oral gel with ZLC is measured in comparison with an oral gel without ZLC for potential anti-hypersensitivity benefit. A Flodec instrument is used to measure the flow of fluid through the dentin tubules. A Pashley cell method (eg, Pashley DH, O'Meara JA Kepler EE, and others, Dentin permeability effects of desensitizing dentrifices in vitro. J. Periodontol. 1984; 55 (9): 522-525) sequence of a procedure used to measure dentinal occlusion in formulations of S. Mello mouthwash. Two 10-minute treatments and 400 gL sample are applied with a pipette on dentin discs at 10-minute intervals. After each treatment, the discs are washed with phosphate buffered saline (PBS) and measured for flow using a FLODEC device, a device that controls the position of a meniscus inside a capillary tube to measure small changes in volume. Table 11 shows the average flow of the oral gel with ZLC and percentage of flow reduction after application of the sample.
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Table 11
Average flow (pL / min.) Of Oral Gel with ZLC % Flow ReductionLine ofbase Treatment# 2 Difference (from baseline) Rep # 1 7.51 3.47 4.05 53.87 Rep # 2 13.02 7.20 5.82 44.68 Rep # 3 25.74 19.79 5.95 23.13 AVG 40.56 STDEV 15.78
As shown above, the average percentage reduction in oral gel flow with ZLC triplicates is about 41% through dentinal tubules.
[00084] Table 12 shows the average flow of oral gel without ZLC (control) and the percentage of flow reduction after application of the sample.
Table 12
Average flow (pL / min.) Of Oral Gel without ZLC % Flow ReductionLine ofbase Treatment# 2 Difference (from baseline) Rep # 1 7.25 5, 02 2.23 30, 85 Rep # 2 13, 94 8.43 5.51 39, 57 Rep # 3 22.84 17.93 4.91 21.53 AVG 30.65 STDEV 9, 02
As shown above, the average percentage reduction in oral gel flow without ZLC in triplicate (control) is about 31% through the dentinal tubules.
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55/60 [00085] The oral gel with ZLC shows directionally better performance, compared to the oral gel without ZLC (control) in an in vitro hydraulic conductance model using a FLODEC device.
Example 5 [00086] Various dilutions of ZLC are prepared to assess their efficiency in producing visible precipitates and / or flocculation, which can be released in situ on an oral surface or in a dental opening, such as open tubules.
[00087] A pure ZLC solution is prepared by 1), reacting 0.5 mol of ZnO powder with 1 mol of lysine HC1 in 1 liter of water at room temperature for about 2 hours, and 2) collecting the supernatant by centrifugation followed by filtration through a 0.45 pm membrane. The pure solution has a zinc concentration of 2.39% by weight, and a pH of about 7.03.
[00088] The dilution experiment is conducted by mixing the solution with pure deionized water. The pure solution is diluted 2x, 4x, 6x, 7x, 8x, 10x, 12x, 16x, 20x, 24x, 28x, and 32x corresponding to the initial zinc concentrations of 1.20%, 0.598%, 0.398%, 0.341%, 0.299%, 0.239%, 0.199%, 0.149%, 0.120%, 0.0996%, 0.0854%, 0.0747%, by weight, respectively. Diluted samples are kept at 37 ° C, and the rates at which flocculation / precipitation occurred are monitored. Dilutions with initial concentrations of zinc at 0.149% and 0.199% are able to generate some visible flocculation within 30 minutes of the time point when the master solution is mixed with water. One hour after
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56/60 the mixture, the visible flocculation is observed in dilutions with initial zinc concentrations between 0.0854% and 0.239%. One and a half hours after mixing, visible flocculation is observed in dilutions with initial zinc concentrations between 0.0747% and 0.239%. Two hours after mixing, additional sampling with the initial zinc concentration of 0.299% also showed the presence of flocculation. After a total of 19 hours, flocculation and / or precipitation can be observed in all samples except with an initial zinc concentration of 1.20%, and those with initial zinc concentrations between 0.0747% and 0.239%, that exhibit most precipitates.
[00089] The pH values of the final diluted samples are suitable for oral care applications. Samples with initial zinc concentrations of 0.0747%, 0.0854%, 0.0996%, 0.120%, 0.149%, 0.199% by weight and 0.239% had a final pH value of 7.99, 8.13 , 8.11, 7.97, 7.99, 6.80 and 6.70, respectively. These pH values were found to be well within the range of 5.5 to 10, which defines the appropriate range for formulations for oral care.
[00090] Zinc is present in precipitates mainly in the form of zinc oxide. Lysine is present in the precipitate as an integral component of it and / or as an impurity.
Example 6 [00091] Confocal images demonstrate the efficiency of ZLC in generating surface deposits and occlusion of tubule openings on the dentin surface, under conditions where visible precipitation can be formed.
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57/60 [00092] The deposition / occlusion test is conducted using slices of human dentin and the pure solution of Example 5. The dentin slices were prepared by cutting human tooth into thin sections of dentin about 800 microns thick , choosing a test side, sanding said test side using sandpaper of around 600 grains, polishing said test side using a Buehler polishing cloth and 5 microns of Buehler aluminum oxide, attacking said dentin section with acid 1% citric acid solution (by weight), sonicating said dentin section for 10 minutes and storing the dentin section in phosphate buffered saline (PBS, pH 7.4).
[00093] For the treatment, the pure solution is diluted several times with water, obtaining a treatment solution with an initial zinc concentration of about 0.149% by weight. The dentin section is immersed in the treatment solution for 1 hour at 37 ° C. The treated dentin section is then removed from the treatment solution and washed 4 times, each time with 1 ml of PBS. The dentin section is then dried using a paper-based tissue and examined under a confocal microscope in both XYZ and XYZ modes. Subsequent treatments are carried out in the same way.
[00094] Progressive deposition and occlusion can be seen through confocal imaging.
The first treatment leads to noticeable deposition.
The second treatment leads to complete coverage of the surface, including blocking substantially all tubular openings. Deposits or more in thickness.
surface can be 10 microns
After the third treatment,
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58/60 observed complete coverage of the surface and complete blockage of the tubular openings. Surface deposits can be 25 microns or more in thickness. The deposits give a white color to the dentin surface.
[00095] Surface deposits provide several benefits, including those normally associated with zinc and lysine, as well as protection against erosion by neutralizing erosive acids by deposits, protection against sensitivity by blocking the tubules and controlled release of active ingredients , due to the gradual release of zinc and lysine from deposits, particularly after acid challenge.
Example 7 [00096] Confocal images demonstrate the efficiency of ZLC in generating surface deposits and occlusion of tubule openings on the dentin surface, under conditions where visible precipitation is not observed.
[00097] Dentin sections, as prepared in Example 6, are treated repeatedly with ZLC dilutions with an initial zinc concentration of 0.0747% by weight. Each treatment involved 32 ml of diluted solution (1 ml of a pure solution of Example 5 and 31 ml of deionized water) lasting 10 minutes at 37 ° C, during which time no precipitation is observed with the naked eye. The dentin section is examined under the confocal microscope after each treatment. After four consecutive treatments, significant surface deposition is observed. After 12 consecutive treatments, complete coverage of the
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59/60 surface is observed leaving no sign of the presence of tubular openings.
[00098] Consequently, surface deposition and tubule occlusion can occur under conditions, both in terms of dilution ratios and treatment durations that do not produce visible precipitation.
Example 8 [00099] Test toothpaste comprising zincolysin, 1,450 ppm fluoride and phosphates is prepared as described in Table 13:
Table 13
Ingredient % by weight PEG600 3 CMC-7 0.65 Xanthan 0.2 Sorbitol 27 Glycerin 20 Saccharin 0.3 Tetrasodium pyrophosphate 0.5 Calcium pyrophosphate 0.25 Sodium dibasic phosphate 3.5 Sodium fluoride (to provide 1,450 ppm of fluoride) 0.32 Titanium dioxide 0.5 Abrasive silica 8 Thickener silica 8 ZLC 7 Sodium lauryl sulfate 1.5 Flavoring 1.2
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Water QS
[000100] Although the invention has been described with respect to specific examples including presently preferred ways of carrying out the invention, those skilled in the art will appreciate that there are numerous variations of the systems and techniques described above. It should be understood that other modalities can be used and structural and functional modifications can be made without departing from the scope of the present invention. Thus, the scope of the invention must be interpreted widely, as set out in the appended claims.

权利要求:
Claims (11)
[1]
1. Composition for oral care, characterized by the fact that it comprises an amino acid-zinc halide complex, in which the amino acid is arginine or lysine and in which the composition is a toothpaste, powder, cream, strip or gum.
[2]
2. Composition according to claim 1, characterized by the fact that the amino acid and zinc halide is formed from precursors, optionally in which the precursors are a source of zinc ion, a source of amino acid, in which the source and a halide source, still optionally halide may be part of the zinc ion source, the amino acid source or a halogen acid.
[3]
3. Composition according to claim 1, characterized by the fact that the complex is a lysine-zinc halide complex.
[4]
Composition according to claim 2, characterized by the fact that the precursors comprise lysine in the form of a free or orally acceptable acid addition salt.
[5]
Composition according to any one of claims 1 to 4, characterized in that the amount of zinc is 0.05-4% by weight.
[6]
6. Composition according to any one of claims 1 to 5, characterized by the fact that zinc is solubilized in the formulation, but provides a zinc precipitate when diluted 1:16 with saliva and / or rinse.
[7]
7. Composition according to any one of claims 1 to 6, characterized by the fact that the
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2/3 amino acid-zinc halide complex is lysine-zinc chloride complex or arginine-zinc chloride complex.
[8]
Composition according to any one of claims 1 to a halide complex of
7, characterized by the fact that the amino acid-zinc is a lysine-zinc chloride complex having the chemical structure [Zn (C6H14N2O2) 2Cl] ⁺ Cl ^- both in cationic cation solution (for example, [Zn (CóH14N2O2) 2Cl] ⁺ the chloride anion or in the form of mono- or dihydrate.
solid salt, optionally in
9. Composition, according with any an of claims 1 to 8, characterized by the fact what is at shape of a toothpaste ^. 10. Composition, according with any an of claims 1 to 9, characterized by the fact what is in an orally acceptable basis, for example, a base in Toothpaste. 11. Composition, according with any an of claims 1 to 10, characterized by the fact in what further comprises an effective amount of a source of ion fluoride. 12. Composition, according with any an of claims 1 to 11, characterized by the fact in what
comprises an orally acceptable base comprising ingredients selected from one or more of abrasives, buffering agents, humectants, surfactants, thickeners, fragments or binder strips, breath fresheners, flavoring agents, fragrances, dyes, antibacterial agents, bleaching agents, agents that interfere or prevent fixation
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3/3 bacterial, calcium sources, phosphate sources, orally acceptable potassium salts, anionic polymers and combinations thereof.
[9]
Composition according to any one of claims 1 to 12, characterized in that the pH of the composition is between pH 6 and pH 8.
[10]
14. Use of an amino acid-zinc halide complex, characterized by the fact that it is for the production of an oral care composition as defined in any one of claims 1 to 13.
[11]
15. Use of an amino acid-zinc halide complex characterized by the fact that it is used to prepare a composition, as defined in any one of claims 1 to 13, to treat or reduce dental enamel erosion, cleaning teeth, reducing biofilm and plaque generated by bacteria, reduction of gingivitis, inhibition of tooth decay and formation of cavities, and / or reduction of dentin hypersensitivity, which includes the application of said composition to teeth.

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法律状态:
2018-10-30| B07A| Technical examination (opinion): publication of technical examination (opinion)|

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2019-02-05| B09A| Decision: intention to grant|

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2019-04-09| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 19/12/2012, OBSERVADAS AS CONDICOES LEGAIS. (CO) 20 (VINTE) ANOS CONTADOS A PARTIR DE 19/12/2012, OBSERVADAS AS CONDICOES LEGAIS |

优先权:

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申请号 | 申请日 | 专利标题

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PCT/US2012/070525|WO2014098826A1|2012-12-19|2012-12-19|Oral care compositions comprising zinc amino acid halides|

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